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12,000 | 23,415,577 | Depression significantly increases the risk of mortality among individuals with diabetes .
Early detection and treatment of depression may improve health outcomes in this population | OBJECTIVES To estimate risk of comorbid depression on all-cause mortality over time among individuals with diabetes . | OBJECTIVE Diabetes negatively impacts the health-related quality of life ( HRQOL ) of patients with type 2 diabetes . An earlier analysis showed HRQOL to be associated with mortality , which suggests that measuring HRQOL could have clinical implication s. We studied the association between HRQOL and total and cardiovascular mortality in patients with type 2 diabetes during long-term follow-up and specifically focused on old age and sex differences . RESEARCH DESIGN AND METHODS HRQOL was measured in a prospect ively followed cohort of 1,353 patients with type 2 diabetes using the R AND -36 . Cox proportional hazard models were used to measure the independent effect of baseline HRQOL on mortality . RESULTS During a mean follow-up of 9.6 years , 570 ( 42 % ) patients died , 280 of whom died of cardiovascular disease ( 49 % ) . The Physical Component Score ( PCS ) and the Mental Component Score ( MCS ) were inversely associated with total mortality , with hazard ratios of 0.988 ( 95 % CI 0.983–0.993 ) and 0.990 ( 95 % CI 0.985–0.995 ) , respectively . A 10-point-higher score on the PCS and MCS decreased the risk for total mortality by 11 and 10 % , respectively . An inverse relationship with mortality was also seen for men , women , and for patients aged > 75 years . Mental health was significantly related to mortality in men but not in women . CONCLUSIONS Lower physical and mental HRQOL was associated with a higher total mortality and cardiovascular mortality in patients with type 2 diabetes ; this is also the case when study ing men and women and the elderly separately . The dimension mental health , related to depression and anxiety , was only associated with mortality in men , not in women PURPOSE Recent evidence suggests that depression is linked to increased mortality among patients with diabetes . This study examines the association of depression with all-cause and cause-specific mortality in diabetes . METHODS We conducted a prospect i ve cohort study of primary care patients with type 2 diabetes at Group Health Cooperative in Washington state . We used the Patient Health Question naire ( PHQ-9 ) to assess depression at baseline and review ed medical records supplemented by the Washington state mortality registry to ascertain the causes of death . RESULTS Among a cohort of 4,184 patients , 581 patients died during the follow-up period . Deaths occurred among 428 ( 12.9 % ) patients with no depression , among 88 ( 17.8 % ) patients with major depression , and among 65 ( 18.2 % ) patients with minor depression . Causes of death were grouped as cardiovascular disease , 42.7 % ; cancer , 26.9 % ; and deaths that were not due to cardiovascular disease or cancer , 30.5 % . Infections , dementia , renal failure , and chronic obstructive pulmonary disease were the most frequent causes in the latter group . Adjusting for demographic characteristics , baseline major depression ( relative to no depression ) was significantly associated with all-cause mortality ( hazard ratio [HR]=2.26 , 95 % confidence interval [ CI ] , 1.79–2.85 ) , with cardiovascular mortality ( HR = 2.00 ; 95 % CI , 1.37–2.94 ) , and with noncardiovascular , noncancer mortality ( HR = 3.35 ; 95 % CI , 2.30–4.89 ) . After additional adjustment for baseline clinical characteristics and health habits , major depression was significantly associated only with all-cause mortality ( HR = 1.52 ; 95 % CI , 1.19–1.95 ) and with death not caused by cancer or atherosclerotic cardiovascular disease ( HR = 2.15 ; 95 % CI , 1.43–3.24 ) . Minor depression showed similar but nonsignificant associations . CONCLUSIONS Patients with diabetes and coexisting depression face substantially elevated mortality risks beyond cardiovascular deaths CONTEXT Depression and diabetes mellitus have been associated with an increased risk of all-cause and cardiovascular disease ( CVD ) mortality . However , data evaluating the joint effects of these 2 conditions on mortality are sparse . OBJECTIVES To evaluate the individual and joint effects of depression and diabetes on all-cause and CVD mortality rate . DESIGN Prospect i ve cohort study . SETTING The 11 states of the Nurses ' Health Study . PARTICIPANTS A total of 78 282 women who participated in the Nurses ' Health Study aged 54 to 79 years at baseline in 2000 were followed up until 2006 . Depression was defined as having self-reported diagnosed depression , treatment with antidepressant medications , or a score indicating severe depressive symptoms ( ie , a 5-item Mental Health Index score ≤52 ) . Self-reported type 2 diabetes was confirmed using a supplementary question naire . MAIN OUTCOME MEASURES All-cause and CVD-specific mortality rate . RESULTS During 6 years of follow-up ( 433 066 person-years ) , 4654 deaths were documented , including 979 deaths from CVD . Compared with participants without either condition , the age-adjusted relative risks ( RRs ) ( 95 % confidence interval ) for all-cause mortality were 1.76 ( 1.64 - 1.89 ) for women with depression only , 1.71 ( 1.54 - 1.89 ) for individuals with diabetes only , and 3.11 ( 2.70 - 3.58 ) for women with both conditions . The corresponding age-adjusted RRs of CVD mortality were 1.81 ( 1.54 - 2.13 ) , 2.67 ( 2.20 - 3.23 ) , and 5.38 ( 4.19 - 6.91 ) , respectively . These associations were attenuated after multivariate adjustment for other demographic variables , body mass index , smoking status , alcohol intake , physical activity , and major comorbidities ( including hypertension , hypercholesterolemia , heart diseases , stroke , and cancer ) but remained significant , with the highest RRs for all-cause and CVD mortality found in those with both conditions ( 2.07 [ 1.79 - 2.40 ] and 2.72 [ 2.09 - 3.54 ] , respectively ) . Furthermore , the combination of depression with a long duration of diabetes mellitus ( ie , > 10 years ) or insulin therapy was associated with a particularly higher risk of CVD mortality after multivariate adjustment ( RRs , 3.22 and 4.90 , respectively ) . CONCLUSIONS Depression and diabetes are associated with a significantly increased risk of all-cause and CVD mortality rate . The coexistence of these conditions identifies women at particularly high risk Context Many patients have both diabetes and depression . Some hypothesize that treating depression might improve diabetes outcomes . Contribution In this r and omized trial , 12 months of depression care management for depressed patients with diabetes improved depression-related outcomes and increased the frequency of exercise . However , care management did not affect diet , diabetes medication adherence , glucose testing , or glycemic control . Caution s The study sample had reasonably good diabetes control at baseline . Whether patients with poorly controlled diabetes would benefit from depression care is not known . The Editors Major depression and dysthymic disorder affect 5 % to 10 % of older adults seen in primary care setting s ( 1 - 3 ) . Late-life depression is often chronic or recurrent ( 4 - 6 ) and is associated with substantial suffering , functional impairment , and diminished health-related quality of life ( 7 ) . Diabetes mellitus affects 7.8 % of all adults and almost 1 in 5 of those age 60 years and older ( 8) . Individuals with diabetes mellitus have a 2-fold higher rate of major depression than those without diabetes ( 9 , 10 ) . Depression adversely affects the course of coexisting medical illness , contributing to increased symptom burden , functional impairment , and mortality ( 11 , 12 ) . For patients with diabetes mellitus , depression is associated with decreased glycemic control and increased number of micro- and macrovascular complications ( 13 , 14 ) . The mechanism of effect is not understood but may be related to depression-induced abnormalities in neuroendocrine and neurotransmitter function or decreased self-care behaviors ( 15 - 20 ) . Integrating evidence -based depression care for persons with diabetes may improve both depression and diabetes outcomes . Three small r and omized , controlled trials have studied the effect of treatment for depression on affective and glycemic outcomes in patients with depression and diabetes mellitus ( 21 - 23 ) . These studies have consistently shown improvements in affective outcomes , but effects on glycemic control have been mixed . Primary care physicians are well positioned to provide integrated care for depression and diabetes mellitus but face many barriers . Controlled trials report that treatment for depression is efficacious in approximately 70 % of persons who complete treatment compared with 30 % of those who receive placebo ( 24 ) . However , these results are difficult to replicate in routine primary care practice . Barriers to high- quality care include suboptimal recognition ; inconsistent treatment with lack of close follow-up and monitoring ; and organizational barriers , such as brief visits , poor integration with specialty mental health care , competing clinical priorities , and lack of decision support systems ( 25 - 27 ) . Simple interventions , such as depression screening and physician education , have little impact on these barriers and patient outcomes ( 28 - 30 ) . Treatment models that use a depression specialist working collaboratively with primary care physicians have shown clinical ly important improvement in patient outcomes ( 31 - 37 ) . We recently reported robust effects of such a model for older adults with major depression or dysthymia ( 37 ) . In this preplanned analysis , we evaluate the effects on affective and diabetes-specific outcomes . If effective care for depression also benefits adherence to self-care regimens , functional status , and other medical illness outcomes , it would add powerful quality -of-care and economic incentives for the dissemination and maintenance of these models . In addition , if effective care for depression improves self-care behaviors , it may also positively affect other chronic medical illnesses with important self-care components . For this prespecified subgroup analysis , we focused on older adults with clinical depression and coexisting diabetes mellitus . We hypothesized that the collaborative care intervention would improve affective symptoms , functional status , self-care behaviors , and glycemic control . In addition , we hypothesized that effects on glycemic control would be greatest for patients with baseline hemoglobin A1c values of 8.0 % or greater . Methods The Improving MoodPromoting Access to Collaborative Treatment ( IMPACT ) study is a multisite r and omized , controlled trial of a collaborative care intervention program for late-life depression in primary care ( 37 , 38 ) . Institutional review boards at participating sites approved study protocol s , and all participants gave written informed consent . Patients Seven study sites representing 8 diverse health care organizations with a total of 18 primary care clinics in 5 states participated in the study . From July 1999 to August 2001 , depressed older adults were recruited through referrals from primary care practitioners and other clinic staff or through systematic depression screening with a 2-item depression screener adapted from the Primary Care Evaluation of Mental Disorders ( 39 ) . Of the 2190 patients referred to the study , 308 ( 14 % ) declined the initial eligibility screening or additional interviews , 54 ( 3 % ) had incomplete initial screenings , and 202 ( 9 % ) were ineligible because they were younger than 60 years of age or they did not plan to use the participating clinic over the coming 12 months . Of the 32908 patients approached for screening , 5246 ( 16 % ) declined the initial screening or follow-up interviews . A total of 1791 ( 5 % ) of the initial screenings were incomplete and 23233 ( 71 % ) of those screened were not eligible because they did not have one of the core depression symptoms ( 95 % ) or because of logistic reasons such as lack of transportation or access to a telephone ( 5 % ) . The remaining 1626 ( 74 % ) of those referred and 2638 ( 8 % ) of those screened completed a computer-assisted structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders , fourth edition ( DSM-IV ) , to assess whether patients met research diagnostic criteria for major depression or dysthymia ( 40 ) . Inclusion criteria were age 60 years or older , plans to use one of the participating clinics as the main source of general medical care in the coming year , and a diagnosis of current major depression or dysthymic disorder according to the structured clinical interview for DSM-IV . Otherwise eligible persons were excluded because of a current drinking problem ( a score of 2 on the CAGE question naire ) ( 41 ) , a history of bipolar disorder or psychosis ( 38 ) , ongoing treatment with a psychiatrist , or severe cognitive impairment defined by a score less than 3 on a 6-item cognitive screener ( 42 ) . We identified 2102 eligible older adults with major depression or dysthymic disorder , of whom 1801 ( 86 % ) enrolled in the study . As part of the structured baseline interview , enrolled patients were asked Has a doctor or another health care worker diagnosed you with or treated you for high blood sugar or diabetes in the past 3 years ? The 417 patients who endorsed this question are the focus of the diabetes-specific analyses . After the baseline interview , we r and omly assigned participants to the IMPACT intervention or usual care . The r and omization was stratified by recruitment method ( screening or referral ) and clinic . R and omization information was contained in a set of numbered , sealed envelopes for each stratum that were used sequentially for newly enrolled patients at each clinic ( 38 ) . Diagnoses were communicated to enrolled patients and their primary care physicians . Intervention Patients in the intervention group received a 20-minute educational videotape and a booklet about late-life depression and were encouraged to have an initial visit with a depression care manager at the primary care clinic ( 43 , 44 ) . Care managers were nurses or psychologists who were trained for the study as a depression clinical specialist ( 38 , 45 ) . During the initial visit , the depression clinical specialist conducted a clinical and psychosocial history , review ed the educational material s , and discussed patient preferences for depression treatment ( antidepressant medications or psychotherapy ) . New patients and patients needing treatment plan adjustments were discussed with a supervising team psychiatrist and a liaison primary care physician during a weekly team meeting . The depression clinical specialist then worked with the patient and his or her regular primary care provider to establish a treatment plan according to an evidence -based treatment algorithm ( 38 ) . The IMPACT algorithm suggested an initial choice of an antidepressant ( usually a selective serotonin reuptake inhibitor ) or a course of Problem-Solving Treatment in Primary Care ( PST-PC ) , which consisted of 6 to 8 brief sessions of structured psychotherapy for depression , delivered by the depression clinical specialist in primary care ( 46 - 49 ) . For patients who were already receiving antidepressant medications but who were still depressed , the recommendation for partial responders was to increase the dose or augment the antidepressant with a trial of PSTPC ; the recommendation for nonresponders was to switch to a different medication or use a trial of PSTPC . Depression clinical specialists also encouraged patients to increase behavioral activation and referred them to additional health or social services , as clinical ly indicated . The intervention did not specifically address diabetes mellitus or other coexisting medical illnesses . As care managers , depression clinical specialists attempted to follow patients for up to 12 months ; they monitored treatment response with the Primary Care Evaluation of Mental Disorders Patient Health Question naire ( 50 ) and a Web-based clinical information system ( 51 ) . During the acute treatment phase , in-person or telephone follow-up contacts were suggested at least every other week . Patients who recovered from depression ( 50 % reduction in the Patient Health Question naire score and <3 of 9 symptoms of major depression ) were engaged in developing a relapse prevention plan and were then OBJECTIVE We sought to test our a priori hypothesis that depressed patients with diabetes in practice s implementing a depression management program would have a decreased risk of mortality compared with depressed patients with diabetes in usual-care practice s. RESEARCH DESIGN AND METHODS We used data from the multisite , practice -r and omized , controlled Prevention of Suicide in Primary Care Elderly : Collaborative Trial ( PROSPECT ) , with patient recruitment from May 1999 to August 2001 , supplemented with a search of the National Death Index . Twenty primary care practice s participated from the greater metropolitan areas of New York City , New York ; Philadelphia , Pennsylvania ; and Pittsburgh , Pennsylvania . In all , 584 participants identified though a two-stage , age-stratified ( aged 60 - 74 or > or=75 years ) depression screening of r and omly sample d patients and classified as depressed with complete information on diabetes status are included in these analyses . Of the 584 participants , 123 ( 21.2 % ) reported a history of diabetes . A depression care manager worked with primary care physicians to provide algorithm-based care . Vital status was assessed at 5 years . RESULTS After a median follow-up of 52.0 months , 110 depressed patients had died . Depressed patients with diabetes in the intervention category were less likely to have died during the 5-year follow-up interval than depressed diabetic patients in usual care after accounting for baseline differences among patients ( adjusted hazard ratio 0.49 [ 95 % CI 0.24 - 0.98 ] ) . CONCLUSIONS Older depressed primary care patients with diabetes in practice s implementing depression care management were less likely to die over the course of a 5-year interval than depressed patients with diabetes in usual-care practice OBJECTIVE —The aim was to evaluate over 18 months whether depression was associated with mortality in people with their first foot ulcer . RESEARCH DESIGN AND METHODS —A prospect i ve cohort design was used . Adults with their first diabetic foot ulcer were recruited from foot clinics in southeast London , U.K. At baseline , the Schedules for Clinical Assessment in Neuropsychiatry 2.1 was used to define those who met DSM ( Diagnostic and Statistical Manual of Mental Disorders)-IV criteria for minor and major depressive disorders . Potential covariates were age , sex , marital status , socioeconomic status , smoking , antidepressant use , A1C , macro- and microvascular complications , and University of Texas classification – based severity and size of ulcer . The main outcome was mortality 18 months later , and A1C was the secondary outcome . The proportion who had an amputation , had recurrence , and whose ulcer had healed was recorded . RESULTS —A total of 253 people with their first diabetic foot ulcer were recruited . The prevalence of minor and major depressive disorder was 8.1 % ( n = 21 ) and 24.1 % ( n = 61 ) , respectively . There were 40 ( 15.8 % ) deaths , 36 ( 15.5 % ) amputations , and 99 ( 43.2 % ) recurrences . In the adjusted Cox regression analysis , minor and major depressive disorders were associated with an approximately threefold hazard risk for mortality compared with no depression ( 3.23 [ 95 % CI 1.39–7.51 ] and 2.73 [ 1.38–5.40 ] , respectively ) . There was no association between minor and major depression compared with no depression and A1C ( P = 0.86 and P = 0.43 , respectively ) . CONCLUSIONS —One-third of people with their first diabetic foot ulcer suffer from clinical depression , and this is associated with increased mortality OBJECTIVE Depression is a major contributor to death and disability , but few follow-up studies of depression have been carried out in the primary -care setting . The authors sought to assess whether depression in older patients is associated with increased mortality after a 2-year follow-up interval and to estimate the population -attributable fraction ( PAF ) of depression on mortality in older primary -care patients . METHODS Longitudinal cohort analysis was carried out in 20 primary -care practice s. Participants were identified though a two-stage , age-stratified ( 60 - 74 or 75 + ) depression screening of r and omly sample d patients ; enrollment included patients who screened positive and a r and om sample of screened-negative patients . In all , 1,226 persons were assessed at baseline . Vital status at 2 years was the outcome of interest . RESULTS Of 1,226 persons in the sample , 598 were classified as depressed . After 2 years , 64 persons had died . Persons with depression at baseline were more likely to die at the end of the 2-year follow-up interval than were persons without depression , even after accounting for potentially influential covariates such as whether the participant reported a history of myocardial infa rct ion ( MI ) or diabetes . CONCLUSIONS Among older , primary -care patients over the course of a 2-year follow-up interval , depression contributed as much to mortality as did MI or diabetes Analysis of prospect i ve follow-up data usually includes a Cox regression model . When a hazard rate ratio , obtained as the exponential of an estimated regression coefficient from the Cox model , is greater than 1.0 , it consistently exceeds relative risk , and is exceeded by the odds ratio . The divergence of these distinct epidemiologic measures increases with the product of three factors : ( 1 ) the length of follow-up , ( 2 ) the average rate of the end point occurence over the follow-up period , and ( 3 ) the magnitude of risk , either above or below 1 . Cornfield 's rare disease assumption is basically the product of the first two of these factors . However , risks in excess of 2.5 have a powerful effect on the divergence of these measures , and this point has received less emphasis . Conversely , and as seen frequently in applications , relative risk , hazard rate ratio , and odds ratio numerically approximate one another with shorter follow-up , rarer end points , and risks closer to 1 . Although the hazard rate ratio is not always distinguished from relative risk , it is commonly close to , and is always between , relative risk and the odds ratio . Consistent and accurate terminology would have us use hazard rate ratio with Cox regression and odds ratio with logistic regression . The term " relative risk " seems to be a default choice , regardless of the model being used . However , when relative risk is the object of the model chosen , as in a Poisson regression approximation of two binomial proportions or an equivalent weighted least squares , then for us , relative risk is the accurate terminology CONTEXT Although depression is a risk factor for dementia in the general population , its association with dementia among patients with diabetes mellitus has not been well studied . OBJECTIVE To determine whether comorbid depression in patients with type 2 diabetes increases the risk of development of dementia . DESIGN The Diabetes and Aging Study was a cohort investigation that surveyed a racially/ethnically stratified r and om sample of patients with type 2 diabetes . SETTING A large , integrated , nonprofit managed care setting in Northern California . PARTICIPANTS A sample of 19,239 diabetes registry members 30 to 75 years of age . MAIN OUTCOME MEASURES The Patient Health Question naire 8 , International Classification of Diseases , Ninth Revision ( ICD-9 ) diagnoses of depression , and /or antidepressant prescriptions in the 12 months prior to baseline were used to identify prevalent cases of depression . Clinical ly recognized dementia was identified among subjects with no prior ICD-9 Clinical Modification ( ICD-9-CM ) diagnoses of dementia . To exclude the possibility that depression was a prodrome of dementia , dementia diagnoses were only based on ICD-9-CM diagnoses identified in years 3 to 5 postbaseline . The risk of dementia for patients with depression and diabetes relative to patients with diabetes alone was estimated using Cox proportional hazard regression models that adjusted for sociodemographic , clinical , and health risk factors and health use . RESULTS During the 3- to 5-year period , 80 of 3766 patients ( 2.1 % ) with comorbid depression and diabetes ( incidence rate of 5.5 per 1000 person-years ) vs 158 of 15,473 patients ( 1.0 % ) with diabetes alone ( incidence rate of 2.6 per 1000 person-years ) had 1 or more ICD-9-CM diagnoses of dementia . Patients with comorbid depression had a 100 % increased risk of dementia during the 3 to 5 years postbaseline ( adjusted hazard ratio , 2.02 ; 95 % confidence interval , 1.73 - 2.35 ) . CONCLUSION Depression in patients with diabetes was associated with a substantively increased risk for development of dementia compared with those with diabetes alone OBJECTIVES The authors prospect ively examined whether depressive symptoms ( DS ) in older adults negatively affected active live expectancy ( ALE ) , or remaining years free of disability , and mortality , independently and in the presence of chronic diseases , and after stratification by gender . DESIGN Prospect i ve cohort study , first three waves ( 1993 - 1998 ) of the Asset and Health Dynamics Among the Oldest Old . SETTING DATA COLLECTION University of Michigan ; analysis : University of South Florida . PARTICIPANTS Nationally representative sample of community-dwelling adults age 70 and older ( N = 7,381 ) . MEASUREMENTS DS ( Center for Epidemiological Studies Depression , 8-item version ) , self-reported cancer , diabetes , heart disease , or stroke , difficulty with activities of daily living , death , and estimates of total , active , and disabled life expectancy . RESULTS DS reduced ALE by 6.5 years for young-old men ( age 70 ) , 3.2 years for old-old men ( age 85 ) , 4.2 years for young-old women , and 2.2 years for old-old women , and these effects remained significant at all ages and across gender even after controlling for chronic disease , the one exception being DS and cancer in old-old women . DS also reduced total life expectancy significantly , although controlling for some chronic diseases ( particularly cancer and stroke ) eliminated the effect of DS across age and gender groups . CONCLUSION Depressive symptoms represent a serious and distinct threat to independent functioning in older adults . Whether experienced alone , or in combination with chronic diseases , depressive symptoms shorten ALE substantially . Timely diagnosis and treatment of depressive symptoms in older adults may delay the onset of disability and improve the quality of life Aims /hypothesisIndividuals with diabetes have increased mortality rates compared with the general population . In patients with type 2 diabetes depression further contributes to the increased mortality . Depression and mortality rates in patients with type 1 diabetes are an understudied phenomenon . We therefore studied their association in a prospect i ve setting . Methods We followed 4,174 participants ( 51 % men , age 39 ± 12 years , diabetes duration 22 ± 12 years [ mean ± SD ] ) in the Finnish Diabetic Nephropathy Study ( FinnDiane ) for an average of 9 years . Depression was defined as purchase of antidepressant agents at baseline and during follow-up . These data were obtained from the Finnish Drug Prescription Register . Data on all-cause mortality and cause of death were obtained from the Finnish Cause of Death Register . Results At baseline , 313 ( 7.5 % ) patients had purchased antidepressant agents . During follow-up 758 ( 18.2 % ) additional cases were observed . Purchasers of antidepressant agents at baseline had the highest 10-year cumulative mortality rate ( 22.5 % [ 95 % CI 18.1 , 26.6 ] ) , followed by those with such purchases during follow-up ( 18.0 % [ 15.4 , 20.5 ] ) and those with no purchases ( 10.1 % [ 9.0 , 11.2 ] , p < 0.001 ) . In the adjusted Cox regression models ( age , diabetes duration , diastolic blood pressure , smoking , HbA1c and nephropathy ) , the purchase of antidepressant agents at baseline was associated with mortality in women , but not in men . Cardiovascular diseases were the major cause of death in non-purchasers of antidepressant agents . In antidepressant purchasers , chronic diabetic complications were the most frequent underlying cause of death . Conclusions /interpretationIn a population of patients with type 1 diabetes , purchase of antidepressant agents was associated with increased mortality rates in women , but not in men BACKGROUND There is a high prevalence of depression in patients with diabetes mellitus . Depression has been shown to be associated with poor self-management ( adherence to diet , exercise , checking blood glucose levels ) and high hemoglobin A1c ( HbA1c ) levels in patients with diabetes . OBJECTIVE To determine whether enhancing quality of care for depression improves both depression and diabetes outcomes in patients with depression and diabetes . DESIGN R and omized controlled trial with recruitment from March 1 , 2001 , to May 31 , 2002 . SETTING Nine primary care clinics from a large health maintenance organization . PARTICIPANTS A total of 329 patients with diabetes mellitus and comorbid major depression and /or dysthymia . Intervention Patients were r and omly assigned to the Pathways case management intervention ( n = 164 ) or usual care ( n = 165 ) . The intervention provided enhanced education and support of antidepressant medication treatment prescribed by the primary care physician or problem-solving therapy delivered in primary care . MAIN OUTCOME MEASURES Independent blinded assessment s at baseline and 3 , 6 , and 12 months of depression ( Hopkins Symptom Checklist 90 ) , global improvement , and satisfaction with care . Automated clinical data were used to evaluate adherence to antidepressant regimens , percentage receiving specialty mental health visits , and HbA1c levels . RESULTS When compared with usual care patients , intervention patients showed greater improvement in adequacy of dosage of antidepressant medication treatment in the first 6-month period ( odds ratio [ OR ] , 4.15 ; 95 % confidence interval [ CI ] , 2.28 - 7.55 ) and the second 6-month period ( OR , 2.90 ; 95 % CI , 1.69 - 4.98 ) , less depression severity over time ( z = 2.84 , P = .004 ) , a higher rating of patient-rated global improvement at 6 months ( intervention 69.4 % vs usual care 39.3 % ; OR , 3.50 ; 95 % CI , 2.16 - 5.68 ) and 12 months ( intervention 71.9 % vs usual care 42.3 % ; OR , 3.50 ; 95 % CI , 2.14 - 5.72 ) , and higher satisfaction with care at 6 months ( OR , 2.01 ; 95 % CI , 1.18 - 3.43 ) and 12 months ( OR , 2.88 ; 95 % CI , 1.67 - 4.97 ) . Although depressive outcomes were improved , no differences in HbA1c outcomes were observed . CONCLUSION The Pathways collaborative care model improved depression care and outcomes in patients with comorbid major depression and /or dysthymia and diabetes mellitus , but improved depression care alone did not result in improved glycemic control OBJECTIVE To examine diabetes prevalence , incidence , and mortality from 1993 to 2001 among fee-for-service Medicare beneficiaries > or = 67 years of age . RESEARCH DESIGN AND METHODS This study was a retrospective analysis of a 5 % r and om sample of Medicare fee-for-service beneficiaries > or = 65 years of age in each year . RESULTS In 1993 , the prevalence of diabetes among those > or = 67 years of age was 145 cases per 1,000 individuals . By 2001 , it was 197/1,000 , an increase of 36.0 % . The 2001 prevalence among Hispanics ( 334/1,000 ) was significantly higher than among blacks ( 296/1,000 ) , Asians ( 243/1,000 ) , and whites ( 184/1,000 , P < 0.0001 ) . During the 7-year period the greatest increase in diabetes prevalence was among Asians ( 68.0 % ) . Between 1994 and 2001 , the annual rate of newly diagnosed elderly individuals with diabetes increased by 36.9 % . Hispanics had the greatest increase at 55.0 % . The mortality rate among individuals with diabetes decreased by approximately 5 % between 1994 and 2001 from 92.1/1,000 to 87.2/1,000 ( P < 0.001 ) , due to a 6 % decrease among whites . No decrease in mortality was seen among elderly individuals without diabetes , it was 55/1,000 in 1994 and 54/1,000 in 2001 . CONCLUSIONS The dramatic increase in the incidence and prevalence of diabetes likely reflect a combination of true increases , as well as changes in the diagnostic criteria and increased interest in diagnosing and appropriately treating diabetes in the elderly . Improved treatment may have had an impact on mortality rates among individuals with diabetes , although they could have been influenced by the duration of diabetes before diagnosis , which has likely decreased . Changes in incidence , prevalence , and mortality in elderly individuals with diabetes need to continue to be monitored |
12,001 | 11,687,137 | A small but statistically significant positive effect of opioids was seen on breathlessness in the analysis of studies using non-nebulised opioids .
No evidence was found to support the use of nebulised opioids . | BACKGROUND Breathlessness is a common symptom in people with advanced disease .
The most effective treatments are aim ed at treating the underlying cause of the breathlessness but this may not be possible and symptomatic treatment is often necessary .
Strategies for the symptomatic treatment of breathlessness have never been systematic ally evaluated .
Opioids are commonly used to treat breathlessness : the mechanisms underlying their effectiveness are not completely clear and there have been few good-sized trials in this area .
OBJECTIVES To determine the effectiveness of opioid drugs given by any route in relieving the symptom of breathlessness in patients who are being treated palliatively . | Previous studies have shown that opiates increase the maximal external work performed at exhaustion in patients with chronic obstructive pulmonary disease ( COPD ) . The mechanism responsible for this improvement in exercise tolerance is unknown . The purpose of this study was to determine the effects of an oral morphine solution ( 0.8 mg/kg ) on the exercise tolerance , perception of dyspnea , and arterial blood gases of patients with COPD . Thirteen eucapnic patients with stable COPD ( FEV1 = 0.99 + /- 0.48 ) underwent duplicate incremental cycle ergometer tests to exhaustion ( Emax ) after the ingestion of placebo and after the ingestion of morphine . After the ingestion of morphine , the maximal workload increased by 18 % ( p less than 0.001 ) and the VO2 increased by 19.3 % ( p less than 0.001 ) . Ten of the 13 patients had a higher ventilation at Emax after morphine ingestion . Despite the higher ventilation at Emax after morphine , the mean Borg score was not significantly higher . At Emax after morphine ingestion , the PaO2 ( 65.8 + /- 11.6 mm Hg ) was significantly lower and the PaCO2 ( 43.5 + /- 8.3 mm Hg ) was significantly higher than at Emax after placebo ( 71.9 + /- 15.5 and 38.3 + /- 8.5 , respectively ) . When data at the highest equivalent workload were analyzed , the ventilation and the Borg scores were significantly lower , whereas the VO2 and VCO2 were comparable . From this study , we conclude that the administration of opiates can substantially increase the exercise capacity of patients with COPD . The improved exercise tolerance appears to be related to both a higher PaCO2 result ing in lowered ventilation requirements for a given workload and also to a reduced perception of breathlessness for a given level of ventilation In six healthy subjects , respiration and the sensation of breathlessness were assessed during submaximal exercise and the subsequent recovery . The overall responses were expressed by the relationship of breathlessness to minute volume . Because of the high subjective component in the assessment s , validation of the method in these particular subjects was an integral part of the study . The relationship of breathlessness to ventilation during identical periods of exercise was highly reproducible and sensitivity was demonstrated by an alteration in this relationship in the presence of an inspiratory resistance . Codeine at a dose of 60 mg by mouth was compared with placebo , each treatment being given on two occasions . The study was conducted in a double-blind fashion with r and omization of the order of treatments . Codeine at this dose allowed higher levels of carbon dioxide to be tolerated during breath-holding ; oxygen uptakes at rest and during exercise were unaffected . Ventilation and breathlessness at the end of exercise were each slightly but significantly reduced by codeine but the relationship between breathlessness and ventilation was not changed . Codeine did not prevent detection of an inspiratory resistance We have shown previously that the administration of morphine ( 0.8 mg/kg ) to patients with COPD increases the VO2max by 19.3 percent . A recent study demonstrated that the administration of low-dose nebulized morphine ( approximately 2 mg ) increased the endurance time of patients with severe lung disease by 1 min ( 35 percent ) with few systemic side effects . This double-blind crossover study evaluated the effects of various doses of nebulized morphine ( 0 , 1 , 4 , and 10 mg ) on the exercise tolerance and the psychologic status of COPD patients . In the present study , eight COPD patients ( FEV1 = 0.90 + /- 0.26 L , workload max = 76 + /- 29 W , VO2max = 950 + /- 264 ml , VEmax = 34 + /- 7 L ) , who were ventilatory limited were tested on four separate days . On each testing day , the patients underwent incremental exercise testing and psychologic testing before and 45 min after receiving the nebulized solution . The mean changes ( + /- SD ) in the exercise test results after each of the four different regimens were as follows : [ table : see text ] Although there tended to be larger increases in the workload , VO2max , and VEmax after the largest dose of morphine , none of the changes was statistically significant . Likewise , there were no significant differences in spirometry , resting metabolic measurements , or psychologic test scores after the four different regimens . We conclude that aerosolized morphine in the doses used in this study has no significant beneficial effect on the exercise tolerance of patients with COPD OBJECTIVES We sought to test the hypothesis that suppression of chemosensitivity ( respiratory response to arterial blood gases ) with dihydrocodeine may improve dyspnea and exercise tolerance in patients with chronic heart failure . BACKGROUND Exertional dyspnea is a common limiting symptom in patients with chronic heart failure . The mechanisms underlying this symptom are not fully understood but may be related to increased ventilation caused , in part , by the augmentation of chemosensitivity . Suppression of chemosensitivity with mild opiates may thus improve this symptom as well as exercise tolerance . METHODS Twelve men with chronic heart failure ( mean [ + /-SE ] age 65.5 + /- 1.5 years , range 58 to 75 ; left ventricular ejection fraction 21.3 + /- 3.0 % , range 8 to 39 ) received placebo or dihydrocodeine ( 1 mg/kg body weight ) on two separate days in a r and omized , double-blind design . One hour later , hypoxic and hypercapnic chemosensitivities were assessed using the transient inhalations of pure nitrogen and the rebreathing of 7 % carbon dioxide in 93 % oxygen , followed by treadmill cardiopulmonary exercise testing . The symptoms of dyspnea and fatigue during the exercise test were assessed using a modified Borg scale from 0 to 10 . RESULTS There was a significant fall in hypoxic and hypercapnic chemosensitivities with dihydrocodeine administration compared with placebo ( 0.447 + /- 0.096 vs. 0.746 + /- 0.104 liter/min per percent arterial oxygen saturation , p = 0.005 ; 2,480 + /- 0.234 vs. 2.966 + /- 0.283 liter/min per mm Hg , p = 0.01 , respectively ) . Exercise duration was prolonged from 455 + /- 27 s on placebo to 512 + /- 27 s ( p = 0.001 ) with dihydrocodeine , and peak oxygen consumption increased from 18.0 + /- 0.6 to 19.7 + /- 0.6 ml/kg per min ( p = 0.002 ) . The ventilatory response to exercise , characterized by the regression slope relating minute ventilation to carbon dioxide output , decreased from 34.19 + /- 2.35 to 30.85 + /- 1.91 ( p = 0.01 ) . With dihydrocodeine administration , the change in the modified Borg score for dyspnea was -0.80 ( p = 0.003 ) at 6 min and -0.33 ( p = 0.52 ) at peak exercise , whereas that for fatigue did not change significantly . Arterial oxygen saturation was maintained during exercise despite dihydrocodeine administration ( 99.3 % at rest vs. 98.9 % at peak exercise , p = 0.21 ) . CONCLUSIONS Augmented chemosensitivity is important in the pathophysiology of chronic heart failure . Its suppression with dihydrocodeine was associated with a reduction of exercise ventilation , an improvement in exercise tolerance and a decrease in breathlessness . Pharmacologic modulation of chemosensitivity may benefit patients with chronic heart failure and merits further investigation OBJECTIVE We have shown that the administration of 0.8 mg/kg of morphine ( M ) to patients with COPD result ed in a 20 % increase in the maximum oxygen consumption ( Vo2max ) , but was associated with significant drowsiness and euphoria . The objective of the present study was to ascertain whether lower doses of M alone or in combination with prochlorperazine ( PC ) or promethazine ( P ) could elicit significant increases in exercise tolerance . DESIGN The exercise capacity , psychological status , and reaction times were assessed before and 60 min after the patients received placebo ( PLAC ) , 30 mg M orally , 30 mg M plus 10 mg PC ( M-PC ) , or 30 mg M plus 25 mg P ( M-P ) in a r and omized double-blind crossover study . In a secondary study , nine patients were tested on three separate days before and after receiving PLAC , 25 mg P , or 30 mg M plus 25 mg P. PATIENTS Seven COPD patients ( FEV1=0.99 + /- 0.30 L , Vo2max=990 + /- 315 mL/min ) who were ventilatory-limited . SETTING Veterans Affairs medical center . RESULTS After the patients ingested M-P , the increase in the Vo2max ( 129.0 + /- 104 mL/min ) , the workload ( 10.0 + /- 6.5 W ) and the maximum minute ventilation ( 4.0 + /- 3.9 L/min ) were significantly greater ( p<0.05 ) than after PLAC ingestion ( -4.8 + /- 79 mL/min , 1.4 + /- 6.9 W , and -1.6 + /- 2.4 L/min , respectively ) . Changes after the ingestion of M , P , o r M-PC were intermediate . The M-PC combination adversely affected the patient 's reported mental status ( Bond visual analog scale ) more than the M-P or M regimens . No regimen significantly affected the reaction time . CONCLUSIONS We conclude that the administration of 30 mg of M plus 25 mg of P significantly improves the exercise tolerance of patients with COPD , without significantly impairing the mental capabilities of the subjects . The utility of this regimen over longer time periods needs to be evaluated Systemic opiates may relieve dyspnoea and improve exercise tolerance in patients with chronic obstructive pulmonary disease ( COPD ) . Small doses of inhaled opiates may have similar effects ; however , recent studies have shown no benefit . We studied higher doses of inhaled morphine and measured systemic absorption to determine whether any beneficial actions are local or systemic . Twenty and 40 mg doses and 0.9 % saline were nebulized in a r and omized , double-blind study of 16 patients with stable COPD . Patients performed 6 min walk tests immediately after the nebulized test solution ( Walk 1 ) and again 60 min later ( Walk 2 ) . Arterial oxygen saturation ( Sa , O2 ) , modified Borg dyspnoea score and cardiac frequency were recorded during each walk . There was no difference between placebo and either dose of nebulized morphine on these measurements . The higher dose of nebulized morphine achieved a higher plasma concentration . The highest plasma concentration was measured immediately after nebulization , and this decreased steadily in the hour thereafter ( p<0.002 ) . There was no correlation between the change in walk distance and the change in plasma morphine concentration after either dose of nebulized morphine . We conclude that higher doses of nebulized morphine do not improve exercise endurance or relieve dyspnoea in patients with chronic obstructive pulmonary disease , and that morphine is rapidly absorbed systemically after inhalation BACKGROUND : Inhaled morphine has previously been shown to increase exercise endurance in patients with chronic lung disease . A similar study was performed to determine whether inhaled morphine reduces the sensation of breathlessness in this group of patients . METHODS : A r and omised double blind study on the effect of nebulised morphine on both exercise induced breathlessness and maximum achievable power output using isotonic saline as a control was performed in 10 patients with stable chronic lung disease . Each subject performed a progressive exercise test ( Jones ' stage I ) on an electrically braked cycle ergometer . The work load was increased by 10 watts per minute and subjects exercised to exhaustion . At the end of each minute of exercise patients were asked to rate their degree of breathlessness according to a modified Borg scale . All subjects were r and omised to receive either inhaled morphine sulphate 1 mg/ml ( 5 ml ) or isotonic saline ( 5 ml ) by wet nebulisation . The effect of morphine and saline on the achieved exercise capacity and the development of breathlessness during exercise was tested on separate days . RESULTS : The mean dose of morphine inhaled was 1.24 mg . There was no difference in maximum power output achieved , minute ventilation at maximum power output , nor the degree of breathlessness at maximum power output between the groups treated with morphine and placebo . The degree of breathlessness was related to the power output achieved during exercise by a power function relationship ( mean r : morphine = 0.86 , saline = 0.87 ) . However , there was a wide variation in the sensation for any given power output in both groups . There was no difference in the group mean slopes ( morphine = 1.15 , saline = 1.00 ) or intercepts ( morphine = 0.07 , saline = 0.15 ) in this relationship between the morphine and saline treatment groups . CONCLUSIONS : In patients with severe chronic lung disease inhaled morphine in the doses used in this study does not relieve exercise induced breathlessness nor does it increase maximum power output achieved during progressive exercise The purpose of this placebo-controlled , double-blind , r and omized study was to assess the effect of nebulized morphine on dyspnoea perceived at rest by patients with advanced disease . Seventeen hospital in- patients with disabling dyspnoea received isotonic saline or morphine via nebulization for 10 min through a mouthpiece , combined with oxygen via nasal prongs . On four consecutive days , they were given one of the four following treatments in r and om order : saline with 2 L x min(-1 ) oxygen ; 10 mg morphine with 2 L x min(-1 ) oxygen ; 20 mg morphine with 2 L x min(-1 ) oxygen ; and 10 mg morphine without oxygen ( prongs fixed , no flow ) . Dyspnoea was assessed on a bipolar visual analogue scale ( VAS ) ( -100 % much more short of breath , + 100 % much less short of breath ) , and arterial oxygen saturation ( Sa , O2 ) and respiratory frequency ( fR ) were recorded at the end of nebulization and 10 min later . In 14 subjects who completed the study , mean VAS ratings 10 min after the end of nebulization ranged + 30 to + 43 % , with no significant difference between the four study days ( VAS 20 mg morphine minus VAS saline , 95 % confidence interval ( 95 % CI ) -6 to + 8 % ) . Sa , O2 significantly increased on the 3 days with supplemental oxygen , and remained stable on the zero flow day . Respiratory frequency significantly decreased on the 4 days , with a trend to correlation between VAS rating and parallel change in respiratory frequency ( Spearman 's rank correlation coefficient ( r(s))=0.46 ; p=0.09 ) . We conclude that the subjects benefited from saline or morphine via a placebo effect and /or a nonspecific effect , and that nebulized morphine had no specific effect on dyspnoea Low dose nebulised morphine may relieve dyspnoea through a direct effect on lung afferent nerves . To study this further 11 adult patients with advanced chronic lung disease ( FEV1 range 0.4 - 1.41 ) , whose exercise endurance was limited by dyspnoea , were entered into a double blind , r and omised , crossover study in which low dose morphine or a placebo was inhaled . The effects were assessed by an endurance exercise test at 80 % of maximum work load . One hour after a control endurance test patients inhaled 5 ml of morphine 1 mg/ml or isotonic saline for 12 minutes from a jet nebuliser . An endurance exercise test was repeated 15 minutes later and change in endurance time recorded . The two endurance tests were repeated on a separate day , before and after inhalation of the alternative solution . In all tests 100 % oxygen was inhaled from a dem and valve . The mean ( SD ) increase in endurance time was significantly greater after the subjects had inhaled morphine ( 64.6 ( 115 ) s , 35 % ) than after placebo ( 8.9 ( 55 ) s , 0.8 % ; p less than 0.01 ) . The mean dose of morphine nebulised was 1.7 ( 0.66 ) mg , giving a mean inhaled dose of about 0.6 mg , on the assumption of 30 % retention of the nebulised dose by each patient . No side effects were reported . Possibly small amounts of morphine delivered to the lungs act directly on lung afferent nerves to reduce dyspnoea BACKGROUND --Inhaled nebulised morphine may reduce breathlessness in patients with lung disease , although the results of controlled trials are conflicting . A direct action of morphine on the lung has been postulated . This study aim ed to investigate whether nebulised morphine reduced exercise-induced breathlessness in patients with chronic obstructive pulmonary disease ( COPD ) and to determine if this was a local pulmonary effect or occurred after systemic morphine absorption . METHODS --A double blind , r and omised , crossover study was performed in 12 men with COPD to compare the effects of nebulised morphine ( 10 and 25 mg ) , equivalent intravenous doses ( 1 and 2.5 mg ) , and placebo . Breathlessness ( visual analogue scale ) , ventilation , gas exchange , and exercise endurance were measured during grade d bicycle exercise . RESULTS --None of the treatments altered breathlessness , ventilation , or gas exchange at rest or at any time during exercise , and exercise endurance was unaffected . At peak exercise mean ( 95 % CI ) changes from placebo in ventilation were -0.8 ( -0.57 to 1.1 ) l/min and -0.4 ( -2.8 to 2.0 ) l/min for the highest intravenous and nebulised doses , respectively . For breathlessness equivalent values were + 2 ( -5 to 9 ) and + 1 ( -9 to 11 ) mm . The study was of sufficient power that it is unlikely that a clinical ly important effect was missed . CONCLUSIONS --Nebulised morphine in these doses has no effect on exercise-induced breathlessness . These findings do not support the hypothesis that intrapulmonary opiates modulate the sensation of breathlessness in patients with COPD It has been reported that short-term treatment with relatively high doses of opiates or promethazine causes improvements in dyspnoea and exercise tolerance in patients with chronic airflow obstruction ( CAO ) . This study was design ed to determine whether initial benefits were sustained during chronic administration of codeine or promethazine and to compare the two drugs in terms of their efficacy and possible mechanisms of action . Eleven patients with stable CAO were entered into a double-blind , r and omized cross-over trial in which codeine ( 30 mg four times daily ) or promethazine ( 25 mg four times daily ) were orally administered for 1-month periods . Treatment effects were assessed by spirometry , arterial blood gases , 12-minute walk distance and subjective dyspnoea ratings . A statistically significant increase from the baseline in mean arterial PCO2 at at 24 hours ( P less than 0.01 ) and at 1 month ( P less than 0.05 ) occurred with codeine administration . There was no significant change from baseline for any other measurement with either drug , and no differences were detected between the two treatment arms . Four of the eleven patients did not complete the study ; three of the four experienced worsening of their CAO requiring hospitalization ( two while receiving codeine , one while receiving promethazine ) . We conclude that chronic treatment with either codeine or promethazine provides uncertain benefits to patients with CAO which may not outweigh potential risks The aim of this study was to evaluate whether endogenous opioids are involved in the regulation of breathing pattern and respiratory drive during bronchoconstriction induced by methacholine ( MCh ) . We studied six male asymptomatic asthmatics 18 to 35 yr of age . In a preliminary study we determined the concentration of MCh causing a 60 % fall in FEV1 ( PC60 FEV1 ) . On two subsequent days , we measured breathing pattern , dyspnea sensation ( Borg scale ) , mouth occlusion pressure ( P0.1 ) , and FEV1 before and 10 min after an intravenous injection of either naloxone ( 0.1 mg/kg ) or saline according to a r and omized double-blind crossover design . A MCh concentration equal to the PC60 FEV1 was then inhaled , and measurements were repeated 5 min later . Neither placebo nor naloxone affected baseline breathing pattern , P0.1 , and FEV1 . Naloxone pretreatment did not influence airway response to MCh ; the mean percent fall in FEV1 was 65.9 + /- 1.3 and 64.7 + /- 1.2 % ( mean + /- 1 SE ) on the placebo day and the naloxone day , respectively . After MCh inhalation no significant changes in VE , VT , and breathing frequency occurred when patients received placebo . However , P0.1 increased from 1.48 + /- 0.17 to 3.43 + /- 0.70 cm H2O ( p less than 0.05 ) , and VT/TI fell from 0.66 + /- 0.08 to 0.52 + /- 0.04 L/s ( p less than 0.05 ) . Naloxone pretreatment result ed in an increase in breathing frequency ( from 18.2 + /- 1.7 to 22.8 + /- 2.6 breaths/min ; p less than 0.05 ) and VT/TI ( from 0.58 + /- 0.06 to 0.74 + /- 0.05 L/s ; p less than 0.05 ) after MCh . ( ABSTRACT TRUNCATED AT 250 WORDS A new test for assessing clinical dyspnoea with greater precision has been devised . This involves walking on a treadmill while ventilation is measured and dyspnoea is assessed serially with visual analogue scales . The test has been applied successfully in patients with chronic bronchitis and emphysema and in asthmatic patients . The reproducibility of the test was determined by comparing identical periods of exercise separated by an interval of five days in patients with chronic bronchitis and emphysema . The relationship between dyspnoea and ventilation showed acceptable within-patient reproducibility . The sensitivity of the test was investigated in asthmatic patients by comparing exercise after placebo and after salbutamol which had increased PEFR by a mean of 33 % . After salbutamol , lower breathlessness scores usually occurred for a given level of ventilation and this indicates that the test was sensitive enough to detect an effective treatment . Thus more precise assessment of dyspnoea in patients is feasible and generally reliable . However , a proportion of patients respond unpredictably and it is necessary to apply this test critically and with an appreciation of its limitations Supplementary doses of opioids are recommended to relieve dyspnea in terminally ill cancer patients . We conducted a r and omized continuous sequential clinical trial to evaluate their efficacy . We recruited 33 terminally ill cancer patients from three palliative care centers , all of whom had persistent dyspnea after rest and treatment with oxygen . Patients formed 15 successive pairs matched on route of administration . Within each pair , the order of allocation was r and omly assigned , one patient receiving 25 % , the other 50 % of his 4-hourly opioid dose . Five measurements of dyspnea intensity and respiratory frequency were made during 4 hours of follow-up . For each pair , a preference was attributed to the more effective regimen . The two regimens received an almost equal number of paired preferences ( 8 vs. 7 ) . Overall , both mean dyspnea intensity and respiratory frequency decreased significantly relative to baseline . Dyspnea reduction was relatively greater in patients with initially low and moderate dyspnea intensity . In terminally ill cancer patients with persistent dyspnea , 25 % of the equivalent 4-hourly dose of opioid may be sufficient to reduce both dyspnea intensity and tachypnea for 4 hours BACKGROUND Dyspnea represents a very frequent and distressing symptom in patients with advanced cancer . This study was undertaken to assess the efficacy of morphine on dyspnea and its safety for ventilatory function in elderly advanced cancer patients . PATIENTS AND METHODS Nine elderly patients with dyspnea due to lung involvement were r and omized to receive either morphine subcutaneously ( 5 mg in seven opioid-naïve patients and 3.75 mg in two patients on top of their regular oral dose of 7.5 mg q4 h ) or placebo on day 1 . On day 2 , they were crossed over to receive the alternate treatment . Dyspnea was assessed every fifteen minutes using a visual analogue scale ( VAS : 0 - 100 mm ) and the ordinal scale developed by Borg ( 0 - 10 points ) . Pain , somnolence and anxiety were assessed using VAS . Respiratory effort , respiratory rate and oxygen saturation were also measured repeatedly . RESULTS Mean changes in dyspnea 45 minutes after injection were -25 + /- 10 mm and -1.2 + /- 1.2 points for morphine , versus 0.6 + /- 7.7 mm ( P < 0.01 ) and -0.1 + /- 0.3 points ( P = 0.03 ) for placebo on VAS and Borg scale , respectively . No relevant changes were observed in somnolence , pain , anxiety , respiratory effort and rate , and oxygen saturation . CONCLUSIONS Morphine appears effective for cancer dyspnea , and it does not compromise respiratory function at the dose level used Morphine has been proposed as a treatment for breathlessness in patients with severe chronic obstructive pulmonary disease ( COPD ) , but there is uncertainty as to whether or not it is effective . Orally administered sustained-release morphine was compared with placebo in a r and omized , double-blind , crossover trial with two 6-wk treatment periods separated by a 2-wk washout period . The primary end point was quality of life measured using the Chronic Respiratory Disease Question naire ( CRQ ) . Secondary end points included 6-min walk ( 6MW ) , distance , and breathlessness scores . Sixteen subjects with a mean age 70.7 yr , FEV1 of 0.6 L , and VC of 1.90 L were studied . There was no change in the total CRQ score with either treatment , but the score on the Mastery subscale was significantly worse with morphine ( p = 0.02 ) . The 6MW distance increased by 21 m from the beginning to the end of the placebo treatment period , but it decreased by 35 m with morphine ( p = 0.04 ) . There were no differences between treatments in breathlessness scored on daily diary cards or on the Dyspnea subscale of the CRQ . Almost all the subjects experienced adverse effects related to morphine . Sustained-release morphine was not a useful treatment for breathlessness in these patients with severe COPD Eighteen patients with severe breathlessness due to chronic airflow obstruction completed a r and omised placebo controlled double blind cross over trial of the effect of dihydrocodeine 15 mg on breathlessness , disability , and exercise tolerance . There were three periods of one week each . During the first two weeks patients were instructed to take dihydrocodeine 15 mg or placebo 30 minutes before exercise as required up to three times daily . During the third week patients received either dihydrocodeine or placebo on alternate days . During the weekly dihydrocodeine period patients were more mobile ( pedometer distance increased by 16.8 % ) and less breathless ( daily visual analogue score of breathlessness reduced by 17.8 % ) . This benefit was confirmed by treadmill testing at the end of each treatment period , when maximum distance walked was 16.5 % higher and breathlessness 11.8 % less after dihydrocodeine compared with placebo . Similar benefit in breathlessness occurred during alternate day treatment . No adverse effects were encountered . Dihydrocodeine 15 mg 30 minutes before exercise offers appreciable benefit to patients with severe breathlessness due to chronic airflow obstruction Dyspnea has been defined as an uncomfortable awareness of breathing [ 1 ] . It occurs in approximately 29 % to 74 % of patients with terminal cancer [ 2 , 3 ] and is perceived as one of the most devastating symptoms by the patient and the family . Controlled single-dose trials have suggested that opioids are effective in the management of dyspnea associated with chronic obstructive lung disease [ 4 ] . However , opioids were poorly tolerated in these patients during repeated administration , mostly because of sedation and nausea [ 5 ] . These side effects usually disappear with the development of tolerance and are rarely a cause for discontinuing treatment among the approximately 80 % of terminal cancer patients who receive opioids for pain [ 6 ] . However , the effects of opioids on the dyspnea of cancer have not been the focus of prospect i ve studies . A previous uncontrolled study by our group suggested that subcutaneous morphine was able to decrease the intensity of dyspnea without statistically modifying oxygen saturation , respiratory rate , or the end tidal Paco 2 [ 7 ] . Methods The purpose of this study was to conduct a crossover , placebo-controlled trial to assess the effects of morphine on the intensity of dyspnea in 10 consecutive patients with terminal cancer . The mechanism of dyspnea was progressive lung tumor in 3 patients , lung metastases in 4 patients , pleural effusion in 1 patient , and carcinomatous lymphangitis in 1 patient , respectively . All patients were fully conscious , had normal cognitive status ( score of 24 in the mini-mental state question naire ) [ 8 ] , were complaining of shortness of breath while in bed , and were receiving continuous oxygen using nasal prongs at a rate of 2 to 6 L/min . All patients received intermittent subcutaneous injections of morphine every 4 hours for the management of cancer pain . The morphine dose had not changed for at least 5 days , and all patients had good pain control ( defined as no or mild pain most of the day and 2 extra analgesic doses/day ) . At 10:00 a.m. ( time of their regular morphine dose ) after at least 1 hour of bed rest , patients were r and omized to receive subcutaneous injections of morphine or placebo . On the following day at 10:00 a.m. a crossover was made , and patients received the alternate treatment . Patients received an average dose of 34 12 mg of morphine . This dose was calculated to be 50 % higher than the regularly scheduled dose in order to overcome potential development of tolerance . Dyspnea was assessed using a visual analog scale ( 0 , no shortness of breath ; 100 , worst shortness of breath ) . Pain was assessed at baseline using a visual analog scale ( 0 , no pain ; 100 , worst pain ) . Results Table 1 shows the results 30 , 45 , and 60 minutes after the injection of morphine or placebo . Baseline results were not different between day 1 and day 2 . Improvement ( P < 0.02 ) was seen in the intensity of dyspnea without any change in respiratory rate or oxygen saturation level measured by pulse oximetry . Table 1 . Effect of Morphine and Placebo on Dyspnea , Oxygen Saturation , and Respiratory Rate * After the completion of the study , the patient and the investigator each blindly chose morphine as more effective for the patient 's dyspnea in 9 and 8 patients , chose placebo in 0 and 1 patient , and had no preference in 1 patient and 1 patient , respectively ( P = 0.01 for patients , P = 0.044 for investigators , binomial distribution ) . After study ing the effects of morphine in these initial controlled patients , we used morphine intermittently for dyspnea in 45 consecutive patients with terminal cancer . In all patients , morphine was prescribed on an as needed basis . All patients were already receiving regular morphine for cancer pain . The dose used for dyspnea was the same as the regular dose used for pain . Patients received a total of 312 subcutaneous doses . Good subjective response ( no dyspnea or mild dyspnea ) was documented by the nurse 30 minutes after the injection in 281 patients ( 90 % ) , poor response was documented in 12 patients ( 4 % ) ( moderate or severe dyspnea ) , and the response was not documented in 17 patients ( 5 % ) . No patients had respiratory depression . Discussion Our results suggest that intermittent injections of morphine are safe and effective for the management of dyspnea in terminal cancer . Because our patients also had cancer pain , it is possible that some patients might have perceived less dyspnea after morphine , because it decreased the intensity of pain . An unpleasant sensation ( dyspnea ) could also be heightened by the presence of another unpleasant sensation ( pain ) . However , this probably did not occur , because all patients had stable pain control ( visual analog scale 21 27 on a 0 - 100 scale and had no change in morphine dose for 5 days ) . Future studies should determine the ideal dosage and modality of administration ( as needed compared with regular dosing ) of morphine , the relation between morphine 's effect on pain and the effect on dyspnea , and the safety on the approximately 20 % of terminal cancer patients who are not receiving opioids Recent reports have suggested that low-dose nebulized morphine may improve exercise tolerance in patients with interstitial lung disease ( ILD ) by acting on peripheral opioid-sensitive pulmonary receptors . We therefore examined whether the administration of low-dose nebulized morphine would influence dyspnea or the breathing pattern during exercise of subjects with ILD and improve their exercise performance . Each of six subjects with ILD underwent three maximal incremental cycle ergometer tests , each test separated from the last by at least 3 d. Each exercise test was similar except that 30 min before exercise , the subjects received nebulized saline ( control ) , morphine 2.5 mg , or morphine 5.0 mg , respectively , in double-blinded fashion . No significant differences were noted in exercise duration , maximal workload , or sense of dyspnea at the end of exercise in the control test and the tests with either morphine 2.5 mg or morphine 5.0 mg . Nor were significant differences noted in resting , submaximal , or end-exercise measurements of oxygen uptake ( VO2 ) , carbon dioxide output ( VCO2 ) , end-tidal CO2 ( PETCO2 ) , oxygen saturation ( SaO2 ) , minute ventilation ( VI ) , respiratory frequency ( f ) , tidal volume ( VT ) , or heart rate ( HR ) in the three tests . Low-dose nebulized morphine did not alter the subjects ' breathing pattern or affect the relationship between dyspnea and ventilation during exercise . No significant side effects were noted . The administration of low-dose nebulized morphine to subjects with ILD neither relieves their dyspnea during exercise nor improves their maximal exercise performance Since the relationships between pulmonary function , exercise capacity , and functional state or quality of life are generally weak , a self report question naire has been developed to determine the effect of treatment on quality of life in clinical trials . One hundred patients with chronic airflow limitation were asked how their quality of life was affected by their illness , and how important their symptoms and limitations were . The most frequent and important items were used to construct a question naire evaluating four dimensions : dyspnoea , fatigue , emotional function , and the patient 's feeling of control over the disease ( mastery ) . Reproducibility , tested by repeated administration to patients in a stable condition , was excellent : the coefficient of variation was less than 12 % for all four dimensions . Responsiveness ( sensitivity to change ) was tested by administering the question naire to 13 patients before and after optimisation of their drug treatment and to another 28 before and after participation in a respiratory rehabilitation programme . In both cases large , statistically significant improvements in all four dimensions were noted . Changes in question naire score were correlated with changes in spirometric values , exercise capacity , and patients ' and physicians ' global ratings . Thus it has been shown that the question naire is precise , valid , and responsive . It can therefore serve as a useful disease specific measure of quality of life for clinical trials We measured breathlessness and exercise tolerance in 12 patients with chronic airways obstruction , moderate or severe breathlessness , and low or normal arterial carbon dioxide tension , after the patients received dihydrocodeine , alcohol , caffeine , or placebo ( through double-blind administration ) . Forty-five minutes after ingestion , dihydrocodeine had reduced breathlessness by 20 per cent and increased exercise tolerance by 18 per cent , with a reduction in ventilation and oxygen consumption at submaximal work loads but with no change in spirometric volumes . Oxygen also reduced breathlessness and provided additional benefit to that achieved with dihydrocodeine ( at three hours after ingestion ) when the two were given together : the reduction of breathlessness was 18 per cent with dihydrocodeine ; 22 per cent with oxygen ; and 32 per cent with dihydrocodeine plus oxygen . Alcohol increased forced vital capacity by 9 per cent , and exercise tolerance by 7 per cent . Caffeine had no deleterious effect on breathlessness or exercise tolerance , despite increasing ventilation during rest and exercise . We conclude that opiates may be valuable for the treatment of breathlessness in selected patients ; further evaluation is needed , particularly of the long-term benefits and safety 1 . Methods were devised and evaluated for inducing breathlessness by submaximal grade d exercise in healthy subjects while objective measurements of cardiorespiratory function were made . Breathlessness was assessed with serial visual analogue scales ( VAS ) , but with various measures to enhance repeatability . 2 . A high level of reproducibility was obtained in spite of the subjective nature of the assessment . Individual responses were described by the relationship between breathlessness and ventilation . The sensitivity of the method was demonstrated by the use of inspiratory resistances which disturbed this relationship and caused greater breathlessness for a given level of ventilation . 3 . These methods were applied to six healthy subjects to analyse the effects of acute doses of diazepam and promethazine on breathlessness induced by grade d exercise or by rebreathing carbon dioxide in a double-blind study . 4 . During exercise , diazepam and promethazine did not reduce breathlessness , although there was a minor trend with promethazine . During exposure to elevated levels of carbon dioxide , diazepam and promethazine had no effect on breathlessness . Diazepam and promethazine produced similar levels of sedation , but neither drug had significant effects on the ventilatory response to carbon dioxide . These preliminary findings contrast with those reported for chronic diazepam in ' pink puffers ' . 5 . Raised levels of carbon dioxide caused greater breathlessness in relation to ventilation than did exercise |
12,002 | 30,254,842 | Interestingly , recent evidence suggests that MR signaling is increased by Rac1 activation , independent of lig and binding to MR , and that Rac1 was shown to be activated by angiotensin II and diabetic conditions [ 5 ] .
There are many convincing data suggesting that MRAs may provide additional reno-protective effects in patients experiencing the aldosterone escape phenomenon during RAS blockade treatment [ 6 ] . | ed that inhibition of the renin-angiotensin-aldosterone system ( RAAS ) has a widespread protective role in various tissues .
Although angiotensin II is the primary mediator of RAAS in the kidney , the effects of blockade with angiotensin-converting enzyme inhibitors ( ACEi ) or angiotensin II receptor antagonists ( ARB ) are limited with respect to prevention of end-stage renal disease .
Previous studies have shown that administration of mineralocorticoid receptor antagonists ( MRAs ) including spironolactone and eplerenone has beneficial effects in a variety of renal injury animal models , such as unilateral ureteral obstruction , cyclosporine-induced nephrotoxicity , and hypertensive renal injury [ 1 ] .
In addition , recent observations also demonstrate that MRAs improved renal function in animal models of transplant vasculopathy and ischemia reperfusion injury [ 2 ] .
Furthermore , many animal and clinical studies showed that MRAs have additional benefit independent of renin-angiotensin system ( RAS ) blockade in diabetic kidney disease [ 3 ] .
Aldosterone induces tissue injury by inflammation , oxidative stress , and fibrosis mechanisms , and MRAs may prevent renal fibrosis via suppression of transforming growth factor β1 , plasminogen activator inhibitor-1 , oxidative stress , and endothelial dysfunction .
Mineralocorticoid receptors ( MRs ) are widely expressed in endothelial cells , mesangial cells , podocytes , and renal fibroblasts as well as distal tubular cells , and accumulating evidence suggests the important role of MRs in these cells as a mediator of renal injury [ 4 ] .
Altogether , these data suggest the possibility that MR signaling may be activated by several mechanisms , including increased aldosterone concentration , upregulation of MRs , and activation of Rac1 in the kidney , all of which have been reported as pathological mediators in chronic kidney disease ( CKD ) .
The major barrier for using MRAs in more advanced stages in CKD patients is the safety concern about hyperkalemia .
Spironolactone and eplerenone are steroidal MRAs that have side effects including significant hyperkalemia .
Recently , a highly selective and potent non-steroidal MRA ( finerenone ) has Mineralocorticoid receptor blockade for | Aims Mineralocorticoid receptor antagonists ( MRAs ) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction ( HFrEF ) , but their use is limited by hyperkalaemia and /or worsening renal function ( WRF ) . BAY 94 - 8862 is a highly selective and strongly potent non-steroidal MRA . We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease ( CKD ) . Methods and results This r and omized , controlled , phase II trial consisted of two parts . In part A , the safety and tolerability of oral BAY 94 - 8862 [ 2.5 , 5 , or 10 mg once daily ( q.d . ) ] was assessed in 65 patients with HFrEF and mild CKD . In part B , BAY 94 - 8862 ( 2.5 , 5 , or 10 mg q.d . , or 5 mg twice daily ) was compared with placebo and open-label spironolactone ( 25 or 50 mg/day ) in 392 patients with HFrEF and moderate CKD . BAY 94 - 8862 was associated with significantly smaller mean increases in serum potassium concentration than spironolactone ( 0.04–0.30 and 0.45 mmol/L , respectively , P < 0.0001–0.0107 ) and lower incidences of hyperkalaemia ( 5.3 and 12.7 % , respectively , P = 0.048 ) and WRF . BAY 94 - 8862 decreased the levels of B-type natriuretic peptide ( BNP ) , amino-terminal proBNP , and albuminuria at least as much as spironolactone . Adverse events related to BAY 94 - 8862 were infrequent and mostly mild . Conclusion In patients with HFrEF and moderate CKD , BAY 94 - 8862 5–10 mg/day was at least as effective as spironolactone 25 or 50 mg/day in decreasing biomarkers of haemodynamic stress , but it was associated with lower incidences of hyperkalaemia and WRF BACKGROUND We evaluated the role of aldosterone as a mediator of renal inflammation and fibrosis in a rat model of aldosterone/salt hypertension using the selective aldosterone blocker , eplerenone . METHODS Unnephrectomized , Sprague-Dawley rats were given 1 % NaCl ( salt ) to drink and r and omized to receive treatment for 28 days : vehicle infusion ( control ) ; 0.75 microg/hour aldosterone subcutaneous infusion ; or aldosterone infusion + 100 mg/kg/day oral dose of eplerenone . Blood pressure and urinary albumin were measured and kidneys were evaluated histologically . Renal injury , inflammation , and fibrosis were assessed by immunohistochemistry , in situ hybridization , and reverse transcription-polymerase chain reaction ( RT-PCR ) . RESULTS Aldosterone/salt induced severe hypertension compared to controls ( 220 + /- 4 mm Hg vs. 131 + /- 4 mm Hg , P < 0.05 ) , which was partially attenuated by eplerenone ( 179 + /- 4 mm Hg , P < 0.05 ) . In aldosterone/salt treated rats , renal histopathologic evaluation revealed severe vascular and glomerular sclerosis , fibrinoid necrosis and thrombosis , interstitial leukocyte infiltration , and tubular damage and regeneration . Aldosterone/salt increased circulating osteopontin ( 925.0 + /- 80.2 ng/mL vs. 53.6 + /- 6.3 ng/mL ) and albuminuria ( 75.8 + /- 10.9 mg/24 hours vs. 13.2 + /- 3.0 mg/24 hours ) compared to controls and increased expression of proinflammatory molecules . Treatment with eplerenone reduced systemic osteopontin ( 58.3 + /- 4.2 ng/mL ) , albuminuria ( 41.5 + /- 7.2 mg/24 hours ) , and proinflammatory gene expression : osteopontin ( OPN ) , monocyte chemoattractant protein-1 ( MCP-1 ) , interleukin-6 ( IL-6 ) , and interleukin-1beta ( IL-1beta ) . CONCLUSION These findings indicate that aldosterone/salt-induced renal injury and fibrosis has inflammatory components involving macrophage infiltration and cytokine up-regulation . Attenuation of renal damage and inflammation by eplerenone supports the protective effects of aldosterone blockade in hypertensive renal disease IMPORTANCE Steroidal mineralocorticoid receptor antagonists , when added to a renin-angiotensin system blocker , further reduce proteinuria in patients with chronic kidney disease but may be underused because of a high risk of adverse events . OBJECTIVE To evaluate the safety and efficacy of different oral doses of the nonsteroidal mineralocorticoid receptor antagonist finerenone , given for 90 days to patients with diabetes and high or very high albuminuria who are receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled , parallel-group study conducted at 148 sites in 23 countries . Patients were recruited from June 2013 to February 2014 and the study was completed in August 2014 . Of 1501 screened patients , 823 were r and omized and 821 received study drug . INTERVENTIONS Participants were r and omly assigned to receive oral , once-daily finerenone ( 1.25 mg/d , n = 96 ; 2.5 mg/d , n = 92 ; 5 mg/d , n = 100 ; 7.5 mg/d , n = 97 ; 10 mg/d , n = 98 ; 15 mg/d , n = 125 ; and 25 mg/d , n = 119 ) or matching placebo ( n = 94 ) for 90 days . MAIN OUTCOMES AND MEASURES The primary outcome was the ratio of the urinary albumin-creatinine ratio ( UACR ) at day 90 vs at baseline . Safety end points were changes from baseline in serum potassium and estimated glomerular filtration rate . RESULTS The mean age of the participants was 64.2 years ; 78 % were male . At baseline , 36.7 % of patients treated had very high albuminuria ( UACR ≥300 mg/g ) and 40.0 % had an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or lower . Finerenone demonstrated a dose-dependent reduction in UACR . The primary outcome , the placebo-corrected mean ratio of the UACR at day 90 relative to baseline , was reduced in the finerenone 7.5- , 10- , 15- , and 20-mg/d groups ( for 7.5 mg/d , 0.79 [ 90 % CI , 0.68 - 0.91 ; P = .004 ] ; for 10 mg/d , 0.76 [ 90 % CI , 0.65 - 0.88 ; P = .001 ] ; for 15 mg/d , 0.67 [ 90 % CI , 0.58 - 0.77 ; P<.001 ] ; for 20 mg/d , 0.62 [ 90 % CI , 0.54 - 0.72 ; P < .001 ] ) . The prespecified secondary outcome of hyperkalemia leading to discontinuation was not observed in the placebo and finerenone 10-mg/d groups ; incidences in the finerenone 7.5- , 15- , and 20-mg/d groups were 2.1 % , 3.2 % , and 1.7 % , respectively . There were no differences in the incidence of the prespecified secondary outcome of an estimated glomerular filtration rate decrease of 30 % or more or in incidences of adverse events and serious adverse events between the placebo and finerenone groups . CONCLUSIONS AND RELEVANCE Among patients with diabetic nephropathy , most receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker , the addition of finerenone compared with placebo result ed in improvement in the urinary albumin-creatinine ratio . Further trials are needed to compare finerenone with other active medications . TRIAL REGISTRATION clinical trials.gov Identifier : NCT1874431 |
12,003 | 30,651,097 | Mixed effects of video game intervention on outcome were found , with conflicting evidence across studies .
Studies that reported on feasibility found most children enjoyed and adhered to the video game interventions . | Background Children with developmental coordination disorder ( DCD ) experience a range of difficulties that can potentially limit their academic , social and physical ability .
Recent research has developed interventions that aim to improve motor outcomes in a variety of paediatric cohorts using video gaming equipment .
Therefore , we aim ed to systematic ally review the literature on virtual reality or video game interventions that aim to improve motor outcomes in children with DCD . | BACKGROUND Impaired motor development can significantly affect a child 's life and may result in an increased risk of a range of physical and psychological disorders . Active video game ( AVG ) interventions have been demonstrated to enhance motor skills in children with Developmental Coordination Disorder ( DCD ) ; however a home-based intervention has not been assessed . OBJECTIVES The primary aim of this study was to compare the changes in motor coordination between a 16 week period of AVG use , with 16 weeks of normal activities ( NAG ) . The secondary aim was to compare the child and parent perceptions of their physical performance between the AVG and NAG conditions . METHODS Twenty-one 9 - 12 year olds ( 10 males ) were confirmed to be at risk of DCD ( ⩽ 16th percentile Movement Assessment Battery for Children-2nd edition ( MABC-2 ) and ⩽ 15th percentile Developmental Coordination Disorder Question naire ( DCDQ ) ) and participated in this crossover r and omised and controlled trial . Data was collected at study entry , after the first 16 week condition and following the final 16 week condition , including ; ( 1 ) the MABC-2 , ( 2 ) three-dimensional motion analysis of single leg balance and finger-nose tasks , and ( 3 ) parent perception of physical skills . Participant perception of physical skills was collected only after the first and second conditions . RESULTS There was no significant difference between AVG and NAG for any of the primary variables including the MABC-2 , balance centre-of-mass path distance and finger-nose path distance . There was no significant intervention effect for secondary measures of motor coordination ; however the children perceived their motor skills to be significantly enhanced as a result of the AVG intervention in comparison to the period of no intervention . CONCLUSION A 16 week home based AVG intervention did not enhance motor skills in children with DCD , although they perceived their physical skills to be significantly improved . TRIAL REGISTRATION Australia and New Zeal and Clinical trials Registry ( ACTRN 12611000400965 ) BACKGROUND Little is known about the influence of practice schedules on motor learning and skills transfer in children with and without developmental coordination disorder ( DCD ) . Underst and ing how practice schedules affect motor learning is necessary for motor skills development and rehabilitation . AIMS The study investigated whether active video games ( exergames ) training delivered under variable practice led to better learning and transfer than repetitive practice . METHODS AND PROCEDURES 111 children aged 6 - 10 years ( M=8.0 , SD=1.0 ) with no active exergaming experience were r and omized to receive exergames training delivered under variable ( Variable Game Group ( VGG ) , n=56 ) or repetitive practice schedule ( Repetitive Game Group ( RGG ) , n=55 ) . Half the participants were identified as DCD using the DSM-5 criteria , while the rest were typically developing ( TD ) , age-matched children . Both groups participated in two 20min sessions per week for 5 weeks . OUTCOMES AND RESULTS Both participant groups ( TD and DCD ) improved equally well on game performance . There was no significant difference in positive transfer to balance tasks between practice schedules ( Repetitive and Variable ) and participant groups ( TD and DCD ) . CONCLUSIONS AND IMPLICATION S Children with and without DCD learn balance skills quite well when exposed to exergames . Gains in learning and transfer are similar regardless of the form of practice schedule employed . WHAT THIS PAPER ADDS This is the first paper to compare the effect of practice schedules on learning in children with DCD and those with typical development . No differences in motor learning were found between repetitive and variable practice schedules . When children with and without DCD spend the same amount of time on exergames , they do not show any differences in acquisition of motor skills . Transfer of motor skills is similar in children with and without DCD regardless of differences in practice schedules Background Adolescents with low motor competence participate less in physical activity and tend to exhibit decreased physical fitness compared to their peers with high motor competence . It is therefore essential to identify new methods of enhancing physical fitness in this population . Active video games ( AVG ) have been shown to improve motor performance , yet investigations of its impact on physical fitness are limited . The objective of this study was to examine the impact of the grade d Wii protocol in adolescent girls with probable Developmental Coordination Disorder ( p-DCD ) . Methods A single-group pre-post design was conducted to assess the impact of a newly developed Wii protocol in adolescent girls attending school in a low income community of Cape Town , South Africa . Sixteen participants ( aged 13 - 16 years ) with p-DCD ( ≤16th percentile on the MABC-2 test ) were recruited . Participants received 45 min Wii training for 14 weeks . Outcome measures included the six-minute walk distance and repeated sprint ability . Information on heart rate , enjoyment and perceived exertion ratings were also collected . Results Significant improvements in aerobic and anaerobic fitness were observed . The participants reported high enjoyment scores and low perceived exertion ratings . The grade d Wii protocol was easily adaptable and required little re sources ( space , equipment and expertise ) to administer . Conclusions The findings provide preliminary evidence to support the use of the grade d Wii protocol for promoting physical fitness in adolescent girls with p-DCD . Further studies are needed to confirm these results and to vali date the clinical efficacy of the protocol in a larger sample with a more robust design The purpose of this study was to investigate the effects of training with the Wii-balance board on balance and balance-related skills of children with poor motor performance . Twenty-nine children ( 23 boys , 6 girls ; aged 7 - 12 years ) participated in this study and were r and omly assigned to an experimental and control group . All children scored below the 16th percentile on a st and ardized test of motor ability and balance skills ( Movement Assessment Battery for children ( M-ABC-2 ) ) . Before and after a six-week Wii-intervention ( M=8h , 22 min , SD=53 min ) , the balance skills of the experimental group and control group were measured with the M-ABC-2 and the Bruininks-Oseretsky test of motor proficiency ( BOT-2 ) . Both groups improved on all tests . The M-ABC-2 and the BOT-2 total balance-scores of the experimental group improved significantly from pre to post intervention , whereas those of the control group showed no significant progress . This result ed in significant interaction-effects , favoring the experimental children . No transfer-effects of the intervention on balance-related skills were demonstrated . Our findings showed that the Wii-balance board is an effective intervention for children with poor balance control . Further development and investigation of the intervention could be directed toward the implementation of the newly acquired balance-skills in daily life Objective Transfer of motor skills is the ultimate goal of motor training in rehabilitation practice . In children with Developmental Coordination Disorder ( DCD ) , very little is known about how skills are transferred from training situations to real life context s. In this study we examined the influence of two types of practice on transfer of motor skills acquired in a virtual reality ( VR ) environment . Method One hundred and eleven children with DCD and their typically developing ( TD ) peers , aged 6–10 years ( M = 8.0 SD = 1.0 ) were r and omly assigned to either variable ( n = 56 ) or repetitive practice ( n = 55 ) . Participants in the repetitive practice played the same exergame ( ski slalom ) twice weekly for 20 minutes , over a period of 5 weeks , while those in the variable group played 10 different games . Motor skills such as balance tasks ( hopping ) , running and agility tasks , ball skills and functional activities were evaluated before and after 5 weeks of training . Results ANOVA repeated measures indicated that both DCD and TD children demonstrated transfer effects to real life skills with identical and non-identical elements at exactly the same rate , irrespective of the type of practice they were assigned to . Conclusion Based on these findings , we conclude that motor skills acquired in the VR environment , transfers to real world context s in similar proportions for both TD and DCD children . The type of practice adopted does not seem to influence children ’s ability to transfer skills acquired in an exergame to life situations but the number of identical elements does Neuromotor Task Training ( NTT ) and Nintendo Wii Fit Training ( Wii training ) are both task-based interventions used to improve performance in children with motor coordination problems . The aim of this study was to compare the efficacy of these two interventions on the motor performance , isometric strength and cardiorespiratory fitness ( aerobic and anaerobic capacity ) of children with Developmental Coordination Disorder ( DCD ) attending mainstream schools in a low-income setting . A pragmatic , quasi-experimental study design was utilized . Children between the ages of 6 - 10 years , who scored at or below the 16th percentile on the Movement Assessment Battery for Children-2 ( MABC-2 ) and whose teacher reported a functional motor problem , were allocated to either NTT ( n=37 ) or Wii training ( n=19 ) groups depending on school of attendance . The MABC-2 , a h and -held dynamometer , the Functional Strength Measure , the Muscle Power Sprint Test and the 20 m Shuttle Run Test were used to assess performance at baseline and after the intervention . The main findings show that the mean motor performance scores of both groups improved over the study period . However , significant differences in improvement were detected between groups , with the NTT group showing greater improvement in motor performance , functional strength and cardiorespiratory fitness . No improvements in isometric strength were seen in either group . The Wii training group showed significant improvement in anaerobic performance . This study provides evidence to support the use of both the Wii Training and NTT for children with DCD . However , in comparison to Wii training , the NTT approach yields superior results across measures of motor proficiency , cardiorespiratory fitness and functional strength . The decision to use either approach may be influenced by re sources and time constraints 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 OBJECTIVES Physical and occupational therapists have started to use the Nintendo Wii ™ gaming system with adults and children as part of their regular treatment . Despite the growing use of the Wii and trend towards evidence -based practice , limited evidence is available on the effectiveness of virtual reality using the Wii for children with developmental delay . The purpose of this study was to determine the feasibility and preliminary effectiveness of a low-cost gaming system for young children with developmental delay . STUDY DESIGN Single-blind , r and omised controlled trial . PARTICIPANTS AND SETTING Forty children with developmental delay ( age 39 to 58 months ) who attended a segregated or integrated preschool participated in this study . All children 's parents read and signed an informed consent form approved by the institutional review board . Children were assigned at r and om to an experimental ( Wii ) group ( n=20 ) or a control group ( n=20 ) . INTERVENTION Two weekly sessions for 10 weeks using Nintendo Wii Sports ™ and Nintendo Wii Fit ™ , including balance , strength training and aerobics games . MAIN OUTCOME MEASURES Participants were evaluated 1 week before and 1 week after the programme by a blinded investigator . Primary outcomes were gait speed , timed up and go test , single leg stance test , five-times-sit-to-st and test , timed up and down stairs test , 2-minute walk test and grip strength . The Gross Motor Function Measure ( GMFM ) was used to assess gross motor skills . RESULTS The two groups were homogenous regarding all parameters at baseline . The Wii training was feasible and enjoyable for those in the experimental group . There were no adverse effects or injuries reported over 267 training sessions . Comparison of groups following the intervention indicated that the experimental group showed significant improvements compared with the control group in single leg stance test { mean difference 1.03 [ st and ard deviation ( SD ) 1.7 ] , 95 % confidence interval ( CI ) 0.2 to 1.9 ; P=0.017 } , right grip strength [ mean difference 1.11 ( SD 1.84 ) , 95 % CI 0.15 to 2.06 ; P=0.024 ] and left grip strength [ mean difference 0.90 ( SD 1.67 ) , 95 % CI 0.03 to 1.77 ; P=0.043 ] . Although changes in other outcome measures were not significant between the study groups , there were trends towards greater improvements in the experimental group compared with the control group . CONCLUSION This study supports use of the Wii as a feasible , safe and potentially effective therapeutic tool to augment the rehabilitation of young children with developmental delay . The potential application of the Wii to increase the intensity of therapy or as a rehabilitation tool in children 's homes and rural setting s is an area worthy of investigation . The promising results of this study suggest that further studies are warranted to vali date the potential benefits of a low-cost commercially available gaming system as a treatment strategy to supplement rehabilitation of children with disabilities BACKGROUND Children with Developmental Co-ordination Disorder ( DCD ) experience poor motor and psychosocial outcomes . Interventions are often limited within the healthcare system , and little is known about how technology might be used within schools or homes to promote the motor skills and /or psychosocial development of these children . This study aim ed to evaluate whether short , regular school-based sessions of movement experience using a commercially available home video game console ( Nintendo 's Wii Fit ) would lead to benefits in both motor and psychosocial domains in children with DCD . METHODS A r and omized crossover controlled trial of children with movement difficulties/DCD was conducted . Children were r and omly assigned to an intervention ( n = 10 ) or comparison ( n = 8) group . The intervention group spent 10 min thrice weekly for 1 month using Wii Fit during the lunch break , while the comparison group took part in their regular Jump Ahead programme . Pre- and post-intervention assessment s considered motor proficiency , self-perceived ability and satisfaction and parental assessment of emotional and behavioural problems . RESULTS Significant gains were seen in motor proficiency , the child 's perception of his/her motor ability and reported emotional well-being for many , but not all children . CONCLUSIONS This study provides preliminary evidence to support the use of the Wii Fit within therapeutic programmes for children with movement difficulties . This simple , popular intervention represents a plausible method to support children 's motor and psychosocial development . It is not possible from our data to say which children are most likely to benefit from such a programme and particularly what the dose and duration should be . Further research is required to inform across these and other questions regarding the implementation of virtual reality technologies in therapeutic services for children with movement difficulties BACKGROUND Children with developmental coordination disorder ( DCD ) are highly inactive and sedentary . The purpose of this study was to assess the impact of a home-based active video game intervention on objective ly measured physical activity and sedentary behaviour in children at risk for DCD . METHODS In a crossover r and omized clinical trial , 21 children ( mean age 11.0 , SD 1.0 ; n = 11 girls ) in Perth , Western Australia participated in two 16-week periods : no active video games ( AVGs ) control period and AVGs intervention period . Two active input consoles were provided to participants along with a selection of non-violent AVGs for participants to play at home . Participants wore accelerometers at baseline and following each period to determine minutes of sedentary , light , moderate and vigorous times in addition to self-reported types of activities in a diary . Linear mixed models , adjusted for the order of periods , compared physical activity and sedentary time during the last week of each period . RESULTS There were no significant differences between the intervention and control periods in time spent in sedentary ( decrease of -1.0 min/day during the intervention period , 95%CI -12.1 , 10.1 ) , light ( increase of 2.2 min/day , 95%CI -8.8 , 13.2 ) , moderate ( decrease of 0.7 min/day , 95%CI -4.6 , 3.3 ) or vigorous ( decrease of -0.6 min/day , 95%CI -1.6 , 0.4 ) . CONCLUSIONS Among children at risk for DCD , participating in this AVG intervention did not improve objective ly measured physical activity and sedentary time |
12,004 | 31,209,562 | Furthermore , there were no significant differences between lasers and bipolar technology in the maximum flow rate ( Qmax ) and international prostate symptom score ( IPSS ) at a minimum of 3 months after treatment .
Complications , including urethral stricture , urinary incontinence , urinary tract infection , re-catheterization and blood transfusion , did not significantly differ between lasers and bipolar technology .
Conclusion Early efficacy and safety profiles were comparable between bipolar and laser treatments .
Differences were observed in terms of smaller reduction in Hb , shorter catheterization duration and shorter hospital stay in favor of lasers .
However , the smaller reduction in Hb , with lasers , did not translate into reduced transfusion requirements . | Purpose To systematic ally review studies comparing the overall efficacy and safety of lasers and bipolar technology for the transurethral treatment of benign prostatic enlargement ( BPE ) . | The objective of this study is to compare the efficacy and safety of diode laser enucleation of the prostate ( DiLEP ) with plasmakinetic enucleation of the prostate ( PKEP ) for symptomatic benign prostatic hyperplasia ( BPH ) patients with large prostate ( volume > 80 ml ) . From January 2013 to June 2014 , 80 consecutive patients were r and omized treated with DiLEP ( n = 40 ) or PKEP ( n = 40 ) . Perioperative and postoperative outcome data were assessed during a 1-year follow-up . There were no significant preoperative differences between the two surgical groups . The mean prostate volumes in the DiLEP and PKEP groups were 98.6 and 93.3 ml , respectively . DiLEP was equivalent to PKEP in improvement in International Prostate Symptom Score ( IPSS ) , quality of life scores , and maximum flow rate . Compared with PKEP , patients treated with DiLEP showed a lower risk of blood loss ( P < 0.01 ) , shorter bladder irrigation and catheterization times ( P < 0.01 ) , as well as shorter hospital stays ( P < 0.01 ) . Moreover , the DiLEP group was significantly superior to bipolar plasmakinetic group in the irritative symptoms . However , the operation time of the DiLEP group was longer than that of PKEP group ( P = 0.02 ) . Both DiLEP and PKEP are safe and effective methods for the treatment of BPH in large prostates ( volume > 80 ml ) . Compared with PKEP , DiLEP provides a decreased risk of hemorrhage , reduced bladder irrigation , and catheterization times , as well as shorter hospital stays Purpose Bipolar endoscopic enucleation of the prostate ( BEEP ) was recommended by the 2016 EAU guidelines as the first choice of surgical treatment in men with a substantially enlarged prostate and moderate-to-severe lower urinary tract symptoms . The main aim of this study was to compare a modified diode laser enucleation of the prostate ( DiLEP ) to BEEP . Methods A total of 114 patients with prostate ( 20–160 mL ) were r and omized 1:1 into either DiLEP or BEEP in a dual-centre , non-inferiority- design r and omized-controlled trial . The primary outcomes included Qmax and IPSS at 12 months . Non-inferiority was evaluated by comparing the two-sided 95 % CI for the mean differences of Qmax and IPSS . Secondary endpoints included other perioperative parameters , postoperative micturition variables , and complication rate . Results A total of 111 patients ( 97 % ) had completed the intent-to-treat analysis , The results showed that DiLEP was comparable to BEEP regarding Qmax ( 28.0 ± 7.0 vs. 28.1 ± 7.2 mL/s ) and IPSS ( 3.0 ± 2.2 vs. 2.9 ± 2.6 ) at 12 months , the non-inferiority was met for both Qmax and IPSS . There were also no significant difference between two groups regarding tissue removal rate ( 71.8 vs. 73.8 % ) , hemoglobin decrease ( 0.33 ± 0.66 vs. 0.36 ± 0.75 g/dL ) , sodium decrease ( 1.0 ± 2.7 vs. 0.3 ± 2.9 mmol/L ) , and Clavien III complications ( 5.3 vs. 1.8 % ) at 12 months . Conclusions This DiLEP is an anatomical endoscopic enucleation technique for the treatment of benign prostatic hyperplasia , it is non-inferior to BEEP regarding Qmax and IPSS at 12 months postoperatively PURPOSE To compare the safety and efficacy of thulium laser enucleation of the prostate ( ThuLEP ) with plasmakinetic enucleation of the prostate ( PKEP ) . METHODS A total of 127 patients with benign prostatic hyperplasia ( BPH ) were r and omized to either ThuLEP ( n = 61 ) or PKEP ( n = 66 ) . All patients were assessed preoperatively and followed up at 3 , 6 , and 12 months postoperatively . Baseline characteristics of the patients , perioperative data , postoperative outcomes , and complications were recorded . RESULTS The decrease in hemoglobin level and the catheter time were statistically significantly lower in the ThuLEP group compared with the PKEP group ( 0.80 ± 0.49 vs 0.99 ± 0.52 , p = 0.037 , and 1.85 ± 0.94 vs 2.28 ± 1.34 , p = 0.042 ) . There were no statistical differences in complications between the two groups ( p > 0.05 ) . There was a significant improvement in 3 , 6 , and 12 months ' parameters compared with preoperative values ( p < 0.001 ) . Assessment at the 12-month follow-up showed no difference in urinary parameters between the two groups . CONCLUSIONS ThuLEP and PKEP are both safe and efficient procedures for the treatment of patients with BPH . Compared with PKEP , ThuLEP provided less risk of hemorrhage and shorter catheter time , although the differences may be of little clinical relevance . Further well- design ed trials with extended follow-up and larger sample size are needed to draw final conclusions about the efficacy of the two procedures OBJECTIVE To compare the clinical outcomes between thulium laser transurethral enucleation of the prostate ( ThuLEP ) and plasmakinetic bipolar resection of the prostate ( PKRP ) for treating benign prostatic hyperplasia ( BPH ) in a prospect i ve r and omized trial with 18 months of follow-up . METHODS The study r and omized 158 consecutive patients with BPH to ThuLEP ( n = 79 ) or PKRP ( n = 79 ) . All patients were evaluated preoperatively and at 1 , 3 , 6 , 12 , and 18 months after surgery by International Prostate Symptom Score ( IPSS ) , quality of life score ( QOLS ) , maximum flow rate ( Qmax ) , and postvoid residual urine volume ( PVR ) . RESULTS The 79 patients in each study arm each showed no significant difference in preoperative parameters . Compared with PKRP , ThuLEP required a longer operation time ( 65.4 vs 47.4 minutes , P = .022 ) but result ed in less hemoglobin decrease ( 0.15 vs 0.30 g/dL , P = .045 ) . ThuLEP also needed less catheterization time ( 2.1 vs 3.5 days , P = .031 ) , irrigation volume ( 12.4 vs 27.2 L , P = .022 ) , and hospital stay ( 2.5 vs 4.6 days , P = .026 ) . During the 1 , 3 , 6 , 12 , and 18 months of follow-up , the procedures did not demonstrate a significant difference in Qmax , IPSS , PVR , and QOLS . CONCLUSION ThuLEP and PKRP both relieve lower urinary tract symptoms equally , with high efficacy and safety . ThuLEP was statistically superior to PKRP in blood loss , catheterization time , irrigation volume , and hospital stay but inferior to PKRP in operation time . However , procedures did not differ significantly in Qmax , IPSS , PVR , and QOLS through the 18 months of follow-up Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more To evaluate the safety and efficacy of plasmakinetic enucleation of the prostate ( PKEP ) for the treatment of symptomatic benign prostatic hyperplasia ( BPH ) compared with 160-W lithium triboride laser photoselective vaporization of the prostate ( PVP ) . From February 2011 to July 2012 , a prospect i ve nonr and omized study was performed . One-hundred one patients underwent PKEP , and 110 underwent PVP . No severe intraoperative complications were recorded , and none of the patients in either group required a blood transfusion . Shorter catheterization time ( 38.14 ± 23.64 h vs 72.54 ± 28.38 h , P < 0.001 ) and hospitalization ( 2.32 ± 1.25 days vs 4.07 ± 1.23 days , P < 0.001 ) were recorded in the PVP group . At 12-month postoperatively , the PKEP group had a maintained and statistically improvement in International Prostate Symptom Score ( IPSS ) ( 4.07 ± 2.07 vs 5.00 ± 2.10 ; P < 0.001 ) , quality of life ( QoL ) ( 1.08 ± 0.72 vs 1.35 ± 0.72 ; P= 0.007 ) , maximal urinary flow rate ( Qmax ) ( 24.75 ± 5.87 ml s−1 vs 22.03 ± 5.04 ml s−1 ; P < 0.001 ) , postvoid residual urine volume ( PVR ) ( 14.29 ± 6.97 ml vs 17.00 ± 6.11 ml ; P= 0.001 ) , and prostate-specific antigen ( PSA ) value ( 0.78 ± 0.57 ng ml−1 vs 1.27 ± 1.07 ng ml−1 ; P < 0.001 ) . Both PKEP and PVP relieve low urinary tract symptoms ( LUTS ) due to BPH with low complication rates . PKEP can completely remove prostatic adenoma while the total amount of tissue removed by PVP is less than that can be removed by PKEP . Based on our study of the follow-up , PKEP provides better postoperative outcomes than PVP PURPOSE Transurethral resection of the prostate has for decades been the st and ard surgical therapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia , the most common benign neoplasm in men . To generate a contemporary reference for evolving medical and minimally invasive therapies we analyzed complications and immediate outcomes of transurethral prostate resection in a statewide multicenter study . MATERIAL S AND METHODS We prospect ively evaluated 10,654 patients undergoing transurethral prostate resection in the state of Bavaria , Germany from January 1 , 2002 until December 31 , 2003 . Case records containing 54 items concerning preoperative status , operation details , complications and immediate outcome , were recorded for each patient . RESULTS The mortality rate for transurethral prostate resection was 0.10 % . The cumulative short-term morbidity rate was 11.1 % . The most relevant complications were failure to void ( 5.8 % ) , surgical revision ( 5.6 % ) , significant urinary tract infection ( 3.6 % ) , bleeding requiring transfusions ( 2.9 % ) and transurethral resection syndrome ( 1.4 % ) . The resected tissue averaged 28.4 gm . Incidental carcinoma of the prostate was diagnosed by histological examination in 9.8 % of patients . Urinary peak flow rate increased significantly to 21.6 + /- 9.4 ml per second ( baseline 10.4 + /- 6.8 ml per second , 1 tail p < 0.0001 ) , while post-void residual decreased to 31.1 + /- 73.0 ml ( baseline 180.3 + /- 296.9 ml , 1-tail p < 0.0001 ) . CONCLUSIONS In a large scale evaluation comprising 44 mostly nonacademic urological departments in Bavaria , unique real-world data for transurethral prostate resection were prospect ively generated . This most contemporary information should be of use to potential patients and facilitate subsumption of emerging surgical and nonsurgical benign prostatic hyperplasia treatment options PURPOSE We compared plasmakinetic resection with holmium laser enucleation of the prostate for the treatment of benign prostatic hyperplasia by analyzing 2-year followup data from a prospect i ve r and omized clinical trial . MATERIAL S AND METHODS A total of 280 patients were r and omly treated with plasmakinetic resection or holmium laser enucleation of the prostate . Perioperative and postoperative outcome data were obtained during a 2-year followup . RESULTS No significant differences between the 2 surgical groups were observed in the preoperative data . Both groups displayed significant improvements after surgery . However , we identified no significant differences between the 2 groups in the 2-year followup data for I-PSS ( International Prostate Symptom Score ) , quality of life scores or maximum flow rate values . Patients in the holmium laser enucleation group displayed a lower risk of hemorrhage , shorter bladder irrigation and catheter times , and shorter hospital stays . A larger amount of prostate tissue was retrieved in the holmium laser enucleation group , but the operation time was longer for this group than for the plasmakinetic resection group . CONCLUSIONS Plasmakinetic resection and holmium laser enucleation of the prostate are effective and safe treatments for benign prostatic hyperplasia . Holmium laser enucleation of the prostate can be applied to prostates of all sizes , and involves less risk of hemorrhage , decreased bladder irrigation and catheter times , as well as reduced hospital stay . Thus , we believe holmium laser enucleation of the prostate should be proposed as a potential new gold st and ard surgical therapy instead of transurethral resection of the prostate for patients with benign prostatic hyperplasia PURPOSE We compared the safety and efficacy of diode laser enucleation of the prostate ( DiLEP ) with plasmakinetic enucleation and resection of the prostate ( PKERP ) . PATIENTS AND METHODS A total of 80 patients with bladder outflow obstruction from benign prostatic hyperplasia ( BPH ) were r and omly assigned to either DiLEP or PKERP prospect ively . All patients were assessed preoperatively and followed up at 3 , 6 , and 12 months postoperatively . Baseline characteristics of the patients , perioperative data , and postoperative outcomes were compared . The operative data and perioperative and postoperative complications were also recorded . RESULTS The preoperative data were comparable between the two groups . The DiLEP group had significantly shorter operative time , postoperative irrigation , time and catheterization time than the PKERP group ( P=0.000 , P=0.000 and P=0.000 ) . The drop in hemoglobin level was statistically significantly less in the DiLEP group ( P=0.002 ) . There were no statistical differences in complications between the two groups except irritative symptoms ( P=0.018 ) . At the 3 , 6 , and 12-month follow-up , no statistically significant differences were observed between the two groups in International Prostate Symptom Score , maximum flow rate , quality of life , postvoid residual , prostate volume , and prostate-specific antigen level ( P>0.05 ) . CONCLUSIONS The efficacy of DiLEP and PKERP were similar for relieving obstruction and low urinary tract symptoms . DiLEP provides less risk of hemorrhage , reduced bladder irrigation , and catheter times . The downward morcellation technique is more efficient than the resection technique . Future well design ed r and omized trials with extended follow-up and larger sample sizes may be needed to better verify the advantage of DiLEP in treating patients with symptomatic BPH The aim of this study was to compare the clinical outcomes between thulium laser enucleation of the prostate ( ThuLEP ) and plasmakinetic bipolar resection of the prostate ( PKRP ) for treating benign prostatic hyperplasia ( BPH ) in a prospect i ve r and omized trial with 5 years of follow-up . One hundred fifty-eight consecutive patients with BPH were r and omized to receive operation of either ThuLEP ( n = 79 ) or PKRP ( n = 79 ) . All cases were evaluated preoperatively , and a part of them were evaluated at 3–5 years postoperatively by the International Prostate Symptom Score ( IPSS ) , quality of life score ( QoLS ) , maximum flow rate ( Qmax ) , and postvoid residual ( PVR ) urine volume . Eighty patients completed the 5-year follow-up . Each study arm showed no significant difference in preoperative parameters . Compared with PKRP , ThuLEP required longer operation time ( 65.4 vs 47.4 min , p = 0.022 ) but result ed in less hemoglobin decrease ( 1.5 vs 3.0 g/L , p = 0.045 ) , catheterization time ( 2.1 vs 3.5 days , p = 0.031 ) , irrigated volume ( 12.4 vs 27.2 L , p = 0.022 ) , and hospital stay ( 2.5 vs 4.6 days , p = 0.026 ) . During the 60-month follow-up , both procedures demonstrated no significant difference in terms of Qmax , IPSS , PVR urine volume , and QoLS . ThuLEP was statistically superior to PKRP in blood loss , catheterization time , irrigated volume , and hospital stay but inferior to PKRP in operation time . However , both procedures showed no significant difference in terms of Qmax , IPSS , PVR urine volume , and QoLS through the 60-month follow-up Purpose To compare the safety and efficiency of thulium laser resection of the prostate-tangerine technique ( TmLRP-TT ) and plasmakinetic resection of the prostate ( PKRP ) for aged symptomatic benign prostatic hyperplasia ( BPH ) patients with large volume prostates ( > 80 ml ) in a prospect i ve r and omized trial with an 18-month follow-up . Material s and methods From January 2010 to November 2011 , 90 BPH patients with large volume prostates were r and omized for surgical treatment with TmLRP-TT ( n = 45 , group 1 ) or PKRP ( n = 45 , group 2 ) . The preoperative and postoperative parameters were recorded and compared . All patients were evaluated at 1 , 6 , 12 and 18 months postoperatively using the International Prostate Symptom Score ( IPSS ) , quality of life score ( QoL ) , maximum flow rate ( Qmax ) , postvoid residual urine volume ( PVR ) and the five-item version of the International Index of Erectile Function score . All perioperative complications were also documented and classified according to the modified Clavien classification system . Results Compared with the PKRP group , the TmLRP-TT group had a statistically lower hemoglobin drop ( 0.86 ± 0.42 vs. 1.34 ± 1.04 g/dl , P < 0.01 ) , shorter catheterization time ( 1.91 ± 0.85 vs. 2.36 ± 0.74 days , P < 0.01 ) and hospital stay ( 3.80 ± 0.46 vs. 5.02 ± 0.54 days , P < 0.01 ) . Within the observation period of 18 months , both groups had significant postoperative improvement in IPSS , QoL , Qmax and PVR , although no difference was observed between the two groups . Only one patient receiving PKRP treatment required a blood transfusion perioperatively . During the 18-month follow-up , one patient in each group experienced urethral stricture and one patient in the PKRP group experienced bladder neck contracture . Minor complications that required no or noninterventional treatment occurred in 6 ( 13.33 % ) of TmLRP-TT group ( Clavien grade 1 , 13.33 % and grade 2 , 0 % ) and 10 ( 22.22 % ) of PKRP group ( Clavien grade 1 , 20.00 % and grade 2 , 2.22 % ) . No severe complications required re interventions in both groups ( Clavien grade 3 , 0 % ; grade 4 , 0 % ; grade 5 , 0 % ) . Conclusions Both TmLRP-TT and PKRP are safe and effective treatment options for large prostates that require resection . Taking into account less blood loss , shorter catheterization time and hospital stay , TmLRP-TT may be a better treatment for patients with large prostates OBJECTIVE To compare the clinical effects and safety between greenlight photoselective vaporization of prostate ( PVP ) and plasmakinetic resection of prostate ( PRP ) in eldly benign prostatic hyperplasia ( BPH ) men with high surgical risk . METHODS ; Fifty three eldly BPH patients , who had the indication of surgical treatment but complicated with at least one internal disease , were r and omly divided into PVP group and PRP group . The clinical data of all the patients were collected and compared between the two groups , including pre-operative and post-operative international prostate symptom score ( IPSS ) , postvoid residual urine ( PVR ) , urine flow rate ( Qmax ) , quality of life ( QOL ) as well as prostate volume ( PV ) , operational time , operative bleeding volume , postoperative recovery , peri-operative complications . RESULTS The complete follow-up data of 44 patients were achieved : 21 of PVP , 23 of PRP . There were significant differences between two groups in operative bleeding , bladder irrigation time , indwelling catheter time and hospital stay ( P < 0.002 ) . The peri-operative bleeding was lower in PVP group , while the bladder irrigation time , indwelling catheter time and hospital stay were shorter in PVP group . The operation time showed no difference ( P = 0.12 ) . No significant differences were found 3 months postoperatively between two groups in all the data associated with urination ( IPSS , Qmax , PVR , QOL ) , P > 0.05 . Complications ( urethrostenosis , retro grade ejaculationwere acceptable in both groups . CONCLUSION For surgical treatment of eldly men with high surgical risk , both PVP and PRP are safe and effective with the internal disease being sufficient control INTRODUCTION Prostate vaporization technology is becoming a st and ard of care for treatment of moderate , symptomatic benign prostatic hyperplasia ( BPH ) . We compared two transurethral prostate vaporization technologies with respect to cost , efficiency , efficacy , safety , and surgical team satisfaction . METHODS Fifty-five patients meeting st and ardized symptom criteria for BPH were r and omized to either Olympus Plasma ButtonTM or Biolitec EVOLVE ® diode laser vaporization . Primary outcome of cost with secondary outcomes of clinical efficacy , resection time , surgical team satisfaction , and safety were analyzed . Followup was carried out at six and 12 weeks . Patient factors included baseline , as well as six- and 12-week International Prostate Symptom Score ( IPSS ) with quality of life ( QoL ) scores . We recorded surgical team satisfaction with a Likert-style survey investigating ease of set-up , reliability , efficiency , and ability to reach desired endpoint . All complications or side effects detected within three months and the result ing management were included in the cost analysis . RESULTS Mean cost per patient was $ 3418 for the Olympus group and $ 4564 for Biolitec ( p<0.05 ) . Surgical vaporization time was significantly less for the Olympus group , 24.3 vs. 33.5 minutes ( p<0.05 ) . Surgical and nursing staff preferred the Olympus device ( p<0.05 ) . IPPS symptom improvement and complication rates were similar between groups . Patients in the Biolitec arm had more intraoperative bleeding episodes requiring conversion to monopolar transurethral resection of the prostate ( TURP ) ( three vs. none ) . CONCLUSIONS In a head-to-head r and omized trial , Olympus Plasma Button transurethral vaporization was more cost-effective , faster , and preferred by surgical staff when compared to Biolitetec Diode Laser vaporization . Both devices showed similar safety and efficacy PURPOSE The first prospect i ve r and omized study to compare the safety and short-term efficacy of monopolar transurethral resection of the prostate ( TURP ) , bipolar TURP , and photoselective vaporization of the prostate ( PVP ) using GreenLight high-performance system 120W laser in patients who presented with benign prostatic obstruction ( BPO ) . PATIENTS AND METHODS The 186 consecutive patients who presented with BPO and who were planned for surgery were r and omized into three groups : Group A , patients who underwent monopolar TURP ; group B , patients who underwent bipolar TURP ; and group C , patients who underwent PVP . All three groups were subdivided into two subgroups based on prostate volume : Subgroup 1 > 20 cc and < 50 cc , and subgroup 2 , between 50 and 80 cc . Patients preoperative , perioperative , and follow-up data were recorded and analyzed . RESULTS The baseline characteristics of the three groups and subgroups 1 and 2 were comparable . The number of patients in whom postoperative irrigation was instituted , amount of fluid used for postoperative irrigation , duration of postoperative irrigation , postoperative hemoglobin concentration , and duration of catheterization were significantly in favor of group C patients except for the mean operative time , which was significantly longer among them . All three groups demonstrated an increase in International Prostate Symptom Score , quality of life score , and maximum flow rate and decrease in prostate volume and postvoid residual urine at 12-month follow-up . The mean Intgernational Index of Erectile Function-5 score did not show improvement in any group . The need for blood transfusion and clot retention necessitating intervention were significantly lower among group C patients compared with group A , whereas these values for group B patients did not reach significant level compared with either group A or C. These complications were comparable among subgroup 1 patients , whereas subgroup 2 patients had shown results in favor of subgroup C2 . CONCLUSION Monopolar TURP , bipolar TURP , and PVP are equally efficacious at 12-month follow-up . PVP has added advantages of lesser blood loss , lesser need for blood transfusion ( especially for prostate volume 50 - 80 cc ) , and shorter catheterization time OBJECTIVE To compare the short-term efficacy and safety results of photoselective vaporization of the prostate ( PVP ) and plasmakinetic resection of prostate ( PKRP ) , 2 methods of treating benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms ( LUTS ) in mainl and China . METHODS One hundred twenty patients with LUTS secondary to BPH were r and omly divided into 2 groups : PVP group ( n = 61 ) and PKRP group ( n = 59 ) . Perioperative data and postoperative complications were recorded for both groups . Patients were followed up for 12 months after treatment . RESULTS Compared with PKRP , PVP required a longer operation time ( 56 vs 41 minutes ; P < .01 ) . PVP also needed shorter catheterization time ( 2.4 vs 3.5 days ; P < .01 ) and shorter length of hospitalization ( 3.5 vs 5.1 days ; P < .01 ) . International Prostate Symptom Score , Qmax , and quality of life score were significantly improved for both groups after surgery , and no significant differences were apparent between the 2 groups , for up to 12 months . Short-term complications were assessed in regard to necessity of blood transfusion ( 1 vs 1 ) , clot retention ( 1 vs 0 ) , reoperation ( 1 vs 0 ) , incontinence ( 0 vs 0 ) , urethral stricture ( 1 vs 0 ) , and retro grade ejaculation ( 4 vs 6 ) in the PVP vs PKRP groups , respectively . CONCLUSION In patients with BPH-related LUTS , PVP may be a superior treatment to PKRP as it relates to the endpoints of this study , with short-term results after a 12-month follow-up as length of hospital stay and catheterization time needed were both less than what was required for PKRP . Long-term comparative data are required to clearly define the role of PVP and PKRP in patients OBJECTIVES To compare the alternative energy sources of the holmium : yttrium-aluminum-garnet laser and bipolar plasmakinetic energy for endoscopic enucleation . METHODS A prospect i ve , r and omized controlled trial was undertaken , with 20 patients assigned to each group . The preoperative and postoperative measures included transrectal ultrasound-assessed prostate volume , postvoid residual urine volume , and urodynamic evaluation findings . The intraoperative measures included procedure length , energy use , and specimen weight . All adverse events were recorded at each postoperative visit in a 1 , 3 , 6 , and 12-month protocol . RESULTS No differences were found in the preoperative characteristics between the two groups . The significant differences favoring holmium laser enucleation of the prostate compared with plasmakinetic enucleation of the prostate were seen in the operative time ( 43.6 versus 60.5 minutes ) , recovery room time ( 47.1 versus 65.6 minutes ) , and bladder irrigation requirement ( 5 % versus 35 % ) . The outcomes after holmium laser enucleation of the prostate and plasmakinetic enucleation of the prostate were in all other respects similar by the postoperative outcome measures assessed . CONCLUSIONS Plasmakinetic enucleation of the prostate is a safe and technically feasible procedure for the enucleation of prostatic adenomata . Plasmakinetic enucleation of the prostate is limited by the longer operative and recovery room times , as well as a more pronounced postoperative irrigation requirement because of reduced visibility and a greater propensity for bleeding . The transfusion rates and catheterization and hospitalization times were similar . The optimal energy source for enucleation should still be considered the holmium laser , but bipolar energy can be considered by users already experienced with holmium laser enucleation of the prostate OBJECTIVES To assess durability of efficacy of monopolar transurethral resection of the prostate ( TURP ) , bipolar TURP , and photoselective vaporization of the prostate ( PVP ) using 120W Green light laser at 36 months follow up . METHOD The 186 patients who presented with benign prostatic obstruction and planned for surgery were r and omized into three groups : Group A - monopolar TURP ; group B - bipolar TURP ; and group C - PVP . International Prostate Symptom Score ( IPSS ) , International Index of Erectile Function-5 ( IIEF-5 ) score , quality of life ( QoL ) score , maximum flow rate ( Qmax ) , prostate volume and postvoid residual urine ( PVRU ) were analyzed up to 36 months follow up . RESULTS The improvement observed in the mean IPSS , QoL score , Qmax , prostate volume and PVRU at 12-month was sustained till 36 months follow up . However , the mean IIEF-5 score did not show improvement in any group . Few complications noted in second and third year of follow up compared to first year follow up . The results of subgroups analysis did not reveal any significant finding , different from group analysis , for efficacy parameters . CONCLUSION Monopolar TURP , Bipolar TURP and PVP provides durable and comparable efficacy at 36 months follow up in patients with prostate size < 80 OBJECTIVE To compare the safety , efficacy , and applicability of holmium laser enucleation of the prostate ( HoLEP ) and bipolar transurethral resection of the prostate ( TURPb ) procedures , whereas the secondary objective is to find out the advantages and disadvantages of each . PATIENTS AND METHODS A prospect i ve r and omized study included 120 patients with benign prostatic hyperplasia that required intervention . The patients were r and omized in 2 equal groups : group A managed by HoLEP and group B managed by TURPb . The mean age , International Prostate Symptom Score , maximum urine flow , residual urine , operative time , blood loss , resected volume , catheterization time , hospital stay , and costs were compared . RESULTS Both groups were comparable regarding the preoperative parameters . The mean operative time was statistically significantly longer in the HoLEP group . The drop in the hemoglobin level was statistically significantly in group B. The mean resected prostatic volume was 61.167 g in the HoLEP group and 58.8 g in the TURPb group . The catheter was removed after 24 hours in 51 and 36 patients in groups A and B , respectively . The International Prostate Symptom Score at 1 and 12 months and the maximum urine flow at 12 months postoperatively were found to be better in the HoLEP group than in the bipolar group , and this difference was found to be statistically significant . CONCLUSION Although the HoLEP technique is associated with a relatively longer operative time , it has proved to be effective in treating large prostates with minimal morbidity , better hemostasis , less blood loss , and better voiding pattern than TURPb after a 12-month follow-up BACKGROUND AND PURPOSE Holmium enucleation of the prostate ( HoLEP ) has been established as an effective therapy for patients with benign prostatic hyperplasia ( BPH ) , with less bleeding , shorter catheterization time , and shorter hospital stay . The evolution of the bipolar transurethral resection of the prostate ( TURP ) raised a question : Would it be able to provide all the advantages of HoLEP and compensate for all its drawbacks , including the higher costs and the steep learning curve ? PATIENTS AND METHODS A r and omized study was performed that compared HoLEP with bipolar TURP . The study included 60 patients with BPH who were r and omized in two groups ( 1:1 fashion ) . The mean age , International Prostate Symptom Score , serum prostate-specific antigen value , maximum urinary flow rate , residual urine , prostate size , operative time , blood loss , resected volume , catheterization time , hospital stay , and intraoperative and postoperative complications were compared in both groups , with a follow-up period of 6 months postoperatively . RESULTS Both techniques were comparable to each other . They shared the same advantages of decreased perioperative morbidity . The longer operative time in the HoLEP group , however , was still statistically significant . In addition , the expense of performing HoLEP was nearly double that of bipolar TURP . CONCLUSION HoLEP and bipolar TURP are effective in treating patients with lower urinary tract symptoms due to BPH , however ; the long operative time , the steep learning curve , as well as the higher expenses of HoLEP are in favor of bipolar TURP |
12,005 | 22,592,674 | Physical training was well tolerated with no adverse effects reported .
None of the studies mentioned worsening of asthma symptoms following physical training .
This review demonstrated that physical training can improve cardiopulmonary fitness and was well tolerated among people with asthma in the included studies . | BACKGROUND People with asthma may show less tolerance to exercise due to worsening asthma symptoms during exercise or other reasons such as deconditioning , as a consequence of inactivity .
Some may also restrict activities as per medical advice or family influence and this might result in reduced physical fitness .
Physical training programs aim to improve physical fitness , neuromuscular coordination and self confidence .
Subjectively , many people with asthma report that they are symptomatically better when fit , but results from trials have varied and have been difficult to compare because of different design s and training protocol s. Also , as exercise can induce asthma , the safety of exercise programmes need to be considered .
OBJECTIVES To gain a better underst and ing of the effect of physical training on the respiratory and general health of people with asthma , from r and omised trials . | Background : Some individuals with moderate/severe persistent asthma develop irreversible airway obstruction . These individuals present with dyspnoea , exercise intolerance and impaired quality of life ( QOL ) , all of which could potentially be alleviated with exercise training . Objective : To investigate whether exercise training improves functional exercise capacity and QOL in middle-aged and older adults with fixed airway obstruction asthma ( FAOA ) . Methods : 35 subjects aged 67.8 ± 10.6 years , with FEV1 59 ± 16 % of predicted , were r and omised to a 6-week ‘ intervention ’ period of supervised exercise training ( n = 20 ) or usual care ( n = 15 ) . This period was preceded by a 3-week run-in period during which asthma control was assessed weekly . Functional exercise capacity ( 6-min walk distance , 6MWD ) and QOL ( Asthma QOL Question naire , AQLQ ) were measured before , immediately following and 3 months after the intervention period . Results : 34 subjects ( exercise group , n = 19 , and control group , n = 15 ) completed the intervention period . Relative to the control group , the exercise group had greater improvements immediately following and 3 months after the intervention in the AQLQ symptom domain ( 0.61 , p = 0.001 , and 0.57 points per item , p = 0.005 ) and AQLQ activity limitation domain ( 0.43 , p = 0.04 , and 0.55 points per item , p = 0.04 ) . 6MWD increased ( 36 ± 37 m , p < 0.01 ) in the exercise group immediately following training and remained elevated ( 34 ± 45 m , p < 0.01 ) at the 3-month follow-up . The magnitude of change in 6MWD between groups was not significant , despite no change in the control group . Conclusions : Supervised exercise training improves symptoms and QOL in adults with FAOA BACKGROUND Aerobic training has a number of well known beneficial effects in both normal and asthmatic children . However , the impact of training on the clinical management of the underlying bronchial asthma remains controversial , particularly in the most severe patients . METHODS Clinical evaluation , spirometric tests , symptom limited maximum exercise testing , and exercise challenge tests were performed in a group of children with stable moderate to severe asthma . Forty two patients ( 24 boys ) aged 8–16 were evaluated twice : before and after supervised aerobic training ( group 1 , n = 26 ) and two months apart ( untrained group 2 , n = 16 ) . RESULTS Spirometric and maximal exercise variables in the initial evaluation were significantly reduced in group 1 ( p<0.05 ) but medication and clinical scores and the occurrence of exercise induced bronchospasm ( EIB ) did not differ between the two groups . Aerobic improvement with training ( maximal oxygen uptake and /or anaerobic threshold increment > 10 % and 100 ml ) was inversely related to the baseline level of fitness and was independent of disease severity . Although the clinical score and the occurrence of EIB did not change after training , aerobic improvement was associated with a significant reduction in the medication score and the daily use of both inhaled and oral steroids ( p<0.05 ) . CONCLUSIONS Aerobic improvement with training in less fit asthmatic children is related to a short term decrease in the daily use of inhaled and oral steroids , independent of the severity of the disease Background . Supervised exercise leads to significant improvements in asthma control and quality -of-life in adults with partly controlled asthma ; however , the role of unsupervised exercise is unknown . Methods . The purpose of this study was to determine the impact of self-directed exercise on subjective and objective indices of asthma-related health . Participants ( n = 24 ) were assigned to an exercise group or a control group for a 12-week period . Those in the exercise group were provided with exercise programs by a qualified exercise professional . These programs were up date d through electronic mail every 3 weeks to ensure progression . Controls maintained their current lifestyle habits for the intervention period . Assessment s of aerobic fitness , lung function , and subjective and objective asthma measures were conducted at baseline and after completion of the 12-week intervention period for both groups . Analysis of covariance was used to detect differences between groups from baseline to week 12 . Qualitative analyses were used to assess responses to open-ended questions . Results . Adherence to the program was poor . Perceived asthma control and self-reported frequency and severity of asthma improved significantly in the exercise group at week 12 compared with that in the control group . Objective measures of asthma such as asthma control , quality -of-life , and lung function , as well as peak and submaximal aerobic fitness did not change relative to controls . Responses to open-ended questions revealed improvements in three areas : asthma management , perceived fitness , and well-being . Conclusion . Adults with partly controlled asthma are able to improve perceived control and subjective measures of asthma-related health with 12 weeks of self-directed exercise ; however , supervision may be required to make significant improvements to measured asthma control , quality of life , and aerobic fitness . Future research should focus on the means to improve adherence of self-directed exercise programs in this population The effect of two types of physical training on patients with perennial asthma were compared in a blind , controlled , r and omized study . Eleven of 27 adults with asthma performed a physical training programme which did not change their oxygen consumption ( control group ) . The remaining 16 asthmatics performed a physical training programme which improved their maximal oxygen consumption ( training group ) . Both of the training programmes were performed for 1 hour , twice a week during a period of 2 months . No complications were reported during the performance of the training programmes . The doses of all medicines apart from beta 2-agonist aerosol were unchanged during the training period . The patients inhaled beta 2-agonist aerosol if their peak expiratory flow ( PEF ) was less than 60 % of their maximal PEF . The training group decreased their use of aerosol from an average of 4.94 puffs per day to 3.41 puffs per day ( P less than 0.05 ) . The control group did not change their use of beta 2-agonist aerosol significantly . It is concluded that physical exercise which improves the maximal oxygen consumption decreases the use of beta 2-agonist spray and that heavy exercise is well tolerated by asthmatics The present multicentre study evaluates the differences in efficacy between a 3 month rehabilitation programme including drug treatment , and a 3 month control period of drug treatment only , for asthmatic patients and patients with chronic obstructive pulmonary disease ( COPD ) . The programme was run by physiotherapists in eight local practice s , and included exercise training , patient education , breathing retraining , evacuation of mucus , relaxation techniques , and recreational activities . In a r and omized controlled trial with a cross-over design , the effects of rehabilitation were evaluated 3 and 6 months after baseline measurements in terms of exercise tolerance and quality of life ( QOL ) . Exercise tolerance was assessed using submaximal cycle ergometer tests and 6 min walking tests . QOL was evaluated by means of the Chronic Respiratory Disease Question naire ( CRDQ ) . After 3 months , the patients who started with rehabilitation showed significant improvements in endurance time ( 421 s ) and cardiac frequency ( 6 beats.min-1 ) during cycling , walking distance ( 39 m ) , and total CRDQ score ( 17 points ) compared to the control group . These improvements were still significant after 6 months . Additional analysis indicated that the asthmatic patients and the patients with COPD responded to rehabilitation in a similar way , with the exception that there was a greater improvement in walking distance for asthmatics . Improvements in exercise tolerance were not significantly correlated with improvements in QOL . Rehabilitation of patients with asthma or chronic obstructive pulmonary disease in local physiotherapy practice s improves exercise tolerance and quality of life The effects of a 3-month physical training programme on airway inflammation and clinical outcomes were studied in school-aged children with asthma . Subjects with persistent allergic asthma ( aged 12.7±3.4 yrs ; n = 34 ) were r and omly allocated into training and control groups . Exercise consisted of twice-weekly 50-min sessions for 12 weeks . Inflammation was assessed by levels of exhaled nitric oxide , blood eosinophils , eosinophil cationic protein , C-reactive protein , and total and mite-specific immunoglobulin (Ig)E. Lung volumes and bronchial responsiveness to methacholine were determined . The Paediatric Asthma Quality of Life Question naire and Paediatric Asthma Caregiver 's Quality of Life Question naire were used to evaluate activity restrictions , symptoms and emotional stress . The efficacy of the training was assessed by accelerometry . Following the programme , the exercise group spent twice as much time as the controls undertaking moderate-to-vigorous activities . No differences in changes were seen between groups for asthma outcomes . However , total IgE decreased more in the exercise group , as did mite-specific IgE. Training did not increase inflammation in children with persistent asthma , and may have decreased both total and allergen-specific immunoglobulin E levels . It is concluded that there is no reason to discourage asthmatic children with controlled disease to exercise Fitness improvement was used to compare morning with afternoon exercise periods for asthmatic children . Children with persistent moderate asthma ( according to GINA criteria ) , 8 to 11 years old , were divided into 3 groups : morning training group ( N = 23 ) , afternoon training group ( N = 23 ) , and non-training group ( N = 23 ) . The program was based on twice a week 90-min sessions for 4 months . We measured the 9-min running distance , resting heart rate and abdominal muscle strength ( sit-up number ) before and after the training . All children took budesonide , 400 microg/day , and an on dem and inhaled ss-agonist . The distance covered in 9 min increased ( mean + /- SEM ) from 1344 + /- 30 m by 248 + /- 30 m for the morning group , from 1327 + /- 30 m by 162 + /- 20 m for the afternoon group , and from 1310 + /- 20 m by 2 + /- 20 m for the control group ( P < 0.05 for the comparison of morning and afternoon groups with the control group by ANOVA and P > 0.05 for morning with afternoon comparison ) . The reduction of resting heart rate from 83 + /- 1 , 85 + /- 2 and 86 + /- 1 bpm was 5.1 + /- 0.8 bpm in the morning group , 4.4 + /- 0.8 bpm in the afternoon group , and -0.2 + /- 0.7 bpm in the control group ( P > 0.05 for morning with afternoon comparison and P < 0.05 versus control ) . The number of sit-ups in the morning , afternoon and control groups increased from 22.0 + /- 1.7 , 24.3 + /- 1.4 and 23 + /- 1.1 sit-ups by 9.8 + /- 0.9 , 7.7 + /- 1.4 , and 1.9 + /- 0.7 sit-ups , respectively ( P > 0.05 for morning with afternoon comparison and P < 0.05 versus control ) . No statistically significant differences were detected between the morning and afternoon groups in terms of physical training of asthmatic children OBJECTIVE To assess the effect of a training protocol on aerobic and anaerobic fitness in children with asthma . STUDY DESIGN Sixteen boys ( mean age : 13 years ; range : 10 - 16 years ) with mild-to-moderate asthma participated in a rehabilitation program that included 6 weeks of individualized training on a cycle ergometer . Two groups were r and omly formed : the control group ( CG , n = 7 ) and the training group ( TG , n = 9 ) , which exercised at an intensity set at the heart rate corresponding to the ventilatory threshold , with 1-minute sprints against the maximal aerobic power ( MAP ) every 4 minutes . Session duration was 45 minutes , 3 sessions per week . Changes in maximal oxygen uptake ( VO(2)max ) , MAP , short-term peak power ( PP ) , and pulmonary function were assessed . RESULTS Two patients of the training group did not complete the study . Pulmonary function remained unchanged in both groups . Improvement in both aerobic and anaerobic fitness was significant only in the training group ( TG vs CG ) : VO(2)max + 18 % + /- 2.1 % versus + 9 % + /- 4.5 % ( P < .05 ) , MAP + 32 % + /- 5 % versus 12 % + /- 7 % ( P < .05 ) , PP + 21 % + /- 5.7 % versus + 8.8 % + /- 10 % ( P < .01 ) . CONCLUSION Exercise training with high-intensity bouts is well tolerated in children with mild-to-moderate asthma . When included in a global rehabilitation program , this type of training improves both aerobic and anaerobic fitness . Anaerobic activities should be considered in sports rehabilitation programs for children with asthma Twenty-six adults ( 23 to 58 years ) with mild to moderate asthma underwent a 10-week supervised rehabilitation program , with emphasis on physical training . In the first 2 weeks , they exercised daily in an indoor swimming pool ( 33 degrees C ) and received education about asthma , medication , and principles of physical training . In the following 8 weeks , they exercised in the pool twice a week . Every training session lasted 45 min . The training sessions were made as suitable as possible for the individual subjects , in order to minimize " drop outs " from the program . The aim of the study was to evaluate the efficacy of the rehabilitation program and to determine if inactive asthmatic adults can exercise at high intensity . The rehabilitation program was preceded by a 6-min submaximal cycle ergometry test , a 12-min walking test , spirometry , and a methacholine provocation test . The subjects also responded to a five-item question naire related to anxiety about exercise , breathlessness , and asthma symptoms using a visual analogue scale . All subjects were able to perform physical training at a very high intensity , to 80 to 90 % of their predicted maximal heart rate . No asthmatic attacks occurred in connection with the training sessions . Twenty-two of the 26 subjects completed the rehabilitation program , felt confident with physical training , and planned to continue regular physical training after the 10-week program . Improvements in cardiovascular conditioning , measured as a decreased heart rate at the same load on the cycle ergometer ( average of 12 beats/min ) , and as a longer distance at the 12-min walking test ( average of 111 m ) , were observed during the program . FEV1 increased significantly from 2.2 to 2.5 L. Forced expiratory flow at 25 % of vital capacity also increased slightly but significantly . Methacholine provocation dose causing a fall in FEV1 by 20 % was unchanged . Seventeen subjects had a peak expiratory flow reduction of more than 15 % after the preprogram ergometry test and were classified as having exercise-induced asthma ( EIA ) . Only three of these subjects had EIA after 10 weeks . The asthmatic subjects were less afraid of experiencing breathlessness during exercise and less anxious about exercising at a high intensity after 10 weeks ( p < 0.05 ) . The asthma symptoms abated significantly during the rehabilitation program and the subjects needed less acute asthma care after the rehabilitation program . The results indicate that asthmatic persons benefit from a rehabilitation period , including physical training . Rehabilitation programs are therefore of value as a supplement to conventional pharmacologic treatment of asthma . This rehabilitation program can be adapted for use in clinical practice The effects of a pulmonary rehabilitation program on 44 patients with chronic obstructive pulmonary disease ( COPD ) were compared to a control group . The treated group was admitted to the program for a period of three months . The program consisted of several parts , such as physical training , health education , and psychological and social matters . Before participation , the patients were thoroughly examined and provided with optimal medical treatment . Both groups were assessed by means of biometrical tests and question naires for a period of 2 years . The rehabilitation group improved significantly in endurance , psychological parameters , and consumption of medical care . Working days increased and their way of life became more active . Smoking habits and body fat percentage decreased . Bronchial hyperreactivity , need for pulmonary drugs , and coughing and sputum production did not improve in the rehabilitation group compared to the control group . Airway obstruction , expressed as forced expiratory volume in one second , and complaints of dyspnea , allergy and hyperreactivity scores on question naires improved only in the short term ( < 1 year ) , but did not improve significantly in the long term . This study shows that pulmonary rehabilitation can result in improvements in patients with asthma or COPD who have many complaints despite the fact that their pulmonary function is not severely disturbed PURPOSE Aerobic training has been shown to be effective in improving cardiopulmonary fitness in asthmatic children . However , the actual impact of physical training on clinical indicators of disease control remains controversial . METHODS Thirty-eight children with moderate to severe persistent asthma were r and omly assigned to control ( N=17 ) and training ( N=21 ) groups . Spirometry , exercise challenge , and maximum incremental cardiopulmonary exercise tests were performed 16 wk apart . Daily doses of inhaled steroids and Pediatric Asthma Quality of Life Question naire ( PAQLQ ) scores were also recorded . RESULTS Physical training was associated with significant improvements in physiological variables at peak and submaximal exercise ( P<0.05 ) ; in contrast , no significant changes were found in controls . Severity of exercise-induced bronchoconstriction ( EIB ) and postexercise breathlessness were significantly lessened in trained patients ; improvement in fitness and EIB , however , were not linearly related ( P>0.05 ) . In addition , PAQLQ scores improved only in trained children ( P<0.01 ) . Daily doses of inhaled steroids were reduced in trained patients ( 52 % ) , but they remained unchanged or increased in controls ( 70.6 % ) ( P=0.07 ) . CONCLUSION Supervised exercise training might be associated with beneficial effects on disease control and quality of life in asthmatic children . These data suggest an adjunct role of physical conditioning on clinical management of patients with more advanced disease PURPOSE The purpose of this study was to assess the validity of the 20-m shuttle test with 1-min stages ( 20-MST ) to estimate maximal oxygen uptake ( VO2 max ) and its ability to register cardiorespiratory modifications over the course of an individualized aerobic training program for mild to moderately asthmatic children acclimatized to moderate altitude . METHODS Forty-eight asthmatic subjects aged 12 to 17 years performed both a maximal incremental exercise test on a cycle ergometer and the 20-MST . Ten of the subjects were then r and omly chosen and trained three times per week at their ventilatory threshold ( Vth ) intensity level for three months . Another group of ten asthmatic subjects served as control subjects . Training intensity was adjusted monthly ; heart rate values at Vth were increased by the same proportion as the increase in Vo2 max as measured by the 20-MST . At the end of training , both groups were again evaluated with the two tests . The Vo2 max values by direct measurement and by the 20-MST were not significantly different for the entire population ( 46.5 + /- 1.6 vs 47.2 + /- 2.1 ml.min-1.kg-1 ) . In addition , the two test results were in close agreement ( r = 0.84 ; p < 0.01 ) . After training , a sharp improvement in the direct Vo2 max ( 44.1 + /- 2.4 to 51.2 + /- 1.9 ml.min-1.kg-1 ) was noted in the training group as well as an increase in the Vth ( 25.6 + /- 1.9 to 32.1 + /- 3.4 ml.min-1.kg-1 ) , the maximal power ( 152 + /- 7.1 to 185 + /- 3.8 W ) , and the maximal oxygen pulse ( 0.24 + /- 0.007 to 0.27 + /- 0.008 ml.beat-1.kg-1 ) . CONCLUSION The indirect measure confirmed these results : a simultaneous increase in VO2 max ( 43.7 + /- 2.5 to 53.8 + /- 2.1 ml.min-1.kg-1 ) , maximal oxygen pulse ( 0.22 + /- 0.004 to 0.27 + /- 0.006 ml.beat-1.kg-1 ) , and the number of stages completed ( 7 + /- 1.4 to 10.1 + /- 1.3 ) was observed . It was concluded that the 20-MST has sufficient validity to assess VO2 max and to register cardiorespiratory modifications over the course of individualized aerobic training programs in mild and moderately asthmatic children . It thus may be used to adjust training intensities during these programs BACKGROUND AND OBJECTIVE Asthma is a common paediatric airway disease with increasing prevalence . Studies comparing swimming with other sports have found that swimming is unlikely to provoke unstable asthma but possible benefits are not defined . This study investigated the benefits of a 6 week swimming intervention on pulmonary function tests ( PFT ) , PEF and severity of asthma in children . METHODS Young asthmatics were r and omly assigned to the experimental or the control group , with 15 subjects in each group . In addition to regular treatment for asthma , the experimental group received swimming training for 6 weeks . PFT , PEF and severity of asthma were measured . RESULTS There was a significant improvement ( P < 0.01 ) in PEF in the experimental group compared with the control group ( 330 L/min , 95 % CI : 309 - 351 vs. 252 L/min , 95 % CI : 235 - 269 ) after the swimming intervention . There was also a significant improvement ( P < 0.05 ) in the severity of asthma in the experimental group compared with the control group . CONCLUSIONS These data suggest that a swimming programme for asthmatic children can improve some disease parameters ( PEF and the severity of asthma ) . Swimming may be an effective non-pharmacological intervention for the child or adolescent with asthma Objective : To evaluate the effects of a physical exercise programme for children with asthma on an outpatient basis . Design : Intervention study : a r and omized pretest – post-test control group design . Setting and subjects : Forty-seven children with clinical ly diagnosed asthma participated in the intervention study , including 34 boys and 13 girls , from 8 to 13 years of age ( mean age 10.6 ) . Interventions : The physical exercise programme consisted of regular group exercises and home exercises for a period of three months . It was based on a theoretical model describing the relationships between physical competence ( condition ) , perceived physical competence , self-esteem and coping behaviour . Main outcome measures : Maximum incremental exercise test , endurance test , the Self-Perception Profile for Children ( CBSK ) , the Asthma Coping Test ( ACBT ) , lung function and exercise-induced bronchoconstriction . Results : The results showed significant effects of the intervention programme on physical condition . There was a significant improvement of 15 W on the maximal workload ( Wmax ) ( p < 0.001 ) , of 7 % on VO 2max ( oxygen uptake ) ( p = 0.002 ) and a significant decrease on heart rate submaximal of 6 % ( p = 0.001 ) . There was also a significant improvement of 50 % in running time measured with the endurance test ( p = 0.021 ) . Furthermore , a significant effect of the intervention was seen on coping with asthma ( p = 0.003 ) . Conclusion : It was concluded that participation in the physical exercise programme not only enhanced physical fitness , but also improved coping behaviour with asthma We estimated the association between bronchial responsiveness and hours of exercise per week in children with and without asthma . A r and om sample of school children ( n = 2188 ) , 6 - 16 years old , was enrolled in a cross-sectional study of asthma in Oslo using the ISAAC question naire . Lung function and bronchial responsiveness ( BR ) using methacholine was measured in a r and om sample of 80 children with asthma , wheeze and no asthma/no wheeze . The relation between hours of exercise per week and BR [ log ( DRS ) ] was estimated by linear regression . Sex and age were included as covariates . Hours of exercise were categorized in : none , 30 min , 1 h , 2 - 3 h , 4 - 6 h and 7 h or more . The mean values of log ( DRS ) were different in the low and high exercise groups for children with asthma ( P = 0.02 ) , whereas there was no effect of exercise on BR for children without asthma . BR increased with decreasing hours of exercise per week in children with asthma . The bronchial responsiveness decreased with 0.11 ( 95 % CI -0.20 , -0.01 ) pr unit in scale . This pattern was not present in children without asthma . The results suggest that there is a relation between hours of exercise per week and bronchial responsiveness in children with asthma PURPOSE there is evidence suggesting that physical activity has anti-inflammatory effects in many chronic diseases ; however , the role of exercise in airway inflammation in asthma is poorly understood . We aim ed to evaluate the effects of an aerobic training program on eosinophil inflammation ( primary aim ) and nitric oxide ( secondary aim ) in patients with moderate or severe persistent asthma . METHODS sixty-eight patients r and omly assigned to either control ( CG ) or aerobic training ( TG ) groups were studied during the period between medical consultations . Patients in the CG ( educational program + breathing exercises ; N = 34 ) and TG ( educational program + breathing exercises + aerobic training ; N = 34 ) were examined twice a week during a 3-month period . Before and after the intervention , patients underwent induced sputum , fractional exhaled nitric oxide ( FeNO ) , pulmonary function , and cardiopulmonary exercise testing . Asthma symptom-free days were quantified monthly , and asthma exacerbation was monitored during 3 months of intervention . RESULTS at 3 months , decreases in the total and eosinophil cell counts in induced sputum ( P = 0.004 ) and in the levels of FeNO ( P = 0.009 ) were observed after intervention only in the TG . The number of asthma symptom-free days and VO(2max ) also significantly improved ( P < 0.001 ) , and lower asthma exacerbation occurred in the TG ( P < 0.01 ) . In addition , the TG presented a strong positive relationship between baseline FeNO and eosinophil counts as well as their improvement after training ( r = 0.77 and r = 0.9 , respectively ) . CONCLUSIONS aerobic training reduces sputum eosinophil and FeNO in patients with moderate or severe asthma , and these benefits were more significant in subjects with higher levels of inflammation . These results suggest that aerobic training might be useful as an adjuvant therapy in asthmatic patients under optimized medical treatment BACKGROUND Asthma symptoms reduce patients ' daily activities , impair their health-related quality of life ( HRQoL ) , and increase their reports of anxiety and depression , all of which seem to be related to a decrease in asthma control . Aerobic exercise training is known to improve aerobic fitness and reduce dyspnea in asthmatics ; however , its effect in reducing psychologic distress and symptoms remains poorly understood . We evaluated the role of an aerobic training program in improving HRQoL ( primary aim ) and reducing psychologic distress and asthma symptoms ( secondary aims ) for patients with moderate or severe persistent asthma . METHODS A total of 101 patients were r and omly assigned to either a control group or an aerobic training group and studied during the period between medical consultations . Control group patients ( educational program plus breathing exercises ) ( n = 51 ) and training group patients ( educational program plus breathing exercises plus aerobic training ) ( n = 50 ) were followed twice a week during a 3-month period . HRQoL and levels of anxiety and depression were quantified before and after treatment . Asthma symptoms were evaluated monthly . RESULTS At 3 months , the domains ( physical limitations , frequency of symptoms , and psychosocial ) and total scores of HRQoL significantly improved only in the training group patients ( P < .001 ) ; the number of asthma-symptom-free days and anxiety and depression levels also significantly improved in this group ( P < .001 ) . In addition , a linear relationship between improvement in aerobic capacity and the days without asthma symptoms was observed ( r = 0.47 ; P < .01 ) . CONCLUSIONS Our results suggest that aerobic training can play an important role in the clinical management of patients with persistent asthma . Further , they may be especially useful for patients with higher degrees of psychosocial distress . TRIAL REGISTRATION clinical trials.gov ; Identifier : NCT-00989365 STUDY OBJECTIVES To answer the following questions : in patients with chronic airway obstruction ( CAO ) , ( 1 ) can pulmonary rehabilitation lead to similar short-term gains at successive , yearly interventions , and ( 2 ) is there any real clinical or physiologic long-term benefit by yearly repetition of pulmonary rehabilitation programs ( PRPs ) ? DESIGN R and omized , controlled clinical study . SETTING Pulmonary rehabilitation center . PATIENTS Sixty-one CAO patients studied 1 year after completing an initial 8-week outpatient PRP ( PRP1 ) . INTERVENTION Patients were r and omly classified into two groups . A second PRP ( PRP2 ) was completed by the first group ( group 1 ) but not by the second group ( group 2 ) . One year later , a third PRP ( PRP3 ) was performed by both groups . MEASUREMENTS Lung function , cycloergometry , walking test , dyspnea , and health-related quality of life ( HRQL ) were assessed before and after PRP2 , and before and after PRP3 . The numbers of hospitalizations and exacerbations over the year were also recorded . RESULTS Complete data sets were obtained from 36 patients ( 17 patients in group 1 and 19 patients in group 2 ) . The two groups did not differ in any parameter either before PRP1 , after PRP1 , or at r and omization . There was no significant change over time for airway obstruction in either group . After PRP2 , exercise tolerance , dyspnea , and HRQL improved in group 1 . Nevertheless , 1 year later , patients of group 1 did not differ from patients of group 2 in any outcome parameter , such that in comparison to before PRP1 , only HRQL was still better in both groups 24 months after PRP1 . Yearly hospitalizations and exacerbations per patient significantly decreased in both groups in the 2 years following PRP1 , when compared to the 2 years prior . Nevertheless , at the 24-month follow-up visit , a further reduction in yearly exacerbations was observed only in group 1 but not in group 2 in comparison to what was observed at the 12-month follow-up visit . The PRP3 result ed in improvement in exercise tolerance in both groups . CONCLUSION In patients with CAO , an outpatient PRP can achieve benefits in HRQL and a decreased number of hospitalizations , which persist for a period of 2 years . Successive , yearly interventions lead to similar short-term gains but do not result in additive long-term physiologic benefits . Further reduction in yearly exacerbations seems to be the main benefit of an additional PRP BACKGROUND A study was undertaken to determine whether swimming training improved aerobic capacity , exercise induced bronchoconstriction ( EIB ) , and bronchial responsiveness to inhaled histamine in children with asthma . METHODS Eight children with mild or moderate asthma participated in swimming training every day for six weeks . The intensity of training was individually determined and set at 125 % of the child ’s lactate threshold ( LT ) , measured using a swimming ergometer . Another group of eight asthmatic children served as control subjects . Aerobic capacity and the degree of EIB were assessed by both cycle ergometer and swimming ergometer before and after swimming training . RESULTS The mean ( SD ) aerobic capacity at LT increased by 0.26 ( 0.11 ) kp after training when assessed with the swimming ergometer and by 10.6 ( 4.5 ) W when assessed with the cycle ergometer , and these changes were significantly different from the control group . The mean ( SD ) maximum % fall in forced expiratory volume in one second ( FEV1 ) to an exercise challenge ( cycle ergometer ) set at 175 % of LT decreased from 38.7 (15.4)% before training to 17.9 (17.6)% after training , but with no significant difference from the control group . There was , however , no difference in histamine responsiveness when compared before and after the training period . CONCLUSION A six week swimming training programme has a beneficial effect on aerobic capacity but not on histamine responsiveness in children with asthma The purpose of this study was to determine whether inactive asthmatic patients could perform high-intensity physical training equally well on l and as in water , and to compare the effects of these training forms . Thirty-two adults with asthma , r and omized into two groups , underwent a 10-week supervised rehabilitation program with emphasis on physical training . All patients , irrespective of training form , were able to exercise to maximal intensity ( 80 - 90 % of estimated maximal heart rate ) . No asthmatic attacks occurred in connection with the training sessions . Respiratory variables remained almost unchanged in both groups . The asthma symptoms declined during the rehabilitation period , and the subjects needed less acute asthma care after the rehabilitation . The cardiovascular condition improved significantly and similarly in the two groups . Ten patients , 5 in each group , had exercise-induced asthma at the start of the rehabilitation . Only 3 patients , 2 from the water group and 1 from the l and group , had exercise-induced asthma after 10 weeks . We conclude that indoor training , either on l and or in water , is beneficial . The effects of these two training forms are almost equivalent STUDY OBJECTIVE To determine the effect of an aerobic conditioning program on fitness , respiratory physiology , and resting lung function in patients with mild asthma . DESIGN Prospect i ve cohort study . SETTING Outpatient rehabilitation facility . METHODS Five patients with mild intermittent asthma and five normal control subjects completed a 10-week aerobic conditioning program . Pulmonary function studies and noninvasive cardiopulmonary exercise tests were performed before and after the conditioning program . RESULTS After aerobic conditioning , there were significant gains in maximum oxygen consumption ( VO(2)max ; 22.73 mL/kg/min vs 25.29 mL/kg/min , p = 0.01 , asthma ; 22.94 mL/kg/min vs 27.85 mL/kg/min , p = 0.03 , control ) and anaerobic threshold ( 0.99 L/min vs 1.09 L/min , p = 0.03 , asthma ; 0.89 L/min vs 1.13 L/min , p = 0.01 , control ) in both groups . Although FEV(1 ) was unchanged , the maximum voluntary ventilation ( MVV ) improved in the asthma group ( 96.0 L/min vs 108.2 L/min , p = 0.08 , asthma ; 134.0 L/min vs 131.2 L/min , p = 0.35 , control ) . During exercise , minute ventilation ( VE ) for each level of work was decreased in the asthma group after conditioning , while little change occurred in the control group ( 68 . 48 L/min vs 51.70 L/min at initial VO(2)max , p = 0 . 02 , asthma ; 65.82 L/min vs 63.12 L/min at initial VO(2)max , p = 0.60 , control ) . A significant decrease in the ventilatory equivalent ( VE/oxygen consumption , 40.8 vs 30.4 at VO(2)max , p = 0.02 , asthma ; 37.2 vs 35.8 4 at VO(2)max , p = 0.02 , control ) and the dyspnea index ( VE/MVV ) at submaximal ( 0.44 vs 0.38 , p = 0.05 , asthma ; 0.32 vs 0.38 , p < 0.01 , control ) and maximal exercise ( 0.72 vs 0.63 , p = 0.03 , asthma ; 0.49 vs 0.62 , p = 0.02 , control ) occurred in the asthma group . CONCLUSIONS Exercise rehabilitation improves aerobic fitness in both asthmatic and nonasthmatic participants of a 10-week aerobic fitness program . Additional benefits of improved ventilatory capacity and decreased hyperpnea of exercise occurred in patients with mild asthma Physiotherapy is an established treatment in asthmatic children . One purpose is to increase tolerance towards physical activity , decrease broncho-obstruction and promote elimination of secretions . A positive effect of physical training in asthmatic children has been reported in many studies . An improved working capacity has e.g. been shown after supervised physical training at least twice a week for a period of three months ( 1 ) . This was not a realistic level of training intensity in our clinical practice . Therefore , the goal of this study was to test whether physiotherapy combined with physical training once a week had any effect on working capacity or lung function tests in asthmatic children BACKGROUND Previous research suggests that physical activity programs may improve fitness and reduce symptoms in children with asthma , but few studies have included severe asthmatics and focused on safety and parental satisfaction with the programs . OBJECTIVE To examine safety , parental satisfaction , and pre- to post-intervention changes in symptoms and quality of life ( QOL ) in a pilot study of the impact of vigorous physical activity ( swimming ) and moderate-intensity activity ( golf ) on inner-city children with asthma . DESIGN / METHODS Children with asthma ( 7 - 14 years old ) residing in Milwaukee 's highest asthma prevalence zip codes were r and omized to a 9-week swimming or golf program . Pre- and post-intervention data were obtained on safety , parental satisfaction , asthma symptoms , quality of life , and urgent asthma physician visits . RESULTS Twenty-eight children in the swimming group and 17 in the golf group completed the program . Combined group analysis ( N = 45 ) revealed that only six symptom exacerbations occurred during 1,125 person-sessions of swimming and golf ( all resolved with bronchodilator therapy ) , 92 % of parents were very or extremely satisfied with the program , and post-exercise decreases were observed in asthma symptom severity scores ( 9.3 - 7.3 , P < 0.001 ) , improved parental QOL ( 4.9 - 5.4 , P < 0.001 ) , and reduced urgent physician visits for asthma ( 1.3 - 0.2 visits per person , P = 0.04 ) . The study lacked sufficient power to perform intergroup comparisons . CONCLUSIONS Findings from this pilot study indicate that vigorous ( swimming ) and moderate-intensity ( golf ) physical activity programs are well-tolerated , safe , and achieve high parental satisfaction . Participants and parents reported reduced childhood asthma symptoms and physician office visits and improved parental QOL . These findings suggest a potentially beneficial role for moderate to vigorous physical activity in childhood asthma A 5-day , non-residential exercise and living course for children with asthma is described as a feature of a programme of outpatient physiotherapy . Eleven children undertaking such a course were compared with 10 asthmatic children in a control group . The subject group showed , in the short term at least , an improvement in bronchial lability , peak flow rates , nocturnal and daytime wheeze , and activity compared with the controls . These findings were statistically significant . There was no difference between the groups in the number of days on which extra medication was taken . A short , sharp course is of benefit physically , socially and psychologically to children with asthma OBJECTIVE To investigate the effects of regular submaximal exercise on quality of life , exercise capacity and pulmonary function in asthmatic children . PATIENTS AND METHODS Sixty-two children with mild-moderate asthma ( mean age 10.4 ( SD 2.1 ) years ) were r and omly allocated into exercise and control groups . The exercise group underwent a moderately intensive basketball training program for 8 weeks . A home respiratory exercise program was advised to both groups . Pediatric Asthma Quality of Life Question naire ( PAQLQ ) was used for the evaluation of activity limitation , symptoms and emotional functions . Exercise capacity was evaluated through the physical work capacity ( PWC 170 test ) on a cycle ergometer and 6-minute walk test . Spirometric tests were also performed and medication and symptom scores were recorded . RESULTS Although PAQLQ scores improved in both groups , the improvement in the exercise group was significantly higher . The exercise group performed better in the PWC 170 and 6-minute walk tests , whereas no improvement was detected in the control group at the end of the trial . Medication scores improved in both groups , but symptom scores improved only in the exercise group . No significant changes were detected in pulmonary function in either group , except for peak expiratory flow values in the exercise group . CONCLUSION Eight weeks of regular submaximal exercise has beneficial effects on quality of life and exercise capacity in children with asthma . Submaximal basketball training is an effective alternative exercise program for asthmatic children |
12,006 | 23,780,745 | Subgroup analyses showed no statistically significant differences by intervention setting or type of participants .
Studies included in this review showed no evidence of effectiveness of interventions on episodes of relationship violence or on attitudes , behaviours and skills related to relationship violence .
We found a small increase in knowledge but there was evidence of substantial heterogeneity among studies . | BACKGROUND Educational and skills-based interventions are often used to prevent relationship and dating violence among young people .
OBJECTIVES To assess the efficacy of educational and skills-based interventions design ed to prevent relationship and dating violence in adolescents and young adults . | The authors evaluated a coeducational program for teenagers on preventing sexual coercion in dating situations . Students examined individual and social attitudes underlying coercive sexual behavior and learned communication skills aim ed at preventing or dealing with unwanted sexual advances . Instruction was enhanced by video and an interactive video " virtual date . " Outcomes were assessed using sexual attitude scales with a sample of 458 high school students . Student health education classes were r and omly assigned to either a treatment or a control condition . Findings , based on a latent variable model of differential effectiveness , showed that students in the treatment group with initial coercive attitude scores at or above the mean benefited significantly more than students with the same range of scores in the control group Motivational interviewing is a brief non-confrontational intervention design ed to enhance motivation to reduce harmful behavior ( Miller and Rollnick 2002 ) . The purpose of this study was to examine the effectiveness of motivational interviewing as a targeted prevention approach for partner aggression in emerging adulthood . Participants were 50 college dating couples between 18 and 25 years old who reported at least one act of male-to-female physical aggression in their current relationships . After completing a 2-hour assessment session , half of all couples were r and omly assigned to a 2-hour individualized motivational feedback session targeting physical aggression and risk factors for aggression . The remaining couples received minimal , non-motivational feedback . Follow-up surveys were conducted 3 , 6 , and 9 months later . Hierarchical linear modeling analyses indicated that , compared to the control condition , the motivational feedback intervention led to reductions in physical aggression and harmful alcohol use and to less acceptance of female psychological aggression and male psychological aggression ( among women only ) . Lagged analyses indicated that changes in physical aggression were predicted by reductions in psychological aggression and by lower acceptance of both male and female psychological aggression . Reductions in physical aggression predicted lower anxiety and greater relationship investment and male relationship commitment over time . These findings suggest that a brief motivational intervention is a useful prevention approach for high-risk dating couples , with benefits to both individual and relationship functioning OBJECTIVES This study assessed the effects of the Safe Date s program on the primary and secondary prevention of adolescent dating violence . METHODS Fourteen schools were r and omly allocated to treatment conditions . Eighty percent ( n=1886 ) of the eighth and ninth grade rs in a rural county completed baseline question naires , and 1700 ( 90 % ) completed follow-up question naires . RESULTS Treatment and control groups were comparable at baseline . In the full sample at follow-up , less psychological abuse , sexual violence , and violence perpetrated against the current dating partner were reported in treatment than in control schools . In a sub sample of adolescents reporting no dating violence at baseline ( a primary prevention sub sample ) , there was less initiation of psychological abuse in treatment than in control schools . In a sub sample of adolescents reporting dating violence at baseline ( a secondary prevention sub sample ) , there was less psychological abuse and sexual violence perpetration reported at follow-up in treatment than in control schools . Most program effects were explained by changes in dating violence norms , gender stereotyping , and awareness of services . CONCLUSIONS The Safe Date s program shows promise for preventing dating violence among adolescents A study was undertaken to determine the effectiveness of a 5-session relationship violence prevention program involving a middle school of predominantly African-American students . A composite measure assessed changes in knowledge , attitudes , and methods of dealing with relationship violence . A pretest-posttest control group design was used . Results indicated that treatment group scores were significantly higher than control group scores at posttest ( p < .001 ) and treatment group posttest scores were significantly higher than pretest scores ( p < .001 ) . There were significant differences in scores between regular-level students and those with a higher level of academic ability ( advanced students ) . Within the treatment group , there was a level-by-gender interaction revealing that male advanced students made the highest gains . In examining specific items , improvements were made in knowledge about relationship violence and attitudes about nonphysical violence . No changes were seen in attitudes about physical violence or in methods of dealing with relationship violence OBJECTIVES This study determined 4-year postintervention effects of Safe Date s on dating violence , booster effects , and moderators of the program effects . METHODS We gathered baseline data in 10 schools that were r and omly allocated to a treatment condition . We collected follow-up data 1 month after the program and then yearly thereafter for 4 years . Between the 2- and 3-year follow-ups , a r and omly selected half of treatment adolescents received a booster . RESULTS Compared with controls , adolescents receiving Safe Date s reported significantly less physical , serious physical , and sexual dating violence perpetration and victimization 4 years after the program . The booster did not improve the effectiveness of Safe Date s. CONCLUSIONS Safe Date s shows promise for preventing dating violence but the booster should not be used This study evaluated a community-based intervention to help at-risk teens develop healthy , nonabusive relationships with dating partners . Participants were 158 14 - 16-year-olds with histories of child maltreatment who were r and omly assigned to a preventive intervention group or a no-treatment control group . They completed measures of abuse and victimization with dating partners , emotional distress , and healthy relationship skills at bimonthly intervals when dating someone . Intervention consisted of education about healthy and abusive relationships , conflict resolution and communication skills , and social action activities . Growth curve analyses showed that intervention was effective in reducing incidents of physical and emotional abuse and symptoms of emotional distress over-time . Findings support involvement of youths in reducing the cycle of violence as they initiate dating in midadolescence In this experiment , 123 sixth and seventh grade classrooms from Clevel and area schools were r and omly assigned to one of two five-session curricula addressing gender violence/sexual harassment ( GV/SH ) or to a no-treatment control . Three-student surveys were administered . Students in the law and justice curricula , compared to the control group , had significantly improved outcomes in awareness of their abusive behaviors , attitudes toward GV/SH and personal space , and knowledge . Students in the interaction curricula experienced lower rates of victimization , increased awareness of abusive behaviors , and improved attitudes toward personal space . Neither curricula affected perpetration or victimization of sexual harassment . While the intervention appeared to reduce peer violence victimization and perpetration , a conflicting finding emerged — the intervention may have increased dating violence perpetration ( or at least the reporting of it ) but not dating violence victimization This article summarizes the results of the Ohio University Sexual Assault Risk Reduction Project , which is a program design ed to reduce college women 's risk for sexual assault . The program was evaluated at 2 separate universities with 762 women . Participants were r and omly assigned either to the program or to the no-treatment comparison group , and they completed measures that assessed sexual victimization , dating behaviors , sexual communication , and rape empathy at the pretest and at the 2-month and 6-month follow-ups . At the 2-month follow-up , there were no differences between the groups on any of the outcome measures . However , those women who were moderately victimized during the 2-month follow-up were significantly less likely to be revictimized during the 6-month follow-up period if they participated in the program Men and women living in r and omly selected 1st-year dormitories participated in tailored single-sex sexual assault prevention or risk-reduction programs , respectively . An evaluation of the men ’s project is presented ( N = 635 ) . The program incorporated social norms and byst and er intervention education and had an impact on self-reported sexual aggression and an effect on men ’s perceptions that their peers would intervene when they encountered inappropriate behavior in others . Relative to the control group , participants also reported less reinforcement for engaging in sexually aggressive behavior , reported fewer associations with sexually aggressive peers , and indicated less exposure to sexually explicit media Fast Track is a multisite , multicomponent preventive intervention for young children at high risk for long-term antisocial behavior . Based on a comprehensive developmental model , intervention included a universal-level classroom program plus social skills training , academic tutoring , parent training , and home visiting to improve competencies and reduce problems in a high-risk group of children selected in kindergarten . At the end of Grade 1 , there were moderate positive effects on children 's social , emotional , and academic skills ; peer interactions and social status ; and conduct problems and special-education use . Parents reported less physical discipline and greater parenting satisfaction/ease of parenting and engaged in more appropriate/consistent discipline , warmth/positive involvement , and involvement with the school . Evidence of differential intervention effects across child gender , race , site , and cohort was minimal Abstract Objective : To investigate possible risk factors and mechanisms behind the four times higher and diverging mortality from coronary heart disease in Lithuanian compared with Swedish middle aged men . Design : Concomitant cross sectional comparison of r and omly selected 50 year old men without serious acute or chronic disease . Methods and equipment were identical or highly st and ardised between the centres . Setting : LinkÖping ( Sweden ) and Vilnius ( Lithuania ) . Subjects : 101 and 109 men aged 50 in LinkÖping and Vilnius respectively . Main outcome measures : Anthropometric data , blood pressure , smoking , plasma lipid and lipoprotein concentrations , susceptibility of low density lipoprotein to oxidation , and plasma concentrations of fat soluble antioxidant vitamins . Results : Systolic blood pressure was higher ( 141v 133 mm Hg , P<0.01 ) , smoking habits were similar , and plasma total cholesterol ( 5.10 v 5.49 mmol/l , P<0.01 ) and low density lipoprotein cholesterol ( 3.30 v 3.68 mmol/l , P<0.01 ) lower in men from Vilnius compared with those from LinkÖping . Triglyceride , high density lipoprotein cholesterol , and Lp(a ) lipoprotein concentrations did not differ between the two groups . The resistance of low density lipoprotein to oxidation was lower in the men from Vilnius ; lag phase was 67.6 v 79.5 minutes ( P<0.001 ) . Also lower in the men from Vilnius were mean plasma concentrations of lipid soluble antioxidant vitamins ( ß carotene 377v 510 nmol/l , P<0.01 ; lycopene 327 v 615 nmol/l , P<0.001 ; and lipid adjusted tocopherol 0.25v 0.46 µmol/mmol , P<0.001 . Tocopherol concentration did not differ ) . Regression analysis showed that the lag phase was still significantly shorter by 10 minutes in men from Vilnius when the influence of other known factors was taken into account . Conclusions : The high mortality from coronary heart disease in Lithuania is not caused by traditional risk factors alone . Mechanisms related to antioxidant state may be important . Key messages Mortality from coronary heart disease in 50 - 54 year old men is four times higher in Lithuania than in Sweden Differences in traditional risk factors for coronary heart disease in 50 year old men in LinkÖping ( Sweden ) and Vilnius ( Lithuania ) were small – systolic blood pressure was higher in men from Vilnius , but total and low density lipoprotein cholesterol concentrations were lower and smoking habits similar The resistance of low density lipoprotein to oxidation was lower in men from Vilnius and remained after adjustment for antioxidant vitamin concentrations Plasma concentrations of the antioxidant vitamins , ß carotene , lycopene , and lipid adjusted tocopherol were lower in men from Vilnius ; tocopherol did not differ Mechanisms related to antioxidant state may be important in explaining the much higher mortality from coronary heart disease in Lithuanian compared with Swedish middle aged A r and omized controlled trial , using parent-based intervention ( PBI ) was design ed to reduce the incidence of alcohol-involved sexual victimization among first-year college students . The PBI , adapted from Turrisi et al. ( 2001 ) , was design ed to increase alcohol-specific and general communication between mother and daughter . Female graduating high school seniors and their mothers were recruited from the community and r and omly assigned to one of four conditions : Alcohol PBI ( n = 305 ) , Enhanced Alcohol + Sex PBI ( n = 218 ) , Control ( n = 288 ) or Unmeasured Control ( n = 167 ) . Mothers in the intervention conditions were provided an informational h and book and encouraged to discuss its contents with their daughters prior to college matriculation . Consistent with hypotheses , PBI , either st and ard or enhanced , was associated with lower incidence of incapacitated rape in the first year of college relative to controls . Path analysis revealed support for a hypothesized indirect effects model , by which intervention increased mother-daughter communication , which predicted lower frequency of first semester heavy episodic drinking , result ing in lower rates of alcohol-involved sexual victimization in the first year of college The Safe Date s Project is a r and omized trial for evaluating a school-based adolescent dating violence prevention program . Five waves of data were used to examine the effects of Safe Date s over time including primary and secondary prevention effects , moderators , and mediators of program effects . Using r and om coefficients models , with multiple imputation of missing data , significant program effects were found at all four follow-up periods on psychological , moderate physical , and sexual dating violence perpetration and moderate physical dating violence victimization . Marginal effects were found on sexual victimization . Effects on severe physical perpetration at all four follow-up periods were moderated by prior involvement in that type of violence . Primary and secondary prevention effects were found and the program was equally effective for males and females and for whites and non-whites . Program effects were mediated by changes in dating violence norms , gender-role norms , and awareness of community services PURPOSE Dating violence (DV)--physical , sexual , and psychological aggression in adolescent romantic relationships -- is prevalent among youth . Despite broad calls for primary prevention , few programs with demonstrated effectiveness exist . This cluster-r and omized trial examined the effectiveness of a DV perpetration prevention program targeting coaches and high school male athletes . METHODS The unit of r and omization was the high school ( 16 schools ) , and the unit of analysis was the athlete ( N = 2,006 students ) . Primary outcomes were intentions to intervene , recognition of abusive behaviors , and gender-equitable attitudes . Secondary outcomes explored byst and er behaviors and abuse perpetration . Regression models for clustered , longitudinal data assessed between-arm differences in over-time changes in mean levels of continuous outcomes in 1,798 athletes followed up at 3 months . RESULTS Intervention athletes ' changes in intentions to intervene were positive compared with control subjects , result ing in an estimated intervention effect of .12 ( 95 % CI : .003 , .24 ) . Intervention athletes also reported higher levels of positive byst and er intervention behavior than control subjects ( .25 , 95 % CI : .13 , .38 ) . Changes in gender-equitable attitudes , recognition of abusive behaviors , and DV perpetration were not significant . Secondary analyses estimated intervention impacts according to intensity of program implementation . Compared with control subjects , athletes exposed to full-intensity implementation of the intervention demonstrated improvements in intentions to intervene ( .16 , 95 % CI : .04 , .27 ) , recognition of abusive behaviors ( .13 , 95 % CI : .003 , .25 ) , and positive byst and er intervention ( .28 , 95 % CI : .14 , .41 ) . CONCLUSION This cluster-r and omized controlled trial supports the effectiveness of a school athletics-based prevention program as one promising strategy to reduce DV perpetration PURPOSE Given the high rate of dating violence between teens and associated deleterious outcomes , the need for effective prevention and early intervention programs is clear . Break the Cycle 's Ending Violence curriculum , a three-class-session prevention program focused on legal issues , is evaluated here for its impact on Latino/a youth . METHODS Tracks within large urban high schools that had at least 80 % Latino/a students were r and omized to immediate or delayed curriculum . Classrooms were r and omly selected within tracks and individual student outcomes were assessed pre- and postintervention and six months later . RESULTS Students in intervention classrooms showed improved knowledge , less acceptance of female-on-male aggression , and enhanced perception of the helpfulness and likelihood of seeking assistance from a number of sources immediately after the program . Improved knowledge and perceived helpfulness of an attorney were maintained six months later . There were no differences in recent abusive/fearful dating experiences or violence victimization or perpetration . CONCLUSIONS The Ending Violence curriculum has an impact on teen norms , knowledge , and help-seeking proclivities that may aid in early intervention for dating violence among Latino/a students The prevalence of date rape among college students is a major concern . Although much research has been done on risk factors for date rape , few research ers have specifically described interventions for the various stages of developing a date -rape prevention program . Previous programs have often relied on educational videos that feature a " typical " date -rape scenario , a format that some research ers suggest may have a negative effect on the way people engage in aggressive sexual behavior . A less violent theatrical production based on social learning theory and risk-factor reduction that result ed in a significant improvement in attitudes related to date rape among both male and female students at an elite Texas university is described Adolescent girls are involved in physical dating violence as both perpetrators and victims , and there are negative consequences associated with each of these behaviors . This article used a prospect i ve design with 519 girls dating in grade 9 to predict profiles of dating violence in grade 11 based on relationships with families of origin ( child maltreatment experiences , harsh parenting ) , and peers ( harassment , delinquency , relational aggression ) . In addition , dating violence profiles were compared on numerous indices of adjustment ( school connectedness , grade s , self-efficacy and community connectedness ) and maladjustment ( suicide attempts , distress , delinquency , sexual behavior ) for descriptive purpose s. The most common profile was no dating violence ( n = 367 ) followed by mutual violence ( n = 81 ) . Smaller numbers of girls reported victimization or perpetration only ( ns = 39 and 32 , respectively ) . Predicting grade 11 dating violence profile membership from grade 9 relationships was limited , although delinquency , parental rejection , and sexual harassment perpetration predicted membership to the mutually violent group , and delinquency predicted the perpetrator-only group . Compared to the non-violent group , the mutually violent girls in grade 11 had lower grade s , poorer self-efficacy , and lower school connectedness and community involvement . Furthermore , they had higher rates of peer aggression and delinquency , were less likely to use condoms and were much more likely to have considered suicide . There were fewer differences among the profiles for girls involved with dating violence . In addition , the victims-only group reported higher rates of sexual intercourse , comparable to the mutually violent group and those involved in nonviolent relationships . Implication s for prevention and intervention are highlighted The present study prospect ively explored the predictors of resistance strategies to a sexual assault situation . Participants were assessed at the beginning of an academic quarter on a number of variables , including past history of sexual victimization , perceived risk of sexual victimization , and intentions to use specific types of resistance strategies . Only women who reported being victimized over the interim ( N = 68 ) were included in the analyses , which suggested that women 's Time 1 intentions to utilize assertive resistance strategies ( e.g. , physically fight , run away ) and offender aggression predicted women 's use of assertive resistance strategies in response to the assault that occurred over the follow-up . Women 's utilization of nonforceful verbal resistance ( e.g. , reason , plead , quarrel ) was predicted by perpetrator aggression and previous sexual victimization . Women 's immobility ( e.g. , turn cold , freeze ) during the assault that took place over the interim was predicted by experiences of childhood sexual victimization and previous sexual victimization This study evaluates the effectiveness of a theoretically based rape prevention intervention with college men who were at high or low risk to perpetrate sexually coercive behavior . Participants ( N = 146 ) are r and omly assigned to the intervention or control group . Outcomes include rape myth acceptance , victim empathy , attraction to sexual aggression , sex-related alcohol expectancies , and behavioral indicators , measured across three time points . Positive effects are found for rape myth acceptance , victim empathy , attraction to sexual aggression , and behavioral intentions to rape . Only rape myth acceptance and victim empathy effects sustain at the 5-week follow-up . High-risk men are generally unaffected by the intervention although low-risk men produced larger effects than the entire sample . Results suggest rape prevention studies must assess risk status moderation effects to maximize prevention for high-risk men . More research is needed to develop effective rape prevention with men who are at high risk to rape This study determined the shape of trajectories from ages 13 to 19 of four types of dating abuse perpetration and examined whether the demographic characteristics of sex , minority status , socioeconomic status , and family structure systematic ally explained variation in the trajectories . The data are from 5 waves of data collected from 973 adolescents participating in the control group of a r and omized trial . The mean trajectory for psychological dating abuse was positive linear , but the mean trajectories were curvilinear for moderate physical , severe physical , and sexual dating abuse . At all ages , boys reported more severe physical and sexual dating abuse than girls , minorities reported more moderate and severe physical dating abuse than whites , adolescents in single-parent-households reported more psychological and severe physical dating abuse than those in two-parent-households , and parental education was negatively associated with psychological and moderate physical dating abuse perpetration . The findings have implication s for future research and for practice A r and omized , posttest-only experimental design was used to compare the date -rape attitudes of university students who were exposed to a mixed-gender date -rape workshop ( n = 163 ) with those of students who were not exposed ( n = 168 ) . A previously vali date d instrument , the 25-item Date Rape Attitudes Survey ( DRAS ) , was used as the criterion measure . Three hypotheses were tested , with the following results : ( 1 ) Men reported attitudes that were more tolerant of date rape than those reported by women ( ie , the men were more likely to condone date rape ) ; ( 2 ) students in the control group reported attitudes that were more tolerant of date rape than those reported by students in the treatment group ; and ( 3 ) men exhibited a greater effect from the program than did women . Finally , the authors discuss implication s of the study and offer recommendations for future research evaluating date -rape prevention programs Approximately 20 % of adolescents have experienced violence from a dating partner . The Safe Date s Project tests the effects of a program on the primary and secondary prevention of dating violence among adolescents living in a rural North Carolina county . The program being evaluated aims to prevent dating violence by changing dating violence norms , gender stereotyping , conflict-management skills , help-seeking , and cognitive factors associated with help-seeking . School activities include a theater production , a 10-session curriculum , and a poster contest . Community activities include special services for adolescents in violent relationships and community service provider training . A pretest-posttest experimental design with r and om allocation of 14 schools to treatment condition was used to test study hypotheses . Data were collected in schools using self-administered question naires . Eighty-one percent ( n = 1,967 ) of the eighth- and ninth- grade rs in the county completed baseline question naires , and 91 % of those adolescents completed follow-up question naires . The sample is 75.9 % Caucasian and 50.4 % female . Baseline data indicate that 25.4 % and 8.0 % of this sample have been victims of nonsexual and sexual dating violence , respectively , and 14.0 % and 2.0 % have been perpetrators of nonsexual and sexual dating violence , respectively . Consistent with other adolescent dating violence studies , both boys and girls report being victims and perpetrators of dating violence . Control and treatment groups are similar at baseline on all demographic , mediating , and outcome variables . Findings suggest that dating violence is prevalent among adolescents and that prevention programs are warranted This study examined the effects of a gender-specific HIV/STD prevention intervention with two dosage levels ( four-session , eight-session ) among women reporting physical abuse by a current or recent ( past year ) intimate partner . From 360 women included in the full r and omized trial , we conducted subgroup analyses among 152 women who experienced partner physical abuse within the past year . Unprotected vaginal and anal sex occasions and negotiation skills were examined as outcomes . We also assessed whether the intervention increased previously abused women 's subsequent risk of physical abuse . Among abused women , those in the eight-session , but not the four-session , intervention decreased their unprotected sex occasions or maintained consistent safer sex at both 1-month ( OR = 3.63 , 95 % CI = 1.50–8.80 ) and 1-year ( OR = 2.88 , 95 % CI = 1.17–7.10 ) postintervention . In the short-term , abused women in both the four- and eight-session groups had a greater odds of using an alternative strategy ( e.g. , refusal , “ outercourse , ” or mutual testing ) and of having a safer sex discussion with their partners relative to their controls , and they scored higher on intention to negotiate safer sex . The intervention did not increase or decrease the incidence of subsequent abuse during the 1-year follow-up period . A gender-specific intervention that focuses on negotiation skills in the context of potentially abusive partners benefits , and does not appear to harm , recently abused women Two model-based interventions design ed to reduce the amount of date rape attempted by male college students were developed and evaluated . The Rape Supportive Cognitions ( RSC ) intervention targeted commonly held false beliefs that promote or condone coercive sexual behavior . The Victim Empathy/ Outcome Expectancies ( VE/OE ) intervention targeted poor victim empathy and problematic rape outcome expectancies . Seventy-four high-risk subjects as determined by scores on the Attraction to Sexual Aggression scale ( ASA ) ( Malamuth , 1989 ) were r and omly assigned to one of the treatment groups ( RSC or VE/OE ) or to a no-treatment control group . Treatment effects were assessed using subjects ' pre- and posttreatment scores on the ASA , the Rape Myth Acceptance , the Acceptance of Interpersonal Violence , and the Adversarial Sexual Beliefs scales ( Burt , 1980 ) , as well as subjects ' posttreatment scores on the Rape Conformity Assessment ( Schewe and O'Donohue , 1995 ) . Results indicated that both treatments were significantly more effective than no treatment . The RSC group showed clinical ly significant changes on three of the five dependent measures , while the VE/OE group evidence d clinical ly significant changes on only one measure . This is the first well-controlled rape prevention study to demonstrate clear improvements in treated high-risk males over control group subjects OBJECTIVES The purpose of this pilot study was to evaluate a five-session dating violence prevention curriculum in terms of its effect on attitudes justifying the use of dating violence . METHODS The curriculum was implemented in all health classes in a Long Isl and , New York , school . A total of 193 students participated ( boys , n = 106 ; girls , n = 87 ) . A quasi-experimental design was used to evaluate change in attitudes justifying dating violence , with health classes r and omly assigned to the treatment or no-treatment conditions . RESULTS Pre- to postprogram assessment s indicated that there were significant decreases in overall attitudes justifying the use of dating violence as a means to resolve conflict among students exposed to the curriculum material , whereas those who were not exposed did not show attitude change from pre- to postprogram evaluation . CONCLUSIONS The curriculum shows promise as an effective tool for changing attitudes condoning dating violence . Future research is needed to determine whether the observed attitude change is also linked to reduction in aggressive behaviors This study prospect ively follows 135 children 5 - 12 years of age with sexual behavior problems from a r and omized trial comparing a 12-session group cognitive-behavioral therapy ( CBT ) with group play therapy and follows 156 general clinic children with nonsexual behavior problems . Ten-year follow-up data on future juvenile and adult arrests and child welfare perpetration reports were collected . The CBT group had significantly fewer future sex offenses than the play therapy group ( 2 % vs. 10 % ) and did not differ from the general clinic comparison ( 3 % ) , supporting the use of short-term CBT . There were no group differences in nonsexual offenses ( 21 % ) . The findings do not support assumptions about persistent or difficult to modify risk and raise questions about policies and practice s founded on this assumption This study examines peer resistance skills following a 21-lesson classroom-based intervention to build healthy relationships and decrease abusive and health-risk behaviors among adolescents . The Fourth R instructs students in positive relationship skills , such as negotiation and delay , for navigating challenging peer and dating scenarios . Observational data from 196 grade 9 students participating in a larger cluster r and omized controlled trial were used to evaluate post-intervention acquisition of peer resistance skills . Pairs of students engaged in a role play paradigm with older student actors , where they were subjected to increasing pressure to comply with peer requests related to drugs and alcohol , bullying , and sexual behavior . Specific and global measures of change in peer resistance responses were obtained from two independent sets of observers , blinded to condition . Specific peer resistance responses ( negotiation , delay , yielding to pressure , refusal , and compliance ) were coded by research assistants ; global peer resistance responses were rated by teachers from other schools ( thinking / inquiry , application , communication , and perceived efficacy ) . Students who received the intervention were more likely to demonstrate negotiation skills and less likely to yield to negative pressure relative to controls . Intervention students were also more likely to use delay than controls ; control girls were more likely to use refusal responses ; the number of times students complied with peer requests did not differ . Teacher ratings demonstrated significant main effects favoring intervention youth on all measures . Program and research implication s are highlighted Six classes of students attending private parochial high schools were matched according to geographic and grade level variables and were r and omly assigned as intact groups to view either a film concerning wife abuse or a neutral control film . The experimental film had no significant impact on attitude ratings given for the two most common student-generated situations of abuse : the intoxicated husb and and the unfaithful wife . Correlational assessment s between demographic variables and attitude ratings revealed that greater suspicion of abuse was associated with higher justifiability ratings for the intoxicated husb and situation . Estimations of higher frequencies of spouse abuse were associated with higher justifiability ratings for the unfaithful wife situation . Results are discussed in light of current wife abuse education programs and prevention strategies The present study utilizes the National College Health Risk Behavior Survey to examine the relationship between health-risk behaviors and sexual victimization among a sample of college women . A prospect i ve design is utilized to examine the relationship between health-risk behaviors as measured at baseline and sexual victimization during a 3-month follow-up period . After controlling for age and parents ' education , a history of adolescent sexual victimization was associated with the following health-risk behaviors as measured at pretest : increased likelihood of cigarette smoking , marijuana use , suicidal ideation , experience of physical violence within a dating relationship , use of diet pills and vomiting or laxatives to lose weight , multiple sexual partners , and early sexual intercourse . Prospect ively , women 's history of adolescent sexual victimization was the strongest predictor of sexual victimization during the 3-month follow-up . Implication s of univariate associations between early sexual intercourse , suicidal ideation , and problematic weight loss behaviors and subsequent experience of sexual victimization are discussed Abstract Rape myth acceptance , likelihood of raping , and sexually coercive behavior of 145 fraternity men r and omly assigned to a control group or a rape-prevention program were surveyed . One third of 23 fraternities on a mid-Atlantic public university campus volunteered to participate in the study . The rape-prevention intervention consisted of “ the men 's program , ” a victim empathy-based presentation titled “ How to help a sexual assault survivor : What men can do . ” Although no evidence of change in sexually coercive behavior was found , significant 7-month declines in rape myth acceptance and the likelihood of committing rape were shown among program participants . In the case of rape myth acceptance , the 7-month decrement remained lower in the participant group than in the control group . Implication s of using these initial findings from the men 's program for rape-prevention programming are discussed The majority of studies evaluating the relationship between childhood sexual assault and subsequent sexual assault perpetration by men have been conducted retrospectively and with incarcerated population s. The present study seeks to improve on previous research by prospect ively investigating the relationship between childhood sexual assault and subsequent perpetration of dating violence in adulthood in men . Although there is a significant relationship between childhood sexual abuse and history of sexual assault perpetration at baseline , prospect i ve analyses indicate that childhood sexual assault is not predictive of perpetration during the follow-up period . The role of family factors , including parental conflict resolution , is implicated in subsequent sexual aggression . These results are supportive of the idea that the effects of childhood sexual abuse may be mediated by a variety of factors OBJECTIVES An earlier report described desirable 1-month follow-up effects of the Safe Date s program on psychological , physical , and sexual dating violence . Mediators of the program-behavior relationship also were identified . The present report describes the 1-year follow-up effects of the Safe Date s program . METHODS Fourteen schools were in the r and omized experiment . Data were gathered by question naires in schools before program activities and 1 year after the program ended . RESULTS The short-term behavioral effects had disappeared at 1 year , but effects on mediating variables such as dating violence norms , conflict management skills , and awareness of community services for dating violence were maintained . CONCLUSIONS The findings are considered in the context of why program effects might have decayed and the possible role of boosters for effect maintenance The purpose of this investigation was to empirically evaluate a sexual assault prevention program . Of the 360 female college students who participated in the investigation , 181 students were in the treatment group and 165 students were in the control group . Although the program was not effective in decreasing the incidence of sexual assault for women with a sexual assault history , it was effective in decreasing the incidence of sexual assault for women without a sexual assault history . The program also led to a decrease in dating behaviors found to be associated with acquaintance rape and an increase in knowledge about sexual assault for the treatment group . The implication s of these results for future preventive efforts are discussed PURPOSE To examine the effects of a family-based teen dating abuse prevention program , Families for Safe Date s , primarily on outcomes related to testing the conceptual underpinnings of the program including ( 1 ) factors motivating and facilitating caregiver engagement in teen dating abuse prevention activities , and 2 ) risk factors for teen dating abuse , and secondarily on dating abuse behaviors . METHODS Families were recruited nationwide using listed telephone numbers . Caregivers and teens completed baseline and 3-month follow-up telephone interviews ( n = 324 ) . Families r and omly allocated to treatment condition received the Families for Safe Date s program including six mailed activity booklets followed-up by health educator telephone calls . RESULTS There were significant ( < .05 ) treatment effects in hypothesized directions on most of the factors motivating and facilitating caregiver engagement in teen dating abuse prevention activities including caregiver perceived severity of dating abuse , response efficacy for preventing dating abuse , self-efficacy for talking about dating abuse , knowledge of dating abuse , acceptance of dating abuse , communication skills with the teen , and belief in the importance of involvement in their male ( but not female ) teen 's dating . The latter effect was the only one moderated by sex of the teen . The targeted risk factor affected by the program was teen acceptance of dating abuse . Treatment was also significantly associated with less physical dating abuse victimization . CONCLUSIONS Modifications to the program are warranted , but overall , the findings are very favorable for the first family-based teen dating abuse prevention program to be evaluated This study evaluated a CD-ROM educational program in sexual violence prevention for middle school students . A r and omized control-group pretest-posttest design was used . Seventy-nine students were r and omly assigned to either an experimental ( n = 39 ) or control ( n = 40 ) group . The experimental group watched the CD-ROM , whereas the control group did not . Both groups were pretested for the levels of knowledge and attitude about sexual violence prevention prior to intervention . A CD-ROM titled Educational Program for the Prevention of Sexual Violence was used for the intervention . The instrument contains 32 true-false items that measure knowledge level and 20 items comprising a four-point Likert-type scale that measure the attitude to sexual violence . There was a significant increase in knowledge in the experimental group , while no differences on attitude were found between the experimental and control groups . A CD-ROM-based program can be effective for delivering instructions on sexual violence prevention in the classroom |
12,007 | 18,828,848 | There is no reliable trial evidence for interventions in inherited EB . | BACKGROUND Many interventions have been described for inherited epidermolysis bullosa ( EB ) , but it is unclear which are beneficial .
AIMS A systematic review of r and omized controlled trials ( RCTs ) was performed to inform practice and highlight research gaps . | Although , as yet , there is no specific treatment of epidermolysis bullosa ( EB ) simplex , anecdotal reports suggest the possible efficacy of one of the newer topical nonsteroidal anti-inflammatory agents , bufexamac . To determine whether bufexamac has any role in the management of this disease , a double-blind placebo-controlled crossover clinical trial was undertaken with ten patients ( nine , Weber-Cockayne variant ; one , generalized EB simplex ) . Each of the two preparations was applied four times daily during the 2 four-week treatment periods . Weekly assessment s included counts of blisters , crusts , and erosions , and assessment s of alterations in cutaneous pain , healing times , and activity times before further blister formation . Although considerable variability in individual responses was noted , no significant difference was detectable between the active drug and its matched placebo . On the basis of these findings , it was concluded that 5 % topical bufexamac is ineffective in the treatment of EB simplex BACKGROUND Recessive dystrophic epidermolysis bullosa is an uncommon , severely disabling , heritable disorder characterized by abnormal fragility of the skin . Open trials have suggested that phenytoin is an effective treatment , and this therapy is now widely used . METHODS To determine the efficacy of phenytoin in the treatment of recessive dystrophic epidermolysis bullosa , we performed a r and omized , double-blind , placebo-controlled , crossover trial in 36 patients . Each treatment was given for five to seven months , separated by a two-month period . We measured the total number of blisters and erosions on the entire body , the size of three plaques containing blisters and erosions , and the number of blisters and erosions in the three plaques at the beginning and end of each treatment period in each patient . RESULTS Twenty-two patients completed both courses of therapy , seven patients completed one course , and seven patients withdrew before completing a single course . There was no significant difference in disease activity between phenytoin treatment and placebo treatment , as measured by changes in the number of blisters and erosions on the entire body ( 7 percent decrease vs. 6 percent increase ) , in the area of three design ated plaques ( 0.4 percent decrease vs. 0.2 percent increase ) , or in the number of blisters and erosions in the design ated plaques ( 12 percent decrease vs. 31 percent increase ) . CONCLUSIONS Phenytoin is not an effective treatment for patients with recessive dystrophic epidermolysis bullosa |
12,008 | 28,367,429 | Our findings suggest that 12 weeks of SOF/LDV can not be considered noninferior to 12 weeks of SOF/LDV/RBV to achieve SVR12 in patients with CHC who have cirrhosis and failed prior therapy | Background .
The recommended therapy for patients with chronic hepatitis C ( CHC ) , genotype 1 , who have cirrhosis and have failed prior therapy is 12 weeks of sofosbuvir ( SOF ) , ledipasvir ( LDV ) , and ribavirin ( RBV ) .
This recommendation is based on expert opinion , and the efficacy of 12 weeks of SOF/LDV compared to SOF/LDV/RBV in this patient population has not yet been established . | BACKGROUND Interferon-based treatment is not suitable for many patients with hepatitis C virus ( HCV ) infection because of contraindications such as psychiatric illness , and a high burden of adverse events . We assessed the efficacy and safety of an interferon-free regimen -- a fixed-dose combination of the nucleotide polymerase inhibitor sofosbuvir ( 400 mg ) and the HCV NS5A inhibitor ledipasvir ( 90 mg ) , with and without ribavirin -- in patients with genotype-1 hepatitis C infection who were treatment-naive or previously treated with a protease-inhibitor regimen . METHODS For this open-label study , we enrolled 100 adult patients ( > 18 years ) with HCV infection at a centre in the USA between Nov 2 , 2012 , and Dec 21 , 2012 . In cohort A , we used a computer-generated sequence to r and omly assign ( 1:1:1 ; stratified by HCV genotype [ 1a vs 1b ] ) 60 non-cirrhotic , treatment-naive patients to receive sofosbuvir plus ledipasvir for 8 weeks ( group 1 ) , sofosbuvir plus ledipasvir and ribavirin for 8 weeks ( group 2 ) , or sofosbuvir plus ledipasvir for 12 weeks ( group 3 ) . In cohort B , we r and omly allocated ( 1:1 ; stratified by genotype and presence or absence of cirrhosis ) 40 patients who previously had virological failure after receiving a protease inhibitor regimen to receive sofosbuvir plus ledipasvir for 12 weeks ( group 4 ) or sofosbuvir plus ledipasvir and ribavirin for 12 weeks ( group 5 ) . 22 ( 55 % ) of 40 patients in cohort B had compensated cirrhosis . The primary endpoint was sustained virological response 12 weeks after treatment ( SVR12 ) , analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT01329978 . FINDINGS In cohort A , SVR12 was achieved by 19 ( 95 % ) of 20 patients ( 95 % CI 75 - 100 ) in group 1 , by 21 ( 100 % ) of 21 patients ( 84 - 100 ) in group 2 , and by 18 ( 95 % ) of 19 patients ( 74 - 100 ) in group 3 . In cohort B , SVR12 was achieved by 18 ( 95 % ) of 19 patients ( 74 - 100 ) in group 4 and by all 21 ( 100 % ) of 21 patients ( 84 - 100 ) in group 5 . Two patients had viral relapse ; one patient was lost to follow-up after achieving sustained virological response 8 weeks after treatment . The most common adverse events were nausea , anaemia , upper respiratory tract infection , and headache . One patient in group five had a serious adverse event of anaemia , thought to be related to ribavirin treatment . INTERPRETATION These findings suggest that the fixed-dose combination of sofosbuvir-ledipasvir alone or with ribavirin has the potential to cure most patients with genotype-1 HCV , irrespective of treatment history or the presence of compensated cirrhosis . Further clinical trials are needed to establish the best treatment duration and to further assess the contribution of ribavirin . FUNDING Gilead Sciences Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND The phase 2 C-SALVAGE study ( Hepatitis C-Salvage Study for Patients who Failed DAA/PR Therapy ) demonstrated a 96.2 % sustained virologic response at 12 weeks ( SVR12 ) rate using the NS3/4A protease inhibitor grazoprevir and the NS5A inhibitor elbasvir together with ribavirin in treatment-experienced patients with chronic hepatitis C virus ( HCV ) genotype 1 infection . METHODS C-SALVAGE was a prospect i ve open-label trial of grazoprevir 100 mg once daily and elbasvir 50 mg once daily coadministered with weight-based ribavirin twice daily for 12 weeks in genotype 1-infected cirrhotic and noncirrhotic patients who had failed treatment with ≥ 4 weeks of pegylated interferon and ribavirin plus either boceprevir , telaprevir , or simeprevir . Although the primary efficacy outcome was SVR12 , patients were also evaluated 24 weeks after cessation of study therapy . Population sequencing was performed at baseline and periodically in virologic failures throughout the 24-week posttherapy follow-up period . RESULTS SVR24 rates were 76 of 79 ( 96.2 % ) overall , with all 3 relapses occurring by posttherapy week 8 . Every NS3 and NS5A variant detected at baseline reappeared at the time of relapse and persisted throughout the available follow-up period . NS3_A156 T emerged in virus from each patient at relapse , but rapidly disappeared over the ensuing 2 weeks in 2 patients . NS5A_Y93H emerged in virus from 2 patients at relapse and persisted for the entire follow-up period . CONCLUSIONS Grazoprevir and elbasvir with ribavirin for 12 weeks maintained HCV suppression for at least 24 weeks posttherapy without late relapses . Baseline resistance-associated variants ( RAVs ) stably reappeared at relapse in all 3 patients with virologic failure . NS5A_RAVs emerging at relapse persisted for the full 24-week follow-up period . If confirmed , this finding could complicate retreatment of the small number of patients failing regimens containing an NS5A inhibitor . CLINICAL TRIALS REGISTRATION NCT02105454 BACKGROUND Effective treatment for hepatitis C virus ( HCV ) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need . METHODS We conducted a phase 3 , r and omized , open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin , with or without a protease inhibitor . Patients were r and omly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily , fixed-dose combination tablet for 12 weeks , ledipasvir-sofosbuvir plus ribavirin for 12 weeks , ledipasvir-sofosbuvir for 24 weeks , or ledipasvir-sofosbuvir plus ribavirin for 24 weeks . The primary end point was a sustained virologic response at 12 weeks after the end of therapy . RESULTS Among the 440 patients who underwent r and omization and were treated , 20 % had cirrhosis and 79 % had HCV genotype 1a infection . The rates of sustained virologic response were high in all treatment groups : 94 % ( 95 % confidence interval [ CI ] , 87 to 97 ) in the group that received 12 weeks of ledipasvir-sofosbuvir ; 96 % ( 95 % CI , 91 to 99 ) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin ; 99 % ( 95 % CI , 95 to 100 ) in the group that received 24 weeks of ledipasvir-sofosbuvir ; and 99 % ( 95 % CI , 95 to 100 ) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin . No patient discontinued treatment owing to an adverse event . The most common adverse events were fatigue , headache , and nausea . CONCLUSIONS Treatment with a once-daily , single-tablet regimen of ledipasvir and sofosbuvir result ed in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment . ( Funded by Gilead Sciences ; ION-2 Clinical Trials.gov number , NCT01768286 . ) A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was discovered . Optimization of antiviral potency and pharmacokinetics led to the identification of 39 ( ledipasvir , GS-5885 ) . Compound 39 ( GT1a replicon EC50 = 31 pM ) has an extended plasma half-life of 37 - 45 h in healthy volunteers and produces a rapid > 3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients . 39 has been shown to be safe and efficacious , with SVR12 rates up to 100 % when used in combination with direct-acting antivirals having complementary mechanisms BACKGROUND Compared with other countries , patients with chronic hepatitis C infection in Japan tend to be older , have more advanced liver disease , and are more likely to have been previously treated for hepatitis C. We aim ed to assess the efficacy and safety of an all-oral , fixed-dose combination of the hepatitis C virus NS5A inhibitor ledipasvir and the NS5B nucleotide polymerase inhibitor sofosbuvir with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with chronic genotype 1 hepatitis C virus infection . METHODS In this r and omised , open-label study , we enrolled patients from 19 clinical Japanese centres . Patients were r and omly assigned ( 1:1 ) to receive either ledipasvir ( 90 mg ) and sofosbuvir ( 400 mg ) or ledipasvir , sofosbuvir , and ribavirin ( dosed according to the Japanese Copegus product label-ie , patients ≤60 kg received 600 mg daily , patients > 60 kg to ≤80 kg received 800 mg daily , and patients > 80 kg received 1000 mg daily ) orally once daily for 12 weeks . After completion or early discontinuation of treatment , patients were followed up off-treatment for 24 weeks . Eligible patients were at least 20 years of age with chronic genotype 1 hepatitis C virus infection with serum hepatitis C virus RNA concentrations of at least 5 log10 IU/mL , creatinine clearance of at least 1·0 mL/s , and a platelet count of at least 50 × 10(9 ) per L. An interactive web response system was used to manage patient r and omisation and treatment assignment . R and omisation was stratified by the presence or absence of cirrhosis for treatment-naive patients and stratified by presence or absence of cirrhosis and by previous treatment category ( relapser or breakthrough , non-responder , or interferon-intolerant ) for previously treated patients . Within each strata , patients were sequentially assigned to either treatment with ledipasvir-sofosbuvir or ledipasvir-sofosbuvir plus ribavirin in a 1:1 ratio with block size of 4 . The primary endpoint was sustained virological response 12 weeks after completion of treatment ( SVR12 ) assessed in all patients who were r and omly assigned and received at least one dose of study drug ; safety outcomes were assessed in all patients who received at least one dose of study drug . This trial is registered with Clinical Trials.gov , number NCT01975675 . FINDINGS Between Oct 15 , 2013 and Dec 13 , 2013 , 341 patients were r and omly assigned to treatment groups and received at least one dose of study treatment . SVR12 was achieved in all 171 ( 100 % ) patients ( 83 of 83 treatment naive and 88 of 88 treatment experienced ) receiving ledipasvir-sofosbuvir ( 95 % CI 98 - 100 ) and 167 ( 98 % ) of 170 patients ( 80 of 83 treatment naive and 87 of 87 treatment experienced ) receiving ledipasvir-sofosbuvir plus ribavirin ( 95 % CI 95 - 100 ) . Of the 76 patients with baseline NS5A resistant variants , 75 ( 99 % ) achieved SVR12 . Two ( 1·2 % ) of 170 patients in the ledipasvir-sofosbuvir plus ribavirin group discontinued treatment because of adverse events . The most common adverse events were nasopharyngitis ( 50 [ 29·2 % ] of 171 ) , headache ( 12 [ 7·0 % ] of 171 ) , and malaise ( nine [ 5·3 % ] of 171 ) in patients receiving ledipasvir-sofosbuvir ; and nasopharyngitis ( 40 [ 23·5 % ] of 170 ) , anaemia ( 23 [ 13·5 % ] of 170 ) , and headache in those receiving ledipasvir-sofosbuvir and ribavirin ( 15 [ 8·8 % ] of 170 ) . INTERPRETATION Although existing regimens for the treatment of hepatitis C virus are effective for many patients , medical needs remain unmet , particularly in Japan where the population with hepatitis C virus genotype 1 is generally older and treatment-experienced , with advanced liver disease . The efficacy , tolerability , and absence of drug-drug interactions of ledipasvir-sofosbuvir suggest that it could be an important option for treatment of genotype 1 hepatitis C virus in Japanese patients . FUNDING Gilead Sciences BACKGROUND & AIMS We evaluated an all-oral regimen comprising the nucleotide polymerase inhibitor sofosbuvir ( SOF ) with the NS5A inhibitor ledipasvir ( LDV ) or the NS5B non-nucleoside inhibitor GS-9669 in patients with genotype 1 hepatitis C virus ( HCV ) infection . METHODS A total of 113 patients were enrolled . Sofosbuvir ( 400 mg once daily ) and LDV ( 90 mg once daily ) plus ribavirin ( RBV ) were given for 12 weeks to treatment-naïve ( TN ) patients ( n = 25 ) and those who did not respond to previous therapy ( prior null responders , n = 9 ) . Sofosbuvir and GS-9669 ( 500 mg once daily ) plus RBV were given for 12 weeks to TN patients ( n = 25 ) and prior null responders ( n = 10 ) . Additionally , prior null responders with cirrhosis were r and omly assigned to groups given a fixed-dose combination of SOF and LDV , with RBV ( n = 9 ) or without RBV ( n = 10 ) . Finally , a group of TN patients received SOF , LDV , and RBV for 6 weeks ( n = 25 ) . The primary efficacy end point was sustained virologic response 12 weeks after therapy ( SVR12 ) . RESULTS SVR12 was achieved by 25 of 25 ( 100 % ) TN patients receiving SOF , LDV , and RBV and 23 of 25 ( 92 % ) of those receiving SOF , GS-9669 , and RBV . Of TN patients receiving 6 weeks of SOF , LDV , and RBV , 17 of 25 ( 68 % ) achieved SVR12 . All noncirrhotic prior null responders receiving 12 weeks of SOF along with another direct-acting antiviral agent plus RBV achieved SVR12 - 9 of 9 ( 100 % ) of those receiving SOF , LDV , and RBV and 10 of 10 ( 100 % ) of those receiving SOF , GS-9669 , and RBV . Among cirrhotic prior null responders , SVR12 was achieved by 9 ( 100 % ) of those receiving SOF , LDV , and RBV and 7 ( 70 % ) of those receiving SOF and LDVD without RBV . The most common reported adverse events were headache , fatigue , and nausea . CONCLUSIONS The combination of SOF and a second direct-acting antiviral agent is highly effective in TN patients with HCV genotype 1 infection and in patients that did not respond to previous treatment . Clinical Trials.gov ID NCT01260350 |
12,009 | 22,073,154 | In the treatment of lung cancers , selenium may reduce cisplatin-induced nephrotoxicity and side effects associated with radiation therapy .
CONCLUSIONS Selenium may be effective for lung cancer prevention among individuals with lower selenium status , but at present should not be used as a general strategy for lung cancer prevention . | BACKGROUND Selenium is a natural health product widely used in the treatment and prevention of lung cancers , but large chemoprevention trials have yielded conflicting results .
We conducted a systematic review of selenium for lung cancers , and assessed potential interactions with conventional therapies . | Interest in the chemopreventive effects of the trace element selenium has spanned the past three decades . Of > 100 studies that have investigated the effects of selenium in carcinogen-exposed animals , two-thirds have observed a reduction in tumor incidence and /or preneoplastic endpoints ( G. F. Combs and S. B. Combs , The Role of Selenium in Nutrition Chapter 10 , pp . 413 - 462 . San Diego , CA : Academic Press , 1986 , and B. H. Patterson and O. A. Lev and er , Cancer Epidemiol . Biomark . Prev . , 6 : 63 - 69 , 1997 ) . The Nutritional Prevention of Cancer Trial , a r and omized clinical trial reported by Clark et al. ( L. C. Clark et al. , JAMA , 276 : 1957 - 1963 , 1996 ) , showed as a secondary end point , a statistically significant decrease in lung cancer incidence with selenium supplementation . The adjusted hazard ratio ( HR ) was 0.56 [ 95 % confidence interval ( CI ) , 0.31 - 1.01 ; P = 0.05 ] . These results were based on active follow-up of 1312 participants . This re analysis used an extended Nutritional Prevention of Cancer Trial participant follow-up through the end of the blinded clinical trial on February 1 , 1996 . The additional 3 years added 8 cases to the selenium-treated group and 4 cases to the placebo group , and increased follow-up to 7.9 years . The relative risk of 0.70 ( 95 % CI , 0.40 - 1.21 ; P = 0.18 ) is not statistically significant . Whereas the overall adjusted HR is not significant ( HR = 0.74 ; 95 % CI , 0.44 - 1.24 ; P = 0.26 ) , and the HR for current and former smokers was not significant , the trend is toward a reduction in risk of incident lung cancer with selenium supplementation . In a subgroup analysis there was a nominally significant HR among subjects with baseline plasma selenium in the lowest tertile ( HR = 0.42 ; 95 % CI , 0.18 - 0.96 ; P = 0.04 ) . The analysis for the middle and highest tertiles of baseline showed HRs of 0.91 and 1.25 . The current re analysis indicates that selenium supplementation did not significantly decrease lung cancer incidence in the full population , but a significant decrease among individuals with low baseline selenium concentrations was observed Controlled trials that use r and omized allocation are the best tool to control for bias and confounding in trials testing clinical interventions . Investigators must be sure to include information that is required by the reader to judge the validity and implication s of the findings in the reports of these trials . In part , complete reporting of trials will allow clinicians to modify their clinical practice to reflect current evidence toward the improvement of clinical outcomes . The consoli date d st and ards of reporting trials ( CONSORT ) statement was developed to assist investigators , authors , review ers , and editors on the necessary information to be included in reports of controlled clinical trials . The CONSORT statement is applicable to any intervention , including herbal medicinal products . Controlled trials of herbal interventions do not adequately report the information suggested in CONSORT . Recently , reporting recommendations were developed in which several CONSORT items were elaborated to become relevant and complete for r and omized controlled trials of herbal medicines . We expect that these recommendations will lead to more complete and accurate reporting of herbal trials . We wrote this explanatory document to outline the rationale for each recommendation and to assist authors in using them by providing the CONSORT items and the associated elaboration , together with examples of good reporting and empirical evidence , where available , for each . These recommendations for the reporting of herbal medicinal products presented here are open to revision as more evidence accumulates and critical comments are collected BACKGROUND Brazil nuts provide a rich natural source of selenium , yet no studies have investigated the bioavailability of selenium in humans . OBJECTIVE We investigated the efficacy of Brazil nuts in increasing selenium status in comparison with selenomethionine . DESIGN A r and omized controlled trial was conducted with 59 New Zeal and adults . Participants consumed 2 Brazil nuts thought to provide approximately 100 mug Se , 100 mug Se as selenomethionine , or placebo daily for 12 wk . Actual intake from nuts averaged 53 mug Se/d ( possible range : 20 - 84 mug Se ) . Plasma selenium and plasma and whole blood glutathione peroxidase ( GPx ) activities were measured at baseline and at 2 , 4 , 8 , and 12 wk , and effects of treatments were compared . RESULTS Plasma selenium increased by 64.2 % , 61.0 % , and 7.6 % ; plasma GPx by 8.3 % , 3.4 % , and -1.2 % ; and whole blood GPx by 13.2 % , 5.3 % , and 1.9 % in the Brazil nut , selenomethionine , and placebo groups , respectively . Change over time at 12 wk in plasma selenium ( P < 0.0001 for both groups ) and plasma GPx activity in the Brazil nut ( P < 0.001 ) and selenomethionine ( P = 0.014 ) groups differed significantly from the placebo group but not from each other . The change in whole blood GPx activity was greater in the Brazil nut group than in the placebo ( P = 0.002 ) and selenomethionine ( P = 0.032 ) groups . CONCLUSION Consumption of 2 Brazil nuts daily is as effective for increasing selenium status and enhancing GPx activity as 100 mug Se as selenomethionine . Inclusion of this high-selenium food in the diet could avoid the need for fortification or supplements to improve the selenium status of New Zeal and ers This pilot study evaluated the feasibility and effectiveness of conducting a double-blind clinical trial for the prevention of lung cancer with selenium ( Se ) in Yunnan Tin Corporation , the People 's Republic of China , where the incidence rates of lung cancer are extraordinarily high among the miners . Forty healthy miners were r and omized to either 300 μg of Se in high Se malt cakes or an identical placebo of malt cakes daily for one year . Subjects consumed their usual daily diet . The low Se concentrations in plasma ( 0.05±0.008 μg/mL ) and hair ( 0.442±0.085 μg/g ) reflected their low dietary Se intake in the control subjects . In Se-supplemented group , the Se status was increased by 178 % for serum and 194.8 % for hair . The serum GSHpx activity was increased by 155.7 % , whereas the lipid peroxide level was reduced by 74.5 % compared to the placebo . The results of UDS assay indicated that the lymphocyte DNA damage induced by ultraviolet irradiation and carcinogen 3,4-benzpyrene could be protected by Se supplementation . Se-supplementation did not affect the liver function test ( SGPT ) , as well as the concentrations of hemoglobin , albumin , and cholesterol . Thus , daily intake of 300 μg Se in form of Se-malt as a chemopreventive measure is safe and effective to humans with low Se status The Nutritional Prevention of Cancer Trial was a r and omized , clinical trial design ed to evaluate the efficacy of selenium as selenized yeast ( 200 microg daily ) in preventing the recurrence of nonmelanoma skin cancer among 1312 residents of the Eastern United States . Original secondary analyses through December 31 , 1993 showed striking inverse associations between treatment and the incidence of total [ hazard ratio ( HR ) = 0.61 , 95 % confidence interval ( CI ) = 0.46 - 0.82 ] , lung , prostate , and colorectal cancer and total cancer mortality . This report presents results through February 1 , 1996 , the end of blinded treatment . Effect modification by baseline characteristics is also evaluated . The effects of treatment overall and within subgroups of baseline age , gender , smoking status , and plasma selenium were examined using incidence rate ratios and Cox proportional hazards models . Selenium supplementation reduced total ( HR = 0.75 , 95 % CI = 0.58 - 0.97 ) and prostate ( HR = 0.48 , 95 % CI = 0.28 - 0.80 ) cancer incidence but was not significantly associated with lung ( HR = 0.74 , 95 % CI = 0.44 - 1.24 ) and colorectal ( HR = 0.46 , 95 % CI = 0.21 - 1.02 ) cancer incidence . The effects of treatment on other site-specific cancers are also described . The protective effect of selenium was confined to males ( HR = 0.67 , 95 % CI = 0.50 - 0.89 ) and was most pronounced in former smokers . Participants with baseline plasma selenium concentrations in the lowest two tertiles ( < 121.6 ng/ml ) experienced reductions in total cancer incidence , whereas those in the highest tertile showed an elevated incidence ( HR = 1.20 , 95 % CI = 0.77 - 1.86 ) . The Nutritional Prevention of Cancer trial continues to show a protective effect of selenium on cancer incidence , although not all site-specific cancers exhibited a reduction in incidence . This treatment effect was restricted to males and to those with lower baseline plasma selenium concentrations Nonexperimental studies suggest that individuals with higher selenium ( Se ) status are at decreased risk of cancer . The Nutritional Prevention of Cancer ( NPC ) study r and omized 1,312 high-risk dermatology patients to 200-mcg/day of Se in selenized yeast or a matched placebo ; selenium supplementation decreased the risk of lung , colon , prostate , and total cancers but increased the risk of nonmelanoma skin cancer . In this article , we report on a small sub study in Macon , GA , which began in 1989 and r and omized 424 patients to 400-mcg/day of Se or to matched placebo . The subjects from both arms had similar baseline Se levels to those treated by 200 mcg , and those treated with 400-mcg attained plasma Se levels much higher than subjects treated with 200 mcg . The 200-mcg/day Se treatment decreased total cancer incidence by a statistically significant 25 % ; however , 400-mcg/day of Se had no effect on total cancer incidence Summary □ Patients and Method : In order to test the hypothesis that a dietary supplement of selenium ( Se ) may reduce cancer risk , 1312 patients with histories of basa/squamous cell carcinomas of the skin were assigned in r and om , double-blind fashion to daily oral supplements of either Se-enriched yeast ( 200 µg Se/day ) , or a low-Se yeast placebo . Patients were recruited in 1983 to 1990 and were followed with regular dermatologic examinations through , 1993 for a total of 8269 person-years of observation . Skin cancer diagnoses were confirmed histologically and plasma Se concentration was determined at 6 to 12 months intervals . All deaths and patient-reported illnesses were confirmed and documented by consultation with the patient medical care providers . □ Results : Results showed that Se-supplementation did not significantly affect the incidences of recurrent basal/squamous cell carcinomas of the skin . However , Se-treatment was associated with reductions in total cancer mortality and in the incidences of lung , colorectal , prostate and total cancers . These effects were consistent over time and between study clinics . □ Conclusion : The results strongly suggest benefits of Se-supplementation for this cohort of patients and support the hypothesis that supplemental Se can reduce risks to at least some types of cancer Purpose We conducted a phase I study to determine the recommended dose of selenomethionine ( SLM ) in combination with irinotecan that consistently results in a protective plasma selenium ( Se ) concentrations > 15 μM after 1 week of SLM loading . Experimental Design A 3 - 3 st and ard escalation design was followed . SLM was given orally twice daily ( BID ) for one week ( loading ) followed by continuous once daily ( QD ) dosing ( maintenance ) . Seven dose levels of selenomethionine were investigated . Irinotecan was given intravenously at a fixed st and ard weekly dose , starting on the first day of maintenance SLM . Results Thirty-one patients were treated on study . Dose limiting diarrhea complicated by sepsis was noted in one of six patients at each of the dose-levels 1 and 7 . Dose-levels ≥ 5 ( 4,800 mcg/dose loading maintenance ) result ed in day 8 Se concentrations > 15 μM while dose-level 7 ( 7,200 mcg/dose loading and maintenance ) result ed in day 8 Se concentrations > 20 μM. No significant variations in SN-38 or biliary index were noted between weeks 1 and 4 of treatment . Despite achieving target Se concentrations , gastrointestinal and bone marrow toxicities were common and irinotecan dose modification was prevalent . Objective responses were seen in two patients and nine patients had disease control for 6 months or longer . Conclusions Selenomethionine can be escalated safely to 7,200 mcg BID × 1 week followed by 7,200 mcg QD in combination with a st and ard dose of irinotecan . No major protection against irinotecan toxicity was established ; however , interesting clinical benefits were noted-supporting the investigation of this combination in future efficacy trials CONTEXT Secondary analyses of 2 r and omized controlled trials and supportive epidemiologic and pre clinical data indicated the potential of selenium and vitamin E for preventing prostate cancer . OBJECTIVE To determine whether selenium , vitamin E , or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men . DESIGN , SETTING , AND PARTICIPANTS A r and omized , placebo-controlled trial ( Selenium and Vitamin E Cancer Prevention Trial [ SELECT ] ) of 35,533 men from 427 participating sites in the United States , Canada , and Puerto Rico r and omly assigned to 4 groups ( selenium , vitamin E , selenium + vitamin E , and placebo ) in a double-blind fashion between August 22 , 2001 , and June 24 , 2004 . Baseline eligibility included age 50 years or older ( African American men ) or 55 years or older ( all other men ) , a serum prostate-specific antigen level of 4 ng/mL or less , and a digital rectal examination not suspicious for prostate cancer . INTERVENTIONS Oral selenium ( 200 microg/d from L-selenomethionine ) and matched vitamin E placebo , vitamin E ( 400 IU/d of all rac-alpha-tocopheryl acetate ) and matched selenium placebo , selenium + vitamin E , or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years . MAIN OUTCOME MEASURES Prostate cancer and prespecified secondary outcomes , including lung , colorectal , and overall primary cancer . RESULTS As of October 23 , 2008 , median overall follow-up was 5.46 years ( range , 4.17 - 7.33 years ) . Hazard ratios ( 99 % confidence intervals [ CIs ] ) for prostate cancer were 1.13 ( 99 % CI , 0.95 - 1.35 ; n = 473 ) for vitamin E , 1.04 ( 99 % CI , 0.87 - 1.24 ; n = 432 ) for selenium , and 1.05 ( 99 % CI , 0.88 - 1.25 ; n = 437 ) for selenium + vitamin E vs 1.00 ( n = 416 ) for placebo . There were no significant differences ( all P>.15 ) in any other prespecified cancer end points . There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group ( P = .06 ) and type 2 diabetes mellitus in the selenium group ( relative risk , 1.07 ; 99 % CI , 0.94 - 1.22 ; P = .16 ) but not in the selenium + vitamin E group . CONCLUSION Selenium or vitamin E , alone or in combination at the doses and formulations used , did not prevent prostate cancer in this population of relatively healthy men . TRIAL REGISTRATION clinical trials.gov identifier : NCT00006392 The effect of selenium ( Se ) in reducing the toxicity of cisplatin in cancer patients was studied . Forty-one patients were r and omized into group A ( 20 patients with Se administration in first cycle of chemotherapy as study cases and without Se in second cycle of chemotherapy as control ) and group B ( 21 patients without Se in first cycle of chemotherapy and with Se in second cycle of chemotherapy ) . The 400 μg per day of Se as Seleno-Kappacarrageenan were administered from 4 before to 4 d after chemotherapy for study cases . The serum Se increased from 70.4±22.86 to 157.04±60.23 ng/mL ( P<0.001 ) in patients received Se . The cisplatin dosage was iv administration in 60–80 mg/m2 on the first day . The results showed that the peripheral WBC counts on day 14 after initiation of chemotherapy in study cases was significantly higher than the controls ( 3.35±2.01 vs 2.31±1.38 [ × 109L])/L , p<0.05 ) . On the other h and , the consumption of GCSF for the cases was significantly less than the controls ( 110.1±82.2 vs 723.6±192.6 IU , p<0.05 ) . The volumes of blood transfusion for the study group were also significantly less than the controls ( 0 vs 62±38mL , p<0.05 ) . The nephrotoxicity of cisplatin was measured by urine enzymes ( NAG , GGT , AAP , LAP , and ALP ) were determined prior to and at 2 , 24 , 48 , and 72h after initiation of chemotherapy . The urine enzymes NAG , GGT , AAP , and ALP after chemotherapy for cases were significantly lower than the controls . No toxicity of Seleno-Kappacarrageenan was noted . The above results suggest that the Se can be used as an agent for reducing the nephrotoxicity and bone marrow suppression induced by cisplatin PURPOSE We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy ( RT ) for cervical and uterine cancer . METHODS AND MATERIAL S Whole-blood selenium concentrations were measured in patients with cervical cancer ( n = 11 ) and uterine cancer ( n = 70 ) after surgical treatment , during RT , at the end of RT , and 6 weeks after RT . Patients with initial selenium concentrations of less than 84μg/L were r and omized before RT either to receive 500 μg of selenium ( in the form of sodium selenite [ selenase , biosyn Arzneimittel GmbH , Fellbach , Germany ] ) by mouth on the days of RT and 300 μg of selenium on the days without RT or to receive no supplement during RT . The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT ; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects . RESULTS A total of 81 patients were r and omized . We enrolled 39 in the selenium group ( SG ) and 42 in the control group ( CG ) . Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT . The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria ( version 2 ) in the SG was 20.5 % compared with 44.5 % in the CG ( p = 0.04 ) . Other blood parameters , Eastern Cooperative Oncology Group performance status , and self-reported quality of life were not different between the groups . CONCLUSIONS Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea The hypothesis that a dietary supplement of selenium ( Se ) may reduce cancer risk was tested experimentally in humans . Patients with histories of basal/squamous cell carcinomas of the skin were assigned r and omly in double-blind fashion to daily oral supplements of either Se-enriched yeast ( 200 micrograms Se/day ) , or a low-Se yeast placebo . A total of 1312 patients recruited in 1983 - 1990 were followed with regular dermatologic examinations through 1993 for a total of 8269 person-years of observation . Skin cancer diagnoses were confirmed histologically . Plasma Se concentration was determined at 6 - 12 months intervals . All deaths and patient-reported illnesses were recorded ; reported cancers were confirmed and documented by consultation with the patient medical care providers . The results indicate that Se did not significantly affect the primary endpoints : incidences of recurrent basal/squamous cell carcinomas of the skin . However , Se-treatment was associated with reductions in several secondary endpoints : total mortality , mortality from all cancers combined , as well as the incidence of all cancers combined , lung cancer , colorectal cancer and prostate cancer . The consistencies of these associations over time , between study clinics and for the leading cancer sites strongly suggests benefits of Se-supplementation for this cohort of patients , supporting the hypothesis that supplemental Se can reduce cancer risk . Although Se did not shown protective effects against non-melanoma skin cancers , the suggested reductions in risks to other frequent cancers dem and further evaluation in well controlled clinical intervention trials Epidemiological studies have suggested that low levels of selenium are associated with a higher incidence of both lung and prostate cancer . We analyzed the selenium serum concentration in 356 Carotene and Retinol Efficacy Trial ( CARET ) participants who later developed lung cancer and 356 matched controls and in 235 prostate cancer cases and 456 matched controls . Serum sample s were obtained a mean of 4.7 years before diagnosis for both tumor types . Controls were matched to cases by year of r and omization , age , smoking status , treatment arm , exposure population ( asbestos workers or cigarette smokers ) , and year of blood draw . In the control population ( n = 820 ) , significant predictors of low serum selenium concentration were current smoking status and East Coast locations of the study center . Overall , there was no significant difference in mean serum selenium in lung cancer cases versus controls ( 11.91 microg/dl versus 11.77 microg/dl ) or prostate cancer cases versus controls ( 11.48 microg/dl versus 11.43 microg/dl ) . No statistically significant trend in odds ratio was seen across quartiles of serum selenium for lung cancer ( P = 0.49 ) or prostate cancer ( P = 0.69 ) . In a sub population of 174 prostate cancer patients who had clinical and pathological staging material review ed , there was no association between serum selenium and Gleason score or clinical or pathological stage . In the CARET population of current and former smokers consuming an ad libitum diet , the serum concentration of selenium was not a risk factor for either lung cancer or prostate cancer The objective of this double-blind , r and omized study was to establish whether sodium selenite administered orally or intravenously reduces postoperative lymphedema after oral tumor surgery and to study the effect of sodium selenite on glutathione peroxidase ( GPX ) activity and oxygen radical production . Twenty patients were enrolled in the study . Each of the participants received 1000 μg sodium selenite intravenously or orally daily for 3 wk during the pre- , intra- , and postoperative period . The extent of lymphedema was measured for 2 wk and the plasma and whole-blood selenium concentration , GPX , reactive oxygen species ( ROS ) , NO , and malonic dialdehyde were measured for 1 yr postoperatively . There was an inverse correlation between the severity of the lymphedema and the wholeblood/plasma selenium concentration and GPX activity . In addition , a positive correlation between the ROS concentration and the extent of lymphedema was observed . A significant reduction of lymphedema occurred in the sodium selenite-treated group . It is concluded that sodium selenite represents a suitable adjuvant treatment of secondary lymphedema in surgically treated patients with tumors in the oral and maxillofacial areas . Treatment with sodium selenite is especially advantageous as it can be instituted immediately after surgery prior to wound healing when manual lymphatic decongestion therapy can not be applied Abstract Objective : To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case – control study nested in an occupational cohort of tin miners . Methods : Male workers free of cancer enrolled in the cohort . During up to 6 years of follow-up , 339 lung cancer cases were diagnosed and , among these cases , those who donated blood prospect ively ( n = 108 ) were eligible for this study . For each case , two controls alive and free of cancer at the time of case diagnosis were matched on age and date of blood collection . Results : Overall , we observed no association between serum alpha-tocopherol , gamma-tocopherol or selenium levels and lung cancer risk . However , a significant gradient of decreasing lung cancer risk with increasing serum alpha-tocopherol was apparent for men less than 60years old ( odds ratio by tertile : 1.0 , 0.9 , 0.2 ; trend p = 0.002 ) . Alpha-tocopherol was also protective in men who reported no alcohol drinking ( OR by tertile : 1.0 , 0.6 , 0.3 ; trend p = 0.008 ) . Conclusion : Although there were no significant overall associations between prospect ively collected serum alpha-tocopherol , gamma-tocopherol or selenium and incidence of lung cancer , results from this study suggest that higher alpha-tocopherol levels may be protective in men less than 60 years old and in those who do not drink alcohol Concerns about the toxicity of selenium has limited the doses used in chemoprevention . Based on previous studies , intakes of 400 microg/day and plasma selenium of 1000 ng/ml ( Dietary Reference Intakes , Academy Press , New York , 2000 , p. 384 ) were established as the no observed adverse effect level ( NOAEL ) . This investigation summarizes the plasma response and toxicity reports from 24 men with biopsy-proven prostate cancer who were r and omized to either 1600 or 3200 microg/day of selenized yeast as part of a controlled clinical trial testing selenium as a chemopreventive agent for prostate cancer progression . Subjects were on these doses for averages of almost 12 months . Plasma selenium levels were monitored throughout the course of follow-up . Symptoms of selenium toxicity were assessed by patient interview with specific questions regarding breath , hair and nail changes . Several liver and kidney function tests and hematology were measured at 6-month intervals . 8 subjects were r and omized to the 1600 microg/day and 16 to the 3200 microg/day group . The mean plasma selenium levels achieved with supplementation were 492.2 ng/ml ( SD = 188.3 ) and 639.7 ng/ml ( SD = 490.7 ) for the 1600 and 3200 microg/ day doses , respectively . The 3200 microg/day group reported more selenium-related side effects . Blood chemistry and hematology results were all within normal limits for both treatment groups . More subjects on 3200 microg/day reported symptoms of selenium toxicity ; however , these reports did not correspond to peaks in plasma selenium levels . We observed no obvious selenium-related serious toxicities . As selenium is used in more chemoprevention and therapeutic setting s , additional information on selenium species , sequestration of selenium in specific organs , excretion , and toxicities is needed We examined the effect of supplementation with four different combinations of vitamins and minerals in the prevention of lung cancer mortality among 29,584 healthy adults from Linxian , China . In accord with a partial factorial design , the participants were r and omly assigned to take either a vitamin/mineral combination or a placebo for 5.25 years . The combinations tested in this trial were as follows : factor A , retinol and zinc ; factor B , riboflavin and niacin ; factor C , ascorbic acid and molybdenum ; factor D , β-carotene , α-tocopherol , and selenium . Lung cancer deaths ( n = 147 ) identified during the trial period ( 1986 - 1991 ) and 10 years after the trial ended ( 1991 - 2001 ) were the study outcome . No significant differences in lung cancer death rates were found for any of the four combinations of supplements tested in this study , using log-rank tests ( all P values are > 0.20 ) or Cox proportional hazards models adjusted for age , sex , commune , and other treatments . No significant interactions were seen for age , sex , or smoking status . Supplementation with combinations of vitamins and minerals at nutrient-repletion levels for 5.25 years did not reduce lung cancer mortality in this nutrient-inadequate population in Linxian , China . ( Cancer Epidemiol Biomarkers Prev 2006;15(8):1562–4 The present study was undertaken to explore the effect of administration of high doses of sodium selenite on the expression of Bcl-2 in patients with non-Hodgkin ’s lymphoma ( NHL ) . Fifty patients with newly diagnosed NHL were r and omly divided into two groups . Group A-I received st and ard chemotherapy whereas group A-II received adjuvant sodium selenite 0.2 mg kg−1 day−1 for 30 days in addition to chemotherapy . Enzyme-linked immunosorbent assay was used to assess Bcl-2 at the time of diagnosis and after therapy in the two groups . Sodium selenite administration result ed in significant decline of Bcl-2 level after therapy in group A-II ( 8.6 ± 6.9 ng/ml vs 3 6.9 ± 7.9 ng/ml , P < 0.05 ) . Also , complete response reached 60 % in group A-II compared to 40 % in group A-I. Significant increase in CD4/CD8 ratio was noticed in group A-II compared to group A-I after therapy ( 1.45 ± 0.36 vs 1.10 ± 0.28 p 0.04 ) . Overall survival time in months was significantly longer in complete remission patients in group A-II ( 21.87 ± 1.41 ) compared to group A-I ( 19.70 ± 1.95 ) ( p = 0.01 ) . It is concluded that sodium selenite administration at the dosage and duration chosen acts as a downregulator of Bcl-2 and improves clinical outcome OBJECTIVE To determine whether a nutritional supplement of selenium will decrease the incidence of cancer . DESIGN A multicenter , double-blind , r and omized , placebo-controlled cancer prevention trial . SETTING Seven dermatology clinics in the eastern United States . PATIENTS A total of 1312 patients ( mean age , 63 years ; range , 18 - 80 years ) with a history of basal cell or squamous cell carcinomas of the skin were r and omized from 1983 through 1991 . Patients were treated for a mean ( SD ) of 4.5 ( 2.8 ) years and had a total follow-up of 6.4 ( 2.0 ) years . INTERVENTIONS Oral administration of 200 microg of selenium per day or placebo . MAIN OUTCOME MEASURES The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin . The secondary end points , established in 1990 , were all-cause mortality and total cancer mortality , total cancer incidence , and the incidences of lung , prostate , and colorectal cancers . RESULTS After a total follow-up of 8271 person-years , selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer . There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group ( relative risk [ RR ] , 1.10 ; 95 % confidence interval [ CI ] , 0.95 - 1.28 ) , and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls ( RR , 1.14 ; 95 % CI , 0.93 - 1.39 ) . Analysis of secondary end points revealed that , compared with controls , patients treated with selenium had a nonsignificant reduction in all-cause mortality ( 108 deaths in the selenium group and 129 deaths in the control group [ RR ; 0.83 ; 95 % CI , 0.63 - 1.08 ] ) and significant reductions in total cancer mortality ( 29 deaths in the selenium treatment group and 57 deaths in controls [ RR , 0.50 ; 95 % CI , 0.31 - 0.80 ] ) , total cancer incidence ( 77 cancers in the selenium group and 119 in controls [ RR , 0.63 ; 95 % CI , 0.47 - 0.85 ] ) , and incidences of lung , colorectal , and prostate cancers . Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group , the blinded phase of the trial was stopped early . No cases of selenium toxicity occurred . CONCLUSIONS Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin . However , results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of , and mortality from , carcinomas of several sites . These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be PURPOSE : We conducted a phase I study to determine the maximum tolerated dose ( MTD ) of irinotecan with fixed , nontoxic high dose of selenomethionine . EXPERIMENTAL DESIGN : Selenomethionine was given orally as a single daily dose containing 2,200 mug of elemental selenium ( Se ) starting 1 week before the first dose of irinotecan . Irinotecan was given i.v . once weekly x 4 every 6 weeks ( one cycle ) . The starting dose of irinotecan was 125 mg/m(2)/wk . Escalation occurred in cohorts of three patients until the MTD was defined . Pharmacokinetic studies were done for selenium and irinotecan and its metabolites . RESULTS : Three of four evaluable patients at dose level 2 of irinotecan ( 160 mg/m(2)/wk ) had a dose-limiting diarrhea . None of the six evaluable patients at dose level 1 ( 125 mg/m(2)/wk irinotecan ) had a dose-limiting toxicity . One patient with history of irinotecan-refractory colon cancer achieved a partial response . The long half-life of selenium result ed in a prolonged accumulation towards steady-state concentrations . No significant changes in the pharmacokinetics of CPT-11 , SN-38 , or SN-38 G were identified ; however , the coadministration of selenomethionine significantly reduced the irinotecan biliary index , which has been associated with gastrointestinal toxicity . CONCLUSIONS : Selenomethionine at 2,200 mug/d did not allow the safe escalation of irinotecan beyond the previously defined MTD of 125 mg/m(2 ) . None of the patients receiving 125 mg/m(2 ) of irinotecan had grade > 2 diarrhea . Unexpected responses and disease stabilizations were noted in a highly refractory population . Further escalation of selenomethionine is recommended in future trials to achieve defined protective serum concentrations of selenium BACKGROUND Oxidative stress is implicated in oral carcinogenesis and has been found to be aggravated during radiotherapy . A great deal of attention has been focused on the possible therapeutic implication s of selenium as a potent antioxidant . We determined whether selenium supplementation to radiation treated oral cancer patients render improvement in the antioxidant status against oxidative stress . METHOD Blood sample s were collected from stage ( III ) oral cancer patients before initiating radiotherapy ( Group B ) ( n=63 ) and this group is bifurcated into Group C- patients given radiotherapy alone ( n=27 ) and Group D- patients given radiotherapy and supplemented with selenium ( 400 mug/day for 6 months ) ( n=36 ) . Both Group C and D were followed up for 6 months . We evaluated the plasma selenium concentration , non-enzymatic system including GSH , vitamins E , C , A and ceruloplasmin and enzymatic antioxidant system including superoxide dismutase , catalase , glutathione peroxidase , glutathione reductase , glucose-6-phosphate dehydrogenase . RESULTS The concentrations of selenium , all non-enzymatic antioxidants and the activities of enzymatic antioxidants were found to be lowered in oral cancer patients ( Group B ) , compared to normal ( Group A ) ( p<0.05 ) . Similar decrease in the concentration of selenium and antioxidants status was observed in radiotherapy group ( Group C ) ( p<0.05 ) . On the contrary , selenium group ( Group D ) showed marked increase in the concentrations of selenium and antioxidant status at 6 months compared to radiation group ( Group C ) ( p<0.05 ) . CONCLUSION The observed result represents the antioxidant property of selenium through the improvement of antioxidant defense system . Selenium supplementation could be of great interest in protecting cells against oxidative stress PURPOSE The aim of this explorative study was to evaluate the impact of selenium in the treatment of lymphedema after radiotherapy . MATERIAL S AND METHODS Between June 1996 and June 2001 , 12 patients with edema of the arm and 36 patients with edema of the head- and -neck region were treated with selenium for therapy-related lymphedema . Of these 36 patients , 20 had interstitial endolaryngeal edema associated with stridor and dyspnea . All patients received sodium selenite over 4 to 6 weeks . RESULTS Self- assessment using a visual analog scale ( n = 48 ) showed a reduction of 4.3 points when comparing pre- and posttreatment values ( p < 0.05 ) . Of 20 patients with endolaryngeal edema , 13 underwent no tracheostomy , 5 underwent a temporary tracheostomy , and only 2 underwent a permanent tracheostomy . Ten of 12 patients with arm edema showed a circumference reduction of the edematous limb and improvement in the Skin-Fold Index by 23.3 points . An improvement of one stage or more was shown by the Földi or the Miller score ( n = 28 ) in 22 ( Földi score ) and in 24 ( Miller score ) patients . CONCLUSIONS Treatment with sodium selenite is well tolerated and easy to deliver . Additionally , our results suggest that sodium selenite has a positive effect on secondary -developing lymphedema caused by radiation therapy alone or by irradiation after surgery |
12,010 | 15,533,124 | Despite a high survival of FPDs , biological and technical complications are frequent .
This , in turn , means that substantial amounts of chair time have to be accepted by the clinician following the incorporation of implant-supported FPDs . | OBJECTIVES The objective of this systematic review was to assess the 5- and 10-year survival of implant supported fixed partial dentures ( FPDs ) and to describe the incidence of biological and technical complications . | The clinical question at issue , whether it is possible to combine implants and natural teeth via fixed bridges , is of current interest . The treatment of the subjects of this prospect i ve study was performed between June 1984 and December 1986 . This article presents the 5-year results of the study . The consecutive patient material comprised 23 patients with Applegate Kennedy Class I residual dentition in the m and ible and a complete maxillary denture . All 23 patients were provided with implants ad modum Brånemark in each m and ibular quadrant . One side was r and omized to rehabilitation with fixed bridge between the distal tooth of the residual dentition and an implant ; the other side received a free-st and ang bridge on 2 implants . The fixture survival rate was 88 % . No difference was found between the two sides . Bridge stability was 89 % for the implant bridges and 91 % for the combination bridges . The change in marginal bone level at the implants was small during the 5-year follow up period ( on average 0.1 - 0.3 mm ) and with no difference between the two sides . In conclusion , it was not possible to demonstrate any higher risk of implant or prosthetic failure for tooth-implant fixed bridges compared with implant-supported bridges This study conducted a longitudinal prospect i ve clinical study of the single-crystal sapphire ( Al2O3 ) cylindrical screw-shaped endosteal dental implant , and attempted to establish clinical parameters to evaluate implant success or failure . Twenty-eight m and ibular implants ( 17 patients ) were placed . After six weeks ' healing , 23 implants in 15 patients served as distal abutments for fixed prostheses ( baseline ) . Implants were evaluated for bleeding index , crevicular fluid volume index , plaque accumulation index , radiographic index , mobility index , and patient comfort . Any implant failing in three of these criteria or implants removed were judged as failures . After 10 years , of the 21 baseline implants recalled ( two implants were lost to recall ) , 17 were fully functional , for an 81 % success rate . The use of qualitative and quantitative clinical evaluation parameters as utilized in this study appears to be important and useful in assessment s of the clinical serviceability of dental implants . These parameters can be used in human clinical trials as well as in experimental animal studies 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 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 This long-term follow-up study aim ed to compare the outcome of fixed prostheses supported by teeth and implants and by freest and ing implants only . MATERIAL S AND METHODS From prosthesis insertion up to 14 years ( mean 6.5 y ) , 18 patients were followed . Implant-supported prostheses with and without tooth connection were compared within the same jaw . The tooth-implant prostheses were supported by 30 implants and 30 teeth , and the freest and ing prostheses were supported by 48 implants . Implant outcome , marginal bone stability , and mechanical complications were recorded . RESULTS Neither implant mobility nor fractures of any component of the implants were observed . No prosthesis complications were observed , and the same applied for crown cement failure and intrusion of teeth . Only one periapical lesion was detected at the first follow up . The annual change of the marginal bone level around connected and freest and ing implants did not differ significantly . The mean marginal bone loss ( over the 2 groups ) for the first 6 months amounted to 1.08 mm . After the first 6 months , an annual marginal bone loss of 0.015 mm was observed . There was no difference between the 3 connection types ( single implant connected to single tooth , multiple implants and /or multiple teeth connected with single connector , and multiple connectors ) for the first 6 months or thereafter . The marginal bone loss ( over the 3 groups ) for the first 6 months was 1.15 mm . After the first 6 months , the annual bone loss ( over the 3 groups ) amounted to 0.015 mm . CONCLUSION Based on the results of this study , splinting teeth with implants for implant-supported fixed prostheses did not affect the long-term outcome in comparison to freest and ing implants In 123 patients , 339 implants were connected to 313 teeth by means of fixed partial prostheses ( test ) and followed up for 1.5 - 15 years ( mean : 6.5 ) . In another ad r and om selected 123 patients , 329 implants were connected to each other by means of 123 freest and ing fixed partial prostheses ( control ) and were followed up for 1.3 - 14.5 years ( mean : 6.2 ) . The aim of this study was to compare both treatment modalities with each other based on implant , tooth and prosthesis complications . The cumulative implant success , based on implant immobility and /or lack of implant fractures after loading , in the test and control groups amounted to 95 % and 98.5 % , respectively . Although in the test group 10 implants versus only 1 in the control group failed , a regression analysis of the survival data , based on the cox proportional hazards model , revealed no significant difference . In the test group periapical lesions ( 3.5 % ) , tooth fracture ( 0.6 % ) and tooth extraction due to fatal decay or periodontitis ( 1 % ) were observed , besides tooth intrusion ( 3.4 % ) and crown cement failure ( 8 % ) . Framework fracture occurred in 3 patients . In the control group , only 2 abutment screws fractured . The treatment of partial edentulism by means of oral implants was beneficial for our patients . Because of a clear tendency of more implant failures ( mobility or fractures ) and tooth complications in the tooth-implant connected prostheses , the freest and ing solution is the primary option to be considered . To avoid intrusion of abutment teeth , the connection , if made , should be completely rigid Intramobile cylinder ( IMZ ) implants with either of two coatings , hydroxyapatite ( HA ) or titanium plasma-flame ( TPF ) , as distal abutments for combined tooth implant-supported restorations , were compared in 313 partially edentulous m and ibles with respect to postprosthetical failure patterns and complication frequencies in a r and omized multicenter clinical trial . Within the treatment protocol s , the two coatings do not show evidence of different efficacy with respect to occurrence of postprosthetical integration deficiency ( ID ) or functional deficiency ( FD ) . Statistical equivalence for an absolute effect of + /-15 % in event-free survival could only be demonstrated for FD , not for ID , however . Intent-to-treat and per- protocol population analyses gave consistent results . Hazards of occurrence of ID and FD , adjusted for years of follow-up , were estimated for ID as 7 % per year ( 95%CI 4 - 10 % per year ) with HA and 5 % per year ( 95%CI 3 - 7 % per year ) with TPF , and for FD as 5 % per year ( 95%CI 3 - 7 % per year ) with HA and 4 % per year ( 95%CI 2 - 6 % per year ) with TPF . The 5-year cumulative success rates for no ID were 69.5 % ( 95%CI 58 - 81 % ) with HA and 82.2 % ( 95%CI 74 - 91 % ) with TPF . With respect to frequencies of complications , there was no relevant statistically significant difference between the two coatings 49 patients participated in a prospect i ve study of treatment of total or partial edentulism with fixed prosthodontics supported by Bioceram sapphire implants . 15 patients were treated for maxillary or m and ibular edentulism , and 7 for a missing maxillary anterior tooth . The remaining 27 patients , with Applegate-Kennedy Class I-IV residual dentitions , were treated with fixed bridges supported by free-st and ing implants , or bridges supported by teeth and implants . Implant success , prosthesis stability , radiographic marginal bone level as well as parameters for peri-implant health were evaluated . The study began in 1982 , and clinical treatment of the last patients was completed in 1988 , i.e. , a follow-up period ranging from 7 to 13 years . Of the patients treated for total m and ibular edentulism , one implant fractured after 6 years in situ . The bone implant score ( BIS ) values for those implants were at the time for the bridge cementation 63.5 + /- 1.4 and at 1 , 2 , 3 and 5 year follow-ups 62.1 + /- 1.4 , 61.9 + /- 1.5 , 61.5 + /- 1.6 , and 60.95 + /- 1.3 , respectively . The success rate was 100 % , 100 % and 97.7 % for the m and ible at 3 , 5 and 10 years , respectively . Of the 7 edentulous patients treated with maxillary fixed bridges , 6 implants in 1 patient had to be removed after 1 year in service . Another 2 patients lost all their implants , 6 each , after 36 months . 6 implants in the 4th patient did not fulfil the criteria for success and were rated as failures at the four year follow-up . The success rate was thus 58.1 % , 44.2 % and 44.2 % for the maxilla at 3 , 5 and 10 year follow-ups , respectively . Of the 7 patients in whom single missing teeth were replaced , 1 implant in the premolar region was lost during the 1st year post-operatively , but no other complications or changes in BIS were observed . Of the 27 patients treated for partial edentulism ( 56 implants total ) 1 implant , of a 4-unit free st and ing maxillary bridge fractured after 6 years and was later replaced . There were no statistically significant differences in BIS changes for the implants when used as abutments for partial maxillary or m and ibular edentulism . The cumulative success rates for the implants in the partially maxilla were 96.3 , 92.6 and 92.6 at the 3 , 5 and 10 years respectively and 100 % in the m and ible over the whole period PURPOSE This prospect i ve clinical trial examined the effect on teeth and implants when rigidly or non-rigidly connected in a cross-arch model . MATERIAL S AND METHODS Thirty patients received 2 implants , 1 on each side of the m and ible , and were restored with 3-unit fixed partial dentures connected either rigidly or non-rigidly to an abutment tooth . Patients were followed for at least 5 years post-restoration . RESULTS Repeated- measures analysis revealed no significant difference in crestal bone loss at implants ( rigid versus non-rigid methods ) . An overall significant difference ( P < .001 ) was found comparing methods for teeth . Paired t tests revealed no significant differences in crestal bone levels for implants or teeth at the 5-year recall . Kaplan-Meier methods and the Cox proportional hazards model showed no differences between attachment methods with regard to success based on survival and bone loss criteria . During the 5-year recall period , 1 implant ( rigid side ) was removed . Four implants developed bone loss greater than 2 mm during the course of this trial . One tooth on the rigid side and 2 teeth on the non-rigid side had greater than 2 mm of crestal bone loss and were removed secondary to fractures . In all , 5 abutment teeth were removed , all of which had been treated with root canal therapy and fractured at the interface of the post within the tooth . There was no clear relationship of tooth fracture to attachment . Repeated- measures analysis of mobility values revealed no significant changes over the time course of this study , and paired t tests revealed no statistically significant differences between implants for mobility . Repeated- measures analysis and paired t tests for probing depth revealed no significant changes over the time course of this study . There were no significant differences in soft tissue indices for either attachment method . The percentage of patients who had measurable intrusion was 66 % for the non-rigid group , and 44 % for the rigid group ; 25 % of the non-rigid teeth had greater than 0.5 mm intrusion , compared with 12.5 % for the rigid group . For the 2 time periods evaluated , there was no significant increase in intrusion over time . The non-rigid-side implant required more nonscheduled visits to treat problems than the rigid implant and the teeth . DISCUSSION Most patients were treated successfully with rigid or non-rigid attachment of implants to teeth . CONCLUSION The high incidence of intrusion and non-scheduled patient visits suggest that alternative treatments without connecting implants to teeth may be indicated |
12,011 | 25,332,808 | CONCLUSIONS In conclusion , while poor quality unblinded studies provide evidence that renal denervation using catheter-based systems is effective in reducing systolic and diastolic blood pressure in resistant hypertension , the largest r and omised controlled trial to date ( SYMPLICITY HTN-3 ) failed to demonstrate any benefit | OBJECTIVE The objective of this study is to evaluate the efficacy and safety of renal denervation in patients with resistant hypertension . | OBJECTIVES The aim of this prospect i ve r and omized study was to assess the impact of renal artery denervation in patients with a history of refractory atrial fibrillation ( AF ) and drug-resistant hypertension who were referred for pulmonary vein isolation ( PVI ) . BACKGROUND Hypertension is the most common cardiovascular condition responsible for the development and maintenance of AF . Treating drug-resistant hypertension with renal denervation has been reported to control blood pressure , but any effect on AF is unknown . METHODS Patients with a history of symptomatic paroxysmal or persistent AF refractory to ≥2 antiarrhythmic drugs and drug-resistant hypertension ( systolic blood pressure > 160 mm Hg despite triple drug therapy ) were eligible for enrolment . Consenting patients were r and omized to PVI only or PVI with renal artery denervation . All patients were followed ≥1 year to assess maintenance of sinus rhythm and to monitor changes in blood pressure . RESULTS Twenty-seven patients were enrolled , and 14 were r and omized to PVI only , and 13 were r and omized to PVI with renal artery denervation . At the end of the follow-up , significant reductions in systolic ( from 181 ± 7 to 156 ± 5 , p < 0.001 ) and diastolic blood pressure ( from 97 ± 6 to 87 ± 4 , p < 0.001 ) were observed in patients treated with PVI with renal denervation without significant change in the PVI only group . Nine of the 13 patients ( 69 % ) treated with PVI with renal denervation were AF-free at the 12-month post-ablation follow-up examination versus 4 ( 29 % ) of the 14 patients in the PVI-only group ( p = 0.033 ) . CONCLUSIONS Renal artery denervation reduces systolic and diastolic blood pressure in patients with drug-resistant hypertension and reduces AF recurrences when combined with PVI Renal sympathetic hyperactivity is seminal in the maintenance and progression of hypertension . Catheter-based renal sympathetic denervation has been shown to significantly reduce blood pressure ( BP ) in patients with hypertension . Durability of effect beyond 1 year using this novel technique has never been reported . A cohort of 45 patients with resistant hypertension ( systolic BP ≥160 mm Hg on ≥3 antihypertension drugs , including a diuretic ) has been originally published . Herein , we report longer-term follow-up data on these and a larger group of similar patients subsequently treated with catheter-based renal denervation in a nonr and omized manner . We treated 153 patients with catheter-based renal sympathetic denervation at 19 centers in Australia , Europe , and the United States . Mean age was 57±11 years , 39 % were women , 31 % were diabetic , and 22 % had coronary artery disease . Baseline values included mean office BP of 176/98±17/15 mm Hg , mean of 5 antihypertension medications , and an estimated glomerular filtration rate of 83±20 mL/min per 1.73 m2 . The median time from first to last radiofrequency energy ablation was 38 minutes . The procedure was without complication in 97 % of patients ( 149 of 153 ) . The 4 acute procedural complications included 3 groin pseudoaneurysms and 1 renal artery dissection , all managed without further sequelae . Postprocedure office BPs were reduced by 20/10 , 24/11 , 25/11 , 23/11 , 26/14 , and 32/14 mm Hg at 1 , 3 , 6 , 12 , 18 , and 24 months , respectively . In conclusion , in patients with resistant hypertension , catheter-based renal sympathetic denervation results in a substantial reduction in BP sustained out to ≥2 years of follow-up , without significant adverse events BACKGROUND Renal sympathetic hyperactivity is associated with hypertension and its progression , chronic kidney disease , and heart failure . We did a proof-of-principle trial of therapeutic renal sympathetic denervation in patients with resistant hypertension ( ie , systolic blood pressure > /=160 mm Hg on three or more antihypertensive medications , including a diuretic ) to assess safety and blood-pressure reduction effectiveness . METHODS We enrolled 50 patients at five Australian and European centres ; 5 patients were excluded for anatomical reasons ( mainly on the basis of dual renal artery systems ) . Patients received percutaneous radiofrequency catheter-based treatment between June , 2007 , and November , 2008 , with subsequent follow-up to 1 year . We assessed the effectiveness of renal sympathetic denervation with renal noradrenaline spillover in a subgroup of patients . Primary endpoints were office blood pressure and safety data before and at 1 , 3 , 6 , 9 , and 12 months after procedure . Renal angiography was done before , immediately after , and 14 - 30 days after procedure , and magnetic resonance angiogram 6 months after procedure . We assessed blood-pressure lowering effectiveness by repeated measures ANOVA . This study is registered in Australia and Europe with Clinical Trials.gov , numbers NCT 00483808 and NCT 00664638 . FINDINGS In treated patients , baseline mean office blood pressure was 177/101 mm Hg ( SD 20/15 ) , ( mean 4.7 antihypertensive medications ) ; estimated glomerular filtration rate was 81 mL/min/1.73m(2 ) ( SD 23 ) ; and mean reduction in renal noradrenaline spillover was 47 % ( 95 % CI 28 - 65 % ) . Office blood pressures after procedure were reduced by -14/-10 , -21/-10 , -22/-11 , -24/-11 , and -27/-17 mm Hg at 1 , 3 , 6 , 9 , and 12 months , respectively . In the five non-treated patients , mean rise in office blood pressure was + 3/-2 , + 2/+3 , + 14/+9 , and + 26/+17 mm Hg at 1 , 3 , 6 , and 9 months , respectively . One intraprocedural renal artery dissection occurred before radiofrequency energy delivery , without further sequelae . There were no other renovascular complications . INTERPRETATION Catheter-based renal denervation causes substantial and sustained blood-pressure reduction , without serious adverse events , in patients with resistant hypertension . Prospect i ve r and omised clinical trials are needed to investigate the usefulness of this procedure in the management of this condition BACKGROUND Activation of renal sympathetic nerves is key to pathogenesis of essential hypertension . We aim ed to assess effectiveness and safety of catheter-based renal denervation for reduction of blood pressure in patients with treatment-resistant hypertension . METHODS In this multicentre , prospect i ve , r and omised trial , patients who had a baseline systolic blood pressure of 160 mm Hg or more ( ≥150 mm Hg for patients with type 2 diabetes ) , despite taking three or more antihypertensive drugs , were r and omly allocated in a one-to-one ratio to undergo renal denervation with previous treatment or to maintain previous treatment alone ( control group ) at 24 participating centres . R and omisation was done with sealed envelopes . Data analysers were not masked to treatment assignment . The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months . Primary analysis included all patients remaining in follow-up at 6 months . This trial is registered with Clinical Trials.gov , number NCT00888433 . FINDINGS 106 ( 56 % ) of 190 patients screened for eligibility were r and omly allocated to renal denervation ( n=52 ) or control ( n=54 ) groups between June 9 , 2009 , and Jan 15 , 2010 . 49 ( 94 % ) of 52 patients who underwent renal denervation and 51 ( 94 % ) of 54 controls were assessed for the primary endpoint at 6 months . Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg ( SD 23/11 , baseline of 178/96 mm Hg , p<0·0001 ) , whereas they did not differ from baseline in the control group ( change of 1/0 mm Hg [ 21/10 ] , baseline of 178/97 mm Hg , p=0·77 systolic and p=0·83 diastolic ) . Between-group differences in blood pressure at 6 months were 33/11 mm Hg ( p<0·0001 ) . At 6 months , 41 ( 84 % ) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more , compared with 18 ( 35 % ) of 51 controls ( p<0·0001 ) . We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups ; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion , but required no treatment . INTERPRETATION Catheter-based renal denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertensive patients . FUNDING Ardian Hypertension represents a significant global public health concern , contributing to vascular and renal morbidity , cardiovascular mortality , and economic burden . The opportunity to influence clinical outcomes through hypertension management is therefore paramount . Despite adherence to multiple available medical therapies , a significant proportion of patients have persistent blood pressure elevation , a condition termed resistant hypertension . Recent recognition of the importance of the renal sympathetic and somatic nerves in modulating blood pressure and the development of a novel procedure that selectively removes these contributors to resistant hypertension represents an opportunity to provide clinical ly meaningful benefit across wide and varied patient population s. Early clinical evaluation with catheter‐based , selective renal sympathetic denervation in patients with resistant hypertension has mechanistically correlated sympathetic efferent denervation with decreased renal norepinephrine spillover and renin activity , increased renal plasma flow , and has demonstrated clinical ly significant , sustained reductions in blood pressure . The SYMPLICITY HTN‐3 Trial is a pivotal study design ed as a prospect i ve , r and omized , masked procedure , single‐blind trial evaluating the safety and effectiveness of catheter‐based bilateral renal denervation for the treatment of uncontrolled hypertension despite compliance with at least 3 antihypertensive medications of different classes ( at least one of which is a diuretic ) at maximal tolerable doses . The primary effectiveness endpoint is measured as the change in office‐based systolic blood pressure from baseline to 6 months . This manuscript describes the design and methodology of a regulatory trial of selective renal denervation for the treatment of hypertension among patients who have failed pharmacologic therapy . Clin . Cardiol . 2012 . doi : |
12,012 | 24,872,341 | No studies were found that investigated librarians providing direct services to research ers or patients in healthcare setting s. CONCLUSIONS Librarian-provided services directed to participants in training programs ( eg , students , residents ) improve skills in search ing the literature to facilitate the integration of research evidence into clinical decision-making .
Services provided to clinicians were shown to be effective in saving time for health professionals and providing relevant information for decision-making .
Two studies indicated patient length of stay was reduced when clinicians requested literature search es related to a patient 's case | OBJECTIVE To assess the effects of librarian-provided services in healthcare setting s on patient , healthcare provider , and research er outcomes . | PURPOSE The study assesses potential for improving residents ' evidence -based medicine search ing skills in MEDLINE through real-time librarian instruction . SUBJECTS Ten residents on a rotation in a neonatal intensive care unit participated . METHODOLOGY Residents were r and omized into an instruction and a non-instruction group . Residents generated questions from rounds and search ed MEDLINE for answers . Data were collected through observation , search strategy analysis , and surveys . Librarians observed search es and collected data on questions , search ing skills , search problems , and the test group 's instruction topics . Participants performed st and ardized search es before , after , and six-months after intervention and were scored using a search strategy analysis tool ( 1 representing highest score and 5 representing lowest score ) . Residents completed pre- and post-intervention surveys to measure opinions about MEDLINE and search satisfaction . RESULTS Post-intervention , the test group formulated better questions , used limits more effectively , and reported greater confidence in using MEDLINE . The control group expressed less satisfaction with retrieval and demonstrated more errors when limiting . The test and control groups had the following average search scores respectively : 3.0 and 3.5 ( pre-intervention ) , 3.3 and 3.4 ( post-intervention ) , and 2.0 and 3.8 ( six-month post-intervention ) . CONCLUSION Data suggest that measurable learning outcomes were achieved . Residents receiving instruction improved and retained search ing skills six-months after intervention BACKGROUND The " Just-in-time Information " ( JIT ) librarian consultation service was design ed to provide rapid information to answer primary care clinical questions during patient hours . This study evaluated whether information provided by librarians to answer clinical questions positively impacted time , decision-making , cost savings and satisfaction . METHODS AND FINDING A r and omized controlled trial ( RCT ) was conducted between October 2005 and April 2006 . A total of 1,889 questions were sent to the service by 88 participants . The object of the r and omization was a clinical question . Each participant had clinical questions r and omly allocated to both intervention ( librarian information ) and control ( no librarian information ) groups . Participants were trained to send clinical questions via a h and -held device . The impact of the information provided by the service ( or not provided by the service ) , additional re sources and time required for both groups was assessed using a survey sent 24 hours after a question was su bmi tted . The average time for JIT librarians to respond to all questions was 13.68 minutes/ question ( 95 % CI , 13.38 to 13.98 ) . The average time for participants to respond their control questions was 20.29 minutes/ question ( 95 % CI , 18.72 to 21.86 ) . Using an impact assessment scale rating cognitive impact , participants rated 62.9 % of information provided to intervention group questions as having a highly positive cognitive impact . They rated 14.8 % of their own answers to control question as having a highly positive cognitive impact , 44.9 % has having a negative cognitive impact , and 24.8 % with no cognitive impact at all . In an exit survey measuring satisfaction , 86 % ( 62/72 responses ) of participants scored the service as having a positive impact on care and 72 % ( 52/72 ) indicated that they would use the service frequently if it were continued . CONCLUSIONS In this study , providing timely information to clinical questions had a highly positive impact on decision-making and a high approval rating from participants . Using a librarian to respond to clinical questions may allow primary care professionals to have more time in their day , thus potentially increasing patient access to care . Such services may reduce costs through decreasing the need for referrals , further tests , and other courses of action . TRIAL REGISTRATION Controlled-Trials.com IS RCT N96823810 OBJECTIVE This article presents the results of complementary research studies on the behaviors of hospital clinicians in asking clinical questions and the relationship between asking of questions , outcome of information search es , and success in problem solving . METHODS Triangulation in research methods --a combination of mailed question naires , interviews , and a r and omized controlled study --was employed to provide complementary views of the research problems under study . RESULTS The survey and interviews found that clinical problems ( concerned mainly with therapy and equipment or technology ) were expressed as statements rather than questions ( average number of concepts = 1.7 ) , that only slightly more than half ( higher for doctors ) of problems could be solved , and that the majority of clinical questions were not well formed . An educational workshop however improved clinicians ' formulation of questions , but the use of structured prompting was found to improve building of hypotheses in the doctors ' group without training . The workshop also improved satisfaction with the obtained information and success in problem solving . Nonetheless , for both the experimental and control groups , more structured and complete questions or statements did not mean higher success rates in problem solving or higher satisfaction with obtained information . CONCLUSION The triangulation methods have gathered complementary evidence to reject the hypothesis that building well-structured clinical questions would mean higher satisfaction with obtained information and higher success in problem solving OBJECTIVE To determine the effectiveness of providing synthesized research evidence to inform patient care practice s via an evidence based informatics program , the Clinical Informatics Consult Service ( CICS ) . DESIGN Consults were r and omly assigned to one of two conditions : CICS Provided , in which clinicians received synthesized information from the biomedical literature addressing the consult question or No CICS Provided , in which no information was provided . MEASUREMENT Outcomes were measured via online post-consult forms that assessed consult purpose , actual and potential impact , satisfaction , time spent search ing , and other variables . RESULTS Two hundred twenty six consults were made during the 19-month study period . Clinicians primarily made requests in order to up date themselves ( 65.0 % , 147/226 ) and were satisfied with the service results ( Mean 4.52 of possible 5.0 , SD 0.94 ) . Intention to treat ( ITT ) analyses showed that consults in the CICS Provided condition had a greater actual and potential impact on clinical actions and clinician satisfaction than No CICS consults . Evidence provided by the service primarily impacted the use of a new or different treatment ( OR 8.19 95 % CI 1.04 - 64.00 ) . Reasons for no or little impact included a lack of evidence addressing the issue or that the clinician was already implementing the practice s indicated by the evidence . CONCLUSIONS Clinical decision-making , particularly regarding treatment issues , was statistically significantly impacted by the service . Programs such as the CICS may provide an effective tool for facilitating the integration of research evidence into the management of complex patient care and may foster clinicians ' engagement with the biomedical literature OBJECTIVE To determine if a preceptor and individualized feedback improves the performance of physicians in search ing MEDLINE in clinical setting s. DESIGN R and omized controlled trial with 2 to 10 months follow-up . SETTING A 300-bed teaching hospital . PARTICIPANTS All 392 physicians and physicians-in-training from 6 major clinical departments were invited to participate if they made patient-care decisions during the study period ; 79.4 % agreed . INTERVENTIONS All participants were given 2 hours of basic training , then r and omized to a control group ( no further intervention ) or an intervention group in which each person chose a clinical preceptor experienced in MEDLINE search ing and received individualized feedback from a study librarian on each of their 1st 10 search es . MAIN OUTCOME MEASURES The number and proportion of relevant and irrelevant references retrieved for 1st , 4th , and 8th search es of participants were compared with independent librarian search es on the same topics . RESULTS Intervention group members did not search more often than controls ( 5.9 search es per month versus 4.7 , respectively ; P = 0.26 ) and there were no significant differences in the quality of search es . Rather , search performance for both groups improved , with the average number of relevant references retrieved per search increasing from 4.5 to 7.4 ( P < 0.01 ) . The librarian retrieved more relevant citations than participants for the 1st search ( P = 0.001 ) but not for the 4th ( P = 0.60 ) or 8th ( P = 0.76 ) search es . CONCLUSIONS A program of assigning preceptors and providing feedback on individual search es did not enhance the quantity or quality of search es . Soon after a basic introduction to search ing , however , clinicians in both groups improved their search performance Background Cost consequences analysis was completed from r and omized controlled trial ( RCT ) data for the Just-in-time ( JIT ) librarian consultation service in primary care that ran from October 2005 to April 2006 . The service was aim ed at providing answers to clinical questions arising during the clinical encounter while the patient waits . Cost saving and cost avoidance were also analyzed . The data comes from eighty-eight primary care providers in the Ottawa area working in Family Health Networks ( FHNs ) and Family Health Groups ( FHGs ) . Methods We conducted a cost consequences analysis based on data from the JIT project [ 1 ] . We also estimated the potential economic benefit of JIT librarian consultation service to the health care system . Results The results show that the cost per question for the JIT service was $ 38.20 . The cost could be as low as $ 5.70 per question for a regular service . Nationally , if this service was implemented and if family physicians saw additional patients when the JIT service saved them time , up to 61,100 extra patients could be seen annually . A conservative estimate of the cost savings and cost avoidance per question for JIT was $ 11.55 . Conclusions The cost per question , if the librarian service was used at full capacity , is quite low . Financial savings to the health care system might exceed the cost of the service . Saving physician 's time during their day could potentially lead to better access to family physicians by patients . Implementing a librarian consultation service can happen quickly as the time required to train professional librarians to do this service is short A double-blind r and omised controlled trial was conducted on a group of Hong Kong hospital clinicians . The objective was to test if a three-hour educational workshop ( with supervised h and s-on practice ) is more effective ( than no training ) to improve clinical question formulation , information-seeking skills , knowledge , attitudes , and search outcomes . The design was a post-test-only control group ; recruitment by stratified r and omization ( by profession ) , blocked at 800 . End-user training was more effective than no training in improving clinical question formulation , in raising awareness , knowledge , confidence and use of data bases , but had made no impact on preference for secondary data bases . It changed the attitude of clinicians to become more positive towards the use of electronic information services ( EIS ) . Participants had higher search performance and outcomes ( satisfaction with information obtained ( NNT = 3 ) , EIS satisfaction ( NNT = 3 ) and success in problem solving ( NNT = 4 ) ) . The workshop improved knowledge and skills in evidence -based search ing , but this effect gradually eroded with time . Search logs confirmed that follow-up is required if effects are to be sustained . Longer effects on search behaviours appear to be positive . A r and omised controlled trial is valuable in identifying cause- and -effect relations and to quantify the magnitude of the effects for management decision-making This is a prospect i ve study of clinical questions generated in primary care consultations and a comparison of two approaches to answering those clinical questions . Twenty-one doctors in a university-based primary care clinic su bmi tted 78 clinical questions arising from patient consultations during 24 clinic days ( 0.01 question per patient encounter ) . These doctors subsequently found answers to 40 % of their questions but were satisfied with only 67 % of these answers . The investigators were able to provide answers for 95 % of the questions asked and the doctors rated these answers as satisfactory in 86 % of instances . Answers obtained by investigators had significantly higher satisfaction score than those obtained by doctors ' search ( p = 0.002 ) . The two main findings of this study are ( 1 ) almost all questions arising in clinic setting could be answered by intensive search ; ( 2 ) answers found by intensive search es were judged to be more satisfactory than those found routinely by doctors . Provision of an information retrieval service in addition to training in the search ing and appraisal of medical literature are possible solutions to the information needs of busy clinicians BACKGROUND Librarians at the University of Alberta have been involved with teaching undergraduate medical and dental education for several years . After 1 year of increased librarian involvement at the problem-based learning ( PBL ) , small-group level , informal feedback from faculty and students suggested that librarians ' participation in PBL groups was beneficial . There was , however , no real evidence to support this cl aim or justify the high dem and on librarians ' time . OBJECTIVES The study aim ed to determine whether having a librarian present in the small-group , problem-based learning modules for first-year medical and dental students results in an improved underst and ing of evidence -based medicine concepts , the nature of medical literature , and information access skills . METHODS One hundred and sixty-four first-year medical and dental students participated in the study . There were a total of 18 PBL groups , each with approximately nine students and one faculty tutor . Six librarians participated and were assigned r and omly to the six intervention groups . Students were given pre- and post-tests at the outset and upon completion of the 6-week course . RESULTS Post-test scores showed that there was a small positive librarian impact , but final exam scores showed no impact . There was also no difference in attitudes or comfort levels between students who had a librarian in their group and those who did not . CONCLUSIONS Impact was not sufficient to warrant continued participation of librarians in PBL . In future instruction , librarians at the John W. Scott Health Sciences Library will continue to teach at the larger group level AIM To compare the effectiveness of an online information literacy tutorial with a face-to-face session for teaching information literacy skills to nurses . DESIGN R and omised control trial . PARTICIPANTS Seventy-seven first year undergraduate pre- registration diploma nursing students . INTERVENTION Online in-house information literacy tutorial COMPARISON One hour face-to-face session , covering the same material as the intervention , delivered by the nursing subject librarian . METHODS Search histories were scored using a vali date d checklist covering keyword selection , boolean operators , truncation and synonyms . Skills retention was measured at 1 month using the same checklist . Inferential statistics were used to compare search skills within and between groups pre and post-session . RESULTS The search ing skills of first year pre- registration nursing students improve following information literacy sessions ( p<0.001 ) , and remain unchanged 1 month later , regardless of teaching method . The two methods produce a comparable improvement ( p=0.263 ) . There is no improvement or degradation of skills 1 month post-session for either method ( p=0.216 ) . CONCLUSION Nurses Information literacy skills improve after both face-to-face and online instruction . There is no skills degradation at 1 month post-intervention for either method OBJECTIVE Usage of computer re sources at the point of care has a positive effect on physician decision making . Pediatricians ' information-seeking behaviors are not well characterized . The goal of this study was to characterize quantitatively the information-seeking behaviors of general pediatricians and specifically compare their use of computers , including digital libraries , before and after an educational intervention . METHODS General pediatric residents and faculty at a US Midwest children 's hospital participated . A control ( year 1 ) versus intervention group ( year 2 ) research design was implemented . Eligible pediatrician pools overlapped , such that some participated first in the control group and later as part of the intervention . The intervention group received a 10-minute individual training session and h and out on how to use a pediatric digital library to answer professional questions . A general medical digital library was also available . Pediatricians in both the control and the intervention groups were surveyed using the critical incident technique during 2 6-month time periods . Both groups were telephoned for 1- to 2-minute interviews and were asked , " What pediatric question ( s ) did you have that you needed additional information to answer ? " The main outcome measures were the differences between the proportion of pediatricians who use computers and digital libraries and a comparison of the number of times that pediatricians use these re sources before and after intervention . RESULTS A total of 58 pediatricians were eligible , and 52 participated ( 89.6 % ) . Participant demographics between control ( N = 41 ; 89.1 % ) and intervention ( N = 31 ; 70.4 % ) were not statistically different . Twenty pediatricians were in both groups . Pediatricians were slightly less likely to pursue answers after the intervention ( 94.7 % vs 89.2 % ) ; the primary reason cited for both groups was a lack of time . The pediatricians were as successful in finding answers in each group ( 95.7 % vs 92.7 % ) , but the intervention group took significantly less time ( 8.3 minutes vs 19.6 minutes ) . After the intervention , pediatricians used computers and digital libraries more to answer their questions and spent less time using them . CONCLUSION This study showed higher rates of physician questions pursued and answered and higher rates of computer use at baseline and after intervention compared with previous studies . Pediatricians who seek answers at the point of care therefore should begin to shift their information-seeking behaviors toward computer re sources , as they are as effective but more time-efficient OBJECTIVE To evaluate the effect of a three-hour training session in formulating questions and search ing data bases . DESIGN A r and omised controlled trial and before and after study , with blinded outcome assessment . SETTING Oxford University Medical School , first clinical year . SUBJECTS Altogether 108 medical students were r and omly assigned to an experimental group ( 54 ) or a control group ( 54 ) , and all were given the task of search ing for evidence around an ulcer related problem or a cardiac problem . Students in the experimental group were r and omly allocated to research one of the two problems before training and the remaining problem afterwards . Control students received no training and were r and omly allocated to search for evidence around either of these problems . MAIN OUTCOME MEASURES Search ing performance ; the quality of evidence retrieved ; student satisfaction . RESULTS Training improved the students ' search performance and the quality of evidence retrieved . Students ' satisfaction with the training was high . CONCLUSIONS A three-hour interactive training session improved the students ' ability to search data bases and retrieve evidence and was well received by the students Purpose Many educational programs seek to develop skills in evidence -based medicine ( EBM ) . The authors examined the efficacy of teaching the EBM skill of efficiently search ing the research literature . They compared students who received brief training in EBM search ing skills with those who did not , and assessed the quality of literature search ing one month after that training . Method The authors used a nonr and omized control group study design to quantify the impact of a single , brief ( two-hour ) instructional intervention on EBM-based techniques for search ing Medline for evidence related to a clinical problem provided to the students . Ninety-two fourth-year medical students ( 34 intervention , 58 control ) at the University of Michigan participated in a four-week EBM elective between 2001 and 2003 . The authors conducted a preintervention assessment of search ing skills , followed by a repeat assessment one month after the intervention . Search quality was judged by medical librarians using a structured clinical scenario and scoring algorithm . Results Data for 30 intervention and 40 control students could be analyzed . Intervention students had fewer search errors and correspondingly higher quality search es than did control students . The educational intervention accounted for approximately 8 % of the variance in both of these outcomes . The most common search errors were a lack of Medical Subject Headings ( MeSH ) explosion , missing MeSH terms , lack of appropriate limits , failure to search for best evidence , and inappropriate combination of all search concepts . Conclusions This study provides evidence that a single , brief training session can have a marked beneficial effect on the quality of subsequent , short-term EBM literature search ing performance outcomes PURPOSE . To examine the associations between ( 1 ) the economic indicators of hospital costs , charges , and length of stay ( LOS ) for inpatient cases and ( 2 ) the use of MEDLINE search es for such cases . METHOD . An outcome -based , objective , prospect i ve study with an economic evaluation was conducted from September 1989 to September 1990 at three metropolitan Detroit teaching hospitals representing both allopathic and osteopathic care . The study consisted of ( 1 ) 192 test cases , derived from a consecutive sample of in patients of all ages for whom MEDLINE search es were requested at the participating medical libraries , and ( 2 ) 10,409 control cases , which were of the same diagnosis-related groups ( DRGs ) as the test cases but did not involve identified MEDLINE search es . Statistical analysis included the use of multivariate analyses of variance and correlation coefficients . Comparisons of cases were made on case-by-case and DRG bases regarding total patient costs , charges , and lengths of stay for cases with or without MEDLINE search es . RESULTS . The test cases were found to have a higher severity of illness . Among test cases , statistically significant relationships existed between ( 1 ) hospital expenses and LOS and ( 2 ) hospital expenses and the timing of the search during hospitalization when controlling for LOS . When cases were matched for DRG and LOS , the cases with early search es ( i.e. , conducted during the first half of hospitalization ) had significantly lower expenses . CONCLUSION . Of the test-case patients ( for whom MEDLINE search es were conducted during hospitalization ) , those whose search es were conducted earlier had statistically significantly lower costs , charges , and lengths of stay than those whose search es were conducted later OBJECTIVES Constructing an answerable question and effectively search ing the medical literature are key steps in practicing evidence -based medicine ( EBM ) . This study aim ed to identify the effectiveness of delivering a single workshop in EBM literature search ing skills to medical students entering their first clinical years of study . METHODS A r and omized controlled trial was conducted with third-year undergraduate medical students . Participants were r and omized to participate in a formal workshop in EBM literature search ing skills , with EBM literature search ing skills and perceived competency in EBM measured at one-week post-intervention via the Fresno tool and Clinical Effectiveness and Evidence -Based Practice Question naire . RESULTS A total of 121 participants were enrolled in the study , with 97 followed-up post-intervention . There was no statistical mean difference in EBM literature search ing skills between the 2 groups ( mean difference = 0.007 ( P = 0.99 ) ) . Students attending the EBM workshop were significantly more confident in their ability to construct clinical questions and had greater perceived awareness of information re sources . CONCLUSIONS A single EBM workshop did not result in statistically significant changes in literature search ing skills . Teaching and reinforcing EBM literature search ing skills during both pre clinical and clinical years may result in increased student confidence , which may facilitate student use of EBM skills as future clinicians OBJECTIVE To determine if a preceptor and timely , individualized feedback improves the performance of physicians in search ing MEDLINE using GRATEFUL MED in clinical setting s. DESIGN R and omized controlled trial . SETTING A 300 bed primary to tertiary care teaching hospital . Computers were installed in wards and clinics of 6 major clinical services , and the emergency room , intensive care and neonatal intensive care units . SUBJECTS All physicians and physicians-in-training from the departments of Medicine , Family Medicine , Surgery , Psychiatry , Pediatrics , and Obstetrics and Gynecology were included if they made patient care decisions for at least 8 weeks during the study period . INTERVENTION All participants were given a 1-hour training class and 1 hour of individualized search ing with 1 of the 2 study librarians . After training , participants were r and omized to a control group who received no further intervention or to an intervention group in which each person chose a clinical preceptor experienced in MEDLINE search ing and received individualized feedback by a study librarian on their first 10 search es , indicating search quality and providing suggestions for improvement . Feedback was mailed the first week day after the search was done . MAIN MEASURES Baseline characteristics by study group , department and level of training , study participation rates , and search ing rates . MAIN RESULTS 308 of 392 eligible physicians joined the study . Participation was almost 80 % with some variation by department and level of training . Excellent balance in the baseline characteristics was achieved for the 2 groups , as well as for the number who did first search es . Intervention group participants search ed MEDLINE more often than did controls ( 3.5 search es per month vs 2.5 per month for controls , P = 0.046 ) . The recall and precision for first search es for both groups was significantly less than that of librarians . The analysis of study data will be completed by September 1991 . CONCLUSIONS Clinicians are willing to do self-service search ing of MEDLINE in clinical setting s but their precision and recall are less than a trained librarian at baseline . Search skills enhancements are needed and the effect of feedback and preceptors is being tested . SOURCE OF FUNDING U.S. National Library of Medicine and Ontario Ministry of Health BACKGROUND Considerable barriers still prevent paediatricians from successfully using information retrieval technology . OBJECTIVES To verify whether the assistance of biomedical librarians significantly improves the outcomes of search es performed by paediatricians in biomedical data bases using real-life clinical scenarios . METHODS In a controlled trial at a paediatric teaching hospital , nine residents and interns were r and omly allocated to an assisted search group and nine to a non-assisted ( control ) group . Each participant search ed PubMed and other online sources , performing pre-determined tasks including the formulation of a clinical question , retrieval and selection of bibliographic records . In the assisted group , participants were supported by a librarian with ≥5 years of experience . The primary outcome was the success of search sessions , scored against a specific assessment tool . RESULTS The median score of the assisted group was 73.6 points interquartile range ( IQR = 13.4 ) vs. 50.4 ( IQR = 17.1 ) of the control group . The difference between median values in the results was 23.2 points ( 95 % CI 4.8 - 33.2 ) , in favour of the assisted group ( P-value , Mann-Whitney U test : 0.013 ) . CONCLUSIONS The study has found quantitative evidence of a significant difference in search performance between paediatric residents or interns assisted by a librarian and those search ing the literature alone OBJECTIVE To improve underst and ing of the information-seeking behaviors of public health professionals , the authors conducted this r and omized controlled trial involving sixty participants to determine whether library and informatics training , with an emphasis on PubMed search ing skills , increased the frequency and sophistication of participants ' practice -related questions . METHODS The intervention group ( n = 34 ) received evidence -based public health library and informatics training first , whereas the control group ( n = 26 ) received identical training two weeks later . The frequency and sophistication of the questions generated by both intervention and control groups during the interim two-week period served as the basis for comparison . RESULTS The intervention group reported an average of almost 1.8 times more questions than those reported by the control group ( 1.24 vs. 0.69 questions per participant ) ; however , this difference did not reach statistical significance . The intervention group overall produced more sophisticated ( foreground ) questions than the control group ( 18 vs. 9 ) ; however , this difference also did not reach statistical significance . CONCLUSION The training provided in the current study seemed to prompt public health practitioners to identify and articulate questions more often . Training appears to create the necessary precondition for increased information-seeking behavior among public health professionals Over the past decade , on-line data bases have become increasingly popular among health care professionals . As a group , these ' end-users ' report utilizing data bases to keep abreast of medical progress , to conduct research and to address specific patient care issues . Throughout the literature , medical professionals ( ' content experts ' ) have proved to be less effective search ers than librarians ( ' search experts ' ) . The potential implication s of this discrepancy are worrysome . For any given clinical scenario , for example , published reports may reach contradictory conclusions . A poorly skilled search er may not retrieve enough articles to appreciate this fact . Optimizing search ing skills is therefore a worthwhile goal . As a first step , many medical schools introduce students to on-line data bases , most notably MEDLINE . Residency is an ideal time to continue this training . A recognized obstacle to provide residents with formal MEDLINE instruction is time constraint . We therefore conducted this study to ascertain the impact an individual 1-hour tutorial session would have on MEDLINE utilization among obstetrics and gynecology residents training at an academic medical centre . Outcome measures included MEDLINE search frequency , duration , recall , precision and search er satisfaction . Search recall measures the search er 's ability to retrieve articles deemed relevant to the question at h and . Search precision gauges the search ers ' ability to eliminate irrelevant articles . Although the sessions were well received , we were unable to demonstrate an improvement in the outcome measures analysed . Further research is therefore indicated so that cost-effective educational strategies can be recommended for wide-scale use Objectives To characterize the information needs of family physicians by collecting the questions they asked about patient care during consultations and to classify these in ways that would be useful to developers of knowledge bases . Design An observational study in which investigators visited physicians for two half-days and collected their questions . Taxonomies were developed to characterize the clinical topic and generic type of information sought for each question . Setting Eastern Iowa . Participants R and om sample of 103 family physicians . Main outcome measures Number of questions posed , pursued , and answered ; topic and generic type of information sought for each question ; time spent pursuing answers ; and information re sources used . Results Participants asked a total of 1,101 questions . Questions about drug prescribing , obstetrics and gynecology , and adult infectious disease were most common , comprising 36 % of the total . The taxonomy of generic questions included 69 categories ; the three most common types , comprising 24 % of all questions , were " What is the cause of symptom X ? " " What is the dose of drug X ? " and " How should I manage disease or finding X ? " Answers to most questions ( n = 702 [ 64 % ] ) were not immediately pursued , but of those pursued , most ( n = 318 [ 80 % ] ) were answered . Physicians spent an average of less than 2 minutes pursuing an answer , and they used readily available print and human re sources . Only two questions led to a formal literature search . Conclusions Family physicians in this study did not pursue answers to most of their questions . Questions about patient care can be organized into a limited number of generic types , which could help guide the efforts of knowledge-base developers |
12,013 | 22,970,851 | Evidence -based , practice recommendations for the treatment of FOD are provided that will hopefully inform clinical decision making for those treating this common condition | INTRODUCTION As the field of sexual medicine evolves , it is important to continually improve patient care by developing contemporary " st and ard operating procedures " ( SOPs ) , reflecting the consensus view of experts in sexual medicine .
Few , if any , consensus SOPs have been developed for the diagnosis and treatment of Female Orgasmic Disorder ( FOD ) .
AIM The objective is to provide st and ard operating procedures for FOD . | BACKGROUND The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy are unknown . METHODS We conducted a double-blind , placebo-controlled , 52-week trial in which 814 women with hypoactive sexual desire disorder were r and omly assigned to receive a patch delivering 150 or 300 microg of testosterone per day or placebo . Efficacy was measured to week 24 ; safety was evaluated over a period of 52 weeks , with a subgroup of participants followed for an additional year . The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes . RESULTS At 24 weeks , the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 microg of testosterone per day than in the placebo group ( an increase of 2.1 episodes vs. 0.7 , P<0.001 ) but not in the group receiving 150 microg per day ( 1.2 episodes , P=0.11 ) . As compared with placebo , both doses of testosterone were associated with significant increases in desire ( 300 microg per day , P<0.001 ; 150 microg per day , P=0.04 ) and decreases in distress ( 300 microg per day , P<0.001 ; 150 microg per day , P=0.04 ) . The rate of and rogenic adverse events - primarily unwanted hair growth - was higher in the group receiving 300 microg of testosterone per day than in the placebo group ( 30.0 % vs. 23.1 % ) . Breast cancer was diagnosed in four women who received testosterone ( as compared with none who received placebo ) ; one of the four received the diagnosis in the first 4 months of the study period , and one , in retrospect , had symptoms before undergoing r and omization . CONCLUSIONS In postmenopausal women not receiving estrogen therapy , treatment with a patch delivering 300 microg of testosterone per day result ed in a modest but meaningful improvement in sexual function . The long-term effects of testosterone , including effects on the breast , remain uncertain . ( Clinical Trials.gov number , NCT00131495 . INTRODUCTION A wide range of prevalence estimates of female sexual dysfunctions ( FSD ) have been reported . AIM Compare instruments used to assess FSD to determine if differences between instruments contribute to variation in reported prevalence . MAIN OUTCOME MEASURES Sexual Function Question naire combined with Female Sexual Distress Scale ( SFQ-FSDS ) was our gold st and ard , vali date d instrument for assessing FSD . Alternatives were SFQ alone and two sets of simple questions adapted from Laumann et al. 1994 . Methods . A postal survey was administered to a r and om sample of 356 Australian women aged 20 to 70 years . RESULTS When assessed by SFQ-FSDS , prevalence estimates ( 95 % confidence intervals ) of hypoactive sexual desire disorder , sexual arousal disorder ( lubrication ) , orgasmic disorder , and dyspareunia were 16 % ( 12 % to 20 % ) , 7 % ( 5 % to 11 % ) , 8 % ( 6 % to 12 % ) , and 1 % ( 0.5 % to 3 % ) , respectively . Prevalence estimates varied across alternative instruments for these disorders : 32 % to 58 % , 16 % to 32 % , 16 % to 33 % , and 3 % to 23 % , respectively . Compared with SFQ-FSDS alternative instruments produced higher estimates of desire , arousal and orgasm disorders and displayed a range of sensitivities ( 0.25 to 1.0 ) , specificities ( 0.48 to 0.99 ) , positive predictive values ( 0.01 to 0.56 ) , and negative predictive values ( 0.95 to 1.0 ) across the disorders investigated . Kappa statistics comparing SFQ-FSDS and alternative instruments ranged from 0 to 0.71 but were predominantly 0.44 or less . Changing recall from previous month to 1 month or more in the previous year produced higher estimates for all disorders investigated . Including sexual distress produced lower estimates for desire , arousal , and orgasm disorders . CONCLUSIONS Prevalence estimates of FSD varied substantially across instruments . Relatively low positive predictive values and kappa statistics combined with a broad range of sensitivities and specificities indicated that different instruments identified different subgroups . Consequently , the instruments research ers choose when assessing FSD may affect prevalence estimates and risk factors they report University of Illinois Thirty subjects seeking treatment for primary inorgasmia accompanied by sexual anxiety or aversion were assigned to one of three groups : systematic desensitization ( SD ) , directed masturbation ( DM ) , or waiting list control ( WL ) . Following treatment , subjects were retested , and the WL group then received directed masturbation treatment . A third testing constituted a follow-up for the SD and DM groups and a posttreatment testing for the WL . Both treatments were equally effective in improving subjects ' sexual self-acceptance and increasing sexual pleasure . Changes in anxiety were negligible ; however , sexual arousal and orgasm for DM and WL subjects increased . The gains of the WL group not only replicated the findings of the DM group but also were of greater magnitude Ginkgo biloba extract ( GBE ) facilitates blood flow , influences nitric oxide systems , and has a relaxant effect on smooth muscle tissue . These processes are important to the sexual response in women and , hence , it is feasible that GBE may have a therapeutic effect . The present study was the first to provide an empirical examination of the effects of both short- and long-term GBE administration on subjective and physiological ( vaginal photoplethysmography ) measures of sexual function in women with Sexual Arousal Disorder . A single dose of 300 mg GBE had a small but significant facilitatory effect on physiological , but not subjective , sexual arousal compared to placebo in 99 sexually dysfunctional women . The long-term effects of GBE on sexual function were assessed in 68 sexually dysfunctional women who were r and omly assigned to 8 weeks treatment of either ( 1 ) GBE ( 300 mg/daily ) , ( 2 ) placebo , ( 3 ) sex therapy which focused on training women to attend to genital sensations , or ( 4 ) sex therapy plus GBE . When combined with sex therapy , but not alone , long-term GBE treatment significantly increased sexual desire and contentment beyond placebo . Sex therapy alone significantly enhanced orgasm function compared with placebo . Long-term GBE administration did not significantly enhance arousal responses beyond placebo . It was concluded that ( 1 ) neither short- or long-term administration of GBE alone substantially impacts sexual function in women , ( 2 ) a substantial placebo effect on sexual function exists in women with sexual concerns , and ( 3 ) teaching women to focus on genital sensations during sex enhances certain aspects of women ’s sexual functioning This paper presents the results of a prospect i ve controlled study evaluating a programme of directed masturbation against a combined sensate focus and supportive psychotherapeutic approach in the management of female primary orgasmic failure . Of the 20 patients who followed the masturbation programme 90 per cent gained orgasmic capacity compared with 53 per cent of 15 patients who were treated conventionally . Eighty-five per cent of the patients treated by the masturbation programme and 47 per cent of the control group of patients became coitally orgasmic on at least 75 per cent of coital occasions . The difference is statistically significant at the 5 per cent level . The results suggest that directed masturbation is an effective adjunct in the management of primary female orgasmic failure BACKGROUND Oophorectomy reduces serum testosterone levels . We studied the efficacy and safety of transdermal testosterone in treating hypoactive sexual desire disorder in surgically menopausal women . METHODS A 24-week , r and omized , double-blind , placebo-controlled , parallel-group , multicenter trial was conducted in women ( aged 24 - 70 years ) who developed distressful low sexual desire after bilateral salpingo-oophorectomy and hysterectomy and who were receiving oral estrogen therapy . Women were r and omized to receive placebo ( n = 119 ) or testosterone patches in dosages of 150 microg/d ( n = 107 ) , 300 microg/d ( n = 110 ) , or 450 microg/d ( n = 111 ) twice weekly for 24 weeks . Sexual desire and frequency of satisfying sexual activity were primary efficacy outcome measures . RESULTS Of the 447 women r and omized , 318 ( 71 % ) completed the trial . Compared with placebo , women receiving the 300-microg/d testosterone patch had significantly greater increases from baseline in sexual desire ( 67 % vs 48 % ; P = .05 ) and in frequency of satisfying sexual activity ( 79 % vs 43 % ; P = .049 ) . The 150-microg/d group showed no evidence of a treatment effect . The 450-microg/d group also was not statistically different from the 300-microg/d or placebo groups . Marginally significant linear dose-response trends were observed for total satisfying sexual activity and sexual desire at 24 weeks ( P = .06 and .06 , respectively ) . Adverse events occurred with similar frequency in both groups ; no serious safety concerns were observed . CONCLUSIONS The 300-microg/d testosterone patch increased sexual desire and frequency of satisfying sexual activity and was well tolerated in women who developed hypoactive sexual desire disorder after surgical menopause Three components commonly utilized in sex therapy for secondary orgasmic dysfunction ( Sensate Focus I , Sensate Focus II , and ban on intercourse ) were studied , with the aim of not only exploring their effects on therapy outcome but also , in part , of sensitizing investigators to the benefits of incorporating component analyses within larger investigations of therapy outcome . The subjects were 23 married couples with the problem of secondary orgasmic dysfunction in the wife . Subjects were administered a multicomponent therapy program over a 14-week period . Daily self-monitoring data were analyzed to assess the impact of Sensate Focus exercises and banning intercourse on both broad ( e.g. , enjoyment ) and narrow ( e.g. , orgasmic response ) criteria of therapeutic effectiveness . Results indicated that for females , sensate focus exercises , in combination with a ban on intercourse , led to a significant increase in level of enjoyment for subsequent noncoital sexual caressing as well as intercourse . Orgasmic responsiveness , however , was not affected . The method ological issues of broad versus narrow therapeutic effects , compliance with treatment , and cost-effective techniques for the study of sex therapy components are discussed In an open study , sildenafil ( Viagra ) was prescribed for nine women out patients who reported sexual dysfunction induced by antidepressant medication , primarily selective serotonin reuptake inhibitors . A 50 mg dose of sildenafil was prescribed , and patients were instructed to take it approximately one hour before sexual activity . They were told to increase the dose to 100 mg on the next occasion if they experienced a partial response or a lack of response to sildenafil . The nine patients , all of whom had experienced either anorgasmia or delayed orgasm with or without associated disturbances , reported significant reversal of sexual dysfunction , usually with the first dose of 50 mg of sildenafil We conducted a double-blind , placebo-controlled study to determine the role of dietary supplementation on sexual function in women of differing menopausal status . One hundred eight ( 108 ) women , age 22–73 years , who reported a lack of sexual desire , enrolled as participants . Of these , 55 received ArginMax for women and 53 received placebo . ArginMax for women contains L-arginine , ginseng , ginkgo , damiana , multivitamins , and minerals . The 108 women , given definitions , self-reported as 59 premenopausal ( PRE ) ; 20 perimenopausal ( PERI ) , and 29 postmenopausal ( POST ) . After 4 weeks , PRE women on ArginMax primarily reported significant improvement in level of sexual desire ( 72 % ; p = 0.03 ) and satisfaction with overall sex life ( 68 % ; p = 0.007 ) , compared with placebo group , according to the Female Sexual Function Index ( FSFI ; Kaplan et al. , 1999 ) scales . Frequency of sexual desire ( 60 % ; p = 0.05 ) and frequency of intercourse ( 56 % p = 0.01 ) also increased among the PRE women . In contrast , among PERI women , primary improvements were reported for frequency of intercourse ( 86 % ; p = 0.002 ) , satisfaction with sexual relationship ( 79 % ; p = 0.03 ) , and vaginal dryness ( 64 % ; p = 0.03 ) compared with placebo group . POST women primarily showed an increased in level of sexual desire , with 51 % showing improvement , compared with only 8 % in the placebo group ( p = 0.008 ) . Nutritional intervention plays an important role in women 's sexual health , but issues and areas of greatest improvement differ among women of different menopausal states . The largest number of attribute improvements were seen in PRE and PERI women , although attribute types vary among these groups . Level of desire was shown to increase significantly in POST women . Since ArginMax for women has been shown to exhibit no estrogen activity , it may be desirable alternative to hormone therapy for sexual concerns Abstract Forty-eight couples complaining of secondary orgasmic dysfunction were r and omly allocated to one of three treatment methods or to a control group . Sexual function , sexual anxiety and satisfaction with the total relationship were evaluated in a pretest , an intermediate test ( after 12 therapeutic sessions ) and a follow-up test . The intermediate test revealed significant improvement in the sexual function of women treated by systematic desensitization , and that of women and men treated by an adapted version of the Masters and Johnson method . The follow-up test showed significant improvement in women and men treated by desensitization . Both methods significantly improved the satisfaction with the total relationship in men and women , and desensitization significantly reduced sexual anxiety in men and women . The results of combined treatment —desensitization followed by treatment according to Masters and Johnson — were very poor . The control group showed no significant changes . Evaluation of the differences between the treatments revealed a near-significant difference in sexual function of women in the intermediate test , with desensitization and the Masters and Johnson method yielding better results than combined treatment or no treatment To evaluate the effectiveness of two sexual therapy techniques , a non- clinical population of 36 married women were r and omly assigned with their spouses to either a sexual enrichment workshop with instruction on the coital alignment technique ( 19 women ) or directed masturbation ( 17 women ) . Both workshops yielded clinical ly significant improvements in orgasm consistency during sexual intercourse , orgasm strength , and the overall number of orgasms experienced in partner-related activities . In instances where differences in the workshop were discovered ( increases in orgasm consistency during sexual intercourse ) , the coital alignment technique yielded a somewhat more positive outcome than did directed masturbation . Treatment approaches that combine the two techniques , such as orgasm consistency training , may prove more beneficial than a treatment model that depends on either one or the other BACKGROUND Sexual dysfunction may significantly affect quality of life and marital relations in the postmenopausal period . The aim of the study was to assess the effect of tibolone on climacteric symptoms and sexuality in late postmenopausal but still symptomatic women . PATIENTS AND METHODS A six-month prospect i ve study was conducted of two groups of clinical ly healthy postmenopausal women : a control group ( n = 18 ; mean age 57.8 + /- 4.1 yrs ; menopause at 49.7 + /- 2.5 ; years of amenorrhea 8.1 + /- 4.0 yrs ) and a tibolone group ( n = 22 ; mean age 57 + /- 4.5 yrs ; menopause at 47.7 + /- 3.9 ; years of amenorrhea 9.2 + /- 4.6 yrs ) , who received 2.5 mg tibolone daily for six months . The Kupperman menopausal index ( KI ) was calculated for both groups at baseline and at six months . Sexual function was assessed by the Female Sexual Function Index ( FSFI ) question naire at the beginning and at the end of the study . The FSFI comprised five main domains : desire , arousal , lubrication , orgasm and pain . Satisfaction and a total score were also recorded . RESULTS The results showed that during the observation period KI decreased significantly in the tibolone group ( 15.7 + /- 9.2 vs 11.3 + /- 6.8 , p < 0.001 ) , while in the control group no difference was observed . There was a significant improvement of sexual function in the tibolone group in all domains : desire -- from 2.6 + /- 1.0 to 3.1 + /- 1.0 ( p < 0.001 ) ; arousal -- from 2.3 + /- 1.8 to 3.4 + /- 1.1 ( p < 0.001 ) ; lubrication - 2.6 + /- 2.1 and 3.5 + /- 1.4 ( p < 0.05 ) . The ability to reach orgasm increased ( p < 0.001 ) and pain and discomfort during and after sexual intercourse significantly decreased ( p < 0.01 ) . The overall satisfaction and the total score in the treated group changed favourably in a statistically significant manner , while these parameters did not change in the control group . CONCLUSIONS Treatment with tibolone had a beneficial effect on the climacteric symptoms and sexual function of late postmenopausal women . Moreover , tibolone seems to have an advantage over conventional hormone replacement therapy ( HRT ) in improving desire and arousal |
12,014 | 12,435,258 | Hemodialysis care in private not-for-profit centers is associated with a lower risk of mortality compared with care in private for-profit centers | CONTEXT Private for-profit and private not-for-profit dialysis facilities provide the majority of hemodialysis care in the United States .
There has been extensive debate about whether the profit status of these facilities influences patient mortality .
OBJECTIVE To determine whether a difference in adjusted mortality rates exists between hemodialysis patients receiving care in private for-profit vs private not-for-profit dialysis centers . | Death rates of end-stage renal disease ( ESRD ) patients treated with hemodialysis vary substantially among treatment centers . The association between facility-to-facility differences in delivered hemodialysis dose and facility-specific mortality rates was examined among 5817 r and omly selected patients treated with hemodialysis on October 1 , 1994 , from all 213 hemodialysis treatment centers reporting to ESRD Network 6 . The mean urea reduction ratio ( URR ) for each treatment center , a measure of hemodialysis adequacy , was calculated for each facility , using measurements made by center staff members during one treatment for each of the r and omly selected patients . During 7 mo of follow-up ( ending April 30 , 1995 ) , 441 ( 7.6 % ) patients died . The average URR among the treatment centers was 64.9 % . There was a strong , inverse association between increasing treatment center URR and adjusted mortality count ( P = 0.009 ) . Other treatment center characteristics associated with increased mortality included free-st and ing status ( P = 0.009 ) and decreasing frequency of reported physician supervision of care ( P = 0.01 ) . It was concluded that lower average levels of dialysis adequacy in treatment centers are associated with higher rates of death , and this association persists after controlling for facility-to-facility differences in patient and nonpatient characteristics This historic prospect i ve study assessed the relationship between dialyzer reuse practice s and hemodialysis patient mortality through 1 year of follow-up . Medicare patient demographic and survival data were combined with dialyzer reuse data from the Centers for Disease Control and Prevention 's annual survey of dialysis-related diseases . Data were analyzed for the US Medicare hemodialysis population of never transplanted patients prevalent on January 1 , 1989 , and January 1 , 1990 , who were treated in freest and ing dialysis units that used primarily conventional ( not high-flux ) dialyzers . Time to mortality , or transplant , and other censoring on December 31st of each year was regressed with proportional hazards models on patient , dialysis unit , and reuse measures . Age- , race- , and diagnosis-st and ardized mortality ratios for dialysis units were also regressed with weighted least squares techniques against dialysis unit and reuse measures . The results showed that patients treated in dialysis units that disinfected dialyzers with a peracetic acid , hydrogen peroxide , acetic acid mixture , or glutaraldehyde experienced higher mortality than patients treated in units that used formalin or in units that did not reuse dialyzers . The relative risk of mortality , compared with patients treated in nonreuse dialysis units , was 1.17 ( P = 0.010 ) for glutaraldehyde and 1.13 ( P < 0.001 ) for the peracetic acid mixture . The relative risk for formalin compared with the reference group of nonreuse was 1.06 ( P = 0.088 ) . With adjustment for several patient and dialysis unit characteristics , dialyzer reuse with certain germicides was associated with a significantly elevated mortality risk . This elevated risk , the etiology of which is currently not known , may represent a large number of potentially avoidable deaths per year . Only a large , nationally based analysis of this type has sufficient sample size to detect mortality risks such as these We analyzed the effect of patient and dialysis unit characteristics on access to kidney transplantation using several different approaches , including an analysis of individual patient data from a systematic r and om sample of 2900 new dialysis patients from each year 1981 to 1985 ( 14721 patients total ) . Additional analyses focused on the composition of transplant waiting lists and aggregate data from a 1984 census of 1133 dialysis and transplant units . White , male , young , nondiabetic , high-income patients treated in smaller units are more likely to receive a cadaver transplant under Medicare than are other kidney patients . Profit status of the dialysis unit was not found to be correlated to access to transplantation , although size of the unit may be correlated to access . Future analysis should focus on whether patient access has been inappropriately compromised . Possible factors unexplored in this analysis include differential patient preferences and medical suitability , as well as differential medical access The diverse patient and dialysis unit characteristics in the United States pose challenges for assessing the safety and efficacy of reuse practice s. A 10 % r and om sample of period-prevalent hemodialysis patients from units practicing conventional dialysis ( < 25 % of patients with high-efficiency/high-flux dialysis ) were analyzed . The data included 13,926 patient observations in 1989 - 1990 and 20,422 in 1991 - 1993 . Centers for Disease Control and Prevention and Health Care Financing Administration facility survey Medicare data were analyzed with a Cox regression model , evaluating the risk of reuse compared with no reuse and adjusting for comorbidity , unit characteristics , and profit status . In 1989 - 1990 , freest and ing and hospital-based units that did not reuse dialyzers were not significantly different from each other in mortality rates . In 1991 - 1993 , however , no-reuse , freest and ing , for-profit units had higher risks ( relative risk [ RR ] = 1.23 , P = 0.003 ) compared with no-reuse , hospital-based , nonprofit units . No-reuse , hospital-based , for-profit units , in contrast , were associated with a lower mortality risk ( RR = 0.70 , P = 0.0001 ) . An isolated higher risk associated with peracetic acid manual reuse in freest and ing units ( 1989 - 1990 ) was identified in for-profit units only . In the 1991 - 1993 period , an increased mortality risk was noted in hospital-based , nonprofit units practicing formaldehyde automatic reuse , and in freest and ing , for-profit units using glutaraldehyde , which accounted for < 5 % of all units . All other interactions of reuse germicide and technique were not different from no-reuse . The varying mortality rates identified in both no-reuse and reuse units using conventional dialysis suggest that other factors , such as dialysis therapy and anemia correction ( both known predictors of patient survival ) , have a greater influence on U.S. mortality than reuse germicides and techniques Decrease in the average duration of hemodialysis treatment time is a continuing phenomenon . We investigated the relationship of 3-year mortality to duration of dialysis in a 1984 - 1985 national r and om sample of 600 hemodialysis patients from 36 dialysis units . Mortality was negatively associated with duration of dialysis treatments , as shown by the Cox model , adjusted for other patient and dialysis unit covariates . With adjustment for other covariates , patients receiving an average dialysis treatment duration of less than 3.5 hours had relative mortality risks of 1.17 to 2.18 compared with those with treatments longer than 3.5 hours ( mortality risk of 1.0 ) . Reverse causation ( the possibility that more seriously ill patients received dialysis for a shorter time ) appears unlikely . We conclude that duration of the dialysis procedure is an important element in determining patient mortality as one of the factors determining the adequacy of dialysis |
12,015 | 25,534,834 | Systematic evaluation demonstrated the following : ( 1 ) H and therapy can possibly reduce pain .
2 ) Although both steroid and hyaluronate intra-articular injections can provide pain relief , most authors conclude that injection of hyaluronate is more effective .
3 ) The use of orthoses reduces pain without effect on function , strength , or dexterity .
6 ) There are no high-level evidence studies specifically evaluating the effect of analgesics and patient education in joint protection in patients with thumb base OA .
Available evidence suggests only some effect of orthoses and intra-articular hyaluronate or steroid injections | PURPOSE To provide a systematic review of r and omized controlled trials regarding the conservative treatment of thumb base osteoarthritis ( OA ) . | The aims of this r and omized controlled trial were to evaluate the efficacy of intra-articular Hylan G-F 20 on the pain , pinch strength , and functional status in patients with thumb base osteoarthritis ( OA ) . Sixty-six h and s of 33 female patients ( mean age , 62.6 ± 6.4 years ) with bilateral clinical and radiological thumb base OA were included into this study . H and s of the same patient were divided to Hylan G-F 20 and saline-injection groups . VAS pain 100 mm , pinch strength ( key , tripod and pulp to pulp pinch ) and functionality ( Dreiser functional index ) were assessed at baseline , at sixth and 24th weeks . Statistically significant improvements were detected in function ( p = 0.001 ) , VAS pain ( p = 0.002 ) , and pinch strength ( p = 0.004 ) at the 24th week in the Hylan G-F 20 group . However , only VAS pain scores decreased temporarily in control h and s at the 6th week ( p = 0.02 ) . Although short-term placebo analgesic effect could not be ignored , intra-articular hylan was effective on pain , pinch strength , and function at the 24th week Objective : To determine the difference in the usability of three types of thenar eminence ( TE ) orthoses . Design : Prospect i ve comparative pre-experimental study with r and omized cross-over design . Setting : Rehabilitation centre . Subjects : Ten patients with osteoarthritis of the carpometacarpal I joint confirmed by X-ray . Intervention : Three types of TE orthoses , made of either supple elastic material , elastic material with a semi-rigid thumb busk or a semi-rigid ( polyethylene ) material . Main outcome measurements : Pain at the thenar eminence , pinch force , h and function , cosmesis , comfort and function of the TE orthosis . Results : The supple elastic TE orthosis scores significantly better than the more rigid types on the subjects ‘ comfort ’ , ‘ function ’ and the Green Test , while the semi-rigid orthosis scores best on ‘ cosmesis ’ . The score on the subject ‘ pain reduction ’ shows no significant difference between the three types of TE orthoses . The scores obtained correspond with the outcome of structured interviews about the usability of the TE orthoses . Conclusion : Eight out of 10 patients prefer the permanent use of a TE orthosis . Six patients chose the supple elastic orthosis and two chose the semi-rigid orthosis The purpose of this study was to compare the effects of two 6-week splint and exercise regimens for patients with trapeziometacarpal osteoarthritis . Forty participants were enrolled in a r and omised , controlled clinical trial . The experimental group received a newly design ed thumb strap splint and an abduction exercise regimen , whereas the control group received current clinical practice consisting of a short opponens splint and a pinch exercise regimen . Outcome measures included pain ( VAS at rest in cm ) , strength ( tip pinch in kg ) , and h and function ( Sollerman Test of H and Function scored out of 80 ) , measured by a blinded assessor at Weeks 0 , 2 , and 6 . By Week 6 there was no significant difference in the extent of mean improvement between the groups in : pain , 0.5 cm ( 95 % CI -1.1 to 2.1 ) ; strength , 0.1 kg ( 95 % CI -0.8 to 0.9 ) ; or h and function , 0.7 points ( 95 % CI -3.6 to 5.0 ) . While both groups improved , neither regimen is superior to the other in patients with trapeziometacarpal osteoarthritis OBJECTIVE Prospect i ve assessment of the efficacy and tolerability of intra-articular sodium hyaluronate ( SH ; Ostenil mini ) and triamcinolone acetonide ( TA ; Volon A10 ) for treatment of osteoarthritis ( OA ) of the carpometacarpal ( CMC ) joint of the thumb in a 26-week , controlled , r and omized , on an intention to treat , masked-observer study . METHODS Patients were treated with three intra-articular injections of either SH ( n = 28 ) or TA ( n = 28 ) . Primary assessment s were pain according to a 100 mm visual analogue scale and extensive clinical and functional parameters such as swelling , grip power and range of motion . The population was analysed using one- and two-sided Mann-Whitney ( MW ) estimators . RESULTS Maximum pain relief occurred at 2 - 3 weeks for TA and at week 26 for SH after the first intra-articular injection . At weeks 2 - 3 TA was significantly better than SH ( MW : 0.3319 and 0.3063 ; P = 0.9827 and 0.9929 ) . At week 26 a slight superiority of SH could be observed ( MW : 0.53 ; P = 0.3624 ) and non-inferiority could be proven . After 26 weeks lateral pinch power was significantly better in the SH-group ( MW : 0.6331 ; P = 0.0226 ) . In all , 88.0 % of patients treated with SH and 79.1 % of the TA-group described pain improvement after 26 weeks . Both agents were well tolerated . No adverse events with causal connection to the investigational products occurred . CONCLUSION A single course of three SH injections is effective in relieving pain and improving joint function in patients with OA of the CMC joint of the thumb . Although in comparison with triamcinolone its effects are achieved more slowly , the results indicate a superior long-lasting effect of hyaluronan at 6 months after end of treatment period PURPOSE Conservative , nonsurgical therapies for basal joint osteoarthritis , such as thumb spica splinting and intra-articular corticosteroid injections , remain the mainstays for symptomatic treatment . This study compares intra-articular hylan , corticosteroid , and placebo injections with regard to pain relief , strength , symptom improvement , and metrics of manual function in a r and omized , controlled , double-blinded study . METHODS Sixty patients with basal joint arthritis were r and omized to receive 2 intra-articular hylan injections 1 week apart , 1 placebo injection followed by 1 corticosteroid injection 1 week later , or 2 placebo injections 1 week apart . Patients were evaluated at 2 , 4 , 12 , and 26 weeks and assessed with Visual Analog Scale pain scores , strength measures , difference scores , Disabilities of the Arm , Shoulder , and H and ( DASH ) scores , and range of motion measurements . RESULTS All groups reported pain relief at 2 weeks . The steroid and placebo groups had significantly less pain at week 4 compared with baseline , but this effect disappeared by week 12 . Only hylan injections continued to provide pain relief at 12 and 26 weeks compared with baseline . There were no significant differences in pain between groups at any time . At 12 and 26 weeks , the hylan group had improved grip strength compared with baseline , whereas the steroid and placebo groups were weaker . At 4 weeks , the steroid group reported in the difference score a greater improvement in symptoms ( 68 % ) compared with the hylan ( 44 % ) and placebo ( 50 % ) groups . Whereas at 26 weeks the hylan group reported the largest improvement in symptoms ( 68 % ) , this was not statistically different from the placebo ( 47 % ) and steroid ( 58 % ) groups . There were no significant differences in Disabilities of the Arm , Shoulder , and H and scores or range of motion among the groups . There were no complications from any injection . CONCLUSIONS There were no statistically significant differences among hylan , steroid , and placebo injections for most of the outcome measures at any of the follow-up time points . However , based on the durable relief of pain , improved grip strength , and the long-term improvement in symptoms compared with preinjection values , hylan injections should be considered in the management of basal joint arthritis of the thumb . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic The purpose of this study was to compare the objective , subjective , and radiographic responses of patients with carpometacarpal joint osteoarthritis ( CMCJ-OA ) wearing a prefabricated neoprene splint ( PFN ) , which crosses the CMCJ and metacarpophalangeal joint , with those of patients wearing a custom-made thermoplastic short opponens splint ( CMT ) , which crosses only the CMCJ . Patients ( N = 25 ) with first CMCJ stage I and II osteoarthritis were assigned r and omly to wear either the PFN splint or the CMT splint for one week . After one week , the subjects rated their function in the splint and their satisfaction and pain levels on visual analogue scales . Pinch measurements were performed and x-rays were taken to assess carpometacarpal subluxation . The second splint was then applied for one week and all measures were repeated . The subjects rated the PFN splint significantly higher , and most reported that they would choose the PFN splint over the CMT splint for daily and long-term use . Both pain and function were improved with splinting , but the effect was amplified with the PFN splint compared with the CMT splint . Both splints reduced subluxation at the first carpometacarpal joint , but the CMT effect was greater . This study further supports current evidence that subjects with stage I and II first CMCJ-OA will have pain relief with thumb splinting . In addition , the PFN splint will provide greater relief when compared with the CMT splint . Furthermore , this study reveals that patients prefer the PFN splint to the CMT splint |
12,016 | 31,029,118 | Socio-cultural and peer influences were major contributing factors that encouraged students to initiate WTS .
Furthermore , WTS dependence had two components : psychological and social .
This was compounded by the general perception that WTS is a less harmful , less addictive and more sociable alternative to cigarette smoking .
Knowledge of WTS harms failed to correlate with a reduced risk of WTS use , and some students reported symptoms of WTS addiction .
A large proportion of students believed that quitting WTS was easy , yet few were able to do so successfully .
Finally , students believed current public health campaigns to educate on WTS harms were inadequate and , particularly in the global north , were not required .
Conclusion Reasons for WTS amongst university students are multi-faceted . | Background Despite evidence for the harms of waterpipe tobacco smoking ( WTS ) , its use is increasing amongst college and university students worldwide .
This systematic review aims to assess the knowledge of , attitudes towards and perceptions of WTS among college or university students . | INTRODUCTION While cross-sectional studies have shown that hookah tobacco smoking ( HTS ) is an increasingly popular behavior among university students , little is known about factors associated with initiation . This study sought to determine associations between knowledge , attitudes , and normative beliefs and initiation of HTS among university students . METHODS Data were from a prospect i ve longitudinal cohort study of 569 r and omly selected first- and second-year university students . Online question naires that were developed in accordance with our composite theoretical model were completed in September 2010 and April 2011 . RESULTS About one-seventh ( 13 % ) of participants initiated HTS by follow-up . Positive attitudes and favorable normative beliefs were associated with increased adjusted odds of initiation ( AOR = 4.12 , 95 % CI = 2.56 , 6.59 ; and AOR = 2.01 , 95 % CI = 1.35 , 2.99 , respectively ) , while negative attitudes were associated with decreased adjusted odds ( AOR = 0.62 , 95 % CI = 0.48 , 0.80 ) . Correct knowledge regarding toxicants associated with HTS was not significantly associated with initiation . CONCLUSIONS While positive attitudes and favorable normative beliefs are associated with initiation of HTS in a cohort of never-users , increased knowledge about toxins is not associated with lower initiation . It may be particularly valuable for educational interventions to attempt to alter positive attitudes and normative beliefs related to HTS Background Although waterpipe tobacco smoking seems to be increasing on U.S. university campuses , these data have come from convenience sample s. Purpose We aim ed to determine the prevalence of and associations with waterpipe tobacco smoking among a r and om sample of students . Methods We surveyed a r and om sample of graduate and undergraduate students at a large , urban university . We used multivariate modeling to determine independent associations between belief-related predictors and waterpipe tobacco smoking . Results Of the 647 respondents , waterpipe smoking was reported in 40.5 % , over the past year in 30.6 % , and over the past 30 days in 9.5 % . Over half of the sample ( 52.1 % ) perceived that tobacco smoking from a waterpipe was less addictive than cigarette smoking . In fully adjusted multivariate models , 1-year waterpipe smoking was associated with low perceived harm ( OR = 2.54 , 95 % CI = 1.68 , 3.83 ) , low perceived addictiveness ( OR = 4.64 , 95 % CI = 3.03 , 7.10 ) , perception of high social acceptability ( OR = 20.00 , 95 % CI = 6.03 , 66.30 ) , and high perception of popularity ( OR = 4.72 , 95 % CI = 2.85 , 7.82 ) . Conclusions In this sample , lifetime waterpipe use was as common as lifetime cigarette use . Perception of harm , perception of addictiveness , social acceptability , and popularity were all strongly related to waterpipe smoking INTRODUCTION Tobacco use in low- to middle-income countries is a major public health concern for both smokers and those exposed to environmental tobacco smoke ( ETS ) . Egypt has made important strides in controlling tobacco use , but smoking and ETS remain highly prevalent . This r and omized intervention sought to improve the target population 's knowledge regarding the hazards of smoking and ETS and to change attitudes and smoking behaviors within the community and the household . METHODS In this 2005 - 2006 study in Egypt 's Qalyubia governorate , trained professionals visited schools , households , mosques , and health care centers in rural villages r and omly selected for the intervention to discuss the adverse effects of smoking and ETS exposure and ways to reduce one 's ETS exposure . Data collected in interviewer-facilitated surveys before and after the intervention period were analyzed in pairwise comparisons with data from control villages to assess the effectiveness of the intervention in achieving its aims . RESULTS The intervention group showed a greater increase in underst and ing the dangers associated with smoking cigarettes and waterpipes and became more proactive in limiting ETS exposure by asking smokers to stop , avoiding areas with ETS , and enacting smoking bans in the home . However , the intervention had little to no impact on the number of smokers and the amount of tobacco smoked . CONCLUSIONS Results are consistent with previous studies showing that changing smokers ' behavior can be difficult , but community-wide efforts to reduce ETS exposure through smoking bans , education , and empowering people to ask smokers to stop are effective . The method can be generalized to other setting INTRODUCTION Although water pipe tobacco smoking is common in Lebanon and Syria , prevalence in neighboring Jordan is uncertain . The purpose s of this study were ( a ) to assess the prevalence of water pipe tobacco smoking among university students in Jordan and ( b ) to determine associations between sociodemographic variables and water pipe tobacco smoking in this population . METHODS A trained interviewer administered a question naire among r and omly selected students at four prominent universities in Jordan . The question naire assessed sociodemographic data , personal history of water pipe tobacco use , and attitudes regarding water pipe tobacco smoking . We used logistic regression to determine independent associations between sociodemographic and attitudinal factors and each of two dependent variables : ever use of water pipe and use at least monthly . RESULTS Of the 548 participants , 51.8 % were male and mean age was 21.7 years . More than half ( 61.1 % ) had ever smoked tobacco from a water pipe , and use at least monthly was reported by 42.7 % . Multivariable analyses controlling for all relevant factors demonstrated significant associations between ever use and only two sociodemographic factors : ( a ) gender ( for women compared with men , odds ratio [ OR ] = 0.11 , 95 % CI = 0.07 - 0.17 ) and ( b ) income ( for those earning 500 - 999 Jordanian dinar ( JD ) monthly vs. < 250 JD monthly , OR = 2.37 , 95 % CI = 1.31 - 4.31 ) . There were also significant associations between perception of harm and addictiveness and each outcome . DISCUSSION Water pipe tobacco smoking is highly prevalent in Jordan . Although use is associated with male gender and upper middle income levels , use is widespread across other sociodemographic variables . Continued surveillance and educational interventions emphasizing the harm and addictiveness of water pipe tobacco smoking may be valuable in Jordan INTRODUCTION In Egypt , each faculty has it own students ' union , which represents the students and collaborates in organizing all educational , sporting and social activities . The objectives of the current study were to evaluate the knowledge of members of students ' unions about cigarette and Shisha smoking together with assessing their attitudes towards smoking in public places in general and in the university . METHODOLOGY A r and om sample of members of Ain Shams University Students ' Unions was subjected to an interview question naire . All participants were individually interviewed face-to-face by a trained interviewer from March 1 , 2005 to April 30 , 2005 . RESULTS Our study showed that 34 ( 31.5 % ) students were smokers . The mean knowledge score percentage was 79.4 + /- 20.7 . Regarding knowledge about Shisha smoking hazards , the majority of the students ( 84.3 % ) knew that Shisha smoking is hazardous . The mean attitude score percentage was 56.8 + /- 22.2 . Smokers had less mean knowledge as regard smoking hazards compared to non-smokers ( p < 0.01 ) . Also , smokers had a lower mean attitude compared to non-smokers ( p < 0.001 ) . More than one-third ( 38.9 % ) of the interviewed students did n't know if the students ' union has a policy for prevention of smoking or not . CONCLUSION Our findings point that although our students had a moderately high mean knowledge score yet this did n't increase their attitude about the smoking problem in the university and in the community . This supports the notion that , in addition to knowledge about smoking hazards , efforts are needed to change beliefs that allow this offensive habit to continue SETTING Waterpipe smoking is becoming a global health crisis among youth . OBJECTIVE To identify the prevalence of waterpipe use among Iranian university students and to explore perceived reasons for use . METHODS A r and om sample of 1024 university students at two major universities in South Iran was enrolled in the study . A three-part question naire ( baseline data , tobacco smoking status and perceived reasons for waterpipe use ) was used . Students filled out the self-administered question naire in their classrooms . RESULTS The prevalence of waterpipe smoking in the respondents ' lifetime and in the last 30 days was 42.5 % and 18.7 % , respectively . The mean age at initiation of waterpipe smoking was 16.3 ± 3.2 years . Ever smoking was positively associated with age and male sex , whereas no association was found regarding marital status . The highest odds of lifetime waterpipe smoking were observed in students with close friends who smoked the waterpipe ( 5.94 , 95%CI 4.26 - 8.30 ) . The most important perceived reason for waterpipe smoking as stated by students was enjoyment ( 55.8 % ) . CONCLUSION Given the alarming prevalence of waterpipe smoking , preventive measures should be adopted among university students taking into account the influence of peers , siblings and parents in the lessening social tolerance of waterpipe smoking Background and objectives Narghile is becoming the favorite form of tobacco use by youth globally . This problem has received more attention in recent years . The aim of this study was to investigate the prevalence and pattern of narghile use among students in three public Jordanian universities ; to assess their beliefs about narghile 's adverse health consequences ; and to evaluate their awareness of oral health and oral hygiene . Methods The study was a cross-sectional survey of university students . A self-administered , anonymous question naire was distributed r and omly to university students in three public Jordanian universities during December , 2008 . The question naire was design ed to ask specific questions that are related to smoking in general , and to narghile smoking in specific . There were also questions about oral health awareness and oral hygiene practice s. Results 36.8 % of the surveyed sample indicated they were smokers comprising 61.9 % of the male students and 10.7 % of the female students in the study sample . Cigarettes and narghile were the preferred smoking methods among male students ( 42 % ) . On the other h and , female students preferred narghile only ( 53 % ) . Parental smoking status but not their educational level was associated with the students smoking status . Smokers had also significantly poor dental attendance and poor oral hygiene habits . Conclusion This study confirmed the spreading narghile epidemic among young people in Jordan like the neighboring countries of the Eastern Mediterranean region . Alarming signs were the poor oral health awareness among students particularly smokers National data indicate nearly a quarter of college students smoked from a hookah at some point in their lifetime regardless of gender . To address this issue , research ers assessed the perceptions , knowledge , beliefs of hookah users at a large Midwestern University and also determined what other drug related high-risk behaviors were associated with this behavior . An anonymous , online survey was sent to 2,000 r and omly selected undergraduate students from a large Midwestern University . Research ers used a cross sectional research design to determine the prevalence and motivating factors associated with hookah use . Respondents included 438 individuals ( 60 % female ) with an average age of 23.1 ( SD = 12.32 ) , yielding a response rate of 22 % . Approximately 15.4 % of the sample had previously smoked hookah , while 6 % used hookah within the past 30 days . Common motivating factors associated with smoking hookah included socializing/partying ( 29 % ) , peer influence ( 27 % ) , and for relaxation ( 25 % ) . Correlations were calculated comparing hookah use to other high risk behaviors with the two highest correlations consisted of 30-day tobacco use ( r = 0.67 ) and marijuana ( r = 0.39 ) . The results from this study suggest hookah use is limited to a small percentage of students . Students appear to smoke hookah for social reasons and underestimate the addictive properties associated with the product . Research ers and practitioners need to develop and evaluate specific interventions to educate college students about the health hazards associated with hookah use Introduction Hookah smoking is becoming increasingly popular among young adults and is often perceived as less harmful than cigarette use . Prior studies show that it is common for youth and young adults to network about substance use behaviors on social media . Social media messages about hookah could influence its use among young people . We explored normalization or discouragement of hookah smoking , and other common messages about hookah on Twitter . Methods From the full stream of tweets posted on Twitter from April 12 , 2014 , to May 10 , 2014 ( approximately 14.5 billion tweets ) , all tweets containing the terms hookah , hooka , shisha , or sheesha were collected ( n = 358,523 ) . The hookah tweets from Twitter users ( tweeters ) with high influence and followers were identified ( n = 39,824 ) and a r and om sample of 5,000 tweets was taken ( 13 % of tweets with high influence and followers ) . The sample of tweets was qualitatively coded for normalization ( ie , makes hookah smoking seem common and normal or portrays positive experiences with smoking hookah ) or discouragement of hookah smoking , and other common themes using crowdsourcing . Results Approximately 87 % of the sample of tweets normalized hookah use , and 7 % were against hookah or discouraged its use . Nearly half ( 46 % ) of tweets that normalized hookah indicated that the tweeter was smoking hookah or wanted to smoke hookah , and 19 % were advertisements/promotions for hookah bars or products . Conclusion Educational campaigns about health harms from hookah use and policy changes regarding smoke-free air laws and tobacco advertising on the Internet may be useful to help offset the influence of pro-hookah messages seen on social media Background Among Arab citizens in Israel , cigarette and nargila ( hookah , waterpipe ) smoking is a serious public health problem , particularly among the young adult population . With the dramatic increase of Internet and computer use among Arab college and university students , a Web-based program may provide an easy , accessible tool to reduce smoking rates without heavy re source dem and s required by traditional methods . Objective The purpose of this research was to examine the acceptability and feasibility of a pilot Web-based program that provides tailored feedback to increase smoking knowledge and reduce cigarette and nargila smoking behaviors among Arab college/university students in Israel . Methods A pilot Web-based program was developed , consisting of a self-administered question naire and feedback system on cigarette and nargila smoking . Arab university students were recruited to participate in a mixed- methods study , using both quantitative ( pre-/posttest study design ) and qualitative tools . A posttest was implemented at 1 month following participation in the intervention to assess any changes in smoking knowledge and behaviors . Focus group sessions were implemented to assess acceptability and preferences related to the Web-based program . Results A total of 225 participants —response rate of 63.2 % (225/356)—completed the intervention at baseline and at 1-month post study , and were used for the comparative analysis . Statistically significant reductions in nargila smoking among participants ( P=.001 ) were found . The intervention did not result in reductions in cigarette smoking . However , the tailored Web intervention result ed in statistically significant increases in the intention to quit smoking ( P=.021 ) . No statistically significant increases in knowledge were seen at 1-month post study . Participants expressed high satisfaction with the intervention and 93.8 % ( 211/225 ) of those who completed the intervention at both time intervals reported that they would recommend the program to their friends , indicating excellent acceptability and feasibility of the intervention . This was further emphasized in the focus group sessions . Conclusions A tailored Web-based program may be a promising tool to reduce nargila smoking among Arab university students in Israel . The tailored Web intervention was not successful at significantly reducing cigarette smoking or increasing knowledge . However , the intervention did increase participants ’ intention to quit smoking . Participants considered the Web-based tool to be an interesting , feasible , and highly acceptable strategy . Trial Registration Trial Registration : IS RCT N registry IS RCT N59207794 ; http://www.is rct n.com/IS RCT N59207794 ( Archived by WebCite at http://www.webcitation.org/6VkYOBNOJ ) Hookah tobacco smoking is increasing among US college students , including those who would not otherwise use tobacco . Part of hookah 's appeal is attributed to the perception that hookah is less harmful than cigarettes . The aims of this study were to assess knowledge of harmful exposures associated with hookah smoking relative to cigarette smoking and to determine associations between this knowledge and hookah smoking outcomes . Students ( N = 852 ) at the University of Florida were r and omly sample d via e-mail to obtain information on demographics , hookah smoking behavior and knowledge of five exposures ( e.g. tar and nicotine ) . Multivariable logistic regression models assessed independent associations between knowledge and hookah smoking outcomes . Of the five factual knowledge items asked , 475 ( 55.8 % ) of the respondents answered none correctly . In multivariable models , correct responses to any knowledge items were not associated with lower odds of hookah smoking or susceptibility to hookah smoking in the future . Although college students are largely unaware of the toxicant exposures associated with hookah smoking , there is little association between knowledge and hookah smoking behavior OBJECTIVES To study the awareness , perceptions and practice of university students in Karachi , Pakistan , with regard to shisha ( waterpipe ) smoking . DESIGN Cross-sectional survey conducted among students at four different universities of Karachi , selected through r and om cluster sampling . RESULTS A total of 450 participants , 59.6 % males ( n=268 ) and 40.4 % females ( n=182 ) , were included in the study . About half of the participants reported having ever smoked shisha ( n=241 , 53.6 % ) . On examining factors associated with starting shisha smoking , curiosity was found to be the most common reason ( n=148 , 61.4 % ) , followed by pleasure-seeking ( n=113 , 46.9 % ) , peer pressure ( n=55 , 22.8 % ) , boredom ( n=43 , 17.8 % ) and stress ( n=26 , 10.8 % ) . Of 241 participants who had ever smoked waterpipes , the majority ( n=149 , 61.8 % ) were current smokers . A vast majority of participants ( n=269 , 60 % ) considered waterpipe smoking to be less unhealthy than cigarette smoking . Boredom in youth , use of waterpipe in leisure activities and peer pressure were identified as the most common reasons for the escalating popularity of waterpipe smoking in Pakistan . CONCLUSIONS Waterpipe smoking is very popular among Pakistani university students , and knowledge among university students about the dangers of waterpipe smoking is alarmingly low The study describes the prevalence of different forms of smoking , and the correlates of current smoking , by male students of King Faisal University , Saudi Arabia . A r and om sample of 1382 students at 9 colleges answered a self-administered question naire based on the Global Youth Tobacco Survey plus the modified Fagerström Test for Nicotine Dependence . The prevalence of current smoking was 28.1 % ( 21.6 % for cigarettes , 14.6 % for waterpipe ) . Of current smokers , 41.4 % were living in homes where others smoke and 17.0 % initiated smoking below age 12 years . In logistic regression analysis older age , living away from home , smoking by family and close friends and exposure to tobacco promotion were predictors of current smoking status OBJECTIVE Guided by the Theory of Reasoned Action , this study examined the association of behavioral beliefs , attitudes , normative beliefs , and subjective norms with waterpipe tobacco smoking intention in college students . DESIGN AND SAMPLE A cross-sectional design was used . A Web-based survey was sent to a r and om sample of 1,000 undergraduate students from a public institution in the southeast to recruit participants . MEASURES The Theory of Reasoned Action Waterpipe Question naire , a modified version of the Fishbein-Ajzen-Hanson Question naire , was used to capture modal constructs of the Theory of Reasoned Action related to waterpipe use . Cronbach 's α coefficients for the scales of the Theory of Reasoned Action Waterpipe Question naire ranged from .76 to .95 . RESULTS Of the sample ( n=223 ) , 13.5 % currently smoked a waterpipe and 61 % had ever done so . Using multiple regression , attitudes , behavioral beliefs , and subjective norms were associated with intention to smoke a waterpipe in the next 3 months and collectively explained 35 % of the variance in intention . The full model , which included all the constructs of the Theory of Reasoned Action , demographic variables , and tobacco use variables , explained 83 % of the variance in intention to smoke a waterpipe in the next 3 months . CONCLUSIONS This study provides valuable information that may be used to target students at risk for waterpipe smoking and serves as a starting point in developing theoretically driven interventions to prevent waterpipe smoking OBJECTIVES To investigate tobacco use , beliefs and attitudes among medical students in Syria . METHODS A cross-sectional study of a r and om sample of 570 medical students ( first and fifth year ) registered at the Damascus University Faculty of Medicine in 2006 - 2007 . We used a self-administered question naire for demo-graphic information , smoking behaviour ( cigarette , waterpipe ) , family and peer smoking , attitudes and beliefs about smoking and future role in advising patients to quit smoking . RESULTS The overall prevalence of tobacco use was 10.9 % for cigarettes ( 15.8 % men , 3.3 % women ) , 23.5 % for waterpipe ( 30.3 % men , 13.4 % women ) and 7.3 % for both ( 10.1 % men , 3.1 % women ) . Both smoking methods were more popular among the fifth year students ( 15.4 % and 27 % ) compared to their younger counterparts ( 6.6 % and 19.7 % ) . Regular smoking patterns predominated for cigarettes ( 62 % ) , while occasional use patterns predominated for waterpipes ( 83 % ) . More than two thirds of students ( 69 % ) thought they might not address or would have difficulty addressing smoking in their future patients . CONCLUSION The level of tobacco use among Syrian medical students is alarming and highlights the rapidly changing patterns of waterpipe use , especially among female students . Medical schools should work harder to tackle this phenomenon and address it more efficiently in their curricula OBJECTIVE To determine the frequency of waterpipe smoking in students of different age groups . STUDY DESIGN Cross-sectional survey . PLACE AND DURATION OF STUDY Karachi , Pakistan , from February 2012 to February 2013 . METHODOLOGY The subjects were divided into two age groups . Group-I comprised of 13 - 17 years old r and omly selected students from O ' Level schools in Karachi and group-2 included 23 - 27 years old undergraduate and postgraduate students again r and omly selected from various institutions in Karachi . A question naire was filled with prior consent , basic education on waterpipe smoking was given , and all the questions of the survey form were explained to the subjects according to context . RESULTS In group-1 , 39 % students smoked waterpipe . Most students had been smoking waterpipe for the last 2 years . In group-2 , 48 % individuals smoked waterpipe , majority of smokers indulged in the last 5 years and among them , most were falling within the last 2 years . CONCLUSION The frequency of waterpipe smoking in teenage students was 39 % and older students for 48 % . Social and recreational use of waterpipes is widespread among both groups despite being acknowledged by majority as a health hazard OBJECTIVE The objective of this study was to determine the prevalence of waterpipe ( shisha ) smoking and associated factors among Malaysian university students . METHODOLOGY A total of 200 university students from Management and Science University participated in this study . The survey was conducted by simple r and om sampling by r and omly distributing self-administered question naires to the library , cafeterias and classes . The protocol of this study was approved by the ethics committee of Management and Science University . Consent forms were obtained from the students before they answered the question naire . Statistical analyses were performed using the Statistical Package for Social Science ( SPSS ) version 13 . with the Student 's t-test for comparison of the mean practice and backward multiple linear regression for multivariate analysis . RESULTS The majority of the subjects were male , single , Malay and from urban areas ( 61.5 % , 94.5 % , 66 % , 76.5 % ; respectively ) . In this study 30 % of the study participants were shisha smokers . Regarding knowledge about shisha smoking , the majority ( 48.5 % ) mentioned that shisha is less harmful than cigarettes and 55 % reported that shisha is less addictive . Univariate analysis showed that age , race , sex and income significantly influenced the practice of smoking shisha among university students ( p=0.019 , p=0.002 , p=0.001 , p=0.018 ; respectively ) . For multivariate analysis , income and gender demonstrated significant influence ( both p=0.001 ) . CONCLUSION There was a high prevalence of shisha smoking among Malaysian university students and knowledge about the dangers is low . Income and gender significantly influenced the practice of smoking shisha in our population . Banning of smoking including shisha smoking in public places is strongly recommended INTRODUCTION There is a rising prevalence of waterpipe smoking worldwide , but still a paucity of information on perceptions toward quitting waterpipe use . We set out to establish the beliefs and perceptions of café waterpipe smokers toward quitting waterpipe smoking in the Kingdom of Bahrain . METHODS A cross-sectional study . A r and om sample of 20 of 91 cafés serving waterpipe tobacco in Bahrain was taken . A question naire was administered in each café to 20 participants aged 18 and above . RESULTS Three hundred eighty participants completed question naires from waterpipe smokers . Eighty-four percent of participants were Bahraini and 71 % had a university degree . Mean age was 28.9 years . Average age of waterpipe smoking initiation was 20.3 years . The majority of waterpipe users chose flavored tobacco . Sixty-one percent smoked waterpipe tobacco daily with a mean smoking time of 2.6hr/day . Seventy-two percent considered waterpipe tobacco as harmful as or more harmful than cigarettes , but 67 % considered cigarettes as more addictive . Eighty-two percent stated that they could quit waterpipe at any time , but only 40 % were interested in quitting . Interest in quitting smoking was related to 4 variables : a physician mentioning the need to quit smoking , being non-Bahraini , having a family with a hostile attitude toward waterpipe smoking , and not considering oneself " hooked " on waterpipe tobacco . CONCLUSIONS Waterpipe smokers in Bahrain cafés are frequent and high users . Health professionals must consider waterpipe smoking in all consultations and health promotion messages . A partnership between health professionals and disapproving members of families may be an effective strategy in encouraging waterpipe smokers to quit ABSTRACT Objective : This study 's purpose was to describe urban college students ’ communication about hookah with health care providers . Participants : Participants included a r and om sample of undergraduate urban college students and health care providers . Methods : Students surveyed determined the epidemiology of hookah use in this population , how many health care providers asked about hookah , and how many students admitted hookah use to a physician . Results : Of 375 students surveyed , 78 ( 20.8 % ) had never tried it , 284 ( 75.7 % ) had smoked hookah at least once , and 64 students ( 22.6 % ) were classified as frequent hookah smokers . Only 15 ( 4.7 % ) reported a health care provider asking about hookah during visits , whereas 36 ( 12.7 % ) admitted their hookah use to a health care provider . Conclusion : Hookah use was found to be highly prevalent among students in one urban university . This study supports the hypothesis that few health care providers broach the topic with patients . Additional research on health consequences of hookah use , education , and improved screening is warranted |
12,017 | 25,437,000 | PRIMARY OUTCOMES symptom scores and quality of life scores There were no important differences between groups in either the patient-reported disease-specific symptom scores or the health-related quality of life scores .
No differences were found for any objective measurements or olfactory tests in those studies in which they were measured .
The evidence does not show that one treatment is better than another in terms of patient-reported symptom scores and quality of life measurements . | BACKGROUND Nasal polyps cause nasal obstruction , discharge and reduction in or loss of sense of smell , but their aetiology is unknown .
The management of chronic rhinosinusitis with nasal polyps , aim ed at improving these symptoms , includes both surgical and medical treatments , but there is no universally accepted management protocol .
OBJECTIVES To assess the effectiveness of endonasal/endoscopic surgery versus medical treatment in chronic rhinosinusitis with nasal polyps . | A r and omized comparison of the usual surgical removal of nasal polyps versus systemic steroid treatment was performed in 53 patients . In all , continuous topical steroid treatment was given during the one year period of observation . In both groups the initial treatment result ed in a continuous increase in mean nasal expiratory peak flow as well as in the sense of smell ; these two parameters showed a temporary statistically significant difference in favour of the medically treated group . In general though , the results in the two treatment groups were alike . Therefore medical treatment is recommended for routine use . Surgical removal should be reserved for those few cases in which the presence of residual or recurrent polyps justifies the inherent risks and discomfort for the patient Patients with nasal polyps present repeatedly in otorhinolaryngology practice s , but the prevalence of nasal polyps in the general population is not known . Our objective was to investigate the prevalence of nasal polyps in an adult Swedish population in relation to age , gender , asthma , and aspirin intolerance . A r and om sample of 1,900 inhabitants over the age of 20 years , stratified for age and gender , was drawn from the municipal population register in Skövde , Sweden , in December 2000 . The subjects were called to clinical visits that included questions about rhinitis , asthma , and aspirin intolerance and examination by nasal endoscopy . In total , 1,387 volunteers ( 73 % of the sample ) were investigated . The sample size was adequate , with a good fit to the whole population . The prevalence of nasal polyps was 2.7 % ( 95 % confidence interval , 1.9–3.5 ) , and polyps were more frequent in men ( 2.2 to 1 ) , the elderly ( 5 % at ≥60 years of age ) , and asthmatics . Subjective symptoms of aspirin intolerance were not found to correlate with polyps . Nasal polyps were more common in adults than was stated by the a priori estimate . The Skövde population -based study is considered representative for the Swedish population OBJECTIVE To reevaluate the current criteria for diagnosing allergic fungal sinusitis ( AFS ) and determine the incidence of AFS in patients with chronic rhinosinusitis ( CRS ) . METHODS This prospect i ve study evaluated the incidence of AFS in 210 consecutive patients with CRS with or without polyposis , of whom 101 were treated surgically . Collecting and culturing fungi from nasal mucus require special h and ling , and novel methods are described . Surgical specimen h and ling emphasizes histologic examination to visualize fungi and eosinophils in the mucin . The value of allergy testing in the diagnosis of AFS is examined . RESULTS Fungal cultures of nasal secretions were positive in 202 ( 96 % ) of 210 consecutive CRS patients . Allergic mucin was found in 97 ( 96 % ) of 101 consecutive surgical cases of CRS . Allergic fungal sinusitis was diagnosed in 94 ( 93 % ) of 101 consecutive surgical cases with CRS , based on histopathologic findings and culture results . Immunoglobulin E-mediated hypersensitivity to fungal allergens was not evident in the majority of AFS patients . CONCLUSION The data presented indicate that the diagnostic criteria for AFS are present in the majority of patients with CRS with or without polyposis . Since the presence of eosinophils in the allergic mucin , and not a type I hypersensitivity , is likely the common denominator in the pathophysiology of AFS , we propose a change in terminology from AFS to eosinophilic fungal rhinosinusitis The effects of rhinosinusitis treatment upon asthma are disputed . The first r and omised prospect i ve study of surgical compared with medical therapy of chronic rhinosinusitis in 90 patients with and without nasal polyps was previously reported . Asthma symptoms , control , forced expiratory volume in one second ( FEV1 ) , peak flow , exhaled nitric oxide , medication use and hospitalisation at 6 and 12 months from the start of the study were also monitored . This paper reports these results in 43 of those patients with concomitant asthma . Both medical and surgical treatment of chronic rhinosinusitis were associated with subjective and objective improvements in asthma . Overall asthma control improved significantly following both treatment modalities , but was better maintained after medical therapy , where improvement could also be demonstrated in the subgroup with nasal polyps . Medicine was superior to surgery with respect to a decrease in exhaled nitric oxide and increase in FEV1 in the polyp patients . Two patients noted worsening of asthma post-operatively . Improvement in upper airway symptoms , as assessed using a visual analogue scale , correlated with improvement in asthma symptoms and control . Treatment of chronic rhinosinusitis , medical or surgical , benefits concomitant asthma ; that associated with nasal polyposis benefits more from medical therapy OBJECTIVES To conduct the first prospect i ve r and omized controlled trial , evaluating and comparing the effect of medical and surgical treatment of chronic rhinosinusitis ( CRS ) on quality of life . MATERIAL S AND METHODS Ninety patients with CRS , who remained symptomatic after initial medical treatment with Dexarhinaspray duo and nasal douche , were r and omized either to medical or surgical therapy . All patients underwent pre- and post-treatment assessment s of the Sinonasal Outcome Test-20 ( SNOT-20 ) , and the Short Form 36 Health Survey ( SF-36 ) . Each patient had three assessment s : before starting the r and omized treatment , after six months and finally after one year . RESULTS Both the medical and surgical treatment of CRS significantly improved almost all the parameters of SNOT and SF-36 ( p<0.05 ) , with no significant difference being found between the medical and surgical groups ( p>0.05 ) . CONCLUSION Both maximal medical and surgical therapy of CRS improves the quality of life of CRS patients , providing further evidence that chronic rhinosinusitis should be targeted with maximal medical therapy in the first instance , with surgical treatment being reserved for cases refractory to medical therapy . The presence of nasal polyps does not imply any negative effect on the quality of life after CRS therapy , either medical or surgical BACKGROUND The treatment of nasal polyps is controversial , and medical treatment alone has been little investigated to our knowledge . OBJECTIVE To examine the efficacy of therapy using only topical budesonide powder and topical budesonide powder supplemented with surgical removal or intramuscular betamethasone . DESIGN R and omized , double-blind comparison of 2 dosages and additional treatment , if therapy failed . After 1 year , treatment with medication was stopped , and the dem and for renewed treatment was monitored for another year . PATIENTS Patients with bilateral nasal polyps who dem and ed treatment were consecutively enrolled in a hospital outpatient clinic or specialty private practice . During a 15-month period from 1990 to 1992 , a total of 126 patients entered the 2-year study . INTERVENTIONS In phase 1 , r and omized and double-blind treatment with a topical medication , budesonide powder , 800 micrograms or 400 micrograms daily , or a placebo was given for 1 month . In phase 2 , r and omized and double-blind treatment with budesonide powder , 800 micrograms or 400 micrograms daily , was given . At the end of phase 1 , failed therapy was supplemented by r and omly assigned treatment of either surgical removal or a single injection of sustained released betamethasone . In phase 3 , treatment with the medication was discontinued , and patients were monitored for another year . The time when treatment was required again was noted . The present article deals with phases 2 and 3 . MAIN OUTCOME MEASURES Patients ' scores of treatment efficacy as well as symptoms and signs . Semiquantitative measurement of sense of smell and calculation of peak expiratory flow rate index based on nasal and oral peak expiratory flow . RESULTS In all outcome measures , a comparison of the data before treatment with the corresponding figures during phase 2 showed statistically significant efficacy . The clinical course was described at the end of phase 2 . About 85 % of the patients , including those who received additional therapy because the initial therapy failed , rated total or substantial control over the symptoms . The 2 dosages investigated showed equal results . These findings were consistent with the signs recorded and the peak expiratory flow rate index . The results of phase 3 showed that 50 % of patients had dem and ed treatment after 4 months , while 34 % managed without medication after 1 year . CONCLUSIONS The clinical course in this study showed that most patients with nasal polyps do well with medical treatment . Therefore , surgery was required in few patients . However , the potential of medical treatment should be further explored in future studies BACKGROUND Nasal polyposis ( NP ) is a frequent inflammatory chronic disease of the upper respiratory tract , which may impair quality of life ( QOL ) . The NP impact , which is frequently associated with lower respiratory disorders , has never before been studied . OBJECTIVE We initiated this prospect i ve study to establish internal validity and reliability of the generic SF-36 question naire in NP and to determine to what level daily functioning becomes impaired as a result of NP . METHODS Forty-nine consecutive patients with NP were included . They were assessed for the severity of nasal symptoms and underwent pulmonary function tests . The QOL profiles in patients with NP were compared with those of patients with perennial rhinitis ( n = 111 ) and healthy subjects ( n = 116 ) . RESULTS Cronbach 's coefficient alpha demonstrated the high reliability and validity of the SF-36 question naire for patients with NP ( alpha = .89 ) . NP impaired QOL more than perennial allergic rhinitis ( P < .05 ) . The impairment of QOL was greater when NP was associated with asthma ( P < .05 ) . SF-36 scores appeared highly correlated to pulmonary function ( FEV1 , maximal midexpiratory flow , forced vital capacity ) , suggesting relationships between QOL in NP and associated bronchial obstruction . Severity of nasal symptoms were not related to QOL scales . In addition , sequential evaluations of QOL , nasal symptoms , and pulmonary function were performed 10 months after the first evaluation in 28 patients with NP . These evaluations demonstrated that NP treatment either with nasal steroids or endonasal ethmoidectomy significantly improved both nasal symptoms and QOL without significant change of pulmonary function . CONCLUSION Our study clearly demonstrated that the SF-36 question naire presented a high internal validity and reliability in patients with NP . NP impaired QOL to a greater degree than perennial allergic rhinitis . QOL improvement after NP treatment is related to nasal symptoms improvement OBJECTIVES /HYPOTHESIS Genetic etiology is suspected in the development of nasal polyposis on the basis of familial aggregation . This study investigated whether there is an association between HLA-DRB1 , -DQA1 , and -DQB1 alleles and developing nasal polyposis . STUDY DESIGN Data from 50 polypectomized patients were compared with data from 50 healthy r and omly selected controls . Polyp score , possible asthma , aspirin sensitivity , and ASA triad were also recorded . METHODS Genotyping of HLA-DRB1 alleles was carried out with the Dynal RELI SSO HLA-DRB , a direct DNA probe test that utilizes a polymerase chain reaction ( PCR ) and nucleic acid hybridization for the differentiation of 70 HLA-DRB alleles and 9 supertypes . For DQA1 * genotyping PCR-RFLP ( restriction fragment length polymorphism ) was used , differentiating eight alleles . The DQB1 * typing was carried out using a INNO-LiPA DQB PCR-reverse hybridization kit , allowing the discrimination of 30 alleles . RESULTS People carrying the HLA-DR7-DQA1 * 0201 , and -DQB1 * 0202 haplotype were found to have a two to three times higher odds ratios ( ORs ) for developing the disease , compared with controls . Patients with ASA triad carried the above-mentioned DR7 allele with the linked alleles significantly more often ( P < .001 ) . Subjects carrying HLA-DR5 allele and the linked alleles had lower odds ratio values . CONCLUSION These results underline that allergy is not conditional for the formation of nasal polyps as thought before . Nasal polyposis associated with asthma and aspirin sensitivity is probably a unique form of nasal polyps . The authors plan further investigations in this field Our underst and ing of fungi in chronic rhinosinusitis ( CRS ) has been limited by previously employed detection techniques . This study examines the fungal component of the microbiome in CRS patients and controls using a highly sensitive culture‐independent molecular technique . The aims of this study include the characterization of fungal richness , prevalence , abundance , temporal changes , and their relationship with patient outcomes OBJECTIVES To conduct the first prospect i ve , r and omized , controlled trial evaluating and comparing the medical and surgical treatment of polypoid and nonpolypoid chronic rhinosinusitis ( CRS ) . MATERIAL S AND METHODS Ninety patients with CRS were equally r and omized either to medical or surgical therapy . All patients underwent pre- and posttreatment assessment s of visual analogue score ( VAS ) , the Sinonasal Outcome Test-20 ( SNOT-20 ) , the Short Form 36 Health Survey ( SF-36 ) , nitric oxide ( NO ) , acoustic rhinometry , saccharine clearance time ( SCT ) , and nasal endoscopy . Each patient had three assessment s : before starting the treatment , after 6 months , and , finally , after 1 year . RESULTS Both the medical and surgical treatment of CRS significantly improved almost all the subjective and objective parameters of CRS ( P < .01 ) , with no significant difference being found between the medical and surgical groups ( P > .05 ) , except for the total nasal volume in CRS ( P < .01 ) and CRS without polyposis ( P < .01 ) groups , in which the surgical treatment demonstrated greater changes . CONCLUSION CRS should be initially targeted with maximal medical therapy ( e.g. , a 3 month course of a macrolide antibiotic , douche , and topical steroid ) , with surgical treatment being reserved for cases refractory to medical therapy . The presence of nasal polyps is not a poor prognostic factor for the efficacy of CRS therapy , either surgical or medical Nasal polyposis ( NP ) is a common condition in patients consulting ENT practitioners in France . A multicenter prospect i ve study was performed to evaluate symptoms , demography , environmental factors , personal and family history and associated conditions like asthma , and food or drugs sensitivity ( FDS ) in patients suffering from NP . In each investigation center assessment s were performed at the moment of the initial consultation by the same investigator , then up date d with complementary exploration results required by the protocol . The chi 2 test and the Fisher test were used for statistical analysis . In this study 224 patients were included . Males were predominant at 63 % . Asthma was found in 45 % of cases without relevant sex difference . However , FDS , positive in 31 % of the patients , was statistically higher in females than in males ( 42.9 % vs. 24.4 % ) . Severe and major symptoms were more frequently found in the female population . Environment and habitat factors did not appear to be relevant . High rates of NP ( 52.66 % ) and asthma ( 43.58 % ) were found in the family history . Hereditary factors were suggested and lead us to further study the genetic factors potentially involved in this pathology OBJECTIVE The objective of this study was to determine the rate of complications of surgery for nasal polyposis and chronic rhinosinusitis as well as their risk factors . STUDY DESIGN , SETTING , PARTICIPANTS , AND OUTCOME MEASURES : The authors conducted a prospect i ve study of 3,128 patients who underwent sinonasal surgery during 2000 and 2001 in 87 National Health Service hospitals in Engl and and Wales . Patients completed a preoperative question naire that included the Sino-Nasal Outcome Test , a measure of sinonasal symptoms severity and health-related quality of life . Surgeons provided information about polyp extent , opacity of the sinuses on computed tomography ( Lund-Mackay score ) , comorbidity ( American Society of Anesthesiologists score ) , and the occurrence of perioperative complications . RESULTS Major complications ( orbital or intracranial complications , bleeding requiring ligation or orbital decompression , or return to the operating room ) occurred in 11 patients ( 0.4 % ) . Minor complications ( all other untoward events ) occurred in 207 patients ( 6.6 % ) . Most frequently reported minor complications were excessive perioperative hemorrhage bleeding ( 5.0 % ) as well as postoperative hemorrhage requiring treatment ( 0.8 % ) . Multivariate analysis indicated that the complication rate was linked to the extent of disease measured in terms of symptom severity and health-related quality of life , the extent of polyposis , level of opacity of the sinuses on computed tomography , and the presence of comorbidity , but not surgical characteristics ( extent of surgery , use of endoscope or microdebrider , grade of surgeon , and adjunctive turbinate surgery ) . CONCLUSIONS The risk of complications depended on patient characteristics rather than on the surgical technique used . Measures of the extent of disease and comorbidity may help in identifying patients at high risk of complications Budesonide has been used for a number of years as a topical nasal corticosteroid in the treatment of nasal allergy and nasal polyps . Recently , a new device for powder insufflation where no constituents or preservatives are included has been developed ( Rhinocort Turbuhaler , Astra Draco AB , Sweden ) . The present investigation was design ed in order to study the efficacy of topical budesonide powder as the only treatment of nasal polyps . A total of 126 patients entered the study . The medical history and clinical recordings included symptoms and signs , a semiquantitative test of smell and measurement of nasal expiratory peak flow index . Medication was either 200 or 400 micrograms of budesonide powder b.i.d . or placebo . After 1 month an overall assessment of treatment efficacy was made to determine whether the treatment had been a success or a failure . The results showed a statistically significant improvement of symptoms and signs in the actively treated groups . The increase in expiratory peak flow index was about 60 % in the actively treated groups as opposed to 16 % in the placebo group . The overall assessment of treatment efficacy showed success in about 82 % of actively treated patients as opposed to about 43 % in the placebo group . It is concluded that budesonide powder is useful in the treatment of nasal polyps Background : Nasal polyposis ( NP ) is not a life‐threatening disorder but may have a great impact on the quality of life ( QoL ) . The objective of this study : ( i ) to investigate the health burden incurred by NP compared with the Spanish general population using the Short Form‐36 Health Survey ( SF‐36 ) question naire ; ( ii ) to compare the QoL outcome after medical or surgical treatment ; and ( iii ) to assess and compare the effect of medical and surgical treatment on nasal symptoms |
12,018 | 27,541,334 | Although these trials may not have completely reported adverse effects , they did not note any significant toxicity attributable to radiation .
Attrition , performance , detection and reporting bias for the outcome of overall survival was low .
There was unclear attrition , performance , detection and reporting bias relating to the outcomes of adverse effects , progression free survival and quality of life .
AUTHORS ' CONCLUSIONS Postoperative conventional daily radiotherapy improves survival for adults with good performance status and HGG as compared to no postoperative radiotherapy .
Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy , particularly for individuals aged 60 and older with glioblastoma .
There is insufficient data regarding hyperfractionation versus conventionally fractionated radiation ( without chemotherapy ) and for accelerated radiation versus conventionally fractionated radiation ( without chemotherapy).There are HGG subsets who have poor prognosis even with treatment ( e.g. glioblastoma histology , older age and poor performance status ) .
No r and omised trial has compared comfort measures or best supportive care with an active intervention using radiotherapy or chemotherapy in these poor prognosis patients | BACKGROUND The incidence of high grade glioma ( HGG ) is approximately 5 per 100,000 person-years in Europe and North America .
OBJECTIVES To assess the effects of postoperative external beam radiation dose escalation in adults with HGG .
Daily conventionally fractionated radiation therapy versus no radiation therapy.2 .
Hypofractionated radiation therapy versus daily conventionally fractionated radiation therapy.3 . | PURPOSE To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high grade glioma , where acceleration is used as a means of delivering a shortened course of radical radiotherapy . PATIENTS AND METHODS Two-hundred and eleven patients with primary high grade glioma were treated at the Royal Marsden NHS Trust between 1987 and 1997 with accelerated radiotherapy ( 55 Gy in 34 fractions twice daily ) , to planning target volume ( PTV ) defined as enhancing tumour and a 3 cm margin . All had histologically confirmed high grade glioma ( 53 anaplastic astrocytoma , 137 glioblastoma multiforme , 4 gliosarcoma , 5 gemistocytic astrocytoma , 12 high grade astrocytoma not otherwise specified ) . The mean Karnofsky performance status ( KPS ) was 90 and median age was 54 years ( range 19 - 77 ) . RESULTS Of 211 patients entered , 201 were able to complete radiotherapy ; 39 patients ( 19 % ) had deterioration in KPS during radiotherapy and this was transient in 11 . Median survival of 211 patients was 10 months with 1 year , 2 year , and 3 year survival probabilities of 38 % , 14 % , and 8 % respectively . Age and extent of excision were independent prognostic factors for survival . Previous comparison to matched cohort receiving 60 Gy in 30 daily fractions did not demonstrate significant survival difference . CONCLUSION Accelerated radiotherapy is a feasible treatment approach for patients with high grade glioma . The survival and functional outcome are comparable to conventional radiotherapy and the treatment is without serious acute toxicity . While acceleration of conventional dose irradiation could be tested in r and omised studies , it is unlikely this approach would result in a clinical ly meaningful survival benefit . Accelerated radiotherapy therefore remains one of the ways of delivering radical irradiation in patients with high grade glioma . However , it adds complexity to what is a palliative treatment regimen and the rationale and advisability should be re-examined , particularly in terms of impact on quality of life , true patient preference , and health economic considerations BACKGROUND It is controversial if distant recurrence of glioblastoma is more common after temozolomide ( TMZ ) concurrent with radiotherapy ( RT ) . Optimal therapy for patients with recurrent disease after RT/TMZ is unclear . Our purpose was to evaluate recurrence patterns in glioblastoma and the effect of treatment at recurrence upon survival . METHODS We performed a retrospective review of 67 patients with newly diagnosed glioblastoma treated with RT/TMZ between 2003 - 2007 . Statistical analyses included Kaplan-Meier method for survival , and multivariate Cox proportional hazards model for the effect of salvage treatment on survival . RESULTS 58 patients ( 86.6 % ) recurred locally ; 9 patients ( 13.4 % ) had a distant non-contiguous focus of new disease . Median survival(MS ) was 17 months ; median time-to-progression(TTP ) 6.8 months . The local and distant groups had comparable prognostic factors . There was no difference in MS(p=0.35 ) or TTP(p=0.95 ) by location of recurrence . At relapse , 26 patients ( 38.8 % ) received continuous , dose-intense TMZ , 24(35.8 % ) other therapy(4.5 % RT ; 20.9 % lomustine+/-procarbazine ; 4.5 % etoposide ; 1.5 % conventional TMZ ; 4.5 % TMZ then lomustine ) , and 17(25.4 % ) were untreated . Dose-intense TMZ was associated with prolonged MS compared to all other patients ( 21.5 months vs. 12.4 months , p=0.019 , HR=3.86 , 95%CI : 1.81 - 8.22 ) and similar to MS with other chemotherapy regimens(18.8 months , p=0.40 , HR=1.30 , 95 % CI : 0.65 - 2.61 ) . CONCLUSION The pattern of recurrence of glioblastoma treated with RT/TMZ was predominantly local . Second-line treatment with continuous dose-intense TMZ may prolong survival in patients with recurrent glioblastoma . Overall survival is similar to other conventional salvage regimens ; however TMZ may be better tolerated . This study is limited by its retrospective nature and potential selection bias . Prospect i ve controlled studies are needed PURPOSE In patients with newly diagnosed glioblastoma multiforme , to determine whether cisplatin plus carmustine ( BCNU ) administered before and concurrently with radiation therapy ( RT ) improves survival compared with BCNU and RT and whether survival using accelerated RT ( ART ) is equivalent to survival using st and ard RT ( SRT ) . PATIENTS AND METHODS After surgery , patients were stratified by age , performance score , extent of surgical resection , and histology ( glioblastoma v gliosarcoma ) and then r and omly assigned to arm A ( BCNU plus SRT ) , arm B ( BCNU plus ART ) , arm C ( cisplatin plus BCNU plus SRT ) , or arm D ( cisplatin plus BCNU plus ART ) . RESULTS Four hundred fifty-one patients were r and omly assigned , and 401 were eligible . Frequent toxicities included myelosuppression , vomiting , sensory neuropathy , and ototoxicity and were worse with cisplatin . There was no difference in toxicity between SRT and ART . Median survival times and 2-year survival rates for patients who received BCNU plus RT ( arms A and B ) compared with cisplatin , BCNU , and RT ( arms C and D ) were 10.1 v 11.5 months , respectively , and 11.5 % v 13.7 % , respectively ( P = .19 ) . Median survival times and 2-year survival rates for patients who received SRT ( arms A and C ) compared with ART ( arms B and D ) were 11.2 v 10.5 months , respectively , and 13.8 % v 11.4 % , respectively ( P = .33 ) . CONCLUSION Cisplatin administered concurrently with BCNU and RT result ed in more toxicity but provided no significant improvement in survival . SRT and ART produced similar toxicity and survival In Brain Tumor Cooperative Group Study 77 - 02 , eleven institutions r and omized 603 adult patients with supratentorial malignant glioma to one of four treatment groups following surgery : conventional radiotherapy ( 6000 cGy in 30 - 35 fractions ) + BCNU , conventional radiotherapy + streptozotocin , hyperfractionated ( twice daily ) radiotherapy ( 6600 cGy in 60 fractions ) + BCNU , and conventional radiotherapy with misonidazole followed by BCNU . Data were analyzed for the total r and omized population and for the 557 patients ( 86 % with glioblastoma multiforme ) who met protocol eligibility specifications ( including confirmed histopathology on central review ) . Median survival was approximately 10 months following r and omization . Overall there was no statistically significant difference in survival among the four groups . Among non-glioblastoma patients , the misonidazole group appeared to have poor survival . Peripheral neuropathy was a dose-limiting toxicity with misonidazole . It is concluded that neither the addition of misonidazole nor hyperfractionated radiotherapy as given in this protocol offered any advantage over conventional radiotherapy plus either BCNU or streptozotocin for treatment of malignant glioma A total of 474 adult patients with malignant glioma ( astrocytoma ) grade 3 or 4 were r and omised into an MRC study ( BR2 ) comparing 45 Gy ( in 20 fractions over 4 weeks ) with 60 Gy ( in 30 fractions over 6 weeks ) of radiotherapy given post-operatively . Using 2:1 r and omisation , 318 patients were allocated the 60 Gy course and 156 the 45 Gy course . Adjuvant chemotherapy was not given . The results show that a 60 Gy course produces a modest lengthening of progression-free and overall survival . They suggest a statistically significant prolongation of median survival from 9 months in the 45 Gy group to 12 months in the 60 Gy group ( hazard ratio = 0.75 , chi 2 = 7.36 , d.f . = 1 , P = 0.007 ) . Over 80 % of patients reported no morbidity from the radiotherapy , and there was no evidence of increased short-term morbidity in the higher dose group . Late morbidity was not assessed . A prognostic index defined in a previous MRC study was vali date d in this new cohort . It identifies a group of patients ( 20 % of the total ) with a 2 year survival rate of 28 % ( 95 % confidence interval 19 % to 38 % ) . It was apparent that the survival advantage to the higher dose was maintained even in the poorest prognostic groups defined by this index A controlled , prospect i ve , r and omized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea ( BCNU ) and /or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma . A total of 303 patients were r and omized into this study , of whom 222 ( 73 % ) were within the Valid Study Group ( VSG ) , having met the protocol criteria of neuropathology , corticosteroid control , and therapeutic approach . Patients were divided into four r and om groups , and received BCNU ( 80 mg/sq m/day on 3 successive days every 6 to 8 weeks ) , and /or radiotherapy ( 5000 to 6000 rads to the whole brain through bilateral opposing ports ) , or best conventional care but no chemotherapy or radiotherapy . Analysis was performed on all patients who received any amount of therapy ( VSG ) and on the Adequately Treated Group ( ATG ) , who had received 5000 or more rads radiotherapy , two or more courses of chemotherapy , and had a minimum survival of 8 or more weeks ( the interval that would have been required to have received either the radiotherapy or chemotherapy ) . Median survival of patients in the VSG was , best conventional care : 14 weeks ( ATG : 17.0 weeks ) ; BCNU : 18.5 weeks ( ATG : 25.0 weeks ) ; radiotherapy : 35 weeks ( ATG : 37.5 weeks ) ; and BCNU plus radiotherapy : 34.5 weeks ( ATG : 40.5 weeks ) . All therapeutic modalities showed some statistical superiority compared to best conventional care . There was no significant difference between the four groups in relation to age distribution , sex , location of tumor , diagnosis , tumor characteristics , signs or symptoms , or the amount of corticosteroid used . An analysis of prognostic factors indicates that the initial performance status ( Karnofsky rating ) , age , the use of only a surgical biopsy , parietal location , the presence of seizures , or the involvement of cranial nerves II , III , IV , and VI are all of significance . Toxicity included acceptable , reversible thrombocytopenia and leukopenia A prospect i ve r and omized study of 108 patients with cerebral malignant gliomas was carried out at the Department of Radiation Oncology of Maria Sklodowska-Curie Memorial Center in Kraków . 44 patients with histologically proven glioblastoma multiforme and 64 patients with anaplastic astrocytoma received postoperative radiotherapy . Patients were r and omized to two treatment arms : Conventionally Fractionated Radiotherapy ( CFR ) and Hypofractionated Radiotherapy ( HF ) . In the CFR group , the whole brain was irradiated to the total dose of 50 Gy in 25 fractions over 5 weeks , then a 10 Gy ‘ boost ’ in 5 fractions in 5 days was delivered to the site of the primary lesion . In the HF group , there were 3 courses of irradiation separated by a one month interval . In each of the two first series the patients received 20 Gy in 5 fractions in 5 days to the whole brain , and in the third course , 10 Gy ‘ boost ’ in 5 days was delivered as in the CFR regimen . The tolerance to treatment has been found to be good in both groups . The 2-year actuarial survival rate for patients with anaplastic astrocytoma was 22 % for CFR and 18 % for HF . Patients with glioblastoma multiforme treated with HF had a better prognosis in comparison to the CFR group with the two-year actuarial survival rates being 23 % and 10 % , respectively . This difference is statistically significant at the 0.05 level Summary Purpose : To assess the effect of cisplatin ( CDDP ) plus concurrent radiation therapy on hearing loss . Methods : 451 patients with glioblastoma multiforme ( GBM ) were r and omly assigned after surgery to : Arm A : Carmustine ( BCNU ) + st and ard radiation therapy ( SRT ) ; Arm B : BCNU + accelerated radiation therapy ( ART : 160 cGy twice daily for 15 days ) ; Arm C : CDDP + BCNU + SRT ; or Arm D : CDDP + BCNU + ART . Patients on arms C and D received audiograms at baseline , and prior to the start of RT , and prior to cycles 3 and 6 . Otologic toxicities were recorded at each visit . Results : 56 % of patients had hearing loss at baseline . 13 % and 50 % of patients experienced worsening ototoxicity after 1 year of treatment in arms A and B vs. C and D , respectively , with 13 % of those on arms C and D experiencing significant ototoxicity ( ≥ grade 3 ) at 6 months . Increasing age was associated with an increased risk of ototoxicity . Conclusions : Increased exposure to CDDP increases the risk of ototoxicity over time . Older patients are more susceptible to hearing loss with CDDP . The low proportion of patients with clinical ly significant ototoxicity suggests that baseline screening is unnecessary in GBM patients BACKGROUND Radiotherapy is the st and ard care in elderly patients with malignant astrocytoma and the role of primary chemotherapy is poorly defined . We did a r and omised trial to compare the efficacy and safety of dose-dense temozolomide alone versus radiotherapy alone in elderly patients with anaplastic astrocytoma or glioblastoma . METHODS Between May 15 , 2005 , and Nov 2 , 2009 , we enrolled patients with confirmed anaplastic astrocytoma or glioblastoma , age older than 65 years , and a Karnofsky performance score of 60 or higher . Patients were r and omly assigned 100 mg/m(2 ) temozolomide , given on days 1 - 7 of 1 week on , 1 week off cycles , or radiotherapy of 60·0 Gy , administered over 6 - 7 weeks in 30 fractions of 1·8 - 2·0 Gy . The primary endpoint was overall survival . We assessed non-inferiority with a 25 % margin , analysed for all patients who received at least one dose of assigned treatment . This trial is registered with Clinical Trials.gov , number NCT01502241 . FINDINGS Of 584 patients screened , we enrolled 412 . 373 patients ( 195 r and omly allocated to the temozolomide group and 178 to the radiotherapy group ) received at least one dose of treatment and were included in efficacy analyses . Median overall survival was 8·6 months ( 95 % CI 7·3 - 10·2 ) in the temozolomide group versus 9·6 months ( 8·2 - 10·8 ) in the radiotherapy group ( hazard ratio [ HR ] 1·09 , 95 % CI 0·84 - 1·42 , p(non-inferiority)=0·033 ) . Median event-free survival ( EFS ) did not differ significantly between the temozolomide and radiotherapy groups ( 3·3 months [ 95 % CI 3·2 - 4·1 ] vs 4·7 [ 4·2 - 5·2 ] ; HR 1·15 , 95 % CI 0·92 - 1·43 , p(non-inferiority)=0·043 ) . Tumour MGMT promoter methylation was seen in 73 ( 35 % ) of 209 patients tested . MGMT promoter methylation was associated with longer overall survival than was unmethylated status ( 11·9 months [ 95 % CI 9·0 to not reached ] vs 8·2 months [ 7·0 - 10·0 ] ; HR 0·62 , 95 % CI 0·42 - 0·91 , p=0·014 ) . EFS was longer in patients with MGMT promoter methylation who received temozolomide than in those who underwent radiotherapy ( 8·4 months [ 95e% CI 5·5 - 11·7 ] vs 4·6 [ 4·2 - 5·0 ] ) , whereas the opposite was true for patients with no methylation of the MGMT promoter ( 3·3 months [ 3·0 - 3·5 ] vs 4·6 months [ 3·7 - 6·3 ] ) . The most frequent grade 3 - 4 intervention-related adverse events were neutropenia ( 16 patients in the temozolomide group vs two in the radiotherapy group ) , lymphocytopenia ( 46 vs one ) , thrombocytopenia ( 14 vs four ) , raised liver-enzyme concentrations ( 30 vs 16 ) , infections ( 35 vs 23 ) , and thromboembolic events ( 24 vs eight ) . INTERPRETATION Temozolomide alone is non-inferior to radiotherapy alone in the treatment of elderly patients with malignant astrocytoma . MGMT promoter methylation seems to be a useful biomarker for outcomes by treatment and could aid decision-making . FUNDING Merck Sharp & Dohme Background The grading of recommendation , assessment , development and evaluation ( GRADE ) approach is widely implemented in health technology assessment and guideline development organisations throughout the world . GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention , but is complex and therefore challenging to apply in a consistent manner . Methods We developed a checklist to guide the research er to extract the data required to make a GRADE assessment . We applied the checklist to 29 meta-analyses of r and omised controlled trials on the effectiveness of health care interventions . Two review ers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome . Results For most ( 70 % ) checklist items , there was good agreement between review ers . The main problems were for items relating to indirectness where considerable judgement is required . Conclusions There was consistent agreement between review ers on most items in the checklist . The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessment s , particularly for inexperienced users or in rapid review s without the re sources to conduct assessment s by two research ers independently Multiple daily fractionated radiation therapy ( MDF ) may be more effective than conventionally fractionated radiation therapy ( CF ) in the treatment of malignant glioma . The hypoxic cell sensitizer misonidazole ( MISO ) could be more effective when employed with small fractions of radiation every 4 hours to take advantage of the long half-life of the drug . To evaluate MDF and MDF in combination with MISO , a r and omized prospect i ve trial was initiated . Between January 1981 , and December 1982 , patients with histologically verified astrocytoma with anaplastic foci or glioblastoma multiforme were r and omized to CF ( 5800 cGy , 30 fractions , 6 weeks ) , MDF ( 6141 cGy , 69 fractions , 4 1/2 weeks , at 89 cGy every 4 hours 3 times daily ) and MDF in combination with MISO ( 1.25 gm/M2 three times weekly for the first 3 weeks ) . In January 1983 , the CF arm was dropped and a high dose MDF arm added ( 7120 cGy , 80 fractions , 5 1/2 weeks , at 89 cGy per fraction every 4 hours 3 times daily ) . CCNU chemotherapy was given at the time of tumor progression . One hundred and twenty-eight patients were evaluated ( 38 CF , 42 MDF , 37 MDF plus MISO , and 11 high dose MDF ) . Median survival was 29 weeks for CF , 45 weeks for MDF and 50 weeks for MDF plus MISO . Survival was significantly improved for patients treated with MDF compared to patients treated with CF ( p less than .002 ) . The addition of MISO to MDF did not result in further improvement in survival . Acute toxicity was acceptable . No clinical ly apparent delayed toxicity was observed PURPOSE Anaplastic oligodendroglioma are chemotherapy-sensitive tumors . We now present the long-term follow-up findings of a r and omized phase III study on the addition of six cycles of procarbazine , lomustine , and vincristine ( PCV ) chemotherapy to radiotherapy ( RT ) . PATIENTS AND METHODS Adult patients with newly diagnosed anaplastic oligodendroglial tumors were r and omly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV . An exploratory analysis of the correlation between 1p/19q status and survival was part of the study . Retrospectively , the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase ( IDH ) gene were determined . The primary end points were overall survival ( OS ) and progression-free survival based on intent-to-treat analysis . RESULTS A total of 368 patients were enrolled . With a median follow-up of 140 months , OS in the RT/PCV arm was significantly longer ( 42.3 v 30.6 months in the RT arm , hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.60 to 0.95 ) . In the 80 patients with a 1p/19q codeletion , OS was increased , with a trend toward more benefit from adjuvant PCV ( OS not reached in the RT/PCV group v 112 months in the RT group ; HR , 0.56 ; 95 % CI , 0.31 to 1.03 ) . IDH mutational status was also of prognostic significance . CONCLUSION The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors . 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non-1p/19q-deleted tumors BACKGROUND There is no community st and ard for the treatment of glioblastoma in patients 70 years of age or older . We conducted a r and omized trial that compared radiotherapy and supportive care with supportive care alone in such patients . METHODS Patients 70 years of age or older with a newly diagnosed anaplastic astrocytoma or glioblastoma and a Karnofsky performance score of 70 or higher were r and omly assigned to receive supportive care only or supportive care plus radiotherapy ( focal radiation in daily fractions of 1.8 Gy given 5 days per week , for a total dose of 50 Gy ) . The primary end point was overall survival ; secondary end points were progression-free survival , tolerance of radiotherapy , health-related quality of life , and cognition . RESULTS We r and omly assigned 85 patients from 10 centers to receive either radiotherapy and supportive care or supportive care alone . The trial was discontinued at the first interim analysis , which showed that with a preset boundary of efficacy , radiotherapy and supportive care were superior to supportive care alone . A final analysis was carried out for the 81 patients with glioblastoma ( median age , 73 years ; range , 70 to 85 ) . At a median follow-up of 21 weeks , the median survival for the 39 patients who received radiotherapy plus supportive care was 29.1 weeks , as compared with 16.9 weeks for the 42 patients who received supportive care alone . The hazard ratio for death in the radiotherapy group was 0.47 ( 95 % confidence interval , 0.29 to 0.76 ; P=0.002 ) . There were no severe adverse events related to radiotherapy . The results of quality -of-life and cognitive evaluations over time did not differ significantly between the treatment groups . CONCLUSIONS Radiotherapy results in a modest improvement in survival , without reducing the quality of life or cognition , in elderly patients with glioblastoma . ( Clinical Trials.gov number , NCT00430911 [ Clinical Trials.gov ] . ) PURPOSE Older age and poor performance status at presentation are unfavorable prognostic factors for patients with glioblastoma multiforme . Some studies suggest a shorter , palliative course of radiotherapy may confer similar benefits as compared to a radical course in such patients . We report a prospect i ve , single arm trial , describing the use of a short-course of radiation in patients with glioblastoma and poor prognostic features . METHODS AND MATERIAL S Twenty-nine patients with pathologically confirmed glioblastoma and age > or = 65 years or with initial KPS < or = 50 were treated with a short-course of whole brain radiotherapy ( 30 Gy/10 fractions/2 weeks ) . Computer tomography tumor volume , dexamethasone requirements , Spitzer quality of life index , and Karnofsky performance status were measured pre and 1 month postradiation . Overall survival for the study patients was compared with that of radically treated and supportive care only historical controls . RESULTS Indices of tumor response were stable or improved in 60 % of patients evaluable 1 month postradiotherapy . Median survival for all study patients was 6 months . Median survivals in similar groups of radically treated and supportive care only patients were 10 and 1 month(s ) , respectively . A survival advantage for the radical vs. short-course treatment was observed for the subset of patients with a pretreatment KPS > 50 . CONCLUSION Elderly patients with a low pretreatment KPS ( < or = 50 ) may be treated adequately with a short , palliative course of radiotherapy . Elderly patients with a higher pretreatment KPS ( > 50 ) , however , may benefit from a higher dose radiotherapy regimen PURPOSE To prospect ively compare st and ard radiation therapy ( RT ) with an abbreviated course of RT in older patients with glioblastoma multiforme ( GBM ) . PATIENTS AND METHODS One hundred patients with GBM , age 60 years or older , were r and omly assigned after surgery to receive either st and ard RT ( 60 Gy in 30 fractions over 6 weeks ) or a shorter course of RT ( 40 Gy in 15 fractions over 3 weeks ) . The primary end point was overall survival . The secondary end points were proportionate survival at 6 months , health-related quality of life ( HRQoL ) , and corticosteroid requirement . HRQoL was assessed using the Karnofsky performance status ( KPS ) and Functional Assessment of Cancer Therapy-Brain ( FACT-Br ) . RESULTS All patients had died at the time of analysis . Overall survival times measured from r and omization were similar at 5.1 months for st and ard RT versus 5.6 months for the shorter course ( log-rank test , P = .57 ) . The survival probabilities at 6 months were also similar at 44.7 % for st and ard RT versus 41.7 % for the shorter course ( lower-bound 95 % CI , -13.7 ) . KPS scores varied markedly but were not significantly different between the two groups ( Wilcoxon test , P = .63 ) . Low completion rates of the FACT-Br ( 45 % ) precluded meaningful comparisons between the two groups . Of patients completing RT as planned , 49 % of patients ( st and ard RT ) versus 23 % required an increase in posttreatment corticosteroid dosage ( chi(2 ) test , P = .02 ) . CONCLUSION There is no difference in survival between patients receiving st and ard RT or short-course RT . In view of the similar KPS scores , decreased increment in corticosteroid requirement , and reduced treatment time , the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM PURPOSE To report the results of a prospect i ve Phase III trial for patients with newly diagnosed glioblastoma multiforme ( GBM ) , treated with either accelerated hyperfractionated irradiation with or without difluromethylornithine ( DFMO ) or st and ard fractionated irradiation with or without DFMO . METHODS AND MATERIAL S Adult patients with newly diagnosed GBM were registered and r and omized following surgery to one of 4 treatment arms : Arm A , accelerated hyperfractionation alone using 2 fractions a day of 1.6 Gy to a total dose of 70.4 Gy in 44 fractions ; Arm B , accelerated hyperfractionation as above plus DFMO 1.8 gm/m2 by mouth every 8 h beginning one week before radiation until the last fraction was given ; Arm C , single-fraction irradiation of 1.8 Gy/day to 59.4 Gy ; Arm D , single-fraction irradiation as in Arm C plus DFMO given as in Arm B. Patients were followed for progression-free survival ( PFS ) and overall survival ( OS ) , as well as for toxicity . Eligibility required histologically proven GBM , age > or = 18 , Karnofsky performance status ( KPS ) > or = 60 , and no prior chemotherapy or radiotherapy . Adjuvant chemotherapy was not used in this protocol . RESULTS A total of 231 eligible patients were enrolled . There were 95 men and 136 women with a median age of 57 years , and median KPS of 90 . Extent of resection was total in 23 , subtotal in 152 , and biopsy only in 56 patients . The 4 arms were balanced with respect to age , KPS , and extent of resection . Times to event measurements are from date of diagnosis . Median OS and PFS were 40 and 19 weeks for Arm A ; 42 and 22 weeks for Arm B ; 37 and 16 weeks for Arm C ; and 44 and 19 weeks for Arm D ( p = 0.48 for survival ; p = 0.32 for PFS ) . Comparison of the 2 arms treated with DFMO to the 2 arms without DFMO revealed no difference in OS ( 37 weeks vs. 42 weeks , p = 0.12 ) or PFS and thus no benefit to the use of DFMO . Comparison of the 2 st and ard fractionation arms to the 2 accelerated hyperfractionation arms also result ed in no difference in OS ( 42 weeks vs. 41 weeks , p = 0.75 ) or PFS , showing no benefit to accelerated hyperfractionated irradiation . CONCLUSION In this prospect i ve Phase III study , no survival or PFS benefit was seen with accelerated hyperfractionated irradiation to 70.4 Gy , nor was any benefit seen with DFMO as a radiosensitizer . St and ard fractionated irradiation to 59.4 Gy remains the treatment of choice for newly diagnosed patients with glioblastoma multiforme A prospect i ve r and omized trial of 157 patients with malignant astrocytoma ( Grade III or IV ) was carried out at a single institution . The minimization technique ensured balanced distribution of prognostic factors between the treatment groups . All received oral lomustine ( CCNU , 80 mg/m2 ) six weekly and hydroxyurea ( HU , 3.5 gm/m2 over 5 days ) three weekly , for one year or until recurrence , with doses adjusted for myelosuppression . Patients were r and omized to daily ( 5000 rad in 25 fractions ( fr ) in 5 weeks ) or Q3h ( every 3 hours ) Cobalt 60 irradiation ( 3600–4000 rad in 36–40 fr of 100 rad each , given 4 fr per day at 3‐hour intervals over two weeks ) Steroid therapy ( up to 16 mg day dexamethasone ) was permitted . Complications were moderate and equivalent in the two groups . No significant survival or toxicity differences were seen between the two groups . Age , initial performance status , and extent of surgical resection were found to be significant ( P < 0.01 ) prognostic factors for survival . Median survival of the whole group was 48 weeks with a minimum follow‐up of one year . There was no advantage to large radiation fields . The hyperfractionation and daily regimes had similar efficacy and toxicity . Hyperfractionation with chemotherapy offers a useful alternative approach in the management of this disease BACKGROUND In 2004 , a r and omised phase III trial by the European Organisation for Research and Treatment of Cancer ( EORTC ) and National Cancer Institute of Canada Clinical Trials Group ( NCIC ) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy . We report the final results with a median follow-up of more than 5 years . METHODS Adult patients with newly diagnosed glioblastoma were r and omly assigned to receive either st and ard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide . The methylation status of the methyl-guanine methyl transferase gene , MGMT , was determined retrospectively from the tumour tissue of 206 patients . The primary endpoint was overall survival . Analyses were by intention to treat . This trial is registered with Clinical trials.gov , number NCT00006353 . FINDINGS Between Aug 17 , 2000 , and March 22 , 2002 , 573 patients were assigned to treatment . 278 ( 97 % ) of 286 patients in the radiotherapy alone group and 254 ( 89 % ) of 287 in the combined-treatment group died during 5 years of follow-up . Overall survival was 27.2 % ( 95 % CI 22.2 - 32.5 ) at 2 years , 16.0 % ( 12.0 - 20.6 ) at 3 years , 12.1 % ( 8.5 - 16.4 ) at 4 years , and 9.8 % ( 6.4 - 14.0 ) at 5 years with temozolomide , versus 10.9 % ( 7.6 - 14.8 ) , 4.4 % ( 2.4 - 7.2 ) , 3.0 % ( 1.4 - 5.7 ) , and 1.9 % ( 0.6 - 4.4 ) with radiotherapy alone ( hazard ratio 0.6 , 95 % CI 0.5 - 0.7 ; p<0.0001 ) . A benefit of combined therapy was recorded in all clinical prognostic subgroups , including patients aged 60 - 70 years . Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy . INTERPRETATION Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up . A few patients in favourable prognostic categories survive longer than 5 years . MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide . FUNDING EORTC , NCIC , Nélia and Amadeo Barletta Foundation , Schering-Plough The authors undertook a controlled , prospect i ve , r and omized study of 171 patients with supratentorial astrocytoma Grade s 3 and /or 4 ( classified according to Kernohan ) . All patients were given chemotherapy consisting of procarbazine , vincristine , and lomustine ( CCNU ) ( PVC ) . Half of the patients received whole‐brain irradiation ( RT ) to a dose of 5800 cGy in the tumor‐bearing hemisphere and 5000 cGy in the contralateral hemisphere . After diagnosis of progressive tumor growth , patients received individual treatment . The endpoint of the study was time to progression , but cases were followed until the patients died . Median time to progression ( MTP ) for the whole r and omized population was 21 weeks . Median survival time ( MST ) was 53 weeks ; 18 % of patients survived for 2 years or longer . Survival analysis showed that patients less than 50 years of age treated with PVC plus RT had significantly longer MTP ( 81 weeks ) and MST ( 124 weeks ) than all other patients . For patients less than 50 years of age treated with PVC alone , MTP was 21 weeks and MST was 66 weeks . For patients more than 50 years of age treated with PVC plus RT , MTP was 23 weeks and MST was 51 weeks ; in the PVC group , MTP was 17 weeks and MST was 39 weeks . Age , Karnofsky index , areas of Grade 2 , and absence of extensive necrosis in the tumor were significant prognostic factors in the univariate analyses . Patients less than 50 years of age treated with PVC plus RT had significantly longer survival ( P = 0.037 ) when correcting for these factors in a multi‐variate analysis Preliminary results of superfractionation in the treatment of glioblastoma led to a r and omized trial consisting of 76 patients . All patients received whole brain irradiation followed by a 1000 cGy boost to the primary site . Thirty-four patients received st and ard daily treatment to 4000 cGy , whereas 42 patients received superfractionated radiation , treating three times a day to a total dose of 4760 cGy . No significant difference was found between the 5-year survival of the superfractionated group and the st and ard treatment group . Early reactions were greater for superfractionation whereas late effects were less A material of 108 patients with glioblastoma is presented . The series was r and omized in two groups : cases only operated upon and cases with postoperative irradiation in addition . Patients dead within 2 months after operation were excluded in estimating the real value of the postoperative irradiation . The irradiated cases had a 6-month survival rate of 64 per cent and a one-year survival rate of 19 per cent ; the non-irradiated cases a 6-month survival rate of 28 per cent and a one-year survival rate of 0 per cent PURPOSE The optimal radiotherapy regimen for elderly and /or frail patients with newly diagnosed glioblastoma remains to be established . This study compared two radiotherapy regimens on the outcome of these patients . PATIENTS AND METHODS Between 2010 and 2013 , 98 patients ( frail = age ≥ 50 years and Karnofsky performance status [ KPS ] of 50 % to 70 % ; elderly and frail = age ≥ 65 years and KPS of 50 % to 70 % ; elderly = age ≥ 65 years and KPS of 80 % to 100 % ) were prospect ively r and omly assigned to two arms in a 1:1 ratio , stratified by age ( < and ≥ 65 years old ) , KPS , and extent of surgical resection . Arm 1 received short-course radiotherapy ( 25 Gy in five daily fractions over 1 week ) , and arm 2 received commonly used radiotherapy ( 40 Gy in 15 daily fractions over 3 weeks ) . RESULTS The short-course radiotherapy was noninferior to commonly used radiotherapy . The median overall survival time was 7.9 months ( 95 % CI , 6.3 to 9.6 months ) in arm 1 and 6.4 months ( 95 % CI , 5.1 to 7.6 months ) in arm 2 ( P = .988 ) . Median progression-free survival time was 4.2 months ( 95 % CI , 2.5 to 5.9 ) in arm 1 and 4.2 months ( 95 % CI , 2.6 to 5.7 ) in arm B ( P = .716 ) . With a median follow-up time of 6.3 months , the quality of life between both arms at 4 weeks after treatment and 8 weeks after treatment was not different . CONCLUSION There were no differences in overall survival time , progression-free survival time , and quality of life between patients receiving the two radiotherapy regimens . In view of the reduced treatment time , the short 1-week radiotherapy regimen may be recommended as a treatment option for elderly and /or frail patients with newly diagnosed glioblastoma Background Trials on the effect of systemic chemotherapy on survival and recurrence in adults with high- grade glioma have had inconclusive results . We undertook a systematic review and meta- analysis to assess the effects of such treatment on survival and recurrence . Objectives To compare radiotherapy plus chemotherapy with radiotherapy alone in completely resected adults with high- grade glioma . To investigate whether or not pre-defined patient subgroups benefit more or less from chemotherapy . Search methods MEDLINE and CancerLit search es were supplemented with information from trial registers and by h and search ing relevant meeting proceedings and by discussion with relevant trialists and organisations . These search es were carried out in June 1997 , June 1999 , December 2000 and August 2003 . Selection criteria Trials comparing radiotherapy versus radiotherapy + chemotherapy were eligible for inclusion provided that they r and omized adult patients using a method which precluded prior knowledge of treatment assignment . Data collection and analysis A quantitative meta- analysis using up date d information from individual patients from all available r and omized trials was carried out . Data from all patients r and omized in all eligible trials were sought directly from those responsible . Up date d information on survival and date of follow-up were obtained , as were details of treatment allocation , date of r and omization , age , sex , histological cell type , stage and performance status . To avoid potential bias , information was requested for all r and omized patients including those who had been excluded from the investigators ' original analyses . All analyses were done on an intention to treat basis on the endpoint of survival . For trials using cisplatin-based regimens , subgroup analyses by age , sex , histological cell type , tumour stage and performance status were also done . Main results Data from 12 r and omized trials and 3004 patients were included . The results show a significant prolongation of survival associated with chemotherapy , with a hazard ratio of 0.85 ( 95 % CI 0.78 - 0.91 , p=0.00004 ) or 15 % relative decrease in the risk of death . This is equivalent to an absolute increase in one year survival rate of 6 % ( 95 % confidence interval 3 % to 9 % ) from 40 % to 46 % and a two-month increase in median survival time ( 95 % confidence interval one month to three months ) . There was no evidence that the effect of chemotherapy was different in any group of patients defined by age , sex , histology , performance status or extent of resection . Authors ' conclusions This small but clear improvement in survival from chemotherapy encourages further study of drug treatment of these Various attempts have been made to improve the effectiveness of radiation in the treatment of cerebral malignant astrocytomas . A trend favoring multiple daily fractionated ( MDF ) radiation therapy over conventional single daily fractionated ( CF ) radiation therapy was identified in our previous study . In order to assess the effect of MDF with and without misonidazole , a province‐wide prospect i ve r and omized trial was initiated in January 1981 . By March 1984 , 124 patients with histologically verified grade III and IV astrocytomas were r and omized to CF ( 5800 cGy/6 weeks/30 fractions ) MDF ( 6141 cGy/4.5 weeks/69 fractions at 89 cGy every 3–4 hours , three times a day ) and MDF in combination with misonidazole ( 1.25 g/m2 three times weekly for the first 3 weeks ) . Thirty‐eight patients were r and omized to CF , 43 patients to MDF , and 43 patients to MDF and misonidazole . At the preliminary assessment in July 1984 , the median survival time was 27 weeks for the CF group , 39 weeks for the MDF group and 49 weeks for MDF and misonidazole group . The 1‐year actuarial survival rate from surgery was 20 % for CF group , 41 % for MDF group , and 45 % for MDF and misonidazole group . There is a statistically significant difference ( P < 0.001 ) between the CF and MDF group . However , the addition of misonidazole does not significantly alter survival BACKGROUND Most patients with glioblastoma are older than 60 years , but treatment guidelines are based on trials in patients aged only up to 70 years . We did a r and omised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma . METHODS Patients with newly diagnosed glioblastoma were recruited from Austria , Denmark , France , Norway , Sweden , Switzerl and , and Turkey . They were assigned by a computer-generated r and omisation schedule , stratified by centre , to receive temozolomide ( 200 mg/m(2 ) on days 1 - 5 of every 28 days for up to six cycles ) , hypofractionated radiotherapy ( 34·0 Gy administered in 3·4 Gy fractions over 2 weeks ) , or st and ard radiotherapy ( 60·0 Gy administered in 2·0 Gy fractions over 6 weeks ) . Patients and study staff were aware of treatment assignment . The primary endpoint was overall survival . Analyses were done by intention to treat . This trial is registered , number IS RCT N81470623 . FINDINGS 342 patients were enrolled , of whom 291 were r and omised across three treatment groups ( temozolomide n=93 , hypofractionated radiotherapy n=98 , st and ard radiotherapy n=100 ) and 51 of whom were r and omised across only two groups ( temozolomide n=26 , hypofractionated radiotherapy n=25 ) . In the three-group r and omisation , in comparison with st and ard radiotherapy , median overall survival was significantly longer with temozolomide ( 8·3 months [ 95 % CI 7·1 - 9·5 ; n=93 ] vs 6·0 months [ 95 % CI 5·1 - 6·8 ; n=100 ] , hazard ratio [ HR ] 0·70 ; 95 % CI 0·52 - 0·93 , p=0·01 ) , but not with hypofractionated radiotherapy ( 7·5 months [ 6·5 - 8·6 ; n=98 ] , HR 0·85 [ 0·64 - 1·12 ] , p=0·24 ) . For all patients who received temozolomide or hypofractionated radiotherapy ( n=242 ) overall survival was similar ( 8·4 months [ 7·3 - 9·4 ; n=119 ] vs 7·4 months [ 6·4 - 8·4 ; n=123 ] ; HR 0·82 , 95 % CI 0·63 - 1·06 ; p=0·12 ) . For age older than 70 years , survival was better with temozolomide and with hypofractionated radiotherapy than with st and ard radiotherapy ( HR for temozolomide vs st and ard radiotherapy 0·35 [ 0·21 - 0·56 ] , p<0·0001 ; HR for hypofractionated vs st and ard radiotherapy 0·59 [ 95 % CI 0·37 - 0·93 ] , p=0·02 ) . Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation ( 9·7 months [ 95 % CI 8·0 - 11·4 ] vs 6·8 months [ 5·9 - 7·7 ] ; HR 0·56 [ 95 % CI 0·34 - 0·93 ] , p=0·02 ) , but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy ( HR 0·97 [ 95 % CI 0·69 - 1·38 ] ; p=0·81 ) . As expected , the most common grade 3 - 4 adverse events in the temozolomide group were neutropenia ( n=12 ) and thrombocytopenia ( n=18 ) . Grade 3 - 5 infections in all r and omisation groups were reported in 18 patients . Two patients had fatal infections ( one in the temozolomide group and one in the st and ard radiotherapy group ) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed . INTERPRETATION St and ard radiotherapy was associated with poor outcomes , especially in patients older than 70 years . Both temozolomide and hypofractionated radiotherapy should be considered as st and ard treatment options in elderly patients with glioblastoma . MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide . FUNDING Merck , Lion 's Cancer Research Foundation , University of Umeå , and the Swedish Cancer Society Abstract In a r and omized trial , 134 patients suffering from Glioblastoma Multiforme were r and omly assigned to three radiation treatment schedules wherein patients were treated at S hr or 24 hr intervals over a period of 1 week or 3 weeks , initially receiving 3000 rad TD ¶ ¶TD , Tumor dose . and subsequently 4000 rad TD . There were no significant differences in immediate or delayed complications amongst the various groups . Survival was not significantly different in the various study groups , and was not influenced by the patient 's age and sex , the extent of surgery or the tumor grade To report health-related quality of life ( HRQOL ) in glioblastoma ( GBM ) patients treated on a phase II trial of hypofractionated intensity-modulated radiotherapy ( hypo-IMRT ) with temozolomide ( TMZ ) . GBM patients received postoperative hypo-IMRT to 60 Gy in 10 fractions with TMZ . HRQOL was assessed using the EORTC quality of life question naire core-30 and the EORTC brain cancer module , performed at baseline , RT completion , 1 mo post-RT , and every 3 mos thereafter . Changes from baseline were calculated for each specific HRQOL scale . A ≥ 10 point change in any HRQOL scale from the mean baseline score was significant . 24 patients were treated . Compliance with HRQOL assessment s at baseline , RT completion , and 1 , 3 , 6 , 9 , and 12 mos post-RT was 100 , 96 , 92 , 79 , 70 , 68 and 53 % , respectively . Up to 12 mos post-RT , no significant changes were seen in global health status , physical functioning , role functioning , emotional functioning , fatigue , nausea , vision , headache or seizure . Significant improvement was seen in insomnia , future uncertainty , motor dysfunction and drowsiness . Significant worsening was observed in cognitive functioning , social functioning , appetite loss and communication deficit . 60 Gy hypo-IMRT in 6-Gy fractions with TMZ does not appear to negatively impact overall HRQOL A r and omized prospect i ve clinical trial was conducted to compare conventional high dose radiotherapy with hypofractionated , short course radiotherapy in poor prognosis patients with high grade glioma . The primary endpoint was overall survival BACKGROUND Glioblastoma , the most common primary brain tumor in adults , is usually rapidly fatal . The current st and ard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible , followed by adjuvant radiotherapy . In this trial we compared radiotherapy alone with radiotherapy plus temozolomide , given concomitantly with and after radiotherapy , in terms of efficacy and safety . METHODS Patients with newly diagnosed , histologically confirmed glioblastoma were r and omly assigned to receive radiotherapy alone ( fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks , for a total of 60 Gy ) or radiotherapy plus continuous daily temozolomide ( 75 mg per square meter of body-surface area per day , 7 days per week from the first to the last day of radiotherapy ) , followed by six cycles of adjuvant temozolomide ( 150 to 200 mg per square meter for 5 days during each 28-day cycle ) . The primary end point was overall survival . RESULTS A total of 573 patients from 85 centers underwent r and omization . The median age was 56 years , and 84 percent of patients had undergone debulking surgery . At a median follow-up of 28 months , the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone . The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 ( 95 percent confidence interval , 0.52 to 0.75 ; P<0.001 by the log-rank test ) . The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone . Concomitant treatment with radiotherapy plus temozolomide result ed in grade 3 or 4 hematologic toxic effects in 7 percent of patients . CONCLUSIONS The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma result ed in a clinical ly meaningful and statistically significant survival benefit with minimal additional toxicity In a controlled , prospect i ve , r and omized investigation , started in 1974 , 118 patients with supratentorial astrocytoma Grade III – IV were divided into three groups . Groups 1 and 2 received 45 Gy postoperatively to the whole supratentorial brain . Bleomycin in 15‐mg doses and a total dose of 180 mg or placebo was given intravenously three times a week , one hour prior to radiotherapy , during weeks 1,2,4 and 5 . Group 3 received conventional care but no radiotherapy or chemotherapy . Median survival rates of patients were 10.8 months in Groups 1 and 2 , and 5.2 months in Group 3 , a statistically significant difference . With regard to performance , the patients in Group 3 deteriorated faster than patients in Groups 1 and 2 . Bleomycin had no positive or negative influence on survival PURPOSE Anaplastic oligodendrogliomas , pure ( AO ) and mixed ( anaplastic oligoastrocytoma [ AOA ] ) , are chemosensitive , especially if codeleted for 1p/19q , but whether patients live longer after chemoradiotherapy is unknown . PATIENTS AND METHODS Eligible patients with AO/AOA were r and omly assigned to procarbazine , lomustine , and vincristine ( PCV ) plus radiotherapy ( RT ) versus RT alone . The primary end point was overall survival ( OS ) . RESULTS Two hundred ninety-one eligible patients were r and omly assigned : 148 to PCV plus RT and 143 to RT . For the entire cohort , there was no difference in median survival by treatment ( 4.6 years for PCV plus RT v 4.7 years for RT ; hazard ratio [ HR ] = 0.79 ; 95 % CI , 0.60 to 1.04 ; P = .1 ) . Patients with codeleted tumors lived longer than those with noncodeleted tumors ( PCV plus RT : 14.7 v 2.6 years , HR = 0.36 , 95 % CI , 0.23 to 0.57 , P < .001 ; RT : 7.3 v 2.7 years , HR = 0.40 , 95 % CI , 0.27 to 0.60 , P < .001 ) , and the median survival of those with codeleted tumors treated with PCV plus RT was twice that of patients receiving RT ( 14.7 v 7.3 years ; HR = 0.59 ; 95 % CI , 0.37 to 0.95 ; P = .03 ) . For those with noncodeleted tumors , there was no difference in median survival by treatment arm ( 2.6 v 2.7 years ; HR = 0.85 ; 95 % CI , 0.58 to 1.23 ; P = .39 ) . In Cox models that included codeletion status , the adjusted OS for all patients was prolonged by PCV plus RT ( HR = 0.67 ; 95 % CI , 0.50 to 0.91 ; P = .01 ) . CONCLUSION For the subset of patients with 1p/19q codeleted AO/AOA , PCV plus RT may be an especially effective treatment , although this observation was derived from an unplanned analysis Thirty-three patients with malignant glioma were r and omly divided into two groups after extensive tumor resection . Those in group A received , every five to eight weeks , a course of chemotherapy consisting of intravenously administered carmustine , 80 mg/sq m/day for three days , and vincristine sulfate , 1.4mg/sq m on days 1 and 8 . Patients in group B were treated identically and received radiation therapy ( RT ) as well , 4,500 rads whole brain plus 1,500 rads to the side of the tumor . The median survival time of group A was 30 weeks , while that of group B was 44.5 weeks , but the overall survival curves were not significantly different . The median survival times exceeded the 17 weeks reported elsewhere in comparable patients not receiving postoperative therapy . Estimates of the quality of survival suggested ( 1 ) the two groups were not comparable following r and omization , possibly influencing the results ; and ( 2 ) postoperative radiation and chemotherapy do not increase morbidity and offer a longer period than other treatments during which patients ' conditions remain stable or improve Within three weeks of definitive surgical intervention , 467 patients with histologically proved malignant glioma were r and omized to receive one of four treatment regimens : semustine ( MeCCNU ) , radiotherapy , carmustine ( BCNU ) plus radiotherapy , or semustine plus radiotherapy . We analyzed the data for the total r and omized population and for the 358 patients in whom the initial protocol specifications were met ( the valid study group ) . Observed toxicity included acceptable skin reactions secondary to radiotherapy and reversible leukopenia and thrombocytopenia due to chemotherapy . Radiotherapy used alone or in combination with a nitrosourea significantly improved survival in comparison with semustine alone . The group receiving carmustine plus radiotherapy had the best survival , but the difference in survival between the groups receiving carmustine plus radiotherapy and semustine plus radiotherapy was not statistically significant . The combination of carmustine plus radiotherapy produced a modest benefit in long-term ( 18-month ) survival as compared with radiotherapy alone , although the difference between survival curves was not significiant at the 0.05 level . This study suggests that it is best to use radiotherapy in the post-surgical treatment of malignant glioma and to continue the search for an effective chemotherapeutic regimen to use in addition to radiotherapy Background Glioblastoma is associated with a poor prognosis in the elderly . Survival has been shown to increase among patients 70 years of age or younger when temozolomide chemotherapy is added to st and ard radiotherapy ( 60 Gy over a period of 6 weeks ) . In elderly patients , more convenient shorter courses of radiotherapy are commonly used , but the benefit of adding temozolomide to a shorter course of radiotherapy is unknown . Methods We conducted a trial involving patients 65 years of age or older with newly diagnosed glioblastoma . Patients were r and omly assigned to receive either radiotherapy alone ( 40 Gy in 15 fractions ) or radiotherapy with concomitant and adjuvant temozolomide . Results A total of 562 patients underwent r and omization , 281 to each group . The median age was 73 years ( range , 65 to 90 ) . The median overall survival was longer with radiotherapy plus temozolomide than with radiotherapy alone ( 9.3 months vs. 7.6 months ; hazard ratio for death , 0.67 ; 95 % confidence interval [ CI ] , 0.56 to 0.80 ; P<0.001 ) , as was the median progression‐free survival ( 5.3 months vs. 3.9 months ; hazard ratio for disease progression or death , 0.50 ; 95 % CI , 0.41 to 0.60 ; P<0.001 ) . Among 165 patients with methylated O6‐methylguanine – DNA methyltransferase ( MGMT ) status , the median overall survival was 13.5 months with radiotherapy plus temozolomide and 7.7 months with radiotherapy alone ( hazard ratio for death , 0.53 ; 95 % CI , 0.38 to 0.73 ; P<0.001 ) . Among 189 patients with unmethylated MGMT status , the median overall survival was 10.0 months with radiotherapy plus temozolomide and 7.9 months with radiotherapy alone ( hazard ratio for death , 0.75 ; 95 % CI , 0.56 to 1.01 ; P=0.055 ; P=0.08 for interaction ) . Quality of life was similar in the two trial groups . Conclusions In elderly patients with glioblastoma , the addition of temozolomide to short‐course radiotherapy result ed in longer survival than short‐course radiotherapy alone . ( Funded by the Canadian Cancer Society Research Institute and others ; Clinical Trials.gov number , NCT00482677 . PURPOSE To perform a subset analysis of survival outcomes in elderly patients with glioblastoma from a r and omized phase 3 trial comparing 2 short-course radiation therapy ( RT ) regimens in elderly and /or frail patients . METHODS AND MATERIAL S The original trial population included elderly and /or frail patients with a diagnosis of glioblastoma . Patients joined the phase 3 , r and omized , multicenter , prospect i ve , noninferiority trial ; were assigned to 1 of 2 groups in a 1:1 ratio , either short-course RT ( 25 Gy in 5 fractions , arm 1 ) or commonly used RT ( 40 Gy in 15 fractions , arm 2 ) ; and were stratified by age ( < 65 years and ≥65 years ) , Karnofsky Performance Status ( KPS ) , and extent of surgery . For the subset analysis in this study , only patients aged ≥65 years were evaluated ( elderly and frail patients were defined as patients aged ≥65 years with KPS of 50%-70 % ; elderly and non-frail patients were defined as patients aged ≥65 years with KPS of 80%-100 % ) ; 61 of the 98 initial patients comprised the patient population , with 26 patients r and omized to arm 1 and 35 to arm 2 . RESULTS In this unplanned analysis , the short-course RT results were not statistically significantly different from the results of commonly used RT in elderly patients . The median overall survival time was 6.8 months ( 95 % confidence interval [ CI ] , 4.5 - 9.1 months ) in arm 1 and 6.2 months ( 95 % CI , 4.7 - 7.7 months ) in arm 2 ( P=.936 ) . The median progression-free survival time was 4.3 months ( 95 % CI , 2.6 - 5.9 months ) in arm 1 and 3.2 months ( 95 % CI , 0.1 - 6.3 months ) in arm 2 ( P=.706 ) . CONCLUSIONS A short-course RT regimen of 25 Gy in 5 fractions is an acceptable treatment option for patients aged ≥65 years , mainly those with a poor performance status or contraindication to chemotherapy , which would be indicated in cases of methylated O6 methylguanine-DNA-methyltransferase promoter tumors |
12,019 | 28,621,166 | CONCLUSIONS ASP-based CT significantly improved ORR and CR in patients with newly diagnosed both early-stage and advanced-stage ENKTL | OBJECTIVES The aim of this review was to compare the efficacy of asparaginase (ASP)-containing vs ASP-absent regimens in the first-line treatment of ENKTL patients . | We design ed a new treatment protocol incorporating concurrent administration of L-asparaginase ( to reduce the probability of systemic progression during concurrent chemoradiotherapy ( CCRT ) ) plus high-dose methotrexate to consolidation chemotherapy to intensify the regimen for treating localized extranodal NK/T cell lymphoma , nasal type ( ENKTL ) . CCRT comprised radiation ( 36–44 Gy ) with weekly cisplatin ( 30 mg/m2 ) and tri-weekly L-asparaginase ( 4 000 IU ) . Chemotherapy — MIDLE ( methotrexate 3 g/m2 on day 1 , etoposide 100 mg/m2 and Ifosfamide 1 000 mg/m2 on days 2–3 , dexamethasone 40 mg on days 1–4 , and L-asparaginase 6 000 IU/m2 on days 4 , 6 , 8 , 10)—was repeated every 28 days for two cycles . One of the 28 patients developed distant lesions after CCRT . The final complete response rate was 82.1 % . Four patients dropped out during or after their first MIDLE cycle due to toxicities ( recurrent G3 hyperbilirubinemia [ n = 1 ] , G3 - 5 increased creatinine [ n = 2 ] , and G5 infection [ n = 1 ] ) . With a median follow-up of 46 months ( 95 % CI : 39–47 months ) , the estimated 3-year progression-free survival rate and overall survival rate were 74.1 % and 81.5 % , respectively . This MIDLE protocol may be effective for localized ENKTL . However , concurrent administration of L-asparaginase during CCRT does not seem to provide additional benefits Extranodal natural killer/T‐cell lymphoma ( ENKTL ) , nasal‐type , is a distinct entity of lymphoid tissue . ENKTL is sensitive to radiotherapy ( RT ) , but the prognosis is poorer than for other types of early lymphoma . The treatment schedule is controversial The optimal treatment strategy for elderly patients with natural killer/T-cell lymphoma ( NKTCL ) remains to be established . A total of 63 elderly patients with newly diagnosed NKTCL were retrospectively review ed . Among the patients with stage I – II disease , 58.3 % received radiotherapy ( RT ) ± chemotherapy , and 41.7 % received chemotherapy alone . Compared with chemotherapy alone , RT ± chemotherapy elicited a significantly higher overall response rate ( ORR ) ( 100 vs. 57.1 % , P < 0.001 ) and substantially prolonged 5-year overall survival ( OS ) ( 55.3 vs. 18.0 % , P < 0.001 ) in patients with stage I – II disease . Compared with other chemotherapeutic regimens , pegaspargase plus gemcitabine and oxaliplatin (PGEMOX)/L-asparaginase plus gemcitabine and oxaliplatin ( GELOX ) was associated with a significantly higher ORR ( 92.9 vs. 51.6 % , P = 0.009 ) and a significantly improved 5-year OS ( 78.6 vs. 23.9 % , P = 0.010 ) in patients with stage I – II disease . Nine patients with stage I – II disease who were treated with PGEMOX/GELOX followed by RT had an encouraging outcome ( 5-year OS 100 % , 5-year progression-free survival ( PFS ) 85.7 % ) , which was superior to that of patients receiving other regimens followed by RT . In conclusion , RT played an important role for elderly patients with early-stage NKTCL , and the PGEMOX/GELOX regimen was superior to other regimens . The combination of them may be a promising treatment option The aim of this study was to investigate the impact of the induction treatment with SMILE ( dexamethasone , methotrexate , ifosfamide , l-asparaginase , and etoposide ) chemotherapy and consolidation with upfront autologous stem cell transplantation ( ASCT ) on clinical outcomes of patients with stage IV extranodal natural killer/T-cell lymphoma ( ENKTL ) . We analyzed the treatment response to SMILE and toxicity , and explored the feasibility of upfront ASCT in 27 patients with stage IV ENKTL out of patients who were enrolled into our prospect i ve cohort studies . The median age of patients was 45 years ( range : 17–65 years ) , and all patients had disseminated disease . The overall response rate to SMILE induction treatment was 59 % ( 16/27 ) including nine complete responses . However , five patients died due to grade IV febrile neutropenia during SMILE and six patients did not respond to SMILE . Eleven patients could undergo ASCT , and there was no transplantation-related mortality . The survival outcome of patients underwent ASCT was better than patients who could not ( P < 0.05 ) . However , four patients relapsed even after ASCT , thus , the median overall survival was 10.6 months , and the median progression-free survival was 5.1 months . Pretreatment Epstein – Barr virus ( EBV ) DNA titer was only independent prognostic factor for overall survival . In conclusion , our results suggest SMILE followed by ASCT might be an effective treatment strategy for stage IV ENKTL . However , considering frequent occurrences of disease relapse and treatment-related mortality , additional efforts are required to improve treatment outcomes of stage IV ENKTL patients PURPOSE To explore a more effective treatment for newly diagnosed stage IV , relapsed , or refractory extranodal natural killer/T-cell lymphoma , nasal type ( ENKL ) , we conducted a phase II study of the steroid ( dexamethasone ) , methotrexate , ifosfamide , L-asparaginase , and etoposide ( SMILE ) regimen . PATIENTS AND METHODS Patients with newly diagnosed stage IV , relapsed , or refractory disease and a performance status of 0 to 2 were eligible . Two cycles of SMILE chemotherapy were administered as the protocol treatment . The primary end point was the overall response rate ( ORR ) after the protocol treatment . RESULTS A total of 38 eligible patients were enrolled . The median age was 47 years ( range , 16 to 67 years ) , and the male : female ratio was 21:17 . The disease status was newly diagnosed stage IV in 20 patients , first relapse in 14 patients , and primary refractory in four patients . The eligibility was revised to include lymphocyte counts of 500/μL or more because the first two patients died from infections . No treatment-related deaths were observed after the revision . The ORR and complete response rate after two cycles of SMILE chemotherapy were 79 % ( 90 % CI , 65 % to 89 % ) and 45 % , respectively . In the 28 patients who completed the protocol treatment , 19 underwent hematopoietic stem-cell transplantation . The 1-year overall survival rate was 55 % ( 95 % CI , 38 % to 69 % ) . Grade 4 neutropenia was observed in 92 % of the patients . The most common grade 3 or 4 nonhematologic complication was infection ( 61 % ) . CONCLUSION SMILE chemotherapy is an effective treatment for newly diagnosed stage IV , relapsed or refractory ENKL . Myelosuppression and infection during the treatment should be carefully managed Circulating Epstein-Barr virus ( EBV ) DNA is a biomarker of EBV-associated malignancies . Its prognostic value in early stage NK/T-cell lymphoma ( NKTCL ) in the era of asparaginase was investigated . 68 patients were treated with a median of 4 cycles of asparaginase-based chemotherapy followed by a median of 54.6Gy ( range 50–60Gy ) radiation . The amount of EBV-DNA was prospect ively measured in both pretreatment and post-treatment plasma sample s by real-time quantitative PCR . At the end of treatment , complete response ( CR ) rate was 79.4 % , and overall response rate ( ORR ) was 88.2 % . Patients with negative pretreatment EBV-DNA had a higher CR rate ( 96.0 % vs. 69.8 % , p = 0.023 ) . The 3-year progression-free survival ( PFS ) rate and overall survival ( OS ) rate was 71 % and 83 % , respectively . In multivariate survival analysis , post-treatment EBV-DNA positivity and treatment response ( non-CR ) were prognostic factors for both worse PFS and OS ( p < 0.05 ) . Local tumor invasion was also a prognostic factor for worse OS ( p = 0.010 ) . In patients with CR , post-treatment EBV-DNA positivity correlated with inferior PFS and OS ( both p < 0.0001 ) . In patients with positive pretreatment EBV-DNA , negative post-treatment EBV-DNA correlated with better PFS and OS ( both p < 0.0001 ) . These findings indicate that post-treatment EBV-DNA positivity can predict early relapse and poor prognosis for patients with early stage NKTCL in the era of asparaginase , and may be used as an indicator of minimal residual disease We conducted a phase II trial of concurrent chemoradiotherapy ( CCRT ) followed by 2 cycles of l-asparaginase-containing chemotherapy for patients who were newly diagnosed with stages IE and IIE nasal extranodal NK/T cell lymphoma ( ENKTL ) . CCRT consisted of 40–44 Gy of radiotherapy with weekly administration of 30 mg/m2 of cisplatin for 4 weeks . Two cycles of VIDL ( etoposide ( 100 mg/m2 ) , ifosfamide ( 1,200 mg/m2 ) , and dexamethasone ( 40 mg ) from days 1 to 3 , and l-asparaginase ( 4,000 IU/m2 ) every other day from days 8 to 20 ) were administered sequentially . CCRT yielded a 90 % overall response rate without significant side effects in 30 patients , including 20 patients with complete response ( CR ) ; however , two patients showed distant disease progression . After CCRT , VIDL chemotherapy showed an 87 % final CR rate ( 26/30 ) . Although grade III or IV hematologic toxicity was frequent during VIDL chemotherapy , no treatment-related mortality was observed , and l-asparaginase-associated toxicity was manageable . With a median follow-up of 44 months , 11 patients showed local ( n = 4 ) and distant ( n = 7 ) relapse or progression . The estimated 5-year progression-free and overall survival rates were 73 and 60 % , respectively . In conclusion , CCRT followed by l-asparaginase-containing chemotherapy is a feasible treatment for newly diagnosed stages IE/IIE nasal ENKTL Purpose To explore the efficacy and safety of L-asparaginase in newly-diagnosed extranodal nature killer (NK)/T –cell lymphoma ( ENKTL ) , we conducted a prospect i ve phase II study of L-asparaginase , cyclophosphamide , vincristine , doxorubicin and dexamethasone ( CHOP-L ) regimen in combination with radiotherapy . Patients and methods Patients with newly diagnosed ENKTL and an ECOG performance status of 0 to 2 were eligible for enrollment . Treatment included 6–8 cycles of CHOP-L ( cyclophosphamide , 750 mg/m2 day 1 ; vincristine , 1.4 mg/m2 day 1 ( maximal dose 2 mg ) , doxorubicin 50 mg/m2 day 1 ; dexamethasone 10 mg days 1–8 ; L-asparaginase 6000 u/m2 days 2–8 ) . Radiotherapy was scheduled after 4–6 cycles of CHOP-L regimen , depending on stage and primary anatomic site . The primary endpoint was complete response ( CR ) rate . Results A total of 38 eligible patients were enrolled . The median age was 40.5 years ( range , 15 to 71 years ) . Their clinical characteristics were male to female ratio , 24:14 ; Ann Arbor stage I , 20 ; II , 11 ; III , 3 ; IV , 4 . CR and overall response rates were 81.6 % ( 95 % CI , 69.3 % to 93.9 % ) and 84.2 % , respectively . With a median follow-up of 25 months , the 2-year overall survival , progression-free survival and disease-free survival rates were 80.1 % ( 95%CI , 73.3 % to 86.9 % ) , 81 % ( 95%CI , 74.5 % to 87.5 % ) and 93.6 % ( 95%CI , 89.3 % to 97.9 % ) , respectively . The major adverse events were myelosuppression , liver dysfunction , and digestive tract toxicities . Grade 3 to 4 leukopenia and neutropenia were 76.3 % and 84.2 % , respectively . No treatment-related death was observed . Conclusion CHOP-L chemotherapy in combination with radiotherapy is a safe and highly effective treatment for newly diagnosed ENKTL The purpose of this study was to investigate the role of early radiotherapy in patients with localized-stage nasal-type natural killer (NK)/T cell lymphoma treated with l-asparaginase-containing chemotherapy . Sixty-four patients with stage I-II nasal-type NK/T cell lymphoma were enrolled in this study . All patients received an l-asparaginase-containing regimen . Thirty-four patients received late radiotherapy ( RT ) , which was defined as receiving 6 cycles of prior chemotherapy ( CT ) followed by RT , and 30 patients received early RT , which was defined as receiving no more than 3 cycles of CT followed by early RT . With a median follow-up of 35 months ( range , 12–49 months ) , 19 patients ( 29.7 % ) died from lymphoma-related causes , and 22 patients ( 34.4 % ) developed local and /or distant relapse . The 3-year overall survival ( OS ) and progression-free survival ( PFS ) were 84.2 and 74.3 % for early RT and 57.6 and 55.9 % for late RT , respectively , and these differences were significant ( OS , p = 0.027 ; PFS , p = 0.034 ) . After 2 cycles of initial CT , 58 patients achieved treatment response ( complete response and partial response ) . For the 58 patients , there were still significant differences for 3-year OS and PFS when early RT was compared with late RT ( 3-year OS 94.4 vs. 58 % , P = 0.005 ; 3-year PFS 82.9 vs. 56.3 % , P = 0.01 ) . Early RT has an essential role in improving survival for localized-stage nasal-type NK/T cell lymphoma ( TCL ) patients even when used in combination with l-asparaginase-containing CT . Prospect i ve , r and omized studies should to be performed to confirm these results BACKGROUND AND PURPOSE This study was conducted to analyze the influence of radiotherapy doses and chemotherapy doses and clinical parameters on in-field disease control in order to assess the optimal radiation doses for treatment of mature T/NK-cell lymphomas according to the newly proposed WHO classification . PATIENTS AND METHODS Subjects consisted of 62 patients with mature T/NK-cell lymphomas treated with radiotherapy at four Japanese institutions between 1983 and 2002 . We reevaluated all histopathological specimens of non-Hodgkin 's lymphomas ( NHL ) , using the WHO classification . Radiation therapy was usually delivered to the involved field . The majority of patients also received adriamycin-based chemotherapy such as CHOP , modified CHOP , or more intensive chemotherapy . RESULTS There were no significant differences in radiosensitivity among subtypes of mature T/NK-cell lymphomas , at least between extranodal NK/T-cell lymphomas , nasal type and peripheral T-cell lymphomas , unspecified . There was a radiation dose-response in non-bulky mature T/NK-cell lymphomas , indicating that radiation doses of more than 52 Gy may be required to obtain in-field control . However , it was difficult to obtain local control of bulky T-cell lymphomas , even with high doses of irradiation . CONCLUSIONS Mature T/NK-cell lymphomas were more radioresistant than B-cell lymphomas such as diffuse large B-cell lymphomas ( DLBCL ) . The chemotherapy including adriamycin did not improve the in-field control of mature T/NK-cell lymphomas . These results were obtained by using non-r and omized data and the significance of these results is limited by bias in data . However , our results suggest that the treatment strategy which is usually used for DLBCL , that is , a combined modality of CHOP and around 40 Gy of radiotherapy , may not be sufficiently effective for mature T/NK-cell lymphomas To evaluate the outcome of CHOP chemotherapy and radiotherapy in Stage IE and IIE nasal natural killer (NK)/T-cell lymphoma , 53 patients with stage IE and IIE nasal NK/T-cell lymphoma were studied . By the Ann Arbor Lymphoma Staging Classification , 41 patients ( 77 % ) had Stage IE disease and 12 patients ( 23 % ) had Stage IIE disease . All patients were treated curatively using chemotherapy , followed by radiotherapy . Chemotherapy consisted of up to six cycles of the st and ard CHOP based regimen . The median radiation dose to the tumor bed was 45 Gy for all patients . The median follow-up for all 39 surviving patients was 30.2 months ( range , 6 – 104 months ) . Twenty-six patients had complete response after chemotherapy , and all patients who completed first line chemotherapy achieved complete response after radiotherapy . The 2-year overall survival and progression-free survival rates were 75.6 % and 61.8 % , respectively . Multivariate analysis revealed that perforation as a presenting symptom , elevated pretreatment serum lactate dehydrogenase level , and ECOG performance status ≥2 were significant independent prognostic factors for this group of patients . Combined chemotherapy followed by involved field radiation produced suboptimal outcome for patients with early stage nasal NK/T-cell lymphoma . Further investigations , preferably prospect i ve clinical trials , for more efficacious treatment strategies are needed to improve the treatment outcome of this malignancy BACKGROUND We performed a phase II study to evaluate the efficacy of bortezomib in combination with CHOP ( cyclophosphamide , doxorubicin , vincristine and prednisone ) as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas ( PTCLs ) based on our phase I study results . METHODS Patients received bortezomib on days 1 and 8 at a dose of 1.6 mg/m(2 ) in addition to CHOP every 3 weeks for a total of six cycles . RESULTS Forty-six patients were enrolled : PTCL , not otherwise specified ( PTCL-NOS , n=16 ) , extranodal NK/T-cell lymphoma , nasal type ( ENKTL , n=10 ) , angioimmunoblastic T-cell lymphoma ( AITL , n=8 ) , ALK-negative anaplastic large-cell lymphoma ( ALCL , n=6 ) , cutaneous T-cell lymphoma ( CTCL , n=5 ) and hepatosplenic T-cell lymphoma ( n=1 ) . Thirty patients achieved complete response ( CR , 65 % ) and the overall response rate was 76 % ( 35/46 ) . Although the CR rate of ENKTL was only 30 % ( 3/10 ) , three subtypes of PTCLs ( PTCL-NOS , AITL and ALCL ) showed 87 % of overall response rate ( ORR ) ( 26/30 ) and 73 % of CR rate ( 22/30 ) . However , the 3-year overall survival and progression-free survival were 47 % and 35 % , respectively due to frequent relapse after remission . Grade 3/4 leucopenia was the most frequent toxicity whereas neurotoxicity was tolerable : grade 1 or 2 of peripheral neuropathy . CONCLUSIONS The combined treatment of bortezomib and CHOP is an effective and feasible regimen for advanced-stage PTCLs other than ENKTL , with acceptable toxicity . However , future studies exploring new drug combinations are warranted to overcome relapse after remission BACKGROUND Combination chemotherapy consisting of ifosfamide , methotrexate , etoposide , and prednisolone ( IMEP ) was active as first-line and second-line treatment for extranodal natural killer/T-cell lymphoma ( NTCL ) . METHODS Forty-four patients with chemo-naïve stage I/II NTCL were enrolled in a prospect i ve , multicenter , phase II study and received six cycles of IMEP ( ifosfamide 1.5 g/m(2 ) on days 1 - 3 ; methotrextate 30 mg/m(2 ) on days 3 and 10 ; etoposide 100 mg/m(2 ) on days 1 - 3 ; and prednisolone 60 mg/m(2 ) per day on days 1 - 5 ) followed by involved field radiotherapy ( IFRT ) . RESULTS Overall response rates were 73 % ( complete remission [ CR ] in 11 of 41 evaluable patients [ 27 % ] ) after IMEP chemotherapy and 78 % ( CR 18 of 27 evaluable patients [ 67 % ] ) after IMEP followed by IFRT . Neutropenia and thrombocytopenia were documented in 33 patients ( 75 % ) and 7 patients ( 16 % ) , respectively . Only 8 patients ( 18 % ) experienced febrile neutropenia . Three-year progression-free survival ( PFS ) and overall survival ( OS ) were 66 % and 56 % , respectively . High Ki-67 ( ≥70 % ) and Ann Arbor stage II independently reduced PFS ( p = .004 ) and OS ( p = .001 ) , respectively . CONCLUSION Due to the high rate of progression during IMEP chemotherapy , IFRT needs to be introduced earlier . Moreover , active chemotherapy including an l-asparaginase-based regimen should be use to reduce systemic treatment failure in stage I/II NTCL Nasal NK/T cell is a rare form of usually localized non-Hodgkin 's lymphoma ( NHL ) which generally carries a poor prognosis when treated with conventional NHL chemotherapy protocol s. We review ed 20 consecutive localized stage I/II nasal NK/T cell lymphomas treated at our institution over a 29 year period . Median age was 44 ( range 23–71 ) . Front-line therapy was generally radiotherapy alone ( 35–70 Gy ) before 1980 and combination chemotherapy after 1980 . Six patients were treated with first-line radiotherapy and they achieved complete remission ( CR ) . Two subsequently received combination chemotherapy . Five of those patients remained in complete remission , after 97 + to 277 + months . Twelve patients were treated with first-line chemotherapy including CHOP or CHOP-like regimen in seven cases , and COP in five cases . Only three of them achieved CR , five had partial response and four had progressive disease . Five of the seven patients treated with CHOP did not achieve complete remission . The nine patients who failed to achieve CR with chemotherapy subsequently received salvage radiotherapy but only two of them obtained CR . Finally , two patients were treated with alternated chemotherapy and radiotherapy and achieved CR , which persisted after 14 + and 26 + months . Median survival was not reached in patients who received front-line radiotherapy , and was 35 months in patients who received front-line chemotherapy . These findings confirm that chemotherapy gives a low complete remission rate in localized nasal NK/T cell lymphoma . By contrast , first-line radiotherapy seems to give favorable results , whereas its results are poorer when administered after resistance to chemotherapy . Whether the use of chemotherapy after radiotherapy , or alternated chemotherapy – radiotherapy regimens give better clinical results than radiotherapy alone will have to be evaluated prospect ively in this type of NHL Stage III/IV extranodal natural killer/T cell lymphoma ( ENKL ) has a poor response and poor survival . Given the sensitivity of ENKL to radiotherapy and the fact that there is no consensus on st and ard chemotherapy , we conducted a clinical trial of LVDP regimen , combining LVDP chemotherapy ( containing etoposide , dexamethasone , l-asparaginase , and cisplatin ) , followed by radiotherapy as a consolidation therapy regimen , for newly diagnosed patients with stage III/IV ENKL to evaluate the efficacy and safety of this regimen . The primary endpoints were overall response rate ( ORR ) and survival [ overall survival ( OS ) and progression-free survival ( PFS ) ] at 1 or 2 years , while the secondary endpoints were toxicity and adverse effects . In total , 18 patients were enrolled in this trial from July 2010 to September 2013 . The mean completed cycles of chemotherapy was 4.04 ( range 1–8 cycles ) , and the ORR was 50 % . During a mean follow-up of 21.8 months ( range 2–51 months ) , the 1-year OS and PFS rates were 72.2 and 50.0 % , respectively , the 2-year OS and PFS rates were 33.3 and 22.2 % , respectively , and the median OS and PFS were 23.0 and 10.5 months , respectively . Severe adverse effects during therapy included six cases of grade 3/4 bone marrow suppression and one case of grade 3 transaminase increase . Sex , eastern cancer oncology group , performance status , Korean Prognostic Index , International Prognostic index , and bone marrow infiltration may influence the prognosis of advanced-stage ENKL Purpose : Optimal treatment strategies for advanced natural killer/T (NK/T)-cell lymphoma have not been fully defined . We compared the safety and efficacy of DDGP and SMILE regimens for advanced NK/T-cell lymphoma in a r and omized controlled , multicenter , and open-label clinical trial . Experimental Design : Patients were newly diagnosed in stages III – IV and had performance scores in 0 to 2 . Six cycles of DDGP ( dexamethasone , cisplatin , gemcitabline , and pegaspargase ) or SMILE ( dexamethasone , methotrexate , ifosfamide , L-asparaginase , and etoposide ) chemotherapy were r and omly assigned to them . The primary end point was progression-free survival ( PFS ) . Secondary end points included response rate and overall survival ( OS ) . The trial is ongoing and is registered with Clinical Trials.gov ( No. NCT01501149 ) . Results : Of 42 patients enrolled , 21 were treated with DDGP therapy , and 21 patients were treated with SMILE therapy . The 1-year PFS and 2-year OS rates were better in the DDGP group than that in the SMILE group ( 86 % vs. 38 % for 1-year PFS , P = 0.006 ; 74 % vs. 45 % for 2-year OS , P = 0.027 ) . Complete remission ( CR ) rate and overall response rate ( ORR ) of the DDGP group were higher than that in the SMILE group ( 71 % vs. 29 % , P = 0.005 for CR rate ; 95 % vs. 67 % , P = 0.018 for ORR ) . The SMILE group showed more serious leucopenia ( P = 0.030 ) and severe allergic reaction ( P = 0.015 ) than the DDGP group . In addition , two cases in the SMILE group underwent grade 4 mucosal reaction . Conclusions : DDGP chemotherapy result ed in significant improvement in PFS , OS , and better tolerability compared with SMILE chemotherapy for newly diagnosed advanced NK/T-cell lymphoma patients . Clin Cancer Res ; 22(21 ) ; 5223–8 . © 2016 AACR PURPOSE On the basis of the benefits of frontline radiation in early-stage , extranodal , natural killer (NK)/T-cell lymphoma ( ENKTL ) , we conducted a phase II trial of concurrent chemoradiotherapy ( CCRT ) followed by three cycles of etoposide , ifosfamide , cisplatin , and dexamethasone ( VIPD ) . PATIENTS AND METHODS Thirty patients with newly diagnosed , stages IE to IIE , nasal ENKTL received CCRT ( ie radiation 40 to 52.8 Gy and cisplatin 30 mg/m(2 ) weekly ) . Three cycles of VIPD ( etoposide 100 mg/m(2 ) days 1 through 3 , ifosfamide 1,200 mg/m(2 ) days 1 through 3 , cisplatin 33 mg/m(2 ) days 1 through 3 , and dexamethasone 40 mg days 1 through 4 ) were scheduled after CCRT . RESULTS All patients completed CCRT , which result ed in 100 % response that included 22 complete responses ( CRs ) and eight partial responses ( PRs ) . The CR rate after CCRT was 73.3 % ( ie , 22 of 30 responses ; 95 % CI , 57.46 to 89.13 ) . Twenty-six of 30 patients completed the planned three cycles of VIPD , whereas four patients did not because they withdrew ( n = 2 ) or because they had an infection ( n = 2 ) . The overall response rate and the CR rate were 83.3 % ( ie ; 25 of 30 responses ; 95 % CI , 65.28 to 94.36 ) and 80.0 % ( ie , 24 of 30 responses ; 95 % CI , 65.69 to 94.31 ) , respectively . Only one patient experienced grade 3 toxicity during CCRT ( nausea ) , whereas 12 of 29 patients experienced grade 4 neutropenia . The estimated 3-year , progression-free and overall survival rates were 85.19 % ( 95 % CI , 72.48 to 97.90 ) and 86.28 % ( 95 % CI , 73.97 to 98.59 ) , respectively . CONCLUSION Patients with newly diagnosed , stages IE to IIE , nasal ENKTL are best treated with frontline CCRT The nasal type of extranodal natural killer/T‐cell lymphoma is a rare aggressive lymphoma with poor prognosis . To discover a successful treatment , we investigated the efficacy and safety of chemotherapy with methotrexate , etoposide , dexamethasone , and polyethylene glycol‐asparaginase ( MESA ) . Three cycles of MESA were administered to 46 patients with new or relapsed/refractory natural killer/T‐cell lymphoma . Complete response after 3 treatment cycles was 43.5 % , the overall response rate was 87 % , and 2‐year overall survival was 83.4 % . Complete response was significantly better for newly diagnosed patients than for patients with relapsed/refractory disease . Patients with newly diagnosed disease had a significantly better overall response rate after 1 , but not after 2 or 3 treatment cycles . Overall survival and progression‐free survival did not differ over 2 years . Grade 1/2 toxicities were frequent , but MESA was associated with fewer grade 3/4 events or treatment‐related deaths . These results will require confirmation in larger prospect i ve trials The prognosis of advanced stage natural killer/T-cell lymphoma ( NKTCL ) remains relatively disappointing , and the optimal treatment strategy for this disease has yet to be discovered . Seventy-three patients with Ann Arbor stage III or IV NKTCL were retrospectively review ed . The treatment efficacies of asparaginase-containing and asparaginase-absent chemotherapy regimens were compared , and the effects of postchemotherapeutic radiotherapy were explored . The overall response rate ( ORR ) of the asparaginase-containing regimens was marginally higher than that of the asparaginase-absent regimens ( 56.5 vs 32.6 % , P = 0.057 ) . However , no significant difference was observed in 2-year overall survival ( OS ) ( 38.3 vs 22.7 % , P = 0.418 ) or 2-year progression-free survival ( PFS ) ( 25.4 vs 14.9 % , P = 0.134 ) between the asparaginase-containing and asparaginase-absent groups . Postchemotherapeutic radiotherapy was associated with a significantly prolonged survival ( 2-year OS 57.5 vs 14.5 % , P < 0.001 ; 2-year PFS 46.3 vs 8.4 % , P < 0.001 ) and was an independent predictor of both OS and PFS . Radiotherapy significantly improved the prognosis among the patients who exhibited complete or partial remission after initial chemotherapy ( 2-year OS 81.5 vs 40.2 % , P = 0.002 ; 2-year PFS 65.6 vs 23.4 % , P = 0.008 ) but failed to provide a significant survival advantage among those who experienced stable or progressive disease after initial chemotherapy . In conclusion , the use of asparaginase did not significantly improve survival for the treatment of patients with stage III/IV NKTCL . Postchemotherapeutic radiotherapy provided additional prognostic benefits to patients who responded well to the initial chemotherapy , which requires further validation in future prospect i ve studies using larger sample sizes PURPOSE To explore a more effective treatment for localized nasal natural killer (NK)/T-cell lymphoma , we conducted a phase I/II study of concurrent chemoradiotherapy . PATIENTS AND METHODS Treatments comprised concurrent radiotherapy ( 50 Gy ) and 3 courses of dexamethasone , etoposide , ifosfamide , and carboplatin ( DeVIC ) . Patients with a newly diagnosed stage IE or contiguous IIE disease with cervical node involvement and a performance status ( PS ) of 0 to 2 were eligible for enrollment . The primary end point of the phase II portion was a 2-year overall survival in patients treated with the recommended dose . RESULTS Of the 33 patients enrolled , 10 patients were enrolled in the phase I portion and a two thirds dose of DeVIC was established as the recommended dose . Twenty-seven patients ( range , 21 to 68 ; median , 56 years ) treated with the recommended dose showed the following clinical features : male : female , 17:10 ; stage IE , 18 ; stage IIE , 9 ; B symptoms present , 10 ; elevated serum lactate dehydrogenase , 5 ; and PS 2 , 2 . With a median follow-up of 32 months , the 2-year overall survival was 78 % ( 95 % CI , 57 % to 89 % ) . This compared favorably with the historical control of radiotherapy alone ( 45 % ) . Of the 26 patients assessable for a response , 20 ( 77 % ) achieved a complete response , with one partial response . The overall response rate was 81 % . The most common grade 3 nonhematologic toxicity was mucositis related to radiation ( 30 % ) . No treatment-related deaths were observed . CONCLUSION Concurrent chemoradiotherapy using multidrug resistance-nonrelated agents and etoposide is a safe and effective treatment for localized nasal NK/T-cell lymphoma and warrants further investigation |
12,020 | 32,202,316 | Compared with supportive care only , NMA evidence suggested that all treatments apart from BEV_RT prolonged survival to some extent .
When treatments were ranked according to their effects on OS , CRT ranked higher than TMZ , RT and supportive care only , with the latter ranked last .
BEV plus RT was the only treatment for which there was no clear benefit in OS over supportive care only .
Findings from the trial suggest that the intervention probably improves overall survival in this selected patient population .
For elderly people with glioblastoma who are self-caring , evidence suggests that CRT prolongs survival compared with RT and may prolong overall survival compared with TMZ alone .
For those undergoing RT or TMZ therapy , there is probably little difference in QoL overall .
Systemic anti-cancer treatments TMZ and BEV carry a higher risk of severe haematological and thromboembolic events and CRT is probably associated with a higher risk of these events . | BACKGROUND A glioblastoma is a fatal type of brain tumour for which the st and ard of care is maximum surgical resection followed by chemoradiotherapy , when possible .
Age is an important consideration in this disease , as older age is associated with shorter survival and a higher risk of treatment-related toxicity .
OBJECTIVES To determine the most effective and best-tolerated approaches for the treatment of elderly people with newly diagnosed glioblastoma .
To summarise current evidence for the incremental re source use , utilities , costs and cost-effectiveness associated with these approaches . | BACKGROUND 5-Aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas-a finding that is under investigation for intraoperative identification and resection of these tumours . We aim ed to assess the effect of fluorescence-guided resection with 5-aminolevulinic acid on surgical radicality , progression-free survival , overall survival , and morbidity . METHODS 322 patients aged 23 - 73 years with suspected malignant glioma amenable to complete resection of contrast-enhancing tumour were r and omly assigned to 20 mg/kg bodyweight 5-aminolevulinic acid for fluorescence-guided resection ( n=161 ) or to conventional microsurgery with white light ( n=161 ) . The primary endpoints were the number of patients without contrast-enhancing tumour on early MRI ( ie , that obtained within 72 h after surgery ) and 6-month progression-free survival as assessed by MRI . Secondary endpoints were volume of residual tumour on postoperative MRI , overall survival , neurological deficit , and toxic effects . We report the results of an interim analysis with 270 patients in the full- analysis population ( 139 assigned 5-aminolevulinic acid , 131 assigned white light ) , which excluded patients with ineligible histological and radiological findings as assessed by central review ers who were masked as to treatment allocation ; the interim analysis result ed in termination of the study as defined by the protocol . Primary and secondary endpoints were analysed by intention to treat in the full- analysis population . The study is registered at http://www . clinical trials.gov as NCT00241670 . FINDINGS Median follow-up was 35.4 months ( 95 % CI 1.0 - 56.7 ) . Contrast-enhancing tumour was resected completely in 90 ( 65 % ) of 139 patients assigned 5-aminolevulinic acid compared with 47 ( 36 % ) of 131 assigned white light ( difference between groups 29 % [ 95 % CI 17 - 40 ] , p<0.0001 ) . Patients allocated 5-aminolevulinic acid had higher 6-month progression free survival than did those allocated white light ( 41.0 % [ 32.8 - 49.2 ] vs 21.1 % [ 14.0 - 28.2 ] ; difference between groups 19.9 % [ 9.1 - 30.7 ] , p=0.0003 , Z test ) . Groups did not differ in the frequency of severe adverse events or adverse events in any organ system class reported within 7 days after surgery . INTERPRETATION Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour , leading to improved progression-free survival in patients with malignant glioma Efforts to improve local control and survival by increasing the dose of once‐daily radiation therapy beyond 70 Gray ( Gy ) for patients with malignant gliomas have as yet been unsuccessful . Hyperfractionated radiation therapy ( HF ) should allow for delivery of a higher total dose without increasing normal tissue late effects , whereas accelerated hyperfractionated radiation therapy ( AHF ) may minimize tumor re population by shortening overall treatment time . The Radiation Therapy Oncology Group ( RTOG ) conducted a r and omized Phase I/II study of escalating doses of HF and AHF with carmustine ( bis‐chloroethyl nitrosourea [ BCNU ] ) for adults with supratentorial glioblastoma multiforme ( GBM ) or anaplastic astrocytoma ( AA ) . Primary study endpoints were overall survival and acute and chronic treatment‐related toxicity PURPOSE Alternative dosing schedules of temozolomide may improve survival in patients with newly diagnosed glioblastoma ( GBM ) by increasing the therapeutic index , overcoming common mechanisms of temozolomide resistance , or both . The goal of this r and omized phase II study was to evaluate two different temozolomide regimens in the adjuvant treatment of newly diagnosed GBM . PATIENTS AND METHODS Adult patients with newly diagnosed GBM were r and omly assigned to receive st and ard radiotherapy with concurrent daily temozolomide followed by six adjuvant cycles of either dose-dense ( 150 mg/m(2 ) days 1 to 7 and 15 to 21 ) or metronomic ( 50 mg/m(2 ) continuous daily ) temozolomide . Maintenance doses of 13-cis-retinoic acid were then administered until tumor progression . The primary end point was overall survival ( OS ) at 1 year . Tumor tissue was assayed to determine O(6)-methylguanine-DNA methyltransferase ( MGMT ) promoter methylation status . RESULTS Eighty-five eligible patients were enrolled ; 42 were r and omly assigned to dose-dense and 43 to metronomic temozolomide . The 1-year survival rate was 80 % for the dose-dense arm and 69 % for the metronomic arm ; median OS was 17.1 months ( 95 % CI , 14.0 to 28.1 months ) and 15.1 months ( 95 % CI , 12.3 to 18.9 months ) , respectively . The most common toxicities were myelosuppression ( leukopenia , neutropenia , and thrombocytopenia ) and elevated liver enzymes . Pseudoprogression was observed in 37 % of assessable patients and may have had an impact on estimates of progression-free survival ( 6.6 months in the dose-dense arm and 5.0 months in the metronomic arm ) . CONCLUSION Both dose-dense and metronomic temozolomide regimens were well tolerated with modest toxicity . The dose-dense regimen appears promising , with 1-year survival of 80 % One hundred and three patients with hemispheric supratentorial glioblastoma multiforme were studied . All patients were operated on and a histologic diagnosis of glioblastoma multiforme was made . Patients were r and omly placed in one of three treatment schedules within 3 weeks of surgery : Group A : combined radiation therapy and drug ( CCNU ) therapy ( 26 cases ) ; Group B : CCNU given orally every 6–8 weeks ( 27 cases ) ; Group C : st and ard radiation therapy alone ( 50 cases ) . All patients were periodically controlled by clinical and instrumental ( EEG , scan , EMG , CAT ) evaluations ; laboratory data examinations were also frequently performed . The treatment results have been evaluated according to length of survival , social quality of life , and positive or negative response to chemotherapy . In our opinion the clinical findings are interesting but the statistical results are somewhat negative , especially when the groups of patients are not homogeneous A prospect i ve r and omized controlled multicenter phase III trial was conducted to evaluate the effects of neoadjuvant chemotherapy with nimustine (ACNU)-cisplatin ( CDDP ) when used in conjunction with radiotherapy plus adjuvant temozolomide in patients with newly diagnosed glioblastoma . The study population was r and omly assigned into one treatment and one control group . Both groups received radiotherapy followed by six cycles of adjuvant oral temozolomide ( 150–200 mg/m2 ) for 5 days every 28 days after surgery . Prior to radiotherapy , the treatment group also received two cycles , 6 weeks apart , of neoadjuvant chemotherapy with ACNU ( 40 mg/m2/day ) and CDDP ( 40 mg/m2/day ) infused continuously for 72 h. The primary end-point was median survival time . The study has closed after interim analysis with a total of 82 patients ( 48.8 % of target number ) due to unacceptable high frequency of toxicity profiles in spite of the promising actuarial survival outcome . Median survival time was 28.4 months [ 90 % confidence interval ( CI ) , 21.1 months to not available ] in the treatment group and 18.9 months ( 90 % CI , 17.1–27.4 months ) in the control group ( P = 0.2 ) . The 2-year survival rate and progression-free survival time were 50.9 % and 6.6 months ( 90 % CI , 3.5–9.5 months ) in the treatment group and 27.8 % and 5.1 months ( 90 % CI , 3.8–8.8 months ) in the control group . Grade 3 or 4 toxicity was documented in 26 ( 68.4 % ) patients in the treatment group , including three neutropenic fever and one death from sepsis , while grade 3 or 4 toxicity occurred in 6 patients ( 15.8 % ) in the control group . The high frequency of serious hematological toxicity with ACNU-CDDP neoadjuvant chemotherapy followed by radiotherapy and adjuvant temozolomide limits its usage as primary treatment for glioblastoma . Future studies should aim to identify a sub population at reduced risk for ACNU-CDDP toxicity so that the potential of this protocol can be realized BACKGROUND In this r and omized phase III study , the effectiveness as well as the side-effects of intraarterial [ i.a . ] ( 17 patients ) versus intravenous [ i.v . ] ( 16 patients ) ACNU [ Nimustine ] administration in newly diagnosed glioblastoma , were compared . PATIENTS AND METHODS All patients undenwent extensive surgical resection , and both groups were homogeneous for the other known risk factors . Thirty-three patients with glioblastoma were treated with ACNU at the dose of 80 - 100 mg/m2 . Treatment was repeated every 5 - 8 weeks for a minimum of 2 and maximum of 14 cycles . Total survival time ( TST ) and to time to progression were chosen as outcome variables . RESULTS AND CONCLUSION No significant differences in systemic and hematological toxicity between the i.a . and iv . ACNU administration routes were detected . In both groups , tolerance of the procedure was excellent . Analysis of the main outcome measured showed no significant differences between i.a . and i.v . ACNU administration : time to progression was 6 months for i.a . ACNU and 4 months for i.v . ACNU and total survival time was 17 months for i.a . ACNU and 20 months for i.v . ACNU . In spite of ACNU dose incrementation , obtained through i.a . route administration , and subsequent higher concentration in the tumor bed , no improvement could be achieved in effectiveness The effect of intratumoral recombinant interferon gamma ( rIFN-gamma ) as adjuvant to open cytoreduction and external irradiation of 60 Gy on survival in adults with a newly diagnosed high- grade cerebral glioma was studied . The patients were r and omised during surgery into the rIFN-gamma group ( n = 14 ) or the control group ( n = 17 ) , and the latter received a subcutaneous reservoir of rIFN-gamma injections . Intratumoral rIFN-gamma was given three times a week for 4 weeks until radiotherapy , escalating the dose from 5 micrograms to 50 micrograms . Both groups received external whole-brain irradiation of 40 Gy and a local boost of 20 Gy . After radiotherapy , rIFN-gamma was continued with 50 micrograms twice a week up to 9 weeks . The patients received no chemotherapy . Intratumoral rIFN-gamma was tolerated well with transient fever only . There were 12 glioblastomas ( GBs ) in the control group and nine in the rIFN-gamma group with completed irradiation . The patients were followed clinical ly and by computerised tomography ( CT ) every third month until death . Tumour responses were seen in three interferon-treated ( one still alive 45 months after operation ) and in two conventionally treated patients . The progression of the tumour volumes on CT did not differ between the IFN-treated and control groups . There were no differences in the survival times . Median survival of the rIFN-gamma-treated patients was 54 weeks ( 95 % CI 35 - 68 ) and of the control patients 55 weeks ( 95 % CI 41 - 77 ) . Intratumoral rIFN-gamma given in the study doses does not seem to inhibit tumour growth or improve the prognosis of patients with high- grade glioma Abstract BACKGROUND : Five-aminolevulinic acid ( 5-ALA ) is used for fluorescence-guided resections of malignant glioma at a dose of 20 mg/kg ; yet , it is unknown whether lower doses may also provide efficacy . OBJECTIVE : To perform a double-blinded r and omized study comparing 3 different doses of 5-ALA . METHODS : Twenty-one patients with suspected malignant glioma were r and omly assigned to 0.2 , 2 , or 20 mg/kg 5-ALA . Investigators were unaware of dose . Intraoperatively , regions of interest were first defined in tumor core , margin , and adjacent white matter under white light . Under violet – blue illumination , the surgeon 's impression of fluorescence was recorded per region , followed by spectrometry and biopsy . Plasma was collected after administration and analyzed for 5-ALA and protoporphyrin IX ( PPIX ) content . RESULTS : The positive predictive value of fluorescence was 100 % . Visual and spectrometric fluorescence assessment showed 20 mg/kg to elicit the strongest fluorescence in tumor core and margins , which correlated with cell density . Spectrometric and visual fluorescence correlated significantly . A 10-fold increase in 5-ALA dose ( 2 - 20 mg/kg ) result ed in a 4-fold increase of fluorescence contrast between marginal tumor and adjacent brain . tmax for 5-ALA was 0.94 h for 20 mg/kg ( 0.2 kg : 0.50 h , 2 mg/kg : 0.61 h ) . Integrated PPIX plasma levels were 255.8 and 779.9 mcg*h/l ( 2 vs 20 mg/kg ) . Peak plasma concentrations were observed at 1.89 ± 0.71 and 7.83 ± 0.68 h ( 2 vs 20 mg/kg ; average ± St and ard Error of Mean [ SEM ] ) . CONCLUSION : The highest visible and measurable fluorescence was yielded by 20 mg/kg . No fluorescence was elicited at 0.2 mg/kg . Increasing 5-ALA doses did not result in proportional increases in tissue fluorescence or PPIX accumulation in plasma , indicating that doses higher than 20 mg/kg will not elicit useful increases in fluorescence BACKGROUND AND PURPOSE Short-course radiotherapy ( 25 Gy in five fractions ) was recently shown in a r and omized phase III trial to be non-inferior to 40 Gy in 15 fractions in elderly and /or frail patients with glioblastoma multiforme . This study compared the cost-effectiveness of the two regimens . MATERIAL AND METHODS The direct unit costs of imaging , radiotherapy ( RT ) , and dexamethasone were collected from the five primary contributing countries to the trial , constituting the data of 88 % of all patients . Effectiveness was measured by the restricted mean overall survival ( RMOS ) and progression free survival ( RMPFS ) . The incremental cost-effectiveness ratio ( ICER ) was calculated . Indirect costs were also estimated for comparison . RESULTS The median OSs for the short-course and commonly used RTs were 8.2 ( 95 % confidence interval [ CI ] 6.1 - 10.3 ) and 7.7 ( 95 % CI 5.5 - 9.9 ) months , respectively ( log rank p = 0.340 ) . Median PFSs were also not different ( p = 0.686 ) . The differences in the RMOS and the ICER , however , were + 0.11 life-years and -$3062 United States dollars ( USD ) per life-year gained , respectively . The differences in the RMPFS and the ICER were + 0.02 PFS and -$17,693 USD , respectively . CONCLUSION The ICER of -$3062 per life-year gained and -$17,693 per PFS gained indicates that the short-course RT is less costly compared to the longer RT regimen Concomitant radiochemotherapy followed by six cycles of temozolomide (= short term ) is considered as st and ard therapy for adults with newly diagnosed glioblastoma . In contrast , open-end administration of temozolomide until progression (= long-term ) is proposed by some authors as a viable alternative . We aim ed to determine the cost-effectiveness of long-term temozolomide therapy for patients newly diagnosed with glioblastoma compared to st and ard therapy . A Markov model was constructed to compare medical costs and clinical outcomes for both therapy types over a time horizon of 60 months . Transition probabilities for st and ard therapy were calculated from r and omized controlled trial data by Stupp et al. The data for long-term temozolomide therapy was collected by matching a cohort treated in the Department of Neurosurgery at Jena University Hospital . Health utilities were obtained from a previous cost utility study . The cost perspective was based on health insurance . The base case analysis showed a median overall survival of 17.1 months and a median progression-free survival of 7.4 months for patients in the long-term temozolomide therapy arm . The cost-effectiveness analysis using all base case parameters in a time-dependent Markov model result ed in an incremental effectiveness of 0.022 quality -adjusted life-years ( QALYs ) . The incremental cost-effectiveness ratio ( ICER ) was € 351,909/QALY . Sensitivity analyses showed that parameters with the most influence on ICER were the health state utility of progression in both therapy arms . Although open-ended temozolomide therapy is very expensive , the ICER of this therapy is comparable to that of the st and ard temozolomide therapy for patients newly diagnosed with glioblastoma From 1990 to 1994 , patients with newly diagnosed malignant gliomas were enrolled and r and omized between hyperfractionated radiation ( HFX ) of 72.0 Gy in 60 fractions given twice daily and 60.0 Gy in 30 fractions given once daily . All patients received 80 mg/m2 of 1,3 bis(2 chloroethyl)-1 nitrosourea on days 1–3 q8 weeks for 1 year . Patients were stratified by age , KPS , and histology . The primary endpoint was overall survival ( OS ) , with secondary endpoints including progression-free survival ( PFS ) and toxicity . Out of the 712 patients accrued , 694 ( 97.5 % ) were analyzable cases ( 350 HFX , 344 st and ard arm ) . There was no significant difference between the arms on overall acute or late treatment-related toxicity . No statistically significant effect for HFX , as compared to st and ard therapy , was found on either OS , with a median survival time ( MST ) of 11.3 versus 13.1 months ( p = 0.20 ) or PFS , with a median PFS time of 5.7 versus 6.9 months ( p = 0.18 ) . The treatment effect on OS remained insignificant based on the multivariate analysis ( hazard ratio 1.16 ; p = 0.0682 ) . When OS was analyzed by histology subgroup there was also no significant difference between the two arms for patients with glioblastoma multiforme ( MST : 10.3 vs. 11.2 months ; p = 0.34 ) , anaplastic astrocytoma ( MST : 69.8 vs. 50.0 months ; p = 0.91 ) or anaplastic oligodendroglioma ( MST : 92.1 vs. 66.5 months ; p = 0.33 ) . Though this trial provided many invaluable secondary analyses , there was no trend or indication of a benefit to HFX radiation to 72.0 Gy in any subset of malignant glioma patients Abstract Lessons Learned . Results suggest that the combination of bevacizumab plus temozolomide is active in terms of response rate , survival , performance , quality of life , and cognition in elderly patients with glioblastoma multiforme with poor performance status . Whether this combination is superior to temozolomide alone remains to be demonstrated by a r and omized study . Background . The optimal treatment of glioblastoma multiforme ( GBM ) in patients aged ≥70 years with a Karnofsky performance status ( KPS ) < 70 is not established . This clinical trial evaluated the efficacy and safety of upfront temozolomide ( TMZ ) and bevacizumab ( Bev ) in patients aged ≥70 years and a KPS < 70 . Material s and Methods . Patients aged ≥70 years with a KPS < 70 and biopsy‐proven GBM were eligible for this multicenter , prospect i ve , nonr and omized , phase II trial of older patients with impaired performance status . Treatment consisted of TMZ administered at 130–150 mg/m2 per day for 5 days every 4 weeks plus Bev administered at 10 mg/kg every 2 weeks . Results . The trial included 66 patients ( median age of 76 years ; median KPS of 60 ) . The median overall survival ( OS ) was 23.9 weeks ( 95 % confidence interval [ CI ] , 19–27.6 ) , and the median progression‐free survival ( PFS ) was 15.3 weeks ( 95 % CI , 12.9–19.3 ) . Twenty‐two ( 33 % ) patients became transiently capable of self‐care ( i.e. , KPS > 70 ) . Cognition and quality of life significantly improved over time during treatment . Grade ≥3 hematological adverse events occurred in 13 ( 20 % ) patients , high blood pressure in 16 ( 24 % ) , venous thromboembolism in 3 ( 4.5 % ) , cerebral hemorrhage in 2 ( 3 % ) , and intestinal perforation in 2 ( 3 % ) . Conclusion . This study suggests that TMZ + Bev treatment is active in elderly patients with GBM with low KPS and has an acceptable tolerance level Purpose Adoptive cell immunotherapy involves an ex vivo expansion of autologous cytokine-induced killer ( CIK ) cells before their reinfusion into the host . We evaluated the efficacy and safety of CIK cell immunotherapy with radiotherapy-temozolomide ( TMZ ) for the treatment of newly diagnosed glioblastomas . Experimental design In this multi-center , open-label , phase 3 study , we r and omly assigned patients with newly diagnosed glioblastoma to receive CIK cell immunotherapy combined with st and ard TMZ chemoradiotherapy ( CIK immunotherapy group ) or st and ard TMZ chemoradiotherapy alone ( control group ) . The efficacy endpoints were analyzed in the intention-to-treat set and in the per protocol set . Results Between December 2008 and October 2012 , a total of 180 patients were r and omly assigned to the CIK immunotherapy ( n = 91 ) or control group ( n = 89 . In the intention-to-treat analysis set , median PFS was 8.1 months ( 95 % confidence interval ( CI ) , 5.8 to 8.5 months ) in the CIK immunotherapy group , as compared to 5.4 months ( 95 % CI , 3.3 to 7.9 months ) in the control group ( one-sided log-rank , p = 0.0401 ) . Overall survival did not differ significantly between two groups . Grade 3 or higher adverse events , health-related quality of life and performance status between two groups did not show a significant difference . Conclusions The addition of CIK cells immunotherapy to st and ard chemoradiotherapy with TMZ improved PFS . However , the CIK immunotherapy group did not show evidence of a beneficial effect on overall survival YKL-40 is a glycoprotein with pro-angiogenic functions . We hypothesized that patients with newly diagnosed glioblastoma and low baseline plasma YKL-40 levels derive greater benefit from first-line bevacizumab . Plasma sample s were collected from 563 patients in the r and omized , phase 3 AVAglio trial who received bevacizumab or placebo plus radiotherapy/temozolomide . Raw plasma YKL-40 concentrations were converted to age-corrected percentiles of normal healthy YKL-40 levels and divided into quartiles ( Q ) . The impact of baseline plasma YKL-40 level on survival was investigated using Cox regression analyses . Patients with low baseline plasma YKL-40 ( ≤Q1 ) had an improved progression-free survival hazard ratio ( HR ) for bevacizumab versus placebo ( 0.37 , 95 % confidence interval [ CI ] : 0.25–0.55 ) compared with high plasma YKL-40 ( > Q1 ) ( 0.71 , 95 % CI : 0.57–0.87 ) . Overall survival HRs were comparable between the subgroups ( ≤ Q1 : 0.69 , 95 % CI : 0.44–1.09 ; ( > Q1 : 0.88 , 95 % CI : 0.68–1.13 ) . A trend for improved progression-free survival HR with low versus high YKL-40 was observed in proneural glioblastoma ( 0.41 , 95 % CI : 0.13–1.28 vs 0.80 , 95 % CI : 0.45–1.40 , respectively ) , but not for proliferative/mesenchymal subtypes . Elevated plasma YKL-40 ( > 90th percentile of normal ) was an independent negative prognostic factor . In conclusion , the predictive value of baseline plasma YKL-40 level as a biomarker for bevacizumab efficacy in glioblastoma may be limited to patients with proneural tumors . Independent validation studies are required to confirm these results We characterized health-related quality of life ( HRQoL ) , cognitive , and functional status in newly diagnosed glioblastoma ( GBM ) patients receiving Tumor treating fields ( TTFields ) with temozolomide ( TMZ ) versus TMZ alone in a planned interim analysis of a r and omized phase III trial [ NCT00916409 ] , which showed significant improvement in progression-free and overall survival with TTFields/TMZ . After radiotherapy with concomitant TMZ , newly diagnosed GBM patients were r and omized ( 2:1 ) to TTFields/TMZ ( n = 210 ) or TMZ ( n = 105 ) . Interim analysis was performed in 315 patients with ≥18 months of follow-up . HRQoL , a secondary endpoint , was evaluated in per- protocol patient population and expressed as change from baseline ( CFB ) at 3 , 6 , and 9 months for each subscale in the EORTC QLQ-C30/BN20 . Karnofsky performance scores ( KPS ) and Mini-Mental State Examination scores ( MMSE ) were assessed . CFB in HRQoL was balanced in treatment groups at the 12-month time point . Initially , HRQoL improved in patients treated with TTFields/TMZ ( CFB3 : 24 % and CFB6 : 13 % ) versus TMZ ( CFB3 : −7 % and CFB6 : −17 % ) , though this difference was no longer evident at the 9-month point . General scales , including physical and social functioning , showed no difference at 9 and 12 months . TTFields/TMZ group reported higher concerns of “ itchy skin ” . KPS over 12 months was just below 90 in both groups . Cognitive status ( MMSE ) was stable over time . HRQoL , KPS , and MMSE were balanced in both groups over time . There was no preliminary evidence that HRQoL , cognitive , and functional status is adversely affected by the continuous use of TTFields Background The GLARIUS trial , which investigated the efficacy of bevacizumab (BEV)/irinotecan ( IRI ) compared with st and ard temozolomide in the first-line therapy of O6-methylguanine-DNA methyltransferase (MGMT)-nonmethylated glioblastoma , showed that progression-free survival was significantly prolonged by BEV/IRI , while overall survival was similar in both arms . The present report focuses on quality of life ( QoL ) and Karnofsky performance score ( KPS ) during the whole course of the disease . Methods Patients ( n = 170 ) received st and ard radiotherapy and were r and omized ( 2:1 ) for BEV/IRI or st and ard temozolomide . At least every 3 months KPS was determined and QoL was measured using the European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life and 20-item Brain Neoplasm question naires . A generalized estimating equation ( GEE ) model evaluated differences in the course of QoL and KPS over time . Also , the time to first deterioration and the time to postprogression deterioration were analyzed separately . Results In all dimensions of QoL and KPS , GEE analyses and time to first deterioration analyses did not detect significant differences between the treatment arms . At progression , 82 % of patients receiving second-line therapy in the st and ard arm received BEV second-line therapy . For the dimensions of motor dysfunction and headaches , time to postprogression deterioration was prolonged in the st and ard arm receiving crossover second-line BEV in the vast majority of patients at the time of evaluation . Conclusions GLARIUS did not find indications for a BEV-induced detrimental effect on QoL in first-line therapy of MGMT-nonmethylated GBM patients . Moreover , GLARIUS provided some indirect corroborative data supporting the notion that BEV may have beneficial effects upon QoL in relapsed GBM Background : Glioblastoma ( GBM ) is one of the worst cancers with bad prognosis despite systemic chemotherapy and radiotherapy after surgery . Methods : In this study , 71 patients with GBM were enrolled and r and omly assigned to two groups : Receiving radiotherapy with concomitant and adjuvant temozolomide ( TMZ ) ( TMZ , st and ard therapy ) after surgery , or receiving radiotherapy with concomitant and adjuvant local delivery of nimustine ( ACNU ) rendezvousing with oral TMZ ( rendezvous therapy ) . In the follow-up of all patients and the progression-free survival ( PFS ) , overall survival ( OS ) , Karnofsky performance score ( KPS ) and toxicities were recorded . Results : For the whole cohort , the median OS was 18.0 months , and the median PFS was 7.8 months . A significantly longer OS was observed in patients received rendezvous therapy than those who receiving st and ard therapy ( 18.5 months vs. 16.0 months ; P = 0.014 ) , as well as PFS ( 8.8 months vs. 7.0 months ; P = 0.008 ) . The KPS ≥70 rates were 81.8 % , 40.9 % , 20.5 % in 1 , 2 , and 3 years for the rendezvous therapy group , significantly superior to st and ard therapy group . The most common toxicities were tolerable gastrointestinal reaction , liver dysfunction , and hematological toxicities , which were relieved with symptomatic treatment . Grade 3 or 4 toxicity was documented in 8 ( 18.3 % ) patients in rendezvous therapy group , while it was observed in 6 ( 22.2 % ) patients in st and ard therapy group during whole treatment process . Conclusions : Compared to st and ard therapy , the antitumor effects of rendezvous therapy were more effective in GBM patients without increasing the toxicities Purpose This study explored the superiority of temozolomide ( TMZ ) + interferonβ ( IFNβ ) to st and ard TMZ as treatment for newly diagnosed glioblastoma ( GBM ) via r and omized phase II screening design .Experimental design Eligibility criteria included histologically proven GBM , with 50 % of the tumor located in supratentorial areas , without involvement of the optic , olfactory nerves , and pituitary gl and and without multiple lesions and dissemination . Patients in the TMZ + radiotherapy ( RT ) arm received RT ( 2.0 Gy/fr/day , 30 fr ) with TMZ ( 75 mg/m2 , daily ) followed by TMZ maintenance ( 100–200 mg/m2/day , days 1–5 , every 4 weeks ) for 2 years . Patients in the TMZ + IFNβ + RT arm intravenously received IFNβ ( 3 MU/body , alternative days during RT and day 1 , every 4 weeks during maintenance period ) and TMZ + RT . The primary endpoint was overall survival ( OS ) . The planned sample size was 120 ( one-sided alpha 0.2 ; power 0.8 ) . Results Between Apr 2010 and Jan 2012 , 122 patients were r and omized . The median OS with TMZ + RT and TMZ + IFNβ + RT was 20.3 and 24.0 months ( HR 1.00 , 95 % CI 0.65–1.55 ; one-sided log rank P = 0.51 ) . The median progression-free survival times were 10.1 and 8.5 months ( HR 1.25 , 95 % CI 0.85–1.84 ) . The incidence of neutropenia with the TMZ + RT and the TMZ + IFNβ + RT ( grade 3–4 , CTCAE version 3.0 ) was 12.7 versus 20.7 % during concomitant period and was 3.6 versus 9.3 % during maintenance period . The incidence of lymphopenia was 54.0 versus 63.8 % and 34.5 versus 41.9 % . Conclusions TMZ + IFNβ + RT is not considered as a c and i date for the following phase III trial , and TMZ + RT remained to be a most promising treatment . This trial was registered with the UMIN Clinical Trials Registry : UMIN000003466 Background In this exploratory analysis of AVAglio , a r and omized phase III clinical study that investigated the addition of bevacizumab ( Bev ) to radiotherapy/temozolomide in newly diagnosed glioblastoma , we aim to radiologically characterize glioblastoma on therapy until progression and investigate whether the type of radiologic progression differs between treatment arms and is related to survival and molecular data . Methods Five progression types ( PTs ) were categorized using an adapted algorithm according to MRI contrast enhancement behavior in T1- and T2-weighted images in 621 patients ( Bev , n = 299 ; placebo , n = 322 ) . Frequencies of PTs ( design ated as classic T1 , cT1 relapse , T2 diffuse , T2 circumscribed , and primary nonresponder ) , time to progression ( PFS ) , and overall survival ( OS ) were assessed within each treatment arm and compared with molecular subtypes and O6-methylguanine DNA methyltransferase ( MGMT ) promoter methylation status . Results PT frequencies differed between the Bev and placebo arms , except for " T2 diffuse " ( 12.4 % and 7.1 % , respectively ) . PTs showed differences in PFS and OS ; with " T2 diffuse " being associated with longest survival . Complete disappearance of contrast enhancement during treatment ( " cT1 relapse " ) showed longer survival than only partial contrast enhancement decrease ( " classic T1 " ) . " T2 diffuse " was more commonly MGMT hypermethylated . Only weak correlations to molecular subtypes from primary tissue were detected . Conclusions Progression of glioblastoma under therapy can be characterized radiologically . These radiologic phenotypes are influenced by treatment and develop differently over time with differential outcomes . Complete resolution of contrast enhancement during treatment is a favorable factor for outcome Background The addition of bevacizumab to temozolomide-based chemoradiotherapy ( TMZ/RT → TMZ ) did not prolong overall survival ( OS ) in patients with newly diagnosed glioblastoma in phase III trials . Elderly and frail patients are underrepresented in clinical trials , but early reports suggested preferential benefit in this population . Patients and methods ARTE was a 2 : 1 r and omized , multi-center , open-label , non-comparative phase II trial of hypofractionated RT ( 40 Gy in 15 fractions ) with bevacizumab ( 10 mg/kg × 14 days ) ( arm A , N = 50 ) or without bevacizumab ( arm B , N = 25 ) in patients with newly diagnosed glioblastoma aged ≥65 years . The primary objective was to obtain evidence for prolongation of median OS by the addition of bevacizumab to RT . Response was assessed by RANO criteria . Quality of life ( QoL ) was monitored by the EORTC QLQ-C30/BN20 modules . Exploratory studies included molecular subtyping by 450k whole methylome and gene expression analyses . Results Median PFS was longer in arm A than in arm B ( 7.6 and 4.8 months , P = 0.003 ) , but OS was similar ( 12.1 and 12.2 months , P = 0.77 ) . Clinical deterioration was delayed and more patients came off steroids in arm A. Prolonged PFS in arm A was confined to tumors with the receptor tyrosine kinase ( RTK ) I methylation subtype ( HR 0.25 , P = 0.014 ) and proneural gene expression ( HR 0.29 , P = 0.025 ) . In a Cox model of OS controlling for established prognostic factors , associations with more favorable outcome were identified for age < 70 years ( HR 0.52 , P = 0.018 ) and Karnofsky performance score 90%-100 % ( HR 0.51 , P = 0.026 ) . Including molecular subtypes into that model identified an association of the RTK II gene methylation subtype with inferior OS ( HR 1.73 , P = 0.076 ) . Conclusion Efficacy outcomes and exploratory analyses of ARTE do not support the hypothesis that the addition of bevacizumab to RT generally prolongs survival in elderly glioblastoma patients . Molecular biomarkers may identify patients with preferential benefit from bevacizumab . Clinical trial registration number NCT01443676 Background This phase II study was design ed to determine the efficacy of the mammalian target of rapamycin ( mTOR ) inhibitor everolimus administered daily with conventional radiation therapy and chemotherapy in patients with newly diagnosed glioblastoma . Methods Patients were r and omized to radiation therapy with concurrent and adjuvant temozolomide with or without daily everolimus ( 10 mg ) . The primary endpoint was progression-free survival ( PFS ) and the secondary endpoints were overall survival ( OS ) and treatment-related toxicities . Results A total of 171 patients were r and omized and deemed eligible for this study . Patients r and omized to receive everolimus experienced a significant increase in both grade 4 toxicities , including lymphopenia and thrombocytopenia , and treatment-related deaths . There was no significant difference in PFS between patients r and omized to everolimus compared with control ( median PFS time : 8.2 vs 10.2 mo , respectively ; P = 0.79 ) . OS for patients r and omized to receive everolimus was inferior to that for control patients ( median survival time : 16.5 vs 21.2 mo , respectively ; P = 0.008 ) . A similar trend was observed in both O6-methylguanine-DNA-methyltransferase promoter hypermethylated and unmethylated tumors . Conclusion Combining everolimus with conventional chemoradiation leads to increased treatment-related toxicities and does not improve PFS in patients with newly diagnosed glioblastoma . Although the median survival time in patients receiving everolimus was comparable to contemporary studies , it was inferior to the control in this r and omized study Background : Angiogenesis is crucial for glioblastoma growth , and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients . The number of circulating endothelial cells ( CECs ) is a surrogate marker for endothelial damage . We assessed their kinetics and explored their prognostic value in patients with recurrent glioblastoma . Methods : In this side study of the BELOB trial , 141 patients with recurrent glioblastoma were r and omised to receive single-agent bevacizumab or lomustine , or bevacizumab plus lomustine . Before treatment , after 4 weeks and after 6 weeks of treatment , CECs were enumerated . Results : The number of CECs increased during treatment with bevacizumab plus lomustine , but not during treatment in the single-agent arms . In patients treated with lomustine single agent , higher absolute CEC numbers after 4 weeks ( log10CEC hazard ratio ( HR ) 0.41 , 95 % CI 0.18–0.91 ) and 6 weeks ( log10CEC HR 0.16 , 95 % CI 0.05–0.56 ) of treatment were associated with improved overall survival ( OS ) . Absolute CEC numbers in patients receiving bevacizumab plus lomustine or bevacizumab single agent were not associated with OS . Conclusion : CEC numbers increased during treatment with bevacizumab plus lomustine but not during treatment with either agent alone , suggesting that this combination induced the greatest vascular damage . Although the absolute number of CECs was not associated with OS in patients treated with bevacizumab either alone or in combination , they could serve as a marker in glioblastoma patients receiving lomustine single agent In recurrent glioblastoma , health-related quality of life ( HRQL ) is a crucial trial endpoint . We examined HRQL outcomes as a secondary endpoint for patients in the CABARET r and omized phase 2 trial . 122 patients were r and omly allocated to bevacizumab monotherapy or bevacizumab plus carboplatin . We calculated change scores from baseline for each HRQL measure on the European Organisation for Research and Treatment of Cancer Quality of Life Question naire Core 30 ( EORTC QLQ-C30 ) and the Brain Cancer Module ( QLQ-BN20 ) , together with time to deterioration in HRQL , and the proportion of participants with clinical ly meaningful improvements in specific disease-related symptoms . At baseline , 117 of 122 r and omized patients ( 96 % ) attempted question naires . Question naire participation rates were > 90 % for patients continuing on treatment , however at the end-of-treatment visit only 72 ( 64 % of eligible participants ) returned a form . There were no differences between arms in change scores over the treatment period . Time to ≥10 point deterioration in scores from baseline was also similar between arms . HRQL deterioration occurred largely before progression for the domains tested , but scores in HRQL domains specifically relevant to symptoms of recurrent glioblastoma also improved for about 50 % of patients with symptoms at baseline . Neither detrimental nor beneficial effects on HRQL were seen with carboplatin added to bevacizumab , with a proportion of patients on both arms experiencing symptomatic benefit . Given the reduced question naire completion at end of treatment , time to HRQL deterioration is a feasible and robust clinical trial endpoint in this patient population . Clinical trials registration number : ACTRN12610000915055 We have evaluated the influence of fluorescein-guided resection on gross total resection ( GTR ) and survival in a series of patients with GBM . Group 1 consisted of 47 patients given fluorescein and group 2 comprised 33 patients , on whom fluorescein was not used . Median survival time was 43.9 weeks in the patients given fluorescein and was 41.8 weeks in the non-fluorescein group . There was no statistically significant difference in survival between the two groups . However , the extent of resection had a powerful influence on the median survival time . Survival was 34.3 weeks after partial resection and 46.5 after GTR . Our data shows that the use of fluorescein injection is a simple procedure , which allows a significant increase in the number of patients having GTR ( 83 vs. 55 % ) . Our findings are similar to a recently published multicentre Phase III r and omized trial in which 5-aminolevulinic acid was used to facilitate resection of malignant glioma PURPOSE High-linear energy transfer ( LET ) radiation beams have potential applications in the treatment of glioblastoma , but have not yet demonstrated significant improvement in results . However , some patients have had local control of glioblastoma with high-LET irradiations such as neutrons and heavy charged particles . METHODS AND MATERIAL S In this collaborative study , 15 patients were entered into a r and omized protocol comparing two dose levels of 20 and 25 Gy in 4 weeks of neon ion irradiation . This trial was intended to determine the optimal neon dose in terms of survival and effects of radiation . RESULTS Fourteen patients were evaluable with no significant differences in median survival ( 13 and 14 months ; p = NS ) or median time to failure ( 7 and 9 months ; p = NS ) between the two dose arms . Three patients died of nontumor-related causes , of whom one ( who died 19 months posttreatment ) had autopsy confirmation of no tumor on pathological exam . The other two patients had stable magnetic resonance imaging scans at 6 and 22 months posttreatment . CONCLUSION Although the results did not demonstrate the optimal high-LET dose level , there is an intriguing effect in that two patients had control of glioblastoma until death at 19 and 22 months . This suggests that better conformation of the high-LET dose to the tumor with neutron capture therapy or dynamic conformal heavy charged particle therapy might control glioblastoma while minimizing brain damage from radiation Purpose : Patients with progressive or recurrent supratentorial high- grade gliomas were entered into a multicentre phase II trial to evaluate the efficacy and toxicity of temozolomide . Methods : The treatment schedule was 150–200 mg/m2 per day orally for 5 days repeated every 28 days . Response evaluation was by a combination of neurological status evaluation ( MRC scale ) and imaging . Results : Of 103 eligible patients enrolled , 11 ( 11 % ) achieved an objective response and a further 48 ( 47 % ) had stable disease . The median response duration was 4.6 months . Response rates were similar for anaplastic astrocytomas ( grade III ) and glioblastoma multiforme ( grade IV ) tumours . Predictable myelosuppression was the major toxicity . Conclusions : The observation of objective responses and tolerable side effects in this heterogeneous population of patients supports the further investigation of this agent in high- grade gliomas Abstract The radioresistance of glioblastoma presumably results from the presence of hypoxic cells . In an attempt to overcome this problem , fast neutrons were compared in a controlled pilot study with conventional megavoltage X-rays ( photons ) . 63 patients entered the study between January , 1973 and July , 1976 , 30 patients received neutron and 33 received X-ray therapy . The overall mean survival was 11.4 months for those who received photon and 10 months for those who received neutron therapy . Survival rates at 6 and 12 months were 72 % and 36 % respectively for photon treated patients , and 77 % and 30 % for those treated with neutrons . Although neutron therapy did not improve overall survival , examination of the histological material indicated a considerably greater antitumor effect after neutron therapy than after treatment with photons . In the neutron treated group , at post-mortem examination no tumor or only minimal tumor was found in 10 of 12 patients and in one of 4 patients where tissue was obtained from a second craniotomy . In some cases , there was evidence of diffuse damage to normal brain which was in keeping with a clinical syndrome of progressive dementia without localizing signs . Dose , time , and volume factors for neutron therapy to the brain and possible ways of improving results are discussed Summary Experimental and early clinical investigations have demonstrated encouraging results for estramustine in the treatment of malignant glioma . The present study is an open r and omized clinical trial comparing estramustine phosphate ( Estracyt ® ) in addition to radiotherapy with radiotherapy alone as first line treatment of astrocytoma grade III and IV . The 140 patients included were in a good clinical condition with a median age of 55 years ( range 22–87 ) . Estramustine was given orally , 280 mg twice daily , as soon as the diagnosis was established , during and after the radiotherapy for a period of in total 3 months . Radiotherapy was delivered on weekdays 2 Gy daily up to 56 Gy . Eighteen patients were excluded due to misclassification , leaving 122 patients eligible for evaluation . Overall the treatment was well tolerated . Mild or moderate nausea was the most common side effect of estramustine . The minimum follow-up time was 5.2 years for the surviving patients . For astrocytoma grade III the median survival time was 10.6 ( 1.3–92.7 ) months for the radiotherapy only group and 17.3 ( 0.4–96.9 + ) months for the estramustine + radiotherapy group . In grade IV the corresponding median survival time was 12.3 ( 2.1–89.2 ) and 10.3 ( 0.3–91.7 + ) months , respectively . Median time to progress for radiotherapy only and radiotherapy and estramustin group in grade III tumours was 6.5 and 10.1 months , respectively . In grade IV tumours the corresponding figures were 5.1 and 3.3 months , respectively . Although there was a tendency for improved survival in grade III , no statistical significant differences were found between the treatment groups . No differences between the two treatment groups were evident with respect to quality of life according to the EORTC QLQ- protocol . In conclusion , this first r and omized study did not demonstrate any significant improvement of using estramustine in addition to conventional radiotherapy , however , a trend for a positive response for the estramustine group was found in patients with grade III glioma PURPOSE Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor ( VEGF ) with demonstrated efficacy in combination with carboplatin and paclitaxel ( PCB ) for the treatment of advanced non-small-cell lung cancer ( NSCLC ) . Administration of bevacizumab is postulated to decrease nitric oxide synthesis and lead to hypertension , which may be a physiological sign that the VEGF pathway is more actively being blocked and could result in improved outcomes . PATIENTS AND METHODS Eastern Cooperative Oncology Group ( ECOG ) 4599 r and omly assigned patients with nonsquamous NSCLC to carboplatin and paclitaxel ( PC ) versus PCB . Hypertensive patients were compared with nonhypertensive patients with respect to overall survival ( OS ) and progression-free survival ( PFS ) using blood pressure data and adverse event data separately . High blood pressure ( HBP ) by the end of cycle 1 was defined as blood pressure > 150/100 at any previous time or at least a 20-mmHg increase in diastolic blood pressure from baseline . Results In a multivariable Cox model adjusting for HBP as a time-varying covariate , comparing those on PCB with HBP with those on PC gave an OS hazard ratio ( HR ) of 0.60 ( 95 % CI , 0.43 to 0.81 ; P = .001 ) ; comparing those on PCB without HBP with those on PC alone , the OS HR was 0.86 ( 95 % CI , 0.74 to 1.00 ; P = .05 ) . Comparing the PCB HBP group with PC gave an adjusted PFS HR of 0.54 ( 95 % CI , 0.41 to 0.73 ; P < .0001 ) and comparing those on PCB without HBP to those on PC , the HR was 0.72 ( 95 % CI , 0.62 to 0.84 ; P < .0001 ) . The 6-month cumulative incidence of hypertension was 6.2 % ( 95 % CI , 3.9 % to 8.6 % ) . CONCLUSION Data from ECOG 4599 suggest that onset of HBP during treatment with PCB may be associated with improved outcomes , and additional studies of the downstream effects of VEGF suppression and hypertension are needed Background The peak incidence of glioblastoma multiforme ( GBM ) occurs in those aged 65 years and older . However , studies on this patient group remain limited . The goal of this study is to evaluate the efficacy of surgery versus biopsy for older patients with these lesions . Methods 133 and 72 consecutive patients aged 65 years and older who underwent surgery and needle biopsy for intracranial primary ( de novo ) GBM between 1997 and 2007 were retrospectively review ed . Among these patients , 40 who underwent surgical resection were matched with 40 who underwent needle biopsy alone for factors consistently shown to be associated with survival [ age , Karnofsky Performance Scale ( KPS ) indexing , eloquent involvement , radiation , temozolomide ] . Survival was expressed as estimated Kaplan – Meier plots , and log-rank analysis was used to compare survival curves . Results Mean ± st and ard deviation age was 73 ± 5 years , and median survival was 4.9 months . There were no significant differences in perioperative outcomes among patients who underwent surgical resection versus needle biopsy . Patients who underwent resection had median survival of 5.7 months as compared with 4.0 months for patients who underwent needle biopsy ( P = 0.02 ) . Likewise , for patients aged 70 years and older , median survival was 4.5 months for 26 patients who underwent surgical resection as compared with 3.0 months for 26 patients who underwent needle biopsy ( P = 0.03 ) . Conclusion This study demonstrates that older patients tolerate aggressive surgery without increased surgery-related morbidity and have prolonged survival as compared with similar patients undergoing needle biopsy . These findings may help guide treatment decisions for patients , their families , and their physicians OBJECT Accumulating data suggest more aggressive surgery in patients with malignant glioma to improve outcome . However , extended surgery may increase morbidity . The r and omized Phase III 5-aminolevulinic acid ( ALA ) study investigated 5-ALA-induced fluorescence as a tool for improving resections . An interim analysis demonstrated more frequent complete resections with longer progression-free survival ( PFS ) . However , marginal differences were found regarding neurological deterioration and the frequency of additional therapies . Presently , the authors focus on the latter aspects in the final study population , and attempt to determine how safety might be affected by cytoreductive surgery . METHODS Patients with malignant gliomas were r and omized for fluorescence-guided ( ALA group ) or conventional white light ( WL ) ( WL group ) microsurgery . The final intent-to-treat population consisted of 176 patients in the ALA and 173 in the WL group . Primary efficacy variables were contrast-enhancing tumor on early MR imaging and 6-month PFS . Among secondary outcome measures , the National Institutes of Health Stroke Scale ( NIH-SS ) score and the Karnofsky Performance Scale ( KPS ) score were used for assessing neurological function . RESULTS More frequent complete resections and improved PFS were confirmed , with higher median residual tumor volumes in the WL group ( 0.5 vs 0 cm(3 ) , p = 0.001 ) . Patients in the ALA group had more frequent deterioration on the NIH-SS at 48 hours . Patients at risk were those with deficits unresponsive to steroids . No differences were found in the KPS score . Regarding outcome , a combined end point of risks and neurological deficits was attempted , which demonstrated results in patients in the ALA group to be superior to those in participants in the WL group . Interestingly , the cumulative incidence of repeat surgery was significantly reduced in ALA patients . When stratified by completeness of resection , patients with incomplete resections were quicker to deteriorate neurologically ( p = 0.0036 ) . CONCLUSIONS Extended resections performed using a tool such as 5-ALA-derived tumor fluorescence , carries the risk of temporary impairment of neurological function . However , risks are higher in patients with deficits unresponsive to steroids The Radiation Therapy Oncology Group ( RTOG ) and the Eastern Cooperative Oncology Group ( ECOG ) conducted a phase III trial in patients with malignant gliomas to evaluate 4 treatment arms : 1 ) 60 Gy to the whole brain ; 2 ) 60 Gy plus 10-Gy boost ; 3 ) 60 Gy plus carmustine ( BCNU ) ; and 4 ) 60 Gy plus semustine plus dacarbazine . Between September 1974 and March 1979 , 626 patients with malignant gliomas were treated on protocol RTOG 7401/ECOG 1374 . Each institution chose a subset of the treatments to which the patients would be r and omized . Patients were stratified according to subset and r and omized to the 4 treatment arms . There were no differences in survival among treatment arms . For patients greater than 60 years of age , the addition of chemotherapy to radiation therapy did not improve survival . For patients aged 40 - 60 years , there was a statistically significant increase in overall survival when BCNU was added to 60 Gy ( P less than .01 ) , with an increase in 2-year survival from 8 % to 23 % . This beneficial effect of BCNU is apparent in both histological groups ( astrocytoma with atypical or anaplastic foci and glioblastoma multiforme ) . Although few confirmatory autopsies are available , long-term survival in patients with astrocytomas with atypical and anaplastic foci who were treated with 60 Gy plus BCNU ( 5-yr survival , 22 % ) suggests no significant late CNS toxicity , compared to 60 Gy alone ( 5-yr survival , 15 % ) . This is confirmed by comparable neurological function in long-term survivors Purpose : Efficacy signals but substantial myelosuppression were demonstrated in a single arm phase II study of paclitaxel poliglumex ( PPX ) in combination with temozolomide ( TMZ ) and radiation therapy ( RT ) for first-line treatment of glioblastoma . The objective of this r and omized phase II trial was to assess the efficacy and safety of single-agent PPX with RT ( PPX/RT ) versus TMZ with RT ( TMZ/RT ) for glioblastoma without O6-methylguanine-DNA methyltransferase ( MGMT ) methylation . Material s and Methods : Patients with glioblastoma with unmethylated MGMT without prior chemotherapy or RT were eligible . Patients were r and omly assigned 2:1 to PPX , 50 mg/m2/wk for 6 weeks , or st and ard TMZ , with concurrent 60.0 Gy RT . One month after completion of chemoradiation all patients received st and ard maintenance TMZ . The primary endpoint was progression-free survival ( PFS ) . Results : Of the 164 patients enrolled , 86 were MGMT unmethylated . Of these , 63 patients were r and omized ( 42 to PPX/RT and 21 to TMZ/RT ) . Fifty-nine patients could be analyzed . The median PFS was 9 months in the PPX/RT group and 9.5 months in the TMZ/RT group ( hazard ratio in the PPX/RT group , 1.10 ; 95 % confidence interval , 0.79 - 2.08 ; P=0.75 ) . Median overall survival was 16 versus 14.8 months for PPX/RT and TMZ/RT groups , respectively ( hazard ratio , 1.44 ; 95 % confidence interval , 0.75 - 2.77 ; P=0.27 ) . In the PPX and TMZ groups 44 % versus 22 % of patients , respectively , experienced one or more grade 3 or higher toxicities during chemoradiation . Conclusions : PPX/RT did not improve PFS or overall survival . This study provides an effective trial design for screening RT sensitizers in glioblastoma One hundred and fifteen eligible patients with histologically verified malignant gliomas ( astrocytoma grade III – IV ) were r and omized to receive either radiotherapy 6 000 rads/7 week plus CCNU 130 mg/ M2 every 6 weeks ( treatment 1 ) or radiotherapy 6000 rads/7 weeks plus CCNU 75 mg/M2 day 1 plus procarbazine 100 Mg/m2 days 1–14 every 6 weeks ( treatment 2 ) within 4 weeks following surgical resection . The response rates showed no statistically significant differences between treatment 1 CR/ PR - 24/ 17 % and treatment 2 CR/ PR - 14/14 % ( P-value = 0.31 ) . The median survival was also not significantly different : 55 and 50 weeks for treatments 1 and 2 , respectively . The most important prognostic parameter identified was age with younger patients showing higher response rates and longer survival . Patients ' performance status was also a useful prognostic parameter for response and survival . Neither the extent of surgical resection nor the tumor grade correlated significantly with the outcome . Further studies are needed to identify active chemotherapeutic agents for the treatment of brain tumors This r and omized , open-label , active-controlled , dose-finding phase IIb study evaluated the efficacy and safety of trabedersen ( AP 12009 ) administered intratumorally by convection-enhanced delivery compared with st and ard chemotherapy in patients with recurrent/refractory high- grade glioma . One hundred and forty-five patients with central reference histopathology of recurrent/refractory glioblastoma multiforme ( GBM ) or anaplastic astrocytoma ( AA ) were r and omly assigned to receive trabedersen at doses of 10 or 80 µM or st and ard chemotherapy ( temozolomide or procarbazine/lomustine/vincristine ) . Primary endpoint was 6-month tumor control rate , and secondary endpoints included response at further timepoints , survival , and safety . Six-month tumor control rates were not significantly different in the entire study population ( AA and GBM ) . Prespecified AA subgroup analysis showed a significant benefit regarding the 14-month tumor control rate for 10 µM trabedersen vs chemotherapy ( p= .0032 ) . The 2-year survival rate had a trend for superiority for 10 µM trabedersen vs chemotherapy ( p = .10 ) . Median survival for 10 µM trabedersen was 39.1 months compared with 35.2 months for 80 µM trabedersen and 21.7 months for chemotherapy ( not significant ) . In GBM patients , response and survival results were comparable among the 3 arms . Exploratory analysis on GBM patients aged ≤55 years with Karnofsky performance status > 80 % at baseline indicated a 3-fold survival at 2 and 3 years for 10 µM trabedersen vs chemotherapy . The frequency of patients with related or possibly drug-related adverse events was higher with st and ard chemotherapy ( 64 % ) than with 80 µM trabedersen ( 43 % ) and 10 µM trabedersen ( 27 % ) . Superior efficacy and safety for 10 µM trabedersen over 80 µM trabedersen and chemotherapy and positive risk – benefit assessment suggest it as the optimal dose for further clinical development in high- grade glioma BACKGROUND Survival outcomes for patients with glioblastoma remain poor , particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase ( MGMT ) gene promoter . This phase II , r and omized , open-label , multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with st and ard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter . METHODS Overall , 265 patients were r and omized ( 1:1:1 ) to st and ard cilengitide ( 2000 mg 2 × /wk ; n = 88 ) , intensive cilengitide ( 2000 mg 5 × /wk during wk 1 - 6 , thereafter 2 × /wk ; n = 88 ) , or a control arm ( chemoradiotherapy alone ; n = 89 ) . Cilengitide was administered intravenously in combination with daily temozolomide ( TMZ ) and concomitant radiotherapy ( RT ; wk 1 - 6 ) , followed by TMZ maintenance therapy ( TMZ/RT→TMZ ) . The primary endpoint was overall survival ; secondary endpoints included progression-free survival , pharmacokinetics , and safety and tolerability . RESULTS Median overall survival was 16.3 months in the st and ard cilengitide arm ( hazard ratio [ HR ] , 0.686 ; 95 % CI : 0.484 , 0.972 ; P = .032 ) and 14.5 months in the intensive cilengitide arm ( HR , 0.858 ; 95 % CI : 0.612 , 1.204 ; P = .3771 ) versus 13.4 months in the control arm . Median progression-free survival assessed per independent review committee was 5.6 months ( HR , 0.822 ; 95 % CI : 0.595 , 1.134 ) and 5.9 months ( HR , 0.794 ; 95 % CI : 0.575 , 1.096 ) in the st and ard and intensive cilengitide arms , respectively , versus 4.1 months in the control arm . Cilengitide was well tolerated . CONCLUSIONS St and ard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ . Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study Background The prognosis of patients bearing high grade glioma remains dismal . Epidermal Growth Factor Receptor ( EGFR ) is well vali date d as a primary contributor of glioma initiation and progression . Nimotuzumab is a humanized monoclonal antibody that recognizes the EGFR extracellular domain and reaches Central Nervous System tumors , in non clinical and clinical setting . While it has similar activity when compared to other anti-EGFR antibodies , it does not induce skin toxicity or hypomagnesemia . Methods A r and omized , double blind , multicentric clinical trial was conducted in high grade glioma patients ( 41 anaplastic astrocytoma and 29 glioblastoma multiforme ) that received radiotherapy plus nimotuzumab or placebo . Treatment and placebo groups were well-balanced for the most important prognostic variables . Patients received 6 weekly doses of 200 mg nimotuzumab or placebo together with irradiation as induction therapy . Maintenance treatment was given for 1 year with subsequent doses administered every 3 weeks . The objectives of this study were to assess the comparative overall survival , progression free survival , response rate , immunogenicity and safety . Results The median cumulative dose was 3200 mg of nimotuzumab given over a median number of 16 doses . The combination of nimotuzumab and RT was well-tolerated . The most prevalent related adverse reactions included nausea , fever , tremors , anorexia and hepatic test alteration . No anti-idiotypic response was detected , confirming the antibody low immunogenicity . The mean and median survival time for subjects treated with nimotuzumab was 31.06 and 17.76 vs. 21.07 and 12.63 months for the control group . Conclusions In this r and omized trial , nimotuzumab showed an excellent safety profile and significant survival benefit in combination with irradiation . Trial registration Cuban National Register for clinical trials ( No. 1745 ) ( http://registroclinico.sld.cu/ensayos ) Summary Purpose Because raised matrix metalloprotease ( MMP ) levels are associated with glioma invasion and angiogenesis , we tested the efficacy of marimastat ( MT ) an orally active drug that can reduce MMP levels , in patients with gliomas . Patients and Methods A total of 162 patients with intracranial glioblastoma multiforme or gliosarcomas who had undergone surgery and radiotherapy participated in this multicenter , double-blind , placebo-controlled , parallel group study conducted at 20 institutions . Seventy-nine patients ( 57 male , 22 female , median age 58 years ) were r and omized to receive placebo ( PB ) , and 83 patients ( 51 male , 32 female , median age 57 years ) were r and omized to receive MT , 10 mg orally twice daily , until tumor progression . Results This intention-to-treat efficacy analysis showed no statistically significant difference between MT and PB groups with respect to survival ( P=0.38 , log rank test ) . The median survival time from protocol initiation was 37.9 weeks for the PB group and 42.9 weeks for the MT group , with a hazard ratio of 1.16 ( 95 % CI 0.83 to 1.60 ) . There were no statistically significant differences in quality of life between the PB and MT groups , as assessed by the FACT-BR question naire . Musculoskeletal toxicities led to dose modification or withdrawal in 20 % of MT-treated and 1.2 % of PB-treated patients . Conclusion MT does not improve survival in patients with glioblastoma or gliosarcoma following surgery and radiotherapy . Therefore , single-agent MT appears unwarranted ; however , MT in combination with cytotoxic chemotherapy may be warranted , as suggested by observations in our study and other studies BACKGROUND Few prospect i ve studies have assessed the role of bevacizumab and included a control arm with st and ard treatments for recurrent glioblastoma . We conducted a noncomparative phase II trial ( AVAREG ) to examine the efficacy of bevacizumab or fotemustine in this setting . METHODS Eligible patients were r and omized 2:1 to receive bevacizumab ( 10 mg/kg every 2 weeks ) or fotemustine ( 75 mg/m(2 ) on days 1 , 8 , and 15 , then 100 mg/m(2 ) every 3 weeks after a 35-day interval ) . The primary endpoint was 6-month overall survival ( OS ) rate ( OS-6 ) . No formal efficacy comparison was made between the treatment arms . RESULTS Ninety-one patients were enrolled ( bevacizumab n = 59 ; fotemustine n = 32 ) . Median age was 57 years ( range , 28 - 78 y ) , and patients had Eastern Cooperative Oncology Group performance status of 0 ( n = 42 ) , 1 ( n = 35 ) , or 2 ( n = 14 ) . OS-6 rate was 62.1 % ( 95 % confidence interval [ CI ] , 48.4 - 74.5 ) with bevacizumab and 73.3 % ( 95 % CI , 54.1 - 87.7 ) with fotemustine . OS-6 rates were lower in bevacizumab-treated patients with MGMT promoter methylated tumors than in those with unmethylated tumors ( 50 % and 85 % , respectively ) , but higher in fotemustine-treated patients ( 87.5 % and 50 % , respectively ) . OS rates at 9 months were 37.9 % ( 95 % CI , 25.5 - 51.6 ) and 46.7 % ( 95 % CI , 28.3 - 65.7 ) with bevacizumab and fotemustine , respectively , and median OS was 7.3 months ( 95 % CI , 5.8 - 9.2 ) and 8.7 months ( 95 % CI , 6.3 - 15.4 ) , respectively . Toxicity was as expected with the 2 agents . CONCLUSION Single-agent bevacizumab may have a role in patients with recurrent glioblastoma PURPOSE O6-methylguanine-methyltransferase ( MGMT ) promoter methylation has been shown to predict survival of patients with glioblastomas if temozolomide is added to radiotherapy ( RT ) . It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine , lomustine , and vincristine ( PCV ) chemotherapy in patients with anaplastic oligodendroglial tumors ( AOT ) . PATIENTS AND METHODS In the European Organisation for the Research and Treatment of Cancer study 26951 , 368 patients with AOT were r and omly assigned to either RT alone or to RT followed by adjuvant PCV . From 165 patients of this study , formalin-fixed , paraffin-embedded tumor tissue was available for MGMT promoter methylation analysis . This was investigated with methylation specific multiplex ligation-dependent probe amplification . RESULTS In 152 cases , an MGMT result was obtained , in 121 ( 80 % ) cases MGMT promoter methylation was observed . Methylation strongly correlated with combined loss of chromosome 1p and 19q loss ( P = .00043 ) . In multivariate analysis , MGMT promoter methylation , 1p/19q codeletion , tumor necrosis , and extent of resection were independent prognostic factors . The prognostic significance of MGMT promoter methylation was equally strong in the RT arm and the RT/PCV arm for both progression-free survival and overall survival . In tumors diagnosed at central pathology review as glioblastoma , no prognostic effect of MGMT promoter methylation was observed . CONCLUSION In this study , on patients with AOT MGMT promoter methylation was of prognostic significance and did not have predictive significance for outcome to adjuvant PCV chemotherapy . The biologic effect of MGMT promoter methylation or pathogenetic features associated with MGMT promoter methylation may be different for AOT compared with glioblastoma Optimal treatment of recurrent glioblastoma multiforme ( rGBM ) in elderly and /or frail patients remains virtually unexplored , the best supportive care ( BSC ) only is routinely administered due to the fatal prognosis . We evaluated the impact of different treatment methods on post-progression survival ( PPS ) and overall survival ( OS ) of such patients . Data from 98 elderly and /or frail rGBM patients , treated initially with 1-week or 3-week radiotherapy ( RT ) within the phase III IAEA study ( 2010–2013 ) , were analyzed . KPS at relapse and salvage treatment methods were recorded . Kaplan – Meier method was used to estimate PPS and OS for different treatment modalities . Eighty-four patients experienced recurrence : 47 ( 56 % ) received BSC , 21 ( 25 % ) —chemotherapy ( CHT ) , 8 ( 9.5 % ) —surgery , 3 ( 3.5 % ) —RT , for 5 ( 6 % ) the data was unavailable . Median OS from r and omization for all 84 patients was 35 weeks : 55 versus 30 weeks for any treatment versus BSC , p < 0.0001 . Median PPS was 15 weeks : 23 weeks with any treatment versus 9 weeks with BSC , p < 0.0001 . For local treatment ( surgery and /or RT ) median PPS was 51 versus 21 weeks for CHT , p = 0.36 . In patients with poor KPS ( ≤60 ) at relapse median PPS was 9 weeks with BSC versus 21 weeks with any treatment , p = 0.014 . In poor KPS patients median PPS for local treatment was 14 weeks versus 21 weeks with CHT , p = 0.88 . An active therapeutic approach may be beneficial for selected elderly and /or frail rGBM patients . Poor KPS patients may also benefit from active treatment , but there is no benefit of local treatment over CHT Purpose . To evaluate efficacy of short-course radiotherapy ( RT ) in elderly ( ≥60 years ) and frail [ Karnofsky performance status ( KPS ) 50–70 ] patients with glioblastoma multiforme ( GBM ) . Material s and methods . Between January 1987 and June 1993 , a total of 47 elderly and frail patients with histological diagnosis of GBM entered into a phase II study . RT alone was administered with tumor dose of 45 Gy in 15 daily fractions in 15 treatment days in 3 weeks to a target volume described as tumor visible on CT scan and a 2-cm margin . Results . Forty-four patients were evaluable for this analysis . There were 15 ( 34 % ) CR and 11 ( 25 % ) PR , making the overall response rate of 60 % . Median duration of response was 9 months ( range , 2–36 months ) . Improvement in pretreatment performance status was observed in 20/44 ( 45 % ) patients , 5 of which improved their KPS for 20 % . Median survival time is 9 months , and 1–4 year survival rates are 39 % , 6.8 % , 4.5 % , and 0 , respectively , while median time to tumor progression is 8 months , and 1–4 year progression-free survival rates are 30 % , 4.5 % , 4.5 % , and 0 , respectively . Females did significantly better than males , patients with KPS 60–70 did significantly better than those with KPS 50 , patients having tumors 4–5 cm did significantly better than those with tumors 6–8 cm as well as did those with more radical surgery when compared to those with biopsy only . On multivariate analysis , only tumor size and extent of surgery were found to independently influence survival . Acute toxicity was generally assessed as mild . One of the 12 ( 8 % ) autopsied patients had RT-induced brain necrosis . Conclusion This shortened RT appears to be an effective tool in palliation of elderly and frail patients with GBM . Further studies with more patients are needed before testing it against more aggressive treatment approaches in this patient population The results are reported of a small clinical trial carried out to assess the potential value of the hypoxic cell radiosensitizer misonidazole in the radiation treatment of Grade 3 and 4 supratentorial astrocytomas . A total of 55 patients were r and omly allocated to one of 3 treatment groups . No significant differences were seen between the median survivals of patients in the 2 control radiation groups and that of the third group in which oral misonidazole at a dose of 3 g/m2 preceded each of 4 weekly radiation doses . Possible reasons why no improvement was seen are discussed in detail PURPOSE Radiation Therapy Oncology Group trial 0525 tested whether dose-intensifying temozolomide versus st and ard chemoradiotherapy improves overall survival ( OS ) or progression-free survival ( PFS ) in newly diagnosed glioblastoma . Tests of neurocognitive function ( NCF ) and symptoms ( using the MD And erson Symptom Inventory-Brain Tumor module ; MDASI-BT ) and of quality of life ( European Organisation for the Research and Treatment of Cancer Quality of Life Question naire [ EORTC QLQ ] -C30/BN20 ) examined the net clinical benefit ( NCB ) of therapy . PATIENTS AND METHODS NCF tests ( Hopkins Verbal Learning Test-Revised , Trail Making Test , and Controlled Oral Word Association ) , MDASI-BT , and EORTC QLQ-C30/BN20 were completed in a subset of patients . Multivariate Cox proportional hazard regression modeling determined the prognostic value of baseline and early change from baseline to cycle 1 for OS and PFS . Two- sample proportional test statistic was used to evaluate differences between treatments ( dose-dense v st and ard-dose ) on NCB measures from baseline to cycle 4 in stable patients . RESULTS Overall , 182 patients participated in the study . Baseline NCF tests and the physical functioning quality of life scale were associated with OS and PFS . Baseline to cycle 1 in all NCB components were associated with OS and PFS . There was greater deterioration in the dose-dense arm from baseline to cycle 4 in the Global Health and Motor Function subscales ( EORTC QLQ-C30/BN20 ) as well as in overall symptom burden , overall symptom interference , and activity-related symptom interference subscales ( MDASI-BT ) . There were no between-arm differences in NCF . CONCLUSION Longitudinal collection of NCB measures is feasible in cooperative group studies and provides an added dimension to st and ard outcome measures . Greater adverse symptom burden and functional interference , as well as decreased global health and motor function were observed in patients r and omly assigned to the dose-dense arm . Baseline and early change in NCB measures were associated with decreased rates of survival Summary Purpose To test the efficacy of intra-arterial ( IA ) cisplatin versus intravenous ( IV ) PCNU for treating primary brain tumors , in a r and omized trial ( Brain Tumor Cooperative Group [ BTCG ] Trial 8420A ) . Methods 311 adult patients ( ages 19–79 years ; median 45 ) with supratentorial tumors ( confirmed histologically ) were r and omized by nine participating institutions . Patients were required to have completed radiotherapy ( 4500–6020 cGy to the tumor bed ) before r and omization . Patients were stratified as either nonprogressive ( clinical ly and radiologically stable ) or progressive . Results were analyzed for the 311 patients in the r and omized population ( RP ) , and for the 281 patients in the Valid Study Group ( VSG ) meeting protocol eligibility requirements . 56 % of patients in the VSG had glioblastoma multiforme , 33 % had other malignant glioma , and 11 % had low- grade glioma . 64 % were stratified as progressive . 12 % had received prior chemotherapy . Results The group r and omized to PCNU had the longer survival ( p = 0.06 for the RP , p = 0.07 for the VSG ) . In the VSG , median survival was 10 months for the cisplatin group , 13 months for the PCNU group . The difference between treatment groups was significant ( p ≤0.02 ) when adjusted for important prognostic factors . PCNU lead to greater hematotoxicity ; cisplatin lead to greater renal toxicity and some ototoxicity . Some cisplatin patients experienced complications associated with IA administration , including six cases of encephalopathy . Conclusion The trial showed a survival advantage to the group r and omized to PCNU , although the difference was modest . Coupled with previous BTCG results , these trials suggest that PCNU is an active drug for brain tumors PURPOSE The st and ard of care for anaplastic gliomas is surgery followed by radiotherapy . The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with the reverse sequence in patients with newly diagnosed anaplastic gliomas . PATIENTS AND METHODS Patients ( N = 318 ) were r and omly assigned 2:1:1 ( A : B1:B2 ) to receive conventional radiotherapy ( arm A ) ; procarbazine , lomustine ( CCNU ) , and vincristine ( PCV ; arm B1 ) ; or temozolomide ( arm B2 ) at diagnosis . At occurrence of unacceptable toxicity or disease progression , patients in arm A were treated with PCV or temozolomide ( 1:1 r and om assignment ) , whereas patients in arms B1 or B2 received radiotherapy . The primary end point was time to treatment failure ( TTF ) , defined as progression after radiotherapy and one chemotherapy in either sequence . RESULTS Patient characteristics in the intention-to-treat population ( n = 274 ) were balanced between arms . All histologic diagnoses were central ly confirmed . Median TTF ( hazard ratio [ HR ] = 1.2 ; 95 % CI , 0.8 to 1.8 ) , progression-free survival ( PFS ; HR = 1.0 ; 95 % CI , 0.7 to 1.3 , and overall survival ( HR = 1.2 ; 95 % CI , 0.8 to 1.9 ) were similar for arms A and B1/B2 . Extent of resection was an important prognosticator . Anaplastic oligodendrogliomas and oligoastrocytomas share the same , better prognosis than anaplastic astrocytomas . Hypermethylation of the O(6)-methylguanine DNA-methyltransferase ( MGMT ) promoter ( HR = 0.59 ; 95 % CI , 0.36 to 1.0 ) , mutations of the isocitrate dehydrogenase ( IDH1 ) gene ( HR = 0.48 ; 95 % CI , 0.29 to 0.77 ) , and oligodendroglial histology ( HR = 0.33 ; 95 % CI , 0.2 to 0.55 ) reduced the risk of progression . Hypermethylation of the MGMT promoter was associated with prolonged PFS in the chemotherapy and radiotherapy arm . CONCLUSION Initial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas . IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas , with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation PURPOSE In patients with newly diagnosed glioblastoma multiforme , to determine whether cisplatin plus carmustine ( BCNU ) administered before and concurrently with radiation therapy ( RT ) improves survival compared with BCNU and RT and whether survival using accelerated RT ( ART ) is equivalent to survival using st and ard RT ( SRT ) . PATIENTS AND METHODS After surgery , patients were stratified by age , performance score , extent of surgical resection , and histology ( glioblastoma v gliosarcoma ) and then r and omly assigned to arm A ( BCNU plus SRT ) , arm B ( BCNU plus ART ) , arm C ( cisplatin plus BCNU plus SRT ) , or arm D ( cisplatin plus BCNU plus ART ) . RESULTS Four hundred fifty-one patients were r and omly assigned , and 401 were eligible . Frequent toxicities included myelosuppression , vomiting , sensory neuropathy , and ototoxicity and were worse with cisplatin . There was no difference in toxicity between SRT and ART . Median survival times and 2-year survival rates for patients who received BCNU plus RT ( arms A and B ) compared with cisplatin , BCNU , and RT ( arms C and D ) were 10.1 v 11.5 months , respectively , and 11.5 % v 13.7 % , respectively ( P = .19 ) . Median survival times and 2-year survival rates for patients who received SRT ( arms A and C ) compared with ART ( arms B and D ) were 11.2 v 10.5 months , respectively , and 13.8 % v 11.4 % , respectively ( P = .33 ) . CONCLUSION Cisplatin administered concurrently with BCNU and RT result ed in more toxicity but provided no significant improvement in survival . SRT and ART produced similar toxicity and survival Recently , the RTOG and ECOG concluded a joint r and omized study on malignant gliomas that was in progress for the past five years . A total of 626 patients entered this protocol . Sixty‐seven percent of the 535 evaluable patients have died and thus this represents a preliminary report of a major joint clinical trial . The objective of this study was to evaluate the efficacy after neurosurgery of three new treatment options as compared with control treatment of radiotherapy alone . The four options were : ( 1 ) control radiation ; 6000 rad/6–7 weeks to whole brain ; ( 2 ) a higher radiation dose ; Control dose plus a booster dose of 1000 rad/1–2 weeks to the tumor ; ( 3 ) control radiation dose plus BCNU ( 80 mg/m2/day IV X 3 and repeat BCNU every 8 weeks ) ; ( 4 ) Control radiation dose plus combination methyl‐CCNU ( 125 mg/m2/day orally X 1 and repeat methyl‐CCNU every 8 weeks ) , and DTIC ( 150 mg/m2/day IV X 5 and repeat DTIC every 4 weeks ) . All pertinent patient characteristics were studied and several important prognostic factors have been identified . Notably , age , histologic type ( Astrocytoma with anaplastic foci , versus glioblastoma multiforme ) , initial performance status , time since first symptoms and presence or absence of seizure . At this time , it appeared that there was no treatment option which was significantly better than the control . The study identified that age was the most important prognostic factor . Patients who were younger than age 40 years had an 18‐month survival of 64 % , patients who were age 40–60 years had an 18‐month survival of 20 % , and patients who were older than age 60 had an 18‐month survival of 8 % . The study also demonstrated that a modified histologic classification of anaplastic astrocytoma versus glioblastoma provided better prognostic information than the astrocytoma grading system of Kernohan . Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma . In further evaluation of any beneficial effect of chemotherapy , it was identified that only among the 40–60‐year‐old groups , BCNU treated patients appeared to have significantly increased survival than patients in the control groups ( P = 0.01 , one‐sided ) . Similarly , methyl‐CCNU + DTIC was suggestively better than the control ( P = 0.08 , one‐sided ) . The higher radiation dose , 7000 rad/8–9 weeks appeared to give no significantly better survival over the control dose option . Both BCNU and methyl‐CCNU + DTIC produced some toxicity . The combination of methyl‐CCNU + DTIC was more toxic than BCNU , producing severe or worse thrombocytopenia in 23 % of the patients as compared to 6 % on BCNU In Brain Tumor Cooperative Group Study 77 - 02 , eleven institutions r and omized 603 adult patients with supratentorial malignant glioma to one of four treatment groups following surgery : conventional radiotherapy ( 6000 cGy in 30 - 35 fractions ) + BCNU , conventional radiotherapy + streptozotocin , hyperfractionated ( twice daily ) radiotherapy ( 6600 cGy in 60 fractions ) + BCNU , and conventional radiotherapy with misonidazole followed by BCNU . Data were analyzed for the total r and omized population and for the 557 patients ( 86 % with glioblastoma multiforme ) who met protocol eligibility specifications ( including confirmed histopathology on central review ) . Median survival was approximately 10 months following r and omization . Overall there was no statistically significant difference in survival among the four groups . Among non-glioblastoma patients , the misonidazole group appeared to have poor survival . Peripheral neuropathy was a dose-limiting toxicity with misonidazole . It is concluded that neither the addition of misonidazole nor hyperfractionated radiotherapy as given in this protocol offered any advantage over conventional radiotherapy plus either BCNU or streptozotocin for treatment of malignant glioma A total of 474 adult patients with malignant glioma ( astrocytoma ) grade 3 or 4 were r and omised into an MRC study ( BR2 ) comparing 45 Gy ( in 20 fractions over 4 weeks ) with 60 Gy ( in 30 fractions over 6 weeks ) of radiotherapy given post-operatively . Using 2:1 r and omisation , 318 patients were allocated the 60 Gy course and 156 the 45 Gy course . Adjuvant chemotherapy was not given . The results show that a 60 Gy course produces a modest lengthening of progression-free and overall survival . They suggest a statistically significant prolongation of median survival from 9 months in the 45 Gy group to 12 months in the 60 Gy group ( hazard ratio = 0.75 , chi 2 = 7.36 , d.f . = 1 , P = 0.007 ) . Over 80 % of patients reported no morbidity from the radiotherapy , and there was no evidence of increased short-term morbidity in the higher dose group . Late morbidity was not assessed . A prognostic index defined in a previous MRC study was vali date d in this new cohort . It identifies a group of patients ( 20 % of the total ) with a 2 year survival rate of 28 % ( 95 % confidence interval 19 % to 38 % ) . It was apparent that the survival advantage to the higher dose was maintained even in the poorest prognostic groups defined by this index A prospect i ve r and omized study of 108 patients with cerebral malignant gliomas was carried out at the Department of Radiation Oncology of Maria Sklodowska-Curie Memorial Center in Kraków . 44 patients with histologically proven glioblastoma multiforme and 64 patients with anaplastic astrocytoma received postoperative radiotherapy . Patients were r and omized to two treatment arms : Conventionally Fractionated Radiotherapy ( CFR ) and Hypofractionated Radiotherapy ( HF ) . In the CFR group , the whole brain was irradiated to the total dose of 50 Gy in 25 fractions over 5 weeks , then a 10 Gy ‘ boost ’ in 5 fractions in 5 days was delivered to the site of the primary lesion . In the HF group , there were 3 courses of irradiation separated by a one month interval . In each of the two first series the patients received 20 Gy in 5 fractions in 5 days to the whole brain , and in the third course , 10 Gy ‘ boost ’ in 5 days was delivered as in the CFR regimen . The tolerance to treatment has been found to be good in both groups . The 2-year actuarial survival rate for patients with anaplastic astrocytoma was 22 % for CFR and 18 % for HF . Patients with glioblastoma multiforme treated with HF had a better prognosis in comparison to the CFR group with the two-year actuarial survival rates being 23 % and 10 % , respectively . This difference is statistically significant at the 0.05 level Summary Purpose : To assess the effect of cisplatin ( CDDP ) plus concurrent radiation therapy on hearing loss . Methods : 451 patients with glioblastoma multiforme ( GBM ) were r and omly assigned after surgery to : Arm A : Carmustine ( BCNU ) + st and ard radiation therapy ( SRT ) ; Arm B : BCNU + accelerated radiation therapy ( ART : 160 cGy twice daily for 15 days ) ; Arm C : CDDP + BCNU + SRT ; or Arm D : CDDP + BCNU + ART . Patients on arms C and D received audiograms at baseline , and prior to the start of RT , and prior to cycles 3 and 6 . Otologic toxicities were recorded at each visit . Results : 56 % of patients had hearing loss at baseline . 13 % and 50 % of patients experienced worsening ototoxicity after 1 year of treatment in arms A and B vs. C and D , respectively , with 13 % of those on arms C and D experiencing significant ototoxicity ( ≥ grade 3 ) at 6 months . Increasing age was associated with an increased risk of ototoxicity . Conclusions : Increased exposure to CDDP increases the risk of ototoxicity over time . Older patients are more susceptible to hearing loss with CDDP . The low proportion of patients with clinical ly significant ototoxicity suggests that baseline screening is unnecessary in GBM patients A r and omized study investigating the value of misonidazole in patients irradiated for grade III and IV supratentorial astrocytomas was started in June 1977 . With a minimum follow-up time of 6 months , 45 patients who completed therapy are available for analysis . All patients received the same radiation treatment ( 66.5 Gy in 31 fractions over 7.5 weeks , field size reduction after 45 Gy ) . In the first , second and eighth week , a 4 Gy tumor dose was given on Monday and Thursday . Misonidazole was given 4 hours before irradiation to 18 r and omized patients on those 6 treatment days ( 2.1 - 2.7 g/m2 per treatment day ) . Daily tumor doses of 1.7 Gy were administered Monday through Friday from the third until the seventh week . Median survival for patients treated with misonidazole is 13.8 months ; for those treated by irradiation alone it was 9.8 months . The corresponding 1 year survival rates are 64 and 25 % , respectively . Survival plots indicate some advantage for the patients treated with misonidazole , however statistically there is no significant difference observed ( p greater than 0.08 ) . There are no significant differences in Karnofsky performance status , sex and in histological grade or in age distribution between the groups . However , the type of surgery ( complete or subtotal ) influenced survival markedly : patients with complete surgery lived significantly longer ( p less than 0.0009 ) . Neurotoxic side effects of misonidazole were minimal Background : Anaplastic astrocytomas ( AA ) and glioblastomas ( GB ) are the most common malignant gliomas , and despite newly developed drugs and combined treatments , they still have an adverse prognosis . Paclitaxel is a cytotoxic agent with radiosensitizing properties and exerts objective growth inhibition in glioma tumor cells . Patients and Methods : From 1998 to 2002 , 61 microneurosurgically treated patients were r and omized to group I ( 18 GB , 14 AA ) which received radiotherapy and weekly paclitaxel at dose of 100 mg/m2 , and group II ( 21 GB , 8 AA ) which received only radiotherapy as a complementary treatment . Results : Median overall survival was 27.96 months in group I and 23.06 months in group II with no statistical difference . The 12-month survival was 81 % in group I and 76 % in group II . Kaplan-Meier curves of both groups did not demonstrate any difference . Analysis of each histological subgroup ( AA or GB ) also showed no statistical difference in the survival curves . All 427 cycles were well tolerated with no treatment-associated deaths . Conclusions : Chemoradiotherapy with weekly paclitaxel is safe and tolerable although there was no increase in the overall survival and 12-month survival of malignant glioma patients . Further investigations modulating the paclitaxel entrance and delivery into the brain should be encouraged Cytomegalovirus is highly prevalent in glioblastomas . In 2006 , we initiated a r and omized , double-blind , placebo-controlled , hypothesis-generating study to examine the safety and potential efficacy of Valganciclovir as an add-on therapy for glioblastoma . Forty-two glioblastoma patients were r and omized in double-blind fashion to receive Valganciclovir or placebo in addition to st and ard therapy for 6 months . Magnetic resonance images were obtained before and immediately and 3 and 6 months after surgery to evaluate treatment efficacy by measuring contrast enhancing tumor volume ( primary end point ) . Survival data were analyzed for patients and controls in explorative analyses to aid the design of future r and omized trials . Trends but no significant differences were observed in tumor volumes in Valganciclovir and placebo patients at 3 ( 3.58 vs. 7.44 cm3 , respectively , p = 0.2881 ) and 6 ( 3.31 vs. 13.75 cm3 , p = 0.2120 ) months . Median overall survival ( OS ) was similar in both groups ( 17.9 vs. 17.4 months , p = 0.430 ) . Patients could take Valganciclovir for compassionate use after the study phase . Explorative analyses showed an OS of 24.1 months ( 95 % CI , 17.4 - 40.3 ) in patients receiving > 6 months of Valganciclovir ( Val > 6 M ) versus 13.1 months ( 95 % CI , 7.9 - 17.7 , p < 0.0001 ) in patients receiving Valganciclovir for 0 or < 6 months , and 13.7 months ( 95 % CI , 6.9 - 17.3 , p = 0.0031 ) in contemporary controls . OS at 4 years was 27.3 % in Val>6 M patients versus 5.9 % in controls ( p = 0.0466 ) . Prolonged OS in Val>6 M patients suggest that future r and omized trials are warranted and should evaluate whether continuous antiviral treatment can improve outcome in glioblastoma patients BACKGROUND Radiotherapy is the st and ard care in elderly patients with malignant astrocytoma and the role of primary chemotherapy is poorly defined . We did a r and omised trial to compare the efficacy and safety of dose-dense temozolomide alone versus radiotherapy alone in elderly patients with anaplastic astrocytoma or glioblastoma . METHODS Between May 15 , 2005 , and Nov 2 , 2009 , we enrolled patients with confirmed anaplastic astrocytoma or glioblastoma , age older than 65 years , and a Karnofsky performance score of 60 or higher . Patients were r and omly assigned 100 mg/m(2 ) temozolomide , given on days 1 - 7 of 1 week on , 1 week off cycles , or radiotherapy of 60·0 Gy , administered over 6 - 7 weeks in 30 fractions of 1·8 - 2·0 Gy . The primary endpoint was overall survival . We assessed non-inferiority with a 25 % margin , analysed for all patients who received at least one dose of assigned treatment . This trial is registered with Clinical Trials.gov , number NCT01502241 . FINDINGS Of 584 patients screened , we enrolled 412 . 373 patients ( 195 r and omly allocated to the temozolomide group and 178 to the radiotherapy group ) received at least one dose of treatment and were included in efficacy analyses . Median overall survival was 8·6 months ( 95 % CI 7·3 - 10·2 ) in the temozolomide group versus 9·6 months ( 8·2 - 10·8 ) in the radiotherapy group ( hazard ratio [ HR ] 1·09 , 95 % CI 0·84 - 1·42 , p(non-inferiority)=0·033 ) . Median event-free survival ( EFS ) did not differ significantly between the temozolomide and radiotherapy groups ( 3·3 months [ 95 % CI 3·2 - 4·1 ] vs 4·7 [ 4·2 - 5·2 ] ; HR 1·15 , 95 % CI 0·92 - 1·43 , p(non-inferiority)=0·043 ) . Tumour MGMT promoter methylation was seen in 73 ( 35 % ) of 209 patients tested . MGMT promoter methylation was associated with longer overall survival than was unmethylated status ( 11·9 months [ 95 % CI 9·0 to not reached ] vs 8·2 months [ 7·0 - 10·0 ] ; HR 0·62 , 95 % CI 0·42 - 0·91 , p=0·014 ) . EFS was longer in patients with MGMT promoter methylation who received temozolomide than in those who underwent radiotherapy ( 8·4 months [ 95e% CI 5·5 - 11·7 ] vs 4·6 [ 4·2 - 5·0 ] ) , whereas the opposite was true for patients with no methylation of the MGMT promoter ( 3·3 months [ 3·0 - 3·5 ] vs 4·6 months [ 3·7 - 6·3 ] ) . The most frequent grade 3 - 4 intervention-related adverse events were neutropenia ( 16 patients in the temozolomide group vs two in the radiotherapy group ) , lymphocytopenia ( 46 vs one ) , thrombocytopenia ( 14 vs four ) , raised liver-enzyme concentrations ( 30 vs 16 ) , infections ( 35 vs 23 ) , and thromboembolic events ( 24 vs eight ) . INTERPRETATION Temozolomide alone is non-inferior to radiotherapy alone in the treatment of elderly patients with malignant astrocytoma . MGMT promoter methylation seems to be a useful biomarker for outcomes by treatment and could aid decision-making . FUNDING Merck Sharp & Dohme Purpose In view of the documented toxicity of continuous daily radiosensitizer doses of temozolomide concomitant with radiation in the treatment of glioblastoma multiforme , we aim ed to compare it with a different schedule of abbreviated radiosensitizer dosing . Patients and methods This was a r and omized prospect i ve study comparing toxicity and survival in 60 Egyptian patients with glioblastoma multiforme . Patients in arm I received temozolomide at a dose of 75 mg/m2 daily with radiotherapy for 42 days , starting 4 weeks after surgery and reaching to a total radiation dose of 60 Gy/30 Fractions/6 weeks , while patients in arm II received temozolomide at a dose of 75 mg/m2 concomitantly with the same radiotherapy schedule daily in the first and last weeks of the same radiotherapy program . Results Common grade 1–2 adverse events were malaise in 28 patients ( 46.7 % ) , followed by alopecia ( 40 % ) and nausea ( 26.7 % ) . Grade 3–4 convulsion and decreased level of consciousness was seen in only four patients who were all from arm I. The median progression-free survival ( PFS ) for the entire study population was 10.6 months ( 95 % confidence interval [ CI ] 7.3–14 ) , and PFS at 12 months was 32 % . The median PFS in arm I was 8.8 months ( 95 % CI 5.9–11.7 ) and in arm II 11.5 months ( 95 % CI 8.9–14.2 ) , and PFS at 12 months for both arms was 32 % and 30 % respectively ( P=0.571 ) . The median overall survival ( OS ) of the whole group of patients was 14.2 months ( 95 % CI 13–15.5 ) , and OS was 70 % at 12 months and 25 % at 18 months . The median OS for patients in arm I was 12.3 months ( 95 % CI 7.7–16.9 ) , whereas in arm II it was 14.3 months ( 95 % CI 14–14.7 ) ( P=0.83 ) . Conclusion Reduced radiosensitizer dosing of temozolomide concomitant with radiotherapy in glioblastoma multiforme exhibited comparable efficacy with a classic continuous daily schedule , though with better tolerability IMPORTANCE Glioblastoma is the most devastating primary malignancy of the central nervous system in adults . Most patients die within 1 to 2 years of diagnosis . Tumor-treating fields ( TTFields ) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly . OBJECTIVE To evaluate the efficacy and safety of TTFields used in combination with temozolomide maintenance treatment after chemoradiation therapy for patients with glioblastoma . DESIGN , SETTING , AND PARTICIPANTS After completion of chemoradiotherapy , patients with glioblastoma were r and omized ( 2:1 ) to receive maintenance treatment with either TTFields plus temozolomide ( n = 466 ) or temozolomide alone ( n = 229 ) ( median time from diagnosis to r and omization , 3.8 months in both groups ) . The study enrolled 695 of the planned 700 patients between July 2009 and November 2014 at 83 centers in the United States , Canada , Europe , Israel , and South Korea . The trial was terminated based on the results of this planned interim analysis . INTERVENTIONS Treatment with TTFields was delivered continuously ( > 18 hours/day ) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device . Temozolomide ( 150 - 200 mg/m2/d ) was given for 5 days of each 28-day cycle . MAIN OUTCOMES AND MEASURES The primary end point was progression-free survival in the intent-to-treat population ( significance threshold of .01 ) with overall survival in the per- protocol population ( n = 280 ) as a powered secondary end point ( significance threshold of .006 ) . This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up . RESULTS The interim analysis included 210 patients r and omized to TTFields plus temozolomide and 105 r and omized to temozolomide alone , and was conducted at a median follow-up of 38 months ( range , 18 - 60 months ) . Median progression-free survival in the intent-to-treat population was 7.1 months ( 95 % CI , 5.9 - 8.2 months ) in the TTFields plus temozolomide group and 4.0 months ( 95 % CI , 3.3 - 5.2 months ) in the temozolomide alone group ( hazard ratio [ HR ] , 0.62 [ 98.7 % CI , 0.43 - 0.89 ] ; P = .001 ) . Median overall survival in the per- protocol population was 20.5 months ( 95 % CI , 16.7 - 25.0 months ) in the TTFields plus temozolomide group ( n = 196 ) and 15.6 months ( 95 % CI , 13.3 - 19.1 months ) in the temozolomide alone group ( n = 84 ) ( HR , 0.64 [ 99.4 % CI , 0.42 - 0.98 ] ; P = .004 ) . CONCLUSIONS AND RELEVANCE In this interim analysis of 315 patients with glioblastoma who had completed st and ard chemoradiation therapy , adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00916409 Purpose : V and etanib , a tyrosine kinase inhibitor of KDR ( VEGFR2 ) , EGFR , and RET , may enhance sensitivity to chemotherapy and radiation . We conducted a r and omized , noncomparative , phase II study of radiation ( RT ) and temozolomide with or without v and etanib in patients with newly diagnosed glioblastoma ( GBM ) . Experimental Design : We planned to r and omize a total of 114 newly diagnosed GBM patients in a ratio of 2:1 to st and ard RT and temozolomide with ( 76 patients ) or without ( 38 patients ) v and etanib 100 mg daily . Patients with age ≥ 18 years , Karnofsky performance status ( KPS ) ≥ 60 , and not on enzyme-inducing antiepileptics were eligible . Primary endpoint was median overall survival ( OS ) from the date of r and omization . Secondary endpoints included median progression-free survival ( PFS ) , 12-month PFS , and safety . Correlative studies included pharmacokinetics as well as tissue and serum biomarker analysis . Results : The study was terminated early for futility based on the results of an interim analysis . We enrolled 106 patients ( 36 in the RT/temozolomide arm and 70 in the v and etanib/RT/temozolomide arm ) . Median OS was 15.9 months [ 95 % confidence interval ( CI ) , 11.0–22.5 months ] in the RT/temozolomide arm and 16.6 months ( 95 % CI , 14.9–20.1 months ) in the v and etanib/RT/temozolomide ( log-rank P = 0.75 ) . Conclusions : The addition of v and etanib at a dose of 100 mg daily to st and ard chemoradiation in patients with newly diagnosed GBM or gliosarcoma was associated with potential pharmacodynamic biomarker changes and was reasonably well tolerated . However , the regimen did not significantly prolong OS compared with the parallel control arm , leading to early termination of the study . Clin Cancer Res ; 21(16 ) ; 3610–8 . © 2015 AACR Background : The radiochemotherapy regimen concomitantly employing temozolomide ( TMZ ) chemotherapy and radiotherapy ( RT ) 4 weeks after surgery , followed by 6 cycles of TMZ is a common treatment for glioblastoma ( GBM ) . However , its median overall survival ( OS ) is only 14.6 months . This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the st and ard concomitant radiochemotherapy regimen . Methods : A r and omized , parallel group , open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012 . Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide ( early TMZ group ) or st and ard concomitant radiochemotherapy regimen ( control group ) . Overall response was assessed based on objective tumor assessment s , administration of corticosteroid and neurological status test . Hematological , biochemical , laboratory , adverse event ( AE ) , and neurological condition were measured for 24 months of follow-up . The primary efficacy endpoint of this study was overall survival ( OS ) . The secondary endpoint was progression free survival ( PFS ) . Results : The median OS time in the early TMZ group was 17.6 months , compared with 13.2 months in the control group ( log-rank test P = 0.021 ) . In addition , the OS rate in the early TMZ group was higher at 6 , 12 , and 18 months than in the control group , respectively ( P < 0.05 ) . The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group ( log-rank test P = 0.695 ) . AEs occurred in 29 ( 55.8 % ) and 31(73.8 % ) patients respectively in early and control groups , including nausea ( 15.4 % vs. 33.3 % ) , vomiting ( 7.7 % vs. 28.6 % ) , fever ( 7.7 % vs. 11.9 % ) , and headache ( 3.8 % vs. 23.8 % ) . Only 30.8 % and 33.3 % were drug-related , respectively . Conclusions : Addition of TMZ chemotherapy in the early break of the st and ard concomitant radiochemotherapy regimen was well tolerated and significantly improved the OS of the GBM patients , compared with st and ard concomitant radiochemotherapy regimen . However , a larger r and omized trial is warranted to verify these results An attempt was made to evaluate the potential advantages of chemotherapy in the treatment of 62 patients with glioblastoma . Twenty-four of the 62 patients received adjuvant nitrosourea chemotherapy with carmustine ( BCNU ) , lomustine ( CCNU ) , or semustine ( methyl CCCNU ) in addition to surgery and radiotherapy . Thirty-three of the 62 patients were involved in a controlled , prospect i ve , r and omly allocated study . Quality or quantity of survival was not prolonged in patients who received chemotherapy . Age greater than 64 years , a severe postoperative neurological deficit , or the onset of symptoms less than 12 months prior to surgery were associated with a worse prognosis . The valid evaluation of the effect of a form of treatment on survival in patients with glioblastoma is contingent on the regorous avoidance of preselected factors that may predispose the treated group to a more favorable prognosis Glioblastoma multiforme ( GBM ) carries dismal prognosis and can not be eradicated surgically because of its wide brain invasion . The objective of this prospect i ve r and omised controlled trial was to evaluate ALA and Photofrin ® fluorescence-guided resection ( FGR ) and repetitive photodynamic therapy ( PDT ) in GBM . We recruited 27 patients ; 13 were in the study group and 14 were in the control group . The mean survival of the study group was 52.8 weeks compared to 24.6 weeks in the control group ( p < 0.01 ) . The study group gained on average 20 points on the Karnofsky performance score ( p < 0.05 ) . There were no differences in complications or hospital stay between the two groups . The mean time to tumour progression was 8.6 months in the study group compared to 4.8 months in the control group ( p < 0.05 ) . Therefore , ALA and Photofrin ® fluorescence-guided resection and repetitive PDT offered a worthwhile survival advantage without added risk to patients with GBM . A multicentre r and omized controlled trial is warranted to confirm these results The study aim ed to compare the cost‐effectiveness of concomitant and adjuvant temozolomide ( TMZ ) for the treatment of newly diagnosed glioblastoma multiforme versus initial radiotherapy alone from a public health care perspective Purpose : EORTC 26082 assessed the activity of temsirolimus in patients with newly diagnosed glioblastoma harboring an unmethylated O6 methylguanine-DNA-methyltransferase ( MGMT ) promoter . Experimental Design : Patients ( n = 257 ) fulfilling eligibility criteria underwent central MGMT testing . Patients with MGMT unmethylated glioblastoma ( n = 111 ) were r and omized 1:1 between st and ard chemo-radiotherapy with temozolomide or radiotherapy plus weekly temsirolimus ( 25 mg ) . Primary endpoint was overall survival at 12 months ( OS12 ) . A positive signal was considered > 38 patients alive at 12 months in the per protocol population . A noncomparative reference arm of 54 patients evaluated the assumptions on OS12 in a st and ard-treated cohort of patients . Prespecified post hoc analyses of markers reflecting target activation were performed . Results : Both therapies were administered per protocol with a median of 13 cycles of maintenance temsirolimus . Median age was 55 and 58 years in the temsirolimus and st and ard arms , the WHO performance status 0 or 1 for most patients ( 95.5 % ) . In the per protocol population , 38 of 54 patients treated with temsirolimus reached OS12 . The actuarial 1-year survival was 72.2 % [ 95 % confidence interval ( CI ) , 58.2–82.2 ] in the temozolomide arm and 69.6 % ( 95 % CI , 55.8–79.9 ) in the temsirolimus arm [ hazard ratio ( HR ) 1.16 ; 95 % CI , 0.77–1.76 ; P = 0.47 ] . In multivariable prognostic analyses of clinical and molecular factors , phosphorylation of mTORSer2448 in tumor tissue ( HR 0.13 ; 95 % CI , 0.04–0.47 ; P = 0.002 ) , detected in 37.6 % , was associated with benefit from temsirolimus . Conclusions : Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter . Phosphorylation of mTORSer2448 in the pretreatment tumor tissue may define a subgroup benefitting from mTOR inhibition . Clin Cancer Res ; 22(19 ) ; 4797–806 . © 2016 AACR A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea ( BCNU ) wafers ( Gliadel wafers ) prolong survival in patients with recurrent glioblastoma multiforme . A previously completed phase 3 trial , also placebo controlled , in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers . Because of the small number of patients in that trial , a larger phase 3 trial was performed to confirm these results . Two hundred forty patients were r and omized to receive either BCNU or placebo wafers at the time of primary surgical resection ; both groups were treated with external beam radiation postoperatively . The two groups were similar for age , sex , Karnofsky performance status ( KPS ) , and tumor histology . Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group ( log-rank P -value stratified by country = 0.03 ) , with a 29 % reduction in the risk of death in the treatment group . When adjusted for factors affecting survival , the treatment effect remained positive with a risk reduction of 28 % ( P = 0.03 ) . Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group ( P < /= 0.05 ) . Adverse events were comparable for the 2 groups , except for CSF leak ( 5 % in the BCNU wafer-treated group vs. 0.8 % in the placebo-treated group ) and intracranial hypertension ( 9.1 % in the BCNU wafer-treated group vs. 1.7 % in the placebo group ) . This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma Multiple daily fractionated radiation therapy ( MDF ) may be more effective than conventionally fractionated radiation therapy ( CF ) in the treatment of malignant glioma . The hypoxic cell sensitizer misonidazole ( MISO ) could be more effective when employed with small fractions of radiation every 4 hours to take advantage of the long half-life of the drug . To evaluate MDF and MDF in combination with MISO , a r and omized prospect i ve trial was initiated . Between January 1981 , and December 1982 , patients with histologically verified astrocytoma with anaplastic foci or glioblastoma multiforme were r and omized to CF ( 5800 cGy , 30 fractions , 6 weeks ) , MDF ( 6141 cGy , 69 fractions , 4 1/2 weeks , at 89 cGy every 4 hours 3 times daily ) and MDF in combination with MISO ( 1.25 gm/M2 three times weekly for the first 3 weeks ) . In January 1983 , the CF arm was dropped and a high dose MDF arm added ( 7120 cGy , 80 fractions , 5 1/2 weeks , at 89 cGy per fraction every 4 hours 3 times daily ) . CCNU chemotherapy was given at the time of tumor progression . One hundred and twenty-eight patients were evaluated ( 38 CF , 42 MDF , 37 MDF plus MISO , and 11 high dose MDF ) . Median survival was 29 weeks for CF , 45 weeks for MDF and 50 weeks for MDF plus MISO . Survival was significantly improved for patients treated with MDF compared to patients treated with CF ( p less than .002 ) . The addition of MISO to MDF did not result in further improvement in survival . Acute toxicity was acceptable . No clinical ly apparent delayed toxicity was observed Summary . Background : Patients with radiologically ( MRI and /or CT images ) suspected malignant glioma is referred to radiotherapy after craniotomy and resection of the tumour or after diagnostic biopsy . Patients with poor preoperative status and elderly patients are diagnosed more often by biopsy and treated by radiotherapy rather than by craniotomy and tumour resection . However , based on previous retrospective studies it is not possible to conclude which procedure is better for elderly patients . Thus a prospect i ve study comparing these two procedures with elderly patients was planned . Methods : 30 patients older than 65 years with radiologically ( CT and /or MRI ) obvious malignant glioma were r and omised into two groups : I ) stereotactic biopsy and II ) open craniotomy and resection of the tumour . Nineteen patients were diagnosed to have grade IV glioma and four patients grade III glioma . Seven out of 30 ( 23 % ) were followed in the “ intention-to-treat ” group with diagnosis of stroke ( n=3 ) , metastasis ( n=2 ) , malignant lymphoma ( n=1 ) and one with out histological diagnosis . Patients with histologically verified malignant glioma ( grade III – IV ) were diagnosed by stereotactic biopsy ( n=13 ) or by open craniotomy and resection ( n=10 ) and all the patients were referred to radiotherapy . Survival and time of deterioration were followed . Findings : The overall median survival time was 146 ( 95 % CI 89–175 ) days after the procedure . The estimated median survival time was 171 ( 95 % CI 146–278 ) days after the craniotomy versus 85 ( 95 % CI 55–157 ) days after the biopsy ( p=0.035 ) . The estimated survival time was 2.757 times longer ( 95 % CI 1.004–7.568 , p=0.049 ) after craniotomy . However , there was no significant difference in the time of deterioration between these two treatments ( p=0.057 ) . Amount of radiotherapy given had a significant effect on survival ( p=0.001 ) . Interpretation : Longer survival time is achieved after open craniotomy and resection of tumour . However , overall benefit of open surgery to patient seems to be modest , while time of deterioration did not differ between two treatment groups . Our results support previous studies on the benefit of radiotherapy in the treatment of malignant glioma Malignant glioma patients were prospect ively enrolled into a clinical trial . All the patients were provided with the internationally recommended oncologic st and ard treatment ( neurosurgery , radiation , basic clinical care according to protocol and indication ) and r and omly divided into a treatment group ( receiving complementary immunotherapy with a galactoside-specific lectin from mistletoe , ML-1 ) and a control group ( without additional complementary treatment ) . Whereas the beneficial effects of ML-1 treatment on immunological rescue and quality of life have been recently shown , evaluation of relapse free/overall survival was performed after a 50 months follow up time . Non-stratified analysis of all the patients revealed non-relevant prolongation of relapse-free intervals/overall survival time for the treatment group . However , analysis of stratified stage III/IV glioma patients demonstrated : 1 . a tendency for a prolongation of relapse-free survival for patients of the treatment group ( 17.43 + /- 8.2 months ) vs. the control group ( 10.45 + /- 3.9 months ) 2 . a statistically significant ( BRESLOW p = 0.035 ) prolongation of the overall survival for the treatment group ( 20.05 + /- 3.5 months ) as compared to the control group ( 9.90 + /- 2.1 months ) . These promising data warrant confirmation in a GCP-based prospect ively r and omized ( multicenter ) study , which is currently under consideration BACKGROUND There is no community st and ard for the treatment of glioblastoma in patients 70 years of age or older . We conducted a r and omized trial that compared radiotherapy and supportive care with supportive care alone in such patients . METHODS Patients 70 years of age or older with a newly diagnosed anaplastic astrocytoma or glioblastoma and a Karnofsky performance score of 70 or higher were r and omly assigned to receive supportive care only or supportive care plus radiotherapy ( focal radiation in daily fractions of 1.8 Gy given 5 days per week , for a total dose of 50 Gy ) . The primary end point was overall survival ; secondary end points were progression-free survival , tolerance of radiotherapy , health-related quality of life , and cognition . RESULTS We r and omly assigned 85 patients from 10 centers to receive either radiotherapy and supportive care or supportive care alone . The trial was discontinued at the first interim analysis , which showed that with a preset boundary of efficacy , radiotherapy and supportive care were superior to supportive care alone . A final analysis was carried out for the 81 patients with glioblastoma ( median age , 73 years ; range , 70 to 85 ) . At a median follow-up of 21 weeks , the median survival for the 39 patients who received radiotherapy plus supportive care was 29.1 weeks , as compared with 16.9 weeks for the 42 patients who received supportive care alone . The hazard ratio for death in the radiotherapy group was 0.47 ( 95 % confidence interval , 0.29 to 0.76 ; P=0.002 ) . There were no severe adverse events related to radiotherapy . The results of quality -of-life and cognitive evaluations over time did not differ significantly between the treatment groups . CONCLUSIONS Radiotherapy results in a modest improvement in survival , without reducing the quality of life or cognition , in elderly patients with glioblastoma . ( Clinical Trials.gov number , NCT00430911 [ Clinical Trials.gov ] . ) From May 1990 to November 1994 , 70 consecutive patients suffering from glioblastoma multiforme were treated following surgery with conventional radiotherapy and adjuvant IV BCNU administered alone or in combination with tamoxifen . Twenty-five patients received BCNU alone ( control group A ) while 24 patients also received 40 mg of tamoxifen ( TMX ) PO daily ( group B ) and 21 received 100 mg of TMX PO daily ( group C ) . There were no significant differences between the 3 groups concerning age , type of resection and median post-operative Karnofsky performance status ( KPS ) . Blood toxicity over grade II occurred in 33.5 % of patients receiving TMX versus 12 % of patients treated with BCNU alone (p<0.05).Deep venous thrombosis complications were observed in 4 patients of each TMX group , whereas they were not observed in the control group ( p<0.04 ) . Median time to tumor progression ( MTTP ) was 35 weeks in the control group and 27 weeks in both TMX groups B and C. Median survival time ( MST ) was 56 , 66 and 51 weeks , respectively . These results suggest that the addition of TMX to st and ard treatment of glioblastomas does not affect the time to tumor progression and overall survival but may increase the risk of deep venous thrombosis or nitrosourea-induced blood toxicity In a group of 139 patients with poorly differentiated brain gliomas controlled clinical trial was carried out for assessment of two methods of postoperative treatment . After possibly radical removal of the glioma the patients were treated by radiotherapy with 60Co teletherapy in doses of 60 Gy ( 30 fr ) in depth during 6 weeks , and r and omly chosen patients received also CCNU in one dose of 100 mg/m repeated at intervals of 6 - 8 weeks . The administration of CCNU failed to improve the therapeutic results . The median survival time in the whole group was 49 weeks . The survival rate after 1 , 2 and 3 years was 45.4 % , 22.8 % and 14.9 % respectively . The survival times of cases of glioblastoma multiforme were not significantly different from those of patients with other poorly differentiated gliomas independently of the treatment method . The complications were not troublesome PURPOSE To prospect ively compare st and ard radiation therapy ( RT ) with an abbreviated course of RT in older patients with glioblastoma multiforme ( GBM ) . PATIENTS AND METHODS One hundred patients with GBM , age 60 years or older , were r and omly assigned after surgery to receive either st and ard RT ( 60 Gy in 30 fractions over 6 weeks ) or a shorter course of RT ( 40 Gy in 15 fractions over 3 weeks ) . The primary end point was overall survival . The secondary end points were proportionate survival at 6 months , health-related quality of life ( HRQoL ) , and corticosteroid requirement . HRQoL was assessed using the Karnofsky performance status ( KPS ) and Functional Assessment of Cancer Therapy-Brain ( FACT-Br ) . RESULTS All patients had died at the time of analysis . Overall survival times measured from r and omization were similar at 5.1 months for st and ard RT versus 5.6 months for the shorter course ( log-rank test , P = .57 ) . The survival probabilities at 6 months were also similar at 44.7 % for st and ard RT versus 41.7 % for the shorter course ( lower-bound 95 % CI , -13.7 ) . KPS scores varied markedly but were not significantly different between the two groups ( Wilcoxon test , P = .63 ) . Low completion rates of the FACT-Br ( 45 % ) precluded meaningful comparisons between the two groups . Of patients completing RT as planned , 49 % of patients ( st and ard RT ) versus 23 % required an increase in posttreatment corticosteroid dosage ( chi(2 ) test , P = .02 ) . CONCLUSION There is no difference in survival between patients receiving st and ard RT or short-course RT . In view of the similar KPS scores , decreased increment in corticosteroid requirement , and reduced treatment time , the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM Aims and Background Malignant gliomas remain untreatable as the different therapeutic combinations are generally only palliative . Recent experimental evidence suggests that endogenous opioid peptides are involved in brain tumor growth . The aim of the present study was to evaluate the effect on survival of concomitant administration of the long-acting opioid antagonist naltrexone ( NTX ) in patients with malignant astrocytomas treated with radiotherapy ( RT ) . Methods 21 patients with high grade malignant gliomas were r and omized to receive RT alone or RT plus NTX . The dose of RT was 60 Gy . NTX was given orally at a dose of 100 mg every other day without interruption until disease progression . Results The objective tumor regression rate in patients treated with RT plus NTX was higher than that of those treated with RT alone but not significantly so . On the contrary , the percentage of survivals at 1 year was significantly higher in patients treated with RT plus NTX than in those treated with RT alone ( 5/10 vs 1/11 , P < 0.05 ) . NTX therapy was substantially well tolerated in most patients . Conclusions The finding of longer survival in brain tumor patients treated with RT plus NTX than in those who received RT alone suggests in vivo involvement of endogenous opioid peptides in regulating the growth of malignant astrocytomas PURPOSE The management of glioblastoma multiforme ( GBM ) in elderly patients with poor performance status is not well established . A trial evaluating the efficacy and safety of temozolomide alone in this population was undertaken . PATIENTS AND METHODS Patients age 70 years or older with newly diagnosed GBM and postoperative Karnofsky performance score ( KPS ) less than 70 were eligible for this nonr and omized phase II trial . Treatment consisted of 150 to 200 mg/m(2)/d temozolomide for 5 days every 4 weeks until disease progression . Radiotherapy was not administered . The primary end point was overall survival ( OS ) ; secondary end points included progression-free survival ( PFS ) , safety , quality of life , and cognition . RESULTS Seventy patients ( median age , 77 years ; median KPS , 60 ) were enrolled between July 2007 and February 2009 . Grade 3 to 4 neutropenia and thrombocytopenia occurred in 13 % and 14 % of patients , respectively . Median PFS was 16 weeks ( 95 % CI , 10 to 20 weeks ) , and median OS was 25 weeks ( 95 % CI , 19 to 28 weeks ) , comparing favorably with a 12- to 16-week OS expected from a purely supportive approach . Twenty-three patients ( 33 % ) improved their KPS by 10 or more points , and 18 ( 26 % ) became capable of self-care ( KPS ≥ 70 ) . Overall quality of life and cognition improved over time before disease progression . In the 31 tumors evaluated for O(6)-methylguanine-DNA methyltransferase ( MGMT ) promoter methylation , a methylated status indicated longer PFS ( 26 v 11 weeks ; P = .03 ) and OS ( 31 v 19 weeks ; P = .03 ) . CONCLUSION Temozolomide has an acceptable tolerance in elderly patients with GBM and KPS less than 70 . It is associated with improvement of functional status in 33 % of patients and appears to increase survival compared with supportive care alone , especially in patients with methylated MGMT promoter BACKGROUND Prognosis of unresectable glioblastoma ( GB ) remains poor , despite temozolomide (TMZ)-based chemoradiation . Activity of bevacizumab ( BEV ) and irinotecan ( IRI ) has been reported in recurrent disease . We evaluated BEV and IRI as neo-adjuvant and adjuvant treatment combined with TMZ-based chemoradiation for unresectable GB . PATIENTS AND METHODS Patients with unresectable GB , age 18 - 70 , IK ≥50 were eligible . The experimental arm ( BEV/IRI ) consisted of neo-adjuvant intravenous BEV , 10 mg/kg , and IRI , 125 mg/m(2 ) , every 2 weeks for four cycles before radiotherapy ( RT ) ( 60 Gy ) , concomitant oral TMZ , 75 mg/m(2)/day , and BEV , 10 mg/kg every 2 weeks . Adjuvant BEV and IRI were given every 2 weeks for 6 months . The control arm consisted of concomitant oral TMZ , 75 mg/m(2)/day during RT , and 150 - 200 mg/m(2 ) for 5 days every 28 days for 6 months . The use of BEV was allowed at progression in the control arm . RESULTS Patients ( 120 ) were included from April 2009 to January 2011 . The working hypothesis was that treatment would increase the progression-free survival at 6 month ( PFS-6 ) from 50 % to 66 % . The primary objective was not achieved , and only 30 out of 60 patients were alive without progression at 6 months ( 50.0 % [ IC95 % ( 36.8 ; 63.1 ) ] in the BEV/IRI arm when 37 out of 60 patients were required according to the Fleming decision rules . PFS-6 was 7.1 months in BEV/IRI versus 5.2 months in the control arm . The median overall survival was not different between the two arms ( 11.1 months ) . Main toxicities were three fatal intracranial bleedings , three bile duct or digestive perforations/infections ( 1 fatal ) , and six thrombotic episodes in the BEV/IRI arm , whereas there was one intracranial bleeding , two bile duct or digestive perforations/infections ( 1 fatal ) , and one thrombotic episode in the control arm . CONCLUSIONS Neo-adjuvant and adjuvant BEV/IRI , combined with TMZ-radiation , is not recommended for further evaluation in the first-line treatment of unresectable GB . CLINICAL TRIAL REGISTRATION Clinical trial registered under EUDRACT number 2008 - 002775 - 28 ( NCT01022918 ) Introduction Elderly patients have glioblastomas ( GBM ) that are aggressive and poorly responsive to treatment . They are also prone to the side effects of treatment of GBM . Methods To shed light on the treatment of elderly patients with GBM , we review ed the treatment toxicities and survival of patients 65 years of age or older who were treated with chemoradiotherapy , which is the new st and ard of care for GBM in younger patients . Results Thirty-nine patients at a single cancer center in Canada met the eligibility criteria for this retrospective study . Nineteen patients were treated initially with TMZ and radiotherapy and 20 others were treated with radiotherapy alone ( only two had TMZ subsequently ) . Eight patients in the chemoradiotherapy group ( 42 % ) experienced Grade III or IV toxicity versus none in the radiotherapy group . The median overall survival in the chemoradiotherapy group was 8.5 months ( range , 2.0–24.7 months ) versus 5.2 months ( range , 1.5–14.2 months ) in the radiotherapy group , an apparent benefit which may have been due to an imbalance in age at diagnosis , extent of resection and performance status . In this series of GBM cases , methylation of the MGMT gene promoter was not associated with longer survival , either overall , or within the chemoradiotherapy treated subset . Conclusions Elderly patients with GBM treated with chemoradiotherapy can be expected to experience significant toxicity . Large r and omized trials will be necessary to determine whether chemoradiotherapy prolongs the survival of elderly patients and whether MGMT promoter status predicts benefit from temozolomide in this subset of patients INTRODUCTION To evaluate the role of limited field radiation therapy in the management of high- grade gliomas and glioblastoma multiforme ( GBM ) . MATERIAL AND METHODS From July ' 96 to January ' 98 , 50 newly diagnosed patients of high- grade gliomas ( Grade III and IV ) and glioblastoma multiforme who underwent surgery in the form of partial , sub-total or near-total excision as the primary treatment were enrolled in this study . The patients were r and omized to receive two different postoperative external radiation protocol s , Study Group A : Localized field external radiotherapy 50 Gy/25#/5 wks followed by Boost 10 Gy/5#/1 wk , Control Group B : Whole brain external radiotherapy 40 Gy/20#/4 wks followed by Boost 20 Gy/10#/2 wks by localized field . RESULTS 20/25 ( 80 % ) patients in the study group and 14/25 ( 56 % ) patients in the control group showed improvement in their Karnofsky Performance Status ( KPS ) . Thus a significant difference in the performance status was noted in favor of limited field irradiation . No significant difference in the local response was seen between the two groups after radiotherapy . Six months progression-free survival of the study group was 44 % as compared to 26 % in the control group . Six months overall survival was 66.67 % in the study group and 50.72 % in the control group ( P<0.01 ) . Maximum recurrences were noticed within 2 cm of the original tumor margin in both the groups . CONCLUSIONS Although local control and survival of the patient in both the groups were same , performance status definitely improved in patients treated with localized field irradiation only From September , 1972 to December , 1976 , 102 consecutive patients operated on for glioblastoma multiforme were r and omized , after total or subtotal tumor resection , to receive irradiation alone , irradiation plus BCNU or irradiation plus CCNU . BCNU and CCNU adjuvant chemotherapy was repeated every 6 - -8 weeks as long as the patients remained in complete remission . Patients were comparable for median age , type of surgery , and histological grade III and IV . Radiotherapy was administered at the tumor dose of about 5000 rads in all three groups . The percent of optimal dose administered was 96 % for BCNU and 93 % for CCNU . In the group treated with radiotherapy alone ( 32 cases ) the median survival was 10.5 months , while in the groups treated with BCNU ( 34 cases ) and CCNU ( 36 cases ) the median survival was 12 and 16 months , respectively . Both relapse-free ( P = 0.05 ) and total survival ( P = 0.03 ) were significantly improved only in patients who were treated with radiotherapy plus CCNU compared to patients receiving radiotherapy alone after surgery . Present results show that in resectable glioblastoma multiforme , a slightly improved survival rate can be achieved by the prolonged use of adjuvant CCNU following maximal surgical resection and radiotherapy . The cure rate was not improved BACKGROUND A r and omised controlled trial of radiotherapy alone versus radiotherapy with concomitant and adjuvant temozolomide for patients with glioblastoma showed that survival was higher for patients assigned combination treatment compared with those assigned st and ard radiotherapy alone . This paper reports the health-related quality of life ( HRQOL ) of the patients in this trial . METHODS 573 patients with newly diagnosed glioblastoma were r and omly allocated either radiotherapy alone or radiotherapy and temozolomide . The primary endpoint was survival , and HRQOL was a secondary endpoint . We assessed HRQOL at baseline and at every 3 months during treatment until progression using the European Organisation for Research and Treatment of Cancer ( EORTC ) quality of life question naire core-30 ( QLQ-C30 ) and the EORTC brain cancer module ( EORTC BN-20 ) . We calculated changes from baseline score for seven predefined HRQOL measures ( fatigue , overall health , social function , emotional function , future uncertainty , insomnia , and communication deficit ) and differences between groups for these measures at every time point . The significance of , and proportions of patients with , improved HRQOL scores -- defined as a change of 10 points or more -- were recorded . This trial is registered on the US National Cancer Institute website http://www.cancer.gov/ search /New Clinical Trials , NCT00006353 . FINDINGS Baseline question naires were available for 490 ( 86 % ) patients . Baseline HRQOL scores did not differ between groups . At first follow-up , groups differed only in social functioning , favouring the radiotherapy-only group ( mean score 79.0 [ SD 3.2 ] for patients assigned radiotherapy vs 67.4 [ 2.7 ] for those assigned radiotherapy and temozolomide ; difference between groups 11.6 points [ 95 % CI 3.5 - 19.7 ] , p=0.0052 ) . Over subsequent assessment s , HRQOL was much the same between treatment groups . INTERPRETATION Addition of temozolomide during and after radiotherapy for patients with newly diagnosed glioblastoma significantly improved survival without a negative effect on HRQOL PURPOSE To evaluate toxicity and outcomes in patients with primary glioblastoma ( GB ) treated with postoperative radiochemotherapy ( RCHT ) with temozolomide ( TMZ ) comparing two dose regimens . METHODS AND MATERIAL S A total of 160 patients with histologically confirmed GB were treated with postoperative RCHT with TMZ . Of the patients , 66 were female and 94 were male , with a median age of 60 years . After the primary diagnosis , a biopsy had been performed in 42 patients ; a subtotal and total resection was conducted in 66 and 52 patients . Postoperative radiotherapy was applied with a median dose of 60 Gy with a median fractionation of 5 x 2Gy/week . Concomitant TMZ was prescribed at 50 mg/m(2 ) in 123 patients ( Group A ) and at 75 mg/m(2 ) in 37 patients ( Group B ) . Patients were followed in 3-months intervals , with a median follow-up of 13 months . RESULTS Overall survival ( OS ) rates in Group A vs. Group B were 67 % and 79 % at 1 year and 43 % vs. 49 % at 2 years , respectively ( p = 0.69 ) . Progression-free survival was 49 % vs. 54 % at 1 year and 22 % vs. 29 % at 2 years ( p = 0.31 ) . Hematologic toxicity was not statistically significant over the 6-week RCHT period except for a significant decrease in platelets during Week 6 ( p = 0.01 ) in Group B. CONCLUSIONS Overall survival seems to be comparable in both groups , although longer follow-up and a larger group of patients are needed to corroborate these results . Lower dosing of TMZ also is associated with a more beneficial toxicity profile PURPOSE To report the results of a prospect i ve Phase III trial for patients with newly diagnosed glioblastoma multiforme ( GBM ) , treated with either accelerated hyperfractionated irradiation with or without difluromethylornithine ( DFMO ) or st and ard fractionated irradiation with or without DFMO . METHODS AND MATERIAL S Adult patients with newly diagnosed GBM were registered and r and omized following surgery to one of 4 treatment arms : Arm A , accelerated hyperfractionation alone using 2 fractions a day of 1.6 Gy to a total dose of 70.4 Gy in 44 fractions ; Arm B , accelerated hyperfractionation as above plus DFMO 1.8 gm/m2 by mouth every 8 h beginning one week before radiation until the last fraction was given ; Arm C , single-fraction irradiation of 1.8 Gy/day to 59.4 Gy ; Arm D , single-fraction irradiation as in Arm C plus DFMO given as in Arm B. Patients were followed for progression-free survival ( PFS ) and overall survival ( OS ) , as well as for toxicity . Eligibility required histologically proven GBM , age > or = 18 , Karnofsky performance status ( KPS ) > or = 60 , and no prior chemotherapy or radiotherapy . Adjuvant chemotherapy was not used in this protocol . RESULTS A total of 231 eligible patients were enrolled . There were 95 men and 136 women with a median age of 57 years , and median KPS of 90 . Extent of resection was total in 23 , subtotal in 152 , and biopsy only in 56 patients . The 4 arms were balanced with respect to age , KPS , and extent of resection . Times to event measurements are from date of diagnosis . Median OS and PFS were 40 and 19 weeks for Arm A ; 42 and 22 weeks for Arm B ; 37 and 16 weeks for Arm C ; and 44 and 19 weeks for Arm D ( p = 0.48 for survival ; p = 0.32 for PFS ) . Comparison of the 2 arms treated with DFMO to the 2 arms without DFMO revealed no difference in OS ( 37 weeks vs. 42 weeks , p = 0.12 ) or PFS and thus no benefit to the use of DFMO . Comparison of the 2 st and ard fractionation arms to the 2 accelerated hyperfractionation arms also result ed in no difference in OS ( 42 weeks vs. 41 weeks , p = 0.75 ) or PFS , showing no benefit to accelerated hyperfractionated irradiation . CONCLUSION In this prospect i ve Phase III study , no survival or PFS benefit was seen with accelerated hyperfractionated irradiation to 70.4 Gy , nor was any benefit seen with DFMO as a radiosensitizer . St and ard fractionated irradiation to 59.4 Gy remains the treatment of choice for newly diagnosed patients with glioblastoma multiforme Controlled , prospect i ve , r and omized studies were performed to evaluate the effects of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)-3-nitrosourea hydrochloride ( ACNU ) and ACNU plus tegafur as additions to radiotherapy for the treatment of malignant gliomas . In the first trial , 105 patients with glioblastoma or anaplastic astrocytoma were r and omly divided into two groups after surgery and received radiotherapy ( RT , 40 to 60 Gy to the whole brain ) , or radiotherapy plus concomitant chemotherapy with ACNU ( 100 mg/m2 on day 1 and 42 ) . Effects of the treatment were compared in 82 evaluable patients from results of CT scans taken before and one month after the completion of radiotherapy . The regression rates more than 50 % of the tumor size were observed in 15.0 % of patients treated with RT alone and in 47.6 % of patients treated with RT plus ACNU . The difference was statistically significant ( p less than 0.005 ) . In the second trial , 87 patients were r and omly divided into two groups and received RT plus ACNU , or RT plus combined chemotherapy with ACNU and tegafur ( 400 mg/m2 , daily for 8 weeks ) . Sixty-nine patients were within the valid study group . The regression rates more than 50 % of the tumor size were observed in 34.2 % of patients treated with RT plus ACNU : and in 41.2 % treated with RT , ACNU plus tegafur . No statistical difference was noted in the response rate between the groups . These results indicate that ACNU is an effective agent in conjunction with radiotherapy for patients with malignant gliomas , and that tegafur does not enhance the effectiveness of ACNU This Phase III trial tested the efficacy and safety of intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea ( BCNU ) for the treatment of newly resected malignant glioma , comparing intra-arterial BCNU and intravenous BCNU ( 200 mg/sq m every 8 weeks ) , each regimen without or with intravenous 5-fluorouracil ( 1 gm/sq m three times daily given 2 weeks after BCNU ) . All patients also received radiation therapy . A total of 505 patients were r and omly assigned within the study . Fifty-seven patients were excluded , primarily because of neuropathology error , and the remaining 448 patients constituted the Valid Study Group . Of the total 505 patients , 190 patients could not receive intra-arterial BCNU and 315 patients were r and omly assigned to receive intra-arterial ( 167 patients ) and intravenous ( 148 patients ) BCNU . Actuarial analysis ( log-rank ) demonstrated reduced survival for the intra-arterial group ( p = 0.03 ) . Serious toxicity was observed in the intra-arterial group ; 16 patients ( 9.5 % ) developed irreversible encephalopathy with computerized tomography evidence of cerebral edema , and 26 patients ( 15.5 % ) developed visual loss ipsilateral to the infused carotid artery . Administration of 5-fluorouracil did not influence survival . The survival rate between the intravenous and the intra-arterial BCNU patients with glioblastoma multiforme did not differ , but was worse for intra-arterial BCNU patients with anaplastic astrocytoma than for those receiving intravenous BCNU ( p = 0.002 ) . Neuropathologically , intra-arterial BCNU produced white matter necrosis . It is concluded that intra-arterial BCNU is neither safe nor effective in prolonging survival when administered by the methods used in this study of newly diagnosed patients with malignant glioma PURPOSE The role of chemotherapy in the primary treatment of malignant glioma remains controversial . The results from the German-Austrian Glioma trial ( GAG , 1983 to 1988 ) demonstrated a survival benefit for chemotherapy using carmustine ( BCNU ) plus teniposide ( VM26 ) over BCNU alone in addition to radiotherapy in patients with a Karnofsky performance score ( KPS ) more than 60 . The Neuro-Oncology Working Group ( NOA ) of the German Cancer Society therefore compared the efficacy of nimustine ( ACNU ) plus VM26 and ACNU plus cytarabine ( Ara-C ) chemotherapy in addition to st and ard radiotherapy in patients with newly diagnosed malignant glioma . PATIENTS AND METHODS From 1994 to 2000 , 375 patients were r and omly assigned to receive radiotherapy and cycles of ACNU 90 mg/m2 intravenously ( IV ) on day 1 and VM26 60 mg/m2 IV on days 1 to 3 ( n = 183 ) , or ACNU 90 mg/m2 IV on day 1 and Ara-C 120 mg/m2 IV on days 1 to 3 ( n = 179 ) , in 6-week intervals . Thirteen patients were not eligible after central neuropathology review . The remaining 362 patients had glioblastoma ( n = 301 ) or anaplastic glioma ( n = 61 ) . RESULTS Median survival and 2-year survival rates were 17.3 months and 25 % for ACNU plus VM26 , and 15.7 months and 29 % for ACNU plus Ara-C in glioblastoma , and 60 months and 88 % for ACNU plus VM26 and 62.5 months and 72 % for ACNU plus Ara-C in anaplastic glioma . Multivariate analysis revealed no survival advantage for either arm or for sub population s defined by histology , age , or KPS . Hematologic toxicity was more prominent in the ACNU plus Ara-C arm . CONCLUSION The median survival times and 2-year survival rates for patients with anaplastic glioma and glioblastoma achieved in the NOA-01 trial compare favorably with historical trials and with the Radiation Therapy Oncology Group data base . The toxicity profile favors ACNU plus VM26 for further evaluation Purpose : We performed a r and omized trial to comparesurvival distributions and toxicity of radiation therapy ( RT ) and DBD with RT and BCNU in patients with high- grade astrocytoma . Methods : A total of 238 patients with supratentorial grade 3 and grade 4astrocytoma were studied . Patients were stratified by age , extent of surgery , tumor grade , and performance score and r and omly assigned to receive RT 55 - 60 Gy and either DBD , 200 mg/m2 orally on Days1–10 every five weeks or BCNU , 200 mg/m2intravenously every seven weeks . Median age was 60years ; 62 % were 55 years or older . Eighty-threepercent had subtotal resection , 58 % had grade 4tumors , and 83 % had performance scores of 0–2 . Results : Survival distributions for all patients in thetwo arms were similar , with median survival of41 weeks in each arm . Time to progressiondistributions were virtually identical , with medians of 22weeks . BCNU produced significantly greater hematologic toxicity ; medianleukocyte and platelet nadirs on the first cyclewere 3.6 vs. 4.7 ( P=0.0001 ) and 117 vs. 162 ( P < 0.0001 ) , and overallplatelet nadirs were 80.5 vs. 114 ( P = 0.0019 ) . Non-hematologic toxicities were also significantly greater withBCNU , including nausea ( 57 % vs. 31 % ; P < 0.0001 ) and vomiting ( 45 % vs. 17 % ; P < 0.0001 ) . Conclusion : This trial found no evidence ofdifferences in treatment efficacy when either DBD orBCNU is combined with radiation therapy for patients with high- grade astrocytoma Aims To determine the efficacy of methylguanine methyltransferase ( MGMT ) depletion + BCNU [ 1,3-bis(2-chloroethyl)-1- nitrosourea : carmustine ] therapy and the impact of methylation status in adults with glioblastoma multiforme ( GBM ) and gliosarcoma . Methods Methylation analysis was performed on GBM patients with adequate tissue sample s. Patients with newly diagnosed GBM or gliosarcoma were eligible for this Phase III open-label clinical trial . At registration , patients were r and omized to Arm 1 , which consisted of therapy with O6-benzylguanine ( O6-BG ) + BCNU 40 mg/m2 ( reduced dose ) + radiation therapy ( RT ) ( O6BG + BCNU arm ) , or Arm 2 , which consisted of therapy with BCNU 200 mg/m2 + RT ( BCNU arm ) . Results A total of 183 patients with newly diagnosed GBM or gliosarcoma from 42 U.S. institutions were enrolled in this study . Of these , 90 eligible patients received O6-BG + BCNU + RT and 89 received BCNU + RT . The trial was halted at the first interim analysis in accordance with the guidelines for stopping the study due to futility ( < 40 % improvement among patients on the O6BG + BCNU arm ) . Following adjustment for stratification factors , there was no significant difference in overall survival ( OS ) or progression-free survival ( PFS ) between the two groups ( one sided p = 0.94 and p = 0.88 , respectively ) . Median OS was 11 [ 95 % confidence interval ( CI ) 8–13 ] months for patients in the O6BG + BCNU arm and 10 ( 95 % CI 8–12 ) months for those in the BCNU arm . PFS was 4 months for patients in each arm . Adverse events were reported in both arms , with significantly more grade 4 and 5 events in the experimental arm . Conclusions The addition of O6-BG to the st and ard regimen of radiation and BCNU for the treatment patients with newly diagnosed GBM and gliosarcoma did not provide added benefit and in fact caused additional toxicity A prospect i ve r and omized trial of 157 patients with malignant astrocytoma ( Grade III or IV ) was carried out at a single institution . The minimization technique ensured balanced distribution of prognostic factors between the treatment groups . All received oral lomustine ( CCNU , 80 mg/m2 ) six weekly and hydroxyurea ( HU , 3.5 gm/m2 over 5 days ) three weekly , for one year or until recurrence , with doses adjusted for myelosuppression . Patients were r and omized to daily ( 5000 rad in 25 fractions ( fr ) in 5 weeks ) or Q3h ( every 3 hours ) Cobalt 60 irradiation ( 3600–4000 rad in 36–40 fr of 100 rad each , given 4 fr per day at 3‐hour intervals over two weeks ) Steroid therapy ( up to 16 mg day dexamethasone ) was permitted . Complications were moderate and equivalent in the two groups . No significant survival or toxicity differences were seen between the two groups . Age , initial performance status , and extent of surgical resection were found to be significant ( P < 0.01 ) prognostic factors for survival . Median survival of the whole group was 48 weeks with a minimum follow‐up of one year . There was no advantage to large radiation fields . The hyperfractionation and daily regimes had similar efficacy and toxicity . Hyperfractionation with chemotherapy offers a useful alternative approach in the management of this disease BACKGROUND In 2004 , a r and omised phase III trial by the European Organisation for Research and Treatment of Cancer ( EORTC ) and National Cancer Institute of Canada Clinical Trials Group ( NCIC ) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy . We report the final results with a median follow-up of more than 5 years . METHODS Adult patients with newly diagnosed glioblastoma were r and omly assigned to receive either st and ard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide . The methylation status of the methyl-guanine methyl transferase gene , MGMT , was determined retrospectively from the tumour tissue of 206 patients . The primary endpoint was overall survival . Analyses were by intention to treat . This trial is registered with Clinical trials.gov , number NCT00006353 . FINDINGS Between Aug 17 , 2000 , and March 22 , 2002 , 573 patients were assigned to treatment . 278 ( 97 % ) of 286 patients in the radiotherapy alone group and 254 ( 89 % ) of 287 in the combined-treatment group died during 5 years of follow-up . Overall survival was 27.2 % ( 95 % CI 22.2 - 32.5 ) at 2 years , 16.0 % ( 12.0 - 20.6 ) at 3 years , 12.1 % ( 8.5 - 16.4 ) at 4 years , and 9.8 % ( 6.4 - 14.0 ) at 5 years with temozolomide , versus 10.9 % ( 7.6 - 14.8 ) , 4.4 % ( 2.4 - 7.2 ) , 3.0 % ( 1.4 - 5.7 ) , and 1.9 % ( 0.6 - 4.4 ) with radiotherapy alone ( hazard ratio 0.6 , 95 % CI 0.5 - 0.7 ; p<0.0001 ) . A benefit of combined therapy was recorded in all clinical prognostic subgroups , including patients aged 60 - 70 years . Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy . INTERPRETATION Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up . A few patients in favourable prognostic categories survive longer than 5 years . MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide . FUNDING EORTC , NCIC , Nélia and Amadeo Barletta Foundation , Schering-Plough Importance Tumor-treating fields ( TTFields ) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor . Objective To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma , a fatal disease that commonly recurs at the initial tumor site or in the central nervous system . Design , Setting , and Participants In this r and omized , open-label trial , 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy ( median time from diagnosis to r and omization , 3.8 months ) were enrolled at 83 centers ( July 2009 - 2014 ) and followed up through December 2016 . A preliminary report from this trial was published in 2015 ; this report describes the final analysis . Interventions Patients were r and omized 2:1 to TTFields plus maintenance temozolomide chemotherapy ( n = 466 ) or temozolomide alone ( n = 229 ) . The TTFields , consisting of low-intensity , 200 kHz frequency , alternating electric fields , was delivered ( ≥ 18 hours/d ) via 4 transducer arrays on the shaved scalp and connected to a portable device . Temozolomide was administered to both groups ( 150 - 200 mg/m2 ) for 5 days per 28-day cycle ( 6 - 12 cycles ) . Main Outcomes and Measures Progression-free survival ( tested at & agr ; = .046 ) . The secondary end point was overall survival ( tested hierarchically at & agr ; = .048 ) . Analyses were performed for the intent-to-treat population . Adverse events were compared by group . Results Of the 695 r and omized patients ( median age , 56 years ; IQR , 48 - 63 ; 473 men [ 68 % ] ) , 637 ( 92 % ) completed the trial . Median progression-free survival from r and omization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group ( HR , 0.63 ; 95 % CI , 0.52 - 0.76 ; P < .001 ) . Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group ( HR , 0.63 ; 95 % CI , 0.53 - 0.76 ; P < .001 ) . Systemic adverse event frequency was 48 % in the TTFields-temozolomide group and 44 % in the temozolomide-alone group . Mild to moderate skin toxicity underneath the transducer arrays occurred in 52 % of patients who received TTFields-temozolomide vs no patients who received temozolomide alone . Conclusions and Relevance In the final analysis of this r and omized clinical trial of patients with glioblastoma who had received st and ard radiochemotherapy , the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone , result ed in statistically significant improvement in progression-free survival and overall survival . These results are consistent with the previous interim analysis . Trial Registration clinical trials.gov Identifier : BACKGROUND Continuous research into new strategies and chemotherapy agents for the treatment of malignant high- grade gliomas have led to the synthesis of a new chemotherapy drug , temozolomide ( TMZ ) , with a lower toxicity profile compared to conventional chemotherapy agents , such as nitrosoureas . Temozolomide is an oral alkylating chemotherapy agent licensed for the treatment of recurrent high- grade gliomas , anaplastic astrocytoma ( AA ) and glioblastoma multiforme ( GBM ) . Because of its favorable pharmacokinetic and pharmacodynamic properties and improved tolerability , TMZ is now under investigation for concomitant use with radiotherapy in patients with newly-diagnosed GBM . We present a phase II clinical trial investigating the efficacy and safety of radio-chemotherapy combined treatment using TMZ , followed by six cycles of adjuvant chemotherapy with TMZ , in patients with newly-diagnosed GBM who have undergone debulking surgery or biopsy only . PATIENTS AND METHODS Twenty-one patients with newly histologically-diagnosed GBM were enrolled into this phase II clinical trial . In phase I of the study , TMZ ( 75 mg/m2/day per 7 days/wk for 6 weeks ) was orally administered to patients concomitantly with radiotherapy ( RT ) ( 2 Gy per fraction once daily , per 5 days/wk for 6 weeks ) . In phase II of the study , four weeks after completion of RT , a monochemotherapy using TMZ was administered at the dosage of 200 mg/m2/day per 5 days every 28 days for 6 cycles . Primary end-points were the safety and tolerability profile of this two-phase combined treatment and secondary end-points were the objective response and survival rates at twelve months and eighteen months from study entry . RESULTS The one-year survival rate of patients treated with the investigated multimodality treatment was 58 % and median survival time was 15.7 months . Concomitant RT plus TMZ ( phase I ) followed by adjuvant TMZ ( phase 2 ) were well-tolerated ; indeed , nonhematological adverse events were rare and mild to moderate in severity ; grade 3 and 4 neutropenia and thrombocytopenia were the major-related hematological side-effects observed in only 2 and 3 of all patients in phase I and 4 patients in phase II . We found that the combination of radio- and chemo-therapy , in phase I of the study did not significantly increase the incidence and severity of hematological toxicity caused by the adjuvant TMZ-based chemotherapy administered in phase II of the study . CONCLUSION The investigated multimodality treatment regimen was well-tolerated and prolonged survival while improving patients ' quality of life Background . The third and final r and omization of Radiation Therapy Oncology Group ( RTOG ) 83–02 was performed to identify the maximal tolerated dose and potential efficacy of accelerated hyperfractionated radiation therapy ( AHRT ) in 1.6 Gy twice‐daily fractions for adult malignant glioma PURPOSE Radiotherapy ( RT ) and chemotherapy may prolong survival in older patients ( age ≥70 years ) with glioblastoma multiforme ( GBM ) , although the survival benefits remain poor . This Phase II multicenter study was design ed to evaluate the efficacy and safety of an abbreviated course of RT plus concomitant and adjuvant temozolomide ( TMZ ) in older patients with GBM . PATIENTS AND METHODS Seventy-one eligible patients 70 years of age or older with newly diagnosed GBM and a Karnofsky performance status ≥60 were treated with a short course of RT ( 40 Gy in 15 fractions over 3 weeks ) plus TMZ at the dosage of 75 mg/m(2 ) per day followed by 12 cycles of adjuvant TMZ ( 150 - 200 mg/m(2 ) for 5 days during each 28-day cycle ) . The primary endpoint was overall survival ( OS ) . Secondary endpoints included progression-free survival and toxicity . RESULTS The Median OS was 12.4 months , and the 1-year and 2-year OS rates were 58 % and 20 % , respectively . The median and 1-year rates of progression-free survival were 6 months and 20 % , respectively . All patients completed the planned programme of RT . Grade 3 or 4 adverse events occurred in 16 patients ( 22 % ) . Grade 3 and 4 neutropenia and /or thrombocytopenia occurred in 10 patients ( 15 % ) , leading to the interruption of treatment in 6 patients ( 8 % ) . Nonhematologic Grade 3 toxicity was rare , and included fatigue in 4 patients and cognitive disability in 1 patient . CONCLUSIONS A combination of an abbreviated course of RT plus concomitant and adjuvant TMZ is well tolerated and may prolong survival in elderly patients with GBM . Future r and omized studies need to evaluate the efficacy and toxicity of different schedules of RT in association with chemotherapy The authors report 63 patients with biopsy-proved malignant ( Grade s 3 and 4 ) astrocytomas who were r and omly placed in one of three treatment schedules within 2 weeks of surgery . One group ( 22 patients ) received radiation therapy alone ; the second group ( 22 patients ) received 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea ( CCNU ) orally at intervals of 8 weeks ; and the third group ( 19 patients ) received combined radiation and drug therapy . Patients who received radiation therapy , with or without the drug , had a significantly longer survival than did those who received the drug alone . There was no difference in survival between the two groups who received radiation . The nitrosourea derivative CCNU does not seem to be an effective agent in the therapy of primary malignant brain tumors BACKGROUND The optimal use of bevacizumab in recurrent glioblastoma ( GBM ) , including the choice of monotherapy or combination therapy , remains uncertain . The purpose of this study was to compare combination therapy with bevacizumab monotherapy . METHODS This was a 2-part r and omized phase 2 study . Eligibility criteria included recurrent GBM after radiotherapy and temozolomide , no other chemotherapy for GBM , and Eastern Cooperative Oncology Group performance status 0 - 2 . The primary objective ( Part 1 ) was to determine the effect of bevacizumab plus carboplatin versus bevacizumab monotherapy on progression-free survival ( PFS ) using modified Response Assessment in Neuro-Oncology criteria . Bevacizumab was given every 2 weeks , 10 mg/kg ; and carboplatin every 4 weeks , ( AUC 5 ) . On progression , patients able to continue were r and omized to continue or cease bevacizumab ( Part 2 ) . Secondary endpoints included objective radiological response rate ( ORR ) , quality of life , toxicity , and overall survival ( OS ) . RESULTS One hundred twenty-two patients ( median age , 55y ) were enrolled to Part 1 from 18 Australian sites . Median follow-up was 32 months , and median on-treatment time was 3.3 months . Median PFS was 3.5 months for each arm ( hazard ratio [ HR ] : 0.92 , 95 % CI : 0.64 - 1.33 , P = .66 ) . ORR was 14 % ( combination ) versus 6 % ( monotherapy ) ( P = .18 ) . Median OS was 6.9 ( combination ) versus 7.5 months ( monotherapy ) ( HR : 1.18 , 95 % CI : 0.82 - 1.69 , P = .38 ) . The incidence of bevacizumab-related adverse events was similar to prior literature , with no new toxicity signals . Toxicities were higher in the combination arm . Part 2 data ( n = 48 ) will be reported separately . CONCLUSIONS Adding carboplatin result ed in more toxicity without additional clinical benefit . Clinical outcomes in patients with recurrent GBM treated with bevacizumab were inferior to those in previously reported studies . CLINICAL TRIALS REGISTRATION NR ACTRN12610000915055 This prospect i ve r and omized trial was performed to compare the effectiveness of intra-arterial ACNU with intravenous ACNU in newly diagnosed patients with supratentorial glioblastoma . The primary end points were overall survival and progression-free survival . Within 3 weeks after surgery , patients were r and omly assigned to receive either intravenous or intra-arterial ACNU ( 80 mg/m2 ) once every 6 weeks concomitant with radiotherapy . Intra-arterial ACNU was administered for the first 3 courses followed by intravenous administration . Eighty-four patients were enrolled onto this study and among them 82 patients who passed eligibility criteria were analyzed . Patients characteristics were not different significantly between 2 treatment arms . Median survival and progression-free survival time was 59 and 24 weeks , respectively for intra-arterial arm and 56 and 45 weeks , respectively for intravenous arm . There was no significant difference respectively between two treatment arms . Among the prognostic variables including age , Karnofsky performance status , extent of surgery and treatment arm , Cox 's proportional hazards model showed that age was the only significant factor for both survival and progression-free survival ( P=0.003 and 0.016 , respectively ) . With regard to toxicity , there was no significant difference between two treatment arms . Leukoencephalopathy was not observed in intra-arterial arm . In conclusion , intra-arterial ACNU when administered by the method in this study does not increase the survival and progression-free survival of newly diagnosed patients with glioblastoma over that afforded by intravenous ACNU UNLABELLED Imatinib mesylate ( Gleevec , Novartis Pharmaceuticals East Manruer , NJ ) received accelerated approval on May 10 , 2001 for the treatment of patients with chronic myeloid leukemia ( CML ) in ( a ) chronic phase after failure of IFN-alpha therapy , ( b ) accelerated phase , and ( c ) blast crisis . The accelerated approval was accompanied by a postmarketing commitment by Novartis Pharmaceuticals to continue patient follow-up to determine duration of treatment response and survival . The present review , based on a safety and efficacy report su bmi tted on December 20 , 2002 , summarizes data applicable to the conversion of these three CML indications to full approval status . RESULTS Chronic phase CML : Five hundred thirty-two chronic phase CML patients who had not benefited from prior IFN therapy were treated at a starting imatinib mesylate dose of 400 mg p.o . qd ; dose escalation to 800 mg p.o . qd was allowed . Patients had received a median of 14 months of IFN therapy at doses > or = 25 million IU/wk and were all in late chronic phase , with a median time from diagnosis of 32 months . Median duration of imatinib mesylate treatment was 29 months , with 81 % of patients treated for > or = 24 months ( maximum 31.5 months ) . Initial favorable treatment responses were sustained . An estimated 87.8 % of patients who had a major cytogenetic response maintained their response 2 years after their initial response . After 2 years of treatment , an estimated 85.4 % of patients were free of progression to accelerated phase or blast crisis , and the estimated overall survival was 90.8 % ( 95 % confidence interval , 88.3 - 93.2 ) . Accelerated phase CML : Patients enrolled totaled 293 : 235 with CML accelerated phase , 48 with relapsed/refractory acute lymphocytic leukemia , 2 with relapsed/refractory acute myelocytic leukemia , and 8 with relapsed/refractory CML in lymphoid blast crisis . Patients received imatinib mesylate 400 or 600 mg p.o . qd . Dose escalation was permitted , to a maximum of 800 mg/d , taken as 400 mg bid . Efficacy results were improved in patients receiving imatinib mesylate 600 mg qd versus patients receiving 400 mg qd . The median duration of hematologic response was 29 versus 17 months and the estimated 24-month maintained hematologic response rate was 61 % versus 42 % . The median survival of patients treated with imatinib mesylate 600 mg qd was not reached versus 20.9 months for patients receiving 400 mg qd . Estimated 24-month survival rate was 66 % versus 46 % . The median survival in the advanced leukemia population ( acute lymphocytic leukemia , acute myelocytic leukemia , and lymphoid blast crisis ) was only 5 months , and only two patients are still on treatment . Blast crisis CML : A total of 260 patients were recruited . The imatinib mesylate dose was initially 400 mg qd ( 37 patients ) but was subsequently increased to 600 mg qd ( 223 patients ) . Patients receiving imatinib mesylate 600 mg qd had a higher hematologic response rate than did patients receiving 400 mg ( 33 % versus 16 % ) . Major cytogenetic responses occurred in 15 % of the 260 study patients . The overall median survival was 6.9 months : 7.1 months for patients treated with imatinib mesylate 600 mg and 4.7 months for patients receiving imatinib mesylate 400 mg . Estimated 12-month survival rate for all study patients was 32.1 % and estimated 24-month survival rate was 18.3 % . SAFETY Imatinib mesylate was generally well tolerated , but relatively frequent reports of common toxicity criteria grade 3/4 neutropenia and thrombocytopenia were encountered . The most frequently reported adverse events included gastrointestinal disturbances , edema , rash , and musculoskeletal complaints . These rarely led to discontinuation of therapy . CONCLUSIONS The results confirm those of the interim analysis and suggest that imatinib mesylate represents an effective therapeutic agent for the treatment of patients with CML in chronic phase after failure of IFN-alpha therapy , in blast crisis , and in accelerated phase OBJECT Until recently the assessment of outcome in patients treated for glioma has emphasized length of survival with the evaluation of quality of life ( QOL ) limited to unidimensional , mostly physical , measures . The authors report the multidimensional assessment of QOL as part of a r and omized clinical trial of brachytherapy as a boost in the initial treatment of patients with glioblastoma multiforme . METHODS A question naire previously developed by the senior authors and psychometrically vali date d was completed by patients on r and omized entry into the study and at follow-up review every 3 months thereafter . The question naire was presented in a linear-analog self- assessment format . Karnofsky Performance Scale ( KPS ) scores were also recorded on each occasion . No differences were found between patients in either arm of the study ( conventional radiation therapy consisting of 50 Gy in 25 fractions or conventional radiation plus a brachytherapy boost of a minimum peripheral tumor dose of 60 Gy ) in KPS and QOL scores during the 1st year of follow-up review . However , there was a statistically significant deterioration in patients ' overall KPS scores during the 1st year of follow up compared with baseline scores . Of QOL items evaluated , statistically significant deteriorations were found in self care , speech , and concentration , and on subscale analyses , cognitive functioning and physical experience ( symptoms ) deteriorated significantly during the 1st year of follow up , compared with baseline values . The correlation between QOL and KPS scores was low . CONCLUSIONS Future studies in patients harboring malignant gliomas must incorporate measures assessing QOL because traditional measures focusing on physical or neurological functioning give an incomplete assessment of the patient 's experience The best treatment of malignant gliomas has been considered to be surgery followed by irradiation and chemotherapy with nitrosourea compounds . Our controlled and r and omized trial was design ed in 1982 to analyze the effectiveness of multiple-drug versus single-drug therapy in patients bearing malignant gliomas . After 3 weeks from surgery and histopathological diagnosis 173 patients were r and omly assigned to receive one of the three chemotherapy regimens : CCNU alone , CCNU plus VM-26 or CCNU plus VM-26 plus 5-FU . Radiotherapy was administered whole-brain ( 40 - 45 Gy ) and coned-down focal ( 15 - 20 Gy ) irradiation for a total of 60 Gy ( 1700 rets ) in conjunction with the first course of chemotherapy . 150/173 patients are evaluable . Statistical analysis of results shows a better quality of life and survival for patients treated with polychemotherapy using a three drug combination than two drug or single drug therapy ( 13.8 vs 14.7 vs 18.2 months MST ; P less than 0.01 ) but with a higher incidence of toxicity problems . An analysis of prognostic factors and their distribution in each arm of the protocol will be made in the near future Preliminary results of superfractionation in the treatment of glioblastoma led to a r and omized trial consisting of 76 patients . All patients received whole brain irradiation followed by a 1000 cGy boost to the primary site . Thirty-four patients received st and ard daily treatment to 4000 cGy , whereas 42 patients received superfractionated radiation , treating three times a day to a total dose of 4760 cGy . No significant difference was found between the 5-year survival of the superfractionated group and the st and ard treatment group . Early reactions were greater for superfractionation whereas late effects were less Summary To assess whether therapeutic efficacy is related to the intra-arterial ( IA ) mannitol infusion prior to ACNU and cisplatin ( CDDP ) for malignant brain tumors , the survival time of patients with and without mannitol infusion was compared . Ninety-eight patients were r and omly assigned to either a mannitol infusion group ( group A ) or a non-mannitol infusion group ( group B ) ; 34 with malignant gliomas ( 18 in group A and 16 in group B ) and 64 with brain metastases ( 36 in group A and 28 in group B ) . During radiotherapy , ACNU and CDDP at a dose of 100mg/body were given through the common carotid artery at a rate of 20mg/min . In group A , 50ml of 20 % mannitol was injected intra-arterially at a rate of 50ml/min immediately prior to the injection of chemotherapeutic agents . Of the patients with malignant gliomas , the median survival time ( MST ) was 52 weeks for all 34 cases , 68 weeks for group A , and 47 weeks for group B. Survival analysis showed no significant differences between the two treatment groups . Of the patients with brain metastases , the MST was 40 weeks for all 64 cases , 47 weeks for group A , and 24 weeks for group B ; the survival time was significantly longer in group A as compared to group B ( p < 0.05 ) . This study has demonstrated that , for the patients with brain metastases , IA mannitol infusion provided a survival benefit in the IA chemotherapy employing ACNU and CDDP . In contrast , IA mannitol infusion offered no survival benefit to the patients with malignant gliomas Background . A Phase I/II r and omized dose‐seeking trial was performed to document the severity , time course , and significance of white matter changes seen on serial imaging scans ( magnetic resonance imaging , computed tomography ) associated with bis‐chlorethyl nitrosourea ( BCNU ) and hyperfractionated cranial irradiation The CNS Cancer Consortium has conducted a phase III study comparing diaziquone ( AZQ ) with carmustine ( BCNU ) in the treatment of adults with primary anaplastic glial brain tumors . Patients eligible for this study were 18 years of age or older at the time of biopsy , subtotal resection , or gross total resection of an anaplastic glial brain tumor . Within 3 weeks of surgery , patients received whole brain radiotherapy at 1.7 to 2 Gy per fraction to a total whole brain dose of 42–48 Gy . This was followed by a boost to the tumor bed as ascertained by computed tomography ( CT ) , angiography , and /or magnetic resonance imaging ( MRI ) of 1.7 to 2 Gy per fraction to a dose of 12–19 Gy . The recommended cumulative dose to the tumor bed was therefore 55–61 Gy . At 8 weeks following radiotherapy , patients were r and omized to receive either AZQ at 15 mg/day for 3 days i.v . every 4 weeks or BCNU at 200 mg i.v . every 8 weeks . Chemotherapy was continued for at least 1 year unless death occurred , treatment failure was declared , or toxicity necessitated alteration of therapy . In the 249 r and omized patients , there was no difference between the AZQ- and BCNU-treated patients in age , sex distribution , race , tumor histology , type of surgical resection , or Karnofsky performance status ( KPS ) . Age and KPS at the initiation of therapy and tumor histology were the best overall predictors of survival . The type of chemotherapy ( AZQ vs BCNU ) was not predictive of survival . Two-year Kaplan-Meier survival was 22 % in the AZQ-treated patients and 25 % in BCNU-treated patients . In an analysis of radiotherapy administered we found that , within the range of doses required for this study , there was no influence of whole brain dose , boost dose , total dose , or size of the boost field on survival . The institution providing radiotherapy ( teaching hospital vs nonteaching facility ) did not influence survival PURPOSE The optimal radiotherapy regimen for elderly and /or frail patients with newly diagnosed glioblastoma remains to be established . This study compared two radiotherapy regimens on the outcome of these patients . PATIENTS AND METHODS Between 2010 and 2013 , 98 patients ( frail = age ≥ 50 years and Karnofsky performance status [ KPS ] of 50 % to 70 % ; elderly and frail = age ≥ 65 years and KPS of 50 % to 70 % ; elderly = age ≥ 65 years and KPS of 80 % to 100 % ) were prospect ively r and omly assigned to two arms in a 1:1 ratio , stratified by age ( < and ≥ 65 years old ) , KPS , and extent of surgical resection . Arm 1 received short-course radiotherapy ( 25 Gy in five daily fractions over 1 week ) , and arm 2 received commonly used radiotherapy ( 40 Gy in 15 daily fractions over 3 weeks ) . RESULTS The short-course radiotherapy was noninferior to commonly used radiotherapy . The median overall survival time was 7.9 months ( 95 % CI , 6.3 to 9.6 months ) in arm 1 and 6.4 months ( 95 % CI , 5.1 to 7.6 months ) in arm 2 ( P = .988 ) . Median progression-free survival time was 4.2 months ( 95 % CI , 2.5 to 5.9 ) in arm 1 and 4.2 months ( 95 % CI , 2.6 to 5.7 ) in arm B ( P = .716 ) . With a median follow-up time of 6.3 months , the quality of life between both arms at 4 weeks after treatment and 8 weeks after treatment was not different . CONCLUSION There were no differences in overall survival time , progression-free survival time , and quality of life between patients receiving the two radiotherapy regimens . In view of the reduced treatment time , the short 1-week radiotherapy regimen may be recommended as a treatment option for elderly and /or frail patients with newly diagnosed glioblastoma Twenty-five patients with malignant glioma were r and omized to receive radiation therapy only or radiation therapy and oral Levamisole . There were no differences in survival between the two groups and therefore no advantage in the use of Levamisole in glioblastoma could be demonstrated We sought to determine the impact of bevacizumab on reduction of tumor size prior to chemoradiotherapy in unresected glioblastoma patients . Patients were r and omized 1:1 to receive temozolomide ( TMZ arm ) or temozolomide plus bevacizumab ( TMZ + BEV arm ) . In both arms , neoadjuvant treatment was temozolomide ( 85 mg/m2 , days 1–21 , two 28-day cycles ) , concurrent radiation plus temozolomide , and six cycles of adjuvant temozolomide . In the TMZ + BEV arm , bevacizumab ( 10 mg/kg ) was added on days 1 and 15 of each neoadjuvant cycle and on days 1 , 15 and 30 of concurrent treatment . The primary endpoint was investigator-assessed response to neoadjuvant treatment . Secondary endpoints included progression-free survival ( PFS ) , overall survival ( OS ) , and the impact on outcome of MGMT methylation in tumor and serum . One hundred and two patients were included ; 43 in the TMZ arm and 44 in the TMZ + BEV arm were evaluable for response . Results favored the TMZ + BEV arm in terms of objective response ( 3 [ 6.7 % ] vs. 11 [ 22.9 % ] ; odds ratio 4.2 ; P = 0.04 ) . PFS and OS were longer in the TMZ + BEV arm , though the difference did not reach statistical significance . MGMT methylation in tumor , but not in serum , was associated with outcome . More patients experienced toxicities in the TMZ + BEV than in the TMZ arm ( P = 0.06 ) . The combination of bevacizumab plus temozolomide is more active than temozolomide alone and may well confer benefit in terms of tumor shrinkage in unresected patients albeit at the expense of greater toxicity BACKGROUND AND PURPOSE The common treatment in patients with newly diagnosed glioblastoma multiforme is the ultimately radical surgical removal of the tumour combined with radiotherapy . This study compared safety and efficacy of radiotherapy alone with radiotherapy combined with temozolomide ( TMZ ) given before , during , and after radiotherapy . MATERIAL AND METHODS The patients operated on for glioblastoma multiforme during the first 21 postoperative days were r and omly assigned to the group treated with radiotherapy alone ( involved-field radiotherapy in 2 Gy fractions daily five times a week up to the total of 60 Gy over 6 weeks of treatment ) or to the group treated with radiotherapy and TMZ , initially in the dose of 200 mg/m² during 5 postoperative days and after 23 days followed by 75 mg/m2 of body surface area daily , 7 days a week ( from the first to the last day of radiotherapy ) . On completion of radiotherapy , five complementary courses of TMZ were introduced ( 150 - 200 mg/m² for 5 days , repeated every 28 days ) . The primary outcome measure was overall survival . RESULTS Fifty-eight patients from 3 centres were included in the study . The mean age of patients was 55 years and all the patients underwent a surgical procedure of glioblastoma removal . The mean overall survival in the group treated with TMZ was 16.0 months , whereas in the group with radiotherapy alone the overall survival reached 12.5 months . 24-month survival reached 23 % in patients treated with TMZ and 6.7 % in those who received radiotherapy only . Haematological complications of third or fourth degree were present in 10 % of patients treated with radiotherapy and TMZ . CONCLUSIONS The introduction of TMZ before , during and after radiotherapy for newly diagnosed glioblastoma multiforme gives clinical ly and statistically significant improvement of survival with unremarkably increased toxicity of the treatment Background Cediranib , an oral pan-vascular endothelial growth factor ( VEGF ) receptor tyrosine kinase inhibitor , failed to show benefit over lomustine in relapsed glioblastoma . One resistance mechanism for cediranib is up-regulation of epidermal growth factor receptor ( EGFR ) . This study aim ed to determine if dual therapy with cediranib and the oral EGFR inhibitor gefitinib improved outcome in recurrent glioblastoma . Methods and Findings This was a multi-center r and omized , two-armed , double-blinded phase II study comparing cediranib plus gefitinib versus cediranib plus placebo in subjects with first relapse/first progression of glioblastoma following surgery and chemoradiotherapy . The primary outcome measure was progression free survival ( PFS ) . Secondary outcome measures included overall survival ( OS ) and radiologic response rate . Recruitment was terminated early following suspension of the cediranib program . 38 subjects ( 112 planned ) were enrolled with 19 subjects in each treatment arm . Median PFS with cediranib plus gefitinib was 3.6 months compared to 2.8 months for cediranib plus placebo ( HR ; 0.72 , 90 % CI ; 0.41 to 1.26 ) . Median OS was 7.2 months with cediranib plus gefitinib and 5.5 months with cediranib plus placebo ( HR ; 0.68 , 90 % CI ; 0.39 to 1.19 ) . Eight subjects ( 42 % ) had a partial response in the cediranib plus gefitinib arm versus five patients ( 26 % ) in the cediranib plus placebo arm . Conclusions Cediranib and gefitinib in combination is tolerated in patients with glioblastoma . Incomplete recruitment led to the study being underpowered . However , a trend towards improved survival and response rates with the addition of gefitinib to cediranib was observed . Further studies of the combination incorporating EGFR and VEGF inhibition are warranted . Trial Registration Clinical Trials.gov PURPOSE Surgery remains the st and ard treatment for glioma , followed by radiotherapy ( RT ) with or without chemotherapy . Despite multidisciplinary approaches , the median survival time for patients with glioblastoma multiform ( GBM ) remains at less than 1 year from initial diagnosis . Temozolomide ( TMZ ) , an oral alkylating agent , has shown promising activity in the treatment of malignant gliomas . We conducted a multicenter r and omized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM . PATIENTS AND METHODS One hundred thirty patients with pathologically confirmed , newly diagnosed GBM were r and omly assigned ( 110 assessable patients ) to receive either TMZ 75 mg/m(2)/d orally , concomitantly with RT ( 60 Gy in 30 fractions ; group A , n = 57 ) , followed by six cycles of TMZ ( 150 mg/m(2 ) on days 1 through 5 and 15 to 19 every 28 days ) , or RT alone ( 60 Gy in 30 fractions ; group B , n = 53 ) . RESULTS Median time to progression was 10.8 months in group A and 5.2 months in group B ( P = .0001 ) . One-year progression-free survival rate was 36.6 % in group A and 7.7 % in group B. Median overall survival ( OS ) time was also significantly better in group A versus group B ( 13.4 v 7.7 months , respectively ; P < .0001 ) , as was the 1-year OS at 56.3 % v 15.7 % ( P < .0001 ) , respectively . Toxicity was mainly hematologic . One patient with grade 4 myelotoxicity died as a result of sepsis . The other side effects were mild . CONCLUSION TMZ combined with RT ( concomitantly and sequentially ) seems to be more effective than RT alone in patients with newly diagnosed GBM . The combined-modality treatment was well tolerated PURPOSE Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme ( GBM ) . This phase II study was performed to determine the safety , tolerability , and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM . PATIENTS AND METHODS Sixty-four patients were enrolled onto this open-label , phase II trial . Temozolomide ( 75 mg/m(2)/d x 7 d/wk for 6 weeks ) was administered orally concomitant with fractionated radiotherapy ( 60 Gy total dose : 2 Gy x 5 d/wk for 6 weeks ) followed by temozolomide monotherapy ( 200 mg/m(2)/d x 5 days , every 28 days for six cycles ) . The primary end points were safety and tolerability , and the secondary end point was overall survival . RESULTS Concomitant radiation plus temozolomide therapy was safe and well tolerated . Nonhematologic toxicities were rare and mild to moderate in severity . During the concomitant treatment phase , grade 3 or 4 neutropenia , thrombocytopenia , or both were observed in 6 % of patients , including two severe infections with Pneumocystis carinii . During adjuvant temozolomide , 2 % and 6 % of cycles were associated with grade 3 and 4 neutropenia or thrombocytopenia , respectively . Median survival was 16 months , and the 1- and 2-year survival rates were 58 % and 31 % , respectively . Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome . CONCLUSION Continuous daily temozolomide and concomitant radiation is safe . This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma . Further investigation is warranted , and a r and omized trial is ongoing PURPOSE Radiotherapy with concomitant and adjuvant temozolomide is the st and ard of care for newly diagnosed glioblastoma ( GBM ) . O(6)-methylguanine-DNA methyltransferase ( MGMT ) methylation status may be an important determinant of treatment response . Dose-dense ( DD ) temozolomide results in prolonged depletion of MGMT in blood mononuclear cells and possibly in tumor . This trial tested whether DD temozolomide improves overall survival ( OS ) or progression-free survival ( PFS ) in patients with newly diagnosed GBM . PATIENTS AND METHODS This phase III trial enrolled patients older than age 18 years with a Karnofsky performance score of ≥ 60 with adequate tissue . Stratification included clinical factors and tumor MGMT methylation status . Patients were r and omly assigned to st and ard temozolomide ( arm 1 ) or DD temozolomide ( arm 2 ) for 6 to 12 cycles . The primary end point was OS . Secondary analyses evaluated the impact of MGMT status . RESULTS A total of 833 patients were r and omly assigned to either arm 1 or arm 2 ( 1,173 registered ) . No statistically significant difference was observed between arms for median OS ( 16.6 v 14.9 months , respectively ; hazard ratio [ HR ] , 1.03 ; P = .63 ) or median PFS ( 5.5 v 6.7 months ; HR , 0.87 ; P = .06 ) . Efficacy did not differ by methylation status . MGMT methylation was associated with improved OS ( 21.2 v 14 months ; HR , 1.74 ; P < .001 ) , PFS ( 8.7 v 5.7 months ; HR , 1.63 ; P < .001 ) , and response ( P = .012 ) . There was increased grade ≥ 3 toxicity in arm 2 ( 34 % v 53 % ; P < .001 ) , mostly lymphopenia and fatigue . CONCLUSION This study did not demonstrate improved efficacy for DD temozolomide for newly diagnosed GBM , regardless of methylation status . However , it did confirm the prognostic significance of MGMT methylation . Feasibility of large-scale accrual , prospect i ve tumor collection , and molecular stratification was demonstrated BACKGROUND Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor . Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with st and ard temozolomide chemoradiotherapy in newly diagnosed glioblastoma ( particularly in tumours with methylated MGMT promoter ) . We aim ed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter . METHODS In this multicentre , open-label , phase 3 study , we investigated the efficacy of cilengitide in patients from 146 study sites in 25 countries . Eligible patients ( newly diagnosed , histologically proven supratentorial glioblastoma , methylated MGMT promoter , and age ≥18 years ) were stratified for prognostic Radiation Therapy Oncology Group recursive partitioning analysis class and geographic region and central ly r and omised in a 1:1 ratio with interactive voice response system to receive temozolomide chemoradiotherapy with cilengitide 2000 mg intravenously twice weekly ( cilengitide group ) or temozolomide chemoradiotherapy alone ( control group ) . Patients and investigators were unmasked to treatment allocation . Maintenance temozolomide was given for up to six cycles , and cilengitide was given for up to 18 months or until disease progression or unacceptable toxic effects . The primary endpoint was overall survival . We analysed survival outcomes by intention to treat . This study is registered with Clinical Trials.gov , number NCT00689221 . FINDINGS Overall , 3471 patients were screened . Of these patients , 3060 had tumour MGMT status tested ; 926 patients had a methylated MGMT promoter , and 545 were r and omly assigned to the cilengitide ( n=272 ) or control groups ( n=273 ) between Oct 31 , 2008 , and May 12 , 2011 . Median overall survival was 26·3 months ( 95 % CI 23·8 - 28·8 ) in the cilengitide group and 26·3 months ( 23·9 - 34·7 ) in the control group ( hazard ratio 1·02 , 95 % CI 0·81 - 1·29 , p=0·86 ) . None of the predefined clinical subgroups showed a benefit from cilengitide . We noted no overall additional toxic effects with cilengitide treatment . The most commonly reported adverse events of grade 3 or worse in the safety population were lymphopenia ( 31 [ 12 % ] in the cilengitide group vs 26 [ 10 % ] in the control group ) , thrombocytopenia ( 28 [ 11 % ] vs 46 [ 18 % ] ) , neutropenia ( 19 [ 7 % ] vs 24 [ 9 % ] ) , leucopenia ( 18 [ 7 % ] vs 20 [ 8 % ] ) , and convulsion ( 14 [ 5 % ] vs 15 [ 6 % ] ) . INTERPRETATION The addition of cilengitide to temozolomide chemoradiotherapy did not improve outcomes ; cilengitide will not be further developed as an anticancer drug . Nevertheless , integrins remain a potential treatment target for glioblastoma . FUNDING Merck KGaA , Darmstadt , Germany PURPOSE A r and omised , open label phase III trial was conducted to evaluate efficacy of nimotuzumab , a monoclonal antibody against epidermal growth factor receptor ( EGF-R ) added to st and ard therapy for newly diagnosed glioblastoma . PATIENTS AND METHODS 149 glioblastoma patients stratified as with or without residual tumour were r and omly assigned to receive either intravenous nimotuzumab 400 mg weekly added to st and ard radiochemotherapy followed by 400 mg biweekly after twelve weeks or st and ard radiochemotherapy . Progression status after 52 weeks ( 12moPFS ) and progression-free survival ( PFS ) based on Macdonald criteria were co- primary and overall survival ( OS ) , toxicity and quality of life secondary end-points . RESULTS 142 patients were evaluated for efficacy ( per protocol cohort ) . 12 moPFS was 25.6 % in the experimental arm and 20.3 % in the control group . In residual tumour patients ( n=81 ) median PFS was 5.6 versus 4.0 months , ( hazard ratio ( HR ) , 0.87 ; 95 % confidence interval ( CI ) , 0.55 - 1.37 ) , for patients without residual tumour ( n=61 ) it was 10.6 versus 9.9 months , ( HR , 1.01 ; 95 % CI , 0.57 - 1.77 ) . Median OS in patients with residual tumour was 19.5 versus 16.7 months , ( HR , 0.90 ; 95 % CI , 0.52 - 1.57 ; P=0.7061 ) , for patients without 23.3 versus 21.0 months ( HR , 0.77 ; 95 % CI , 0.41 - 1.44 ; P=0.4068 ) . A small cohort of MGMT non-methylated patients with residual tumour showed PFS of 6.2 versus 4.0 months ( HR , 0.77 ; 95 % CI , 0.35 - 1.67 ; P=0.4997 ) and OS of 19.0 versus 13.8 months ( HR , 0.66 ; 95 % CI , 0.27 - 1.64 ; P=0.3648 ) . EGF-R amplification did not correlate with clinical efficacy of nimotuzumab . Nimotuzumab was well tolerated . CONCLUSION This study , albeit negative , contains hypothesis generating signals supporting evaluation of correlative , efficacy-predicting tumour parameters for nimotuzumab in the treatment of glioblastoma A r and omised trial is reported of mixed-schedule ( neutron/photon ) irradiation compared with photon therapy for patients with Grade III or Grade IV astrocytoma . Thirty-one patients were allocated to be treated by the neutron/photon regime and 30 patients by photons . The median survival was 4 months in the mixed-schedule group and 8 months in the photon group . The survival rates were not significantly different . All patients who died had evidence of residual brain tumour . None had signs of radiation-related morbidity ✓ This Phase III clinical trial compared the effectiveness of the combination of 1,3-bis(2-chloroethyl)-1-nitrosourea ( BCNU ) , radiation therapy , and hydroxyurea ( BHR group ) to the combination of BCNU and radiation therapy ( BR group ) for the treatment of malignant gliomas . In both arms of the study , BCNU was administered intravenously for 3 consecutive days before the initiation of radiation therapy , and at 8-week intervals thereafter until unequivocal tumor progression . In the BHR arm of the study , hydroxyurea was administered orally on alternate days during radiation therapy . Patients in each arm were stratified almost equally by tumor type ( glioblastoma multiforme ( GM ) or other nonglioblastoma multiforme malignant gliomas ( NGM ) ) and extent of surgical resection of tumor . Patients were also evaluated with the Karnofsky Performance Status ( KPS ) scale . Time to progression was determined by comparing the results of sequential neurological examinations and radionuclide and computerized tomographic scans . Of Summary Thirty-five adult recurrent GBM patients , divided r and omly in two groups of 19 and 16 cases , had been treated with two regimens of chemotherapy : a ) ‘ eight-drugs-in-one-day ’ ; b ) procarbazine + CCNU + vincristine ( PCV ) respectively . Chemotherapy was planned at the tumor relapse and delivered as long as tolerated without irreversible sequelae or until the CT scan showed tumor progression . Multiple agents are used simultaneously in the therapeutic approach using ‘ eight-in-one ’ to kill as many heterogeneous cells of malignant glial tumor as possible and minimize the emergence of cellular resistance to chemotherapy . Rate response to chemotherapy and the median adjunctive survival time ( 6.5 and 6 months , respectively ) are not significantly different in the two arms of this study . Our experience with such an aggressive multi-drugs combination ‘ eight-in-one-day ’ was disappointing if compared with less toxic , better tolerated and easy delivered ( PCV ) regimen PURPOSE This phase III Eastern Cooperative Oncology Group-Southwest Oncology Group intergroup study was conducted to determine whether three 72-hour infusions of carmustine ( BiCNU ) and cisplatin administered monthly before external-beam radiotherapy would improve the survival of patients with newly diagnosed glioblastoma multiforme . The control arm consisted of radiation with st and ard adjuvant BiCNU . PATIENTS AND METHODS A total of 223 patients were accrued from 1996 to 1999 . Of these , 219 patients were eligible ; 109 were r and omly assigned to the experimental arm , and 110 were r and omly assigned to the control arm . R and omization was stratified by age , performance status , and extent of resection . RESULTS The median age of the patients was 55 years ; 55 % were male , 93 % were white , 26 % had a biopsy only , and 84 % were ambulatory . Treatment arms were well balanced with respect to baseline characteristics . Median follow-up time of the 15 patients still alive at the time of analysis was 3.3 years ( range , 2 to 5 years ) . Median survival times for the st and ard and experimental arms were 11.2 and 11.0 months ( P = .33 , two-sided log-rank test ) , and survival at 1 year was 45 % versus 44 % , respectively . Fifty-six percent of patients received all three cycles of BiCNU/cisplatin , 12 % received two cycles , and 31 % received only one cycle . Toxicity was primarily hematologic and was more common in the experimental arm ( P < .01 ) . CONCLUSION This study demonstrates that 72-hour infusions of BiCNU and cisplatin followed by radiation do not improve median survival , survival at 1 year , or time to progression . Furthermore , this treatment requires more time in the hospital and is associated with more serious toxicities than st and ard therapy PURPOSE Conventional treatment of glioblastoma multiforme ( GBM ) cures less than 5 % of patients . We investigated the effect of stereotactic radiosurgery ( SRS ) added to conventional external beam radiation therapy ( EBRT ) with carmustine ( BCNU ) on the survival of patients with GBM . METHODS AND MATERIAL S A total of 203 patients with supratentorial GBM ( tumor < or = 40 mm ) were r and omly assigned either to postoperative SRS followed by EBRT ( 60 Gy ) plus BCNU ( 80 mg/m(2 ) Days 1 - 3 every 8 weeks for six cycles ) or to EBRT with BCNU alone . The dose of radiosurgery was tumor size-dependent and ranged from 15 Gy for largest to 24 Gy for smallest tumors . RT and BCNU were identical in both arms . RESULTS At a median follow-up time of 61 months , the median survival in the radiosurgery group was 13.5 months ( 95 % confidence interval , 11.0 - 14.8 ) as compared with 13.6 months ( 95 % confidence interval , 11.2 - 15.2 , p = 0.5711 ) for the st and ard treatment group . There were also no significant differences in 2- and 3-year survival rates and in patterns of failure between the two arms . Quality of life deterioration and cognitive decline at the end of therapy , compared with baseline , were comparable and there was no difference in quality -adjusted survival between the arms . CONCLUSIONS Stereotactic radiosurgery followed by EBRT and BCNU does not improve the outcome in patients with GBM nor does it change the general quality of life or cognitive functioning Purpose : To evaluate the efficacy of simultaneous postoperative temozolomide radiochemotherapy in glioblastoma patients . Patients and Methods : From February 2002 to July 2004 , n = 65 patients from 11 German centers with macroscopic complete tumor resection were r and omized to receive either postoperative radiotherapy alone ( RT , n = 35 ) or postoperative radiotherapy with simultaneous temozolomide ( RT + TMZ , n = 30 ) . Patients were stratified according to age ( ≤/>50 years ) and WHO performance score ( 0–1 vs. 2 ) . RT consisted of 60 Gy in 30 fractions . In the RT + TMZ arm , oral TMZ was administered daily at a dose of 75 mg/m2 including weekends ( 40–42 doses ) . Adjuvant treatment was not given , but in both arms , patients with recurrent tumors and in good condition ( WHO 0–2 ) were scheduled for salvage chemotherapy with TMZ . Results : The trial was stopped early due to the results of EORTC- study 26981 - 22981 that showed a survival benefit for the combination of concomitant and adjuvant TMZ compared to radiotherapy alone . In total , 62/65 patients were evaluable . Stratification variables were well balanced ( ≤ 50 years 26 % vs. 20 % , WHO 0–1 91 % vs. 100 % ) . Neither overall survival ( median 17 vs. 15 months ) nor progression-free survival ( median 7 vs. 6 months ) differed significantly between the two arms . In the RT ( RT + TMZ ) arm , 76 % ( 62 % ) of the progressing patients received salvage chemotherapy with TMZ , 36 % ( 50 % ) had a second resection . There was a time-constant trend for increased general quality of life ( EORTC question naire QLQ C30 ) and brain-specific quality of life ( EORTC question naire B20 ) in the combined arm . Lymphopenia G3–4 was more frequent ( 33 vs. 6 % ) in the RT + TMZ arm . Conclusion : After early closure of this trial , a benefit for progression-free survival for simultaneous TMZ radiochemotherapy alone could not be demonstrated . In both arms , salvage therapies were frequently used and probably had a major effect on overall survival . Ziel : Bestimmung der Effektivität einer alleinigen simultanen , postoperativen Radiochemotherapie mit Temozolomid bei Patienten mit Glioblastom . Patienten und Method ik : Von Februar 2002 bis Juli 2004 wurden n = 65 Patienten aus 11 Zentren nach makroskopischer Tumorresektion r and omisiert und erhielten entweder eine postoperative lokale Strahlenbeh and lung ( RT , n = 35 ) oder eine simultane Radiochemotherapie mit Temozolomid ( RT + TMZ , n = 30 ) . Die Stratifizierung erfolgte anh and des Alters ( ≤/>50 Jahre ) und des Allgemeinzust and s ( AZ ) nach WHO ( 0–1 vs. 2 ) . Die Bestrahlung wurde mit 60 Gy in 30 Fraktionen durchgeführt . I m RT + TMZ-Arm wurde TMZ oral in einer täglichen Dosis von 75 mg/m2 an allen Bestrahlungstagen und am Wochenende verabreicht ( 40–42 Dosen ) . Eine adjuvante Therapie mit TMZ erfolgte nicht , stattdessen war für die Patienten in gutem AZ ( WHO 0–2 ) i m Falle einer Tumorprogression in beiden Armen eine Rezidiv-Chemotherapie mit TMZ vorgesehen . Ergebnisse : Die Studie wurde vorzeitig nach der Veröffentlichung der EORTC-Studie 26981 - 22981 abgebrochen , die eine Verlängerung der Überlebenszeit durch eine simultane und adjuvante Radiochemotherapie mit TMZ gezeigt hatte . Insgesamt waren 62/65 Patienten auswertbar . Die Arme ( RT vs. RT + TMZ ) waren bezüglich der Stratifikationsvariablen ausgeglichen ( ≤ 50 Jahre 26 % vs. 20 % , WHO 0–1 91 % vs. 100 % ) . Weder das Gesamtüberleben ( Median 17 vs. 15 Monate ) noch das progressionsfreie Überleben ( Median 7 vs. 6 Monate ) unterschieden sich signifikant . In dem RT-(RT + TMZ-)Arm erhielten 76 % ( 62 % ) der progredienten Patienten eine Rezidiv-Chemotherapie mit Temodal , 36 % ( 50 % ) wurden nochmals operiert . Für die allgemeine und hirnfunktionsbezogene Lebensqualität ( EORTC-Fragebögen QLQ C30 und BN20 ) zeigte sich in dem RT + TMZ-Arm ein zeitkonstanter Trend für bessere Werte . I m RT + TMZ-Arm war die Häufigkeit einer Lymphopenie Grad 3–4 erhöht ( 33 % vs. 6%).Schlussfolgerung : Nach dem vorzeitigen Abbruch der Studie konnte ein Vorteil bezüglich des progressionsfreien Überlebens für die alleinige simultane Radiochemotherapie mit Temozolomid nicht gezeigt werden . In beiden Armen wurden Rezidivtherapien häufig eingesetzt , diese hatten wahrscheinlich einen erheblichen Einfluss auf das Gesamtüberleben Within 3 weeks of definitive surgery , 609 patients with histologically demonstrated , supratentorial malignant glioma were r and omized to receive , in addition to 6000 rads of radiotherapy , one of four treatment regimens : carmustine ( BCNU ) , high-dose methylprednisolone , procarbazine , or BCNU plus high-dose methylprednisolone . We analyzed the data for the total r and omized population and for the 527 patients ( 87 % with glioblastoma multiforme ) in whom the initial protocol specifications were met ( the valid study group ) . Significantly longer survival was experienced by patients receiving procarbazine or BCNU alone compared to those receiving only high-dose methylprednisolone . No other pairwise comparisons demonstrated differences significant at the 0.05 level . However , the combination of BCNU plus high-dose methylprednisolone tended to be less effective than BCNU alone in patients with poor prognosis . This study indicates that BCNU and procarbazine are moderately useful agents in conjunction with radiotherapy for patients with malignant glioma . In addition , future protocol s may allow use of corticosteroids in conventional dosages for treating cerebral edema and controlling symptoms ; conclusions based on survival as the endpoint are unlikely to be affected by administering steroids at somewhat greater than the usual dose . More effective regimens for the treatment of malignant glioma should be sought PURPOSE In patients with newly diagnosed glioblastoma that harbors a nonmethylated O(6)-methylguanine-DNA methyltransferase promotor , st and ard temozolomide ( TMZ ) has , at best , limited efficacy . The GLARIUS trial thus explored bevacizumab plus irinotecan ( BEV+IRI ) as an alternative to TMZ . PATIENTS AND METHODS In this phase II , unblinded trial 182 patients in 22 centers were r and omly assigned 2:1 to BEV ( 10 mg/kg every 2 weeks ) during radiotherapy ( RT ) followed by maintenance BEV ( 10 mg/kg every 2 weeks ) plus IRI(125 mg/m(2 ) every 2 weeks ) or to daily TMZ ( 75 mg/m(2 ) ) during RT followed by six courses of TMZ ( 150 - 200 mg/m(2)/d for 5 days every 4 weeks ) . The primary end point was the progression-free survival rate after 6 months ( PFS-6 ) . RESULTS In the modified intention-to-treat ( ITT ) population , PFS-6 was increased from 42.6 % with TMZ ( 95 % CI , 29.4 % to 55.8 % ) to 79.3 % with BEV+IRI ( 95 % CI , 71.9 % to 86.7 % ; P < .001 ) . PFS was prolonged from a median of 5.99 months ( 95 % CI , 2.7 to 7.3 months ) to 9.7 months ( 95 % CI , 8.7 to 10.8 months ; P < .001 ) . At progression , crossover BEV therapy was given to 81.8 % of all patients who received any sort of second-line therapy in the TMZ arm . Overall survival ( OS ) was not different in the two arms : the median OS was 16.6 months ( 95 % CI , 15.4 to 18.4 months ) with BEV+IRI and was 17.5 months ( 95 % CI , 15.1 to 20.5 months ) with TMZ . The time course of quality of life ( QOL ) in six selected domains of the European Organisation for Research and Treatment of Cancer Quality -of-Life Question naire ( QLQ ) -C30 and QLQ-BN20 ( which included cognitive functioning ) , of the Karnofsky performance score , and of the Mini Mental State Examination score was not different between the treatment arms . CONCLUSION BEV+IRI result ed in a superior PFS-6 rate and median PFS compared with TMZ . However , BEV+IRI did not improve OS , potentially because of the high crossover rate . BEV+IRI did not alter QOL compared with TMZ BACKGROUND Besides the use of temozolomide and radiotherapy for patients with favourable methylation status , little progress has been made in the treatment of adult glioblastoma . Local control of the disease by complete removal increases time to progression and survival . We assessed the efficacy and safety of a locally applied adenovirus-mediated gene therapy with a prodrug converting enzyme ( herpes-simplex-virus thymidine kinase ; sitimagene ceradenovec ) followed by intravenous ganciclovir in patients with newly diagnosed resectable glioblastoma . METHODS For this international , open-label , r and omised , parallel group multicentre phase 3 clinical trial , we recruited patients from 38 sites in Europe . Patients were eligible if they were aged 18 - 70 years , had newly diagnosed supratentorial glioblastoma multiforme amenable to complete resection , and had a Karnofsky score of 70 or more at screening . We used a computer-generated r and omisation sequence to allocate patients in a one-to-one ratio ( with block sizes of four ) to receive either surgical resection of the tumour and intraoperative perilesional injection of sitimagene ceradenovec ( 1 × 10(12 ) viral particles ) followed by ganciclovir ( postoperatively , 5 mg/kg intravenously twice a day ) in addition to st and ard care or resection and st and ard care alone . Temozolomide , not being st and ard in all participating countries at the time of the study , was allowed at the discretion of the treating physician . The primary endpoint was a composite of time to death or re-intervention , adjusted for temozolamide use , assessed by intention-to-treat ( ITT ) analysis . This trial is registered with EudraCT , number 2004 - 000464 - 28 . FINDINGS Between Nov 3 , 2005 , and April 16 , 2007 , 250 patients were recruited and r and omly allocated : 124 to the experimental group and 126 to the st and ard care group , of whom 119 and 117 patients , respectively , were included in the ITT analyses . Median time to death or re-intervention was longer in the experimental group ( 308 days , 95 % CI 283 - 373 ) than in the control group ( 268 days , 210 - 313 ; hazard ratio [ HR ] 1·53 , 95 % CI 1·13 - 2·07 ; p=0·006 ) . In a subgroup of patients with non-methylated MGMT , the HR was 1·72 ( 95 % CI 1·15 - 2·56 ; p=0·008 ) . However , there was no difference between groups in terms of overall survival ( median 497 days , 95 % CI 369 - 574 for the experimental group vs 452 days , 95 % CI 437 - 558 for the control group ; HR 1·18 , 95 % CI 0·86 - 1·61 , p=0·31 ) . More patients in the experimental group had one or more treatment-related adverse events those in the control group ( 88 [ 71 % ] vs 51 [ 43 % ] ) . The most common grade 3 - 4 adverse events were hemiparesis ( eight in the experimental group vs three in the control group ) and aphasia ( six vs two ) . INTERPRETATION Our findings suggest that use of sitimagene ceradenovec and ganciclovir after resection can increase time to death or re-intervention in patients with newly diagnosed supratentorial glioblastoma multiforme , although the intervention did not improve overall survival . Locally delivered gene therapy for glioblastoma should be further developed , especially for patients who are unlikely to respond to st and ard chemotherapy . FUNDING Ark Therapeutics PURPOSE We performed a r and omized trial to compare survival distributions and toxicity of radiation therapy ( RT ) and PCNU with those of RT and carmustine ( BCNU ) in patients with malignant glioma . PATIENTS AND METHODS A total of 346 patients with histologically verified supratentorial grade 3 and grade 4 astrocytoma were studied . After surgery , patients were r and omly assigned to receive RT 60 Gy in 30 fractions and either PCNU 100 mg/m2 or BCNU 200 mg/m2 every 7 weeks for 1 year and every 10 weeks for the second year . RT and chemotherapy were started within 72 hours of r and omization and usually on the same day . Of 334 assessable patients , 72 % had partial or radical resection and 71 % had grade 4 tumors . Median age was 59 years , and 85 % had performance scores of 0 to 2 ( Eastern Cooperative Oncology Group [ ECOG ] ) . The follow-up duration of 51 living patients ranged from 10.3 to 63.2 months , with a median of 36.2 months . RESULTS The median survival duration in each group was 47 weeks , and median time to progression was 28 weeks . PCNU produced significantly more leukopenia and thrombocytopenia , whereas BCNU produced significantly more nausea , vomiting , and irritation . CONCLUSION PCNU has no therapeutic advantage at this dose and schedule and does not warrant further study as a single agent for patients with high- grade glioma BACKGROUND Most patients with glioblastoma are older than 60 years , but treatment guidelines are based on trials in patients aged only up to 70 years . We did a r and omised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma . METHODS Patients with newly diagnosed glioblastoma were recruited from Austria , Denmark , France , Norway , Sweden , Switzerl and , and Turkey . They were assigned by a computer-generated r and omisation schedule , stratified by centre , to receive temozolomide ( 200 mg/m(2 ) on days 1 - 5 of every 28 days for up to six cycles ) , hypofractionated radiotherapy ( 34·0 Gy administered in 3·4 Gy fractions over 2 weeks ) , or st and ard radiotherapy ( 60·0 Gy administered in 2·0 Gy fractions over 6 weeks ) . Patients and study staff were aware of treatment assignment . The primary endpoint was overall survival . Analyses were done by intention to treat . This trial is registered , number IS RCT N81470623 . FINDINGS 342 patients were enrolled , of whom 291 were r and omised across three treatment groups ( temozolomide n=93 , hypofractionated radiotherapy n=98 , st and ard radiotherapy n=100 ) and 51 of whom were r and omised across only two groups ( temozolomide n=26 , hypofractionated radiotherapy n=25 ) . In the three-group r and omisation , in comparison with st and ard radiotherapy , median overall survival was significantly longer with temozolomide ( 8·3 months [ 95 % CI 7·1 - 9·5 ; n=93 ] vs 6·0 months [ 95 % CI 5·1 - 6·8 ; n=100 ] , hazard ratio [ HR ] 0·70 ; 95 % CI 0·52 - 0·93 , p=0·01 ) , but not with hypofractionated radiotherapy ( 7·5 months [ 6·5 - 8·6 ; n=98 ] , HR 0·85 [ 0·64 - 1·12 ] , p=0·24 ) . For all patients who received temozolomide or hypofractionated radiotherapy ( n=242 ) overall survival was similar ( 8·4 months [ 7·3 - 9·4 ; n=119 ] vs 7·4 months [ 6·4 - 8·4 ; n=123 ] ; HR 0·82 , 95 % CI 0·63 - 1·06 ; p=0·12 ) . For age older than 70 years , survival was better with temozolomide and with hypofractionated radiotherapy than with st and ard radiotherapy ( HR for temozolomide vs st and ard radiotherapy 0·35 [ 0·21 - 0·56 ] , p<0·0001 ; HR for hypofractionated vs st and ard radiotherapy 0·59 [ 95 % CI 0·37 - 0·93 ] , p=0·02 ) . Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation ( 9·7 months [ 95 % CI 8·0 - 11·4 ] vs 6·8 months [ 5·9 - 7·7 ] ; HR 0·56 [ 95 % CI 0·34 - 0·93 ] , p=0·02 ) , but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy ( HR 0·97 [ 95 % CI 0·69 - 1·38 ] ; p=0·81 ) . As expected , the most common grade 3 - 4 adverse events in the temozolomide group were neutropenia ( n=12 ) and thrombocytopenia ( n=18 ) . Grade 3 - 5 infections in all r and omisation groups were reported in 18 patients . Two patients had fatal infections ( one in the temozolomide group and one in the st and ard radiotherapy group ) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed . INTERPRETATION St and ard radiotherapy was associated with poor outcomes , especially in patients older than 70 years . Both temozolomide and hypofractionated radiotherapy should be considered as st and ard treatment options in elderly patients with glioblastoma . MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide . FUNDING Merck , Lion 's Cancer Research Foundation , University of Umeå , and the Swedish Cancer Society PURPOSE To determine if adjuvant interstitial hyperthermia ( HT ) significantly improves survival of patients with glioblastoma undergoing brachytherapy boost after conventional radiotherapy . METHODS AND MATERIAL S Adults with newly-diagnosed , focal , supratentorial glioblastoma < or = 5 cm in diameter were registered postoperatively on a Phase II/III r and omized trial and treated with partial brain radiotherapy to 59.4 Gy with oral hydroxyurea . Those patients whose tumor was still implantable after teletherapy were r and omized to brachytherapy boost ( 60 Gy at 0.40 - 0.60 Gy/h ) + /- HT for 30 min immediately before and after brachytherapy . Time to progression ( TTP ) and survival from date of diagnosis were estimated using the Kaplan-Meier method . RESULTS From 1990 to 1995 , 112 eligible patients were entered in the trial . Patient ages ranged from 21 - 78 years ( median , 54 years ) and KPS ranged from 70 - 100 ( median , 90 ) . Most commonly due to tumor progression or patient refusal , 33 patients were never r and omized . Of the patients , 39 were r and omized to brachytherapy ( " no heat " ) and 40 to brachytherapy + HT ( " heat " ) . By intent to treat , TTP and survival were significantly longer for " heat " than " no heat " ( p = 0.04 and p = 0.04 ) . For the 33 " no heat " patients and 35 " heat " patients who underwent brachytherapy boost , TTP and survival were significantly longer for " heat " than " no heat " ( p = 0.045 and p = 0.02 , respectively ; median survival 85 weeks vs. 76 weeks ; 2-year survival 31 % vs. 15 % ) . A multivariate analysis for these 68 patients adjusting for age and KPS showed that improved survival was significantly associated with r and omization to " heat " ( p = 0.008 ; hazard ratio 0.51 ) . There were no Grade 5 toxicities , 2 Grade 4 toxicities ( 1 on each arm ) , and 7 Grade 3 toxicities ( 1 on " no heat " and 6 on the " heat " arm ) . CONCLUSION Adjuvant interstitial brain HT , given before and after brachytherapy boost , after conventional radiotherapy significantly improves survival of patients with focal glioblastoma , with acceptable toxicity Abstract In a r and omized trial , 134 patients suffering from Glioblastoma Multiforme were r and omly assigned to three radiation treatment schedules wherein patients were treated at S hr or 24 hr intervals over a period of 1 week or 3 weeks , initially receiving 3000 rad TD ¶ ¶TD , Tumor dose . and subsequently 4000 rad TD . There were no significant differences in immediate or delayed complications amongst the various groups . Survival was not significantly different in the various study groups , and was not influenced by the patient 's age and sex , the extent of surgery or the tumor grade PURPOSE As glioblastoma progresses , patients experience a decline in health-related quality of life ( HRQoL ) . Delaying this decline is an important treatment goal . In newly diagnosed glioblastoma , progression-free survival was prolonged when bevacizumab was added to radiotherapy plus temozolomide ( RT/TMZ ) versus placebo plus RT/TMZ ( phase III AVAglio study ; hazard ratio , 0.64 ; 95 % CI , 0.55 to 0.74 ; P < .001 ) . To ensure that addition of bevacizumab to st and ard-of-care therapy was not associated with HRQoL detriment , HRQoL assessment was a secondary objective . PATIENTS AND METHODS Patients completed European Organisation for Research and Treatment of Cancer Quality of Life Question naires C30 and BN20 at each tumor assessment ( Appendix Table A1 , online only ) . Raw scores were converted to a 100-point scale and mean changes from baseline scores were evaluated ( stable : < 10-point change ; clinical ly relevant deterioration/improvement : ≥ 10-point change ) . Deterioration-free survival was the time to deterioration/progression/death ; time to deterioration was the time to deterioration/death . RESULTS Most evaluable patients who had not progressed ( > 74 % ) completed all HRQoL assessment s for at least 1 year of treatment , and almost all completed at least one HRQoL assessment at baseline ( 98.3 % and 97.6 % , bevacizumab and placebo arms , respectively ) . Mean changes from baseline did not reach a clinical ly relevant difference between arms for most items . HRQoL declined at progression in both arms . The addition of bevacizumab to RT/TMZ result ed in statistically longer ( P < .001 ) deterioration-free survival across all items . Time to deterioration was not statistically longer in the placebo plus RT/TMZ arm ( v bevacizumab ) for any HRQoL item . CONCLUSION The addition of bevacizumab to st and ard-of-care treatment for newly diagnosed glioblastoma had no impact on HRQoL during the progression-free period A r and omized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy . An effect was defined as a reduction in tumor size , changes in neurological signs and performance status within 1 month after the completion of radiotherapy , or statistically improved survival times . Seventy-seven patients from 14 neurosurgical clinics were included in this vali date d study group . Radiotherapy with a total dose of 5000 to 6000 rads , given in 25 to 30 subdoses , was applied to the whole brain and to a generous field surrounding the tumor . Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area . The response rate ( more than 50 % reduction of the tumor size ) was 13.5 % in the group treated by radiotherapy alone and 47.5 % in the group with radiotherapy and ACNU . The hematological toxicity was more severe in the group treated with radiotherapy and ACNU . Other toxicity was mild and acceptable . The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9 % and 0 % for radiotherapy alone and 59.0 % and 16.3 % for radiotherapy plus ACNU , respectively . The differences between the survival curves were not significant at the p = 0.05 level . This study has demonstrated that , although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone , the survival time was not extended significantly . It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas BACKGROUND In this post-hoc , exploratory analysis , we examined outcomes for patients enrolled in the AVAglio trial of front-line bevacizumab or placebo plus radiotherapy/temozolomide who received only a single line of therapy . METHODS Patients with newly diagnosed glioblastoma received protocol -defined treatment until progressive disease ( PD ) . Co- primary endpoints were investigator-assessed progression-free survival ( PFS ) and overall survival ( OS ) . After confirmed PD , patients were treated at the investigators ' discretion . PFS/OS were assessed in patients with a PFS event who did not receive post-PD therapy ( Group 1 ) and patients with a PFS event who received post-PD therapy plus patients who did not have a PFS event at the final data cutoff ( Group 2 ) . Kaplan-Meier methodology was used . A multivariate Cox proportional hazards model for known prognostic variables was generated . RESULTS Baseline characteristics were balanced . In patients with a PFS event who did not receive post-PD therapy ( Group 1 ; n = 225 [ 24.4 % of the intent-to-treat population ] ) , the addition of bevacizumab to radiotherapy/temozolomide result ed in a 3.6-month extension in both median PFS ( hazard ratio [ HR ] : 0.62 , P = .0016 ) and median OS ( HR : 0.67 , P = .0102 ) . Multivariate analyses supported this OS benefit ( HR : 0.66 ) . In the remaining patients ( Group 2 ; n = 696 ) , a 5.2-month PFS extension was observed in bevacizumab-treated patients ( HR : 0.61 , P < .0001 ) ; OS was comparable between the treatment arms ( HR : 0.88 , P = .1502 ) . No significant differences in safety were observed between the 2 groups . CONCLUSION This exploratory analysis suggests that the addition of bevacizumab to st and ard glioblastoma treatment prolongs PFS and OS for patients with PD who receive only one line of therapy Glioblastoma ( GBM ) is the most common malignant primary brain tumour . It disproportionately affects the older segment of the population , as approximately half of the patients with GBM are above 65 years [ 1,2 ] . Moreover , the aging of the baby boom generation foreshadows a ‘ silver tsunami ’ of GBM [ 1 ] . Overlapping problems complicate management decisions for elderly patients , whether or not they have GBM . These may include multiple comorbidities and poor physiologic reserves , polypharmacy , limited mobility , cognitive decline , and social and financial vulnerability [ 3 ] . In addition , survival among elderly patients with GBM has been consistently shorter than among younger patients , with a population based median survival of approximately 6 months ( m ) [ 4 ] . It is unclear if this is due to more aggressive tumor biology [ 5 ] , the use of less intense treatment approaches [ 3 ] or increased susceptibility to treatment toxicities [ 6 ] . The st and ard of care for GBM management for patients below 70 years of age , has been defined by the EORTC 26981/22981 NCIC-CE3 trial [ 7 ] , fondly referred to as the ‘ Stupp regimen ’ . This international , r and omized controlled trial compared concurrent and adjuvant temozolomide ( TMZ ) with conventionally fractionated radiation therapy ( RT ; 60 Gy/30 fractions ) to RT alone ( 60 Gy/30 fractions ) . The combined modality therapy ( CMT ) group had improved overall survival ( OS ) compared with the RT alone group ( hazard ratio [ HR ] : 0.63 95 % ; CI : 0.52–0.75 ; p < 0.001 ) . The 2-year OS were 27 and 10 % , respectively . The presence of O(6)-methylguanine-DNA methyltransferase ( MGMT ) methylation greatly accentuated the survival benefit with TMZ . The 5-year analysis [ 8 ] was published in 2009 and investigated if the benefit of TMZ was seen in older patients . Patients between 60 and 70 years of age comprised 30 % of the participants . The median survival for this subgroup was lower with CMT ( 10.9 vs 11.8 m ) . An unplanned subgroup analysis showed that survival differences for the 65–70-years old cohort failed to reach statistical significance ( HR : 0.78 ; 95 % CI : 0.5–1.24 ; p = 0.29 ) [ 2 ] . This suggested that older patients derived less benefit from CMT , although it had to be interpreted with caution due to the small patient numbers . Many elderly patients with GBM seen in daily clinical practice do not qualify for the ‘ Stupp regimen ’ because of their age . Unfortunately , elderly patients have been excluded from many r and omized clinical trials , and hence there is a lack of consensus on how this group should be managed – especially with regard to CMT . Across various cancer types [ 9–11 ] , hypofractionated radiotherapy regimens have Combined-modality hypofractionated radiotherapy for elderly patients with glioblastoma : setting a new st and A r and omized prospect i ve clinical trial was conducted to compare conventional high dose radiotherapy with hypofractionated , short course radiotherapy in poor prognosis patients with high grade glioma . The primary endpoint was overall survival BACKGROUND Glioblastoma , the most common primary brain tumor in adults , is usually rapidly fatal . The current st and ard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible , followed by adjuvant radiotherapy . In this trial we compared radiotherapy alone with radiotherapy plus temozolomide , given concomitantly with and after radiotherapy , in terms of efficacy and safety . METHODS Patients with newly diagnosed , histologically confirmed glioblastoma were r and omly assigned to receive radiotherapy alone ( fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks , for a total of 60 Gy ) or radiotherapy plus continuous daily temozolomide ( 75 mg per square meter of body-surface area per day , 7 days per week from the first to the last day of radiotherapy ) , followed by six cycles of adjuvant temozolomide ( 150 to 200 mg per square meter for 5 days during each 28-day cycle ) . The primary end point was overall survival . RESULTS A total of 573 patients from 85 centers underwent r and omization . The median age was 56 years , and 84 percent of patients had undergone debulking surgery . At a median follow-up of 28 months , the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone . The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 ( 95 percent confidence interval , 0.52 to 0.75 ; P<0.001 by the log-rank test ) . The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone . Concomitant treatment with radiotherapy plus temozolomide result ed in grade 3 or 4 hematologic toxic effects in 7 percent of patients . CONCLUSIONS The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma result ed in a clinical ly meaningful and statistically significant survival benefit with minimal additional toxicity Although the efficacy of the nitrosourea-based combination chemotherapy procarbazine , N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosurea , and vincristine ( PCV ) has been previously demonstrated in the setting of anaplastic/intermediate- grade gliomas , the benefit for glioblastoma patients remains unproven . In the current study , we sought to determine whether the addition of alpha-difluoromethylornithine ( eflornithine ) , an inhibitor of ornithine decarboxylase , which has shown encouraging results in the setting of recurrent glioma patients , to a nitrosourea-based therapy ( PCV ) would constitute a more effective adjuvant therapy in the treatment of glioblastoma multiforme patients in the postradiation therapy setting . Following conventional radiation therapy , 272 glioblastoma ( GBM ) patients were r and omized to receive either alpha-difluoromethylornithine-PCV ( DFMO-PCV ; 134 patients ) or PCV alone ( 138 patients ) , with survival and time to tumor progression being the primary endpoints . The starting dosage of DFMO was 3.0 g/m2 p.o . q8h for 14 days before and after treatment with N-(2-chloroethyl)-N-cyclohexyl-N-nitrosurea ; PCV was administered as previously described1 . Clinical and radiological ( Gadolinium-enhanced MRI ) follow-ups were nominally at the end of each 6 or 8 week cycle ( PCV at 6 weeks ; DFMO-PCV at 8 weeks ) . Laboratory evaluations for hematologic and other adverse effects were at 2 week intervals . There was no difference in median survival or median time-to-tumor progression between the two treatment groups , as measured from day of commencement of postradiotherapy chemotherapy [ MS ( months ) : DFMO-PCV , 10.5 ; Overall survival , as measured from time of tumor diagnosis at first surgery , was 13.3 and 14.2 months at the median and 6.2 and 8.7 % at 5 years , respectively , for the DFMO-PCV and PCV arms . The treatment effect was unchanged after adjustment for age , performance status ( KPS ) , extent of surgery , and other factors using the multivariate Cox proportional hazard model . Adverse effects associated with DFMO consisted of gastrointestinal ( diarrhea nausea/vomiting ) , cytopenias , and minimal ototoxicity ( limited to tinnitus ) at the dose range tested . The addition of DFMO to the nitrosourea-based PCV regimen in this phase III study demonstrated no additional benefit in glioblastoma patients , underscoring the resistance of glioblastoma multiforme tumors to alkylating agents . For patients with anaplastic ( intermediate grade ) gliomas , in which the previously demonstrated benefit of post-radiation chemotherapy is more substantial , the evaluation of DFMO-PCV vs. PCV is still ongoing and hopefully will yield more encouraging results Objective : We tested adjuvant chemotherapy combining dibromodulcitol ( DBD ) and bischloroethyl-nitrosourea ( BCNU ) given postoperatively to adults with newly diagnosed supratentorial malignant gliomas . Methods : We enrolled 269 patients , 255 of whom were eligible . After surgery , we treated all patients with radiation therapy , using a median dose of 60 Gy given in 30 fractions . After r and omization , patients in the chemotherapy group also received ( 1 ) six weekly courses , administered during irradiation , of DBD 700 mg/m2 and ( 2 ) one to nine ( median , four ) courses , administered during the first year following radiation therapy , of DBD 1,000 mg/m2 on day 1 and BCNU 150 mg/m2 on day 2 , with the course being repeated every 6 weeks . Results : Patients treated with radiation therapy along with DBD plus BCNU ( group 2 ) had significantly longer survival time ( p = 0.044 ) and time to progression ( p = 0.003 ) than did those treated with radiation therapy alone ( group 1 ) . The median survival time was 13.0 months for group 2 and 10.4 months for group 1 ; the median time to progression was 8.1 months for group 2 and 6.7 months for group 1 . The percentage of patients alive at 18 and 24 months was 34 % and 21 % in group 2 compared with 21 % and 12 % in group 1 . Conclusion : DBD plus BCNU is an effective adjuvant therapy for malignant glioma PURPOSE A r and omized , phase III , placebo-controlled , partially blinded clinical trial ( REGAL [ Recent in in Glioblastoma Alone and With Lomustine ] ) was conducted to determine the efficacy of cediranib , an oral pan-vascular endothelial growth factor ( VEGF ) receptor tyrosine kinase inhibitor , either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma . PATIENTS AND METHODS Patients ( N = 325 ) with recurrent glioblastoma who previously received radiation and temozolomide were r and omly assigned 2:2:1 to receive ( 1 ) cediranib ( 30 mg ) monotherapy ; ( 2 ) cediranib ( 20 mg ) plus lomustine ( 110 mg/m(2 ) ) ; ( 3 ) lomustine ( 110 mg/m(2 ) ) plus a placebo . The primary end point was progression-free survival based on blinded , independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted magnetic resonance imaging ( MRI ) brain scans . RESULTS The primary end point of progression-free survival ( PFS ) was not significantly different for either cediranib alone ( hazard ratio [ HR ] = 1.05 ; 95 % CI , 0.74 to 1.50 ; two-sided P = .90 ) or cediranib in combination with lomustine ( HR = 0.76 ; 95 % CI , 0.53 to 1.08 ; two-sided P = .16 ) versus lomustine based on independent or local review of postcontrast T1-weighted MRI . CONCLUSION This study did not meet its primary end point of PFS prolongation with cediranib either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma , although cediranib showed evidence of clinical activity on some secondary end points including time to deterioration in neurologic status and corticosteroid-sparing effects Hazard ratios ( HRs ) are used commonly to report results from r and omized clinical trials in oncology . However , they remain one of the most perplexing concepts for clinicians . A good underst and ing of HRs is needed to effectively interpret the medical literature to make important treatment decisions . This article provides clear guidelines to clinicians about how to appropriately interpret HRs . While this article focuses on the commonly used methods , the authors acknowledge that other statistical methods exist for analyzing survival data Background We evaluated patterns of tumor growth in patients with newly diagnosed MGMT-non-methylated glioblastoma who were assigned to undergo radiotherapy in conjunction with bevacizumab/irinotecan ( BEV/IRI ) or st and ard temozolomide ( TMZ ) within the r and omized phase II GLARIUS trial . Methods In 142 patients ( 94 BEV/IRI , 48 TMZ ) , we review ed magnetic resonance imaging scans at baseline and first tumor recurrence . Based on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery images , we assessed tumor growth patterns and tumor invasiveness . Tumor growth patterns were classified as either multifocal or local at baseline and recurrence ; at first recurrence , we additionally assessed whether distant lesions appeared . Invasiveness was determined as either diffuse or non-diffuse . Associations with treatment arms were calculated using Fisher ’s exact test . Results At baseline , 115 of 142 evaluable patients ( 81 % ) had a locally confined tumor . Between treatment arms , there was no significant difference in the fraction of tumors that changed from an initially local tumor growth pattern to a multifocal pattern ( 12 and 13 % , p = 0.55 ) . Distant lesions appeared in 17 % ( BEV/IRI ) and 13 % ( TMZ ) of patients ( p = 0.69 ) . 15 % of patients in the BEV/IRI arm and 8 % in the TMZ arm developed a diffuse growth pattern from an initially non-diffuse pattern ( p = 0.42 ) . Conclusions The tumor growth and invasiveness patterns do not differ between BEV/IRI and TMZ-treated MGMT-non-methylated glioblastoma patients in the GLARIUS trial . BEV/IRI was not associated with an increased rate of multifocal , distant , or highly invasive tumors at the time of recurrence BACKGROUND The proposed use of bevacizumab with radiotherapy/temozolomide for newly diagnosed glioblastoma raised potential safety concerns . Bevacizumab has been linked with stroke , bleeding events , and wound-healing complications in other tumor types ; these events are of particular concern for glioblastoma ( highly vascular tumors that are usually resected ) . Published data on the interaction of bevacizumab with radiotherapy/temozolomide are also limited . We report safety data from a phase III r and omized trial ( Avastin in Glioblastoma ) , focusing on these considerations . METHODS Eligible patients received : radiotherapy and temozolomide plus bevacizumab/placebo , 6 cycles ; a 4-week treatment break ; temozolomide plus bevacizumab/placebo , 6 cycles ; and bevacizumab/placebo until progression . Data on adverse events ( AEs ) were collected throughout . RESULTS Bevacizumab-treated patients ( n = 461 ) had a longer median safety follow-up time ( 12.3 vs 8.5 mo ) , and a higher proportion completed 6 cycles of maintenance temozolomide ( 64.6 % vs 36.9 % ) versus placebo ( n = 450 ) . The incidences of relevant AEs ( bevacizumab vs placebo , respectively ) were : arterial thromboembolic events ( 5.9 % vs 1.6 % ) ; cerebral hemorrhage ( 3.3 % vs 2.0 % ) ; wound-healing complications ( 6.9 % vs 4.7 % ) ; thrombocytopenia ( 34.1 % vs 27.3 % ) ; radiotherapy-associated skin injury ( 8.2 % vs 9.3 % ) ; alopecia ( 39.0 % vs 36.0 % ) ; gastrointestinal perforation ( including gastrointestinal abscesses and fistulae , 1.7 % vs 0.4 % ) ; and radiotherapy-associated injury ( 0.4 % vs 0.0 % ) . Overall , 15.8 % and 23.8 % of bevacizumab- and placebo-treated patients had surgery ( including biopsy ) after progression . Within 30 days of postprogression surgery , AE incidence was 10.9 % ( bevacizumab ) and 23.4 % ( placebo ) . CONCLUSION The safety profile was consistent with that expected from radiotherapy/temozolomide plus bevacizumab . The increased AE incidence with bevacizumab did not impact patients ' ability to receive st and ard-of-care treatment or to undergo further surgery Thirty-three patients with malignant glioma were r and omly divided into two groups after extensive tumor resection . Those in group A received , every five to eight weeks , a course of chemotherapy consisting of intravenously administered carmustine , 80 mg/sq m/day for three days , and vincristine sulfate , 1.4mg/sq m on days 1 and 8 . Patients in group B were treated identically and received radiation therapy ( RT ) as well , 4,500 rads whole brain plus 1,500 rads to the side of the tumor . The median survival time of group A was 30 weeks , while that of group B was 44.5 weeks , but the overall survival curves were not significantly different . The median survival times exceeded the 17 weeks reported elsewhere in comparable patients not receiving postoperative therapy . Estimates of the quality of survival suggested ( 1 ) the two groups were not comparable following r and omization , possibly influencing the results ; and ( 2 ) postoperative radiation and chemotherapy do not increase morbidity and offer a longer period than other treatments during which patients ' conditions remain stable or improve Introduction Maximal safe surgical resection followed by adjuvant chemoradiation has been st and ard for newly diagnosed glioblastoma multiforme ( GBM ) . Hypofractionated accelerated radiotherapy ( HART ) has the potential to improve outcome as it reduces the overall treatment time and increases the biological effective dose . Methods Between October 2011 and July 2017 , a total of 89 newly diagnosed GBM patients were r and omized to conventional fractionated radiotherapy ( CRT ) or HART . Radiotherapy was delivered in all patients with a three-dimensional conformal radiotherapy technique in CRT arm ( 60 Gy in 30 fractions over 6 weeks @ 2 Gy/per fraction ) or simultaneous integrated boost intensity modulated radiotherapy in HART arm ( 60 Gy in 20 fractions over 4 weeks @ 3 Gy/per fraction to high-risk planning target volume ( PTV ) and 50 Gy in 20 fractions over 4 weeks @ 2.5 Gy/per fraction to low-risk PTV ) . The primary endpoint of the trial was overall survival ( OS ) . Results After a median follow-up of 11.4 months ( Range : 2.9–42.5 months ) , 26 patients died and 39 patients had progression of the disease . Median OS for the entire cohort was 23.4 months . Median OS in the CRT and HART arms were 18.07 months ( 95 % CI 14.52-NR ) and 25.18 months ( 95 % CI 12.89-NR ) respectively , p = 0.3 . Median progression free survival ( PFS ) for the entire cohort was 13.5 months ( Range : 11.7–15.7 months ) . In multivariate analysis patients younger than 40 years of age , patients with a gross total resection of tumor and a mutated IDH-1 had significantly better OS . PFS was significantly better for patients with a gross total resection of tumor and a mutated IDH-1 . All patients included in the trial completed the planned course of radiation . Only two patients required hospital admission for features of raised intracranial tension . One patient in the HART arm required treatment interruption . Conclusion HART is comparable to CRT in terms of survival outcome . HART arm had no excess treatment interruption and minimal toxicity . Dose escalation , reduction in overall treatment time , is the advantages with use of HART Background Glioblastoma predominantly occurs in the 6th and 7th decades of life . The optimal treatment paradigm for elderly patients is not well established . We sample d current worldwide management strategies for elderly patients with newly diagnosed glioblastoma . Methods A web-based survey was developed and distributed to 168 radiation oncologists , neuro-oncologists and neurosurgeons identified through the United Council for Neurologic Subspecialties and the CNS committees for North American , European and Asian Organizations . Questions addressed treatment recommendations in order to determine whether management consensus exists in this patient subset . Results There were 68 ( 40 % ) respondents . Across respondents , the most important factors directing treatment were KPS ( 94 % ) and MGMT methylation status ( 71 % ) . Only 37 % of respondents strictly factor in age when making treatment recommendations with 59 % defining elderly as greater than 70 years-old . The most common treatment recommendations for MGMT-methylated elderly patients with KPS > 70 were as follows : st and ard chemoRT ( 49 % ) , short course chemoRT ( 39 % ) , and temozolomide alone ( 30 % ) . The most common treatment recommendations for MGMT-unmethylated patients with KPS > 70 were as follows : short course RT alone ( 51 % ) , st and ard chemoRT ( 38 % ) , and short course chemoRT ( 28 % ) . Treatment recommendations for patients with KPS < 50 were short course RT alone ( 40 % ) , best supportive care ( 57 % ) , or TMZ alone ( 17 % ) . Individuals practicing in North America were significantly more likely to recommend st and ard chemoradiation for patients compared to their European counterparts . Conclusion Worldwide treatment recommendations for elderly patients with newly diagnosed GBM vary widely . Further r and omized studies are needed to eluci date the optimal treatment strategy for this subset of patients BACKGROUND St and ard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide . In this phase 3 study , we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma . METHODS We r and omly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab ( 10 mg per kilogram of body weight every 2 weeks ) or placebo , plus radiotherapy ( 2 Gy 5 days a week ; maximum , 60 Gy ) and oral temozolomide ( 75 mg per square meter of body-surface area per day ) for 6 weeks . After a 28-day treatment break , maintenance bevacizumab ( 10 mg per kilogram intravenously every 2 weeks ) or placebo , plus temozolomide ( 150 to 200 mg per square meter per day for 5 days ) , was continued for six 4-week cycles , followed by bevacizumab monotherapy ( 15 mg per kilogram intravenously every 3 weeks ) or placebo until the disease progressed or unacceptable toxic effects developed . The co primary end points were investigator-assessed progression-free survival and overall survival . RESULTS A total of 458 patients were assigned to the bevacizumab group , and 463 patients to the placebo group . The median progression-free survival was longer in the bevacizumab group than in the placebo group ( 10.6 months vs. 6.2 months ; stratified hazard ratio for progression or death , 0.64 ; 95 % confidence interval [ CI ] , 0.55 to 0.74 ; P<0.001 ) . The benefit with respect to progression-free survival was observed across subgroups . Overall survival did not differ significantly between groups ( stratified hazard ratio for death , 0.88 ; 95 % CI , 0.76 to 1.02 ; P=0.10 ) . The respective overall survival rates with bevacizumab and placebo were 72.4 % and 66.3 % at 1 year ( P=0.049 ) and 33.9 % and 30.1 % at 2 years ( P=0.24 ) . Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group , and the glucocorticoid requirement was lower . More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events ( 66.8 % vs. 51.3 % ) and grade 3 or higher adverse events often associated with bevacizumab ( 32.5 % vs. 15.8 % ) . CONCLUSIONS The addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma . Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab ; however , the rate of adverse events was higher with bevacizumab than with placebo . ( Funded by F. Hoffmann-La Roche ; Clinical Trials.gov number , NCT00943826 . ) Background Glioblastoma is associated with a poor prognosis in the elderly . Survival has been shown to increase among patients 70 years of age or younger when temozolomide chemotherapy is added to st and ard radiotherapy ( 60 Gy over a period of 6 weeks ) . In elderly patients , more convenient shorter courses of radiotherapy are commonly used , but the benefit of adding temozolomide to a shorter course of radiotherapy is unknown . Methods We conducted a trial involving patients 65 years of age or older with newly diagnosed glioblastoma . Patients were r and omly assigned to receive either radiotherapy alone ( 40 Gy in 15 fractions ) or radiotherapy with concomitant and adjuvant temozolomide . Results A total of 562 patients underwent r and omization , 281 to each group . The median age was 73 years ( range , 65 to 90 ) . The median overall survival was longer with radiotherapy plus temozolomide than with radiotherapy alone ( 9.3 months vs. 7.6 months ; hazard ratio for death , 0.67 ; 95 % confidence interval [ CI ] , 0.56 to 0.80 ; P<0.001 ) , as was the median progression‐free survival ( 5.3 months vs. 3.9 months ; hazard ratio for disease progression or death , 0.50 ; 95 % CI , 0.41 to 0.60 ; P<0.001 ) . Among 165 patients with methylated O6‐methylguanine – DNA methyltransferase ( MGMT ) status , the median overall survival was 13.5 months with radiotherapy plus temozolomide and 7.7 months with radiotherapy alone ( hazard ratio for death , 0.53 ; 95 % CI , 0.38 to 0.73 ; P<0.001 ) . Among 189 patients with unmethylated MGMT status , the median overall survival was 10.0 months with radiotherapy plus temozolomide and 7.9 months with radiotherapy alone ( hazard ratio for death , 0.75 ; 95 % CI , 0.56 to 1.01 ; P=0.055 ; P=0.08 for interaction ) . Quality of life was similar in the two trial groups . Conclusions In elderly patients with glioblastoma , the addition of temozolomide to short‐course radiotherapy result ed in longer survival than short‐course radiotherapy alone . ( Funded by the Canadian Cancer Society Research Institute and others ; Clinical Trials.gov number , NCT00482677 . BACKGROUND RTOG 0625/ACRIN 6677 is a multicenter , r and omized , phase II trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma ( GBM ) . This study investigated whether early posttreatment progression on FLAIR or postcontrast MRI assessed by central reading predicts overall survival ( OS ) . METHODS Of 123 enrolled patients , 107 had baseline and at least 1 posttreatment MRI . Two central neuroradiologists serially measured bidimensional ( 2D ) and volumetric ( 3D ) enhancement on postcontrast T1-weighted images and volume of FLAIR hyperintensity . Progression status on all posttreatment MRIs was determined using Macdonald and RANO imaging threshold criteria , with a third neuroradiologist adjudicating discrepancies of both progression occurrence and timing . For each MRI pulse sequence , Kaplan-Meier survival estimates and log-rank test were used to compare OS between cases with or without radiologic progression . RESULTS Radiologic progression occurred after 2 chemotherapy cycles ( 8 weeks ) in 9 of 97 ( 9 % ) , 9 of 73 ( 12 % ) , and 11 of 98 ( 11 % ) 2D-T1 , 3D-T1 , and FLAIR cases , respectively , and 34 of 80 ( 43 % ) , 21 of 58 ( 36 % ) , and 37 of 79 ( 47 % ) corresponding cases after 4 cycles ( 16 weeks ) . Median OS among patients progressing at 8 or 16 weeks was significantly less than that among nonprogressors , as determined on 2D-T1 ( 114 vs 278 days and 214 vs 426 days , respectively ; P < .0001 for both ) and 3D-T1 ( 117 vs 306 days [ P < .0001 ] and 223 vs 448 days [ P = .0003 ] , respectively ) but not on FLAIR ( 201 vs 276 days [ P = .38 ] and 303 vs 321 days [ P = .13 ] , respectively ) . CONCLUSION Early progression on 2D-T1 and 3D-T1 , but not FLAIR MRI , after 8 and 16 weeks of anti-vascular endothelial growth factor therapy has highly significant prognostic value for OS in recurrent GBM PURPOSE To perform a subset analysis of survival outcomes in elderly patients with glioblastoma from a r and omized phase 3 trial comparing 2 short-course radiation therapy ( RT ) regimens in elderly and /or frail patients . METHODS AND MATERIAL S The original trial population included elderly and /or frail patients with a diagnosis of glioblastoma . Patients joined the phase 3 , r and omized , multicenter , prospect i ve , noninferiority trial ; were assigned to 1 of 2 groups in a 1:1 ratio , either short-course RT ( 25 Gy in 5 fractions , arm 1 ) or commonly used RT ( 40 Gy in 15 fractions , arm 2 ) ; and were stratified by age ( < 65 years and ≥65 years ) , Karnofsky Performance Status ( KPS ) , and extent of surgery . For the subset analysis in this study , only patients aged ≥65 years were evaluated ( elderly and frail patients were defined as patients aged ≥65 years with KPS of 50%-70 % ; elderly and non-frail patients were defined as patients aged ≥65 years with KPS of 80%-100 % ) ; 61 of the 98 initial patients comprised the patient population , with 26 patients r and omized to arm 1 and 35 to arm 2 . RESULTS In this unplanned analysis , the short-course RT results were not statistically significantly different from the results of commonly used RT in elderly patients . The median overall survival time was 6.8 months ( 95 % confidence interval [ CI ] , 4.5 - 9.1 months ) in arm 1 and 6.2 months ( 95 % CI , 4.7 - 7.7 months ) in arm 2 ( P=.936 ) . The median progression-free survival time was 4.3 months ( 95 % CI , 2.6 - 5.9 months ) in arm 1 and 3.2 months ( 95 % CI , 0.1 - 6.3 months ) in arm 2 ( P=.706 ) . CONCLUSIONS A short-course RT regimen of 25 Gy in 5 fractions is an acceptable treatment option for patients aged ≥65 years , mainly those with a poor performance status or contraindication to chemotherapy , which would be indicated in cases of methylated O6 methylguanine-DNA-methyltransferase promoter tumors OBJECTIVES To estimate models , via ordinary least squares regression , for predicting Euro Qol 5D ( EQ-5D ) , Short Form 6D ( SF-6D ) , and 15D utilities from scale scores of the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) . METHODS Forty-eight gastric cancer patients , split up into equal subgroups by age , sex , and chemotherapy scheme , were interviewed , and the survey included the QLQ-C30 , SF-36 , EQ-5D , and 15D instruments , along with sociodemographic and clinical data . Model predictive ability and explanatory power were assessed by root mean square error ( RMSE ) and adjusted R(2 ) values , respectively . Pearson 's r between predicted and reported utility indices was compared . Three r and om sub sample s , half in size the initial sample , were created and used for " external " validation of the modeling equations . RESULTS Explanatory power was high , with adjusted R(2 ) reaching 0.909 , 0.833 , and 0.611 for 15D , SF-6D , and EQ-5D , respectively . After normalization of RMSE to the range of possible values , the prediction errors were 12.0 , 5.4 , and 5.6 % for EQ-5D , SF-6D , and 15D , respectively . The estimation equations produced a range of utility scores similar to those achievable by the st and ard scoring algorithms . Predicted and reported indices from the validation sample s were comparable thus confirming the previous results . CONCLUSIONS Evidence on the ability of QLQ-C30 scale scores to validly predict 15D and SF-6D utilities , and to a lesser extent , EQ-5D , has been provided . The modeling equations must be tried in future studies with larger and more diverse sample s to confirm their appropriateness for estimating quality -adjusted life-year in cancer-patient trials including only the QLQ-C30 Abstract Background . Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is st and ard therapy in newly diagnosed glioblastoma multiforme ( GBM ) . Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM . In a r and omized phase II study , we investigated the efficacy of neoadjuvant bevacizumab combined with irinotecan ( Bev-Iri ) versus bevacizumab combined with temozolomide ( Bev-Tem ) before , during and after radiotherapy in newly diagnosed GBM . Material and methods . After surgery , patients were r and omized to Bev-Iri or Bev-Tem for eight weeks , followed by st and ard radiotherapy ( 60 Gy/30 fractions ) and concomitant Bev-Iri or Bev-Tem followed by adjuvant Bev-Iri or Bev-Tem for another eight weeks . Bev-Iri : Bevacizumab and irinotecan were given every 14 days before , during and after radiotherapy . Bev-Tem : Bevacizumab was given as in Bev-Iri and temozolomide was given for five days every four weeks before and after radiotherapy and once daily during radiotherapy . The primary endpoint was response after neoadjuvant chemotherapy and a pre-specified response rate of 30 % or more was considered of interest for future studies . Secondary endpoints were progression-free survival ( PFS ) and toxicity . Results . The response rate was 32 % ( 95 % CI 17–51 % ) for Bev-Tem ( n = 32 ) and 23 % ( 95 % CI 9–44 % ) for Bev-Iri ( n = 31 ) ( p = 0.56 ) . Median PFS was 7.7 and 7.3 months for Bev-Tem and Bev-Iri , respectively . Hematological toxicity was more frequent with Bev-Tem including one death from febrile neutropenia whereas non-hematological toxicity was manageable . Conclusions . Only the Bev-Tem arm met the pre-specified level of activity of interest . Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS |
12,021 | 20,082,718 | Reported barriers included sociocultural factors such as stigma , fear of abuse for having an STI , and infrastructural factors related to the limited number of STD clinics , and trained providers and reliable diagnostic methods .
Client-oriented counselling was found to be effective in improving partner referral outcomes .
Conclusions STD clinics can improve PN with client-oriented counselling , which should help clients to overcome perceived barriers . | Background The feasibility and acceptability of partner notification ( PN ) for sexually transmitted infections ( STIs ) in developing countries was assessed through a comprehensive literature review , to help identify future intervention needs . | The objective of this study was to determine acceptability and feasibility of patient-based partner referral ( PBPR ) and patient-delivered partner medication ( PDPM ) among female sexually transmitted infection ( STI ) patients in a community-based STI screening study . Women were r and omized to STI screening at home or at a clinic . STI patients could choose between PBPR and PDPM . Six-week follow-up interviews , and in-depth interviews , were conducted . STI prevalence was high . Most of the 106 women with an STI chose PDPM , mainly because partners would not have time or would not want to attend a clinic , and to ensure that partners received treatment . Nearly all partners reportedly took medication ( 94 ; 89 % took it in front of the woman ) or went to a clinic for treatment ( 92 % ) . No adverse events were reported . Good communication emerged as the key to successful partner notification . In conclusion , PDPM could be used as a strategy to improve STI treatment coverage Objective : To measure quality of sexually transmitted disease ( STD ) syndromic case management and aspects of health-seeking behaviour at baseline in an intervention trial . Setting : Ten rural primary care clinics , Hlabisa district , South Africa . Design : Simulated patients ( fieldworkers trained to present with STD syndromes ) made a total of 44 clinic visits ; 49 STD patients were interviewed when exiting clinics ; facilities were assessed for availability of necessary equipment and drugs ; 10 focus group discussion s were held with staff ; and STD syndrome surveillance was performed in all 10 clinics . Results : A total of 9 % of simulated patients were correctly managed ( given correct drugs , plus condoms and partner notification cards ) , recommended drug treatment was given in only 41 % of visits , and appropriate counselling was given in 48 % of visits . Among patients leaving the clinic , although 39 % waited over an hour to be seen and only 37 % were consulted in private , all reported staff attitudes as satisfactory or good . Only six clinics had syndromic management protocol s available , three reported intermittent drug shortages , and seven lacked partner notification cards . Focus group discussion s revealed good staff knowledge about STD , but showed lack of training in syndromic management and low morale . Surveillance data showed that while 75 % of those presenting for care did so within 1 week of symptom onset , 27 % had been treated for an STD in the preceding 3 months , and only 6 % of those treated were contacts . Conclusions : Quality of STD case management was poor despite good staff knowledge and availability of most essential re sources . An intervention comprising staff training and STD syndrome packets has been design ed to improve quality of case management Objectives : To describe important details of the design and operational features of the Mwanza sexually transmitted diseases ( STD ) control programme . To assess the feasibility of the intervention , the distribution of STD syndromes observed , the clinical effectiveness of syndromic STD case management , the utilisation of STD services by the population , and the quality of syndromic STD services delivered at rural health units . Methods : The intervention was integrated into rural primary healthcare ( PHC ) units . It comprised improved STD case management using the syndromic approach , facilitated by a regional programme office which ensured the training of health workers , a reliable supply of effective drugs , and regular support supervision . Five studies were performed to evaluate operational performance : ( i ) a survey of register books to collect data on patients presenting with STDs and reproductive tract infections ( RTIs ) to rural health units with improved STD services , ( ii ) a survey of register books from health units in communities without improved services , ( iii ) a survey of register books from referral clinics , ( iv ) a home based cross sectional study of STD patients who did not return to the intervention health units for follow up , ( v ) a cross sectional survey of reported STD treatment seeking behaviour in a r and om cohort of 8845 adults served by rural health units . Results : During the 2 years of the Mwanza trial , 12 895 STD syndromes were treated at the 25 intervention health units . The most common syndromes were urethral discharge ( 67 % ) and genital ulcers ( 26 % ) in men and vaginal discharge ( 50 % ) , lower abdominal tenderness ( 33 % ) , and genital ulcers ( 13 % ) in women . Clinical treatment effectiveness was high in patients from whom complete follow up data were available , reaching between 81 % and 98 % after first line treatment and 97%–99 % after first , second , and third line treatment . Only 26 % of patients referred to higher levels of health care had presented to their referral institutions . During the trial period , data from the cohort showed that 12.8 % of men and 8.6 % of women in the intervention communities experienced at least one STD syndrome . Based on various approaches , utilisation of the improved health units by symptomatic STD patients in these communities was estimated at between 50 % and 75 % . During the first 6 months of intervention attendance at intervention units increased by 53 % . Thereafter , the average attendance rate was about 25 % higher than in comparison communities . Home visits to 367 non-returners revealed that 89 % had been free of symptoms after treatment , but 28 % became symptomatic again within 3 months of treatment . 100 % of these patients reported that they had received treatment , but only 74 % had been examined , only 57 % had been given health education , and only 30 % were offered condoms . Patients did not fully recall which treatment they had been given , but possibly only 63 % had been treated exactly according to guidelines . Conclusions : This study demonstrated that it is feasible to integrate effective STD services into the existing PHC structure of a developing country . Improved services attract more patients , but additional educational efforts are needed to further improve treatment seeking behaviour . Furthermore , clear treatment guidelines , a reliable drug supply system , and regular supervision are critical . All efforts should be made to treat patients on the spot , without delay , as referral to higher levels of care led to a high number of dropouts . The syndromic approach to STD control should be supported by at least one reference clinic and laboratory per country to ensure monitoring of prevalent aetiologies , of the development of bacterial resistance , and of the effectiveness of the syndromic algorithms in use STUDY OBJECTIVE To assess quality of care of sexually transmitted diseases ( STDs ) and evaluate interactive training methods aim ed at improving providers ' performance . DESIGN AND SETTING This comparative study , with a baseline , intervention , and evaluation phases was conducted at two urban health centers in Zambia . The personnel at one health center were trained in STD management using interactive training methods . The other health center acted as a control . SUBJECTS AND METHODS Two-hundred patients with STD were interviewed and their interaction with health care providers observed before and after the training . Another 200 interviews and observations were conducted at the control health center . RESULTS The proportion of patients being examined , given health education and informed about partner notification increased significantly after the intervention . The proportion of patients who had complaints about the health care did not decrease . Long waiting time and lack of time to discuss the disease were the main complaints . CONCLUSION The training solved some , but not all , problems of poor case management . This indicates the need for a more process-oriented approach for improving quality of care Objective : To explore the role of primary health centers in provision of voluntary counseling and testing ( VCT ) in Kenya . Design and Setting : Prospect i ve service evaluation at 3 ( 1 urban and 2 rural ) government health centers . Subjects : Consecutive adult clients . Main Outcome Measures : Uptake of services , user characteristics , quality of service . Results : Counseling services received 2315 new clients over 26 months . The last quarter averaged 101 clients per clinic . More than 80 % of clients lived locally . Overall 93 % opted to test , 91 % receiving results , 82 % on the same day . Most clients tested HIV negative ( 81 % ) . Youth and men were well represented . Few couples ( 10 % ) attended . Seventeen percent of women were pregnant . Self-referral was common and illness was an uncommon reason for testing ( < 20 % ) . Thirty-one percent of clients were referred from VCT to other health center services . Counseling was perceived as high quality by users and providers . Validation of the test algorithm showed a sensitivity of 98.0 % and specificity of 98.7 % . Conclusion : Government health centers in Kenya can be appropriate providers of VCT . This pilot helped initiate a new strategy of health center-based VCT in Kenya and this has facilitated rapid expansion and more equitable provision for Kenyans Unlike contact-tracing procedures for syphilis and gonorrhea , field follow-up to locate and treat patients with Chlamydia trachomatis infections has not been extensively applied in the United States . We implemented two studies to assess the efficiency and cost-effectiveness of using field follow-up for contact of two groups : patients with chlamydial infection detected as part of a screening program and women who were sexual partners of men with nongonococcal urethritis ( NGU ) . Of the 142 patients with chlamydial infection who had not been treated empirically , 112 ( 79 % ) returned for treatment when a reminder system was used , as compared with a return rate of 97 % ( 259/266 ) achieved by field follow-up ( P less than 0.0001 ) . Among the 678 men with NGU enrolled in a r and omized trial of field follow-up vs. two self-referral methods , field follow-up yielded over three times as many partners returning to the clinic for treatment as did either of the other two methods ( P less than 0.001 ) . Analyses using the estimated costs of the intervention strategies and the medical costs associated with an untreated chlamydial infection showed that field follow-up by trained investigators proved to be not only the most efficient method for locating patients with chlamydial infection and /or patients who were at risk for it , but also the most cost-effective in terms of total health-care dollars spent BACKGROUND Treatment of sexually-transmitted infections ( STIs ) and behavioural interventions are the main methods to prevent HIV in developing countries . We aim ed to assess the effect of these interventions on incidence of HIV-1 and other sexually-transmitted infections . METHODS We r and omly allocated all adults living in 18 communities in rural Ug and a to receive behavioural interventions alone ( group A ) , behavioural and STI interventions ( group B ) , or routine government health services and community development activities ( group C ) . The primary outcome was HIV-1 incidence . Secondary outcomes were incidence of herpes simplex virus type 2 ( HSV2 ) and active syphilis and prevalence of gonorrhoea , chlamydia , reported genital ulcers , reported genital discharge , and markers of behavioural change . Analysis was per protocol . FINDINGS Compared with group C , the incidence rate ratio of HIV-1 was 0.94 ( 0.60 - 1.45 , p=0.72 ) in group A and 1.00 ( 0.63 - 1.58 , p=0.98 ) in group B , and the prevalence ratio of use of condoms with last casual partner was 1.12 ( 95 % CI 0.99 - 1.25 ) in group A and 1.27 ( 1.02 - 1.56 ) in group B. Incidence of HSV2 was lower in group A than in group C ( incidence rate ratio 0.65 , 0.53 - 0.80 ) and incidence of active syphilis for high rapid plasma reagent test titre and prevalence of gonorrhoea were both lower in group B than in group C ( active syphilis incidence rate ratio , 0.52 , 0.27 - 0.98 ; gonorrhoea prevalence ratio , 0.25 , 0.10 - 0.64 ) . INTERPRETATION The interventions we used were insufficient to reduce HIV-1 incidence in rural Ug and a , where secular changes are occurring . More effective STI and behavioural interventions need to be developed for HIV control in mature epidemics Background Patient-based partner referral ( PBPR ) , which is the main method for treating sexual partners of patients with sexually transmitted diseases ( STDs ) , has limited effectiveness . Goal The authors compared the efficacy of PBPR with patient-delivered partner medication ( PDPM ) among patients attending the Mulago STD clinic in Kampala , Ug and a. Study Design A total of 383 patients ( 187 women , 196 men ) with STDs were r and omized to the PBPR or PDPM group . The proportion of sexual partners treated in either group was compared using the chi-square statistic by intention to treat for partners whose follow-up status was unknown . Results The two groups had similar background characteristics . Of the 237 partners elicited , 176 ( 74 % ) were reported treated in the PDPM group . In the PBPR group , in which 234 partners were elicited , 79 ( 34 % ) were referred to the treatment clinic . This difference was statistically significant ( risk ratio [ RR ] , 2.44 ; 95 % CI , 1.95–3.07;P < 0.001 ) . Furthermore , PDPM was more effective than PBPR for women and for casual partners for whom PBPR is considered difficult . For women , 86 of 103 partners in the PDPM group were reported treated , compared with 23 of 104 partners in the PBPR group ( RR , 4.55 ; 95 % CI , 2.92–7.08;P < 0.001 ) . For casual partners , 18 of 51 ( 34 % ) were reported treated in the PDPM group , compared with only three of 45 partners ( 7 % ) who were referred in the PBPR group ( RR , 1.43 ; 95 % CI , 1.40–2.65;P < 0.01 ) . Conclusion Patient-delivered partner medication is more effective than patient-based partner referral in the treatment of sexual partners CONTEXT Sexual communication and appropriate treatment of sexual partners is critical to the success of STD and HIV/AIDS prevention and control . AIMS To underst and factors influencing intention of STD patients to inform their regular sexual partners and identify predictors influencing actual return of the partners . SETTING S AND DESIGN A non-r and omised survey of patients attending STD clinic in a district hospital between May and November 2000 . METHODS AND MATERIAL 182 patients were administered structured question naires to underst and their intention to notify their regular sexual partners and encouraged to refer their regular sexual partners to the clinic for management . Factors related to intent to notify partners and actual partner referral were analysed . STATISTICAL ANALYSIS USED Chi square test and forward stepwise logistic regression . RESULTS Of the 182 STD patients 77.47 % expressed their positive intention to notify their regular sexual partners . However , overall partner return rate was 40.65 % . Patients from a better economic class ( p=0.014 ) , those who had sex since having the disease ( p=0.001 ) , those who felt it was easy to tell their partners ( p=0.047 ) and perceived the necessity of investigating their partners ( p<0.001 ) were more likely to have an intention to notify their partners . Independent predictors of actual return of sexual partners were patients ' perception of partners ' susceptibility ( p=0.044 ) , positive intention to notify partners ( p=0.001 ) , partners already informed before clinic visit ( p=0.030 ) and presence of genital ulcerative diseases ( p=0.033 ) . CONCLUSIONS STD clinic counselling and education should focus on risk reduction , partner susceptibility , role of STDs in HIV transmission and improving spousal communication |
12,022 | 27,258,958 | RESULTS Decolonization with topical chlorhexidine and intranasal mupirocin result ed in reduction of S aureus SSI and methicillin-resistant S aureus nosocomial infection and eradication of S aureus nasal carriage .
CONCLUSION The results of this review indicate the combination of topical chlorhexidine and intranasal mupirocin is effective in reducing S aureus-associated SSIs | BACKGROUND Surgical site infections ( SSI ) are a serious complication of surgery .
Staphylococcus aureus ( S aureus ) is 1 of the most common causative organisms responsible for SSI .
Patients who are carriers of methicillin-resistant S aureus and methicillin-sensitive S aureus are at increased risk of developing S aureus-associated SSIs .
Decolonization of skin with chlorhexidine and nares with mupirocin may reduce the risk of SSI .
OBJECTIVE The primary object of this systematic review is to examine the effectiveness of preoperative universal decolonization of skin with chlorhexidine and nares with intranasal mupirocin in preventing SSIs . | BACKGROUND Nasal carriers of Staphylococcus aureus are at increased risk for health care-associated infections with this organism . Decolonization of nasal and extranasal sites on hospital admission may reduce this risk . METHODS In a r and omized , double-blind , placebo-controlled , multicenter trial , we assessed whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase-chain-reaction ( PCR ) assay , followed by treatment with mupirocin nasal ointment and chlorhexidine soap , reduces the risk of hospital-associated S. aureus infection . RESULTS From October 2005 through June 2007 , a total of 6771 patients were screened on admission . A total of 1270 nasal swabs from 1251 patients were positive for S. aureus . We enrolled 917 of these patients in the intention-to-treat analysis , of whom 808 ( 88.1 % ) underwent a surgical procedure . All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin . The rate of S. aureus infection was 3.4 % ( 17 of 504 patients ) in the mupirocin-chlorhexidine group , as compared with 7.7 % ( 32 of 413 patients ) in the placebo group ( relative risk of infection , 0.42 ; 95 % confidence interval [ CI ] , 0.23 to 0.75 ) . The effect of mupirocin-chlorhexidine treatment was most pronounced for deep surgical-site infections ( relative risk , 0.21 ; 95 % CI , 0.07 to 0.62 ) . There was no significant difference in all-cause in-hospital mortality between the two groups . The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin-chlorhexidine group ( P=0.005 ) . CONCLUSIONS The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission . ( Current Controlled Trials number , IS RCT N56186788 . BACKGROUND Intensive care units ( ICUs ) are high-risk setting s for the transmission of methicillin-resistant Staphylococcus aureus ( MRSA ) and vancomycin-resistant enterococcus ( VRE ) . METHODS In a cluster-r and omized trial , we evaluated the effect of surveillance for MRSA and VRE colonization and of the exp and ed use of barrier pre caution s ( intervention ) as compared with existing practice ( control ) on the incidence of MRSA or VRE colonization or infection in adult ICUs . Surveillance cultures were obtained from patients in all participating ICUs ; the results were reported only to ICUs assigned to the intervention . In intervention ICUs , patients who were colonized or infected with MRSA or VRE were assigned to care with contact pre caution s ; all the other patients were assigned to care with universal gloving until their discharge or until surveillance cultures obtained at admission were reported to be negative . RESULTS During a 6-month intervention period , there were 5434 admissions to 10 intervention ICUs , and 3705 admissions to 8 control ICUs . Patients who were colonized or infected with MRSA or VRE were assigned to barrier pre caution s more frequently in intervention ICUs than in control ICUs ( a median of 92 % of ICU days with either contact pre caution s or universal gloving [ 51 % with contact pre caution s and 43 % with universal gloving ] in intervention ICUs vs. a median of 38 % of ICU days with contact pre caution s in control ICUs , P<0.001 ) . In intervention ICUs , health care providers used clean gloves , gowns , and h and hygiene less frequently than required for contacts with patients assigned to barrier pre caution s ; when contact pre caution s were specified , gloves were used for a median of 82 % of contacts , gowns for 77 % of contacts , and h and hygiene after 69 % of contacts , and when universal gloving was specified , gloves were used for a median of 72 % of contacts and h and hygiene after 62 % of contacts . The mean ( ±SE ) ICU-level incidence of events of colonization or infection with MRSA or VRE per 1000 patient-days at risk , adjusted for baseline incidence , did not differ significantly between the intervention and control ICUs ( 40.4±3.3 and 35.6±3.7 in the two groups , respectively ; P=0.35 ) . CONCLUSIONS The intervention was not effective in reducing the transmission of MRSA or VRE , although the use of barrier pre caution s by providers was less than what was required . ( Funded by the National Institute of Allergy and Infectious Diseases and others ; STAR*ICU Clinical Trials.gov number , NCT00100386 . ) INTRODUCTION Preoperative nasal mupirocin has been shown to reduce surgical site infections ( SSIs ) in patients undergoing cardiac surgery . We analyzed the effect of mupirocin plus antiseptic body wash on SSI rate and etiology . METHODS Prospect i ve SSI surveillance was done for patients undergoing cardiac surgery before and after implementation of mupirocin nasal ointment and chlorhexidine/octenidine body wash . RESULTS Overall SSI rate was 8.6 % ( 81 out of 945 ) for the control and 6.9 % ( 58 out of 842 ) for the intervention cohort ( P = .19 ) . In multivariable analysis , the study protocol was associated with an odds ratio of 0.61 ( 95 % confidence interval , 0.41 - 0.91 ; P = .015 ) with regard to any SSI . This effect was exclusively due to a reduction in superficial SSIs and was observed both in patients with preoperative and postoperative treatment initiation . Coagulase-negative staphylococci ( CoNS ) , the most commonly isolated pathogen , were found in 37 % and 48 % ( P = .19 ) of patients in the control and the intervention cohort , respectively . CoNS were methicillin resistant in 69 % of cases . CONCLUSIONS Mupirocin and antiseptic body wash reduced the rate of superficial but not deep or organ/space SSIs . Postoperative patient treatment may be critical in reducing the risk for superficial SSI , presumably due to a reduction of bacterial skin load . A high proportion of SSI was due to methicillin-resistant CoNS and thus not covered by routine perioperative antimicrobial prophylaxis CONTEXT Nosocomial infections are an important cause of morbidity and mortality after cardiac surgery . Decolonization of endogenous potential pathogenic microorganisms is important in the prevention of nosocomial infections . OBJECTIVE To determine the efficacy of perioperative decontamination of the nasopharynx and oropharynx with 0.12 % chlorhexidine gluconate for reduction of nosocomial infection after cardiac surgery . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , r and omized , double-blind , placebo-controlled clinical trial conducted at the Onze Lieve Vrouwe Gasthuis , Amsterdam , the Netherl and s , between August 1 , 2003 , and September 1 , 2005 . Of 991 patients older than 18 years undergoing elective cardiothoracic surgery during the study interval , 954 were eligible for analysis . INTERVENTION Oropharyngeal rinse and nasal ointment containing either chlorhexidine gluconate or placebo . MAIN OUTCOME MEASURES Incidence of nosocomial infection , in addition to the rate of Staphylococcus aureus nasal carriage and duration of hospital stay . RESULTS The incidence of nosocomial infection in the chlorhexidine gluconate group and placebo group was 19.8 % and 26.2 % , respectively ( absolute risk reduction [ ARR ] , 6.4 % ; 95 % confidence interval [ CI ] , 1.1%-11.7 % ; P = .002 ) . In particular , lower respiratory tract infections and deep surgical site infections were less common in the chlorhexidine gluconate group than in the placebo group ( ARR , 6.5 % ; 95 % CI , 2.3%-10.7 % ; P = .002 ; and 3.2 % ; 95 % CI , 0.9%-5.5 % ; P = .002 , respectively ) . For the prevention of 1 nosocomial infection , 16 patients needed to be treated with chlorhexidine gluconate . A significant reduction of 57.5 % in S aureus nasal carriage was found in the chlorhexidine gluconate group compared with a reduction of 18.1 % in the placebo group ( P<.001 ) . Total hospital stay for patients treated with chlorhexidine gluconate was 9.5 days compared with 10.3 days in the placebo group ( ARR , 0.8 days ; 95 % CI , 0.24 - 1.88 ; P = .04 ) . CONCLUSION Decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate appears to be an effective method to reduce nosocomial infection after cardiac surgery . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00272675 BACKGROUND Both targeted decolonization and universal decolonization of patients in intensive care units ( ICUs ) are c and i date strategies to prevent health care-associated infections , particularly those caused by methicillin-resistant Staphylococcus aureus ( MRSA ) . METHODS We conducted a pragmatic , cluster-r and omized trial . Hospitals were r and omly assigned to one of three strategies , with all adult ICUs in a given hospital assigned to the same strategy . Group 1 implemented MRSA screening and isolation ; group 2 , targeted decolonization ( i.e. , screening , isolation , and decolonization of MRSA carriers ) ; and group 3 , universal decolonization ( i.e. , no screening , and decolonization of all patients ) . Proportional-hazards models were used to assess differences in infection reductions across the study groups , with clustering according to hospital . RESULTS A total of 43 hospitals ( including 74 ICUs and 74,256 patients during the intervention period ) underwent r and omization . In the intervention period versus the baseline period , modeled hazard ratios for MRSA clinical isolates were 0.92 for screening and isolation ( crude rate , 3.2 vs. 3.4 isolates per 1000 days ) , 0.75 for targeted decolonization ( 3.2 vs. 4.3 isolates per 1000 days ) , and 0.63 for universal decolonization ( 2.1 vs. 3.4 isolates per 1000 days ) ( P=0.01 for test of all groups being equal ) . In the intervention versus baseline periods , hazard ratios for bloodstream infection with any pathogen in the three groups were 0.99 ( crude rate , 4.1 vs. 4.2 infections per 1000 days ) , 0.78 ( 3.7 vs. 4.8 infections per 1000 days ) , and 0.56 ( 3.6 vs. 6.1 infections per 1000 days ) , respectively ( P<0.001 for test of all groups being equal ) . Universal decolonization result ed in a significantly greater reduction in the rate of all bloodstream infections than either targeted decolonization or screening and isolation . One bloodstream infection was prevented per 54 patients who underwent decolonization . The reductions in rates of MRSA bloodstream infection were similar to those of all bloodstream infections , but the difference was not significant . Adverse events , which occurred in 7 patients , were mild and related to chlorhexidine . CONCLUSIONS In routine ICU practice , universal decolonization was more effective than targeted decolonization or screening and isolation in reducing rates of MRSA clinical isolates and bloodstream infection from any pathogen . ( Funded by the Agency for Healthcare Research and the Centers for Disease Control and Prevention ; REDUCE MRSA Clinical Trials.gov number , NCT00980980 ) BACKGROUND Surgical site infection has been identified as one of the most important preventable sources of morbidity and mortality associated with medical treatment . The purpose of the present study was to evaluate the feasibility and efficacy of an institutional prescreening program for the preoperative detection and eradication of both methicillin-resistant and methicillin-sensitive Staphylococcus aureus in patients undergoing elective orthopaedic surgery . METHODS Data were collected prospect ively during a single-center study . A universal prescreening program , employing rapid polymerase chain reaction analysis of nasal swabs followed by an eradication protocol of intranasal mupirocin and chlorhexidine showers for identified carriers , was implemented . Surgical site infection rates were calculated and compared with a historical control period immediately preceding the start of the screening program . RESULTS During the study period , 7019 of 7338 patients underwent preoperative screening before elective surgery , for a successful screening rate of 95.7 % . One thous and five hundred and eighty-eight ( 22.6 % ) of the patients were identified as Staphylococcus aureus carriers , and 309 ( 4.4 % ) were identified as methicillin-resistant Staphylococcus aureus carriers . A significantly higher rate of surgical site infection was observed among methicillin-resistant Staphylococcus aureus carriers ( 0.97 % ; three of 309 ) compared with noncarriers ( 0.14 % ; seven of 5122 ) ( p = 0.0162 ) . Although a higher rate of surgical site infection was also observed among methicillin-sensitive Staphylococcus aureus carriers ( 0.19 % ; three of 1588 ) compared with noncarriers , this difference did not achieve significance ( p = 0.709 ) . Overall , thirteen cases of surgical site infection were identified during the study period , for an institutional infection rate of 0.19 % . This rate was significantly lower than that observed during the control period ( 0.45 % ; twenty-four cases of surgical site infection among 5293 patients ) ( p = 0.0093 ) . CONCLUSIONS Implementation of an institution-wide prescreening program for the identification and eradication of methicillin-resistant and methicillin-sensitive Staphylococcus aureus carrier status among patients undergoing elective orthopaedic surgery is feasible and can lead to significant reductions in postoperative rates of surgical site infection . LEVEL OF EVIDENCE Therapeutic Level III . See Instructions to Authors for a complete description of levels of evidence BACKGROUND Despite a paucity of evidence , decolonization measures are prescribed for out patients with recurrent Staphylococcus aureus skin and soft-tissue infection ( SSTI ) . OBJECTIVE Compare the effectiveness of 4 regimens for eradicating S. aureus carriage . DESIGN Open-label , r and omized controlled trial . Colonization status and recurrent SSTI were ascertained at 1 and 4 months . SETTING Barnes-Jewish and St. Louis Children 's Hospitals , St. Louis , Missouri , 2007 - 2009 . PARTICIPANTS Three hundred patients with community-onset SSTI and S. aureus colonization in the nares , axilla , or inguinal folds . INTERVENTIONS Participants were r and omized to receive no therapeutic intervention ( control subjects ) or one of three 5-day regimens : 2 % mupirocin ointment applied to the nares twice daily , intranasal mupirocin plus daily 4 % chlorhexidine body washes , or intranasal mupirocin plus daily dilute bleach water baths . RESULTS Among 244 participants with 1-month colonization data , modified intention-to-treat analysis revealed S. aureus eradication in 38 % of participants in the education only ( control ) group , 56 % of those in the mupirocin group ( P = .03 vs controls ) , 55 % of those in the mupirocin and chlorhexidine group ( P = .05 ) , and 63 % off those in the mupirocin and bleach group ( P = .006 ) . Of 229 participants with 4-month colonization data , eradication rates were 48 % in the control group , 56 % in the mupirocin only group ( P = .40 vs controls ) , 54 % in the mupirocin and chlorhexidine group ( P = .51 ) , and 71 % in the mupirocin and bleach group ( P = .02 ) . At 1 and 4 months , recurrent SSTIs were reported by 20 % and 36 % of participants , respectively . CONCLUSIONS An inexpensive regimen of dilute bleach baths , intranasal mupirocin , and hygiene education effectively eradicated S. aureus over a 4-month period . High rates of recurrent SSTI suggest that factors other than endogenous colonization are important determinants of infection . Trial registration . Clinical Trials.gov identifier : NCT00513799 Abstract Purpose The reduction in acquired infections ( AI ) due to methicillin-resistant Staphylococcus aureus ( MRSA ) with the mupirocin/chlorhexidine ( M/C ) decontamination regimen has not been well studied in intubated patients . We performed post hoc analysis of a prior trial to assess the impact of M/C on MRSA AI and colonization . Methods We conducted a multicenter , placebo-controlled , r and omized , double-blind study with the primary aim to reduce all-cause AI . The two regimens used [ topical polymyxin and tobramycin ( P/T ) , nasal mupirocin with chlorhexidine body wash ( M/C ) , or corresponding placebos for each regimen ] were administered according to a 2 × 2 factorial design . Participants were intubated patients in the intensive care units of three French university hospitals . The patients enrolled in the study ( n = 515 ) received either active P/T ( n = 130 ) , active M/C ( n = 130 ) , both active regimens ( n = 129 ) , or placebos only ( n = 126 ) for the period of intubation and an additional 24 h. The incidence and incidence rates ( per 1,000 study days ) of MRSA AI were assessed . Due to the absence of a statistically significant interaction between the two regimens , analysis was performed at the margins by comparing all patient receiving M/C ( n = 259 ) to all patients not receiving M/C ( n = 256 ) , and all patients receiving P/T ( n = 259 ) to all patients not receiving P/T ( n = 256 ) . Results Incidence [ odds ratio ( OR ) 0.39 , 95 % confidence interval ( CI ) ( 0.16–0.96 ) , P = 0.04 ] and incidence rates [ incidence rate ratio ( IRR ) 0.41 , 95 % CI 0.17–0.97 , P = 0.05 ] of MRSA AI were significantly lower with the use of M/C. We also observed an increase in the incidence ( OR 2.50 , 95 % CI 1.01–6.15 , P = 0.05 ) and the incidence rate ( IRR 2.90 , 95 % CI 1.20–8.03 , P = 0.03 ) of MRSA AI with the use of P/T. Conclusion Among our study cohort of intubated patients , the use of M/C significantly reduced MRSA AI BACKGROUND Eradication of methicillin-resistant Staphylococcus aureus ( MRSA ) carriage may reduce the risk of MRSA infection and prevent transmission of the organism to other patients . METHODS To determine the efficacy of decolonization therapy , patients colonized with MRSA were r and omized ( 3:1 allocation ) to receive treatment ( 2 % chlorhexidine gluconate washes and 2 % mupirocin ointment intranasally , with oral rifampin and doxycycline for 7 days ) , or no treatment . Follow-up sample s for MRSA culture were obtained from the nares , perineum , skin lesions , and catheter exit sites monthly for up to 8 months . The primary outcome measure was detection of MRSA at 3 months of follow-up . Univariate and multivariable analyses were performed to identify variables associated with treatment failure . RESULTS Of 146 patients enrolled in the study , 112 patients ( 87 treated ; 25 not treated ) were followed up for at least 3 months . At 3 months of follow-up , 64 ( 74 % ) of those treated had culture results negative for MRSA , compared with 8 ( 32 % ) of those not treated ( P=.0001 ) . This difference remained significant at 8 months of follow-up , at which time , 54 % of those treated had culture results negative for MRSA ( chi2=64.4 ; P<.0001 , by log-rank test ) . The results of the multivariable analysis indicated that having a mupirocin-resistant isolate at baseline was associated with treatment failure ( relative risk , 9.4 ; 95 % confidence interval , 2.8 - 31.9 ; P=.0003 ) , whereas decolonization therapy was protective ( relative risk , 0.1 ; 95 % confidence interval , 0.04 - 0.4 ; P=.0002 ) . Mupirocin resistance emerged in only 5 % of follow-up isolates . CONCLUSIONS Treatment with topical mupirocin , chlorhexidine gluconate washes , oral rifampin , and doxycycline for 7 days was safe and effective in eradicating MRSA colonization in hospitalized patients for at least 3 months Staphylococcus aureus ( S. aureus ) is an independent risk factor for orthopaedic surgical site infection ( SSI ) . To determine whether a preoperative decolonization protocol reduces S. aureus SSIs , we conducted a prospect i ve observational study of patients undergoing elective total joint arthroplasty ( TJA ) at our institution , with two control groups . The concurrent control group comprised patients of surgeons who did not participate in the intervention study . The preintervention control group comprised patients of participating surgeons who had undergone elective TJA during the year before the study . Patients in the intervention group were screened preoperatively for S. aureus by nasal swab cultures . S. aureus carriers were decolonized with mupirocin ointment to the nares twice daily and chlorhexidine bath once daily for 5 days before surgery . All 164 of 636 participants ( 26 % ) who tested positive completed the decolonization protocol without adverse events and had no postoperative S. aureus SSIs at 1-year followup . In contrast , 1330 concurrent control patients had 12 S. aureus infections . If these infections had occurred in the 26 % of patients expected to be nasal carriers of S. aureus at a given time , the infection rate would have been 3.5 % ( 12 of 345 ) in the control group . In addition , the overall infection rate of the participating surgeons , including nonstaphylococcal infections , decreased from 2.6 % during the preintervention period to 1.5 % during the intervention period , translating to an adjusted economic gain of $ 231,741 for the hospital . The data suggest a preoperative decolonization protocol reduces S. aureus SSIs in patients undergoing TJA.Level of Evidence : Level II , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence OBJECTIVE To compare an interventional protocol with a st and ard protocol for preventing the acquisition of methicillin-resistant Staphylococcus aureus ( MRSA ) in the intensive care unit ( ICU ) . DESIGN Prospect i ve , r and omized , controlled , parallel-group , nonblinded clinical trial . SETTING Medical ICUs of 2 French university hospitals . PARTICIPANTS Five hundred adults with an expected length of stay in the ICU greater than 48 hours . INTERVENTIONS For the intervention group , the protocol required repeated MRSA screening , contact and droplet isolation pre caution s for patients at risk for MRSA at ICU admission and for MRSA-positive patients , and decontamination with nasal mupirocin and chlorhexidine body wash for MRSA-positive patients . For the st and ard group , the st and ard pre caution s protocol was used , and the results of repeated MRSA screening in the st and ard group were not communicated to investigators . MAIN OUTCOME MEASURE MRSA acquisition rate in the ICU . An audit was conducted to assess compliance with hygiene and isolation pre caution s. RESULTS In the intent-to-treat analysis ( [ Formula : see text ] ) , the MRSA acquisition rate in the ICU was similar in the st and ard ( 13 [ 5.3 % ] of 243 ) and intervention ( 16 [ 6.5 % ] of 245 ) groups ( [ Formula : see text ] ) . The audit showed that the overall compliance rate was 85.5 % in the st and ard group and 84.1 % in the intervention group ( [ Formula : see text ] ) , although compliance was higher when isolation pre caution s were absent than when they were in place ( 88.2 % vs 79.1 % ; [ Formula : see text ] ) . MRSA incidence rates were higher without isolation pre caution s ( 7.57‰ ) than with isolation pre caution s ( 2.36‰ ; [ Formula : see text ] ) . CONCLUSIONS Individual allocation to MRSA screening , isolation pre caution s , and decontamination do not provide individual benefit in reducing MRSA acquisition , compared with st and ard pre caution s , although the collective risk was lower during the periods of isolation . TRIAL REGISTRATION Clinical trials.gov identifier : NCT00151606 OBJECTIVES /HYPOTHESIS Surgical site infections ( SSIs ) are an important cause of morbidity and mortality after head and neck surgery . Our primary objective was to determine the efficacy of preoperative topical antimicrobial decolonization before head and neck surgery . STUDY DESIGN Prospect i ve , r and omized controlled trial . METHODS This study was conducted among 84 patients presenting for head and neck surgery requiring admission to an academic medical center . Preoperative cultures were performed to identify Staphylococcus aureus carriers . Patients were r and omized to preoperative topical antimicrobial decolonization with a 5-day regimen of chlorhexidine skin rinses and intranasal mupirocin coupled with st and ard perioperative systemic antimicrobial prophylaxis , versus st and ard prophylaxis alone . The main outcome was the incidence of SSIs . RESULTS Despite a trend suggesting a decrease in SSIs with perioperative topical antimicrobial decolonization ( 24 % vs. 10 % ) , there was no significant difference ( odds ratio , 0.34 ; 95 % confidence interval , 0.10 - 1.18 ; P = .079 ) . Patients with a higher American Society of Anesthesiologists score ( 3 vs. 1 ; P = .02 ) , with more operative blood loss ( P = .05 ) , and who required operative takeback ( P = .04 ) had a higher rate of SSIs ; there was a trend suggesting a higher rate of SSIs among patients undergoing clean-contaminated surgery compared to clean cases ( P = .08 ) and among those having received prior radiation ( P = .07 ) or chemotherapy ( P = .06 ) . CONCLUSIONS Preoperative antimicrobial decolonization did not significantly decrease the incidence of SSIs after head and neck surgery , but might be considered for high-risk groups despite the lack of conclusive evidence confirming efficacy . Risk factors for SSIs after head and neck surgery are identified for the first time in a prospect i ve study BACKGROUND The optimal method of reducing the risk of surgical site infection ( SSI ) after dermatologic surgery is unclear . Empiric , preoperative antibiotic use is common practice but lacks supporting evidence for its efficacy in preventing SSI . Risk stratification for patients at high risk of postoperative SSI based on a nasal swab is a viable strategy when coupled with topical decolonization for positive carriers . We compared the rates of infection in patients undergoing Mohs micrographic surgery ( MMS ) with nasal carriage of Staphylococcus aureus who received oral antibiotics or topical decolonization . METHODS A r and omized , controlled trial with 693 patients was conducted over a 30‐week period at a single surgical practice . Patients were stratified into nasal carriers or noncarriers of S. aureus based on a preoperative nasal swab . Nasal carriers of S. aureus were r and omized to receive topical decolonization with intranasal mupirocin twice daily plus 4 % chlorhexidine gluconate body wash daily for 5 consecutive days before surgery or statim pre‐ and postoperative doses of oral cephalexin . RESULTS One hundred seventy‐nine patients ( 25.8 % ) were identified as carriers of S. aureus . Ninety received topical decolonization , and 89 received oral antibiotics . These groups were compared with a swab‐negative Mohs surgical cohort over the same time period . There were no significant differences between the groups in terms of demographic characteristics or comorbidities . Nine percent of patients receiving oral antibiotic prophylaxis and 0 % receiving topical decolonization developed early SSI ( p = .003 ) . CONCLUSION In patients with demonstrable carriage of S. aureus , topical decolonization result ed in fewer SSI than in patients receiving perioperative oral antibiotics . Antibiotics should be reserved for clinical ly suspected and swab‐proven infections rather than being prescribed empirically . Further efforts should be directed toward optimizing endogenous risk factor control for all patients presenting for MMS This r and omized controlled trial was design ed to assess the effect of preoperative chlorhexidine showers on skin colonization and postoperative infection rates associated with plastic surgical procedures involving the trunk . Chlorhexidine showers were effective in reducing skin colonization with coagulase-negative staphylococci and yeasts , but there was no difference in postoperative infection rates OBJECTIVE To test the hypothesis that perioperative elimination of nasal carriage of Staphylococcus aureus using mupirocin nasal ointment reduces the surgical-site infection ( SSI ) rate in cardiothoracic surgery . DESIGN Unblinded intervention trial with historical controls . SETTING A university hospital , tertiary referral center for cardiothoracic surgery . PATIENTS Consecutive patients undergoing cardiothoracic surgery between August 1 , 1989 , and February 1 , 1991 ( historical control group ) , and between March 1 , 1991 , and August 1 , 1992 ( intervention group ) . RESULTS The historical control group consisted of 928 patients and the intervention group of 868 , of whom 752 actually were treated . The 116 patients who were unintentionally not treated were considered as a concurrent control group . In the intention-to-treat analysis , a significant reduction in SSI rate was observed after the intervention ( historical-control group 7.3 % and intervention group 2.8 % ; P < .0001 ) . The SSI rate in the concurrent control group was significantly higher than in the treated group ( 7.8 % and 2.0 % , respectively ; P = .0023 ) . Resistance of S aureus to mupirocin was not observed . CONCLUSION The results of this study indicate that perioperative elimination of nasal carriage using mupirocin nasal ointment significantly reduces the SSI rate in cardiothoracic surgery patients and warrants a prospect i ve , r and omized , placebo-controlled efficacy trial . This preventive measure may be beneficial in other categories of surgical patients as well OBJECTIVE To study the efficacy of mupirocin for the elimination of nasal carriage of Staphylococcus aureus in hemodialysis patients . DESIGN The efficacy of mupirocin was studied in a prospect ively followed cohort . The effect of this intervention on the rate of S aureus bacteremia was evaluated using a historic control group . SETTING Patients on the hemodialysis unit of the University Hospital Rotterdam , a tertiary referral center . PATIENTS The study group consisted of consecutive patients on hemodialysis from February 1 , 1992 , until November 1 , 1993 . They were screened by taking nasal cultures monthly during their time on hemodialysis . If S aureus was isolated , treatment with mupirocin nasal ointment was initiated . The control group consisted of patients treated on the same hemodialysis unit from January 1 , 1990 , until January 1 , 1992 . RESULTS The study group consisted of 226 patients , of whom 172 were evaluated to determine the efficacy of mupirocin . Sixty-seven ( 39 % ) were identified as nasal carriers . Following the initial treatment , 66 nasal cultures ( 98.5 % ) became negative . After 3 months and 6 months , respectively , 63 ( 94 % ) and 61 ( 91 % ) of the treated carriers had negative cultures . The rate of bacteremia ( defined as the number of episodes of S aureus bacteremia per patient-year on hemodialysis ) was significantly lower among the 226 patients in the study group ( 0.04 per patient-year ) than among the 273 patients in the control group ( 0.25 per patient year , P < .001 ) . Development of resistance and adverse effects were not observed . CONCLUSIONS Mupirocin nasal ointment effectively eliminates nasal carriage of S aureus in patients on hemodialysis . This was associated with a significant reduction of the incidence of S aureus bacteremia , as compared to historic controls BACKGROUND Two-thirds of surgical site infections ( SSI ) because of Staphylococcus aureus are caused by Methicillin resistant Staphylococcus aureus ( MRSA ) . This study was done to assess the efficacy of topical 2 % mupirocin with 2 % chlorhexidine gluconate body wash in decolonizing MRSA and its impact in preventing SSI because of MRSA . The various risk factors associated with MRSA carriers and SSI were also studied because of paucity of data in the developing world . METHODS We did a non-r and omised interventional trial in 602 patients undergoing elective general surgical operations . All patients in case ( 297 ) group were screened for MRSA and those positive were decolonised with topical 2 % mupirocin calcium ointment and daily baths with 2 % chlorhexidine antiseptic solution for 5 days . Control ( 305 ) group patients underwent surgery without decolonisation . Postoperatively , all patients were followed up for SSI for 30 days . RESULTS Prevalence of MRSA carriers was 7.5 % with decolonisation rate of 95.2 % . The SSI incidence was 21.3 % . The significant risk factors for SSI were type of anaesthesia ( p = 0.002 ) , duration of surgery ( p = 0.001 ) and preoperative hospital stay ( p = 0.001 ) . There was a significant association between MRSA carrier positivity at the time of surgery and SSI ( p = 0.041 ) . CONCLUSIONS There was no reduction in rate of SSI or other nosocomial infections in patients undergoing elective general surgical operations following preoperative MRSA decolonisation with 2 % mupirocin and 2 % chlorhexidine gluconate in MRSA carriers . MRSA carrier status was a significant risk factor for SSI but not for other nosocomial infections We conducted a prospect i ve cohort study on the effectiveness of preoperative bathing with chlorhexidine gluconate ( CHG ) cloths for reducing surgical site infections . We hypothesized that use of CHG cloths as an adjunct to surgical prep would significantly reduce the endogenous flora of surgical patients and therefore reduce surgical site infections . Data from a control group of patients who had undergone general , vascular , and orthopedic surgery were used for comparison . Results indicated an overall reduction of infection in the group that received a 2 % CHG bath before surgery . There also was a possible reduction in postoperative organ space infection , although the sample numbers were extremely small . To reduce surgical site infections , we suggest a nursing protocol of preoperative bathing with a 2 % CHG cloth for patients undergoing general and vascular surgery , and an additional trial to investigate the use of preoperative CHG cloth baths in all surgical patient population Staphylococcus aureus is a common cause of infection in hospitalized neonates . Management of these infections has become complicated by the emergence of methicillin-resistant Staphylococcus aureus ( MRSA ) strains.1 MRSA infections in United States neonatal intensive care units ( NICU ) increased over 300 % between 1995 and 2004.2 Strategies to manage MRSA in the NICU include h and hygiene , cohorting and isolation , periodic surveillance cultures , and screening healthcare workers.3 In response to a cluster of MRSA infections in the 42 bed , level four NICU at The Johns Hopkins Hospital in April 2007 , the Department of Hospital Epidemiology and Infection Control initiated a comprehensive infection prevention and control strategy . The program included admission surveillance cultures on children transferred from outside hospitals and weekly cultures in all patients , cohorting and isolating MRSA colonized patients , and reinforced h and hygiene , environmental cleaning , and strict contact pre caution s. In June 2007 , decolonization ( intranasal mupirocin for all neonates and topical chlorhexidine baths for infants greater than 36 weeks gestational age or greater than 4 weeks chronological age ) was recommended for MRSA colonized infants . In July 2007 , healthcare workers were screened and carriers decolonized . Our objectives were to measure the incidence of MRSA infections over time and to assess the contribution of MRSA decolonization in preventing nosocomial MRSA infections . We retrospectively identified patients in the NICU who grew MRSA or methicillin-susceptible Staphylococcus aureus ( MSSA ) from any culture obtained between January 1 , 2002 and June 30 , 2009 . Healthcare-associated MRSA and MSSA infections met the criteria established by the National Healthcare Safety Network (NHSN).4 Incidence rates for MRSA and MSSA infections were calculated as number of infections per 10,000 patient-days , and rates before and after the intervention were compared using Poisson regression with a linear spline term . Characteristics of patients colonized with MRSA after June 1 , 2007 including occurrence of MRSA infection were collected . Comparisons were made using Fisher ’s exact test and Wilcoxon rank-sum test with a 2-tailed P value of < 0.05 , using Stata version 10.0 ( Stata Corp. , College Station , TX ) . The institutional review board approved this study . From January 2002 to June 2009 , 60 patients in the JHH NICU had a healthcare-associated Staphylococcal infection . Forty-three patients ( 72 % ) had MSSA infections and 17 ( 28 % ) had MRSA infections . There was an increased trend in MRSA infections between 2002 and 2007 ( IRR 1.54 , 95 % confidence interval [ CI ] 1.04–2.29 ) , but no increased trend in MSSA infections ( IRR 1.04 , 95 % CI 0.84–1.29 ) . After initiation of our comprehensive MRSA control program in 2007 , there was a significant reduction in the trend of MRSA infections ( P=0.04 ) , but not a reduction in the trend of MSSA infections ( P=0.82 ) . From June 2007 through June 2009 , 29 patients were identified as MRSA carriers . Four patients were identified upon unit discharge , one patient was identified upon developing an MRSA infection ; 24 patients were eligible for MRSA decolonization . Sixteen colonized patients ( 67 % ) received intranasal mupirocin of whom five received at least one topical chlorhexidine bath . There were no differences in demographic or clinical characteristics between patients who were treated and those who were not treated with intranasal mupirocin [ see Table 1 ] . During 615 days of follow up time for these 24 MRSA colonized patients in the NICU , there were four MRSA infections ; one in the mupirocin treated group and three in the not-treated group ( IRR 0.08 , 95 % CI 0.002–1.03 ) . Table 1 Characteristics of Patients Colonized with Methicillin-Resistant Staphylococcus aureus ( MRSA ) Who Were Eligible for Intranasal Mupirocin Therapy Between 2002 and 2007 , our tertiary care NICU experienced a 54 % average annual increase in incidence of hospital-acquired MRSA infections . After introduction of a comprehensive infection control and prevention strategy to identify and cohort MRSA carriers and attempt MRSA decolonization , there was a significant reduction in the trend of MRSA infections . Active surveillance culturing for MRSA carriers in combination with isolation and decolonization has been used to control MRSA transmission and reduce MRSA infection rates.5–7 Screening alone may not be effective in controlling endemic MRSA in the NICU.8 Our findings agree with previous studies demonstrating that a comprehensive MRSA control strategy including MRSA decolonization significantly reduced rates of MRSA infections.5–7 A “ search and destroy ” strategy is mostly reserved for units with high MRSA prevalence or frequent hospital-acquired MRSA infections despite adherence to best practice infection prevention measures .9 The role of MRSA decolonization in multifaceted MRSA control strategies is difficult to quantify.10 Our findings suggest MRSA infection rates may be lowered by MRSA decolonization with intranasal mupirocin with or without chlorhexidine baths ; however , our cohort had few MRSA infections and our result did not achieve statistical significance . Whether MRSA infections in hospitals are reduced by screening and isolation ( search ) or decolonization ( destroy ) or a combination of both ( search and destroy ) requires further study . As MRSA becomes endemic in NICUs 8 , as evident by six epidemiologically distinct strains circulating in our NICU over a two year period [ data not shown ] , we must optimize infection prevention strategies . Our investigation is limited by its observational design . We did not find differences between mupirocin treated and untreated groups , but we can not account for factors that might impact a clinician ’s decision to attempt decolonization . Larger prospect i ve trials are needed to evaluate the impact of MRSA decolonization on infections in hospitalized neonates . As with all retrospective studies , MRSA and MSSA infections may have been misclassified and rates underestimated , but our findings confirm national trends of increasing MRSA infections 2 and the potential for comprehensive control strategies to reduce MRSA infections . As MRSA becomes endemic in NICUs , further research needs to evaluate best MRSA infection prevention strategies |
12,023 | 29,460,487 | Consensus statements with 100 % agreement and " high " evidence level indicated that specific probiotics help reduce overall symptom burden and abdominal pain in some patients with IBS and duration /intensity of diarrhoea in patients prescribed antibiotics or H. pylori eradication therapy , and have favourable safety .
Statements with 70%-100 % agreement and " moderate " evidence indicated that , in some patients with IBS , specific probiotics help reduce bloating/distension and improve bowel movement frequency/consistency .
CONCLUSIONS This up date d review indicates that specific probiotics are beneficial in certain lower GI problems , although many of the new publications did not report benefits of probiotics , possibly due to inclusion of new , less efficacious preparations .
Specific probiotics can relieve lower GI symptoms in IBS , prevent diarrhoea associated with antibiotics and H. pylori eradication therapy , and show favourable safety . | BACKGROUND In 2013 , a systematic review and Delphi consensus reported that specific probiotics can benefit adult patients with irritable bowel syndrome ( IBS ) and other gastrointestinal ( GI ) problems .
AIM To up date the consensus with new evidence . | Antibiotic-associated diarrhea ( AAD ) is a common complication of antibiotic use . There is growing interest in probiotics for the treatment of AAD and Clostridium difficile infection because of the wide availability of probiotics . The aim of this multicenter , r and omized , placebo-controlled , double-blind trial was to assess the efficacy of probiotic Lactobacillus ( Lacidofil ® cap ) for the prevention of AAD in adults . From September 2008 to November 2009 , a total of 214 patients with respiratory tract infection who had begun receiving antibiotics were r and omized to receive Lactobacillus ( Lacidofil ® cap ) or placebo for 14 days . Patients recorded bowel frequency and stool consistency daily for 14 days . The primary outcome was the proportion of patients who developed AAD within 14 days of enrollment . AAD developed in 4 ( 3.9 % ) of 103 patients in the Lactobacillus group and in 8 ( 7.2 % ) of 111 patients in the placebo group ( P=0.44 ) . However , the Lactobacillus group showed lower change in bowel frequency and consistency ( 50/103 , 48.5 % ) than the placebo group ( 35/111 , 31.5 % ) ( P=0.01 ) . Although the Lacidofil ® cap does not reduce the rate of occurrence of AAD in adult patients with respiratory tract infection who have taken antibiotics , the Lactobacillus group maintains their bowel habits to a greater extent than the placebo group Abstract Objective . The effect of probiotics on IBS symptoms has been mixed , but remains an intriguing treatment option with appeal to the patient . Material and methods . Patients fulfilling the Rome II criteria were r and omized double-blind to a daily intake of 500 ml of fermented milk containing at least 5 × 107 CFU/ml of Lactobacillus paracasei ssp paracasei F19 , Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 or an equal volume of acidified milk for 8 weeks . Symptoms were assessed at baseline and weekly using a disease-specific vali date d symptom rating scale ( IBS-SSI ) . The predefined primary outcome measure was patient reported adequate symptom relief . Adherence to study protocol were assessed by performing stool sample s at the of the treatment period . Results . Eight-one patients were screened . Sixty-four patients were r and omized ; 18 patients did not complete the study due to protocol violations or withdrew due to lack of effect . Fifty-two patients ( 13 males ) completed the study as per protocol ; mean age was 51.3 years ( range 29–67 ) . The proportion of patients reporting adequate symptom relief increased in both patient groups , but there was not any statistical difference between the groups . IBS-SSI scores did not differ statistically between the groups at the end of the treatment period , but improved during the study period in both groups . Conclusions . During this 8-week trial gastrointestinal symptoms improved . However , there was no difference between treatment with fermented milk containing probiotics or acidified milk . The effect of probiotics on IBS symptoms remains uncertain and further studies are warranted Background Probiotics purportedly reduce symptoms of gastrointestinal and upper respiratory-tract illness by modulating commensal microflora . Preventing and reducing symptoms of respiratory and gastrointestinal illness are the primary reason that dietary supplementation with probiotics are becoming increasingly popular with healthy active individuals . There is a paucity of data regarding the effectiveness of probiotics in this cohort . The aim of this study was to evaluate the effectiveness of a probiotic on faecal microbiology , self-reported illness symptoms and immunity in healthy well trained individuals . Methods Competitive cyclists ( 64 males and 35 females ; age 35 ± 9 and 36 ± 9 y , VO2max 56 ± 6 and 52 ± 6 ml.kg-1.min-1 , mean ± SD ) were r and omised to either probiotic ( minimum 1 × 109Lactobacillus fermentum ( PCC ® ) per day ) or placebo treatment for 11 weeks in a double-blind , r and omised , controlled trial . The outcome measures were faecal L. fermentum counts , self-reported symptoms of illness and serum cytokines . Results Lactobacillus numbers increased 7.7-fold ( 90 % confidence limits 2.1- to 28-fold ) more in males on the probiotic , while there was an unclear 2.2-fold ( 0.2- to 18-fold ) increase in females taking the probiotic . The number and duration of mild gastrointestinal symptoms were ~2-fold greater in the probiotic group . However , there was a substantial 0.7 ( 0.2 to 1.2 ) of a scale step reduction in the severity of gastrointestinal illness at the mean training load in males , which became more pronounced as training load increased . The load ( duration ×severity ) of lower respiratory illness symptoms was less by a factor of 0.31 ( 99%CI ; 0.07 to 0.96 ) in males taking the probiotic compared with placebo but increased by a factor of 2.2 ( 0.41 to 27 ) in females . Differences in use of cold and flu medication mirrored these symptoms . The observed effects on URTI had too much uncertainty for a decisive outcome . There were clear reductions in the magnitude of acute exercise-induced changes in some cytokines . Conclusion L. fermentum may be a useful nutritional adjunct for healthy exercising males . However , uncertainty in the effects of supplementation on URTI and on symptoms in females needs to be resolved . Trial registration The trial was registered in the Australia and New Zeal and Clinical Trials Registry ( ACTRN12611000006943 ) Background and aims Meta-analyses point to a modest but significant effect of probiotics on symptoms in irritable bowel syndrome ( IBS ) . We aim ed to assess the effect of the probiotic Lactobacillus casei Shirota ( LcS ) on symptoms and quality of life in IBS patients in a r and omized , double-blind , placebo-controlled intervention study . Material s and methods IBS patients ( Rome II ) between 18 and 65 years of age were included . The study consisted of an 8-week intervention period in which the participants received probiotic ( LcS ) or placebo twice daily , followed by an 8-week follow-up period . Symptom diaries and quality of life were scored at weeks 0 , 8 and 16 . The primary outcome parameter was a decrease of at least 30 % in a composite mean symptom score ( MSS ) at week 8 on the basis of an intention-to-treat analysis . Results Thirty-nine individuals ( 67 % women ) were included in the probiotic group and 41 individuals ( 71 % women ) were included in the placebo group . After the intervention period , the mean relative improvement did not reach 30 % for MSS or any individual symptom score . After follow-up ( week 16 ) , a mean improvement of at least 30 % was achieved for MSS in the probiotic group , but no significant difference was found between both treatment groups ( mean±SD : 34±7 % ; 13±8 % , P=0.06 ) . Conclusion After probiotic treatment with LcS , no improvement of 30 % in MSS was observed after 8 weeks AIMS To clarify the effects of Lactobacillus gasseri CP2305 ( CP2305 ) on quality of life and clinical symptoms and its functional mechanisms in patients with irritable bowel syndrome ( IBS ) . METHODS AND RESULTS After the patients were administered CP2305 daily for 4 weeks , the IBS-severity index score was significantly improved compared with that of the placebo group , and this improvement was accompanied by a reduction in health-related worry and changes in intestinal microbiota . The gene expression profiling of the peripheral blood leucocytes showed that CP2305 treatment significantly up-regulated genes related to eukaryotic initiation factor 2 ( EIF2 ) signalling . Eighty-two genes were down-regulated in IBS patients compared with healthy controls . The expression of 23 of these genes exhibited a CP2305-dependent increase associated with an improvement in IBS severity . The majority of the restored genes were related to EIF2 signalling . CONCLUSIONS CP2305 administration is a potential c and i date therapeutic option for patients with IBS . SIGNIFICANCE AND IMPACT OF THE STUDY Although probiotics have been proposed to benefit IBS patients , objective clinical evidence and elucidation of the functional mechanism remain insufficient . Our study demonstrated that CP2305 administration beneficially influences IBS patients in both subjective and objective evaluations , and gene expression profiling provided insights into the functional mechanism 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 AIM To determine the effects of Lactobacillus acidophilus NCFM on irritable bowel syndrome ( IBS ) symptoms and quality of life ( QoL ) . METHODS In this r and omized triple-blind trial , adult IBS volunteers who were recruited according to Rome III criteria received 109 or 1010 colony-forming units of NCFM or placebo daily for 12 wk . IBS Symptom Severity Score ( IBS-SSS ) , which constituted the primary outcome , and secondary outcomes , including individual IBS symptoms , IBS-related QoL question naire , anxiety and depression , defecation frequency , and stool consistency , were assessed at baseline at the end of the 8-wk run-in period , after 4 and 12 wk of intervention , and after a 4-wk washout . RESULTS A total of 340 of 391 r and omized volunteers completed the trial . IBS-SSS improved over 12 wk of treatment in all treatment groups , decreasing by a mean ± SD of 44.0 ± 80.2 , 50.8 ± 82.4 , and 48.3 ± 72.2 in the placebo , active low-dose , and active high-dose groups , respectively . Similarly , secondary outcomes did not differ between treatment groups . However , in a post hoc analysis of volunteers with moderate to severe abdominal pain at baseline ( VAS > 35/100 ) , the treatment significantly reduced the sensation of abdominal pain . Pain scores fell by 20.8 ± 22.8 , 29.4 ± 17.9 , and 31.2 ± 21.9 in the placebo , active low-dose , and active high-dose groups , respectively ( P value for placebo vs combined active doses = 0.0460 ) . CONCLUSION NCFM alleviates moderate to severe abdominal pain , consistent with earlier observations of this strain mitigating visceral pain through increased analgesic receptor expression Background This r and omized double blind placebo controlled dual site clinical trial compared a probiotic dietary supplement to placebo regarding effects on gastrointestinal symptoms in adults with post-pr and ial intestinal gas-related symptoms ( abdominal pain , distention , flatulence ) but no gastrointestinal ( GI ) diagnoses to explain the symptoms . Methods Sixty-one adults were enrolled ( age 36.5 ± 12.6 years ; height 165.1 ± 9.2 cm ; weight 75.4 ± 17.3 kg ) and r and omized to either Digestive Advantage ™ Gas Defense Formula - ( GanedenBC30Bacillus coagulans GBI-30 , 6086 ) : n = 30 ; or Placebo : n = 31 . Study subjects were evaluated every two weeks over a four-week period using vali date d question naires and st and ard biochemical safety testing . Outcome criteria of interest included change from baseline in Gastrointestinal Symptom Rating Scale ( GSRS ) abdominal pain , abdominal distention , flatus , and the Severity of Dyspepsia Assessment ( SODA ) bloating and gas subscores over four weeks of product use . Results Measured against the placebo , subjects in the probiotic group achieved significant improvements in GSRS abdominal pain subscore ( p = 0.046 ) and the GSRS total score ( p = 0.048 ) , with a strong trend for improvement on the GSRS abdominal distension subscore ( p = 0.061 ) . A strong placebo effect was evident which could explain the lack of statistical significant differences between the groups for many of the efficacy variables . Conclusion In conclusion , the Bacillus coagulans-based product was effective in improving the quality of life and reducing gastrointestinal symptoms in adults with post pr and ial intestinal gas-related symptoms and no GI diagnoses . Trial Registration Clinical Trials.gov Identifier : 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 AIMS To evaluate the effectiveness , safety and tolerability of a probiotic formulation containing Lactobacillus acidophilus LA-5 and Bifidobacterium BB-12 in the prevention of antibiotic associated diarrhoea ( AAD ) . METHODS AND MATERIAL A double-blind r and omised placebo controlled multicentric trial was conducted in adults who were prescribed a seven-day course of oral antibiotic ( either cefadroxil or amoxycillin ) for a documented indication . The effectiveness of a 14-day therapy ( concomitant with antibiotic course and seven days thereafter ) of the probiotic formulation in preventing AAD was evaluated . Safety profile was assessed by monitoring of all treatment emergent adverse events and tolerability on a global well being scale . RESULTS The incidence of AAD in the probiotic group was 10.8 % compared to 15.6 % in the placebo group , the difference being statistically non-significant ( p = 0.19 ) . The relative risk for AAD was 0.7 with the 95 % CI being 0.4 to 1.2 . The diarrhoea duration in the probiotic group was two days with an interquartile range of 1- 3 days and was significantly less ( p = 0.01 ) than the placebo group which was four days with an interquartile range of 3 - 5.5 days . Subgroup analysis of subjects with AAD showed that the incidence of severe diarrhoea ( watery stools ) was 96 % in the placebo group ( 25 out of 26 ) compared to 31.6 % ( 6 out of 19 ) in the probiotic group and this difference was significant statistically ( p < 0.001 ) . Four mild , non-serious , adverse events were detected ( 2.0 % ) in the probiotic group but there were none in the placebo group . CONCLUSION This r and omised controlled trial shows that prophylactic administration of the probiotic formulation containing Lactobacillus acidophilus LA-5 and Bifidobacterium BB-12 , did not effectively lower the incidence of AAD in adults . However , compared to placebo the duration of diarrhoea in the probiotic group was significantly reduced . Its tolerability and safety profile were good ABSTRACT Probiotics are believed to be beneficial in maintaining a healthy gut microbiota whereas antibiotics are known to induce dysbiosis . This study aim ed to examine the effects of the probiotic Saccharomyces boulardii CNCM I-745 ( SB ) , the antibiotic Amoxicillin-Clavulanate ( AC ) and the combination on the microbiota and symptoms of healthy humans . Healthy subjects were r and omized to one of 4 study groups : SB for 14 days , AC for 7 days , SB plus AC , Control ( no treatment ) . Participants gave stool sample s and completed gastro-intestinal symptom question naires . Microbiota changes in stool specimens were analyzed using 16s rRNA gene pyrosequencing ( bTEFAP ) . Only one subject withdrew prematurely due to adverse events . Subjects treated by S boulardii + AC had fewer adverse events and tolerated the study regimen better than those receiving the AC alone . Control subjects had a stable microbiota throughout the study period . Significant microbiota changes were noted in the AC alone group during antibiotic treatment . AC associated changes included reduced prevalence of the genus Roseburia and increases in Escherichia , Parabacteroides , and Enterobacter . Microbiota alterations reverted toward baseline , but were not yet completely restored 2 weeks after antibiotherapy . No significant shifts in bacterial genera were noted in the SB alone group . Adding SB to AC led to less pronounced microbiota shifts including less overgrowth of Escherichia and to a reduction in antibiotic-associated diarrhea scores . Antibiotic treatment is associated with marked microbiota changes with both reductions and increases in different genera . S. boulardii treatment can mitigate some antibiotic-induced microbiota changes ( dysbiosis ) and can also reduce antibiotic-associated diarrhea OBJECTIVES : Several studies show that probiotics may prevent side effects during therapy against Helicobacter pylori ( H. pylori ) . Other reports indicate competitive interaction between some probiotics and H. pylori . We compared efficacy of two different probiotics and one probiotic combination with placebo for preventing anti-H. pylori therapy-related side effects and for improving the eradication rate . METHODS : A total of 85 H. pylori positive , asymptomatic patients were r and omized in four groups to receive probiotic or placebo both during and for 7 days after a 1-wk triple therapy scheme ( rabeprazole 20 mg b.i.d . , clarithromycin 500 mg b.i.d . , and tinidazole 500 mg b.i.d . ) . Group I ( n = 21 ) received Lactobacillus GG ; group II ( n = 22 ) , Saccharomyces boulardii ; group III ( n = 21 ) , a combination of Lactobacillus spp . and biphidobacteria ; and group IV ( n = 21 ) , placebo . Subjects filled in weekly symptom question naires for 4 wk . Blinded investigators collected and analyzed data . H. pylori status was rechecked after 5–7 wk . RESULTS : Side effects occurred mainly during the eradication week . None of them caused therapy discontinuation . In all probiotic-supplemented groups , there was a significantly lower incidence of diarrhea and taste disturbance during the eradication week with respect to the placebo group . Overall assessment of tolerability was significantly better in the actively treated patients than in the placebo group . No differences in the incidence of side effects between the probiotic groups were observed . The H. pylori eradication rate was almost identical between the probiotic and placebo groups . CONCLUSIONS : All the probiotics used were superior to placebo for side effect prevention , but were not associated with better compliance with antibiotic therapy . The effect of probiotic supplementation on side effects during anti-H. pylori regimens seemed to be independent of the probiotic species used The ability of probiotics to improve bowel habits or transit time has been shown in healthy population s. Additional data are required to support the use of specific probiotics to improve gastrointestinal ( GI ) well-being . The present study was design ed to investigate the effect of consuming fermented milk ( FM ) on GI well-being , digestive symptoms and health-related quality of life ( HRQoL ) amongst women without diagnosed GI disorders . In this double-blind , controlled , parallel- design study , subjects were r and omised to ingest daily either 2 x 125 g FM containing Bifidobacterium lactis DN-173 010 and yoghurt strains or a control non-fermented dairy product for 4 weeks followed by a 4-week wash-out period . GI well-being and digestive symptoms were assessed weekly . HRQoL was measured every 4 weeks . Data were analysed using analysis of covariance and logistic regression , correcting for baseline values on the full analysis set population of 197 women ( aged 18 - 60 years ) . The percentage of women reporting an improvement in their GI well-being was significantly ( P < 0.01 ) higher in the FM group v. the control group ( OR 1.69 ; 95 % CI 1.17 , 2.45 ) . A significantly ( P < 0.05 ) more pronounced decrease in the composite score of digestive symptoms was observed in the FM group when comparing with the control group ( least squares mean - 0.57 ; 95 % CI - 1.12 , - 0.02 ) . Among HRQoL dimensions , the digestive comfort score was significantly ( P < 0.05 ) improved in the FM group compared with the control group . The present study showed that the daily consumption of a specific FM is able to improve GI well-being and digestive symptoms in adult women without GI disorders BACKGROUND Therapy trials with bacterial compounds in irritable bowel syndrome ( IBS ) have produced conflicting results and , so far , an E.-coli preparation has not been used . METHODS Two hundred and ninety-eight patients with lower abdominal symptoms diagnosed as IBS were treated for 8 weeks by the compound Symbioflor-2 ( Symbiopharm GmbH , Herborn , Germany ) , an Escherichia coli product ( N = 148 ) , or placebo ( n = 150 ) in a double-blinded , r and omized fashion . Patients were seen weekly by the physician , who assessed the presence of core IBS symptoms . Both an abdominal pain score ( APS ) as well as a general symptom score ( GSS ) were used as primary endpoints . Responders had to have complete absence of IBS core symptoms at > or = 1 visit during treatment . RESULTS The responder rate in GSS to the drug was 27 / 148 ( 18.2 % ) in comparison to placebo with 7 / 150 ( 4.67 % ) ( p = 0.000397 ) . The improvement in APS was 28 / 148 ( 18.9 % ) and 10 / 150 ( 6.67 % ) for placebo ( p = 0.001649 ) . The response was reached from visit 3 onwards with both medication and placebo . Post-hoc analysis revealed no significant differences in efficacy of the drug between the gender and different age groups . CONCLUSION Treatment of IBS with the probiotic Symbioflor-2 is effective and superior to placebo in reducing typical symptoms of IBS patients seen by general practitioners and by gastroenterologists Abstract Objective . Meta-analyses have indicated effect of probiotics on irritable bowel syndrome ( IBS ) . However , few long-term trials have been conducted and uncertainty remains as to effectiveness and long-term effect in a primary care setting . We aim ed to investigate the effect of probiotics compared with placebo in the management of IBS in primary care during a 6-month treatment period and with a 6-month follow-up . Material and methods . We r and omized IBS patients fulfilling Rome III criteria to receive two capsules twice daily either containing placebo or a probiotic mixture of Lactobacillus paracasei ssp paracasei F19 , Lactobacillus acidophilus La5 and Bifidobacterium Bb12 in an amount of 1.3 × 1010 CFU per capsule . Primary endpoint was proportion of responders defined as patients reporting adequate relief ( AR ) at least 50 % of the time in the 6-month treatment period . Secondary outcomes were proportions of patients reporting AR at different time points , and change in gastrointestinal symptoms and health-related quality of life ( HrQOL ) from baseline to 6 and 12 months . Results . A total of 131 patients were included in this study . The proportion of responders in the treatment period was 52 % ( 35/67 ) in the probiotic group versus 41 % ( 26/64 ) in the placebo group , p = 0.18 . Overall we found no difference between the groups in change in gastrointestinal symptoms after treatment . Patients improved in HrQOL , but with no statistically significant difference between the groups . Conclusion . During a 6-month treatment period , we were not able to detect a positive effect of probiotic when compared with placebo Abstract The primary objective in the study is determination of efficacy of probiotic preparation as a supportive therapy in eradication of Helicobacter pylori . The study was multicenter , prospect i ve , r and omized , placebo controlled , and double-blind . The subjects first filled out a specially design ed question naire to assess the severity of the 10 symptoms , which can be related to eradication therapy to be monitored during the trial . Each subject then received 28 capsules of probiotic preparation or matching placebo capsules , which they were supposed to take over the following 14 days , twice a day , at least 2 hours prior to or after the antibiotic therapy administration . A total of 804 patients were enrolled in the trial , of which 650 ( 80.85 % ) were included in the analysis . The results show a significantly larger share of cured subjects in the probiotic arm versus the placebo arm ( 87.38 % vs 72.55 % ; P < 0.001 ) . Additionally , presence and intensity of epigastric pain , bloating , flatulence , taste disturbance , loss of appetite , nausea , vomiting , heartburn , rash , and diarrhea were monitored over the study period . At 15 days post inclusion , probiotic treatment was found superior to placebo in 7 of 10 mentioned symptoms . Average intensity for symptoms potentially related to antibiotic therapy was significantly higher in the placebo group , 0.76 vs 0.55 ( P < 0.001).Adding probiotics to the st and ard triple therapy for H pylori eradication significantly contributes to treatment efficacy and distinctly decreases the adverse effects of therapy and the symptoms of the underlying disease Antibiotic-associated diarrhea is an important clinical problem , associated with morbidity , mortality and healthcare costs . Our r and omized , placebo controlled multicenter trial do not support the efficacy of Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea BACKGROUND AND AIM Evidence suggests that probiotics reduce certain constipation-related symptoms . Lactobacillus casei strain Shirota has never been tested as treatment for functional constipation in otherwise-healthy subjects . To evaluate the efficacy of this probiotic among adults with functional constipation was aim ed . METHODS Subjects with functional constipation ( Rome II-defined ) were r and omized to intake L. casei strain Shirota fermented milk or placebo once daily for 4 weeks under double-blind condition . Primary outcomes were constipation severity and stool frequency ; secondary outcomes were stool consistency and quantity . RESULTS In intent-to-treat population , compared with baseline , constipation severity and stool frequency improved in both probiotic ( n = 47 ) and control groups ( n = 43 ) , but improvements were comparable in both groups at week 4 ( α = 5 % level ) . In probiotic group , stool consistency and quantity at week 4 improved significantly versus baseline but not versus control . Considering that the study agent is non-pharmaceutical and the purpose of supplementation is for long-term effect , re-evaluation at α = 10 % was conducted , which showed significant improvement in constipation severity at week 4 ( P = 0.058 ) . Magnitude of the probiotic effect on stool consistency was small but grew over time , d = 0.19 , 95 % confidence interval 0.00 - 0.35 ( Week 4 ) , d = 0.29 , 95 % confidence interval 0.11 - 0.52 ( postintervention ) . Post-hoc exploratory analysis suggests incomplete evacuation may decrease with probiotic intake . CONCLUSIONS Four-week administration of L. casei strain Shirota did not alleviate constipation severity or stool frequency , consistency , and quantity when compared with control . With re-evaluation at α = 10 % level , improvement in constipation severity was significant at week 4 . To obtain conclusive results , further studies with longer intervention are warranted Background Some probiotics have shown efficacy for patients with irritable bowel syndrome ( IBS ) . Lactobacillus ( L. ) plantarum MF1298 was found to have the best in vitro probiotic properties of 22 strains of lactobacilli . The aim of this study was to investigate the symptomatic effect of L. plantarum MF1298 in subjects with IBS . Primary outcome was treatment preference and secondary outcomes were number of weeks with satisfactory relief of symptoms and IBS sum score . Methods The design was a r and omised double blind placebo-controlled crossover trial . 16 subjects with IBS underwent two three-week periods of daily intake of one capsule of 1010 CFU L. plantarum MF 1298 or placebo separated by a four-week washout period . Results Thirteen participants ( 81 % ; 95 % CI 57 % to 93 % ; P = 0.012 ) preferred placebo to L. plantarum MF1298 treatment . The mean ( SD ) number of weeks with satisfactory relief of symptoms in the periods with L. plantarum MF1298 and placebo were 0.50 ( 0.89 ) and 1.44 ( 1.26 ) , respectively ( P = 0.006 ) . IBS sum score was 6.44 ( 1.81 ) in the period with L. plantarum MF1298 treatment compared with 5.35 ( 1.77 ) in the period with placebo ( P = 0.010 ) . With a clinical ly significant difference in the IBS sum score of 2 in disfavour of active treatment , the number needed to harm was 3.7 , 95 % CI 2.3 to 10.9 . Conclusions This trial shows for the first time an unfavourable effect on symptoms in subjects with IBS after intake of a potential probiotic . The trial registration number Clinical trials NCT00355810 Objective To determine the efficacy of a probiotic drink containing Lactobacillus for the prevention of any diarrhoea associated with antibiotic use and that caused by Clostridium difficile . Design R and omised double blind placebo controlled study . Participants 135 hospital patients ( mean age 74 ) taking antibiotics . Exclusions included diarrhoea on admission , bowel pathology that could result in diarrhoea , antibiotic use in the previous four weeks , severe illness , immunosuppression , bowel surgery , artificial heart valves , and history of rheumatic heart disease or infective endocarditis . Intervention Consumption of a 100 g ( 97 ml ) drink containing Lactobacillus casei , L bulgaricus , and Streptococcus thermophilus twice a day during a course of antibiotics and for one week after the course finished . The placebo group received a longlife sterile milkshake . Main outcome measures Primary outcome : occurrence of antibiotic associated diarrhoea . Secondary outcome : presence of C difficile toxin and diarrhoea . Results 7/57 ( 12 % ) of the probiotic group developed diarrhoea associated with antibiotic use compared with 19/56 ( 34 % ) in the placebo group ( P=0.007 ) . Logistic regression to control for other factors gave an odds ratio 0.25 ( 95 % confidence interval 0.07 to 0.85 ) for use of the probiotic , with low albumin and sodium also increasing the risk of diarrhoea . The absolute risk reduction was 21.6 % ( 6.6 % to 36.6 % ) , and the number needed to treat was 5 ( 3 to 15 ) . No one in the probiotic group and 9/53 ( 17 % ) in the placebo group had diarrhoea caused by C difficile ( P=0.001 ) . The absolute risk reduction was 17 % ( 7 % to 27 % ) , and the number needed to treat was 6 ( 4 to 14 ) . Conclusion Consumption of a probiotic drink containing L casei , L bulgaricus , and S thermophilus can reduce the incidence of antibiotic associated diarrhoea and C difficile associated diarrhoea . This has the potential to decrease morbidity , healthcare costs , and mortality if used routinely in patients aged over 50 . Trial registration National Research Register N0016106821 OBJECTIVES : St and ard therapies for antibiotic-associated diarrhea ( AAD ) and Clostridium difficile-associated diarrhea ( CDAD ) have limited efficacy . Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence . METHODS : In this single-center , r and omized , double-blind , placebo-controlled dose-ranging study , we r and omized 255 adult in patients to one of three groups : two probiotic capsules per day ( Pro-2 , n=86 ) , one probiotic capsule and one placebo capsule per day ( Pro-1 , n=85 ) , or two placebo capsules per day ( n=84 ) . Each probiotic capsule contained 50 billion c.f.u . of live organisms ( Lactobacillus acidophilus CL1285 ® + Lactobacillus casei LBC80R ® Bio-K+ CL1285 ) . Probiotic prophylaxis began within 36 h of initial antibiotic administration , continued for 5 days after the last antibiotic dose , and patients were followed for an additional 21 days . RESULTS : Pro-2 ( 15.5 % ) had a lower AAD incidence vs. Pro-1 ( 28.2 % ) . Each probiotic group had a lower AAD incidence vs. placebo ( 44.1 % ) . In patients who acquired AAD , Pro-2 ( 2.8 days ) and Pro-1 ( 4.1 days ) had shorter symptom duration vs. placebo ( 6.4 days ) . Similarly , Pro-2 ( 1.2 % ) had a lower CDAD incidence vs. Pro-1 ( 9.4 % ) . Each treatment group had a lower CDAD incidence vs. placebo ( 23.8 % ) . Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1 . CONCLUSIONS : The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and , in particular , CDAD in hospitalized patients on antibiotics . A dose-ranging effect was shown with 100 billion c.f.u . , yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u . ( Clinical Trials.gov number NCT00958308 ) BACKGROUND Lactase enzyme supplements and probiotics with high beta-galactosidase activity may be valid treatment options for the lactose intolerance . Aim of this study was to assess whether supplementation with tilactase or Lactobacillus reuteri when compared to placebo affects hydrogen breath excretion and gastrointestinal symptoms in lactose intolerant patients during lactose breath test ( H,-LBT ) . METHODS Sixty lactose intolerant patients participated in the study and were r and omized to three 20 patients -treatment groups : tilactase group ( tilactase 15 minutes before control H2-LBT ) ; placebo group ( placebo 15 minutes before control H2-LBT ) ; Lactobacillus reuteri group ( LR ) ( LR b.i.d . during 10 days before control H2-LBT ) . The outcomes were LBT normalization rate , and influences of treatments on both mean maximum hydrogen concentration and clinical score . RESULTS LBT normalization rate was significantly higher in tilactase and LR groups with respect to placebo . Tilactase was significantly more effective than LR in achieving LBT normalization ( p < 0.01 ) . Both significant reduction of mean peak H2 excretion and improvement of the mean clinical score were observed in tilactase and LR groups after treatment with respect to placebo ( p < 0.0001 ) . Tilactase was significantly more effective than LR in reducing both mean peak hydrogen excretion and mean clinical score . CONCLUSIONS In lactose intolerants , tilactase strongly improves both LBT results and gastrointestinal symptoms after lactose ingestion with respect to placebo . Lactobacillus reuteri also is effective but lesser than tilactase . This probiotic may represent an interesting treatment option for lactose intolerance since its use is simple and its effect may last in the time after stopping administration OBJECTIVES Irritable bowel syndrome ( IBS ) is a common diagnosis in gastroenterology . Its etiology is unknown and therapeutic options limited . Trials suggest probiotics may be beneficial . The aim of this study was to assess the symptomatic efficacy of Lactobacillus plantarum 299 v ( L. plantarum 299 v ) for the relief of abdominal pain in patients with IBS fulfilling Rome II criteria . METHODS This study was conducted in a referral hospital . Trial participants were r and omized to receive either two capsules of L. plantarum 299 v at a dosage of 5 × 10(9 ) cfu per capsule or placebo daily for 8 wk . Severity of abdominal pain was assessed using a visual analog scale at each visit and a quality -of-life IBS ( QoL-IBS ) question naire was also completed . RESULTS There was no significant difference in abdominal pain relief between the study and placebo groups ( P = 0.800 ) . There was also no difference in QoL- IBS scores between the groups ( P = 0.687 ) . Both groups had a significant improvement in abdominal pain scores over the study period , from an average of 251.55 to 197.90 ( P < 0.0001 ) indicating a large placebo effect . CONCLUSION An 8-wk treatment with L. plantarum 299 v did not provide symptomatic relief , particularly of abdominal pain and bloating , in patients fulfilling the Rome II criteria BACKGROUND AND AIM The efficacy of treatment with multispecies probiotics on irritable bowel syndrome ( IBS ) symptoms and the alterations of gut microbiota in patients who have taken probiotics were investigated . METHODS This r and omized , double-blind , placebo-controlled trial involved 49 IBS patients ( probiotics : 25 , placebo : 24 ) diagnosed according to the Rome III criteria . Patients were r and omly assigned to two groups : either to receive multispecies probiotics ( a mixture of Bifidobacterium longum , B. bifidum , B. lactis , Lactobacillus acidophilus , L. rhamnosus , and Streptococcus thermophilus ) twice a day for 4 weeks or to receive a placebo twice a day for 4 weeks . The primary efficacy end-point was the proportion of participants whose IBS symptoms were substantially relieved at week 4 . Secondary end-points were the intensity of abdominal pain/discomfort , bloating , stool frequency/consistency , alterations in fecal microflora over the 4 weeks . Fecal microflora were analyzed in 34 patients ( probiotics : 17 , placebo : 17 ) by quantitative real-time polymerase chain reaction assays . RESULTS The proportion of patients whose IBS symptoms were substantially relieved at week 4 was significantly higher in the probiotics group than in the placebo group : 68.0 % ( 17/25 ) versus 37.5 % ( 9/24 ) ( P < 0.05 ) . Secondary end-points such as improvement in abdominal pain/discomfort and bloating occurred in the probiotics group but not in the placebo group . Fecal analysis revealed that B. lactis , L. rhamnosus , and S. thermophilus had increased significantly in the probiotics group after 4 weeks and that B. lactis had increased in the placebo group . CONCLUSIONS Multispecies probiotics are effective in IBS patients and induce the alterations in the composition of intestinal microbiota BACKGROUND Irritable bowel syndrome ( IBS ) is a common disorder in Iran with challenging treatment . Although trials have suggested that probiotics alleviate the complaints of patients with minimal side effects , they have not been investigated in Iranian adults . METHODS In a r and omized double-blind study , 108 eligible IBS patients ( Rome III Criteria ) aged 20 - 70 years who referred consecutively to a clinical center in Tehran with abdominal bloating from 2010 to 2012 received a combination probiotics or placebo twice daily for 4 weeks . The objective was to evaluate the efficacy and safety of a multi-strain probiotics combination . One week prior to and throughout the treatment , the participants recorded their abdominal symptoms on a daily basis , using visual analogue scale and reported satisfactory relief of general symptoms at the end of each week . Adverse events were evaluated by self-reporting and physical examination . Continuous variables were analyzed by independent t-test and chi-square was used for binomials . RESULTS The baseline characteristics were balanced ( 60 % female , mean age 36.7 ± 11.5 ) . A total of 97 ( 51 intervention , 46 control ) completed the treatment . Intention to treat analysis was done on 108 allocated subjects . 85 % of the probiotic group reported satisfactory relief of general symptoms compared with 47 % in the control group ( P < 0.01 ) . A reduction in abdominal bloating and pain with probiotic was superior to placebo [ -13.0 vs. -3.7 ( P < 0.01 ) , -8.2 vs. -2.1 ( P = 0.02 ) , respectively ] . No severe adverse drug reaction was seen in either group . CONCLUSIONS A 4-week period of treatment with the combination probiotics twice daily was safe , well tolerated , and effective in our patients . Further investigation is recommended for other subgroups of IBS . Trial Registration : I RCT .ir I RCT 2012071010230N1 BACKGROUND Irritable bowel syndrome ( IBS ) is characterized by heterogeneous pathophysiology and low response to treatment . Up to 60 % of IBS patients suffers from visceral hypersensitivity , which is associated with symptom severity and underlying pathophysiological mechanisms . Recently , positive effects of probiotics in IBS have been reported , but overall the response was modest . We performed a study in IBS patients , characterized by visceral hypersensitivity measured with the rectal barostat , aim ing to assess the effect of 6 weeks of multispecies probiotic mix on visceral pain perception . METHODS We conducted a r and omized , placebo-controlled , double-blind trial in forty Rome III IBS patients with visceral hypersensitivity . Prior to intake , patients kept a 2-week symptom diary and underwent a rectal barostat measurement . When hypersensitivity was confirmed , participation was allowed and patients received a multispecies probiotic with in vitro proven potential beneficial effects on mechanisms contributing to visceral hypersensitivity ( six different probiotic strains ; 10(9 ) cfu/g ) , or a placebo product of one sachet ( 5 g ) per day for 6 weeks . At the end of the intervention period , visceroperception and symptoms were reassessed . KEY RESULTS Thirty-five patients completed the trial . The percentage of patients with visceral hypersensitivity decreased significantly in the probiotic and placebo group ( 76.5 % and 71.4 % , respectively ; N.S. between groups ) . Improvement in pain scores and mean symptom score did not differ between the probiotic and placebo group . CONCLUSIONS & INFERENCES In this placebo-controlled trial in IBS patients with visceral hypersensitivity , no significant effect of a multispecies probiotic on viscerperception was observed . The study has been registered in the US National Library of Medicine ( http://www . clinical trials.gov , NCT00702026 ) Certain r and omized , placebo-controlled trials of oral supplementation with B. infantis 35624 have demonstrated the amelioration of symptoms of irritable bowel syndrome . Potential GI colonization by B. infantis 35624 or effects of supplementation on resident GI microbiota may pertain to these clinical observations . In this study , fecal excretion of B. infantis 35624 before , during and after 8 weeks of daily treatment was compared in subjects with IBS who received either the encapsulated oral supplement ( n = 39 ) or placebo ( n = 37 ) and in healthy subjects who received the supplement ( n = 41 ) . Secondarily , changes in assessed fecal microbiota and IBS symptoms were determined . Supplementation significantly increased fecal B. infantis 35624 excretion vs. placebo in IBS subjects ; excretion in healthy subjects receiving supplement was quantitatively similar . Fecal levels of the probiotic declined and approached baseline once dosing ceased , documenting that colonization is transient . Although supplementation increased numbers of B infantis 35624 within the GI tract , limited changes in 10 other fecal taxa were observed either in healthy subjects or those with IBS . No impact on IBS symptoms was observed . Detection of bacterial DNA in fecal sample s suggests that the probiotic is able to survive transit through the GI tract , although strain selective culture techniques were not performed to confirm viability of B. infantis 35624 in the feces . Continuous probiotic administration was necessary to maintain steady-state transit . Given the complex spectrum of GI microbiota , however , monitoring perturbations in selected taxa may not be not a useful indicator of probiotic function Background Probiotics can alter the colonic microbiota and might improve bowel function . Objectives The aim of this study was to evaluate the effect of the consumption of yogurt , enriched with Bifidobacterium and Lactobacillus 4.8 × 1010 ( CFU ) on the symptoms of constipated pregnant women . Material s and Methods This triple-blind r and omized controlled trial was conducted on 60 constipated pregnant women who were diagnosed by the ROME III criteria in Tabriz , Iran from December 2014 to July 2015 . Participants were r and omly put into two groups including the treatment and the control group through block r and omization . The treatment group received 300 g of yogurt enriched with Bifidobacterium and Lactobacillus 4.8 × 1010 colony forming units ( CFU ) ( n = 30 ) while the control group received conventional yogurt ( n = 30 ) for 4 weeks . The defecation frequency , stool consistency , straining during defecation , sensation of anorectal obstruction , sensation of incomplete evacuation and manual manoeuvres to facilitate defecation were primary outcomes while the amount of defecation , stool colure , and quality of life were secondary outcomes . Results The frequency of defecation was increased from 2.1 ( 0.8 ) at baseline to 8.3 ( 4.4 ) in the probiotic yogurt group vs. 2.3 ( 0.7 ) at baseline to 8.1 ( 4.3 ) in the conventional yogurt group at the end of 4th week . These results were based on the repeated measure ANOVA test and there was no statistically significant difference between the two groups ( mean difference : 0.1 ; Confidence Interval 95 % : -1.4 to 1.7 ; P = 0.872 ) . Constipation symptoms including straining , anorectal obstruction , manipulation to facilitate defecation , consistency of stool and color of stool were improved significantly ( P < 0.05 ) in both groups . In addition , the amount of defecation was significantly increased in both groups ( P < 0.05 ) , while incomplete evacuation was significantly reduced in the treatment group ( P = 0.01 ) . There was no statistically significant difference between the groups in the mean scores of physical ( P = 0.726 ) and mental ( P = 0.678 ) aspects of quality of life after the intervention with the adjusting of baseline scores . Conclusions Consumption of 300 g/day probiotic and conventional yogurt can play a role in improving the symptoms of constipation during pregnancy The aim of the present study was to investigate the effect of Bifidobacterium animalis subsp . lactis , BB-12 ® , on two primary end points – defecation frequency and gastrointestinal ( GI ) well-being – in healthy adults with low defecation frequency and abdominal discomfort . A total of 1248 subjects were included in a r and omised , double-blind , placebo-controlled trial . After a 2-week run-in period , subjects were r and omised to 1 or 10 billion colony-forming units/d of the probiotic strain BB-12 ® or a matching placebo capsule once daily for 4 weeks . Subjects completed a diary on bowel habits , relief of abdominal discomfort and symptoms . GI well-being , defined as global relief of abdominal discomfort , did not show significant differences . The OR for having a defecation frequency above baseline for ≥50 % of the time was 1·31 ( 95 % CI 0·98 , 1·75 ) , P=0·071 , for probiotic treatment overall . Tightening the criteria for being a responder to an increase of ≥1 d/week for ≥50 % of the time result ed in an OR of 1·55 ( 95 % CI 1·22 , 1·96 ) , P=0·0003 , for treatment overall . A treatment effect on average defecation frequency was found ( P=0·0065 ) , with the frequency being significantly higher compared with placebo at all weeks for probiotic treatment overall ( all P<0·05 ) . Effects on defecation frequency were similar for the two doses tested , suggesting that a ceiling effect was reached with the one billion dose . Overall , 4 weeks ’ supplementation with the probiotic strain BB-12 ® result ed in a clinical ly relevant benefit on defecation frequency . The results suggest that consumption of BB-12 ® improves the GI health of individuals whose symptoms are not sufficiently severe to consult a doctor ( IS RCT N18128385 ) BACKGROUND Antibiotic-associated diarrhoea ( AAD ) occurs most frequently in older ( ≥65 years ) in patients exposed to broad-spectrum antibiotics . When caused by Clostridium difficile , AAD can result in life-threatening illness . Although underlying disease mechanisms are not well understood , microbial preparations have been assessed in the prevention of AAD . However , studies have been mostly small single-centre trials with varying quality , providing insufficient data to reliably assess effectiveness . We aim ed to do a pragmatic efficacy trial in older in patients who would be representative of those admitted to National Health Service ( NHS ) and similar secondary care institutions and to recruit a sufficient number of patients to generate a definitive result . METHODS We did a multicentre , r and omised , double-blind , placebo-controlled , pragmatic , efficacy trial of in patients aged 65 years and older and exposed to one or more oral or parenteral antibiotics . A computer-generated r and omisation scheme was used to allocate participants ( in a 1:1 ratio ) to receive either a multistrain preparation of lactobacilli and bifidobacteria , with a total of 6 × 10(10 ) organisms , one per day for 21 days , or an identical placebo . Patients , study staff , and specimen and data analysts were masked to assignment . The primary outcomes were occurrence of AAD within 8 weeks and C difficile diarrhoea ( CDD ) within 12 weeks of recruitment . Analysis was by modified intention-to-treat . This trial is registered , number IS RCT N70017204 . FINDINGS Of 17,420 patients screened , 1493 were r and omly assigned to the microbial preparation group and 1488 to the placebo group . 1470 and 1471 , respectively , were included in the analyses of the primary endpoints . AAD ( including CDD ) occurred in 159 ( 10·8 % ) participants in the microbial preparation group and 153 ( 10·4 % ) participants in the placebo group ( relative risk [ RR ] 1·04 ; 95 % CI 0·84 - 1·28 ; p=0·71 ) . CDD was an uncommon cause of AAD and occurred in 12 ( 0·8 % ) participants in the microbial preparation group and 17 ( 1·2 % ) participants in the placebo group ( RR 0·71 ; 95 % CI 0·34 - 1·47 ; p=0·35 ) . 578 ( 19·7 % ) participants had one or more serious adverse event ; the frequency of serious adverse events was much the same in the two study groups and none was attributed to participation in the trial . INTERPRETATION We identified no evidence that a multistrain preparation of lactobacilli and bifidobacteria was effective in prevention of AAD or CDD . An improved underst and ing of the pathophysiology of AAD is needed to guide future studies . FUNDING Health Technology Assessment programme ; National Institute for Health Research , UK Background Irritable bowel syndrome ( IBS ) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain and /or discomfort . Probiotics have been reported to benefit IBS symptoms but the level of benefit remains quite unclear . Objective This study was design ed to assess the benefit of Saccharomyces cerevisiae I-3856 on IBS symptoms . Methods A r and omized , double blind , placebo-controlled trial has been performed in 379 subjects with diagnosed IBS . Subjects were r and omly supplemented with the probiotics ( 1000 mg ) or placebo for 12 weeks . Question naires ( gastrointestinal symptoms , stools , wellbeing , and quality of life ) were completed . Primary endpoint was percentage of responders defined as having a 50 % decrease in the weekly average “ intestinal pain/discomfort score ” for at least 4 out of the last 8 weeks of the study . Results There was no overall benefit of S. cerevisiae I-3856 on IBS symptoms and wellbeing in the study population . Moreover , S. cerevisiae I-3856 was not statistically significant predictor of the responder status of the subjects ( p > 0.05 ) . Planned subgroup analyses showed significant effect in the IBS-C subjects : improvement of gastrointestinal symptoms was significantly higher in active group , compared to placebo , on abdominal pain/discomfort and bloating throughout the study and at the end of the supplementation . Conclusions In this study , S. cerevisiae I-3856 at the dose of 1000 mg per day does not improve intestinal pain and discomfort in general IBS patients . However , it seems to have an effect in the subgroup with constipation which needs further studies to confirm ( NCT01613456 in Clinical Trials.gov registry ) Colonic infection with Clostridium difficile , leading to pseudomembranous colitis , is a common complication of antibiotic therapy , especially in elderly patients . It has been suggested that non-pathogenic probiotic bacteria might prevent the development and recurrence of C. difficile infection . This double-blind , placebo-controlled study examines the role of probiotic administration in the prevention of C. difficile-associated diarrhoea ( CDAD ) in elderly patients receiving antibiotic therapy . Consecutive patients ( 150 ) receiving antibiotic therapy were r and omised to receive either a probiotic containing both Lactobacillus and Bifidobacterium or placebo for 20 days . Upon admission to hospital , bowel habit was recorded and a faecal sample taken . Trial probiotic or placebo was taken within 72 h of prescription of antibiotics , and a second stool sample was taken in the event of development of diarrhoea during hospitalisation or after discharge . Of the r and omised patients , 138 completed the study , 69 with probiotics in conjunction with antibiotics and 69 with antibiotics alone . On the basis of development of diarrhoea , the incidence of sample s positive for C. difficile-associated toxins was 2.9 % in the probiotic group compared with 7.25 % in the placebo-control group . When sample s from all patients were tested ( rather than just those developing diarrhoea ) 46 % of probiotic patients were toxin-positive compared with 78 % of the placebo group Abstract Objective . To assess the impact of Bifidobacterium lactis HN019 supplementation on whole gut transit time ( WGTT ) and frequency of functional gastrointestinal ( GI ) symptoms in adults . Material and methods . We r and omized 100 subjects ( mean age : 44 years ; 64 % female ) with functional GI symptoms to consume a proprietary probiotic strain , B. lactis HN019 ( Fonterra Research Centre , Palmerston North , New Zeal and ) , at daily doses of 17.2 billion colony forming units ( CFU ) ( high dose ; n = 33 ) , 1.8 billion CFU ( low dose ; n = 33 ) , or placebo ( n = 34 ) for 14 days . The primary endpoint of WGTT was assessed by X-ray on days 0 and 14 and was preceded by consumption of radiopaque markers once a day for 6 days . The secondary endpoint of functional GI symptom frequency was recorded with a subject-reported numeric ( 1–100 ) scale before and after supplementation . Results . Decreases in mean WGTT over the 14-day study period were statistically significant in the high dose group ( 49 ± 30 to 21 ± 32 h , p < 0.001 ) and the low dose group ( 60 ± 33 to 41 ± 39 h , p = 0.01 ) , but not in the placebo group ( 43 ± 31 to 44 ± 33 h ) . Time to excretion of all ingested markers was significantly shorter in the treatment groups versus placebo . Of the nine functional GI symptoms investigated , eight significantly decreased in frequency in the high dose group and seven decreased with low dose , while two decreased in the placebo group . No adverse events were reported in any group . Conclusions . Daily B. lactis HN019 supplementation is well tolerated , decreases WGTT in a dose-dependent manner , and reduces the frequency of functional GI symptoms in adults The present study investigated the effect of Bifidobacterium animalis ssp . lactis Bf-6 ( LMG 24 384 ) (Bf-6)-supplemented yogurt on colonic transit time ( CTT ) . A triple-blinded , r and omised , placebo-controlled , two-period cross-over trial was conducted with sixty-eight women with a self-reported history of straining during bowel movements or hard or lumpy stools in the past 2 years . As per regulatory requirements for probiotic studies , eligible women were generally healthy and not actively constipated at the time of enrolment . Participants consumed both Bf-6 and placebo yogurts for 14 d each in a r and omised order , with a 6-week washout period between the treatments . The primary outcome , CTT , was assessed via Sitz marker X-rays . The average CTT was 42·1 h for the active period and 43·3 h for the control period ( mean difference 1·2 h , 95 % CI - 4·9 , 7·4 ) . Since the statistical tests for the cross-over study implied that the mean CTT for the active and control periods in period 2 were biased , the st and ard protocol suggests examining the results of only period 1 as a traditional r and omised controlled trial . This showed that the mean CTT was 35·2 h for the active period v. 52·9 h for the control period ( P= 0·015 ) . Bootstrapping demonstrated that both the mean and median differences remained significant ( P= 0·016 and P= 0·045 , respectively ) . Few adverse events were noted , with no differences among the active and control periods . The paired analysis showed no differences between the active and control periods during the cross-over trial . Further trials should be conducted in population s with underlying problems associated with disordered transit to determine the potential value of probiotic supplementation more accurately Background / Aims Irritable bowel syndrome ( IBS ) is a troublesome disease . Some strains of probiotics reportedly exert remarkable immunomodulatory effects , and so we design ed a prospect i ve double-blind r and omized placebo-controlled clinical study to assess their effects in Korean adults with IBS . Methods IBS patients who met Rome III criteria were r and omly assigned to receive composite probiotics or placebo . A total of 20 billion lyophilized bacteria were administered twice daily for 8 weeks . Primary outcome variables were symptom scores consisting of abdominal pain , flatulence , defecation discomfort , and sum of symptom scores . A visual analogue scale was used to quantify the severity . Secondary outcome variables consisted of the quality of life and bowel habits including defecation frequency and stool form . Results Thirty-six and 34 patients were r and omized to the probiotics and placebo groups , respectively . Intention-to-treat analysis showed significant reductions in pain after 8 weeks of treatment : -31.9 and -17.7 in the probiotics and placebo groups , respectively ( p=0.045 ) . The reductions in abdominal pain , defecation discomfort , and sum of scores were more significant in 58 patients with a score of at least 3 on the baseline stool-form scale . Conclusions Composite probiotics containing Bifidobacterium bifidum BGN4 , Lactobacillus acidophilus AD031 , and other species are safe and effective , especially in patients who excrete normal or loose stools Broad-spectrum antibiotic use can disrupt the gastrointestinal microbiota result ing in diarrhoea . Probiotics may be beneficial in managing this type of diarrhoea . The aim of this 10-week r and omised , double-blind , placebo-controlled , parallel study was to investigate the effect of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 supplementation on antibiotic-associated diarrhoea in healthy adults . Subjects were r and omised to receive 1 week of amoxicillin-clavulanic acid ( 875 mg/125 mg ) once per day , plus a daily dose of 8 × 109 colony-forming units of a multi-strain probiotic ( n 80 ) or placebo ( n 80 ) . The probiotic or placebo intervention was maintained for 1 week after completion of the antibiotic . Primary study outcomes of consistency and frequency of bowel movements were not significantly different between the probiotic and placebo groups . The secondary outcomes of diarrhoea-like defecations , Gastrointestinal Symptoms Rating Scale scores , safety parameters and adverse events were not significantly different between the probiotic intervention and the placebo . A post hoc analysis on the duration of diarrhoea-like defecations showed that probiotic intervention reduced the length of these events by 1 full day ( probiotic , 2·70 ( sem 0·36 ) d ; placebo , 3·71 ( sem 0·36 ) d ; P=0·037 ; effect size=0·52 ) . In conclusion , this study provides novel evidence that L. helveticus R0052 and L. rhamnosus R0011 supplementation significantly reduced the duration of diarrhoea-like defecations in healthy adults receiving antibiotics Background Lactose intolerance is a form of lactose maldigestion where individuals experience symptoms such as diarrhea , abdominal cramping , flatulence , vomiting and bowel sounds following lactose consumption . Lactobacillus acidophilus is a species of bacteria known for its sugar fermenting properties . Pre clinical studies have found that Lactobacillus acidophilus supplementation may assist in breaking down lactose ; however , no human clinical trials exist evaluating its efficacy in alleviating symptoms related to lactose intolerance . Objective The aim of this r and omized , double-blind , placebo-controlled , crossover study was to evaluate the effect of a proprietary strain of Lactobacillus acidophilus on relieving discomfort related to lactose intolerance . Methods The study enrolled healthy volunteers between 18 and 75 years of age who complained of lactose intolerance . Screening visits included a lactose challenge visit to confirm eligibility based on a score of 10 or higher on subjective assessment of the following symptoms after lactose challenge : diarrhea , abdominal cramping , vomiting , audible bowel sounds , flatulence , and overall symptoms . Qualified subjects participated in a 2-arm crossover design , with each arm consisting of 4 weeks of intervention of either active or placebo product , with a 2-week washout period during crossover . The study product consisted of the DDS-1 strain of Lactobacillus acidophilus ( Nebraska Cultures , Walnut Creek , California ) . The placebo was formulated from maltodextrin . Study participants were instructed to take the product once daily for 4 weeks . Data collected included subjective symptom scores related to lactose intolerance . Results Longitudinal comparison between the DDS-1 group and placebo group demonstrated statistically significant reductions in abdominal symptom scores during the 6-h Lactose Challenge at week 4 for diarrhea ( p = 0.033 ) , abdominal cramping ( p = 0.012 ) , vomiting ( p = 0.0002 ) , and overall symptom score ( p = 0.037 ) . No adverse events were reported . Conclusions The present study has found that this unique DDS-1 strain of Lactobacillus acidophilus , manufactured by Nebraska Cultures , is safe to consume and improves abdominal symptom scores compared to placebo with respect to diarrhea , cramping , and vomiting during an acute lactose challenge Objective : This study was performed to investigate the dose – response effects of supplementation with Bifidobacterium animalis subsp lactis ( BB-12 ) and Lactobacillus paracasei subsp paracasei ( CRL-431 ) on blood lipids , recovery from feces and bowel habits . Changes of the fecal microflora was analyzed in the 1010 CFU/day probiotic and placebo group . Design : The study was design ed as a r and omized , placebo-controlled , double-blinded , parallel dose – response study .Subjects : Healthy young adults ( 18–40 years ) were recruited by advertising in local newspapers . Of the 75 persons enrolled , 71 ( 46 women , 25 men , mean age 25.6 years ( range 18–40 years ) ) completed the study .Intervention : The volunteers were r and omly assigned into five groups receiving either placebo or a mixture of the two probiotics in the concentration of 108 , 109 , 1010 or 1011 CFU/day in 2 weeks run-in period , 3 weeks intervention and 2 weeks wash-out . Diary reporting bowel habits and well being ( abdominal bloating , flatulence and headache ) was kept for all 7 weeks and blood lipids , fecal recovery of BB-12 and CRL-431 , as well as fecal microflora was tested before , immediately and 2 weeks after intervention . Results : The fecal recovery of BB-12 increased significantly ( P<0.001 ) with increasing dose . In the group receiving 1011 CFU/day BB-12 was recovered from 13 out of 15 volunteers . CRL-431 was not recovered in any of the fecal sample s. Supplementation with probiotics did not change the fecal bacterial composition . A significant linear increase in fecal consistency ( looser stool ) with increasing probiotic dose ( P=0.018 ) was observed . No overall dose – response effect was found on the blood lipids . High doses of probiotics were well tolerated . Conclusion : A dose-related recovery of BB-12 from feces was observed . Sponsorship : The study was sponsored by Chr . Hansen A/S , Hoersholm , Denmark 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 BACKGROUND AND AIMS Previous observations suggested that an early rise in breath hydrogen after lactulose ( ERBHAL ) may identify patients with irritable bowel syndrome ( IBS ) likely to respond to probiotics . Therefore , we aim ed to ( i ) investigate whether treatment with a probiotic changes breath hydrogen response in patients with ERBHAL and ( ii ) whether these changes identify patients who may benefit symptomatically from probiotics . METHODS In a r and omized , double-blind , placebo-controlled trial , patients with IBS ( Rome III ) were r and omized to either 65 mL/day fermented milk product containing probiotic ( FMPP ) or placebo for 6 weeks , followed by 6 weeks ' open-label treatment and 6 weeks ' withdrawal . Breath hydrogen responses to lactulose ( 15 g ) and liquid-gastric emptying time were evaluated before and at the end of each treatment period . Symptoms were measured using a 100-mm visual analog scale . RESULTS Loss of ERBHAL occurred in 36 % of 23 patients receiving FMPP and 41 % of 22 receiving placebo ( P = 1.00 ) . Amongst 40 patients who completed open-label FMPP treatment , ERBHAL was lost in a further 38 % , continued in 25 % , and regained in 10 % . Similar variability occurred in the withdrawal phase . Variability was unrelated to changes in gastric emptying . No differences in symptom response were seen between treatment groups nor in relation to the loss or retention of ERBHAL . CONCLUSIONS Breath hydrogen patterns after lactulose are poorly reproducible . No FMPP-specific effects on fermentation patterns or symptoms were observed . The presence of ERBHAL is not useful to predict symptomatic response to probiotic therapy in patients with IBS Background : The clinical effect of probiotics on irritable bowel syndrome ( IBS ) is still controversial . Aims : We aim ed to evaluate the effects of a probiotic mixture on IBS symptoms and the composition of fecal microbiota in patients with diarrhea-dominant IBS ( D-IBS ) . Methods : Fifty patients with D-IBS were r and omized into placebo or probiotic mixture ( Lactobacillus acidophilus , Lactobacillus plantarum , Lactobacillus rhamnosus , Bifidobacterium breve , Bifidobacterium lactis , Bifidobacterium longum , and Streptococcus thermophilus 1.0 × 1010 CFU ) groups . Treatment was taken daily for 8 weeks . The primary outcome was adequate relief ( AR ) of overall IBS symptoms , which was assessed weekly for 10 weeks . A responder was defined as a patient who experienced AR for at least half of the 10-week study period . Secondary outcomes included the effects on individual symptoms , stool parameters , and IBS quality of life . The fecal flora compositions were analyzed by polymerase chain reaction denaturing gradient gel electrophoresis ( DGGE ) . Results : The proportion of AR was consistently higher in the probiotics group than in the placebo group throughout the 10-week period ( P<0.05 ) . The proportion of responders was significantly higher in the probiotics group than in the placebo group ( 48 % vs. 12 % , P=0.01 ) . Stool consistency improved significantly in the probiotics group compared with the placebo group . Percent changes in individual symptom scores were similar in the 2 groups , but IBS quality of life improvement tended to be higher in the probiotics group . Comparison of denaturing gradient gel electrophoresis profiles of fecal flora showed that the concordance rate between bacterial compositions before and after treatment was significantly higher in the probiotics group than in the placebo group ( 69.5 % vs. 56.5 % , P=0.005 ) . Conclusions : The probiotic mixture was effective in providing AR of overall IBS symptoms and improvement of stool consistency in D-IBS patients , although it had no significant effect on individual symptoms . The therapeutic effect of probiotics is associated with the stabilization of intestinal microbiota BACKGROUND Recent studies indicate a potential role of Saccharomyces boulardii in the prevention of Helicobacter pylori treatment-related side-effects and also in improvement of eradication rate . Our aim is to investigate the efficacy and safety of S. boulardii in the prevention of side-effects related to H. pylori eradication . The secondary aim of the study was to define the effect of S. boulardii on the eradication success of anti-H. pylori therapy . MATERIAL S AND METHODS One hundred and twenty-four patients with H. pylori infection ( male/female : 44/80 , mean age : 48 + /- 14.25 year ) receiving 14 days of triple therapy ( clarithromycin 500 mg b.i.d . , amoxicillin 1000 mg b.i.d . , and lansoprazole 30 mg b.i.d . ) were r and omly assigned to S. boulardii or placebo . Dyspeptic symptoms were recorded by using modified Glasgow Dyspepsia Question naire ( GDQ ) . Side-effect profile and tolerability were assessed using a symptom-based question naire . H. pylori status was rechecked after 6 weeks after completion of eradication therapy . RESULTS H. pylori eradication rate , although higher in the treatment group , was statistically similar in treatment and control groups : 71 % ( 44/62 ) versus 59.7 % ( 37/62 ) , respectively ( p > .05 ) . Nine ( 14.5 % ) patients in the treatment group and 19 ( 30.6 % ) patients in the placebo group experienced diarrhea ( p < .05 ) . Epigastric discomfort was more frequent in the control group [ 9 ( 14.5 % ) versus 27 ( 43.5 % ) , respectively ( p < .01 ) ] . Diffuse abdominal pain , abdominal gas , taste disturbance , urticaria , nausea symptoms were similar in both groups . GDQ scores after treatment were significantly better for treatment group ( mean + /- SD , range : 1.38 + /- 1.25 ( 0 - 5 ) vs. 2.22 + /- 1.44 ( 0 - 6 ) , respectively ; p < .01 ) . CONCLUSION S. boulardii improved anti-H. pylori antibiotherapy-associated diarrhea , epigastric discomfort , and treatment tolerability . In addition , S. boulardii supplement decreased post-treatment dyspepsia symptoms independent of H. pylori status . However , S. boulardii had no significant affect on the rate of H. pylori eradication A number of recent clinical trials have promoted the use of probiotic bacteria as a treatment for irritable bowel syndrome ( IBS ) . The recent demonstration of abnormal colonic fermentation in some patients with this condition provides an opportunity for the objective assessment of the therapeutic value of these bacteria . This study was design ed to investigate the effects of Lactobacillus plantarum 299V on colonic fermentation . We conducted a double-blind , placebo-controlled , cross-over , four-week trial of Lactobacillus plantarum 299V in 12 previously untreated patients with IBS . Symptoms were assessed daily by a vali date d composite score and fermentation by 24-hr indirect calorimetry in a 1.4-m3 canopy followed by breath hydrogen determination for 3 hr after 20 ml of lactulose . On placebo , the median symptom score was 8.5 [ 6.25–11.25 interquartile range ( IQR ) ] , the median maximum rate of gas production was 0.55 ml/min ( 0.4–1.1 IQR ) , and the median hydrogen production was 189.7 ml/24 hr ( 118.3–291.1 IQR ) . On Lactobacillus plantarum 299V the median symptom score was 8 ( 6.75–13.5 IQR ) , the median maximum rate of gas production 0.92 ml/min ( 0.45–1.5 IQR ) , and the median hydrogen production 208.2 ml/24 hr ( 146–350.9 IQR ) . There was no significant difference . Breath hydrogen excretion after lactulose was reduced by the probiotic ( median at 120 min , 6 ppm ; placebo , 17 ppm ; P = 0.019 ) . In conclusion , Lactobacillus plantarum 299V in this study did not appear to alter colonic fermentation or improve symptoms in patients with the irritable bowel syndrome OBJECTIVES : Antibiotic-associated diarrhea ( AAD ) and Clostridium difficile-associated diarrhea ( CDAD ) are common complications of antibiotic use . Probiotics were effective in preventing AAD and CDAD in several r and omized controlled trials . This study was aim ed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients . METHODS : A single-center , r and omized , double-blind , placebo-controlled , parallel-group trial was performed . Patients being prescribed antibiotics or on antibiotic therapy for < 48 h were eligible . Exclusion criteria were ongoing diarrhea , recent assumption of probiotics , lack of informed consent , inability to ingest capsules , and severe pancreatitis . Patients received a capsule containing S. boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy , continued treatment for 7 days after antibiotic withdrawal , and were followed for 12 weeks after ending antibiotic treatment . RESULTS : Of 562 consecutive eligible patients , 275 patients aged 79.2±9.8 years ( 134 on placebo ) were r and omized and 204 aged 78.4±10.0 years ( 98 on placebo ) completed the follow-up . AAD developed in 13.3 % ( 13/98 ) of the patients receiving placebo and in 15.1 % ( 16/106 ) of those receiving S. boulardii ( odds ratio for S. boulardii vs. placebo , 1.16 ; 95 % confidence interval ( CI ) , 0.53–2.56 ) . Five cases of CDAD occurred , 2 in the placebo group ( 2.0 % ) and 3 in the probiotic group ( 2.8 % ; odds ratio for S. boulardii vs. placebo , 1.40 ; 95 % CI , 0.23–8.55 ) . There was no difference in mortality rates ( 12.7 % vs. 15.6 % , P=0.60 ) . CONCLUSIONS : In elderly hospitalized patients , S. boulardii was not effective in preventing the development of AAD 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 AIM To determine the dose-related effects of a novel probiotic combination , I.31 , on irritable bowel syndrome (IBS)-related quality of life ( IBS-QoL ) . METHODS A multicenter , r and omized , double-blind , placebo-controlled intervention clinical trial with three parallel arms was design ed . A total of 84 patients ( 53 female , 31 male ; age range 20 - 70 years ) with IBS and diarrhea according to Rome-III criteria were r and omly allocated to receive one capsule a day for 6 wk containing : ( 1 ) I.31 high dose ( n = 28 ) ; ( 2 ) I.31 low dose ( n = 27 ) ; and ( 3 ) placebo ( n = 29 ) . At baseline , and 3 and 6 wk of treatment , patients filled the IBSQoL , Visceral Sensitivity Index ( VSI ) , and global symptom relief question naires . RESULTS During treatment , IBS-QoL increased in all groups , but this increment was significantly larger in patients treated with I.31 than in those receiving placebo ( P = 0.008 ) . After 6 wk of treatment , IBS-QoL increased by 18 ± 3 and 22 ± 4 points in the high and the low dose groups , respectively ( P = 0.041 and P = 0.023 vs placebo ) , but only 9 ± 3 in the placebo group . Gut-specific anxiety , as measured with VSI , also showed a significantly greater improvement after 6 wk of treatment in patients treated with probiotics ( by 10 ± 2 and 14 ± 2 points , high and low dose respectively , P < 0.05 for both vs 7 ± 1 score increment in placebo ) . Symptom relief showed no significant changes between groups . No adverse drug reactions were reported following the consumption of probiotic or placebo capsules . CONCLUSION A new combination of three different probiotic bacteria was superior to placebo in improving IBS-related quality of life in patients with IBS and diarrhea To assess the effect of Lactobacillus acidophilus ( American Type Culture Collection ( ATCC ) 700396 ) on enterotoxigenic Escherichia coli ( ETEC ) infection , in the present study , a parallel , double-blind , placebo-controlled 4-week intervention was performed in healthy males . The subjects largely consumed their habitual diet , but had to abstain from consuming dairy foods generally high in Ca . The subjects were r and omised into the L. acidophilus ( dose 10⁹ colony-forming units twice daily ; n 20 ) or the placebo ( n 19 ) group . After an adaptation period of 2 weeks , the subjects were orally infected with a live , but attenuated , ETEC vaccine , able to induce mild , short-lived symptoms . Before and after the challenge , the subjects recorded stool consistency , bowel habits , and frequency and severity of gastrointestinal complaints . The ETEC challenge led to a significant increase in faecal output on the 2nd day and a concomitant increase in Bristol stool scale scores . Likewise , abdominal pain , bloating , flatulence , fever , headache and nausea peaked 1 d after the oral challenge . The concentrations of faecal calprotectin and IgA peaked 2 d after and that of serum IgM peaked 9 and 15 d after the oral challenge . The concentrations of serum IgA and IgG were unaffected . The ETEC challenge led to a reduction in the number of Bacteroides-Prevotella , Bifidobacterium , Clostridium cluster XIVab and total faecal bacteria . Probiotic treatment was associated with a larger increase in Bristol stool scale scores and more fever , headache and nausea after the ETEC challenge compared with the placebo treatment . These differences were , however , small and with substantial variation within the groups . Oral application of an attenuated live ETEC vaccine provides a useful model for food-borne infections . Supplementation with L. acidophilus ATCC 700396 , however , was ineffective in reducing ETEC infection symptoms in healthy men The purpose of this study was to evaluate the efficacy and safety of commonly used probiotics and nutrients available for functional gastrointestinal disorders ( FGID ) . Five different combinations of probiotics and nutrients , or placebo , were taken daily over 12 weeks . In this r and omized controlled clinical trial , men and women 21 to 72 years of age with FGID symptoms of indigestion , bloating , and abdominal discomfort were assigned to one of six groups , 12 patients per group . Gastrointestinal Quality of Life Index ( GIQLI ) and visual analogue scale ( VAS ) for GI symptoms , SF-36 , lactulose and mannitol test ( LMT ) , and urine indican levels were evaluated . GIQLI , VAS scores , and LMT did not change significantly ( P > 0.05 ) . There were clinical ly notable improvements in two of the combination formulations . While the nonsignificant improvements in GI symptoms could suggest that combination probiotics and nutrients may be beneficial in conditions such as FGID , no conclusive evidence was found in this pilot trial . Further investigations to explore the findings are discussed Background : Helicobacter pylori eradication fails in about 10 % of patients , particularly because of the occurrence of resistance to antibiotics and side‐effects . During anti‐H. pylori therapy , probiotics have been successfully used to reduce the incidence of side‐effects Introduction Antibiotic associated diarrhea ( AAD ) is a frequently encountered adverse event following antibiotic administration . Evidence suggests that probiotics may be beneficial in preventing and decreasing the severity of AAD . Material and methods Adult patients who were prescribed antibiotics for 3 - 14 days were enrolled from eight Canadian centers . Study treatment was r and omized at a 1 : 1 ratio of BIO-K+CL1285 ® or placebo and was administered within 24 h of initiation to 5 days after termination of antibiotherapy . Patients were followed for 21 days after last dose of study treatment . The primary outcome was severity and incidence of AAD . Severity was measured by the total number of days with diarrhea and incidence was defined as the number of patients with at least one day with diarrhea over the total number of patients enrolled in the study . Results 216 patients were r and omized to BIO-K+ and 221 to placebo . The mean ( SD ) number of days with diarrhea was 1.19 . ( 3.20 ) days for the placebo and 0.67 ( 2.05 ) days for BIO-K+CL1285 ® ( p = 0.040 ) . Adjusted multivariate linear regression results showed that the duration of diarrhea for BIO-K+CL1285 ® vs. placebo was reduced by 51.5 % ( b[SE ] = 0.515 [ 0.256 ] , p = 0.045 ) . The incidence of diarrhea was 21.8 % for the BIO-K+ and 29.4 % for the placebo group ( OR = 0.667 , p = 0.067 ) . Multivariate logistic regression , showed that the adjusted odds ratio of AAD in patients receiving BIO-K+ vs. placebo was 0.627 ( p = 0.037 ) . Study treatment was well tolerated . Conclusions BIO-K+ is effective for preventing and reducing the severity of AAD in patients receiving antibiotic therapy in a hospital setting OBJECTIVE To assess how fermented oat drink with two selected Bifidobacterium longum strains influences bowel movements among elderly nursing home residents . DESIGN A r and omized , double-blind , placebo-controlled trial . SETTING 12 wards in two nursing homes in Finl and . PARTICIPANTS 209 residents . INTERVENTION Wards were r and omized to receive daily a fermented oat drink with 1 ) 109 CFU/day Bifidobacterium longum strains or 2 ) 109 CFU/day Bifidobacterium lactis Bb12 or 3 ) without viable bacteria ( placebo ) for 7 months . MEASUREMENTS Regularity of bowel movements ( no movements or functioning ) and consistency of stools ( normal , soft or diarrhoea ) were recorded for each resident on a daily basis . RESULTS The fermented oat drinks were well taken by the subjects , compliance being 85 % . The groups receiving active products had more frequent bowel movements than did the placebo group ( B. longum group normal functioning 28.5 % of follow-up days , B.lactis group 26.9 % , and placebo group 20.0 % , respectively ) . The differences between the B. longum and the placebo group ( mean 7.1 , 95 % CI 2.3 - 11.9 , p=0.004 ) and between the B.lactis group and the placebo ( mean 6.7 , 95 % CI 2.5 - 10.9 , p = 0.002 ) were significant even when diarrhoea and constipation in the 3 months prior to the study were used as covariates . CONCLUSIONS It is possible to normalize bowel movements in frail nursing home BACKGROUND Antibiotic-associated diarrhea is an important problem in hospitalized patients . The use of probiotics is gaining interest in the scientific community as a potential measure to prevent this complication . The main objective of the present study was to assess the efficacy and safety of a fermented milk combining Lactobacillus acidophilus and Lactobacillus casei that is widely available in Canada , in the prevention of antibiotic-associated diarrhea . METHODS In this double-blind , r and omized study , hospitalized patients were r and omly assigned to receive either a lactobacilli-fermented milk or a placebo on a daily basis . RESULTS Among 89 r and omized patients , antibiotic-associated diarrhea occurred in seven of 44 patients ( 15.9 % ) in the lactobacilli group and in 16 of 45 patients ( 35.6 % ) in the placebo group ( OR 0.34 , 95 % CI 0.125 to 0.944 ; P=0.05 ) . The median hospitalization duration was eight days in the lactobacilli group , compared with 10 days in the placebo group ( P=0.09 ) . Overall , the lactobacilli-fermented milk was well tolerated . CONCLUSION The daily administration of a lactobacilli-fermented milk was safe and effective in the prevention of antibiotic-associated diarrhea in hospitalized patients AIM To assess the symptomatic efficacy of Lactobacillus plantarum 299v ( L. plantarum 299v ) ( DSM 9843 ) for the relief of abdominal symptoms in a large subset of irritable bowel syndrome ( IBS ) patients fulfilling the Rome III criteria . METHODS In this double blind , placebo-controlled , parallel- design ed study , subjects were r and omized to daily receive either one capsule of L. plantarum 299v ( DSM 9843 ) or placebo for 4 wk . Frequency and intensity of abdominal pain , bloating and feeling of incomplete rectal emptying were assessed weekly on a visual analogue scale while stool frequency was calculated . RESULTS Two hundred and fourteen IBS patients were recruited . After 4 wk , both pain severity ( 0.68 + 0.53 vs 0.92 + 0.57 , P < 0.05 ) and daily frequency ( 1.01 + 0.77 vs 1.71 + 0.93 , P < 0.05 ) were lower with L. plantarum 299v ( DSM 9843 ) than with placebo . Similar results were obtained for bloating . At week 4 , 78.1 % of the patients scored the L. plantarum 299v ( DSM 9843 ) symptomatic effect as excellent or good vs only 8.1 % for placebo ( P < 0.01 ) . CONCLUSION A 4-wk treatment with L. plantarum 299v ( DSM 9843 ) provided effective symptom relief , particularly of abdominal pain and bloating , in IBS patients fulfilling the Rome III criteria Background : Irritable bowel syndrome is a gastrointestinal disorder of unknown aetiology . The effect of probiotics in this syndrome remains unclear BACKGROUND We aim ed to evaluate clinical symptoms in subjects with irritable bowel syndrome receiving Saccharomyces cerevisiae in a r and omized double-blind placebo-controlled clinical trial . METHODS Overall , 179 adults with irritable bowel syndrome ( Rome III criteria ) were r and omized to receive once daily 500 mg of Saccharomyces cerevisiae , delivered by one capsule ( n = 86 , F : 84 % , age : 42.5 ± 12.5 ) , or placebo ( n = 93 , F : 88 % , age : 45.4 ± 14 ) for 8 weeks followed by a 3-week washout period . After a 2-week run-in period , cardinal symptoms ( abdominal pain/discomfort , bloating/distension , bowel movement difficulty ) and changes in stool frequency and consistency were recorded daily and assessed each week . A safety assessment was carried out throughout the study . RESULTS The proportion of responders , defined by an improvement of abdominal pain/discomfort , was significantly higher ( p = 0.04 ) in the treated group than the placebo group ( 63 % vs 47 % , OR = 1.88 , 95 % , CI : 0.99 - 3.57 ) in the last 4 weeks of treatment . A non-significant trend of improvement was observed with Saccharomyces cerevisiae for the other symptoms . Saccharomyces cerevisiae was well tolerated and did not affect stool frequency and consistency . CONCLUSION Saccharomyces cerevisiae is well tolerated and reduces abdominal pain/discomfort scores without stool modification . Thus , Saccharomyces cerevisiae may be a new promising c and i date for improving abdominal pain in subjects with irritable bowel syndrome To investigate matrix-specifity of probiotic effects and particularly of the reduction of antibiotics-associated diarrhea , a controlled , r and omized , double-blind study was performed , in which 88 Helicobacter pylori-infected but otherwise healthy subjects were given for eight weeks either a ) a probiotic fruit yoghurt " mild " containing Lactobacillus acidophilus LA-5 plus Bifidobacterium lactis BB-12 , n = 30 ) , b ) the same product but pasteurized after fermentation ( n = 29 ) or c ) milk acidified with lactic acid ( control , n = 29 ) . During week five , a Helicobacter eradication therapy was performed . Helicobacter activity was measured via 13C-2-urea breath tests and antibiotic-associated diarrhoea and other gastrointestinal complaints were recorded by vali date d question naires . In intervention group a , b and c the mean number of days with diarrhoea was 4 , 10 and 10 ( P<0·05 ) , the frequency of episodes 17 % , 7 % and 27 % ( n.s . ) , and the change in total symptoms score before antibiotics treatment was -1·4 ± 1·1 , -1·2 ± 1·1 , 2·6 ± 1·1 points/four weeks ( P<0·05 ) . All milk products decreased Helicobacter activity by 18 to 45 % without significant differences between groups . The observed decrease in Hel . pylori activity seems to be not or not only due to probiotic bacteria but ( rather ) to components of acidified milk ( most probably lactic acid ) . Fruit-yogurt-like fermented milk products with living probiotic bacteria significantly shorten the duration of antibiotics-associated diarrhoea and improve gastrointestinal complaints . Fruit yogurt-like fermented milk is a matrix suitable for probiotic bacteria BACKGROUND / AIMS To evaluate the effect of probiotics administered as an adjuvant to sequential Helicobacter pylori ( H. pylori ) eradication therapy on treatment outcome and patient compliance . MATERIAL S AND METHODS In total , 159 patients with H. pylori infection receiving sequential H. pylori eradication therapy were included in this r and omized placebo-controlled study . Starting from day 0 of sequential eradication therapy ( ERA ) , patients in the ERA+probiotic group [ n=53 , mean ( SD ) age : 47.7 ( 14.0 ) years , 54.7 % were females ] also received a probiotic supplement with Bifidobacterium animalis subsp . lactis B94 ( 1 capsule/day ) , patients in the ERA+placebo group [ n=52 , mean ( SD ) age : 46.4 ( 13.4 ) years , 51.9 % were males ] received placebo treatment ( 1 capsule/day ) , and patients in the ERA-only group [ n=54 , mean ( SD ) age : 46.3 ( 11.9 ) years , 55.6 % were females ] received no additional treatments . Eradication rates , patient compliance , and side effects of eradication therapy were recorded in each treatment group . RESULTS Significantly higher eradication rates were noted in the ERA+probiotic group ( 86.8 % vs. 70.8 % , p=0.025 ) than in the combined ERA ( ERA-only and ERA-placebo ) group . Non-compliance with anti-H. pylori treatment was noted in 24 ( 15.1 % ) of 159 patients . Lower rates of first week treatment non-compliance due to diarrhea ( 1.88 % vs. 12.26 % , p=0.036 ) were noted in the ERA+probiotic group than in the combined ERA ( ERA-only and ERA-placebo ) group . Treatment resistance ( p : 0.389 ) was similar between the groups , indicating pure antibiotic resistance without any compliance problems . The number needed to treat for an additional beneficial outcome ( NNTB ) was 6.2 ( CI 95 % , 3.5 to 28.9 ) for probiotic use . CONCLUSION In conclusion , adjuvant administration of probiotic ( B. animalis subsp . lactis ) in 2-week sequential H. pylori eradication therapy is associated with a higher H. pylori eradication rate , lower first week diarrhea-related treatment discontinuation rates , less common self-reported side effects , and higher treatment compliance |
12,024 | 29,415,004 | The results indicated that higher education was a common facilitator of HIV testing , while misconception of HIV testing and the fear of negative consequences were the major barriers for using the testing services .
Other factors , such as demographic characteristics , marital dynamics , partner relationship , and relationship with the health care services , also greatly affects the participants ' decision making . | It was estimated that 1.2 million people live with HIV/AIDS in Zambia by 2015 .
Zambia has developed and implemented diverse programs to reduce the prevalence in the country .
HIV-testing is a critical step in HIV treatment and prevention , especially among all the key population s. However , there is no systematic review so far to demonstrate the trend of HIV-testing studies in Zambia since 1990s or synthesis the key factors that associated with HIV-testing practice s in the country . | Background Zambia ’s national HIV testing algorithm specifies use of two rapid blood based antibody assays , Determine ® HIV-1/2 ( Inverness Medical ) and if positive then Uni-GoldTM Recombigen HIV-1/2 ( Trinity Biotech ) . Little is known about the performance of oral fluid based HIV testing in Zambia . The aims of this study are two-fold : 1 ) to compare the diagnostic accuracy ( sensitivity and specificity ) under field conditions of the OraQuick ® ADVANCE ® Rapid HIV-1/2 ( OraSure Technologies , Inc. ) to two blood-based rapid antibody tests currently in use in the Zambia National Algorithm , and 2 ) to perform a cost analysis of large-scale field testing employing the OraQuick ® . Methods This was a operational retrospective research of HIV testing and question naire data collected in 2010 as part of the ZAMSTAR ( Zambia South Africa TB and AIDS reduction ) study . R and omly sample d individuals in twelve communities were tested consecutively with OraQuick ® test using oral fluid versus two blood-based rapid HIV tests , Determine ® and Uni-GoldTM . A cost analysis of four algorithms from health systems perspective were performed : 1 ) Determine ® and if positive , then Uni-GoldTM ( Determine ® /Uni-GoldTM ) ; based on current algorithm , 2 ) Determine ® and if positive , then OraQuick ® ( Determine ® /OraQuick ® ) , 3 ) OraQuick ® and if positive , then Determine ® ( OraQuick ® /Determine ® ) , 4 ) OraQuick ® and if positive , then Uni-GoldTM ( OraQuick ® /Uni-GoldTM ) . This information was then used to construct a model using a hypothetical population of 5,000 persons with varying prevalence of HIV infection from 1–30 % . Results 4,458 participants received both a Determine ® and OraQuick ® test . The sensitivity and specificity of the OraQuick ® test were 98.7 ( 95%CI , 97.5–99.4 ) and 99.8 ( 95%CI , 99.6–99.9 ) , respectively when compared to HIV positive serostatus . The average unit costs per algorithm were US$ 3.76 , US$ 4.03 , US$ 7.35 , and US$ 7.67 for Determine ® /Uni-GoldTM , Determine ® /OraQuick ® , OraQuick ® /Determine ® , and OraQuick ® /Uni-GoldTM , respectively , for an HIV prevalence of 15 % . Conclusions An alternative HIV testing algorithm could include OraQuick ® test which had a high sensitivity and specificity . The current Determine ® /Uni-GoldTM testing algorithm is the least expensive when compared to Determine ® /OraQuick ® , OraQuick ® /Determine ® , and OraQuick ® /Uni-GoldTM in the Zambian setting . From our field experience , oral fluid based testing offers many advantages over blood-based testing , especially with self testing on the horizon Background Despite the substantial investment for providing HIV counselling and testing ( VCT ) services in Zambia , there has been little effort to systematic ally evaluate the quality of VCT services provided by various types of health providers . This study , conducted in 2009 , examines VCT in the public and private sectors including private for-profit and NGO/faith-based sectors in Copperbelt and Luapula . Methods The study used five primary data collection methods to gauge quality of VCT services : closed-ended client interviews with clients exiting VCT sites ; open-ended client interviews ; interviews with facility managers ; review of service statistics ; and an observation of the physical environment for VCT by site . Over 400 clients and 87 facility managers were interviewed from almost 90 facilities . Sites were r and omly selected and results are generalizable at the provincial level . Results The study shows concerning levels of underperformance in VCT services across the sectors . It reveals serious underperformance in counselling about key risk-reduction methods . Less than one-third of clients received counselling on reducing number of sexual partners and only approximately 5 % of clients received counselling about disclosing test results to partners . In terms of client profiles , the NGO sector attracts the most educated clients and less educated Zambians seek VCT services at very low rates ( 7 % ) . The private for-profit performs equally or sometimes better than other sectors even though this sector is not adequately integrated into the Zambian national response to HIV . Conclusion The private for-profit sector provides VCT services on par in quality with the other sectors . Most clients did not receive counselling on partner reduction or disclosure of HIV test results to partners . In a generalized HIV epidemic where multiple concurrent sexual partners are a significant problem for transmitting the disease , risk-reduction methods and discussion should be a main focus of pre-test and post-test counselling This paper explores the effect of social relations and gender-based conflicts on the uptake of HIV testing in the South and Central provinces of Zambia . We conducted a community-based cross-sectional study of 1716 r and omly selected individuals . Associations were examined using mixed-effect multivariable logistic regression . A total of 264 men ( 64 % ) and 268 women ( 56 % ) had never tested for HIV . The strongest determinants for not being tested were disruptive couple relationships ( OR = 2.48 95 % CI = 1.00–6.19 ) ; tolerance to gender-based violence ( OR = 2.10 95 % CI = 1.05–4.32 ) and fear of social rejection ( OR = 1.48 95 % CI = 1.23–1.80 ) . In the Zambian context , unequal power relationships within the couple and the community seem to play a pivotal role in the decision to test which until now have been largely underestimated . Policies , programs and interventions to rapidly increase HIV testing need to urgently address gender-power inequity in relationships and prevent gender-based violence to reduce the negative impact on the lives of couples and families Background Across sub-Saharan Africa , men 's levels of HIV-testing remain inadequate relative to women ’s . Men are less likely to access anti-retroviral therapy and experience higher levels of morbidity and mortality once initiated on treatment . More frequent HIV-testing by men at continued risk of HIV-infection is required to facilitate earlier diagnosis . This study explored the frequency of HIV-testing among a rural population of men and the factors associated with more frequent HIV-testing . Methods We conducted a secondary analysis of a population -based survey in three rural district in Zambia , from February-November , 2013 . Households ( N = 300 ) in r and omly selected squares from 42 study sites , defined as a health facility and its catchment area , were invited to participate . Individuals in eligible households were invited to complete question naires regarding demographics and HIV-testing behaviours . Men were defined as multiple HIV-testers if they reported more than one lifetime test . Upon question naire completion , individuals were offered rapid home-based HIV-testing . Results Of the 2376 men , more than half ( 61 % ) reported having ever-tested for HIV . The median number of lifetime tests was 2 ( interquartile range = 1 - 3 ) . Just over half ( n = 834 ; 57 % ) of ever-testers were defined as multiple-testers . Relative to never-testers , multiple-testers had higher levels of education and were more likely to report an occupation . Among the 719 men linked to a spouse , multiple-testing was higher among men whose spouse reported ever-testing ( adjusted prevalence ratio = 3.02 95 % CI : 1.37 - 4.66 ) . Multiple-testing was higher in study sites where anti-retroviral therapy was available at the health facility on the day of a health facility audit . Among ever-testers , education and occupation were positively associated with multiple-testing relative to reporting one lifetime HIV-test . Almost half ( 49 % ) of ever-testers accepted the offer of home-based HIV-testing . Discussion Reported HIV-testing increased among this population of men since a 2011/12 survey . Yet , only 35 % of all men reported multiple lifetime HIV-tests . The factors associated with multiple HIV-testing were similar to factors associated with ever-testing for HIV . Men living with HIV were less likely to report multiple HIV-tests and employment and education were associated with multiple-testing . The offer of home-based HIV-testing increased the frequency of HIV-testing among men . Conclusion Although men 's levels of ever-testing for HIV have increased , strategies need to increase the lifetime frequency of HIV-testing among men at continued risk of HIV-infection Background We assessed the integration of early infant HIV diagnosis with the exp and ed programme for immunization in a rural Zambian setting with the aim of determining whether infant and postpartum maternal HIV testing rates would increase without harming immunization uptake . Methods In an unblinded , location stratified , cluster r and omised controlled trial , 60 facilities in Zambia ’s Southern Province were equally allocated to a control group , Simple Intervention group that received a sensitization meeting and the resupply of HIV testing commodities in the event of a stock-out , and a Comprehensive Intervention group that received the Simple Intervention as well as on-site operational support to facilitate the integration of HIV testing services with EPI . Findings The average change in number of first dose diphtheria , pertussis , and tetanus vaccine ( DPT1 ) provided per month , per facility was approximately 0.86 doses higher [ 90 % confidence interval ( CI ) -1.40 , 3.12 ] in Comprehensive Intervention facilities compared to the combined average change in the Simple Intervention and control facilities . The interventions result ed in a 16.6 % [ 90 % CI : -7 % , 46 % , P-value = 0.26 ] and 10 % [ 90 % CI : -10 % , 36 % , P-value = 0.43 ] greater change in average monthly infant DBS testing compared to control for the Simple and Comprehensive facilities respectively . We also found 15.76 ( 90 % CI : 7.12 , 24.41 , P-value < 0.01 ) and 10.93 ( 90 % CI : 1.52 , 20.33 , P-value = 0.06 ) additional total maternal re-tests over baseline for the Simple and Comprehensive Facilities respectively . Conclusions This study provides strong evidence to support Zambia ’s policy of integration of HIV testing and EPI services . Actions in line with the interventions , including HIV testing material supply reinforcement , can increase HIV testing rates without harming immunization uptake . In response , Zambia ’s Ministry of Health issued a memo to remind health facilities to provide HIV testing at under-five clinics and to include under-five HIV testing as part of district performance assessment s. Trial Registration Clinical Trials.gov Registration Number : Home-based voluntary HIV counselling and testing ( HB-VCT ) has been reported to have a high uptake , but it has not been rigorously evaluated . We design ed a model for HB-VCT appropriate for wider scale-up , and investigated the acceptance of home-based counselling and testing , equity in uptake and negative life events with a cluster-r and omized trial . Thirty six rural clusters in southern Zambia were pair-matched based on baseline data and r and omly assigned to the intervention or the control arm . Both arms had access to st and ard HIV testing services . Adults in the intervention clusters were offered HB-VCT by local lay counsellors . Effects were first analysed among those participating in the baseline and post-intervention surveys and then as intention-to-treat analysis . The study was registered with www.controlled-trials.com , number IS RCT N53353725 . A total of 836 and 858 adults were assigned to the intervention and control clusters , respectively . In the intervention arm , counselling was accepted by 85 % and 66 % were tested ( n = 686 ) . Among counselled respondents who were cohabiting with the partner , 62 % were counselled together with the partner . At follow-up eight months later , the proportion of adults reporting to have been tested the year prior to follow-up was 82 % in the intervention arm and 52 % in the control arm ( Relative Risk ( RR ) 1.6 , 95 % CI 1.4 - 1.8 ) , whereas the RR was 1.7 ( 1.4 - 2.0 ) according to the intention-to-treat analysis . At baseline the likelihood of being tested was higher for women vs. men and for more educated people . At follow-up these differences were found only in the control communities . Measured negative life events following HIV testing were similar in both groups . In conclusion , this HB-VCT model was found to be feasible , with a very high acceptance and to have important equity effects . The high couple counselling acceptance suggests that the home-based approach has a particularly high HIV prevention potential The objective of this study is to describe HIV-testing among men in rural Lusaka Province , Zambia , using a population -based survey for a cluster-r and omized trial . Households ( N = 120 ) were r and omly selected from each of the 42 clusters , defined as a health facility catchment area . Individuals aged 15–60 years were invited to complete question naires regarding demographics and HIV-testing history . Men testing in the last year were defined as recent-testers . After question naire completion adults were offered home-based rapid HIV-testing . Of the 2,828 men , 53 % reported ever-testing and 25 % recently-testing . Factors independently associated with ever- and recent-testing included age 20 + years , secondary /higher education , being married or widowed , a history of TB-treatment and higher socioeconomic position . 53 % of never-testers and 57 % of men who did not report a recent-test accepted home-based HIV-testing . Current HIV-testing approaches are inadequate in this high prevalence setting . Alternative strategies , including self-testing , mobile- or workplace-testing , may be required to complement facility-based services Objective : Many sub-Saharan African countries report high postpartum loss to follow-up of mother – baby pairs . We aim ed to determine whether interactive text messages improved rates of clinic attendance and early infant HIV testing in the Nyanza region of Kenya . Design : Parallel-group , unblinded , r and omized controlled trial . Methods : HIV-positive pregnant women at least 18 years old and enrolled in the prevention of mother-to-child transmission of HIV programme were r and omized to receive either text messages ( SMS group , n = 195 ) or usual care ( n = 193 ) . Messages were developed using formative focus group research informed by constructs of the Health Belief Model . The SMS group received up to eight text messages before delivery ( depending on gestational age ) , and six messages postpartum . Primary outcomes included maternal postpartum clinic attendance and virological infant HIV testing by 8 weeks postpartum . The primary analyses were intention-to-treat . Results : Of the 388 enrolled women , 381 ( 98.2 % ) had final outcome information . In the SMS group , 38 of 194 ( 19.6 % ) women attended a maternal postpartum clinic compared to 22 of 187 ( 11.8 % ) in the control group ( relative risk 1.66 , 95 % confidence interval 1.02–2.70 ) . HIV testing within 8 weeks was performed in 172 of 187 ( 92.0 % ) infants in the SMS group compared to 154 of 181 ( 85.1 % ) in the control group ( relative risk 1.08 , 95 % confidence interval 1.00–1.16 ) . Conclusions : Text messaging significantly improved maternal postpartum visit attendance , but overall return rates for these visits remained low . In contrast , high rates of early infant HIV testing were achieved in both arms , with significantly higher testing rates in the SMS compared to the control infants HIV-related stigma continues to be a prominent barrier to testing , treatment and care . However , few studies have investigated changes in stigma over time and the factors contributing to these changes , and there is no evidence of the impact of HIV testing and counselling on stigma . This study was nested within a pair-matched cluster-r and omized trial on the acceptance of home-based voluntary HIV counselling and testing conducted in a rural district in Zambia between 2009 and 2011 , and investigated changes in stigma over time and the impact of HIV testing and counselling on stigma . Data from a baseline survey ( n = 1500 ) and a follow-up survey ( n = 1107 ) were used to evaluate changes in stigma . There was an overall reduction of seven per cent in stigma from baseline to follow-up . This was mainly due to a reduction in individual stigmatizing attitudes but not in perceived stigma . The reduction did not differ between the trial arms ( β = -0.22 , p = 0.423 ) . Being tested for HIV was associated with a reduction in stigma ( β = -0.57 , p = 0.030 ) , and there was a trend towards home-based Voluntary Counselling and Testing having a larger impact on stigma than other testing approaches ( β = -0.78 , p = 0.080 vs. β = -0.37 , p = 0.551 ) , possibly explained by a strong focus on counselling and the safe environment of the home . The reduction observed in both arms may give reason to be optimistic as it may have consequences for disclosure , treatment access and adherence . Yet , the change in stigma may have been affected by social desirability bias , as extensive community mobilization was carried out in both arms . The study underscores the challenges in measuring and monitoring HIV-related stigma . Adjustment for social desirability bias and inclusion of qualitative methods are recommended for further studies on the impact of HIV testing on stigma OBJECTIVE To examine factors affecting the readiness for HIV-related voluntary confidential counselling and testing ( VCT ) . METHODS In a population -based HIV survey in selected urban and rural areas in Zambia , adults aged > or = 15 years were selected by stratified r and om cluster sampling . The participants were asked to provide a saliva sample for anonymous HIV testing ( n=4812 , consent rate 93.5 % ) and , as a part of an interview , were asked about previous HIV testing experience and if they wished to be counselled and tested for HIV . Those indicating interest ( initially willing ) were provided with an invitation letter to see a counsellor . In rural areas , VCT was provided by personnel brought in from outside the local community , whereas in urban areas it was provided by locally recruited staff . RESULTS The overall HIV test rate was 6.5 % , but rates appeared to be considerably biased towards higher educational groups . The proportion initially willing was 37 % while 3.6 % actually came for counselling and were tested ( 9.3 % of those initially willing ) , of which 47 % returned for the result . Actual use was four to five times higher in rural compared with urban areas . Self-perceived risk and high-risk behaviour were positively associated with initial willingness but not with actual use . CONCLUSIONS The readiness for VCT in the general population was found to be very low . Provision factors such as concerns about confidentiality and length of time waiting for the test result contributed to the low utilization rate . Results of this study contrast sharply with reported VCT acceptance rates of 70 - 90 % among women attending antenatal care in Zambian and in other African population s , suggesting an urgent need to evaluate testing policy and practice of antenatal VCT in particular Background : Provision of HIV testing in labor provides an opportunity to reach susceptible women and infants . Methods : As part of a cluster r and omized trial of labor ward-based prevention of mother-to-child transmission services in Lusaka , Zambia , we determined predictors of testing acceptance and nevirapine ( NVP ) administration in labor . HIV counseling and testing were offered to women unaware of their HIV status . NVP was administered to women who tested positive , and an inert ( calcium ) tablet was provided to women who tested negative , to avoid stigmatization . Results : Among the 2435 women who presented in labor , 393 ( 16 % ) were unaware of their HIV status , of whom 278 ( 71 % ) met eligibility criteria . We offered counseling to 217 ( 78 % ) of eligible women : 146 ( 67 % ) agreed , 82 ( 56 % ) of those counseled were tested for HIV , and 23 ( 28 % ) were seropositive . Testing rates were higher among primigravida women [ adjusted odds ratio ( AOR ) 1.5 ; 95 % confidence interval ( CI ) : 1.1 to 2.1 ] and among those not offered HIV testing during their pregnancy ( AOR 3.7 ; 95 % CI : 2.8 to 5.1 ) . Cervical dilation ≤3 cm at the time of admission was associated strongly with NVP ingestion > 1 hour ( AOR 11.5 ; 95 % CI : 4.5 to 29.2 ) and > 2 hours ( AOR 11.4 ; 95 % CI : 4.7 to 27.5 ) before delivery . Conclusion : Labor ward HIV testing is feasible in this re source -limited setting OBJECTIVES To examine factors affecting readiness for and acceptability of voluntary HIV counselling and testing ( VCT ) . METHODS Participants in a population -based HIV survey conducted in an urban population in Zambia in 1996 were offered VCT . Although 29 % of them expressed interest in being tested ( readiness ) , only 4 % of this group used the services ( i.e. acceptability ) . When the survey was repeated 3 years later , VCT was design ed differently to assess acceptability . At the cluster level the participants were r and omly allocated to VCT either at the local clinic ( similar to 1996 , n = 1102 ) or at an optional location ( n = 1343 ) . RESULTS Readiness varied significantly by age group ( 47 % in age group 20 - 24 years vs. 18 % in age group 40 - 49 years ) . There were contrasts between young ( 15 - 24 years ) and older age groups ( 25 - 49 years ) regarding the main factors associated with readiness . Whereas self-perceived risk of being HIV infected was the only significant factor among the young , poor self-rated health and ever HIV tested were important factors among the older . The acceptability was 11.8 % among the group allocated to VCT at the local clinic compared with 55.8 % for the group allocated to an optional location ( RR , 4.7 ) . CONCLUSIONS Perceived risk of HIV infection had a major influence on VCT readiness among young people , whereas declining general health status , as indicated by self-rated health , was most evident among those of older age . A strong effect of placement on acceptability of VCT was demonstrated , indicating this barrier to be important in explaining low dem and s for VCT in the past . Differences in perceptions of how confidentiality is h and led at the two locations might be an important underlying factor HIV testing and counselling is a critical gateway to prevention and treatment . Yet , coverage remains insufficient , few couples are tested together and gender differences in access exist . We used an embedded mixed methods approach to investigate possible explanations for the high acceptance of home-based voluntary HIV counselling and testing ( HB-VCT ) in a pair-matched cluster-r and omized trial in Zambia . A baseline survey included 1694 individuals in 36 clusters . Adults in 18 intervention clusters were offered HB-VCT by lay counsellors . St and ard testing services were available in both trial arms . After the completion of the intervention , a follow-up survey was conducted in all trial clusters . In addition , 21 in-depth interviews and one focus group discussion were conducted with home-based VCT clients in the intervention arm . Informants favoured the convenience , confidentiality and credibility of HB-VCT . Counsellors were perceived as trustworthy owing to their closeness and conduct , and the consent process was experienced as convincing . Couple testing was selected by 70 % of cohabiting couples and was experienced as beneficial by both genders . Levels of first-time testing ( 68 % vs. 29 % , p < 0.0001 ) and re-testing ( 94 % vs. 74 % , p < 0.0001 ) were higher in the intervention than in the control arm . Acceptance of HIV testing and counselling is dependent on stigma , trust and gender . The confidentiality of home-based VCT was essential for overcoming stigma-related barriers , and the selection of local counsellors was important to ensure trust in the services . The high level of couple counselling within HB-VCT may contribute to closing the gender gap in HIV testing , and has benefits for both genders and potentially for prevention of HIV transmission . The study demonstrates the feasibility of achieving high test coverage with an opt-in consent approach . The embedded qualitative component confirmed the high satisfaction with HB-VCT reported in the quantitative survey and was crucial to fully underst and the intervention and its consequences |
12,025 | 27,752,078 | Adalimumab , etanercept , infliximab and tocilizumab all showed statistically significant improvements in depressive symptoms .
Meta-regression exploring predictors of response found that the antidepressant effect was associated with baseline symptom severity ( P=0.018 ) but not with improvement in primary physical illness , sex , age or study duration .
The findings indicate a potentially causal role for cytokines in depression and that cytokine modulators may be novel drugs for depression in chronically inflamed subjects . | Inflammatory cytokines are commonly elevated in acute depression and are associated with resistance to monoaminergic treatment . | Background Patient reported outcomes ( PROs ) are especially useful in assessing treatments for rheumatoid arthritis ( RA ) since they measure dimensions of health-related quality of life that can not be captured using strictly objective physiological measures . The aim of this study was to compare the effects of combination etanercept and methotrexate ( ETN + MTX ) versus combination synthetic disease modifying antirheumatic drugs ( DMARDs ) and methotrexate ( DMARD + MTX ) on PRO measures among RA patients from the Asia-Pacific region , a population not widely studied to date . Patients with established moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate were studied . Methods Patients were r and omized to either ETN + MTX ( N = 197 ) or DMARD + MTX ( N = 103 ) in an open-label , active-comparator , multicenter study , with PRO measures design ed as prospect i ve secondary endpoints . The Health Assessment Question naire ( HAQ ) , Functional Assessment of Chronic Illness Therapy Fatigue Scale ( FACIT-Fatigue ) , Medical Outcomes Short Form-36 Health Survey ( SF-36 ) , Hospital Anxiety and Depression Scale ( HADS ) and the Work Productivity and Activity Impairment Question naire : General Health ( WPAI : GH ) were used . Results Significantly greater improvements were noted for the ETN + MTX group at week16 for HAQ mean scores and for proportion of patients achieving HAQ score ≤ 0.5 , compared to patients in the DMARD + MTX group . SF-36 Summary Scores for physical and mental components and for 6 of 8 health domains showed significantly greater improvements at week16 for the ETN + MTX group ; only scores for physical functioning and role-emotional domains did not differ significantly between the two treatment arms . Greater improvements at week16 were noted for the ETN + MTX group for FACIT-Fatigue , HADS , and WPAI : GH mean scores . Conclusion Combination therapy using ETN + MTX demonstrated superior improvements using a comprehensive set of PRO measures , compared to combination therapy with usual st and ard of care DMARDs plus MTX in patients with established rheumatoid arthritis from the Asia-Pacific region . Trial registration clintrials.gov # AIM To study the effect of infliximab on fatigue in relation to cytokine levels in Crohn 's disease ( CD ) patients . METHODS Fourteen CD patients were blinded for treatment and received placebo at baseline , and infliximab 2 wk later , with a follow-up of 4 wk . Blood sample s were drawn on a regular basis , and question naires on fatigue , depression , quality of life , and clinical disease activity were completed at regular intervals . RESULTS After placebo infusion , fatigue scores decreased within 3 d ( 3.5 points + /- 1.1 , P < or= 0.01 ) , but returned to baseline values 14 d after this infusion . The drop of fatigue scores following infliximab infusion sustained until the end of the study ( 3.8 points + /- 1.4 , P < or= 0.05 ) . Quality of life was increased at the end of the study compared to baseline values ( 138.6 + /- 9.4 vs 179.4 + /- 6.7 ; P < or= 0.005 ) , whereas depression scores were decreased ( 20.4 + /- 9.4 vs 11.3 + /- 2.2 ; P < or= 0.01 ) . No correlation between the severity of fatigue and the level of cytokines was observed . CONCLUSION The reduction of fatigue after infliximab infusion is subjective to a placebo effect . The effect of infliximab on fatigue , however , persists while the placebo effect disappears after a short period of time . A clear role of cytokines could not be substantiated BACKGROUND Infectious , autoimmune , and neurodegenerative diseases are associated with profound psychological disturbances . Studies in animals clearly demonstrate that cytokines mediate illness-associated behavioral changes . However , the mechanisms underlying the respective psychological alterations in humans have not been established yet . Therefore , we investigated the effects of low-dose endotoxemia , a well-established and safe model of host-defense activation , on emotional , cognitive , immunological , and endocrine parameters . METHODS In a double-blind , crossover study , 20 healthy male volunteers completed psychological question naires and neuropsychological tests 1 , 3 , and 9 hours after intravenous injection of Salmonella abortus equi endotoxin ( 0.8 ng/kg ) or saline in 2 experimental sessions . Blood sample s were collected hourly , and rectal temperature and heart rate were monitored continuously . RESULTS Endotoxin had no effects on physical sickness symptoms , blood pressure , or heart rate . Endotoxin caused a mild increase in rectal temperature ( 0.5 degrees C ) , and increased the circulating levels of tumor necrosis factor alpha ( TNF-alpha ) , soluble TNF receptors , interleukin (IL)-6 , IL-1 receptor antagonist , and cortisol . After endotoxin administration , the subjects showed a transient significant increase in the levels of anxiety ( effect size [ ES ] = 0.55 ) and depressed mood ( ES = 0.66 ) . Verbal and nonverbal memory functions were significantly decreased ( ES = 0.55 to 0.64 ) . Significant positive correlations were found between cytokine secretion and endotoxin-induced anxiety ( r = 0.49 to r = 0.60 ) , depressed mood ( r = 0.40 to r = 0.75 ) , and decreases in memory performance ( r = 0.46 to r = 0.68 ) . CONCLUSIONS In humans , a mild stimulation of the primary host defense has negative effects on emotional and memory functions , which are probably caused by cytokine release . Hence , cytokines represent a novel target for neuropsychopharmacological research OBJECTIVE To identify factors predicting response to first TNF blocking treatment course in patients with established RA with a special focus on gender differences . METHODS Patients with active RA initiating their first treatment course of TNF-blocking therapy were enrolled . The study period was March 1999 through September 2006 . The prospect i ve protocol included information on demographics , clinical characteristics of patients and response measures . Fulfilment of ACR 50 - 70 % improvement and European League Against Rheumatism ( EULAR ) good response or remission [ 28-joint disease activity score ( DAS28 ) < 2.6 ] at 3 months were chosen as primary outcome measures . Potential predictors of responses were identified using multivariate binary logistic regression models . RESULTS In total , 1565 patients were included in the study . Gender did not influence treatment response . Consistently , concomitant methotrexate ( MTX ) was significantly associated with EULAR remission , EULAR good response , ACR50 response and ACR70 response with odds ratios ( ORs ) 1.97 , 2.13 , 2.10 and 1.75 , respectively . Concurrent treatment with other DMARDs was also significantly associated with EULAR remission , EULAR good response and ACR50 response ( OR : 1.96 , 2.24 and 1.94 , respectively ) . Likewise , low HAQ at baseline consistently predicted good clinical outcome . Disease activity at baseline was directly associated with favourable response when measured by ACR50 and ACR70 ( OR : 1.59 and 1.60 , respectively ) , whereas DAS28 score at baseline was inversely associated with EULAR remission ( OR : 0.78 ) . CONCLUSIONS In this observational study of patients with established RA , gender did not predict response to anti-TNF therapy , whereas treatment with concomitant DMARDs , especially MTX and low disability were associated with good response . Choice of outcome measures may influence the predictive value of baseline features Fatigue is a significant symptom in multiple sclerosis ( MS ) patients . First-generation disease modifying therapies ( DMTs ) are at best moderately effective to improve fatigue . Observations from small cohorts have indicated that natalizumab , an antibody targeting VLA-4 , may reduce MS-related fatigue . The TYNERGY study aim ed to further evaluate the effects of natalizumab treatment on MS-related fatigue . In this one-armed clinical trial including 195 MS patients , natalizumab was prescribed in a real-life setting , and a vali date d question naire , the Fatigue Scale for Motor and Cognitive functions ( FSMC ) , was used both before and after 12 months of treatment to evaluate a possible change in the fatigue experienced by the patients . In the treated cohort all measured variables , that is , fatigue score , quality of life , sleepiness , depression , cognition , and disability progression were improved from baseline ( all p values<0.0001 ) . Walking speed as measured by the six-minute walk-test also increased at month 12 ( p = 0.0016 ) . All patients were aware of the nature of the treatment agent , and of the study outcomes . Conclusion Natalizumab , as used in a real-life setting , might improve MS-related fatigue based on the results from this one-armed un-controlled stud . Also other parameters related to patients ' quality of life seemed to improve with natalizumab treatment . Trial Registration Clinical Trials.gov CONTEXT Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse , and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants . OBJECTIVES To determine whether inhibition of the inflammatory cytokine tumor necrosis factor ( TNF ) reduces depressive symptoms in patients with treatment-resistant depression and whether an increase in baseline plasma inflammatory biomarkers , including high-sensitivity C-reactive protein ( hs-CRP ) , TNF , and its soluble receptors , predicts treatment response . DESIGN Double-blind , placebo-controlled , r and omized clinical trial . SETTING Outpatient infusion center at Emory University in Atlanta , Georgia . PARTICIPANTS A total of 60 medically stable out patients with major depression who were either on a consistent antidepressant regimen ( n = 37 ) or medication-free ( n = 23 ) for 4 weeks or more and who were moderately resistant to treatment as determined by the Massachusetts General Hospital Staging method . INTERVENTIONS Three infusions of the TNF antagonist infliximab ( 5 mg/kg ) ( n = 30 ) or placebo ( n = 30 ) at baseline and weeks 2 and 6 of a 12-week trial . MAIN OUTCOME MEASURES The 17-item Hamilton Scale for Depression ( HAM-D ) scores . RESULTS No overall difference in change of HAM-D scores between treatment groups across time was found . However , there was a significant interaction between treatment , time , and log baseline hs-CRP concentration ( P = .01 ) , with change in HAM-D scores ( baseline to week 12 ) favoring infliximab-treated patients at a baseline hs-CRP concentration greater than 5 mg/L and favoring placebo-treated patients at a baseline hs-CRP concentration of 5 mg/L or less . Exploratory analyses focusing on patients with a baseline hs-CRP concentration greater than 5 mg/L revealed a treatment response ( ≥50 % reduction in HAM-D score at any point during treatment ) of 62 % ( 8 of 13 patients ) in infliximab-treated patients vs 33 % ( 3 of 9 patients ) in placebo-treated patients ( P = .19 ) . Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab-treated responders vs nonresponders ( P < .05 ) , and infliximab-treated responders exhibited significantly greater decreases in hs-CRP from baseline to week 12 compared with placebo-treated responders ( P < .01 ) . Dropouts and adverse events were limited and did not differ between groups . CONCLUSIONS This proof-of-concept study suggests that TNF antagonism does not have generalized efficacy in treatment-resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00463580 Background Inflammatory cytokines are implicated in the pathophysiology of depression . In rodents , systemically administered inflammatory cytokines induce depression-like behavior . Similarly in humans , therapeutic interferon-α induces clinical depression in a third of patients . Conversely , patients with depression also show elevated pro-inflammatory cytokines . Objectives To determine the neural mechanisms underlying inflammation-associated mood change and modulatory effects on circuits involved in mood homeostasis and affective processing . Methods In a double-blind , r and omized crossover study , 16 healthy male volunteers received typhoid vaccination or saline ( placebo ) injection in two experimental sessions . Mood question naires were completed at baseline and at 2 and 3 hours . Two hours after injection , participants performed an implicit emotional face perception task during functional magnetic resonance imaging . Analyses focused on neurobiological correlates of inflammation-associated mood change and affective processing within regions responsive to emotional expressions and implicated in the etiology of depression . Results Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at 3 hours . Inflammation-associated mood deterioration correlated with enhanced activity within subgenual anterior cingulate cortex ( sACC ) ( a region implicated in the etiology of depression ) during emotional face processing . Furthermore , inflammation-associated mood change reduced connectivity of sACC to amygdala , medial prefrontal cortex , nucleus accumbens , and superior temporal sulcus , which was modulated by peripheral interleukin-6 . Conclusions Inflammation-associated mood deterioration is reflected in changes in sACC activity and functional connectivity during evoked responses to emotional stimuli . Peripheral cytokines modulate this mood-dependent sACC connectivity , suggesting a common pathophysiological basis for major depressive disorder and sickness-associated mood change and depression BACKGROUND Despite strong evidence for its effectiveness , cognitive-behavioural therapy ( CBT ) remains difficult to access . Computerised programs have been developed to improve accessibility , but whether these interventions are responsive to individual needs is unknown . We investigated the effectiveness of CBT delivered online in real time by a therapist for patients with depression in primary care . METHODS In this multicentre , r and omised controlled trial , 297 individuals with a score of 14 or more on the Beck depression inventory ( BDI ) and a confirmed diagnosis of depression were recruited from 55 general practice s in Bristol , London , and Warwickshire , UK . Participants were r and omly assigned , by a computer-generated code , to online CBT in addition to usual care ( intervention ; n=149 ) or to usual care from their general practitioner while on an 8-month waiting list for online CBT ( control ; n=148 ) . Participants , research ers involved in recruitment , and therapists were masked in advance to allocation . The primary outcome was recovery from depression ( BDI score < 10 ) at 4 months . Analysis was by intention to treat . This trial is registered , number IS RCT N 45444578 . FINDINGS 113 participants in the intervention group and 97 in the control group completed 4-month follow-up . 43 ( 38 % ) patients recovered from depression ( BDI score < 10 ) in the intervention group versus 23 ( 24 % ) in the control group at 4 months ( odds ratio 2.39 , 95 % CI 1.23 - 4.67 ; p=0.011 ) , and 46 ( 42 % ) versus 26 ( 26 % ) at 8 months ( 2.07 , 1.11 - 3.87 ; p=0.023 ) . INTERPRETATION CBT seems to be effective when delivered online in real time by a therapist , with benefits maintained over 8 months . This method of delivery could broaden access to CBT . FUNDING BUPA Foundation 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 OBJECTIVES : We evaluated the effects of adalimumab maintenance therapy on health-related quality of life ( HRQOL ) in patients with moderate to severe Crohn 's disease . METHODS : In a Phase III , r and omized , double-blind clinical trial ( CHARM ) of moderate to severe Crohn 's disease patients , HRQOL outcomes were compared between the adalimumab maintenance treatment groups ( every other week and weekly injection ) and the adalimumab induction-only group . The Zung Self-Rating Depression Scale , functional assessment of chronic illness therapy (FACIT)-Fatigue , visual analog pain scales , Inflammatory Bowel Disease question naire ( IBDQ ) , and Medical Outcomes Study 36-item Short Form Health Survey ( SF-36 ) were analyzed for 499 r and omized responders ( a decrease of ≥70 points from baseline in the Crohn 's Disease Activity Index [ CDAI ] ) at baseline and weeks 4 , 12 , 26 , and 56 . RESULTS : CHARM patients ' HRQOL was substantially impaired at baseline . Following a 4-week adalimumab induction therapy , patients experienced statistically significant improvements in all HRQOL measures ( P < 0.0001 ) . Compared with patients who were assigned to placebo after induction therapy , patients who continued adalimumab at 40 mg every other week maintenance therapy reported less depression ( P < 0.01 ) , fewer fatigue symptoms ( P < 0.001 ) , greater improvements in the IBDQ ( P < 0.05 ) , greater SF-36 physical component summary scores ( P < 0.05 ) , and less abdominal pain ( P < 0.05 ) from weeks 12 to 56 . They also had greater SF-36 mental component summary scores at week 56 ( P < 0.05 ) . Patients who continued adalimumab at 40-mg weekly maintenance therapy reported less depression and fewer fatigue symptoms at week 56 , greater improvement in IBDQ , and less abdominal pain from weeks 12 to 56 ( all P < 0.05 vs. placebo ) . CONCLUSIONS : Adalimumab maintenance therapy provided sustained improvements in HRQOL for patients with moderate to severe Crohn 's disease through week 56 OBJECTIVE Approximately 30 % of patients with depression fail to respond to a selective serotonin reuptake inhibitor ( SSRI ) . Few studies have attempted to define these patients from a biological perspective . Studies suggest that overall patients with depression show increased production of proinflammatory cytokines . We examined pro- and anti-inflammatory cytokine levels in patients who were SSRI resistant . METHODS Plasma concentrations of IL-6 , IL-8 , IL-10 , TNF-alpha and sIL-6R were measured with enzyme linked immunosorbent assays ( ELISA ) in DSM-1V major depressives who were SSRI resistant , in formerly SSRI resistant patients currently euthymic and in healthy controls . RESULTS Patients with SSRI-resistant depression had significantly higher production of the pro-inflammatory cytokines IL-6 ( p=0.01 ) and TNF-alpha ( p=0.004 ) compared to normal controls . Euthymic patients who were formerly SSRI resistant had proinflammatory cytokine levels which were similar to the healthy subject group . Anti-inflammatory cytokine levels did not differ across the 3 groups . CONCLUSION Suppression of proinflammatory cytokines does not occur in depressed patients who fail to respond to SSRIs and is necessary for clinical recovery BACKGROUND Psoriasis significantly impacts patients ' quality of life . OBJECTIVES The purpose of this study was to prospect ively assess the quality -of-life impact of treatment for moderate to severe plaque psoriasis by using a vali date d quality -of-life psychometric instrument that has been widely used in nondermatologic setting s. METHODS In all , 32 patients with moderate to severe plaque psoriasis received 24 weeks of adalimumab treatment . Patients completed the Psychological General Well-Being ( PGWB ) Index , which evaluates 6 domains including anxiety and depression . The primary end point was the change in total PGWB score at weeks 12 and 24 of adalimumab treatment compared with baseline . RESULTS Statistically significant improvement in the total PGWB score was documented by week 4 . By week 24 , all 6 PGWB domains showed statistically significant improvement from the pretreatment baseline . LIMITATIONS One limitation of this study is that the comparison between our psoriasis data and PGWB data from other major medical conditions was not conducted in a head-to-head manner . Another limitation is that we did not have a controlled ( placebo ) arm . CONCLUSION Based on PGWB scores , patients with untreated psoriasis have as much impairment in psychological well-being as patients with other major medical diseases including breast cancer , coronary artery disease , congestive heart failure , and diabetes and that potent intervention improves psychological well-being to where it is comparable with that of patients with asymptomatic hypertension . A prompt intervention with an effective dermatologic treatment is not only critical , but capable of restoring the physical and psychological well-being of patients with psoriasis BACKGROUND Moderate/severe psoriasis combined with psoriatic arthritis ( PsA ) impairs health-related quality of life ( QoL ) . Etanercept , a fully human tumour necrosis factor-α receptor fusion protein , is approved for treatment of both diseases . OBJECTIVE To compare patient-reported health outcomes ( PROs ) of two etanercept regimens in patients with moderate/severe psoriasis and PsA. METHODS In this r and omized , double-blind , multicenter study , participants received etanercept 50 mg twice weekly ( BIW ; n = 379 ) or 50 mg weekly ( QW ; n = 373 ) for 12 weeks and open-label etanercept 50 mg QW for 12 additional weeks . PROs included : the EuroQOL-5D ( EQ-5D ) , which measures general health status and consists of the utility index measuring five dimensions of health , and a visual analogue scale ( VAS ) allowing patients to assess health status ; the Dermatology Life Quality Index ( DLQI ) , which measures the impact of skin disease on QoL ; the Health Assessment Question naire-Disability Index ( HAQ-DI ) , an assessment of physical function ; the Hospital Anxiety and Depression Scale ( HADS ) , which screens for anxiety and depression symptoms ; and individual questions on general health , disease activity , fatigue , itching , joint pain and morning stiffness . RESULTS At baseline , patients reported QoL worse than that seen in many chronic medical conditions . Significant within-group improvements in each PRO occurred from baseline to Week 12 ( P < 0.001 ) in both groups and were maintained at Week 24 ; DLQI , EQ-5D , HAQ-DI and self assessment s improved significantly ( P < 0.001 ) from baseline as early as Week 3 . At Week 12 , but not Week 24 , improvement in DLQI , itching and psoriasis activity was greater in the BIW arm ( P ≤ 0.004 ) . Improvements in other PROs were always similar between groups . CONCLUSIONS Greater improvements in PROs specific to skin disorders were seen with etanercept BIW than QW at Week 12 , but not at Week 24 . Both etanercept regimens led to sustained PRO improvements , starting as early as Week 3 OBJECTIVE To assess patient-reported outcomes ( PRO ) in patients with moderate-to-severe plaque psoriasis receiving continuous or paused etanercept treatment . METHODS In a multicentre European open-label study , one group ( n = 352 ) received continuous therapy : 25 mg subcutaneously ( SC ) twice weekly ( BIW ) throughout 54-weeks . The other group ( n = 359 ) received paused therapy : 50 mg SC BIW ( < or= 12 weeks ) until response was adequate by Physician Global Assessment ; after psoriasis returned , retreatment ( 25 mg BIW ) was begun . PRO included the Dermatology Life Quality Index ( DLQI ) , EuroQoL-5D ( EQ-5D ) , Hospital Anxiety and Depression Scale ( HADS ) , and the SF-36 Vitality subscale . RESULTS At baseline , mean DLQI for patients in the continuous ( 12.8 ) and paused group ( 13.8 ) , indicated significant quality -of-life impairment ; mean EQ-5D utility scores were 0.65 and 0.66 for continuous and paused patients , respectively ; 30.0 % of continuous and 37.0 % of paused patients had at least mild symptoms of depression ; 40.2 % and 48.6 % , respectively , had at least mild symptoms of anxiety . At week 54 , both groups showed statistically significant ( P < 0.05 ) and meaningful improvement in DLQI and EQ-5D scores ; improvements in HADS-D , HADS-A , and SF-36 vitality were also significant . Improvements in DLQI and EQ-5D were significantly greater in the continuous arm than the paused arm , but the differences were not meaningful . Differences between arms in HADS and SF-36 Vitality at week 54 were not significant . CONCLUSIONS At baseline , patients exhibited significant quality -of-life impairment . Both continuous and paused etanercept treatment provided improvements in PRO measures . Either regimen could be considered and care should be individualized BACKGROUND Anxiety , depression , and impaired health-related quality of life ( HRQoL ) are common in patients with psoriasis . OBJECTIVE We sought to analyze the effect of ustekinumab on these conditions in patients with moderate-to-severe psoriasis . METHODS Patients with moderate-to-severe psoriasis ( n = 1230 ) were r and omized 1:1:1 to receive 45 mg of ustekinumab , 90 mg of ustekinumab , or placebo . The Hospital Anxiety and Depression Scale was used to measure anxiety and depression , and the Dermatology Life Quality Index to measure HRQoL. RESULTS At baseline , 40.3 % and 26.7 % of patients reported symptoms of anxiety and depression , respectively , and 54.6 % reported Dermatology Life Quality Index scores greater than 10 , indicating a very high impact of disease on HRQoL. Greater improvements at week 12 in mean Hospital Anxiety and Depression Scale-Anxiety ( 13.9 % ) , Hospital Anxiety and Depression Scale-Depression ( 29.3 % ) , and Dermatology Life Quality Index ( 76.2 % ) scores were reported in ustekinumab groups compared with placebo ( P < .001 each ) . LIMITATIONS Results for these measures are reported only through 24 weeks . CONCLUSION Patients receiving ustekinumab reported significant improvements in symptoms of anxiety , depression , and We have previously shown that the risk of major depression in patients with malignant melanoma undergoing interferon-α ( IFN-α ) therapy can be reduced by pretreatment with the antidepressant , paroxetine . Using dimensional analyses , the present study assessed the expression and treatment responsiveness of specific clusters of neuropsychiatric symptoms over the first three months of IFN-α therapy . Forty patients with malignant melanoma eligible for IFN-α treatment were r and omly assigned to receive either paroxetine or placebo in a double-blind design . Neuropsychiatric assessment s were conducted at regular intervals during the first twelve weeks of IFN-α therapy and included the 21-item Hamilton Depression Rating Scale , the 14-item Hamilton Anxiety Rating Scale and the Neurotoxicity Rating Scale . Neurovegetative and somatic symptoms including anorexia , fatigue and pain appeared within two weeks of IFN-α therapy in a large proportion of patients . In contrast , symptoms of depressed mood , anxiety and cognitive dysfunction appeared later during IFN-α treatment and more specifically in patients who met DSM-IV criteria for major depression . Symptoms of depression , anxiety , cognitive dysfunction and pain were more responsive , whereas symptoms of fatigue and anorexia were less responsive , to paroxetine treatment . These data demonstrate distinct phenomenology and treatment responsiveness of symptom dimensions induced by IFN-α , and suggest that different mechanisms mediate the various behavioral manifestations of cytokine-induced “ sickness behavior . OBJECTIVES Fatigue is an important aspect of rheumatoid arthritis ( RA ) . The objective was to assess fatigue levels and its determinants over the first 4 months of tocilizumab ( TCZ ) treatment in RA patients . METHODS We performed a multicentre prospect i ve study of RA patients treated with intravenous TCZ in open-label prescription conditions . The first 5 infusions ( 4 months ) were assessed . The primary endpoint was the percentage of patients with variation of the FACIT fatigue scale from inclusion to 4 months , above the minimal clinical ly important difference ( MCID ) of 4 points . Fatigue was also assessed by the patient acceptable symptom state for fatigue ( PASS ) question . Variables related with fatigue and with fatigue improvement including other patient reported outcomes , depression and anxiety , and disease activity , were assessed before and after treatment . ANALYSES univariate and multivariate logistic regressions . RESULTS Of 719 patients , 610 had evaluable data : mean age 56±13 years , disease duration 12±10 years , 490 ( 81 % ) women . At baseline , fatigue levels were high : 73 % patients had unacceptable fatigue . At 4 months , 378 patients ( 62 % ) reached MCID improvement for fatigue . Fatigue reduction was rapid , seen as early as after 2 weeks . Fatigue was mainly related to functional status ( HAQ score ) , depression and anxiety , both before and after TCZ treatment . Moderate predictors of fatigue improvement were evidence d. CONCLUSIONS In these long-st and ing RA patients , fatigue levels were high and mainly explained by HAQ and psychological distress but improved with treatment indicating a link with disease activity . The pathophysiological basis of RA fatigue should be further explored Objectives : To compare the effects of etanercept ( ETN ) 50 mg once weekly plus methotrexate ( MTX ) versus MTX alone on patient-reported outcomes ( PROs ) and the relationship between remission and PRO improvement . Methods : In this double-blind , r and omised clinical trial ( COMET ) , PROs included : the Health Assessment Question naire ( HAQ ) , EuroQoL health status , fatigue and pain visual analogue scales , Hospital Anxiety and Depression Scale , and Medical Outcomes Short-Form-36 . Mean changes from baseline were analysed by analysis of covariance using the last observation carried forward method . Results from week 52 are presented . Results : Most PROs demonstrated significantly greater improvements with ETN+MTX than MTX alone , including physical functioning , pain , fatigue and overall health status . A significantly greater improvement in HAQ score was observed in the ETN+MTX than the MTX group ( −1.02 vs −0.72 ; p<0.001 ) and a greater proportion reached the minimal clinical ly important difference of 0.22 ( 88 % vs 78 % ; p<0.006 ) . The relationship between PRO score and clinical status indicated that improvement was greatest among patients achieving remission . Conclusions : Early treatment with ETN+MTX leads to significantly greater improvements in multiple dimensions of PROs than MTX alone . The close relationship between disease activity and PRO improvement suggests that early treatment , with remission as a goal , should maximise the chance of restoring normal functioning and CONTEXT The pathogenesis of depression is not fully understood , but studies suggest that low- grade systemic inflammation contributes to the development of depression . OBJECTIVE To test whether elevated plasma levels of C-reactive protein ( CRP ) are associated with psychological distress and depression . DESIGN We performed cross-sectional and prospect i ve analyses of CRP levels in 4 clinical ly relevant categories using data from 2 general population studies . SETTING The Copenhagen General Population and the Copenhagen City Heart studies . PARTICIPANTS We examined 73 131 men and women aged 20 to 100 years . MAIN OUTCOME MEASURES We ascertained psychological distress with 2 single-item self-reports and depression using self-reported antidepressant use , register-based prescription of antidepressants , and register-based hospitalization with depression . RESULTS In cross-sectional analyses , increasing CRP levels were associated with increasing risk for psychological distress and depression ( P = 3 × 10 - 8 to P = 4 × 10 - 105 for trend ) . For self-reported use of antidepressants , the odds ratio was 1.38 ( 95 % CI , 1.23 - 1.55 ) for CRP levels of 1.01 to 3.00 mg/L , 2.02 ( 1.77 - 2.30 ) for 3.01 to 10.00 mg/L , and 2.70 ( 2.25 - 3.25 ) for greater than 10.00 mg/L compared with 0.01 to 1.00 mg/L. For prescription of antidepressants , the corresponding odds ratios were 1.08 ( 95 % CI , 0.99 - 1.17 ) , 1.47 ( 1.33 - 1.62 ) , and 1.77 ( 1.52 - 2.05 ) , respectively ; for hospitalization with depression , 1.30 ( 1.01 - 1.67 ) , 1.84 ( 1.39 - 2.43 ) , and 2.27 ( 1.54 - 3.32 ) , respectively . In prospect i ve analyses , increasing CRP levels were also associated with increasing risk for hospitalization with depression ( P = 4 × 10 - 8 for trend ) . CONCLUSIONS Elevated levels of CRP are associated with increased risk for psychological distress and depression in the general population Signs of an inflammatory process , in particular increased pro-inflammatory cytokines and increased levels of prostagl and ine E2 ( PGE2 ) , have repeatedly been described in major depression ( MD ) . As cyclooxygenase-2 ( COX-2 ) inhibitors inhibit the PGE2 production and the production of pro-inflammatory cytokines , we performed a therapeutic trial with the COX-2 inhibitor celecoxib . In a prospect i ve , double-blind , add-on study , 40 patients suffering from an acute depressive episode were r and omly assigned to either reboxetine and celecoxib or to reboxetine plus placebo . After a wash-out period , 20 patients received 4–10 mg reboxetine plus placebo and 20 received reboxetine plus 400 mg celecoxib for 6 weeks . The treatment effect was calculated by analysis of variance . There were no significant differences between groups in age , sex , duration or severity of disease or psychopathology , or reboxetine dose or plasma levels . Over 6 weeks , both groups of patients showed significant improvement in scores of the Hamilton Depression Scale . However , the celecoxib group showed significantly greater improvement compared to the reboxetine-alone group . Additional treatment with celecoxib has significant positive effects on the therapeutic action of reboxetine with regard to depressive symptomatology . Moreover , the fact that treatment with an anti-inflammatory drug showed beneficial effects on MD indicates that inflammation is related to the pathomechanism of the disorder , although the exact mechanisms remain to become eluci date Few studies have investigated the relationship of temperament and character , as conceptualized in the Temperament and Character Inventory-Revised ( TCI-R ) , to symptoms of depression and anxiety in the general population . In this study a r and om sample of subjects ( 20 to 70 years ) , in two Finnish cities , were surveyed with the TCI-R , Beck Depression and Anxiety Inventories , plus questions related to diagnosed lifetime mental disorders , health care use for psychiatric reasons during the past 12 months , and history of mental disorders in first-degree relatives . Altogether 347 subjects ( 38.6 % ) responded . Of the TCI-R dimensions , Harm Avoidance correlated with symptoms of depression ( r(s)=0.555 , p<0.001 ) , anxiety ( r(s)=0.560 , p<0.001 ) , self-reported lifetime mental disorder ( r(s)=0.272 , p<0.001 ) , health care use for psychiatric reason during the past 12 months ( r(s)=0.241 , p<0.001 ) and family history of mental disorder ( r(s)=0.202 , p<0.001 ) . Self-directedness correlated negatively with symptoms of depression ( r(s)=-0.495 , p<0.001 ) , anxiety ( r(s)=-0.458 , p<0.001 ) , lifetime mental disorder ( r(s)=0.225 , p<0.001 ) and health care use ( r(s)=-0.135 , p=0.013 ) . Overall , Harm Avoidance and Self-directedness seem to associate moderately with depressive and anxiety symptoms , and somewhat predict self-reported use of health services for psychiatric reasons , and lifetime mental disorder . High harm avoidance may associate with a family history of mental disorder OBJECTIVES To compare speed and accuracy of graphical data extraction using manual estimation and open source software . STUDY DESIGN AND SETTING Data points from eligible graphs/figures published in r and omized controlled trials ( RCTs ) from 2009 to 2014 were extracted by two authors independently , both by manual estimation and with the Plot Digitizer , open source software . Corresponding authors of each RCT were contacted up to four times via e-mail to obtain exact numbers that were used to create graphs . Accuracy of each method was compared against the source data from which the original graphs were produced . RESULTS Software data extraction was significantly faster , reducing time for extraction for 47 % . Percent agreement between the two raters was 51 % for manual and 53.5 % for software data extraction . Percent agreement between the raters and original data was 66 % vs. 75 % for the first rater and 69 % vs. 73 % for the second rater , for manual and software extraction , respectively . CONCLUSIONS Data extraction from figures should be conducted using software , whereas manual estimation should be avoided . Using software for data extraction of data presented only in figures is faster and enables higher interrater reliability BACKGROUND AND AIMS Evidence suggests tumor necrosis factor-alpha ( TNF-α ) mediates , at least in part , symptoms and signs in complex regional pain syndrome ( CRPS ) . Here , we present a case series of patients with CRPS type 1 , in whom the response to the anti-TNF-α adalimumab was assessed . METHODS Ten patients with CRPS type 1 were recruited . Assessment s were performed before treatment , at 1 week , and 1 , 3 , and 6 months following 3 biweekly subcutaneous injections ( 40 mg/0.8 mL ) adalimumab ( Humira ( ® ) ) and included the followings : Pain intensity using a 0 - 10 cm visual analog scale ; the Short Form of the McGill Pain Question naire ; the Beck Depression Inventory ; the SF-36 question naire and mechanical and thermal thresholds ( Von frey hair and Thermal Sensory Analyzer , respectively ) . In addition to the description of individual patient responses , both intention to treat ( ITT ) and per- protocol ( PP ) analyses were performed for the entire group . RESULTS Three subgroups of patients were identified ( 3 patients in each ) : " nonresponders " , " partial responders " , and " robust responders " in whom improvement in almost all parameters was noted . Both the ITT and PP analyses demonstrated only a trend toward improvement in mechanical pain thresholds following treatment ( ITT χ² = 13.83 , P = 0.008 ; PP χ² = 10.29 , P = 0.036 ) . CONCLUSION These results suggest adalimumab , and possibly other anti-TNF-α , can be potentially useful in some ( although not in all ) patients with CRPS type 1 . These preliminary results along with the growing body of evidence which points to the involvement of TNF-α in the pathogenesis of CRPS justify further studies in this area OBJECTIVE The 24-week Etanercept Assessment of Safety and Effectiveness ( EASE ) study evaluated the effectiveness and tolerability of continuous versus interrupted etanercept treatment in patients with moderate to severe plaque psoriasis . The objective of this analysis was to assess patient-reported outcomes ( PROs ) and health-care re source utilization ( HRU ) data from the EASE study . METHODS Patients received open-label etanercept 50 mg twice weekly for 12 weeks and then received either continued or interrupted ( single round of discontinuation and re-treatment with etanercept ) etanercept 50 mg once weekly for the second 12 weeks . PROs included the following : 1 ) the patient global assessment s of psoriasis , joint pain , and itching scores ; 2 ) the Dermatology Life Quality Index ; 3 ) the Medical Outcomes Study Short Form 36 vitality domain ; 4 ) the Beck Depression Inventory ; 5 ) the European Quality -of-Life Group Feeling Thermometer ; and 6 ) a patient satisfaction survey . HRU was evaluated using the Economic Implication s of Psoriasis patient question naire . RESULTS Continuous treatment with etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks produced sustained and clinical ly important improvements in PROs and reductions in HRU . Reductions in some outcome measures after treatment discontinuation at week 12 were observed in the interrupted group ; however , most changes did not revert to baseline levels , consistent with some residual clinical effect , and re-treatment produced improvements similar to week 12 levels . CONCLUSIONS Continuous etanercept treatment provided greater sustained improvements in PROs than interrupted therapy ; however , interrupting etanercept therapy , if needed , has predictable and manageable effects BACKGROUND A lack of longitudinal studies has made it difficult to establish the direction of associations between circulating concentrations of low- grade chronic inflammatory markers , such as C-reactive protein and interleukin-6 , and cognitive symptoms of depression . The present study sought to assess whether C-reactive protein and interleukin-6 predict cognitive symptoms of depression or whether these symptoms predict inflammatory markers . METHOD In a prospect i ve occupational cohort study of British white-collar civil servants ( the Whitehall II study ) , serum C-reactive protein , interleukin-6 and cognitive symptoms of depression were measured at baseline in 1991 - 1993 and at follow-up in 2002 - 2004 , an average follow-up of 11.8 years . Symptoms of depression were measured with four items describing cognitive symptoms of depression from the General Health Question naire . The number of participants varied between 3339 and 3070 ( mean age 50 years , 30 % women ) depending on the analysis . RESULTS Baseline C-reactive protein ( beta=0.046 , p=0.004 ) and interleukin-6 ( beta=0.046 , p=0.005 ) predicted cognitive symptoms of depression at follow-up , while baseline symptoms of depression did not predict inflammatory markers at follow-up . After full adjustment for sociodemographic , behavioural and biological risk factors , health conditions , medication use and baseline cognitive systems of depression , baseline C-reactive protein ( beta=0.038 , p=0.036 ) and interleukin-6 ( beta=0.041 , p=0.018 ) remained predictive of cognitive symptoms of depression at follow-up . CONCLUSIONS These findings suggest that inflammation precedes depression at least with regard to the cognitive symptoms of depression Background Previous global studies examined etanercept ( ETN ) + methotrexate ( MTX ) for treatment of rheumatoid arthritis ( RA ) , but included few subjects from Latin America . Objective The objective of this study was to compare the safety and efficacy of ETN + MTX versus a st and ard-of-care disease-modifying antirheumatic drug ( DMARD ) + MTX in Latin American subjects with moderate to severe active RA despite MTX therapy . Methods This open-label , active-comparator study ( NCT00848354 ) r and omized subjects 2:1 to ETN 50 mg/wk + MTX or investigator-selected DMARD ( sulfasalazine or hydroxychloroquine ) + MTX ( ETN + MTX , n = 281 ; DMARD + MTX , n = 142 ) . The primary end point was the proportion achieving American College of Rheumatology ( ACR ) 50 at week 24 . Secondary end points included ACR20/70 , disease activity score ( DAS ) 28 measures , and mean change in modified total Sharp score . Patient-reported outcomes were the Health Assessment Question naire , 36-item Short-Form , Hospital Anxiety and Depression Scale , Work Productivity and Activity Impairment : RA ( WPAI : RA ) , and Caregiver Burden and Re source Utilization . Statistical analyses were stratified by country ; & khgr;2 test and analysis of covariance were used . Adverse events were monitored . Results More subjects achieved ACR50 at week 24 with ETN + MTX versus DMARD + MTX ( 62 % vs 23 % , respectively ) , in addition to secondary end points ( P < 0.0001 for all ) ; mean change in modified total Sharp score was lower for the ETN + MTX group ( 0.4 vs 1.4 , respectively ; P = 0.0270 ) . Improvements in patient-reported outcomes favored ETN + MTX for Health Assessment Question naire , 36-item Short-Form , Hospital Anxiety and Depression Scale for depression , WPAI : RA , and Caregiver Burden and Re source Utilization emergency department visits for RA ( P < 0.01 ) . Overall , adverse events were similar between the groups ( 69 % vs 68 % , ) ; serious adverse events were also similar ( 4 % vs 1 % ) . The rate of overall infections was higher with ETN + MTX ( 38 % ) than DMARD + MTX ( 22 % , P ⩽ 0.001 ) . Conclusions Consistent with published global data among RA patients with inadequate response to MTX , adding ETN to MTX demonstrated better efficacy than adding one other conventional DMARD to MTX . No new safety issues were observed . ETN + MTX provided favorable benefit-risk profile among RA patients from LA region Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials BACKGROUND Psoriasis is associated with health-related quality -of-life impairment and depression . OBJECTIVE We sought to determine the effect of adalimumab on depression symptoms in patients with psoriasis . METHODS Patients with moderate to severe psoriasis in a r and omized , placebo-controlled , double-blind clinical trial were assessed for depression symptoms at baseline and week 12 or early termination ( ET ) using the Zung Self-rating Depression Scale ( ZDS ) . The effects of adalimumab ( 40 mg every other week ) versus placebo on ZDS score at week 12/ET were assessed using analysis of covariance . Relationships between ZDS and the Psoriasis Area and Severity Index ( PASI ) , the Dermatology Life Quality Index , and the Short Form 36 Health Survey were assessed using Pearson correlations . Changes in ZDS score were compared for patients with and without a 75 % or greater reduction in baseline PASI score . RESULTS Compared with the placebo group ( n = 52 ) , the adalimumab group ( n = 44 ) experienced an additional 6-point reduction in ZDS score ( 95 % confidence interval : 2.5 - 9.5 ; P < .001 ) by week 12/ET . Depression improvement was correlated with improvement in PASI ( r = 0.5 ; P < .0001 ) and Dermatology Life Quality Index ( r = 0.5 ; P < .0001 ) . Greater ZDS score improvement was observed at week 12/ET in responders with a 75 % or greater reduction in baseline PASI score than in nonresponders ( 10.6 [ SD = 9.4 ] vs 1.4 [ SD = 9.6 ] ; P < .001 ) . LIMITATIONS This analysis can not distinguish whether adalimumab has a direct or indirect effect on depression . CONCLUSIONS Adalimumab treatment reduced psoriasis symptoms , reduced depression symptoms , and improved health-related quality of life in patients with moderate to severe psoriasis |
12,026 | 28,596,496 | Compared to the controls ( placebos or non-steroids ) , adjunctive corticosteroid use reduced the risk of residual pleural fluid after 4 weeks and the number of days to symptom improvement ; however , there was no convincing evidence to support the positive effects of corticosteroids over the long term ( 8 weeks ) on residual pleural fluid , pleural thickening , or pleural adhesions , and there was no statistical difference between the corticosteroid group and control group with respect to 7-days relief of the clinical symptoms or death from any cause .
In addition , more adverse events were observed in patients who received corticosteroids than in those in the control group .
Our results suggest that adjunctive corticosteroid use did not improve long-term efficacy and might induce more adverse events , although the risk of residual pleural fluid at 4 weeks and the number of days to symptom improvement were reduced | PURPOSE To evaluate the efficacy and safety of adjunctive corticosteroids in the treatment of patients with tuberculous pleurisy . | BACKGROUND --Tuberculous pleurisy can result in pleural fibrosis , calcification and thickening . To prevent these complications , corticosteroids are frequently used in addition to antituberculous drugs ; however , new therapeutic regimens can control the disease and minimise the sequelae , and there is no convincing evidence of the benefit of the use of corticosteroids as adjuvant therapy . METHODS -- Patients received isoniazid 5 mg/kg and rifampicin 10 mg/kg daily for six months . Additionally , they were r and omly assigned to a double blind treatment with either prednisone ( 1 mg/kg/day for 15 days and then tapering off ) or placebo during the first month of treatment . Different clinical , radiological , and functional parameters were evaluated to assess the effect of corticosteroids . RESULTS --Fifty seven patients received prednisone and 60 placebo . At the end of the treatment the clinical outcome , the rate of reabsorption of the pleural fluid , the pleural sequelae , as well as lung capacity were similar in both groups . CONCLUSIONS --Corticosteroids do not influence the clinical outcome or the development of long term pleural sequelae in tuberculous pleurisy To determine the effect of adjunct therapy , we carried out a prospect i ve cohort study on 190 patients with tuberculous pleural effusion during May 2003-April 2004 . Patients were divided into 3 groups . All groups were treated with anti-tuberculosis ( TB ) drugs for 6 months ; in group 2 ( n = 46 ) prednisolone , 30 mg/day for 10 days , was added ; group 3 ( n = 78 ) were given paracentesis to remove fluid . Fever and constitutional symptoms disappeared faster in group 2 ( P > 0.05 ) . After 10 days , there was a significantly greater reduction in the size of pleural effusion in group 2 , but after 6 months the difference was not statistically significant . We found corticosteroids and therapeutic paracentesis are not necessary in the management of TB pleural effusion BACKGROUND Active tuberculosis may accelerate progression of human immunodeficiency virus ( HIV ) infection by promoting viral replication in activated lymphocytes . Glucocorticoids are used in pleural tuberculosis to reduce inflammation-induced pathology , and their use also might reduce progression of HIV by suppressing immune activation . We examined the effect that prednisolone has on survival in HIV-1-associated pleural tuberculosis . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of prednisolone as an adjunct to tuberculosis treatment , in adults with HIV-1-associated pleural tuberculosis . The primary outcome was death . Analysis was by intention to treat . RESULTS Of 197 participants , 99 were assigned to the prednisolone group and 98 to the placebo group . The mortality rate was 21 deaths/100 person-years ( pyr ) in the prednisolone group and 25 deaths/100 pyr in the placebo group ( age- , sex- , and initial CD4 + T cell count-adjusted mortality rate ratio , 0.99 [ 95 % confidence interval , 0.62 - 1.56 ] [ P = .95 ] ) . Resolution of tuberculosis was faster in the prednisolone group , but recurrence rates were slightly ( though not significantly ) higher , and use of prednisolone was associated with a significantly higher incidence of Kaposi sarcoma ( 4.2 cases/100 pyr , compared with 0 cases/100 pyr [ P = .02 ] ) . CONCLUSIONS In view of the lack of survival benefit and the increased risk of Kaposi sarcoma , the use of prednisolone in HIV-associated tuberculous pleurisy is not recommended Although several studies on tuberculous ( TB ) pleurisy suggest that the addition of corticosteroids to anti-TB therapy may have beneficial effects , these agents are not used routinely . To assess the effects of short-term oral prednisone therapy in TB pleurisy , 74 patients were r and omly assigned in a double-blind fashion to treatment with either placebo or prednisone at a dose of 0.75 mg/kg/d for up to 4 weeks with gradual reduction over an additional 2 weeks . All subjects received a st and ard 3-drug anti-TB chemotherapy regimen for 6 months . TB pleurisy was diagnosed by histologic study and /or culture of pleural biopsy specimens obtained at thoracoscopy . Complete drainage of the effusion was performed simultaneously . Outcome measures were assessed periodically for 24 weeks , including indexes of morbidity and pleural thickening . After r and omization , four patients were excluded from the final analysis . Of the 70 patients analyzed , 34 received prednisone and 36 received placebo . Demographic and clinical characteristics of the treatment groups were comparable at the time of hospital admission . Although a statistically significant improvement in symptoms occurred earlier in the prednisone group ( 8 weeks ) than in the placebo group ( 12 weeks ) , between-group comparison showed no significant differences at any of the follow-up evaluations . The proportion of subjects in the prednisone group ( 53.1 % ) with residual pleural thickening at 6 months did not differ significantly from that of the placebo group ( 60 % ) . Pleural effusions did not recur in any of the patients . Initial complete drainage of the effusion was associated with greater symptomatic improvement than any subsequent therapy . We conclude that st and ard anti-TB therapy and early complete drainage is adequate for the treatment of TB pleurisy . The addition of short-term oral prednisone therapy neither results in clinical ly relevant earlier symptom relief nor confers a beneficial effect on residual pleural thickening |
12,027 | 19,426,469 | Results We found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality , especially on stillbirths .
Available evidence suggests that operative delivery , especially Caesarean section , contributes to decreased stillbirth rates .
Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact , though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour .
Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures , but studies have not demonstrated impact on perinatal mortality .
There was limited evidence of impact for maternal hyperoxygenation , and concerns remain about maternal safety .
Transcervical amnioinfusion for meconium staining appears promising for low/middle income-country application according to the findings of many small studies , but a large r and omised trial of the intervention had no significant impact on perinatal mortality , suggesting that further studies are needed .
Conclusion Although the global appeal to prioritise access to emergency obstetric care , especially vacuum extraction and Caesarean section , rests largely on observational and population -based data , these interventions are clearly life-saving in many cases of fetal compromise . | Background Approximately one million stillbirths occur annually during labour ; most of these stillbirths occur in low and middle-income countries and are associated with absent , inadequate , or delayed obstetric care .
The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care , including prompt recognition and management of intrapartum complications .
The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematic ally examined . | Background The objective of this r and omized prospect i ve study was to compare the efficacy of 50 mcg vaginal misoprostol and 3 mg dinoprostone , administered every nine hours for a maximum of three doses , for elective induction of labor in a specific cohort of nulliparous women with an unfavorable cervix and more than 40 weeks of gestation . Material and Methods One hundred and sixty-three pregnant women with more than 285 days of gestation were recruited and analyzed . The main outcome measures were time from induction to delivery and incidence of vaginal delivery within 12 and 24 hours . Admission rate to the neonatal intensive care unit within 24 hours post delivery was a secondary outcome . Results The induction-delivery interval was significantly lower in the misoprostol group than in the dinoprostone group ( 11.9 h vs. 15.5 h , p < 0.001 ) . With misoprostol , more women delivered within 12 hours ( 57.5 % vs. 32.5 % , p < 0.01 ) and 24 hours ( 98.7 % vs. 91.4 % , p < 0.05 ) , spontaneous rupture of the membranes occurred more frequently ( 38.8 % vs. 20.5 % , p < 0.05 ) , there was less need for oxytocin augmentation ( 65.8 % vs. 81.5 % , p < 0.05 ) and fewer additional doses were required ( 7.5 % vs. 22 % , p < 0.05 ) . Although not statistically significant , a lower Caesarean section ( CS ) rate was observed with misoprostol ( 7.5 % vs. 13.3 % , p > 0.05 ) but with the disadvantage of higher abnormal fetal heart rate ( FHR ) tracings ( 22.5 % vs. 12 % , p > 0.05 ) . From the misoprostol group more neonates were admitted to the intensive neonatal unit , than from the dinoprostone group ( 13.5 % vs. 4.8 % , p > 0.05 ) . One woman had an unexplained stillbirth following the administration of one dose of dinoprostone . Conclusions Vaginal misoprostol , compared with dinoprostone in the regimens used , is more effective in elective inductions of labor beyond 40 weeks of gestation . Nevertheless , this is at the expense of more abnormal FHR tracings and more admissions to the neonatal unit , indicating that the faster approach is not necessarily the better approach to childbirth Objective To compare vaginal misoprostol with dinoprostone for induction of labour Summary : A prospect i ve r and omised controlled trial was performed to compare the efficacy and safety of intrav‐aginal misoprostol to that of intravaginal dinoprostone when used for cervical priming prior to the induction of labour ; 126 women were recruited to the study and r and omised to receive either intravaginal dinoprostone ( n = 63 ) or misoprostol ( n = 63 ) for cervical priming prior to induction of labour . The mean time from insertion of the priming agent to vaginal delivery was significantly shorter in the misoprostol group ( 925.8 versus 1577.6 minutes ) , the mean duration of the active length of labour was significantly shorter in the misoprostol group ( 353.7 versus 496.8 minutes ) and more women in the misoprostol group delivered in less than 12 hours ( 92 % versus 76.5 % ) The objective of this study was to determine the safety of obstetrics forceps when used under strictly defined criteria compared to vacuum extraction for delivery in the second stage of labour . A r and omised prospect i ve trial was performed on 442 women undergoing instrumental delivery in the second stage . Two hundred and four women were in the forceps group and 238 in the vacuum group . When using forceps traction efforts to deliver the baby were kept to less than three and the head was always delivered in the occipito-anterior position . In the two groups there were no significant difference in the incidence of third-degree perineal tears , post-partum haemorrhage or ruptured uterus . Cervical tears were slightly higher in the forceps group . Babies delivered by vacuum extraction showed a higher incidence of cephalhaematomas . There was no significant difference in babies needing resuscitation at birth , admission to neonatal intensive care unit , stillbirth or neonatal death rates . The failure rate was significantly higher in the vacuum group . The time taken to complete the procedure was significantly less in the forceps group . Forceps deliveries when performed under defined criteria are as safe as vacuum deliveries to the mother with a lesser failure rate and a lower incidence of cephalhaematomas in the neonate compared with vacuum deliveries OBJECTIVE To compare the effectiveness of vaginally administered misoprostol with extra-amniotic prostagl and in F2alpha ( PGF2alpha ) gel for induction of labor . METHOD A r and omized controlled trial , with women allocated to receive either misoprostol 50 microg intra-vaginally or extra-amniotic PGF2alpha gel 5 mg , was conducted in Harare Maternity Hospital . A total of 152 women were admitted for induction of labor with a term singleton , pregnancy and cephalic presentation were recruited . The main outcome was duration of induction . RESULTS There were no differences in the characteristics of women in the two groups at recruitment . In the misoprostol group there was a significantly reduced need for augmentation of labor with oxytocin ( OR=0.36 ; 95 % C.I. 0.17 - 0.73 ) and delivery by cesarean section for failure to progress ( OR=0.11 ; 95 % C.I. 0.00 - 0.88 ) . The risk for duration of induction to vaginal delivery exceeding 12 , 18 or 24 h was reduced by 18 % , 38 % and 68 % , respectively , but only the risk for duration > 24 h was significantly reduced ( OR=0.32 ; 95%C.I. 0.11 - 0.91 ) . The mean duration of induction was shorter in the misoprostol group , 15.2 vs. 23.6 h ( P=0.02 ) . There were no differences in fetal outcome . CONCLUSION Misoprostol 50 microg was associated with less use of oxytocin in labor , a shorter induction to delivery interval and fewer cesarean sections for failure to progress when compared with extra-amniotic PGF2alpha gel BACKGROUND The aims of the present study were to determine whether maternal hyperoxygenation affects human fetal pulmonary circulation and whether there is a gestational age-related response in the fetal pulmonary circulation to maternal hyperoxygenation during the second half of gestation . METHODS AND RESULTS Twenty women between 20 and 26 weeks of gestation and 20 women between 31 and 36 weeks of gestation with normal singleton pregnancies were r and omized to receive either 60 % humidified oxygen or medical compressed air ( room air ) by a face mask . Fetal aortic and pulmonary valve ; ductus arteriosus ( DA ) ; and right ( RPA ) , left ( LPA ) , and distal ( DPA ) pulmonary artery blood velocity waveforms were obtained by Doppler ultrasound before , during , and after maternal administration of either 60 % oxygen or room air . Left and right ventricular cardiac outputs , DA volume blood flow , and RPA and LPA volume blood flows ( Qp ) were calculated . Foramen ovale volume blood flow ( left ventricular cardiac output-Qp ) was estimated . Pulsatility index ( PI ) values of DA , RPA , LPA , and DPA were calculated . Maternal hyperoxygenation did not change any of the measured fetal parameters between 20 and 26 weeks , whereas between 31 and 36 weeks , the PI values of RPA , LPA , and DPA decreased ( P<.0001 ) and the PI of DA increased ( P<.0001 ) . In addition , Qp increased ( P<.001 ) , and DA volume blood flow ( P<.01 ) and foramen ovale volume blood flow ( P<.03 ) decreased . Left and right ventricular cardiac outputs were unchanged . All changes returned to baseline after maternal hyperoxygenation was discontinued . CONCLUSIONS Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases with advancing gestation ; this suggests that fetal pulmonary circulation is under acquired vasoconstriction at least after 31 to 36 weeks of gestation Background Improving maternal health by reducing maternal mortality constitutes the fifth Millennium Development Goal and represents a key public health challenge in the United Republic of Tanzania . In response to the need to evaluate and monitor safe motherhood interventions , this study aims at assessing the coverage of obstetric care according to the Unmet Obstetric Need ( UON ) concept by obtaining information on indications for , and outcomes of , major obstetric interventions . Furthermore , we explore whether this concept can be operationalised at district level . Methods A two year study using the Unmet Obstetric Need concept was carried out in three districts in Tanga Region , Tanzania . Data was collected prospect ively at all four hospitals in the region for every woman undergoing a major obstetric intervention , including indication and outcome . The concept was adapted to address differentials in access to emergency obstetric care between districts and between rural and urban areas . Based upon literature and expert consensus , a threshold of 2 % of all deliveries was used to define the expected minimum requirement of major obstetric interventions performed for absolute maternal indications . Results Protocol s covering 1,260 complicated deliveries were analysed . The percentage of major obstetric interventions carried out in response to an absolute maternal indication was only 71 % ; most major obstetric interventions ( 97 % ) were caesarean sections . The most frequent indication was cephalo-pelvic-disproportion ( 51 % ) . The proportion of major obstetric interventions for absolute maternal indications performed amongst women living in urban areas was 1.8 % of all deliveries , while in rural areas it was only 0.7 % . The high proportion ( 8.3 % ) of negative maternal outcomes in terms of morbidity and mortality , as well as the high perinatal mortality of 9.1 % ( still birth 6.9 % , dying within 24 hours 1.7 % , dying after 24 hours 0.5 % ) raise concern about the quality of care being provided . Conclusion Based on the 2 % threshold , Tanga Region – with an overall level of major obstetric interventions for absolute maternal indications of 1 % and a caesarean section rate of 1.4 % – has significant unmet obstetric need with a considerable rural-urban disparity . The UON concept was found to be a suitable tool for evaluating and monitoring the coverage of obstetric care at district level Objective To investigate the effect of chronic oxygen therapy in fetuses with absent end diastolic flow in the umbilical artery assessed by doppler analysis at 24–30 weeks of gestation OBJECTIVE Our purpose was to determine the optimal management of pregnancies beyond 41 week 's gestation with a cervix unfavorable for induction . MATERIAL AND METHOD All uncomplicated pregnancies that reached 41 weeks'gestation with a Bishop score of < or = 4 , were r and omly assigned to one of two groups RESULTS The duration of labor was shorter in the group " prépidil " compared with the control group ( P=0.002 ) . Identification of an unfavorable cervix at 41 weeks was unlikely to change by 42 weeks and cervical ripening was required in 40 % cases . There was no significant difference in caesarean section rates . Rates of admission into the neonatal unit and fetal outcomes were similar in the two groups . CONCLUSION Cervical ripening with prostagl and in gel at 41 week 's gestation for uncomplicated singleton pregnancies is safe and should be advocated BACKGROUND Research suggests that fetal exposure to magnesium sulfate before preterm birth might reduce the risk of cerebral palsy . METHODS In this multicenter , placebo-controlled , double-blind trial , we r and omly assigned women at imminent risk for delivery between 24 and 31 weeks of gestation to receive magnesium sulfate , administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour , or matching placebo . The primary outcome was the composite of stillbirth or infant death by 1 year of corrected age or moderate or severe cerebral palsy at or beyond 2 years of corrected age . RESULTS A total of 2241 women underwent r and omization . The baseline characteristics were similar in the two groups . Follow-up was achieved for 95.6 % of the children . The rate of the primary outcome was not significantly different in the magnesium sulfate group and the placebo group ( 11.3 % and 11.7 % , respectively ; relative risk , 0.97 ; 95 % confidence interval [ CI ] , 0.77 to 1.23 ) . However , in a prespecified secondary analysis , moderate or severe cerebral palsy occurred significantly less frequently in the magnesium sulfate group ( 1.9 % vs. 3.5 % ; relative risk , 0.55 ; 95 % CI , 0.32 to 0.95 ) . The risk of death did not differ significantly between the groups ( 9.5 % vs. 8.5 % ; relative risk , 1.12 ; 95 % CI , 0.85 to 1.47 ) . No woman had a life-threatening event . CONCLUSIONS Fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate or severe cerebral palsy or death , although the rate of cerebral palsy was reduced among survivors . ( Clinical Trials.gov number , NCT00014989 . OBJECTIVE To see the effect of amnioinfusion on perinatal outcome in cases of meconium staining of liquor . METHODS This study was conducted in department of Obstetrics and Gynaecology , unit 1 , Jinnah Postgraduate Medical Centre , Karachi , from 1st January 1998 to 31st December 2000 . Four hundred patients were included in this study , assigning 200 for amnioinfusion and 200 as control . All patients were matched in both the groups with respect to age , antenatal booking , parity , gestational age , stage of labour , colour of amniotic fluid and fetal birth weight . Both the groups were found to be comparable . RESULTS The rate of Caesarean section was found to be 37 % in amnioinfusion group , which collaborates with other international studies . The fetal outcome was better i.e. 91 % alive and healthy , after amnioinfusion due to dilution of meconium stained amniotic fluid with physiological solutions . The perinatal outcome was recorded by Apgar score at 5 minutes . The perinatal morbidity and mortality both were significantly lowered and was found to be 6 % as compared to 14 % in control , which was also noticed by less number of admissions in nursery i.e. 12 % and perinatal deaths . The incidence of meconium aspiration syndrome was found to be 56 % in control and was reduced to 22 % after amnioinfusion in the other arm of the study . CONCLUSION These results are very encouraging and suggestion can be safely made that in future amnioinfusion will be the ideal method of preventing fetal distress due to meconium stained amniotic fluid Objective To compare the effectiveness of immediate induction of labour with vaginal misoprostol versus expectant management for 24 hours followed by oxytocin induction in women with premature rupture of membranes at term ( term PROM ) In a prospect i ve and controlled study labor was induced electively in 150 gr and multiparae ( GM ) between 38 and 42 wk gestation by intracervical application of PGE2 tablets ( induction group ) . Another 150 GM who went into labor spontaneously served as controls for comparison of labor characteristics and outcome ( control group ) . In the induction group labor was successfully induced in 147 GM ( 98.0 % ) , of whom 142 ( 96.5 % ) delivered vaginally . The mean duration of the active phase of labor was 2.1 + /- 0.79 h in GM who delivered on the first day of induction and 2.8 + /- 0.47 h in women who delivered on the second day , as compared to 4.7 + /- 2.2 h in the controls . Similarly , the mean duration of the second and third stage was longer in the controls . Operative deliveries were 2 - -3-times more frequent among controls , as were complications in the second and third stages . The group profiles of the I.U.P. charts indicating rise time , fall time , amplitude and Montevideo units at different stages of cervical dilatation showed significant differences at 4 - 5 cm dilatation only between the two groups of women . It is concluded that elective induction in GM between 38 and 42 wk is safe for mother and fetus OBJECTIVE To assess the rates of cesarean deliveries and perinatal outcome following intrapartum transcervical amnioinfusion in women with meconium-stained amniotic fluid ( MSAF ) in a setting with no electronic fetal monitoring or specialized neonatal care . MATERIAL S AND METHODS In this prospect i ve comparative study with 150 women who were in labor and had MSAF , 50 of the women received a transcervical amnioinfusion and the remaining 100 women received st and ard care . The inclusion criteria were a pregnancy of at least 37 weeks ' duration , a single live fetus in cephalic presentation , no major medical or obstetric complications , and no known fetal malformation . The amnioinfusion was performed with 1000 mL of normal saline solution through a red rubber catheter . RESULTS Amnioinfusion was associated with a significant decrease in the incidence of low Apgar score ( < 7 ) at 1 min ( 12 % vs. 47 % ; relative risk [ RR ] , 0.26 ; 95 % confidence interval [ CI ] , 0.12 - 0.56 ) ; low Apgar score at 5 min ( 4 % vs. 23 % ; RR , 0.17 ; 95 % CI , 0.04 - 0.71 ) ; and meconium aspiration syndrome ( 4 % vs. 18 % ; RR , 0.22 ; 95 % CI , 0.05 - 0.92 ) . There was also a trend towards a lesser incidence of cesarean deliveries ( 18 % vs. 30 % ; RR , 0.6 ; 95 % CI , 0.31 - 1.16 ) and perinatal deaths ( 4 % vs. 13 % ; RR , 0.31 ; 95 % CI , 0.07 - 1.31 ) . The incidence of maternal hospital stays longer than 3 days was significantly lower in the amnioinfusion than in the control group ( 24 % vs. 48 % ; RR , 0.5 ; 95 % CI , 0.29 - 0.85 ) . There were no major complications related to amnioinfusion . CONCLUSIONS Intrapartum amnioinfusion for MSAF is a simple , safe , effective , and inexpensive procedure feasible in setting s where intrapartum monitoring is limited . It is associated with improved perinatal outcome and could lower cesarean delivery rates in low-re source countries Background . The objectives of the study were to compare the efficacy and safety of intravaginal misoprostol and intravaginal dinoprostone for induction of labor and to quantify the clinical response to suspicious cardiotocographic ( CTG ) readings Objective : To compare the safety and efficacy of vaginal misoprostol versus dinoprostone vaginal inserts for cervical ripening and labor induction . Methods : Two hundred singleton gestations with an indication for cervical ripening and induction of labor were r and omized to receive either 50 μg of misoprostol intravaginally every 3 h or a 10-mg dinoprostone vaginal insert every 12 h for a maximum of 24 h. Statistical analysis included Student 's t test , the Mann-Whitney U test , χ2 analysis and Fisher 's exact test . Results : Ninety-seven women received vaginal misoprostol while 89 women received the dinoprostone vaginal insert . Fourteen women were removed from the study after r and omization . The interval from start of induction to vaginal delivery ( 794.5 ± 408 min vs. 1005.3 ± 523 min ; p < 0.02 ) was significantly shorter in the misoprostol group . Women receiving misoprostol were more likely to deliver vaginally both in < 12 h ( 44 % vs. 12 % ; p < 0.0001 ) and < 24 h ( 68 % vs. 38 % ; p < 0.001 ) . A non-reassuring fetal heart rate tracing was the indication for 71.4 % ( 20/28 ) of Cesarean deliveries in the misoprostol group compared to 40 % ( 14/35 ) in the dinoprostone group ( p = 0.03 ) . There were no significant differences in neonatal outcomes . Conclusion : Intravaginal misoprostol and dinoprostone are safe and effective medications for use in cervical ripening before labor induction . Misoprostol results in a shorter interval from induction to delivery . However , Cesarean delivery for a non-reassuring fetal heart rate tracing was more common with misoprostol OBJECTIVE Our goal was to determine stillbirth rates in a multisite population -based study in community setting s in the developing world . STUDY DESIGN Outcomes of all community deliveries in 5 re source -poor countries ( Democratic Republic of Congo , Guatemala , India , Zambia , and Pakistan ) and in 1 mid-level country ( Argentina ) were evaluated prospect ively over an 18-month period . Births of > 1000 g with no signs of life were defined as stillbirth . RESULTS Outcomes of 60,324 deliveries were included . Stillbirth rates ranged from 34 per 1000 in Pakistan to 9 per 1000 births in Argentina . Increased stillbirth rates were associated significantly with lower skilled providers , out-of-hospital births , and low cesarean section rates . Maceration was present in 17.2 % of stillbirths . CONCLUSION The stillbirth rates among births of > or = 1000 g in these developing countries were substantially higher than reported stillbirth rates in developed countries ( 3 - 5/1000 births ) . Because most developed countries define stillbirth as > or = 20 weeks of gestation or > or = 500 g and because almost one-half of all stillbirths are < 1000 g , the developing/developed country difference is actually larger than apparent from this study . Maceration was uncommon , which indicates that most of the deaths probably occurred during labor . The low rates of physician attendance , hospital delivery , and cesarean section deliveries suggest that stillbirth rates could be reduced by access to higher quality institutional deliveries Background . The success of induced labor depends on the degree of ripening of cervix . Pharmacological preparations are in widespread use for cervical ripening but are not free from side‐effects and complications . Mechanical methods , i.e. the use of Foley catheter balloon , though effective have not gained much popularity because of the fear of infection . Therefore , this study has been conducted to prove the efficacy and safety of extraamniotic Foley catheter balloon and to compare it with intracervical prostagl and in E2 ( PGE2 ) gel OBJECTIVES The aim of this study is to compare the effectiveness of the intracervical Foley balloon catheter and 3 mg prostagl and in E(2 ) tablet(s ) in preinduction cervical ripening . METHODS Ninety women referred to the maternity clinic for induction of labor with a Bishop score of less than or equal to 5 were r and omized to receive an intracervical Foley catheter or prostagl and in E(2 ) tablets . The primary measured outcome was ripening of the cervix as measured with the Bishop score . RESULTS There were no differences in mean Bishop scores between the prostagl and in and the Foley catheter groups . Bishop scores ( mean+/-S.D. ) after ripening were 6.6+/-0.80 and 6.7+/-0.86 for the Foley catheter and prostagl and in groups , respectively ( P=0.54 ) . The Foley catheter group showed a statistically shorter time to ripening compared with the prostagl and in group ( 3.4+/-2.1 and 6.5+/-3.2 h , respectively ( P=0.001 ) . There was no statistically significant difference in induction time ( 4.8+/-1.8 h and 5.3+/-2.4 h , respectively ( P=0.36 ) . CONCLUSIONS There are no differences in preinduction cervical ripening efficacy between prostagl and in E(2 ) and the Foley catheter , but the Foley catheter has the advantage of ripening an unfavorable cervix in a shorter time OBJECTIVE In the current study the efficacy of maternal hyperoxygenation on growth-retarded fetuses was evaluated . STUDY DESIGN Thirty-six pregnant women with intrauterine growth retardation were studied . The patients were divided in oxygen-treated ( n = 17 ) and untreated ( n = 19 ) groups . Doppler analysis of the fetal circulation was performed on the arrival to the hospital , after 12 hours , and thereafter on alternate days until delivery . Fetal blood was sample d by cordocentesis for immediate blood gas analysis at entrance to the study and the day of delivery . RESULTS Significant improvement in Doppler flow patterns in treated patients were found when compared with untreated women . The Doppler variations were associated with complementary modifications in fetal blood gas . These differences result ed in a significant modification in perinatal mortality with an incidence of 29 % and 68 % ( p less than 0.01 ) in treated and untreated groups , respectively . CONCLUSION Our data suggest a benefit of maternal hyperoxygenation in the treatment of fetal growth retardation BACKGROUND For 3 - 4 % of pregnancies , the fetus will be in the breech presentation at term . For most of these women , the approach to delivery is controversial . We did a r and omised trial to compare a policy of planned caesarean section with a policy of planned vaginal birth for selected breech-presentation pregnancies . METHODS At 121 centres in 26 countries , 2088 women with a singleton fetus in a frank or complete breech presentation were r and omly assigned planned caesarean section or planned vaginal birth . Women having a vaginal breech delivery had an experienced clinician at the birth . Mothers and infants were followed-up to 6 weeks post partum . The primary outcomes were perinatal mortality , neonatal mortality , or serious neonatal morbidity ; and maternal mortality or serious maternal morbidity . Analysis was by intention to treat . FINDINGS Data were received for 2083 women . Of the 1041 women assigned planned caesarean section , 941 ( 90.4 % ) were delivered by caesarean section . Of the 1042 women assigned planned vaginal birth , 591 ( 56.7 % ) delivered vaginally . Perinatal mortality , neonatal mortality , or serious neonatal morbidity was significantly lower for the planned caesarean section group than for the planned vaginal birth group ( 17 of 1039 [ 1.6 % ] vs 52 of 1039 [ 5.0 % ] ; relative risk 0.33 [ 95 % CI 0.19 - 0.56 ] ; p<0.0001 ) . There were no differences between groups in terms of maternal mortality or serious maternal morbidity ( 41 of 1041 [ 3.9 % ] vs 33 of 1042 [ 3.2 % ] ; 1.24 [ 0.79 - 1.95 ] ; p=0.35 ) . INTERPRETATION Planned caesarean section is better than planned vaginal birth for the term fetus in the breech presentation ; serious maternal complications are similar between the groups OBJECTIVE : To determine whether a single outpatient dose of intravaginal misoprostol ( versus intracervical dinoprostone gel ) reduces the oxytocin use for induction . Despite the numerous trials examining misoprostol for induction , the efficacy of a single outpatient dose of misoprostol followed by oxytocin induction is unknown . METHODS : Patients with a term , vertex , singleton pregnancy and a Bishop score of 6 or less were r and omly assigned to receive misoprostol ( n = 42 , 0.25 μg intravaginally ) or dinoprostone gel ( n = 42 , 0.5 mg intracervically ) the evening before oxytocin induction . Patients were monitored for 3 hours after administration and discharged to home if fetal assessment was reassuring , for readmission the next morning for oxytocin . Primary outcomes were oxytocin dose , time , and dose intensity ( dose divided by duration ) . Secondary outcomes were incidence of labor , uterine hyperstimulation , cesarean delivery , Apgar score . Statistics used were χ2 , Student t test , Mann-Whitney rank sum test , and Fisher exact test . P < .05 was accepted as statistically significant . RESULTS : A single dose of misoprostol significantly decreased the cumulative dose of oxytocin , the cumulative time of oxytocin administration , and the dose intensity of oxytocin ( dose divided by time ) . Data are as follows ( mean ± st and ard error of the mean ) : oxytocin dose — dinoprostone 10,929 ± 219 mU , misoprostol 6,081 ± 170 mU , P = .008 ; oxytocin time — dinoprostone 798 ± 11 minutes , misoprostol 531 ± 11 minutes , P = .009 ; dose intensity — dinoprostone 11.3 ± 0.1 mU/min , misoprostol 7.4 ± 0.2 mU/min , P = .003 . Misoprostol induced labor during the ripening period in 19 of 41 of patients , compared with 6 of 42 after dinoprostone ( P = .002 ) . There was no difference in cesarean delivery ( dinoprostone , 8/42 ; misoprostol , 9/42 ; P = 1.00 ) . There was no difference in short-term neonatal outcome . No patient had hyperstimulation or required cesarean delivery for nonreassuring fetal assessment during the ripening period . CONCLUSION : A single dose of misoprostol administered in the outpatient setting significantly decreases oxytocin use , largely due to labor within the ripening period . LEVEL OF EVIDENCE : BACKGROUND It is uncertain whether amnioinfusion ( infusion of saline into the amniotic cavity ) in women who have thick meconium staining of the amniotic fluid reduces the risk of perinatal death , moderate or severe meconium aspiration syndrome , or both . METHODS We performed a multicenter trial in which 1998 pregnant women in labor at 36 or more weeks of gestation who had thick meconium staining of the amniotic fluid were stratified according to the presence or absence of variable decelerations in fetal heart rate and then r and omly assigned to amnioinfusion or to st and ard care . The composite primary outcome measure was perinatal death , moderate or severe meconium aspiration syndrome , or both . RESULTS Perinatal death , moderate or severe meconium aspiration syndrome , or both occurred in 44 infants ( 4.5 percent ) of women in the amnioinfusion group and 35 infants ( 3.5 percent ) of women in the control group ( relative risk , 1.26 ; 95 percent confidence interval , 0.82 to 1.95 ) . Five perinatal deaths occurred in the amnioinfusion group and five in the control group . The rate of cesarean delivery was 31.8 percent in the amnioinfusion group and 29.0 percent in the control group ( relative risk , 1.10 ; 95 percent confidence interval , 0.96 to 1.25 ) . CONCLUSIONS For women in labor who have thick meconium staining of the amniotic fluid , amnioinfusion did not reduce the risk of moderate or severe meconium aspiration syndrome , perinatal death , or other major maternal or neonatal disorders Three hundred two low-risk obstetric patients with an unfavorable cervical examination and well-established gestational age of at least 287 days were r and omly selected for management by either antepartum fetal testing or prostagl and in gel cervical ripening followed by aggressive induction of labor and delivery . The patients managed by induction of labor had a lower incidence of meconium-stained amniotic fluid , meconium aspiration , low Apgar scores , postmaturity syndrome , fetal distress , and cesarean delivery than did patients managed with antepartum fetal testing . Our data suggest that prostagl and in gel cervical ripening and induction of labor and delivery by 42 weeks ' gestation may be the most appropriate management for patients with well-established gestational age and an unfavorable cervical examination OBJECTIVE The purpose of this study was to determine stillbirth risk factors and gestational age at delivery in a prospect i ve developing country birth cohort . STUDY DESIGN At 20 - 26 weeks of gestation , 1369 Pakistani women were prospect ively enrolled in the study ; the gestational age was determined by ultrasound evaluation , and risk factors and pregnancy outcomes were assessed . RESULTS The stillbirth rate was 33.6 of 1000 births , despite the fact that 96 % of the women received prenatal care , 83 % of the women were attended by skilled providers in the hospital , and a 20 % of the women underwent cesarean delivery . Fifty-one percent of stillbirths occurred at > or = 37 weeks of gestation and 19 % occurred from 34 - 36 weeks of gestation . Only 4 % of the births had congenital anomalies . Hemoglobin of < 8 g/dL , vaginal bleeding , and preeclampsia were associated with increased stillbirth risk . CONCLUSION In this developing country with reasonable technical re sources defined by hospital delivery and a high cesarean delivery rate , stillbirth rates were much higher than rates in the United States . That most of the stillbirths were term and did not have congenital anomalies and that the death appeared to be recent suggests that many Pakistani stillbirths may be preventable with higher quality obstetric care Two hundred fifty-six vacuum extraction s and 300 r and omly chosen forceps deliveries were analyzed retrospectively . Vacuum extraction use increased from 0.3 to 3.1 % , while forceps use declined from 10.1 to 4.9 % over a five-year period . No differences were found in indications for vacuum extraction and forceps , but the preapplication position differed ( occiput posterior or transverse in 81.2 % in the vacuum group and 27 % in forceps patients ) . Preapplication station also differed , with 59.8 % of vacuum extraction at + 1 or higher stations , compared with 9 % of forceps . Under these conditions we found less maternal trauma , similar failure rates ( 3.9 versus 2 % ) , and no difference in maternal morbidity . There was a higher incidence of shoulder dystocia and neonatal jaundice in the vacuum group , but cephalohematoma frequency did not differ significantly ( 3.9 % vacuum extraction , 4.3 % forceps ) . Cosmetic injuries ( ecchymoses , abrasions ) were more likely with vacuum extraction than with forceps ( 44.1 versus 29.5 % ) . One death occurred in each group . Vacuum extraction replaced midforceps in our institution in the study period . We consider vacuum extraction a useful technique to teach house staff in view of today 's decreasing instrumental delivery rate In a prospect i ve study , 167 vacuum extraction s ( VE ) performed at the Kenyatta National Hospital , Nairobi , formed 6.3 % of the total deliveries . Most patients were young and of low parity . There were no maternal deaths . The overall maternal morbidity rate was 22 % and were mostly minor . Post partum haemorrhage was the most common maternal complication . There were 5 failed VEs . Perinatal morbidity and mortality rates were 16.2 % and 4.8 % respectively . Intrauterine asphyxia was the commonest cause of death . Several complications could have been avoided by more stringent use of the instrument . The place of VE in a busy obstetric unit is discussed OBJECTIVE Our purpose was to evaluate the relationship between the approach to obstetric management and survival of extremely low-birth-weight infants . STUDY DESIGN In this prospect i ve observational study we evaluated 713 singleton births of infants weighing < or = 1000 gm during 1 year at the 11 tertiary perinatal care centers of the National Institutes of Child Health and Human Development network of maternal-fetal medicine units . Major anomalies , extramural delivery , antepartum stillbirth , induced abortion , and gestational age < 21 weeks were excluded . The obstetrician 's opinion of viability and willingness to perform cesarean delivery in the event of fetal distress were ascertained from the medical record or interview when documentation was unclear . Grade 3 and 4 intraventricular hemorrhage , grade 3 and 4 retinopathy of prematurity , necrotizing enterocolitis requiring surgery , oxygen dependence at discharge or 120 days , and seizures were considered serious morbidity . Survival without serious morbidity was considered intact survival . Logistic regression was used to evaluate the influence of the approach to obstetric management , adjusted for birth weight , growth , gender , presentation , and ethnicity . RESULTS Willingness to perform cesarean delivery was associated with increased likelihood of both survival ( adjusted odds ratio 3.7 , 95 % confidence interval 2.3 to 6.0 ) and intact survival ( adjusted odds ratio 1.8 , 95 % confidence interval 1.0 to 3.3 ) . Willingness to intervene for fetal indications appeared to virtually eliminate intrapartum stillbirth and to reduce neonatal mortality . Below 800 gm or 26 weeks , however , willingness to perform cesarean delivery was linked to an increased chance of survival with serious morbidity . Although obstetricians were willing to intervene for fetal indications in most cases by 24 weeks , willingness to perform cesarean delivery was associated with twice the risk for serious morbidity at that gestational age . CONCLUSIONS The approach to obstetric management significantly influences the outcome of extremely low-birth-weight infants . Above 800 gm or 26 weeks the obstetrician should usually be willing to perform cesarean delivery for fetal indications . Between 22 and 25 weeks willingness to intervene results in greater likelihood of both intact survival and survival with serious morbidity . In these cases patients and physicians should be aware of the impact of the approach to obstetric management and consider the likelihood of serious morbidity and mortality when formulating plans for delivery Summary . . The aim of this nationally‐based , matched case‐control study was to assess the impact of birth by caesarean section on intrapartum , and neonatal mortality among twins weighing 1500–2499 g , born in Sweden between 1973 and 1983 . By using data held at the National Medical Birth Registry , Stockholm , 91 such pregnancies ( study cases ) where one or both twins died were identified . For each case , two controls ( in all 182 pregnancies ) were allotted at r and om from the rest of the twin pregnancies , with similar birthweight ( ±100 g ) and year of delivery ( ±1 year ) . The number of twins that died was reduced from 73 during the first four years to 22 between 1977 and 1980 , and to 6 during the last 3 years of the study period . Almost a quarter ( 23.1 % ) had a lethal malformation . The caesarean section rate increased during the study period , but did not differ between cases and controls ( χ2= 1.0 ; P>0.05 ) . The analysis could not confirm a significant difference between cases and controls regarding the number of infants born vaginally in non‐vertex presentation ( χ2= 0.1 ; P>0.05 ) . The results of this study appear to indicate that birth by caesarean section was not a major factor related to the improved fetal outcome OBJECTIVE Our purpose was to assess whether a program of expectant management of uncomplicated pregnancies in mothers with insulin-requiring gestational or pregestational class B reduces the incidence of cesarean birth . STUDY DESIGN Two hundred women with uncomplicated , insulin-requiring diabetes at 38 weeks ' gestation who were compliant with care and whose infants were judged appropriate for gestational age were r and omly assigned to ( 1 ) active induction of labor within 5 days or ( 2 ) expectant management . The expectant management group was monitored with weekly physical examination and twice-weekly nonstress tests and amniotic fluid volume estimation until delivery . RESULTS Expectant management increased the gestational age at delivery by 1 week . Approximately half ( 49 % ) of the mothers in the expectant management group required induction of labor for obstetric indications . The cesarean delivery rate was not significantly different in the expectant management group ( 31 % ) from the active induction group ( 25 % ) . The mean birth weight ( 3672 + /- 407 gm ) and percentage large for gestational age , as defined by birth weight > or = 90th percentile , of infants in the expectantly managed group ( 23 % ) was greater than those in the active induction group ( 3466 + /- 372 gm , p < 0.0001 , 10 % large for gestational age ) . This difference persisted after controlling for gestational age and maternal age and body weight ( p < 0.01 ) . CONCLUSION In women with uncomplicated insulin-requiring gestational or class B pregestational diabetes , expectant management of pregnancy after 38 weeks ' gestation did not reduce the incidence of cesarean delivery . Moreover , there was an increased prevalence of large-for-gestational-age infants ( 23 % vs 10 % ) and shoulder dystocia ( 3 % vs 0 % ) . Because of these risks , delivery should be contemplated at 38 weeks and , if not pursued , careful monitoring of fetal growth must be performed Background . To compare the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in toxemia of pregnancy with a modified Bishop score of ≤4 OBJECTIVE The objective of this study was to compare intracervical prostagl and in E2 gel with insertion of a Foley bulb for efficacy in preinduction cervical ripening . STUDY DESIGN Women who came to the hospital for induction of labor with a Bishop score < /=5 were r and omly assigned to treatment with either prostagl and in E2 gel or a Foley bulb . Prostagl and in E2 gel was used according to the manufacturer 's recommendation . The Foley group had a number 14 Foley catheter inserted , inflated , and placed on traction . Immediately after Foley bulb extrusion or 6 hours after prostagl and in E2 gel course completion , a dilute oxytocin solution was started if the patient was not in labor . RESULTS Seventy-seven women were entered into the Foley group and 72 were entered into the prostagl and in E2 gel group . Both the Bishop score after preinduction ripening ( 6.5 vs 5.1 , P < .001 ) and the change in Bishop score ( 3.5 vs 2.7 , P = .015 ) were significantly higher in the Foley group . There were no differences between the groups in mode of delivery , infant weight , rate of hyperstimulation , shoulder dystocia , patient discomfort , epidural use , oxytocin use , or nonreassuring fetal heart rate patterns . The preinduction time ( 9.9 vs 17.2 hours , P < .001 ) and the total induction time ( 22.4 vs 30.4 hours , P < .001 ) were significantly shorter in the Foley group . Patient charges were 31 % lower in the Foley group ( P < .001 ) . CONCLUSION Use of the Foley catheter result ed in a higher postinduction Bishop score , a greater change in Bishop score , a shorter induction time , and lower patient charges than did intracervical prostagl and in E2 gel Background . We wanted to conduct a prospect i ve study on the dynamics of emergency cesarean section ( ECS ) in terms of fetal survival and morbidity OBJECTIVE To determine the usefulness of antepartum transabdominal amnioinfusion ( APTA ) in reducing perinatal morbidity and mortality due to oligohydramnios . METHODS In this case-control study of 100 pregnant women with oligohydramnios , 50 received APTA and 50 were treated conservatively . These controls were matched for age , parity , and pregnancy duration with the case patients . RESULTS There was a mean 4.02-cm increase in amniotic fluid index ( AFI ) after amnioinfusion . Only 18 % of case patients required cesarean sections vs. 46 % of controls . The perinatal mortality rate was 18 % among controls and 4 % among case patients , and the difference was significant . CONCLUSION Antepartum amnioinfusion is a useful procedure to reduce complications result ing from decreased intra-amniotic volume . It is especially useful in preterm pregnancies , where the procedure allows for a better perinatal outcome by prolonging the duration of pregnancy Eclampsia , the occurrence of a seizure in association with pre-eclampsia , remains an important cause of maternal mortality . Although it is st and ard practice to use an anticonvulsant for management of eclampsia , the choice of agent is controversial and there has been little properly controlled evidence to support any of the options . 1687 women with eclampsia were recruited into an international multicentre r and omised trial comparing st and ard anticonvulsant regimens . Primary measures of outcome were recurrence of convulsions and maternal death . Data are available for 1680 ( 99.6 % ) women : 453 allocated magnesium sulphate versus 452 allocated diazepam , and 388 allocated magnesium sulphate versus 387 allocated phenytoin . Most women ( 99 % ) received the anticonvulsant that they had been allocated . Women allocated magnesium sulphate had a 52 % lower risk of recurrent convulsions ( 95 % CI 64 % to 37 % reduction ) than those allocated diazepam ( 60 [ 13.2 % ] vs 126 [ 27.9 % ] ; ie , 14.7 [ SD 2.6 ] fewer women with recurrent convulsions per 100 women ; 2p < 0.00001 ) . Maternal mortality was non-significantly lower among women allocated magnesium sulphate . There were no significant differences in other measures of serious maternal morbidity , or in perinatal morbidity or mortality . Women allocated magnesium sulphate had a 67 % lower risk of recurrent convulsions ( 95 % CI 79 % to 47 % reduction ) than those allocated phenytoin ( 22 [ 5.7 % ] vs 66 [ 17.1 % ] ie , 11.4 [ SD 2.2 ] fewer women with recurrent convulsions per 100 women ; 2p < 0.00001 ) . Maternal mortality was nonsignificantly lower among women allocated magnesium sulphate . Women allocated magnesium sulphate were also less likely to be ventilated , to develop pneumonia , and to be admitted to intensive care facilities than those allocated phenytoin . The babies of women who had been allocated magnesium sulphate before delivery were significantly less likely to be intubated at the place of delivery , and to be admitted to a special care nursery , than the babies of mothers who had been allocated phenytoin . There is now compelling evidence in favour of magnesium sulphate , rather than diazepam or phenytoin , for the treatment of eclampsia BACKGROUND The rates of perinatal mortality and neonatal morbidity are higher for post-term pregnancies than for term pregnancies . It is not known , however , whether the induction of labor results in better outcomes than does serial fetal monitoring while awaiting spontaneous labor . METHODS We studied 3407 women with uncomplicated pregnancies of 41 or more weeks ' duration . The women were r and omly assigned to undergo induction of labor or to have serial antenatal monitoring and spontaneous labor unless there was evidence of fetal or maternal compromise , in which case labor was induced or cesarean section was performed . In the induction group , labor was induced by the intracervical application of prostagl and in E2 . Serial antenatal monitoring consisted of counts of fetal kicks , nonstress tests , and assessment s of amniotic-fluid volume . The outcomes we measured were the rates of perinatal mortality , neonatal morbidity , and delivery by cesarean section . RESULTS Among the 1701 women in the induction group , 360 ( 21.2 percent ) underwent cesarean section , as compared with 418 ( 24.5 percent ) of the 1706 women in the monitoring group ( P = 0.03 ) . This difference result ed from a lower rate of cesarean section performed because of fetal distress among the women in the induction group ( 5.7 percent vs. 8.3 percent , P = 0.003 ) . When two infants with lethal congenital anomalies were excluded , there were no perinatal deaths in the induction group and two stillbirths in the monitoring group ( P not significant ) . The frequency of neonatal morbidity was similar in the two groups . CONCLUSIONS In post-term pregnancy , the induction of labor results in a lower rate of cesarean section than serial antenatal monitoring ; the rates of perinatal mortality and neonatal morbidity are similar with the two approaches to management |
12,028 | 23,906,171 | RESULTS We found sufficient evidence that interactive education , computerised reminder systems and audit and feedback delivered to clinicians may significantly increase several cancer detection measures in the short term and some evidence that they promote early diagnosis .
Whilst educational outreach and local opinion leaders had some effect , formal education alone seemed ineffectual .
Certain educational interventions delivered at a clinician as well as at a practice level may promote the early diagnosis of cancer in primary care .
There is currently limited evidence for their long-term sustainability and effectiveness | BACKGROUND Primary healthcare professionals seem to lack knowledge and skills in the area of diagnosing cancer which may lead to more advanced stage at diagnosis , poorer cancer survival figures and increased morbidity .
The aim of this study was to examine the evidence of effectiveness of educational interventions for primary healthcare professionals to promote the early diagnosis of cancer . | BACKGROUND Colorectal cancer ( CRC ) screening is underutilized despite evidence that screening reduces mortality . OBJECTIVE To assess the effect of an intervention targeting physicians and their patients on rates of CRC screening . DESIGN A r and omized clinical trial of community physicians and their patients . PARTICIPANTS Ninety-four community primary care physicians r and omly assigned to an intervention consisting of academic detailing and direct mailings to patients or a control group . Patients aged 50 to 79 years in the intervention group physicians received a letter from their physician , a brochure on CRC screening , and a packet of fecal occult blood test ( FOBT ) cards . MEASUREMENTS After 1 year we measured receipt of the following : ( 1 ) FOBT in the past 2 years , ( 2 ) flexible sigmoidoscopy ( SIG ) or colonoscopy ( COL ) in the previous 5 years , and ( 3 ) any CRC screening . We report the percent change from baseline in both groups . RESULTS 9,652 patients were enrolled for 2 years , and 3,732 patients were enrolled for 5 years . There was no increase in any CRC screening that occurred in the intervention group for patients enrolled for 2 years ( 12.7 increase vs 12.5 % , P=.51 ) . Similar results were seen for any CRC screening among patients enrolled for 5 years ( 9.7 % increase vs 8.6 % , P=.45 ) . The only outcome on which the intervention had an effect was on patient rates of screening SIG ( 7.4 % increase vs 4.4 % , P<.01 ) . CONCLUSION With the exception of an increase in rates of SIG in the intervention group , the intervention had no effect on rates of CRC screening . Future interventions should assess innovative approaches to increase rates of CRC screening BACKGROUND Complete diagnostic evaluation or CDE ( i.e. , colonoscopy or combined flexible sigmoidoscopy plus barium enema X-ray ) is often not performed for persons with an abnormal screening fecal occult blood test ( FOBT+ ) result . METHOD This study evaluated the impact of a reminder-feedback and educational outreach intervention on primary care practice CDE recommendation and performance rates . Four hundred seventy primary care physicians ( PCPs ) in 318 practice s participated in the study . Patients were mailed an FOBT kit annually as part of a screening program . Practice s were r and omly assigned to a Control Group ( N = 198 ) or an Intervention Group ( N = 120 ) . During an 18-month pre-r and omization period and a 9-month post-r and omization period , 2992 screening FOBT+ patients were identified . Intervention practice s received the screening program and the intervention . Control practice s received only the screening program . Study outcomes were baseline-adjusted CDE recommendation and performance rates . RESULTS At baseline , about two-thirds of FOBT+ patients received a CDE recommendation , and about half had a CDE performed . At endpoint , CDE recommendation and performance rates were both significantly higher for the Intervention as compared to the Control practice s ( OR = 2.28 ; 95 % CI : 1.37 , 3.78 , and OR = 1.63 ; 95 % CI : 1.06 , 2.50 , respectively ) . CONCLUSIONS The reminder-feedback plus educational outreach intervention significantly increased CDE recommendation and performance BACKGROUND To promote prevention and early detection of cancer , the authors conducted a three-year intervention targeting Vietnamese physicians in solo practice in California . METHODS Twenty subjects who had received their medical training in Vietnam were recruited into a r and omized controlled trial . The intervention included computerized or manual cancer screening reminders , continuing medical education seminars , Vietnamese- language health education material s , newsletters , and oncology data -query programs . Evaluation included chart audits for eight targeted activities pre- and post-intervention . RESULTS Before the intervention , annual physician performance rates were low for all eight activities : routine checkups ( 65.6 % ) , Pap testing ( 13.8 % ) , pelvic examinations ( 19.8 % ) , clinical breast examinations ( 13.3 % ) , mammography ( 6.4 % ) , hepatitis B serologies ( 21.9 % ) , hepatitis B immunizations ( 12.8 % ) , and smoking cessation counseling ( 1.6 % ) . After the intervention , performance rates increased significantly for smoking cessation counseling ( p = 0.02 ) , Pap testing ( p = 0.004 ) , and pelvic examinations ( p = 0.01 ) . CONCLUSIONS The results demonstrate the efficacy of an intervention targeting Vietnamese primary care physicians in promoting smoking cessation counseling , Pap testing , and pelvic examinations , but not other cancer prevention activities A multifaceted , individualized , physician education program design ed to increase the breast cancer screening practice s of community-based primary care physicians is described and the results are evaluated . Community-based surveys identified primary care providers with breast cancer screening educational needs who were assigned , using a factorial design , to an intervention or control condition . The sample included 154 control and 128 intervention physicians . The intervention consisted of a 1 - 2h in-office training program and /or self- study workbook . Self-reported overall breast cancer screening need scores improved for a greater proportion of intervention than control physicians , particularly those receiving the in-office intervention ( P=0.03 ) . Clinical breast examination ( CBE ) need declined ( P=0.01 ) ; use of provider reminder systems increased ( P=0.02 ) ; preparedness to counsel about CBE ( P=0.04 ) and recognition that age is an important risk factor for breast cancer ( P=0.02 ) improved in more intervention compared to control physicians BACKGROUND Urban minority groups , such as those living in northern Manhattan and the South Bronx , are generally underserved with regard to breast cancer prevention and screening practice s. Primary care physicians are critical for the recommendation of mammography and clinical breast examinations to their patients . DESIGN Two medically underserved communities were matched and block r and omized . The aim of the study was to assess the efficacy of academic detailing in increasing recommendations for breast cancer screening in community-based primary care physicians . SETTING / PARTICIPANTS Ninety-four primary care community-based ( ie , not hospital-based ) physicians in northern Manhattan were compared with 74 physicians in the South Bronx who received no intervention . INTERVENTION INTERVENTION participants received multicomponent physician-directed education , academic detailing , using the American Cancer Society guidelines for the early detection of breast cancer . MAIN OUTCOME MEASURES We administered interviews to ask about primary care physicians ' recommendation of mammography and clinical breast examination . They were also queried about their knowledge of major risk factors and perceived barriers to breast cancer screening . We conducted medical audits of 710 medical charts 2 years before and after the intervention . RESULTS Using a mixed models linear analysis , we found a statistically significant intervention effect on the recommendation of mammography and clinical breast examination ( according to medical audit ) by female patients age 40 and over . INTERVENTION group physicians correctly identified significantly more risk factors for breast cancer , and significantly fewer barriers to practice , than did comparison physicians . CONCLUSIONS We found some evidence of improvement in breast cancer screening practice s due to academic detailing among primary care physicians practicing in urban underserved communities BACKGROUND Very little effort has been directed to enable GPs to better informed decisions about PSA screening among their male patients . OBJECTIVES To evaluate an innovative programme design ed to enhance GPs ' capacity to promote informed decision making by male patients about PSA screening . METHODS The study design was a cluster r and omised controlled trial set in New South Wales , Australia 's most populous state . 277 GPs were recruited through a major pathology laboratory . The interventions were three telephone-administered ' peer coaching ' sessions integrated with educational re sources for GPs and patients and the main outcome measures were : GP knowledge ; perceptions of patient involvement in informed decision making ; GPs ' own decisional conflict ; and perceptions of medicolegal risk . RESULTS Compared with GPs allocated to the control group , GPs allocated to our intervention gained significantly greater knowledge about PSA screening and related information [ Mean 6.1 out of 7 ; 95 % confidence interval ( CI ) = 5.9 - 6.3 versus 4.8 ; 95 % CI = 4.6 - 5.0 ; P < 0.001 ] . They were less likely to agree that patients should remain passive when making decisions about PSA screening [ Odds ratio ( OR ) = 0.11 ; 95 % CI = 0.04 - 0.31 ; P < 0.001 ] . They perceived less medicolegal risk when not acceding to an ' uninformed ' patient request for a PSA test ( OR = 0.31 ; 95 % CI 0.19 - 0.51 ) . They also demonstrated lower levels of personal decisional conflict about the PSA screening ( Mean 25.4 ; 95 % CI 24.5 - 26.3 versus 27.8 ; 95 % CI 26.6 - 29.0 ; P = 0.0002 ) . CONCLUSION A ' peer coaching ' programme , supplemented by education material s , holds promise as a strategy to equip GPs to facilitate informed decision making amongst their patients BACKGROUND Screening reduces colorectal cancer mortality , but effective screening tests remain underused . Systematic reminders to patients and physicians could increase screening rates METHODS We conducted a r and omized controlled trial of patient and physician reminders in 11 ambulatory health care centers . Participants included 21 860 patients aged 50 to 80 years who were overdue for colorectal cancer screening and 110 primary care physicians . Patients were r and omly assigned to receive mailings containing an educational pamphlet , fecal occult blood test kit , and instructions for direct scheduling of flexible sigmoidoscopy or colonoscopy . Physicians were r and omly assigned to receive electronic reminders during office visits with patients overdue for screening . The primary outcome was receipt of fecal occult blood testing , flexible sigmoidoscopy , or colonoscopy over 15 months , and the secondary outcome was detection of colorectal adenomas . RESULTS Screening rates were higher for patients who received mailings compared with those who did not ( 44.0 % vs 38.1 % ; P < .001 ) . The effect increased with age : + 3.7 % for ages 50 to 59 years ; + 7.3 % for ages 60 to 69 years ; and + 10.1 % for ages 70 to 80 years ( P = .01 for trend ) . Screening rates were similar among patients of physicians receiving electronic reminders and the control group ( 41.9 % vs 40.2 % ; P = .47 ) . However , electronic reminders tended to increase screening rates among patients with 3 or more primary care visits ( 59.5 % vs 52.7 % ; P = .07 ) . Detection of adenomas tended to increase with patient mailings ( 5.7 % vs 5.2 % ; P = .10 ) and physician reminders ( 6.0 % vs 4.9 % ; P = .09 ) . CONCLUSIONS Mailed reminders to patients are an effective tool to promote colorectal cancer screening , and electronic reminders to physicians may increase screening among adults who have more frequent primary care visits Background Few patients with lower bowel symptoms who consult their general practitioner need a specialist opinion . However data from referred patients suggest that those who are referred would benefit from detailed assessment before referral . Methods A cluster r and omised factorial trial . 44 general practice s in North Trent , UK . Practice s were offered either an electronic interactive referral pro forma , an educational outreach visit by a local colorectal surgeon , both or neither . The main outcome measure was the proportion of cases with severe diverticular disease , cancer or precancerous lesions and inflammatory bowel disease in those referred by each group . A secondary outcome was a referral letter quality score . Semi-structured interviews were conducted to identify key themes relating to the use of the software Results From 150 invitations , 44 practice s were recruited with a total list size of 265,707 . There were 716 consecutive referrals recorded over a six-month period , for which a diagnosis was available for 514 . In the combined software arms 14 % ( 37/261 ) had significant pathology , compared with 19 % ( 49/253 ) in the non-software arms , relative risk 0.73 ( 95 % CI : 0.46 to 1.15 ) . In the combined educational outreach arms 15 % ( 38/258 ) had significant pathology compared with 19 % ( 48/256 ) in the non-educational arms , relative risk 0.79 ( 95 % CI : 0.50 to 1.24 ) . Pro forma practice s documented better assessment of patients at referral . Conclusion There was a lack of evidence that either intervention increased the proportion of patients with organic pathology among those referred . The interactive software did improve the amount of information relayed in referral letters although we were unable to confirm if this made a significant difference to patients or their health care providers . The potential value of either intervention may have been diminished by their limited uptake within the context of a cluster r and omised clinical trial . A number of lessons were learned in this trial of novel innovations BACKGROUND Colorectal cancer is the second leading cause of cancer mortality in israel . Unfortunately , compliance with annual fecal occult blood testing is very low . OBJECTIVE To assess the effectiveness of interventions to increase FOBT screening in primary care clinics in Israel . METHODS A prospect i ve , r and omized study included all 50 - 75 year old enrollees of six family physicians in two primary care clinics . The register of two physicians , one from each clinic , was allocated to one of three groups . Two FOBT reminder strategies were tested : a physician reminder ( 753 patients ) , and a patient reminder that was either a phone call ( 312 patients ) or a letter ( 337 patients ) . The control group ( 913 patients ) of physicians continued administering their regular level of care . The main outcome measure was the percentage of patients undergoing FOBT screening in each study arm at the conclusion of the one year study period . RESULTS In the intervention groups 14.3 % ( 201/1,402 ) were screened using the FOBT over the course of the study year . Using an intent-to-screen analysis , the screening rate in the physician and patient reminder groups was significantly higher than in the control group ( 16.5 and 11.9 % , vs. 1.2 % respectively , P < 0.0001 ) . Phone reminders were significantly more effective than letters ( 14.7 vs. 9.2 % , P = 0.01 ) . CONCLUSIONS Various reminder systems for FOBT are beneficial , especially those centered around the family physician . Further research should focus on this area , in conjunction with other novel approaches OBJECTIVE : To determine whether a brief , multicomponent intervention could improve the skin cancer diagnosis and evaluation planning performance of primary care residents to a level equivalent to that of dermatologists . PARTICIPANTS : Fifty-two primary care residents ( 26 in the control group and 26 in the intervention group ) and 13 dermatologists completed a pretest and posttest . DESIGN : A r and omized , controlled trial with pretest and posttest measurements of residents ’ ability to diagnose and make evaluation plans for lesions indicative of skin cancer . INTERVENTION : The intervention included face-to-face feedback sessions focusing on residents ’s performance deficiencies ; an interactive seminar including slide presentations , case examples , and live demonstrations ; and the Melanoma Prevention Kit including a booklet , magnifying tool , measuring tool , and skin color guide . MEASUREMENTS AND MAIN RESULTS : We compared the abilities of a control and an intervention group of primary care residents , and a group of dermatologists to diagnose and make evaluation plans for six categories of skin lesions including three types of skin cancer — malignant melanoma , squamous cell carcinoma , and basal cell carcinoma . At posttest , both the intervention and control group demonstrated improved performance , with the intervention group revealing significantly larger gains . The intervention group showed greater improvement than the control group across all six diagnostic categories ( a gain of 13 percentage points vs 5 , p<.05 ) , and in evaluation planning for malignant melanoma ( a gain of 46 percentage points vs 36 , p<.05 ) and squamous cell carcinoma ( a gain of 42 percentage points vs 21 , p<.01 ) . The intervention group performed as well as the dermatologists on five of the six skin cancer diagnosis and evaluation planning scores with the exception of the diagnosis of basal cell carcinoma . CONCLUSIONS : Primary care residents can diagnose and make evaluation plans for cancerous skin lesions , including malignant melanoma , at a level equivalent to that of dermatologists if they receive relevant , targeted education BACKGROUND We assessed the efficacy of the Cancer Screening Office Systems ( Cancer SOS ) , an intervention design ed to increase cancer screening in primary care setting s serving disadvantaged population s. METHODS Eight primary care clinics participating in a county-funded health insurance plan in Hillsborough County , Fla , agreed to take part in a cluster-r and omized experimental trial . The Cancer SOS had 2 components : a cancer-screening checklist with chart stickers that indicated whether specific cancer-screening tests were due , ordered , or completed ; and a division of office responsibilities to achieve high screening rates . Established patients were eligible if they were between the ages of 50 and 75 years and had no contraindication for screening . Data abstract ed from charts of independent sample s collected at baseline ( n = 1,196 ) and at a 12-month follow-up ( n = 1,237 ) was used to assess whether the patient was up-to- date on one or more of the following cancer-screening tests : mammogram , Papanicolaou ( Pap ) smear , or fecal occult blood testing ( FOBT ) . RESULTS In multivariate analysis that controlled for baseline screening rates , secular trends , and other patient and clinic characteristics , the intervention increased the odds of mammograms ( odds ratio [ OR ] = 1.62 , 95 % confidence interval [ CI ] , 1.07–9.78 , P = .023 ) and fecal occult blood tests ( OR = 2.5 , 95 % CI , 1.65–4.0 , P < .0001 ) with a trend toward greater use of Pap smears ( OR = 1.57 , 95 % CI , 0.92–2.64 , P = .096 ) . CONCLUSIONS The Cancer SOS intervention significantly increased rates of cancer screening among primary care clinics serving disadvantaged population s. The Cancer SOS intervention is one option for providers or policy makers who wish to address cancer related health disparities Objective : To improve compliance with computer-generated reminders to perform fecal occult blood testing ( FOBT ) , mammography , and cervical Papanicolaou ( Pap ) testing . Design : Six-month prospect i ve , r and omized , controlled trial . Setting : Academic primary care general internal medicine practice .Subjects : Thirty-one general internal medicine faculty , 145 residents , and 5,407 patients with scheduled visits who were eligible for any of the three cancer screening protocol s . Intervention : Primary care teams of internal medicine residents and faculty received either routine computer reminders ( control ) or the same reminders to which they were required to circle one of four responses : 1 ) “ done/order today , ” 2 ) “ not applicable to this patient , ” 3 ) “ patient refused , ” or 4 ) “ next visit . ” Results : Intervention physicians complied more frequently than control physicians with all reminders combined ( 46 % vs 38 % , respectively , p=0.002 ) and separately with reminders for FOBT ( 61 % vs 49 % , p=0.0007 ) and mammography ( 54 % vs 47 % , p=0.036 ) but not cervical Pap testing ( 21 % vs 18 % , p=0.2 ) . Intervention residents responded significantly more often than control residents to all reminders together and separately to reminders for FOBT and mammography but not Pap testing . There was no significant difference between intervention and control faculty , but the compliance rate for control faculty was significantly higher than the rate for control residents for all reminders together and separately for FOBT but not mammography or Pap testing . The intervention ’s effect was greatest for patients ≥70 years old , with significant results for all tests , together and singly , for residents but not faculty . Intervention physicians felt that the reminders were not applicable 21 % of the time ( due to inadequate data in patients ’ electronic medical records ) and stated that their patients refused 10 % of the time . Conclusions : Requiring physicians to respond to computer-generated reminders improved their compliance with preventive care protocol s , especially for elderly patients for whom control physicians ’ compliance was the lowest . However , 100 % compliance with cancer screening reminders will be unattainable due to incomplete data and patient refusal Abstract OBJECTIVE : To evaluate an innovative approach to continuing medical education , an outreach intervention design ed to improve performance rates of breast cancer screening through implementation of office systems in community primary care practice s. DESIGN : R and omized , controlled trial with primary care practice s assigned to either the intervention group or control group , with the practice as the unit of analysis . SETTING : Twenty mostly rural counties in North Carolina . PARTICIPANTS : Physicians and staff of 62 r and omly selected family medicine and general internal medicine practice s , primarily fee-for-service , half group practice s and half solo practitioners . INTERVENTION : Physician investigators and facilitators met with practice physicians and staff over a period of 12 to 18 months to provide feedback on breast cancer screening performance , and to assist these primary care practice s in developing office systems tailored to increase breast cancer screening . MEASUREMENTS AND MAIN RESULTS : Physician question naires were obtained at baseline and follow-up to assess the presence of five indicators of an office system . Three of the five indicators of office systems increased significantly more in intervention practice s than in control practice s , but the mean number of indicators in intervention practice s at follow-up was only 2.8 out of 5 . Cross-sectional review s of r and omly chosen medical records of eligible women patients aged 50 years and over were done at baseline ( n=2,887 ) and follow-up ( n=2,874 ) to determine whether clinical breast examinations and mammography , were performed . Results for mammography were recorded in two ways , mention of the test in the visit note and actual report of the test in the medical record . These review s showed an increase from 39 % to 51 % in mention of mammography in intervention practice s , compared with an increase from 41 % to 44 % in control practice s ( p=.01 ) . There was no significant difference , however , between the two groups in change in mammograms reported ( intervention group increased from 28 % to 32.7 % ; control group increased from 30.6 % to 34.0 % , p=.56 ) . There was a nonsignificant trend ( p=.06 ) toward a greater increase in performance of clinical breast examination in intervention versus control practice s. CONCLUSIONS : A moderately intensive outreach intervention to increase rates of breast cancer screening through the development of office systems was modestly successful in increasing indicators of office systems and in documenting mention of mammography , but had little impact on actual performance of breast cancer screening . At follow-up , few practice s had a complete office system for breast cancer screening . Outreach approaches to assist primary care practice s implement office systems are promising but need further development CONTEXT Prostate cancer screening with prostate-specific antigen ( PSA ) is frequently performed , counter to clinical practice guidelines . BACKGROUND It was hypothesized that an e-mail-based intervention termed " spaced education " could reduce clinicians ' inappropriate screening for prostate cancer . DESIGN The study was conducted as an RCT . SETTING / PARTICIPANTS The study involved 95 primary care clinicians in eight Veterans Affairs medical centers from January 2007 to February 2009 . INTERVENTION Participants were r and omized into two cohorts : spaced education clinicians received four isomorphic cycles of nine e-mails over 36 weeks ( zero to two e-mails per week ) , whereas control clinicians received no intervention . Each e-mail presented a clinical scenario and asked whether it was appropriate to obtain a PSA test . Participants received immediate feedback after su bmi tting their answers . MAIN OUTCOME MEASURES The primary outcome was the number and percentage of inappropriate PSA screening tests ordered . Inappropriate testing was defined as use of PSA for prostate cancer screening in patients aged > 76 or < 40 years . Appropriateness of screening was dichotomized based on patient age at time of screening . Patients with PSA testing for non-screening reasons were excluded using a vali date d protocol . Logistic regression with adjustment for patient clustering by clinician was performed . Analyses were conducted in 2009 . RESULTS During the intervention period ( Weeks 1 - 36 ) , clinicians receiving spaced education e-mails ordered significantly fewer inappropriate PSA screening tests than control clinicians ( 10.5 % vs 14.2 % , p=0.041 ) . Over the 72-week period following the intervention ( Weeks 37 - 108 ) , spaced education clinicians continued to order fewer inappropriate tests compared to controls ( 7.8 % vs 13.1 % , respectively , p=0.011 ) , representing a 40 % relative reduction in inappropriate screening . CONCLUSIONS Spaced education durably improves the prostate cancer screening behaviors of clinicians and represents a promising new methodology to improve patient care across healthcare systems OBJECTIVE To evaluate a health maintenance organization (HMO)-sponsored intervention to improve cancer screening in private physician practice s serving low-income , minority population s. DESIGN A r and omized controlled trial with preintervention and postintervention measurements . Measurements were obtained by abstract ing information from independent r and om sample s of medical charts ( N = 2316 at preintervention and 2238 at postintervention ) . SETTING Forty-seven primary care physician practice s located in low-income and minority urban neighborhoods in Chicago , Ill. INTERVENTION Practice s were encouraged to adopt an office chart reminder system and to use a patient health maintenance card . Activities to facilitate the adoption of these items and for compliance with cancer screening guidelines included on-site training and start-up assistance visits , a physician continuing medical education seminar , and quality assurance visits with feedback to physicians . MAIN OUTCOME MEASURES The proportions of patients with a chart-documented mammogram , clinical breast examination , Papanicolaou smear , or fecal occult blood slide test in the 2 years before preintervention and postintervention chart abstract ions . RESULTS Between baseline and postintervention , there was a net increase in the proportion of HMO members in the intervention , compared with the control practice s , who received in the preceding 2 years a Papanicolaou smear ( 11.9 % ) and a fecal occult blood slide test ( 14.1 % ) . There was a net increase in the proportion of non-HMO patients in the intervention compared with the control practice s who received a clinical breast examination ( 15.3 % ) and a fecal occult blood slide test ( 20.2 % ) . CONCLUSIONS Implementation of an HMO-mediated , multicomponent intervention to improve cancer screening was feasible and effective for the Papanicolaou smear , fecal occult blood slide test , and the clinical breast examination , but not for mammography This study was aim ed at evaluating the effects of an education program for general practitioners on their prescribing behaviour for cervical and breast cancer screening tests , and assessing the feasibility of general practitioners participation in screening programs . All three cytology laboratories and 19 of the 20 radiologists in one administrative region ( " Haute-Savoie " ) in France agreed to participate . The 278 general practice s in this region were r and omly assigned to either the intervention group ( a one-day seminar on screening for breast cancer and cervical cancer ) or the control group ( n for both = 139 ) . The prescriptions of tests for the following year were noted from the laboratories ' and radiologists ' records . No significant differences were observed between the intervention group and the control group for the number of mammographies prescribed with a mean of 19.3 and 15.2 per practice , respectively . However , significantly more mammographies were prescribed in women aged over 50 by the intervention group ( p = 0.038 ) . Inversely , fewer smear tests were prescribed in the intervention group ( mean per practice : 40.5 and 46.1 , respectively ) . A significantly higher number of practice s in the intervention group did not prescribe any smear tests ( p = 0.007 ) . This study suggests that it is possible to influence general practitioners ' participation in screening programs , but that the messages should be carefully presented , since negative effects are possible BACKGROUND Previous interventions to promote performance of cancer prevention activities have largely targeted physicians in university-based practice s. METHODS We r and omly assigned 40 primary care physicians in community-based practice s to either ( 1 ) Cancer Prevention Reminders , computer-generated lists of overdue screening tests , and smoking and dietary assessment and counseling , supplemented by cancer education material s ; or ( 2 ) controls . For each physician , we review ed a r and om sample of 60 medical records for data about screening test , assessment , and counseling performance during 12-month preintervention and intervention periods . We calculated performance scores as percentage compliance with American Cancer Society and /or National Cancer Institute recommendations . Multiple regression analyses provided estimates of incremental differences in performance scores between intervention and control groups . RESULTS Controlling for preintervention performance levels , significant incremental differences in performance scores between intervention and control groups ( P less than .05 ) were achieved for nine maneuvers : stool occult-blood test , + 14.5 ; rectal examination , + 10.5 ; pelvic examination , + 11.8 ; Papanicolaou 's smear , + 30.7 ; breast examination , + 8.7 ; smoking assessment , + 10.2 ; smoking counseling , + 17.3 ; dietary assessment , + 12.3 ; and dietary counseling , + 13.9 . Increments for sigmoidoscopy and mammography were not significant . CONCLUSION Computerized reminders can significantly increase physicians ' performance of cancer prevention activities in community-based practice BACKGROUND Prostate-specific antigen ( PSA ) testing for prostate cancer is controversial . Dem and for PSA testing is likely to rise in the UK , Australia and other western countries . Primary care needs to develop appropriate strategies to respond to this dem and . OBJECTIVES Our aim was to compare the effectiveness of educational outreach visits ( EOVs ) and mailout strategies targeting PSA testing in Australian primary care . METHODS A r and omized controlled trial was conducted in general practice s in southern Adelaide . The main outcome measures at baseline , 6 months and 12 months post-intervention were PSA testing rates and GP knowledge in key areas relating to prostate cancer and PSA testing . RESULTS The interventions were able to demonstrate a change in clinical practice . In the 6 months post-intervention , median PSA testing rate in the EOV group was significantly lower than in the postal group , which in turn was significantly lower than the control group ( P < 0.001 ) . Statistically significant differences were not , however , maintained in the 6 - 12 month post-intervention period . The EOV group , at 6 months follow-up , had a significantly greater proportion of " correct " responses than the control group to questions about prostate cancer treatment effectiveness ( P = 0.004 ) and endorsement of PSA screening by professional bodies ( P = 0.041 ) . CONCLUSIONS Primary care has a central role in PSA testing for prostate cancer . Clinical practice in this area is receptive to evidence -based interventions Background : Family physicians have an important clinical role in assessment and management of suspicious skin lesions . As a result of a previous needs assessment study , an educational intervention based on audit and feedback with opportunity for reflection on practice was introduced to 46 family physicians r and omly allocated to either an intervention ( 23 ) or control group ( 23 ) . As an educational tool , audit allows doctors to systematic ally review their practice and establish the quality of care they provide . When combined with feedback and comparison of clinical performance with peers or st and ards , it has been shown to increase learning and change behavior . Methods : Data based on their own patients , on the correlation between clinical and histologic diagnosis , and excisions of skin lesions were collated and reported to the intervention group . Results : Despite r and omization of the doctors , the patient population of doctors in the intervention and control groups were significantly different in key characteristics , including the types of skin lesions treated . The intervention group of doctors showed improved performance in providing clinical information on pathology requests and in adequate surgical excision of skin lesions . Diagnostic performance did not improve significantly , but physicians ' certainty of diagnosis did . Implication s : This study design has highlighted the difficulty in balancing the use of evidence ‐based educational strategies in an equivalent setting to normal practice with evaluation of performance using measures that include characteristics of practitioners ' patients that can not be controlled Background : Malignant melanoma is rising quickly in incidence and mortality rates . Family physicians ( FPs ) have been reported to lack confidence in diagnosing skin cancers . Objective : The aim of this study was to determine whether an educational intervention can improve FPs ’ abilities to diagnose skin cancers . Methods : The design was a prospect i ve , r and omized trial which included a skin cancer question naire , a video intervention , and a skin biopsy review . Results : Pre-intervention , FPs answered 57 % of the questions correctly on the skin cancer question naire . Post-intervention , the video intervention group scored higher than did the control group . The video intervention group removed 10 % fewer benign lesions and almost 3 times more malignant lesions compared with their pre-intervention biopsy rate . No findings were statistically significant . Conclusion : An educational intervention may improve FPs ’ knowledge and diagnosis of skin cancer . Our results may guide future studies with larger sample sizes in developing a skin cancer continuing medical education ( CME ) course for FPs . Antécédents : L’incidence des mélanomes et le taux de mortalité qui y est associé augmentent rapidement , ce qui laisse suggérer que les médecins de famille n’ont pas la confiance nécessaire pour diagnostiquer le cancer de la peau . Objectif : Déterminer si une campagne d’éducation peut améliorer la capacité des médecins de famille à diagnostiquer les cancers de la peau . Méthodes : Une étude prospect i ve r and omisée a été menée , comprenant un question naire sur le cancer de la peau , une séance éducative sur vidéo et un aperçu d’une biopsie de la peau . Résultats : Avant la séance , les médecins de famille ont obtenu de bonnes réponses à 57 % des questions figurant sur le question naire du cancer de la peau . Le groupe qui a assisté à la séance vidéo a eu un meilleur résultat que le groupe précédent . Le groupe a enlevé 10 % de moins de tumeurs bénignes et 3 fois plus de tumeurs malignes après l’aperçu de la biopsie . Toutefois , ces résultats ne représentent pas des statistiques significatives . Conclusion : Des mesures éducatives pourront améliorer les connaissances des médecins de famille et leurs capacités de diagnostiquer les mélanomes . Nos résultats pourront orienter de futures études , avec un plus large nombre de participants , dans la mise au point d’une stratégie d’éducation médicale continue ( EMC ) sur le cancer de la peau , destinée aux médecins de famille OBJECTIVE To determine the effectiveness of different types of interventions in improving health professional performance and health outcomes . DATA SOURCES MEDLINE , SCI SEARCH , CINAHL and the Research and Development Re source Base in CME were search ed for trials of educational interventions in the health care professions published between 1970 and 1993 inclusive . STUDY SELECTION Studies were selected if they provided objective measurements of health professional performance or health outcomes and employed r and om or quasi-r and om allocation methods in their study design s to assign individual subjects or groups . Interventions included such activities as conferences , outreach visits , the use of local opinion leaders , audit and feedback , and reminder systems . DATA EXTRACTION Details extracted from the studies included the study design ; the unit of allocation ( e.g. , patient , provider , practice , hospital ) ; the characteristics of the targeted health care professionals , educational interventions and patients ( when appropriate ) ; and the main outcome measure . DATA SYNTHESIS The inclusion criteria were met by 102 trials . Areas of behaviour change included general patient management , preventive services , prescribing practice s , treatment of specific conditions such as hypertension or diabetes , and diagnostic service or hospital utilization . Dissemination-only strategies , such as conferences or the mailing of unsolicited material s , demonstrated little or no changes in health professional behaviour or health outcome when used alone . More complex interventions , such as the use of outreach visits or local opinion leaders , ranged from ineffective to highly effective but were most often moderately effective ( result ing in reductions of 20 % to 50 % in the incidence of inappropriate performance ) . CONCLUSION There are no " magic bullets " for improving the quality of health care , but there are a wide range of interventions available that , if used appropriately , could lead to important improvements in professional practice and patient outcomes |
12,029 | 24,795,073 | Few interventions targeting patient-practitioner communication have assessed the impact on cardiovascular-related clinical outcomes , limiting the ability to determine effectiveness . | OBJECTIVE To conduct a systematic literature review appraising the effects of interventions to improve patient-practitioner communication on cardiovascular-related clinical outcomes . | The efficacy of a communication skills training programme was shown through a r and omised trial . Oncologists ( N=160 ) from 34 cancer centres were allocated to written feedback plus course ; course alone ; written feedback alone or control . Each clinician had 6 – 10 interviews with patients videotaped at baseline and 3 months postintervention . Analysis of videotapes revealed improvements in the communication skills of clinicians r and omised to training ( n=80 ) compared with others ( n=80 ) . A 12-month follow-up assessment is reported here . Robust Poisson conditional analyses of counts of changes in communication behaviours revealed no demonstrable attrition in those who had shown improvement previously , including fewer leading questions , appropriate use of focused and open-ended questions and responses to patient cues . Additional skills , not apparent at 3 months , were now evident ; the estimated effect sizes corresponded to 81 % fewer interruptions ( P=0.001 ) and increased summarising of information to 38 % ( P=0.038 ) . However , expressions of empathy ( 54 % , P=0.001 ) declined . The overall results show that 12 – 15 months postintervention , clinicians had integrated key communication skills into clinical practice and were applying others . This is the first RCT to show an enduring effect of communication skills training with transfer into the clinic This study compared an activation intervention to passive education in a r and omized attention-control trial of 232 patients with type 2 diabetes . The activation intervention was based on Exp and ing Patient Involvement in Care ( EPIC ) trials , and was compared to time-matched passive education viewing of ADA video-tapes . Patient demographics and clinical characteristics of their diabetes were assessed with question naires , active involvement was assessed via ratings of taped interactions between patients and providers , and serum sample s were analyzed for HbA1c . Patients in the activation condition were rated as more actively involved in discussion s of diabetes self-management , and rated active involvement was predictive of improvement in glycemic control . No effect of the activation intervention was found on HbA1c . Thus , the activation intervention increased the active involvement of patients with type 2 diabetes in visits with practitioners , and active involvement led to improved glycemic control . However , the activation intervention did not improve glycemic control directly The authors assessed whether patient empowerment in the management of hypertension improved more with the practice of shared decision making ( SDM ) than by education programs . In a prospect i ve controlled clinical study , 15 general practitioners in Nuremberg , Germany who were specially trained to conduct SDM consultations participated in a 12-month study . Hypertensive patients ( N=86 ) were included ; N=40 were in the SDM group and N=46 were in the control group , if blood pressures were > or = 135 / 85 mm Hg ( self measurement ) and patients had no signs of cardiovascular complications or severe hypertension . All participants in the SDM group and the control group were enrolled in an education program on hypertension in small groups . The SDM group participants also had 4 special consultations to share medical decisions . The main outcome measures were the effect of SDM on blood pressure control . After 1 year blood pressure had decreased in all participants : Delta-9.26 + /- 10.2 mm Hg/Delta-5.33 + /- 9.5 mm Hg in the SDM group ( P<0.001 ) compared to Delta-6.0 + /- 11.8 mm Hg/Delta-3.0 + /- 8.3 mm Hg in the control group . There was no significant difference between the 2 groups . The study group practice d more SDM than controls , but blood pressure control was not significantly better . Patient empowerment by means of an education program in small groups and creating awareness of hypertensive disease helps to improve the outcome of hypertension treatment . SDM , however , did not improve management when compared to an education program , which is much easier to implement in general practice OBJECTIVE Despite the importance of self-management support ( SMS ) , few studies have compared SMS interventions , involved diverse population s , or entailed implementation in safety net setting s. We examined the effects of two SMS strategies across outcomes corresponding to the Chronic Care Model . RESEARCH DESIGN AND METHODS A total of 339 out patients with poorly controlled diabetes from county-run clinics were enrolled in a three-arm trial . Participants , more than half of whom spoke limited English , were uninsured , and /or had less than a high school education , were r and omly assigned to usual care , interactive weekly automated telephone self-management support with nurse follow-up ( ATSM ) , or monthly group medical visits with physician and health educator facilitation ( GMV ) . We measured 1-year changes in structure ( Patient Assessment of Chronic Illness Care [ PACIC ] ) , communication processes ( Interpersonal Processes of Care [ IPC ] ) , and outcomes ( behavioral , functional , and metabolic ) . RESULTS Compared with the usual care group , the ATSM and GMV groups showed improvements in PACIC , with effect sizes of 0.48 and 0.50 , respectively ( P < 0.01 ) . Only the ATSM group showed improvements in IPC ( effect sizes 0.40 vs. usual care and 0.25 vs. GMV , P < 0.05 ) . Both SMS arms showed improvements in self-management behavior versus the usual care arm ( P < 0.05 ) , with gains being greater for the ATSM group than for the GMV group ( effect size 0.27 , P = 0.02 ) . The ATSM group had fewer bed days per month than the usual care group ( −1.7 days , P = 0.05 ) and the GMV group ( −2.3 days , P < 0.01 ) and less interference with daily activities than the usual care group ( odds ratio 0.37 , P = 0.02 ) . We observed no differences in A1C change . CONCLUSIONS Patient-centered SMS improves certain aspects of diabetes care and positively influences self-management behavior . ATSM seems to be a more effective communication vehicle than GMV in improving behavior and quality of life OBJECTIVE To determine if a patient-centered , computer-assisted diabetes care intervention increased perceived autonomy support , perceived competence ( from self-determination theory ) , and if these constructs mediated the effect of the intervention on ADA/NCQA recommended diabetes care outcomes . DESIGN A r and omized controlled trial of 866 adult type 2 diabetes patients in heterogeneous primary care setting s in Colorado . MAIN OUTCOME MEASURES Perceived autonomy support , perceived competence , patient satisfaction , glycemic control ( HbA1c ) , ratio of total to HDL cholesterol , diabetes distress , and depressive symptoms . RESULTS The computer-assisted intervention increased patient perception of autonomy support relative to a computer-based control condition ( p = .05 ) . Change in perceived competence partially mediated the effects of increased autonomy support on the change in lipids , diabetes distress , and depressive symptoms . The construct of autonomy support was found to be separate from that of patient satisfaction . CONCLUSIONS A patient-centered , computer-assisted intervention was effective in improving diabetes self-management outcomes , in part , because it increased patients ' perception that their autonomy was supported which changed perceived competence . These findings support the self-determination model for health behavior change and the chronic care model and support the further study of the use of these technologies to motivate patients to improve their health outcomes OBJECTIVE To ascertain whether the quality of physician-patient communication makes a significant difference to patient health outcomes . DATA SOURCES The MEDLINE data base was search ed for articles published from 1983 to 1993 using " physician-patient relations " as the primary medical subject heading . Several bibliographies and conference proceedings were also review ed . STUDY SELECTION R and omized controlled trials ( RCTs ) and analytic studies of physician-patient communication in which patient health was an outcome variable . DATA EXTRACTION The following information was recorded about each study : sample size , patient characteristics , clinical setting , elements of communication assessed , patient outcomes measured , and direction and significance of any association found between aspects of communication and patient outcomes . DATA SYNTHESIS Of the 21 studies that met the final criteria for review , 16 reported positive results , 4 reported negative ( i.e. , nonsignificant ) results , and 1 was inconclusive . The quality of communication both in the history-taking segment of the visit and during discussion of the management plan was found to influence patient health outcomes . The outcomes affected were , in descending order of frequency , emotional health , symptom resolution , function , physiologic measures ( i.e. , blood pressure and blood sugar level ) and pain control . CONCLUSIONS Most of the studies review ed demonstrated a correlation between effective physician-patient communication and improved patient health outcomes . The components of effective communication identified by these studies can be used as the basis both for curriculum development in medical education and for patient education programs . Future research should focus on evaluating such educational programs OBJECTIVE The purpose of this study is to determine whether patient activation is a changing or changeable characteristic and to assess whether changes in activation also are accompanied by changes in health behavior . STUDY METHODS To obtain variability in activation and self-management behavior , a controlled trial with chronic disease patients r and omized into either intervention or control conditions was employed . In addition , changes in activation that occurred in the total sample were also examined for the study period . Using Mplus growth models , activation latent growth classes were identified and used in the analysis to predict changes in health behaviors and health outcomes . DATA SOURCES Survey data from the 479 participants were collected at baseline , 6 weeks , and 6 months . PRINCIPAL FINDINGS Positive change in activation is related to positive change in a variety of self-management behaviors . This is true even when the behavior in question is not being performed at baseline . When the behavior is already being performed at baseline , an increase in activation is related to maintaining a relatively high level of the behavior over time . The impact of the intervention , however , was less clear , as the increase in activation in the intervention group was matched by nearly equal increases in the control group . CONCLUSIONS Results suggest that if activation is increased , a variety of improved behaviors will follow . The question still remains , however , as to what interventions will improve activation OBJECTIVE A case study at the department for heart surgery of an Austrian University Hospital in 2001 , examined the outcome of improved communication aim ed at empowering patients to be more effective co-producers of recuperation after surgery . METHODS Evaluated were the effects of a training program for developing communication skills of health professionals ( physicians , physiotherapists , and nurses ) along with a reorganization of patient information schemes . The clinical outcomes after four types of surgery ( bypass , stent , artificial valve insertion and combination of these ) were observed in 100 patients without ( control group ) and 99 with the intervention administered ( intervention group ) . Two objective and two subjective health outcome parameters were selected for analysis : care level adjusted length of stay in hospital , frequency of post-surgery complications , subjective health , subjective satisfaction with care received . Self-administered breathing exercises were measured as an intermediary outcome parameter . RESULTS In the intervention group length of hospital stay was shorter ( by 1 day ) , incidence of post-surgery tachyarrhythmia was reduced ( by 15 % ) , transfer to less intensive care levels was faster and patient ratings for communicative quality of care by doctors and nurses were improved . CONCLUSION Professional communication aim ed at empowering patients to act as co producers can indeed have an effect on clinical outcome . PRACTICE IMPLICATION S Staff training and reorganization of communication schemes can be an effective intervention in hospital care Background : Preventive guidelines on cardiovascular risk management recommend lifestyle changes . Support for lifestyle changes may be a useful task for practice nurses , but the effect of such interventions in primary prevention is not clear . We examined the effect of involving patients in nurse-led cardiovascular risk management on lifestyle adherence and cardiovascular risk . Methods : We performed a cluster r and omized controlled trial in 25 practice s that included 615 patients . The intervention consisted of nurse-led cardiovascular risk management , including risk assessment , risk communication , a decision aid and adapted motivational interviewing . The control group received a minimal nurse-led intervention . The self-reported outcome measures at one year were smoking , alcohol use , diet and physical activity . Nurses assessed 10-year cardiovascular mortality risk after one year . Results : There were no significant differences between the intervention groups . The effect of the intervention on the consumption of vegetables and physical activity was small , and some differences were only significant for subgroups . The effects of the intervention on the intake of fat , fruit and alcohol and smoking were not significant . We found no effect between the groups for cardiovascular 10-year risk . Interpretation : Nurse-led risk communication , use of a decision aid and adapted motivational interviewing did not lead to relevant differences between the groups in terms of lifestyle changes or cardiovascular risk , despite significant within-group differences OBJECTIVE To assess the effect of additional training of practice nurses and general practitioners in patient centred care on the lifestyle and psychological and physiological status of patients with newly diagnosed type 2 diabetes . DESIGN Pragmatic parallel group design , with r and omisation between practice teams to routine care ( comparison group ) or routine care plus additional training ( intervention group ) ; analysis at one year , allowing for practice effects and stratifiers ; self reporting by patients on communication with practitioners , satisfaction with treatment , style of care , and lifestyle . SETTING 41 practice s ( 21 in intervention group , 20 in comparison group ) in a health region in southern Engl and . SUBJECTS 250/360 patients ( aged 30 - 70 years ) diagnosed with type 2 diabetes and completing follow up at one year ( 142 in intervention group , 108 in comparison group ) . INTERVENTION 1.5 days ' group training for the doctors and nurses-introducing evidence for and skills of patient centred care and a patient held booklet encouraging questions . MAIN OUTCOME MEASURES Quality of life , wellbeing , haemoglobin A1c and lipid concentrations , blood pressure , body mass index ( kg/m2 ) . RESULTS Compared with patients in the C group , those in the intervention group reported better communication with the doctors ( odds ratio 2.8 ; 95 % confidence interval 1.8 to 4.3 ) and greater treatment satisfaction ( 1.6 ; 1.1 to 2.5 ) and wellbeing ( difference in means ( d ) 2.8 ; 0.4 to 5.2 ) . However , their body mass index was significantly higher ( d=2.0 ; 0.3 to 3.8 ) , as were triglyceride concentrations ( d=0.4 mmol/l ; 0.07 to 0.73 mmol/l ) , whereas knowledge scores were lower ( d=-2.74 ; -0.23 to -5.25 ) . Differences in lifestyle and glycaemic control were not significant . CONCLUSIONS The findings suggest greater attention to the consultation process than to preventive care among trained practitioners ; those committed to achieving the benefits of patient centred consulting should not lose the focus on disease management BACKGROUND We design ed this observational cohort study to assess the association between patient-centered communication in primary care visits and subsequent health and medical care utilization . METHODS We selected 39 family physicians at r and om , and 315 of their patients participated . Office visits were audiotaped and scored for patient-centered communication . In addition , patients were asked for their perceptions of the patient-centeredness of the visit . The outcomes were : ( 1 ) patients ' health , assessed by a visual analogue scale on symptom discomfort and concern ; ( 2 ) self-report of health , using the Medical Outcomes Study Short Form-36 ; and ( 3 ) medical care utilization variables of diagnostic tests , referrals , and visits to the family physician , assessed by chart review . The 2 measures of patient-centeredness were correlated with the outcomes of visits , adjusting for the clustering of patients by physician and controlling for confounding variables . RESULTS Patient-centered communication was correlated with the patients ' perceptions of finding common ground . In addition , positive perceptions ( both the total score and the subscore on finding common ground ) were associated with better recovery from their discomfort and concern , better emotional health 2 months later , and fewer diagnostic tests and referrals . CONCLUSIONS Patient-centered communication influences patients ' health through perceptions that their visit was patient centered , and especially through perceptions that common ground was achieved with the physician . Patient-centered practice improved health status and increased the efficiency of care by reducing diagnostic tests and referrals BACKGROUND Research on synergistic effects of patient targeted interventions combined with physician-targeted interventions has been limited . OBJECTIVES To compare a combined physician-patient intervention to physician feedback alone on a composite outcome of glycemic , lipid and blood pressure control . METHODS In this cluster study 417 patients with adult-type 2 diabetes from four primary care clinics were r and omized to receive either a physician-only intervention or a combined physician-plus-patient intervention . Physicians in all clinics received diabetes-related quality performance feedback during staff meetings . Patients at combined-intervention clinics also received a letter encouraging them to remind their doctors to address essential aspects of diabetes care at the next visit . At 1 year follow-up , outcome measurements included hemoglobin A1c , low density lipoprotein-cholesterol and systolic blood pressure : namely , the proportion of patients with HbA1c 9 % , LDL < 130 mg/dl and SBP < 140 mmHg both as separate outcomes and combined . RESULTS After adjusting for patient characteristics and baseline measures , follow-up levels of HbA1c ( 7.5 % vs. 7.8 % , P = 0.09 ) , LDL ( 104.7 vs. 110.7 mg/dl , P < 0.05 ) and SBP ( 135.6 vs. 139.9 , P = 0.10 ) were marginally better for combined-intervention patients compared to physician-only intervention patients . Significantly more patients in the combined-intervention ( 38.8 % ) than physician-only intervention ( 24.2 % ) met all three targets ( HbA1c ( 9 % , LDL ( 130 mg/dl and SBP < 140 mmHg ) as a single combined outcome ( adjusted odds ratio 2.4 , P < .01 ) . CONCLUSIONS Compared to physician-feedback alone , a dual intervention combining a patient letter with physician feedback produced modest improvements in glycemic , lipid and blood pressure control individually , but substantial improvement in a combined measure of these three outcomes together . Using composite outcomes may detect meaningful improvements in the management of complex chronic disease AIM Our objective was to evaluate the effect of training in a patient-centred intervention for GPs and practice nurses on outcomes for patients with Type II diabetes . METHODS We carried out a r and omized controlled trial within general practice s as the basis for r and omization and a before- and -after design for measures of patient outcome . A parallel process study examined the use of the method by professionals . The study was carried out in 29 general practice s in South Glamorgan who had participated for at least 2 years in a local scheme of audit and CME in relation to Type II diabetes care . The subjects were 252 Type II diabetic patients recruited by 15 experimental and 14 control practice s. The main outcome measures were changes in glycosylated haemoglobin , patient satisfaction with care and treatment , functional health status and professional ability to apply the intervention . RESULTS Professionals adopted the innovative method with enthusiasm , but after 2 years only 19 % continued to apply the method systematic ally . The trial was , therefore , unable to demonstrate significant biochemical or functional improvements . This highlights the need to underst and the factors associated with professional uptake and subsequent ability to sustain changes in behaviour . CONCLUSIONS The efficacy of this behavioural intervention remains unproved , despite its acceptability to professional staff . Detailed and prolonged development and testing of behavioural interventions is an essential first step before embarking on r and omized controlled trials which involve complex behavioural changes in professionals or patients To maximize disease control , patients must participate effectively in their medical care . The authors developed an intervention design ed to increase the involvement of patients in medical decision making . In a 20-minute session just before the regular visit to a physician , a clinic assistant review ed the medical record of each experimental patient with him/her , guided by a diabetes algorithm . Using systematic prompts , the assistant encouraged patients to use the information gained to negotiate medical decisions with the doctor . A r and omized trial was conducted in two university hospital clinics to compare this intervention with st and ard educational material s in sessions of equal length . The mean pre-intervention glycosylated hemoglobin ( HbA1 ) values were 10.6 + /- 2.1 % for 33 experimental patients and 10.3 + /- 2.0 % for 26 controls . After the intervention the mean levels were 9.1 + /- 1.9 % in the experimental group ( p less than 0.01 ) and 10.6 + /- 2.22 % for controls . Analysis of audiotapes of the visits to the physician showed the experimental patients were twice as effective as controls in eliciting information from the physician . Experimental patients reported significantly fewer function limitations . The authors conclude that the intervention is feasible and that it changes patient behavior , improves blood sugar control , and decreases functional limitations The aim of this experimental study was to evaluate the effectiveness of three patient-focused interventions design ed to increase patient question asking in clinical consultations . Patients were r and omly allocated to one of five conditions to receive either one of three interventions or to serve as an attention control group or a control group . The primary outcome measure was question asking by the patient of their physician . Participants in the intervention groups did not ask more questions than participants in the control groups . Immediately after the consultation participants in the intervention groups had higher levels of self-efficacy in asking questions . Three months after the index visit patients in the intervention groups were significantly more likely to be satisfied to some degree than patients in the control group . There was no difference in diabetic control . These results suggest that simple brief patient-focused interventions do not change patient behaviour in medical outpatient consultations Abstract OBJECTIVE : To develop and test an inexpensive visual tool to help patients with diabetes improve glycemic control . METHODS : A multidisciplinary team developed a 1-page form , the “ Take-home Diabetes Record ” ( THDR ) , providing feedback to patients by displaying percent glycosylated hemoglobin ( GHb ) values graphically over time , with target levels highlighted . Patients with type 2 diabetes in an inner-city clinic were r and omized to THDR use ( n=57 ) or not ( n=70 ) over 15 months . Self-care activities were discussed , linked with GHb results , and charted at each clinic visit . Initial and final GHb were compared . RESULTS : Mean GHb fell significantly in THDR patients ( −0.94 , P=.003 ) , but not in control patients ( −0.18 , P=.36 ) . Mean GHb decrease was greater in THDR patients ( P=.047 ) . A greater proportion of THDR patients ( 51 % ) than control patients ( 18 % ) achieved a decrease in GHb ≥0.9 ( P=.001 ) . CONCLUSIONS : A graph linking GHb and self-care activities shows promise for improving glycemic control PURPOSE We wanted to determine the effect of promoting the effective communication of absolute cardiovascular disease ( CVD ) risk and shared decision making through disseminating a simple decision aid for use in family practice consultations . METHODS The study was based on a pragmatic , cluster r and omized controlled trial ( phase III ) with continuing medical education ( CME ) groups of family physicians as the unit of r and omization . In the intervention arm , 44 physicians ( 7 CME groups ) consecutively recruited 550 patients in whom cholesterol levels were measured . Forty-seven physicians in the control arm ( 7 CME groups ) similarly included 582 patients . Four hundred sixty patients ( 83.6 % ) of the intervention arm and 466 patients ( 80.1 % ) of the control arm were seen at follow-up . Physicians attended 2 interactive CME sessions and received a booklet , a paper-based risk calculator , and individual summary sheets for each patient . Control physicians attended 1 CME-session on an alternative topic . Main outcome measures were patient satisfaction and participation after the index consultation , change in CVD risk status , and decisional regret at 6 months ’ follow-up . RESULTS Intervention patients were significantly more satisfied with process and result ( Patient Participation Scale , difference 0.80 , P<.001 ) . Decisional regret was significantly lower at follow-up ( difference 3.39 , P = .02 ) . CVD risk decreased in both groups without a significant difference between study arms . CONCLUSION A simple transactional decision aid based on calculating absolute individual CVD risk and promoting shared decision making in CVD prevention can be disseminated through CME groups and may lead to higher patient satisfaction and involvement and less decisional regret , without negatively affecting global CVD risk Growing interest in the doctor-patient relationship focuses attention on the specific elements of that relationship that affect patients ' health outcomes . Data are presented for four clinical trials conducted in varied practice setting s among chronically ill patients differing markedly in sociodemographic characteristics . These trials demonstrated that “ better health ” measured physiologically ( blood pressure or blood sugar ) , behaviorally ( functional status ) , or more subjectively ( evaluations of overall health status ) was consistently related to specific aspects of physician-patient communication . We conclude that the physician-patient relationship may be an important influence on patients ' health outcomes and must be taken into account in light of current changes in the health care delivery system that may place this relationship at risk BACKGROUND African Americans and persons with low socioeconomic status ( SES ) are disproportionately affected by hypertension and receive less patient-centered care than less vulnerable patient population s. Moreover , continuing medical education ( CME ) and patient-activation interventions have infrequently been directed to improve the processes of care for these population s. OBJECTIVE To compare the effectiveness of patient-centered interventions targeting patients and physicians with the effectiveness of minimal interventions for underserved groups . DESIGN R and omized controlled trial conducted from January 2002 through August 2005 , with patient follow-up at 3 and 12 months , in 14 urban , community-based practice s in Baltimore , Maryl and . PARTICIPANTS Forty-one primary care physicians and 279 hypertension patients . INTERVENTIONS Physician communication skills training and patient coaching by community health workers . MAIN MEASURES Physician communication behaviors ; patient ratings of physicians ’ participatory decision-making ( PDM ) , patient involvement in care ( PIC ) , reported adherence to medications ; systolic and diastolic blood pressure ( BP ) and BP control . KEY RESULTS Visits of trained versus control group physicians demonstrated more positive communication change scores from baseline ( −0.52 vs. −0.82 , p = 0.04 ) . At 12 months , the patient+physician intensive group compared to the minimal intervention group showed significantly greater improvements in patient report of physicians ’ PDM ( β = + 6.20 vs. −5.24 , p = 0.03 ) and PIC dimensions related to doctor facilitation ( β = + 0.22 vs. −0.17 , p = 0.03 ) and information exchange ( β = + 0.32 vs. −0.22 , p = 0.005 ) . Improvements in patient adherence and BP control did not differ across groups for the overall patient sample . However , among patients with uncontrolled hypertension at baseline , non-significant reductions in systolic BP were observed among patients in all intervention groups — the patient+physician intensive ( −13.2 mmHg ) , physician intensive/patient minimal ( −10.6 mmHg ) , and the patient intensive/physician minimal ( −16.8 mmHg ) , compared to the patient+physician minimal group ( −2.0 mmHg ) . CONCLUSION Interventions that enhance physicians ’ communication skills and activate patients to participate in their care positively affect patient-centered communication , patient perceptions of engagement in care , and may improve systolic BP among urban African-American and low SES patients with uncontrolled hypertension |
12,030 | 23,777,192 | There was no difference to the face-to-face controls ( group treatment ) .
Sensitivity analysis revealed that there might be a publication bias regarding the comparison to the face-to-face control .
However , the results suggest that CBT self-help interventions are an effective treatment for tinnitus distress . | This study is a review and meta- analysis on the efficacy of cognitive-behavioural therapy ( CBT ) self-help interventions for tinnitus . | Publication bias , sometimes known as the " file-drawer problem " or " funnel-plot asymmetry , " is common in empirical research . The authors review the implication s of publication bias for quantitative research synthesis ( meta- analysis ) and describe existing techniques for detecting and correcting it . A new approach is proposed that is suitable for application to meta-analytic data sets that are too small for the application of existing methods . The model estimates parameters relevant to fixed-effects , mixed-effects or r and om-effects meta- analysis contingent on a hypothetical pattern of bias that is fixed independently of the data . The authors illustrate this approach for sensitivity analysis using 3 data sets adapted from a commonly cited reference work on research synthesis ( H. M. Cooper & L. V. Hedges , 1994 ) The effectiveness of a therapist-supported Internet intervention program for tinnitus distress in an industrial setting was evaluated using a cluster r and omised design . Fifty-six Australian employees of two industrial organisations were r and omly assigned , based on their work site ( 18 work sites from BP Australia and five from BHP Billiton ) , to either a cognitive behavioural therapy ( CBT ) program or an information-only control program . Participants were assessed at pre- and postprogram , measuring tinnitus distress , depression , anxiety , stress , quality of life , and occupational health . The CBT program was not found to be superior to the information program for treating tinnitus distress . A high attrition rate and small sample size limit the generalisability of the findings , and further developments of the program and assessment process are needed to enhance engagement and compliance BACKGROUND Although effective therapies for social phobia exist , many individuals refrain from seeking treatment owing to the embarrassment associated with help-seeking . Internet-based cognitive-behavioural self-help can be an alternative , but adherence is a problem . AIMS To evaluate a 9-week programme of internet-based therapy design ed to increase treatment adherence by the addition of short weekly telephone calls , nine in all , with a total duration of 95 min . METHOD In a r and omised controlled trial the effects of internet-based cognitive-behavioural therapy in the treatment group ( n=29 ) were compared with a waiting-list control group ( n=28 ) . RESULTS Compared with the control group the treated participants experienced greater reductions on measures of general and social anxiety , avoidance and depression . Adherence to treatment was high , with 93 % finishing the complete treatment package . One year later all improvements were maintained . CONCLUSIONS This study provides evidence to support the use of internet-based treatment supplemented by short , weekly telephone calls OBJECTIVE 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 Tinnitus distress can be reduced by means of cognitive-behavior therapy ( CBT ) , and the treatment can be delivered in different ways . The most recent format is Internet-based self-help . The aim of this study was to compare this treatment ( n= 26 ) with st and ard group-based CBT ( n=25 ) in a r and omized controlled trial . Outcomes on self-report inventories measuring tinnitus distress were evaluated immediately after and 1 year after treatment . Results showed that both groups had improved , and there were few differences between them . The effect size for the Internet treatment was d=0.73 ( 95 % CI=0.16 - 1.30 ) and for the group treatment was d=0.64 ( 95 % CI=0.07 - 1.21 ) . The Internet treatment consumed less therapist time and was 1.7 times as cost-effective as the group treatment . At pretreatment patients rated the Internet treatment as less credible than the group treatment . In conclusion , Internet treatment for tinnitus distress merits further investigation , as the outcomes achieved are promising 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 UNLABELLED We conducted a r and omized clinical trial to examine the relative effectiveness of two psychological interventions for treating tinnitus . People with tinnitus were initially offered a single session of psychoeducation about tinnitus , followed 2 months later by six weekly sessions of either mindfulness or relaxation training . Results indicated benefits from psychoeducation in reducing negative emotions , rumination and psychological difficulties of living with tinnitus . These effects were maintained or enhanced by mindfulness training that also emphasized acceptance , although they were eroded in the relaxation condition over the follow-up . Mediating processes are discussed , and suggestions for refining clinical interventions for this population are offered . KEY PRACTITIONER MESSAGE The present results suggest that mindfulness training might constitute a useful addition to psychoeducation for interventions targeting the psychological consequences of tinnitus The study compared the effects of Acceptance and Commitment Therapy ( ACT ) with Tinnitus Retraining Therapy ( TRT ) on tinnitus impact in a r and omised controlled trial . Sixty-four normal hearing subjects with tinnitus were r and omised to one of the active treatments or a wait-list control ( WLC ) . The ACT treatment consisted of 10 weekly 60 min sessions . The TRT treatment consisted of one 150 min session , one 30 min follow-up and continued daily use of wearable sound generators for a recommended period of at least 8h/day for 18 months . Assessment s were made at baseline , 10 weeks , 6 months and 18 months . At 10 weeks , results showed a superior effect of ACT in comparison with the WLC regarding tinnitus impact ( Cohen 's d=1.04 ) , problems with sleep and anxiety . The results were mediated by tinnitus acceptance . A comparison between the active treatments , including all assessment points , revealed significant differences in favour of ACT regarding tinnitus impact ( Cohen 's d=0.75 ) and problems with sleep . At 6 months , reliable improvement on the main outcome measure was found for 54.5 % in the ACT condition and 20 % in the TRT condition . The results suggest that ACT can reduce tinnitus distress and impact in a group of normal hearing tinnitus patients BACKGROUND Chronic tinnitus is a frequent symptom presentation in clinical practice . No drug treatment to date has shown itself to be effective . The aim of the present study was to investigate the effects of cognitive behavioural therapy and meditation in tinnitus sufferers . METHODOLOGY Patients were selected from a dedicated tinnitus clinic in the Welsh Hearing Institute . A waiting list control design was used . Twenty-five chronic tinnitus sufferers were consecutively allocated to two groups , one receiving a cognitive behavioural therapy/meditation intervention of four one hour sessions with the other group waiting three months and subsequently treated in the same way , thereby acting as their own control . The main outcome was measured using the Hallam tinnitus question naire . A four to six month follow up was conducted . RESULTS These showed significant statistical reductions in tinnitus variables both in the active and also in the control group . Post-therapy , no significant change was found after the waiting list period . The improvement was maintained at the four to six month period . CONCLUSION The positive findings give support for the use of cognitive behavioural therapy/meditation for chronic tinnitus sufferers Acute tinnitus can lead to substantial distress and eventually result in long-lasting impairment . The aim of this study was to compare the efficacy of a cognitive-behavioural intervention ( delivered as Internet self-management , bibliotherapy or group training ) to the information-only control condition . Applicants suffered from subjective tinnitus for up to six months , were between 18 and 75 years old and received no other tinnitus-related psychological treatment . A total of 304 participants were r and omly assigned to one of the four study arms . Tinnitus distress , depressive symptoms , psychosomatic discomfort and treatment satisfaction were assessed . At the post- assessment tinnitus distress was significantly lower in the Internet and the group training conditions compared to the control condition . Inter-group effect sizes were moderate to large . At follow-up , all active training conditions showed significantly reduced tinnitus distress compared to the control condition ( intention-to-treat analysis ) . An additional completer analysis showed a significant reduction in tinnitus distress only for the group condition . All effect sizes were moderate . There were no differences regarding psychosomatic discomfort , but depressive symptoms were reduced in the group condition at the post- assessment ( intention-to-treat analysis ) . Treatment satisfaction was significantly higher in the training conditions . The dropout rate was 39 % . The present study shows that distress can be reduced as early as the acute stadium and that minimal-contact interventions are a promising way to do this . In particular , the Internet and group conditions led to a large , immediate decrease in distress , and the participants were highly satisfied with the training In this study conducted in the French-speaking part of Switzerl and , 52 individuals with social phobia were r and omly assigned either to an Internet-based cognitive-behavioral treatment with minimal contact with therapists via e-mail or to a waiting-list control group . Significant differences between the two groups were found at posttreatment on all primary outcome measures ( social anxiety measures ) and on two of the secondary outcome measures ( general symptomatology , therapy goal attainment ) . On average , within-groups effect sizes were large for the primary outcomes ( Cohen 's d=0.82 ) and for secondary outcomes ( Cohen 's d=1.04 ) . Moreover , subjects in the treatment group fulfilled the criteria of clinical ly significant improvement significantly more often than subjects in the control group on all measured dimensions ( 58 % vs. 20 % ) . Users ' acceptance of the program was high . The results from the present study lend further support to the hypothesis that Internet-delivered interventions with minimal therapist contact are a promising treatment approach to social phobia 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 BACKGROUND Counselling is a basic psychological intervention for chronic tinnitus the effectiveness of which has not yet been evaluated . SCIENTIFIC QUESTION The therapeutic effect of counselling was compared to that of a self-help manual . Outcome was analysed for tinnitus disability , tendency to become chronic , and accompanying psychiatric disorders . METHODS A total of 75 tinnitus out patients were r and omly assigned to group counselling ( n=35 ) and self-help ( n=40 ) . Tinnitus disability , general psychological disturbances , depression , anxiety , coping and illness beliefs were measured using question naires ( TQ , SCL-90-R , BDI , BAI , FKV , KKG ) administered before and after treatment and at a 6-month follow-up . Psychiatric disorders ( DSM-IV ) were assessed using the CIDI . RESULTS Counselling and the self-help manual had a significant effect on tinnitus disability , showing most profit for participants with a high level of tinnitus distress . The significant reduction in tinnitus distress was maintained at the 6-month follow-up . There was , however , no difference between the two treatment-groups . Effect-sizes for patients with DSM-IV-diagnoses were smaller . CONCLUSION For tinnitus out patients without psychiatric comorbidity , self-help manuals can be an effective first treatment Internet‐based interventions with therapist support have proven effective for treating a range of mental health conditions . This study examined whether frequency of therapist contact affected treatment outcomes . Fifty‐seven people with panic disorder ( including 32 with agoraphobia ) were r and omly allocated to an 8‐week Internet‐based cognitive behavioural treatment intervention ( Panic Online ) with either frequent ( three e‐mails per week ) or infrequent ( one e‐mail per week ) support from a psychologist . Posttreatment , intention‐to‐treat analyses revealed that both treatments were effective at improving panic disorder and agoraphobia severity ratings , panic‐related cognitions , negative affect , and psychological and physical quality of life domains , with no differences between conditions . High end‐state functioning was achieved by 28.6 % of the frequent and infrequent participants , respectively . Therapist alliance , treatment credibility , and satisfaction also did not differ between groups , despite significantly greater therapist time invested in the frequent contact condition . The results provide evidence that the effectiveness of Internet‐based mental health interventions may be independent of the frequency of therapist support and may , therefore , be more cost‐effective than previously reported OBJECTIVE Our aim in this r and omized controlled trial was to investigate the effects on global tinnitus severity of 2 Internet-delivered psychological treatments , acceptance and commitment therapy ( ACT ) and cognitive behavior therapy ( CBT ) , in guided self-help format . METHOD Ninety-nine participants ( mean age = 48.5 years ; 43 % female ) who were significantly distressed by tinnitus were recruited from the community . Participants were r and omly assigned to CBT ( n = 32 ) , ACT ( n = 35 ) , or a control condition ( monitored Internet discussion forum ; n = 32 ) , and they were assessed with st and ardized self-report measures ( Tinnitus H and icap Inventory ; Hospital Anxiety and Depression Scale ; Quality of Life Inventory ; Perceived Stress Scale ; Tinnitus Acceptance Question naire ) at pre- , posttreatment ( 8 weeks ) , and 1-year follow-up . RESULTS Mixed-effects linear regression analysis of all r and omized participants showed significant effects on the primary outcome ( Tinnitus H and icap Inventory ) for CBT and for ACT compared with control at posttreatment ( 95 % CI [ -17.03 , -2.94 ] , d = 0.70 , and 95 % CI [ -16.29 , -2.53 ] , d = 0.68 , respectively ) . Within-group effects were substantial from pretreatment through 1-year-follow-up for both treatments ( 95 % CI [ -44.65 , -20.45 ] , d = 1.34 ) , with no significant difference between treatments ( 95 % CI [ -14.87 , 11.21 ] , d = 0.16 ) . CONCLUSIONS Acceptance-based procedures may be a viable alternative to traditional CBT techniques in the management of tinnitus . The Internet can improve access to psychological interventions for tinnitus |
12,031 | 28,002,636 | There is very low- to moderate- quality evidence that CME may be a valuable intervention to augment the pallet of therapeutic options for stroke rehabilitation .
Future high- quality research should determine whether CME interventions are (cost-)effective | BACKGROUND Stroke is a major cause of long-term disability in adults .
Several systematic review s have shown that a higher intensity of training can lead to better functional outcomes after stroke .
Currently , the re sources in inpatient setting s are not always sufficient and innovative methods are necessary to meet these recommendations without increasing healthcare costs .
A re source efficient method to augment intensity of training could be to involve caregivers in exercise training .
A caregiver-mediated exercise programme has the potential to improve outcomes in terms of body function , activities , and participation in people with stroke .
In addition , caregivers are more actively involved in the rehabilitation process , which may increase feelings of empowerment with reduced levels of caregiver burden and could facilitate the transition from rehabilitation facility ( in hospital , rehabilitation centre , or nursing home ) to home setting .
As a consequence , length of stay might be reduced and early supported discharge could be enhanced .
OBJECTIVES To determine if caregiver-mediated exercises ( CME ) improve functional ability and health-related quality of life in people with stroke , and to determine the effect on caregiver burden . | OBJECTIVES To assess multiple psychometric characteristics of a new stroke outcome measure , the Stroke Impact Scale ( SIS ) , using Rasch analysis , and to identify and remove misfitting items from the 8 domains that comprise the SIS . DESIGN Secondary analysis of 3-month outcomes for the Glycine Antagonist in Neuroprotection ( GAIN ) Americas r and omized stroke trial . SETTING A multicenter r and omized trial performed in 132 centers in the United States and Canada . PARTICIPANTS A total of 696 individuals with stroke who were community-dwelling and independent prior to acute stroke . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Rasch analysis was performed using WINSTEPS , version 3.31 , to evaluate 4 psychometric characteristics of the SIS : ( 1 ) unidimensionality or fit ( the extent to which items measure a single construct ) , ( 2 ) targeting ( the extent to which the items are of appropriate difficulty for the sample ) , ( 3 ) item difficulty ( the ordering of items from least to most difficult to perform ) , and ( 4 ) separation ( the extent to which the items distinguish distinct levels of functioning within the sample ) . RESULTS ( 1 ) Within each domain , most of the items measured a single construct . Only 3 items misfit the constructs and were deleted ( " add and subtract numbers , " " get up from a chair , " " feel emotionally connected " ) and 2 items ( " h and le money , " " manage money " ) misfit the combined physical domain . These items were deleted to create SIS , version 3.0 . ( 2 ) Overall , the items are well targeted to the sample . The physical and participation domains have a wide range of items that capture difficulties that most individuals with stroke experience in physical and role functions , while the memory , emotion , and communication domains include items that capture limitations in the most impaired patients . ( 3 ) The order of items from less to more difficult was clinical ly meaningful . ( 4 ) The individual physical domains differentiated at least 3 ( high , average , low ) levels of functioning and the composite physical domain differentiated more than 4 levels of functioning . However , because difficulties with communication , memory , and emotion were not as frequently reported and difficulties with h and function were more frequently reported , these domains only differentiated 2 ( high , low ) to 3 ( high , average , low ) strata of patients . Time from stroke onset to administration of the SIS had little effect on item functioning . CONCLUSION Rasch analysis further established the validity of the SIS . The domains are unidimensional , the items have an excellent range of difficulty , and the domain scores differentiated patients into multiple strata . The activities of daily living/instrumental activities of daily living , mobility , strength , composite physical , and participation domains have the most robust psychometric characteristics . The composite physical domain is most able to discriminate difficulty in function in individuals after stroke , while the communication , memory , and emotion domain items only capture limitations in function in the more impaired groups of patients Background and Purpose — This study compared the psychometric properties of 3 clinical balance measures , the Berg Balance Scale ( BBS ) , the Balance subscale of the Fugl-Meyer test ( FM-B ) , and the Postural Assessment Scale for Stroke Patients ( PASS ) , in stroke patients with a broad range of neurological and functional impairment from the acute stage up to 180 days after onset . Methods — One hundred twenty-three stroke patients were followed up prospect ively with the 3 balance measures 14 , 30 , 90 , and 180 days after stroke onset ( DAS ) . Reliability ( interrater reliability and internal consistency ) and validity ( concurrent validity , convergent validity , and predictive validity ) of each measure were examined . A comparison of the responsiveness of each of the 3 measures was made on the basis of the entire group of patients and 3 separate groups classified by degree of neurological severity . Results — The FM-B and BBS showed a significant floor or ceiling effect at some DAS points , whereas the PASS did not show these effects . The BBS , FM-B , and PASS all had good reliability and validity for patients at different recovery stages after stroke . The results of effect size demonstrated fair to good responsiveness of all 3 measures within the first 90 DAS but , as expected , only a low level of responsiveness at 90 to 180 DAS . The PASS was more responsive to changes in severe stroke patients at the earliest period after stroke onset , 14 to 30 DAS . Conclusions — All 3 measures tested showed very acceptable levels of reliability , validity , and responsiveness for both clinicians and research ers . The PASS showed slightly better psychometric characteristics than the other 2 measures OBJECTIVE The objective of this study was to evaluate the strengths and weaknesses of a group support program and a home visiting program for family caregivers of stroke patients . It also examined the best fit between intervention variant and family caregiver and patient characteristics . van den Heuvel 's previous effect study showed positive effects of the same intervention program , but unlike our present study differences between the two support variants could not be measured . METHODS Of 257 family caregivers who were included and r and omly assigned to an intervention variant or a control group , 127 family caregivers completed the intervention in either the group program or the home visiting program . RESULTS Evaluation data showed that both intervention variants had been helpful and feasible , but home visit participants missed peer contact and follow-up contacts were missed in both intervention programs . In comparison to the home visiting program , the group program participants showed more benefit especially with respect to informational and emotional components . Caregivers ' preference for type of intervention revealed that both types of intervention had its supporters . Those that preferred the group program could be clearly characterised : they were burdened , lived with a more psychologically h and icapped relative , were using active coping strategies more frequently or lived in a region which is considered to be more sociable . CONCLUSION The present study adds extensively to van den Heuvel 's effect study with respect to discriminative aspects of group and home intervention programs and their respective benefits for specific family caregiver groups . PRACTICE IMPLICATION S In order to suitably match an intervention type with specific caregiver characteristics the intervention provider should utilize caregiver self- selection or undertake professional screening of caregiver burden . Telephone contacts should be offered in addition to the interventions UNLABELLED Several studies showed that Constraint-Induced Movement Therapy ( CIMT ) leads to a lasting improvement of upper extremity function in chronic stroke patients . The original technique includes an intensive 2-week program with 6 hours of daily physiotherapy . Due to high expenses it is difficult to implement this concept in outpatient care . PURPOSE The objective of this study was to evaluate the effects of a 4-week homebased CIMT program among chronic stroke patients and to compare them with a 2-week CIMT program , based on the original technique . METHODS Seven adults with chronic stroke completed a newly developed variant of CIMT , performed at patients ' homes ( group1 , CIMThome ) , supervised by an instructed family member , constraint of unaffected h and for a target of 60 % of waking hours . The intervention was analysed with pre- , post-treatment and 6-month follow-up measurements . Effects on improvement in upper extremity function were compared with patients treated according to the original protocol ( group2 , CIMTclassic ) , supervised by a physiotherapist , constraint of unaffected h and for a target of 90 % of waking hours . RESULTS Patients from both groups showed almost identical improvement of their motor function according to scores on the Wolf Motor Function Test ( WMFT ) and the Motor Activity Log ( MAL ) immediately after the treatment period as well as at follow-up after 6 months . CONCLUSIONS Our study suggests that CIMThome is not only feasible but also as effective as CIMTclassic . This finding should be replicated in a larger prospect i ve r and omized trial to perform a non-inferiority analysis Background and Purpose — This proof-of-concept trial investigated the effects of an 8-week program of caregiver-mediated exercises commenced in hospital combined with tele-rehabilitation services on patient self-reported mobility and caregiver burden . Methods — Sixty-three hospitalized stroke patients ( mean age 68.7 , 64 % female ) were r and omly allocated to an 8-week caregiver-mediated exercises program with e-health support or usual care . Primary outcome was the Stroke Impact Scale mobility domain . Secondary outcomes included length of stay , other Stroke Impact Scale domains , readmissions , motor impairment , strength , walking ability , balance , mobility , ( extended ) activities of daily living , psychosocial functioning , self-efficacy , quality of life , and fatigue . Additionally , caregiver ’s self-reported fatigue , symptoms of anxiety , self-efficacy , and strain were assessed . Assessment s were completed at baseline and at 8 and 12 weeks . Results — Intention-to-treat analysis showed no between-group difference in Stroke Impact Scale mobility ( P=0.6 ) ; however , carers reported less fatigue ( 4.6 , confidence interval [ CI ] 95 % 0.3–8.8 ; P=0.04 ) and higher self-efficacy ( −3.3 , CI 95 % −5.7 to −0.9 ; P=0.01 ) at week 12 . Per- protocol analysis , examining those who were discharged home with tele-rehabilitation demonstrated a trend toward improved mobility ( −9.8 , CI 95 % −20.1 to 0.4 ; P=0.06 ) , significantly improved extended activities of daily living scores at week 8 ( −3.6 , CI 95 % −6.3 to −0.8 ; P=0.01 ) and week 12 ( 3.0 , CI 95 % −5.8 to −0.3 ; P=0.03 ) , a 9-day shorter length of stay ( P=0.046 ) , and fewer readmissions over 12 months ( P<0.05 ) . Conclusions — Caregiver-mediated exercises supported by tele-rehabilitation show promise to augment intensity of practice , result ing in improved patient-extended activities of daily living , reduced length of stay with fewer readmissions post stroke , and reduced levels of caregiver fatigue with increased feelings of self-efficacy . The current findings justify a larger definite phase III r and omized controlled trial . Clinical Trial Registration — URL : http://www.anzctr.org.au . Unique identifier : ACTRN12613000779774 Background Most acute stroke patients with disabilities do not receive recommended rehabilitation following discharge to the community . Functional and social barriers are common reasons for non-adherence to post-discharge rehabilitation . Home rehabilitation is an alternative to centre-based rehabilitation but is costlier . Tele-rehabilitation is a possible solution , allowing for remote supervision of rehabilitation and eliminating access barriers . The objective of the Singapore Tele-technology Aided Rehabilitation in Stroke ( STARS ) trial is to determine if a novel tele-rehabilitation intervention for the first three months after stroke admission improves functional recovery compared to usual care . Methods / design This is a single blind ( evaluator blinded ) , parallel , two-arm r and omised controlled trial study design involving 100 recent stroke patients . The inclusion criteria are age ≥40 years , having caregiver support and recent stroke defined as stroke diagnosis within 4 weeks . Consenting participants will be r and omized with varying block size of 4 or 6 assuming a 1:1 treatment allocation with the participating centre as the stratification factor . The baseline assessment will be done within 4 weeks of stroke onset , followed by follow-up assessment s at 3 and 6 months . The tele-rehabilitation intervention lasts for 3 months and includes exercise 5-days-a-week using an iPad-based system that allows recording of daily exercise with video and sensor data and weekly video-conferencing with tele-therapists after data review . Those allocated to the control group will receive usual care . The primary outcome measure is improvement in life task ’s social activity participation at three months as measured by the disability component of the Jette Late Life Functional and Disability Instrument ( LLFDI ) . Secondary outcome variables consist of gait speed ( Timed 5-Meter Walk Test ) and endurance ( Two-Minute Walk test ) , performance of basic activities of daily living ( Shah-modified Barthel Index ) , balance confidence ( Activities-Specific Balance Confidence Scale ) , patient self-reported health-related quality -of-life [ Euro-QOL ( EQ-5D ) ] , health service utilization ( Singapore Stroke Study Health Service Utilization Form ) and caregiver reported stress ( Zarit Caregiver Burden Inventory ) . Discussion The goal of this trial is to provide evidence on the potential benefit and cost-effectiveness of this novel tele-rehabilitation programme which will guide health care decision-making and potentially improve performance of post-stroke community-based rehabilitation . Trial Registration This trial protocol was registered under Clinical Trials.gov on 18 July 2013 as study title “ The Singapore Tele-technology Aided Rehabilitation in Stroke ( STARS ) Study ” ( ID : The STARS Study , Clinical Trials.gov Identifier : NCT01905917 ) Background and Purpose — One way that stroke units may improve outcome is by reducing complications of immobility through early mobilization ; however , this intervention needs testing . The purpose of this study was to determine the physical activity patterns of stroke patients managed within acute stroke units as a first step in developing an early mobilization protocol . Methods — We recruited 64 patients within 14 days after stroke from 5 metropolitan stroke units and observed them for 2 consecutive days at 10-minute intervals between the hours of 8 am and 5 pm . At each observation , we ascertained physical activity , location , and other person(s ) present . Therapists recorded therapy details . Results — The 58 patients who completed the study had a mean age of 71.3 years . Stroke severity ranged from mild ( National Institutes of Health Stroke Scale score , 1 ) to severe ( score , 27 ) , and mean time after stroke at observation was 5.6 days ( range , 0 to 13 days ) . Only 9 patients were restricted to bed . During the therapeutic day , patients spent > 50 % resting in bed , 28 % sitting out of bed , and only 13 % engaged in activities with the potential to prevent complications and improve recovery of mobility . Patients were alone > 60 % of the time . Conclusions — This is the first multicenter study of physical activity early after stroke . We believe the next step is to conduct a r and omized controlled trial to evaluate the effect of increased levels of physical activity early after stroke compared with current st and ards of care Background : The purpose of this study was to clarify the effects of voluntary training with family participation in addition to conventional rehabilitation for stroke patients . Methods / Design : The subjects were 49 first-time stroke patients with severe hemiplegia . They were divided into two groups : a family participation group , in which voluntary training was performed with family members ( 21 patients ) , and a nonfamily participation group , in which voluntary training was performed with a physical therapist ( 28 patients ) . The groups were compared by background , cognitive and physical function , postadmission course , and outcome . Results : There were shortened lengths of stay and higher rates of home discharge in family participation group , but no differences in functional recovery . Conclusions : Voluntary training with family participation was effective in shortening the length of hospital stay and in improving the rate of home discharge in a convalescent rehabilitation ward Background and Purpose — Additional exercise therapy has been shown to have a positive impact on function after acute stroke and research is now focusing on methods to increase the amount of therapy that is delivered . This r and omized controlled trial examined the impact of additional family-mediated exercise ( FAME ) therapy on outcome after acute stroke . Methods — Forty participants with acute stroke were r and omly assigned to either a control group who received routine therapy with no formal input from their family members or a FAME group , who received routine therapy and additional lower limb FAME therapy for 8 weeks . The primary outcome measure used was the lower limb section of the Fugl-Meyer Assessment modified by Lindmark . Other measures of impairment , activity , and participation were completed at baseline , postintervention , and at a 3-month follow-up . Results — Statistically significant differences in favor of the FAME group were noted on all measures of impairment and activity postintervention ( P<0.05 ) . These improvements persisted at the 3-month follow-up but only walking was statistically significant ( P<0.05 ) . Participants in the FAME group were also significantly more integrated into their community at follow-up ( P<0.05 ) . Family members in the FAME group reported a significant decrease in their levels of caregiver strain at the follow-up when compared with those in the control group ( P<0.01 ) . Conclusions — This evidence -based FAME intervention can serve to optimize patient recovery and family involvement after acute stroke at the same time as being mindful of available re sources Objective : Unilateral spatial neglect ( USN ) is one of the major behavioral disturbances in patients with cerebral lesions and often impairs the patients ’ independence in activities of daily living ( ADL ) . Although many studies have addressed the mechanism and assessment of USN , there have been only few reports on rehabilitation strategies for patients with USN . The present study examined whether family participation can contribute to an improvement in USN following an acute stroke . Design : This study compared the improvement at 3 weeks among patients treated with conventional exercise sessions and a program including the participation of family members . The study followed 34 stroke patients with hemiparesis and USN . Twenty had family participation in their therapy . The severity of USN was measured using the Behavioral Inattention Test ( BIT ) and a laterality index ( LI ) . Mobility was assessed using the Rivermead Mobility Index ( RMI ) , and ADL were assessed using the Barthel index . Results : The results showed a relationship between BIT score improvement and family participation , and the BIT score improvement reflected the LI improvement . The RMI and BIT scores showed that ADL improved more with than without family participation . Conclusion : Family participation improved not only the mobility but also USN , suggesting that it can make important contributions to acute stroke rehabilitation Background Stroke leads to constant rehabilitation needs even at the chronic stage . However , although many stroke patients receive physical or occupational therapy in primary health care , treatment prescriptions do not generally specify therapeutic goals ; in particular , participation is not established as an explicit therapeutic goal in the ambulatory setting . The primary aim of this study is to evaluate the efficacy of a therapy regimen for chronic stroke patients ( modified ‘ constraint-induced movement therapy ( CIMT ) at home ’ ) with impaired h and or arm function with regard to the prerequisites of participation in everyday activities : a sufficient arm and h and function . ‘ CIMT at home ’ will be compared with conventional physical and occupational therapy ( ‘ therapy as usual ’ ) . Methods / design The study is a parallel cluster r and omized controlled trial with therapy practice s as clusters ( n = 48 ) . After written consent from the patients ( n = 144 ) , the therapists will be r and omly assigned to treat either the intervention or the control group . Blinded external assessors will evaluate the patients using st and ardized outcome measures before and after the intervention , and six months later . The two co primary endpoint assessment s of arm and h and function as prerequisites for participation ( defined as equal involvement in activities of daily living ) are the motor activity log ( quality of arm and h and use ) and the Wolf motor function test ( arm and h and function ) . These assessment s are made four weeks post-treatment and relativized to baseline performance . Changes in primary outcomes will be analyzed with mixed models , which consider the hierarchical structure of the data and will be adjusted to the baseline measurements and sex . The primary analysis will be the comparison of the two r and omized groups , with respect to the adjusted averages for each of the two co primary endpoints . To keep an overall significance level of 5 % , the two endpoints will be tested at the significance level of 5 % each in hierarchical order . Discussion A modification of the CIMT , feasible in the patients ’ homes ( CIMT at home ) , appears to be a promising therapeutic approach in the ambulatory care of chronic stroke patients . With proven efficacy and practicality , a participation-oriented , stroke-specific treatment would be available in primary care . Trial registration Clinical Trials.gov Background Stroke is a leading cause of disability among adults worldwide . Evidence suggests that increased duration of exercise therapy following stroke has a positive impact on functional outcome following stroke . The main objective of this r and omised controlled trial is to evaluate the impact of additional family assisted exercise therapy in people with acute stroke . Methods / Design A prospect i ve multi-centre single blind r and omised controlled trial will be conducted . Forty patients with acute stroke will be r and omised into either an experimental or control group . The experimental group will receive routine therapy and additional lower limb exercise therapy in the form of family assisted exercises . The control group will receive routine therapy with no additional formal input from their family members . Participants will be assessed at baseline , post intervention and followed up at three months using a series of st and ardised outcome measures . A secondary aim of the project is to evaluate the impact of the family mediated exercise programme on the person with stroke and the individual(s ) assisting in the delivery of exercises using a qualitative methodology . The study has gained ethical approval from the Research Ethics Committees of each of the clinical sites involved in the study . Discussion This study will evaluate a structured programme of exercises that can be delivered to people with stroke by their ' family members/friends ' . Given that the progressive increase in the population of older people is likely to lead to an increased prevalence of stroke in the future , it is important to reduce the burden of this illness on the individual , the family and society . Family mediated exercises can maximise the carry over outside formal physiotherapy sessions , giving patients the opportunity for informal practice .Trial Registration The protocol for this study is registered with the US NIH Clinical trials registry ( NCT00666744 Introduction The current study aims to investigate the effects of primary caregiver participation in vestibular rehabilitation ( VR ) on improving the measures of neglect , activities of daily living ( ADL ) , balance , and falls of unilateral neglect ( UN ) patients . Methods This study is a single-blind r and omized controlled trial . Both experimental ( n = 24 ) and control groups ( n = 24 ) received conventional rehabilitation . The experimental group undertook VR for a month . During the first and second weeks , a registered nurse trained the experimental group in VR . The primary caregivers in the experimental group supervised and guided their patients in VR during the third and fourth weeks . The outcome measures were neglect , ADL , balance , and falls . Results The two groups of UN patients showed a significant improvement in neglect , ADL , and balance over time . Based on the generalized estimating equations model , an interaction was observed between groups and times . Significant interactions were observed between the VR group at days 14 and 28 in the areas of neglect , ADL , and balance . No significant difference was observed between the two groups in the number of falls . Conclusion Neglect , ADL , and balance among UN patients with right hemispheric stroke can be improved through the participation of primary caregivers in VR . Trained informal caregivers were recommended to provide VR guidance and supervision to patients who suffer from UN BACKGROUND AND PURPOSE To be useful for clinical research , an outcome measure must be feasible to administer and have sound psychometric attributes , including reliability , validity , and sensitivity to change . This study characterizes the psychometric properties of the Stroke Impact Scale ( SIS ) Version 2.0 . METHODS Version 2.0 of the SIS is a self-report measure that includes 64 items and assesses 8 domains ( strength , h and function , ADL/IADL , mobility , communication , emotion , memory and thinking , and participation ) . Subjects with mild and moderate strokes completed the SIS at 1 month ( n=91 ) , at 3 months ( n=80 ) , and at 6 months after stroke ( n=69 ) . Twenty-five subjects had a replicate administration of the SIS 1 week after the 3-month or 6-month test . We evaluated internal consistency and test-retest reliability . The validity of the SIS domains was examined by comparing the SIS to existing stroke measures and by comparing differences in SIS scores across Rankin scale levels . The mixed model procedure was used to evaluate responsiveness of the SIS domain scores to change . RESULTS Each of the 8 domains met or approached the st and ard of 0.9 alpha-coefficient for comparing the same patients across time . The intraclass correlation coefficients for test-retest reliability of SIS domains ranged from 0.70 to 0.92 , except for the emotion domain ( 0.57 ) . When the domains were compared with established outcome measures , the correlations were moderate to strong ( 0.44 to 0.84 ) . The participation domain was most strongly associated with SF-36 social role function . SIS domain scores discriminated across 4 Rankin levels . SIS domains are responsive to change due to ongoing recovery . Responsiveness to change is affected by stroke severity and time since stroke . CONCLUSIONS This new , stroke-specific outcome measure is reliable , valid , and sensitive to change . We are optimistic about the utility of measure . More studies are required to evaluate the SIS in larger and more heterogeneous population s and to evaluate the feasibility and validity of proxy responses for the most severely impaired patients Background Family caregivers provide invaluable support to stroke survivors during their recovery , rehabilitation , and community re-integration . Unfortunately , it is not st and ard clinical practice to prepare and support caregivers in this role and , as a result , many experience stress and poor health that can compromise stroke survivor recovery and threaten the sustainability of keeping the stroke survivor at home . We developed the Timing it Right Stroke Family Support Program ( TIRSFSP ) to guide the timing of delivering specific types of education and support to meet caregivers ’ evolving needs . The objective of this multi-site r and omized controlled trial is to determine if delivering the TIRSFSP across the stroke care continuum improves caregivers ’ sense of being supported and emotional well-being . Methods / design Our multi-site single-blinded r and omized controlled trial will recruit 300 family caregivers of stroke survivors from urban and rural acute care hospitals . After completing a baseline assessment , participants will be r and omly allocated to one of three groups : 1 ) TIRSFSP guided by a stroke support person ( health care professional with stroke care experience ) , delivered in-person during acute care and by telephone for approximately the first six to 12 months post-stroke , 2 ) caregiver self-directed TIRSFSP with an initial introduction to the program by a stroke support person , or 3 ) st and ard care receiving the educational re source “ Let ’s Talk about Stroke ” prepared by the Heart and Stroke Foundation . Participants will complete three follow-up quantitative assessment s 3 , 6 , and 12-months post-stroke . These include assessment s of depression , social support , psychological well-being , stroke knowledge , mastery ( sense of control over life ) , caregiving assistance provided , caregiving impact on everyday life , and indicators of stroke severity and disability . Qualitative methods will also be used to obtain information about caregivers ’ experiences with the education and support received and the impact on caregivers ’ perception of being supported and emotional well-being . Discussion This research will determine if the TIRSFSP benefits family caregivers by improving their perception of being supported and emotional well-being . If proven effective , it could be recommended as a model of stroke family education and support that meets the Canadian Stroke Best Practice Guideline recommendation for providing timely education and support to families through transitions . Trial registration Clinical Trials.gov : NCT00958607 BACKGROUND AND PURPOSE To improve the accuracy of early postonset prediction of motor recovery in the flaccid hemiplegic arm , the effects of change in motor function over time on the accuracy of prediction were evaluated , and a prediction model for the probability of regaining dexterity at 6 months was developed . METHODS In 102 stroke patients , dexterity and paresis were measured with the Action Research Arm Test , Motricity Index , and Fugl-Meyer motor evaluation . For model development , 23 c and i date determinants were selected . Logistic regression analysis was used for prognostic factors and model development . RESULTS At 6 months , some dexterity in the paretic arm was found in 38 % , and complete functional recovery was seen in 11.6 % of the patients . Total anterior circulation infa rcts , right hemisphere strokes , homonymous hemianopia , visual gaze deficit , visual inattention , and paresis were statistically significant related to a poor arm function . Motricity Index leg scores of at least 25 points in the first week and Fugl-Meyer arm scores of 11 points in the second week increasing to 19 points in the fourth week raised the probability of developing some dexterity ( Action Research Arm Test > or=10 points ) from 74 % ( positive predictive value [ PPV ] , 0.74 ; 95 % confidence interval [ CI ] , 0.63 to 0.86 ) to 94 % ( PPV , 0.83 ; 95 % CI , 0.76 to 0.91 ) at 6 months . No change in probabilities of prediction dexterity was found after 4 weeks . CONCLUSIONS Based on the Fugl-Meyer scores of the flaccid arm , optimal prediction of arm function outcome at 6 months can be made within 4 weeks after onset . Lack of voluntary motor control of the leg in the first week with no emergence of arm synergies at 4 weeks is associated with poor outcome at 6 months Objective : To ” nd patient characteristics in the early post stroke phase that could predict three years functional outcome . Design : Prospect i ve study . Setting : In-hospital rehabilitation department ( admission and discharge ) . Outpatient department one and three years post stroke . Subjects : One hundred and forty-two stroke patients ( 56 % women ) , median age 75 years . Main outcome measures : Barthel Index ( BI ) score ; BI score change ; accommodation status ; Rankin scale score ; and Frenchay Activities Index ( FAI ) score , all registered three years post stroke . Results : The percentages of patients still living at home after one and three years were 88 % and 83 % , respectively . Twenty per cent of the patients had deteriorated according to the BI after three years , mostly due to recurrent strokes ( odds ratio ( OR ) 10.3 ; 95 % con”dence interval ( CI ) 3.0–35.5 ) and co-morbidity with other disabling disorders ( OR 3.9 ; CI 1.1–13.5 ) . Co-morbidity also emerged as an important risk factor for dependency according to BI score ( OR 8.8 ; CI 2.4–32.1 ) as well as for a poor FAI score ( OR 4.9 ; CI 1.9–13.0 ) . BI in the early phase was the strongest predictor for long-term functional outcome . Urinary incontinence emerged as a risk factor for nursing home placement after three years ( OR 3.2 ; CI 0.9–11.3 ) . Cognitive dysfunction was a risk factor for poor FAI scoring ( OR 2.7 ; CI 1.0–7.0 ) . Conclusions : After stroke rehabilitation , concomitant chronic disabling disorders and recurrent strokes seem to play an important role regarding dependency , h and icap and long-term functional decline Objective : To determine the rate , degree , and predictors of recovery from disabling ischemic stroke . Methods : Patients with ischemic stroke enrolled in the Management of Atherothrombosis With Clopidogrel in High-Risk Patients ( MATCH ) study underwent long-term prospect i ve assessment of their modified Rankin Scale ( mRS ) score . Disability ( functionally dependent state ) was defined as mRS ≥ 3 , and recovery ( functionally independent state ) was defined as mRS < 3 . The timing and the independent predictors of recovery were determined using a Cox proportional hazards multiple regression analysis . Results : Of 7,599 patients enrolled with ischemic stroke or TIA , 1,662 ( 21.8 % ) were disabled ( mRS ≥ 3 ) at baseline ( median of 14 [ 0 to 96 ] days after stroke onset ) . Disability was moderate ( mRS 3 ) in 931 ( 56 % ) patients , severe ( mRS 4 ) in 691 ( 42 % ) , and very severe ( mRS 5 ) in 40 ( 2 % ) . By 18 months , 877 ( 52.8 % , 95 % CI 50 % to 55 % ) patients had recovered , 589 ( 63 % , 60 % to 66 % ) with moderate disability , 281 ( 41 % , 37 % to 44 % ) with severe disability , and 7 ( 17 % , 7 to 33 % ) with very severe disability . Median time to recovery was 3 months for patients with moderate disability and 18 months for severe disability ; 82.5 % of severely disabled patients remained so at 18 months . Predictors of recovery were moderate disability ( mRS 3 ) at baseline compared with severe ( mRS 4 : hazard ratio [ HR ] 2.13 , 1.86 to 2.44 ) or very severe disabling stroke ( HR 5.88 , 2.86 to 12.5 ) ; younger women ( aged < 65 years , compared with ≥75 years ; HR 1.85 , 1.47 to 2.33 ) ; decreasing time ( days ) between the qualifying event and the baseline assessment ( HR 1.01 , 1.01 to 1.02 ) ; and the absence of previous ischemic stroke ( HR 1.61 , 1.35 to 1.92 ) , concurrent peripheral artery disease ( HR 1.61 , 1.23 to 2.13 ) , or diabetes ( HR 1.30 , 1.10 to 1.54 ) . Conclusions : Half of patients with disabling ischemic stroke recovered within 18 months , and recovery was greatest within 6 months . Significant predictors of recovery included the severity of the index stroke and no history of ischemic stroke , peripheral artery disease , or diabetes Background Initial severity of upper-limb motor impairment and exercise intensity are important predictors of improved upper-limb function during stroke rehabilitation . Initial severity of motor impairment , however , is not modifiable by rehabilitation , and increased one-on-one treatment is not always feasible . Alternative methods to increase intensity and improve upper-limb function are needed . Objective The purpose of this study was to examine caregiver involvement in upper-limb treatment as a method to improve upper-limb function . Design This study was a secondary analysis of a multi-site r and omized controlled trial for upper-limb recovery during subacute inpatient stroke rehabilitation . Methods Data from 50 individuals with subacute stroke who were r and omly assigned to the experimental group ( upper-limb exercise ) were used for the analysis . Outcome variables were measured at baseline and at completion of the 4-week intervention . Group comparisons between participants with caregiver support and participants without caregiver support were done using an analysis of variance . Using the Fugl-Meyer Upper-Limb Motor Impairment Scale and time spent in treatment ( intensity ) as covariates , a multivariate regression analysis was performed to determine the additive value of caregiver support on upper-limb function , as measured by change scores on the Chedoke Arm and H and Activity Inventory and the Motor Activity Log . Results Group comparisons revealed that participants with caregiver support had improved upper-limb function compared with those without caregiver support and were more likely to increase the amount of time spent doing exercise . The multiple regression analysis showed that Fugl-Meyer score , treatment intensity , and caregiver support were significant predictors of upper-limb improvement ( R2=.240–.292 ) . In the regression models , caregiver support accounted for 5 % to 9 % of upper-limb improvement . Limitations Support was coded as a dichotomous variable , and thus the degree of support or qualitative nature of support was not captured . Conclusions Involvement of caregivers was a determinant of improved upper-limb function over and above initial severity of motor impairment and exercise intensity . Further research is needed to determine the optimal qualitative and quantitative elements of caregiver involvement in stroke rehabilitation in order to maximize results Objective : To investigate an intensified transition concept between neurological inpatient rehabilitation and home care for long-term effects on the care situation two and a half years after stroke patients ' discharge . Design : Controlled clinical trial allocating patients to intervention group ( intensified transition on ward II ) or control group ( st and ard transition on ward I ) ; patients were allocated to whichever ward had a vacancy . The last follow-up assessment was carried out on average 31 months after discharge . Intervention : The intensified transition concept consisted of therapeutic weekend care , bedside teaching and structured information for relatives during the second phase of the rehabilitation . Subjects : Seventy-one patients and their family carers were included , of which one case dropped out . Therefore 70 family carers - 35 individuals in each group - were available for assessment at long-term follow-up . Data collection : Family carers were asked via telephone whether the patient was still alive and if so , where he or she is living - at home or in a nursing home . Statistical methods : Binary logistic regression analysis with the care situation ( home care versus institutionalized care or deceased ) as dependent variable . Results : Two and a half years after discharge ( T3 ) in the intervention group significantly fewer patients were institutionalized ( 2 versus 5 ) or deceased ( 4 versus 11 ) ( P = 0.010 ) . Multivariate analysis showed that besides a higher functional life quality at discharge and lower patient 's age , the participation in the intensified transition programme is the third significant predictor for home care at T3 . Conclusion : Effects of an intensified transition programme can persist over a long-term period . They can sustain home care by reducing institutionalization and mortality Background Birthing in health facilities in India has increased over the last few years , yet maternal and neonatal mortality rates remain high . Clinical mentoring with case sheets or checklists for nurses is viewed as essential for on-going knowledge transfer , particularly where basic training is inadequate . This paper summarizes a study of the effect of such a programme on staff knowledge and skills in a r and omized trial of 295 nurses working in 108 Primary Health Centres ( PHCs ) in Karnataka , India . Methods Stratifying by district , half of the PHCs were r and omly assigned to be intervention sites and provided with regular mentoring visits where case sheet/checklists were a central job and teaching aid , and half to be control sites , where no support was provided except provision of case sheets . Nurses ’ knowledge and skills around normal labour , labour complications and neonate issues were tested before the intervention began and again one year later . Univariate and multivariate analyses were conducted to examine the effect of mentoring and case sheets . Results Overall , on none of the 3 measures , did case sheet use without mentoring add anything to the basic nursing training when controlling for other factors . Only individuals who used both case-sheets and received mentoring scored significantly higher on the normal labour and neonate indices , scoring almost twice as high as those who only used case-sheets . This group was also associated with significantly higher scores on the complications of labour index , with their scores 2.3 times higher on average than the case sheet only control group . Individuals from facilities with 21 or more deliveries in a month tended to fare worse on all 3 indices . There were no differences in outcomes according to district or years of experience . Conclusions This study demonstrates that provision of case sheets or checklists alone is insufficient to improve knowledge and practice s. However , on-site mentoring in combination with case sheets can have a demonstrable effect on improving nurse knowledge and skills around essential obstetric and neonatal care in remote rural areas of India . We recommend scaling up of this mentoring model in order to improve staff knowledge and skills and reduce maternal and neonatal mortality in India . Trial registration This study is registered at clinical trials.gov , Identifier No. NCT02004912 , November 27 , 2013 Background and Purpose — More than 70 % of individuals who have a stroke experience upper limb deficits that impact daily activities . Increased amount of upper limb therapy has positive effects ; however , practical and inexpensive methods of therapy are needed to deliver this increase in therapy . Methods — This was a multi-site single blind r and omized controlled trial to determine the effectiveness of a 4-week self-administered grade d repetitive upper limb supplementary program ( GRASP ) on arm recovery in stroke . 103 in patients with stroke were r and omized to the experimental group ( GRASP group , n=53 ) or the control group ( education protocol , n=50 ) . The primary outcome measure was the Chedoke Arm and H and Activity Inventory ( CAHAI ) , a measure of upper limb function in activities of daily living . Secondary measures were used to evaluate grip strength and paretic upper limb use outside of therapy time . Intention-to-treat analysis was performed . Group differences were tested using analysis of covariance . Results — At the end of the 4-week intervention ( approximately 7 weeks poststroke ) , the GRASP group showed greater improvement in upper limb function ( CAHAI ) compared to the control group ( mean difference 6.2 ; 95 % CI : 3.4 to 9.0 ; P<0.001 ) . The GRASP group maintained this significant gain at 5 months poststroke . Significant differences were also found in favor of the GRASP protocol for grip strength and paretic upper limb use . No serious adverse effects were experienced . Conclusion — A self-administered homework exercise program provides a cost- , time- , and treatment-effective delivery model for improving upper limb recovery in subacute stroke BACKGROUND Constraint-induced movement therapy ( CIMT ) is recommended for patients with upper limb dysfunction after stroke , yet evidence to support the implementation of CIMT in ambulatory care is insufficient . We assessed the efficacy of home CIMT , a modified form of CIMT that trains arm use in daily activities within the home environment . METHODS In this parallel , cluster-r and omised controlled trial , we selected 71 therapy practice s in northern Germany that treat adult patients with upper limb dysfunction after stroke . Practice s were stratified by region and r and omly allocated by an external biometrician ( 1:1 , block size of four ) using a computer-generated sequence . 37 practice s were r and omly assigned to provide 4 weeks of home CIMT and 34 practice s to provide 4 weeks of st and ard therapy . Eligible patients had mild to moderate impairment of arm function at least 6 months after stroke and a friend or family member willing to participate as a non-professional coach . Patients of both groups received 5 h of professional therapist contact in 4 weeks . In the home CIMT group , therapists used the contact time to instruct and supervise patients and coaches in home CIMT . Patients in the st and ard therapy group received conventional physical or occupational therapy , but additional home training was not obligatory . All assessment s were done by masked outcome assessors at baseline , after 4 weeks of intervention , and at 6 month follow-up . The primary outcomes were quality of movement , assessed by the Motor Activity Log ( MAL-QOM , assessor-assisted self-reported ) , and performance time , assessed by the Wolf Motor Function Test ( WMFT-PT , assessor-reported ) . Primary outcomes were tested hierarchically after 4 weeks of intervention and analysed by intention to treat , using mixed linear models . This trial is registered with Clinical Trials.gov , NCT01343602 . FINDINGS Between July 11 , 2011 , and June 4 , 2013 , 85 of 156 enrolled patients were assigned home CIMT and 71 patients were assigned st and ard therapy . 82 ( 96 % ) patients in the home CIMT group and 71 ( 100 % ) patients in the st and ard therapy group completed treatment and were assessed at 4 weeks . Patients in both groups improved in quality of movement ( MAL-QOM ; change from baseline 0·56 , 95 % CI 0·41 - 0·71 , p<0·0001 for home CIMT vs 0·31 , 0·15 - 0·46 , p=0·0003 for st and ard therapy ) . Patients in the home CIMT group improved more than patients in the st and ard therapy group ( between-group difference 0·26 , 95 % CI 0·05 - 0·46 ; p=0·0156 ) . Both groups also improved in motor function performance time ( WMFT-PT ; change from baseline -25·60 % , 95 % CI -36·75 to -12·49 , p=0·0006 for home CIMT vs -27·52 % , -38·94 to -13·94 , p=0·0004 for st and ard therapy ) , but the extent of improvement did not differ between groups ( 2·65 % , -17·94 to 28·40 ; p=0·8152 ) . Nine adverse events ( of which six were serious ) were reported in the home CIMT group and ten ( of which seven were serious ) in the st and ard therapy group ; however , none was deemed related to the study intervention . INTERPRETATION Home-based CIMT can enhance the perceived use of the stroke-affected arm in daily activities more effectively than conventional therapy , but was not superior with respect to motor function . Further research is needed to confirm whether home CIMT leads to clinical ly significant improvements and if so to identify patients that are most likely to benefit . FUNDING German Federal Ministry of Education and Research Background Globally , most strokes occur in low- and middle-income countries , such as India , with many affected people having no or limited access to rehabilitation services . Western models of stroke rehabilitation are often unaffordable in many population s but evidence from systematic review s of stroke unit care and early supported discharge rehabilitation trials suggest that some components might form the basis of affordable interventions in low-re source setting s. We describe the background , history and design of the ATTEND trial , a complex intervention centred on family-led stroke rehabilitation in India . Methods / design The ATTEND trial aims to test the hypothesis that a family-led caregiver-delivered home-based rehabilitation intervention , design ed for the Indian context , will reduce the composite poor outcome of death or dependency at 6 months after stroke , in a multicentre , individually r and omized controlled trial with blinded outcome assessment , involving 1200 patients across 14 hospital sites in India . Discussion The ATTEND trial is testing the effectiveness of a low-cost rehabilitation intervention that could be widely generalizable to other low- and middle-income countries . Trial registration Clinical Trials Registry-India CTRI/2013/04/003557 . Australian New Zeal and Clinical Trials Registry ACTRN12613000078752 . Universal Trial Number U1111 - 1138 - 6707 Abstract Objective : The aim was to study a client-centred activities of daily living ( ADL ) intervention ( CADL ) compared with the usual ADL intervention ( UADL ) in people with stroke regarding : independence in ADL , perceived participation , life satisfaction , use of home-help service , and satisfaction with training and , in their significant others , regarding : caregiver burden , life satisfaction , and informal care . Methods : In this multicentre study , 16 rehabilitation units were r and omly assigned to deliver CADL or UADL . The occupational therapists who provided the CADL were specifically trained . Eligible for inclusion were people with stroke treated in a stroke unit ≤3 months after stroke , dependent in ≥two ADL , not diagnosed with dementia , and able to underst and instructions . Data were collected at inclusion and three months thereafter . To detect a significant difference between the groups in the Stroke Impact Scale ( SIS ) domain “ participation ” , 280 participants were required . Intention-to-treat analysis was applied . Results : At three months , there was no difference in the outcomes between the CADL group ( n = 129 ) and the UADL group ( n = 151 ) , or their significant others ( n = 87/n = 93 ) except in the SIS domain “ emotion ” in favour of CADL ( p = 0.04 ) . Conclusion : The CADL does not appear to bring about short-term differences in outcomes and longer follow-ups are required Although intervention is effective in reducing the disability associated with stroke , limited re sources mean that physiotherapy services often cease by six months after stroke . The purpose of this clinical trial was to investigate the efficacy of re source -efficient physiotherapy services in improving mobility and quality of life after stroke . Twenty-six people with residual walking difficulties after stroke were r and omised into an experimental or control group after discharge from physiotherapy services . The experimental group participated in a six-week , home-based mobility program . The control group participated in a six-week , home-based program of upper-limb exercises ( i.e. ' sham ' mobility exercises ) . Subjects met with the therapist for prescription of exercises only three times during the six weeks . Strategies used to offset potential problems associated with minimal subject-therapist interaction included videotaped instructions to encourage correct performance of exercises , modification of the environment and involvement of carers to enhance safety , and telephone contact and self-monitoring to promote compliance . St and ing ( Functional Reach ) , walking ( MAS Item 5 ) and quality of life ( SA-SIP30 ) were measured prior to , immediately after , and two months after intervention ceased by an assessor who was blinded to group allocation . Subjects in the experimental group demonstrated significant improvement in st and ing compared to the control group ( p = 0.01 ) which was maintained two months after the cessation of intervention ( p = 0.04 ) . There was no difference between the groups in walking ( p = 0.50 ) or quality of life ( p = 0.70 ) . The six-week , re source -efficient mobility program was effective in improving some of the mobility in people after discharge from stroke rehabilitation . The provision of re source -efficient programs is recommended wherever possible so that people affected by stroke may continue rehabilitation for longer Modified constraint-induced movement therapy ( CIMT ) protocol s show motor function and real-world arm use improvement . Meanwhile it usually requires constant supervision by physiotherapists and is therefore more expensive than customary care . This study compared the preliminary efficacy of two modified CIMT protocol s. A two-group r and omized controlled trial with pre and post treatment measures and six months follow-up was conducted . Nineteen patients with chronic stroke received 10 treatment sessions distributed three to four times a week over 22 days . CIMT3h_direct group received 3 hours of CIMT supervised by a therapist ( n=10 ) while CIMT1.5h_direct group had 1.5 hours of supervised CIMT+1.5 hours home exercises supervised by a caregiver ( n=9 ) . Outcome measures were the Fugl-Meyer Assessment , the Motor Activity Log , and the Stroke Specific Quality of Life Scale . The modified CIMT protocol s were feasible and well tolerated . Improvements in motor function , real-world arm use and quality of life did not differ significantly between treated groups receiving either 3 or 1.5 hours mCIMT supervised by a therapist Abstract Background Training care givers reduces their burden and improves psychosocial outcomes in care givers and patients at one year . However , the cost effectiveness of this approach has not been investigated . Objective To evaluate the cost effectiveness of caregiver training by examining health and social care costs , informal care costs , and quality adjusted life years in care givers . Design A single , blind , r and omised controlled trial . Setting Stroke rehabilitation unit . Subjects 300 stroke patients and their care givers . Interventions Caregiver training in basic nursing and facilitation of personal care techniques compared with no caregiver training . Main outcome measures Health and social care costs , informal care costs , and quality adjusted life years in care givers over one year after stroke . Results Total health and social care costs over one year for patients whose care givers received training were significantly lower ( mean difference -£4043 ( $ 7249 ; € , 95 % confidence interval -£6544 to -£1595 ) . Inclusion of informal care costs , which were similar between the two groups , did not alter this conclusion . The cost difference was largely due to differences in length of hospital stay . The EQ-5D did not detect changes in quality adjusted life years in care givers . Conclusion Compared with no training , caregiver training during rehabilitation of patients reduced costs of care while improving overall quality of life in care givers at one year Background Several systematic review s have shown that additional exercise therapy has a positive effect on functional outcome after stroke . However , there is an urgent need for re source -efficient methods to augment rehabilitation services without increasing health care costs . Asking informal caregivers to do exercises with their loved ones , combined with e-health services may be a cost-effective method to promote early supported discharge with increased functional outcome .The primary aim of the CARE4STROKE study is to evaluate the effects and cost-effectiveness of a caregiver-mediated exercises program combined with e-health services after stroke in terms of self-reported mobility and length of stay . Methods An observer-blinded r and omized controlled trial , in which 66 stroke- patients admitted to a hospital stroke unit , rehabilitation center or nursing home are r and omly assigned to either 8 weeks of the CARE4STROKE program in addition to usual care ( i.e. , experimental group ) or 8 weeks of usual care alone ( i.e. , control group ) . The CARE4STROKE program is compiled in consultation with a trained physical therapist . A tablet computer is used to present video-based exercises for gait and gait-related activities in which a caregiver acts as an exercise coach . Primary outcomes are the mobility domain of the Stroke Impact Scale and length of stay . Secondary outcomes are the other domains of the Stroke Impact Scale , motor impairment , strength , walking ability , balance , mobility , ( Extended ) Activities of Daily Living , psychosocial functioning , self-efficacy , fatigue , health-related quality of life of the patient as well as the experienced strain , psychosocial functioning and quality of life of the caregiver . An economic evaluation will be conducted from the societal and health care perspective . Discussion The main aspects of the CARE4STROKE program are 1 ) increasing intensity of training by doing exercises with a caregiver in addition to usual care and 2 ) e-health support . We hypothesize this program leads to better functional outcome and early supported discharge , result ing in reduced costs . Trial registration The study is registered in the Dutch trial register as NTR4300 , registered 2 December 2013 Background It has been reported that following rehabilitation , only 7 % of stroke survivors are able to walk at a level commensurate with community participation . Previous research indicates that treadmill and overground walking training can improve walking capacity in people living in the community after stroke . The main objectives of the AMBULATE trial are to determine ( i ) whether a 4-month treadmill walking program is more effective than a 2-month program , compared to control , in improving walking capacity , health and community participation and ( ii ) the " threshold " walking speed that results in sufficient walking capacity that makes walking self-sustaining . Methods / Design A prospect i ve r and omised controlled trial of unsupported treadmill training with a 12 month follow-up with concealed allocation and blinded assessment will be conducted . 210 community-dwelling people after stroke who are able to walk independently but slowly will be recruited and r and omly allocated to either a 4 month training group , 2 month training group or the control ( no intervention ) group . Intervention for the two training groups will occur 3 days per week for 30 minutes each session . Measurements of walking , health and community participation will be taken at baseline , 2 months , 4 months , 6 months and 12 months . This study has obtained ethical approval from the relevant Human Research Ethics Committees . Discussion By improving stroke survivors ' walking ability , it is likely also to improve their general wellbeing by promoting better health and greater community participation . Furthermore , if stroke survivors can reach a point where their walking and community participation is self-sustaining , this will reduce the burden of care on family and friends as well as the economic burden on the health system . Given the major demographic shift in developed nations involving significant growth in the aged population , this research will make an important evidence -based contribution to the promotion of healthy ageing . Trial registration This trial is registered with the Australian New Zeal and Clinical Trials Registry , ( ACTRN012607000227493 This article describes a 3-year study testing the efficacy of a system of home-based , case-managed care for stroke survivors returning to the community following inpatient poststroke rehabilitation . The Stroke Transition after Inpatient Rehabilitation ( STAIR ) study was a r and omized , controlled trial of a postdischarge management strategy carried out in a group of 55 stroke patients , aged 65 or older , who did not have serious residual cognitive or language impairments and returned to the community following inpatient rehabilitation with the assistance of a primary caregiver . The program was shown to facilitate improvement in the general social activity level of the patients in the experimental group at 6 months compared to the control , and there was a trend for this effect to persist at 1 year . Strong relationships were identified between residual disability , social activity level , patients ' perceptions of efficacy , and caregiver stress Abstract Background Informal care givers support disabled stroke patients at home but receive little training for the caregiving role . Objective To evaluate the effectiveness of training care givers in reducing burden of stroke in patients and their care givers . Design A single , blind , r and omised controlled trial . Setting Stroke rehabilitation unit . Subjects300 stroke patients and their care givers . Interventions Training care givers in basic nursing and facilitation of personal care techniques . Main outcome measures Cost to health and social services , caregiving burden , patients ' and care givers ' functional status ( Barthel index , Frenchay activities index ) , psychological state ( hospital anxiety and depression score ) , quality of life ( EuroQol visual analogue scale ) and patients ' institutionalisation or mortality at one year . Results Patients were comparable for age ( median 76 years ; interquartile range 70 - 82 years ) , sex ( 53 % men ) , and severity of stroke ( median Barthel index 8 ; interquartile range 4 - 12 ) . The costs of care over one year for patients whose care givers had received training were significantly lower ( £ 10 133 v£13 794 ( $ 18 087 v$24 619 ; € 15 204 v€20 697 ) ; P = 0.001 ) . Trained care givers experienced less caregiving burden ( care giver burden score 32 v41 ; P = 0.0001 ) , anxiety ( anxiety score 3 v4 ; P = 0.0001 ) or depression ( depression score 2 v3 ; P = 0.0001 ) and had a higher quality of life ( EuroQol score 80 v70 ; P = 0.001 ) . Patients ' mortality , institutionalisation , and disability were not influenced by caregiver training . However , patients reported less anxiety ( 3 v4.5 ; P < 0.0001 ) and depression ( 3 v4 ; P < 0.0001 ) and better quality of life ( 65 v60 ; P = 0.009 ) in the caregiver training group . Conclusion Training care givers during patients ' rehabilitation reduced costs and caregiver burden while improving psychosocial outcomes in care givers and patients at one year AIM The aim of the prospect i ve cohort study was to assess the impact of the conducted carer training on functional status improvement in patients after stroke . BACKGROUND In recent years , the role of family in unprofessional care provision for patients in their home environment has been emphasized . METHODS The cohort comprised 157 patients after ischemic stroke . The study group consisted of 81 patients and their carers who participated in the education program , and the control group included 76 patients . We used a repeated measures design : the patients ' functional status was assessed on the day of hospital discharge and after 3 and 12 months at home . RESULTS After 12 months the patients ' functional status according to Barthel Index and Modified Rankin Scale significantly improved in both groups , but no difference between the groups was noted in the degree of improvement achieved . CONCLUSIONS The carers ' participation in the education program did not significantly affect the patients ' functional improvement Objectives : To explore whether a group programme for community-dwelling chronic stroke survivors and their carers is feasible in rural setting s ; to measure the impact of the programme on health-related quality of life and functional performance ; and to determine if any benefits gained are maintained . Design : R and omized , assessor blind , cross-over , controlled trial . Setting : Rural outpatient . Subjects : Twenty-five community-dwelling , chronic stroke survivors and 17 carers of participant stroke survivors . Intervention : The intervention group undertook a once-a-week , seven-week group programme combining physical activity , education , self-management principles and a ‘ healthy options ’ morning tea . At completion , the control group crossed over to receive the intervention . Main measures : Stroke Impact Scale ( stroke survivors ) , Health Impact Scale ( carers ) , Six Minute Walk Test , Timed Up and Go , Caregiver Strain Index . Results : There were insufficient participants for results to reach statistical significance . However between-group trends favoured the intervention group in the majority of outcome measures for stroke survivors and carers . The majority of measures remained above baseline at 12 weeks post programme for stroke survivor participants . The programme was well attended . Of the seven sessions all participants attended four or more and 88 % attended six or seven sessions . Conclusions : This novel programme incorporating physical activity , education and social interaction proved feasible to undertake by a stroke-specific multidisciplinary team in three rural Australian setting s. This programme may improve and maintain health-related quality of life and physical functioning for chronic stroke survivors and their carers and warrants further investigation Background The aim of this pilot study was to determine the feasibility of a multicenter , r and omized , controlled trial in India of a family-led , trained caregiver-delivered , home-based rehabilitation intervention vs. routine care . Methods A prospect i ve , r and omized ( within seven-days of hospital admission ) , blinded outcome assessor , controlled trial of structured home-based rehabilitation delivered by trained and protocol -guided family caregivers ( intervention ) vs. routine care alone ( control ) was conducted in patients with residual disability . Key feasibility measures were recruitment , acceptance and adherence to assessment procedures , and follow-up of participants over six-months . CTRI/2014/10/005133 . Results A total of 104 patients from the stroke unit at Christian Medical College , Ludhiana were recruited over nine-months . Recruitment was feasible and accepted by patients and their carers . Important observations were made regarding potential unblinding of the participants , contamination of therapy between the r and omized groups , organization of home visits , and re sources required for a multicenter study . Conclusion The pilot study established the feasibility of conducting a large-scale study of family-led , trained caregiver-delivered , home-based stroke rehabilitation in a low re source setting . The main phase of the trial ‘ ATTEND ’ is currently underway in over 10 centers in India Objectives : To evaluate the effectiveness of an education programme for patients and carers recovering from stroke . Design : R and omized controlled trial . Subjects and setting : One hundred and seventy patients admitted to a stroke rehabilitation unit and 97 carers of these patients . Interventions : The intervention group received a specifically design ed stroke information manual and were invited to attend education meetings every two weeks with members of their multidisciplinary team . The control group received usual practice . Measures : Primary outcome was knowledge of stroke and stroke services . Secondary outcomes were h and icap ( London H and icap Scale ) , physical function ( Barthel Index ) , social function ( Frenchay Activities Index ) , mood ( Hospital Anxiety and Depression Scale ) and satisfaction ( Pound Scale ) . Carer mood was measured by the General Health Question naire-28 . Results : There was no statistical evidence for a treatment effect on knowledge but there were trends that favoured the intervention . The education programme was associated with a significantly greater reduction in patient anxiety score at both three months ( p=0.034 ) and six months ( p=0.021 ) and consequently fewer ‘ cases ’ ( Hospital Anxiety and Depression Scale anxiety subscale score ≥ 11 ) . There were no other significant statistical differences between the patient or carer groups for other outcomes , although there were trends in favour of the education programme . Conclusion : An education programme delivered within a stroke unit did not result in improved knowledge about stroke and stroke services but there was a significant reduction in patient anxiety at six months post stroke onset Objective : Examine feasibility of conducting a r and omized controlled trial of the Timing it Right Stroke Family Support Program ( TIRSFSP ) and collect pilot data . Design : Multi-site mixed method r and omized controlled trial . Setting : Acute and community care in three Canadian cities . Subjects : Caregivers were family members or friends providing care to individuals who experienced their first stroke . Intervention : The TIRSFSP offered in two formats , self-directed by the caregiver or stroke support person-directed over time , were compared to st and ard care . Main measures : Caregivers completed baseline and follow-up measures 1 , 3 and 6 months post-stroke including Centre for Epidemiological Studies Depression , Positive Affect , Social Support , and Mastery Scales . We completed in-depth qualitative interviews with caregivers and maintained intervention records describing support provided to each caregiver . Results : Thirty-one caregivers received st and ard care ( n=10 ) , self-directed ( n=10 ) , or stroke support person-directed ( n=11 ) interventions . We retained 77 % of the sample through 6-months . Key areas of support derived from intervention records ( n=11 ) related to caregiver wellbeing , caregiving strategies , patient wellbeing , community re-integration , and service delivery . Compared to st and ard care , caregivers receiving the stroke support person-directed intervention reported improvements in perceived support ( estimate 3.1 , P=.04 ) and mastery ( estimate .35 , P=.06 ) . Qualitative caregiver interviews ( n=19 ) reflected the complex interaction between caregiver needs , preferences and available options when reporting on level of satisfaction . Conclusions : Preliminary findings suggest the research design is feasible , caregivers ’ needs are complex , and the support intervention may enhance caregivers ’ perceived support and mastery . The intervention will be tested further in a large scale trial Objective : To assess the efficacy of a programme of continuing self-directed exercises for people discharged home after a stroke , supervised once a week by therapists . Design : A r and omized controlled trial of 100 patients discharged from hospital after a stroke , requiring ongoing therapy . The control group received outpatient or day hospital therapy ; the experimental group were visited once a week by an occupational and /or physiotherapist who prescribed a programme of exercises and activities for the following week . Subjects were studied for the first three months after discharge from hospital . Setting : A district general hospital , or the homes of subjects r and omized to the experimental group , in New Zeal and . Main outcome measures : ( 1 ) Characteristics of the groups , ( 2 ) gait speed , limb function , activities of daily living , ( 3 ) time with therapists , ( 4 ) mood of both subjects and caregivers , ( 5 ) anticipation of outcome at entry , compared with perceived outcome at exit . Results : No statistical differences between the control and experimental groups in characteristics , or in any outcomes measured , except that the contact time period , but not the number of visits , was longer in the experimental group ( p = 0.003 ) . Conclusions : A supervised home-based programme is as effective as outpatient or day hospital therapy The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials Background and Purpose . Patients with chronic stroke may benefit from continuing rehabilitation training after hospital discharge . This study examined whether caregiver-mediated , home-based intervention ( CHI ) could improve physical functioning and social participation in these patients . Methods . A single-blind , r and omized , controlled 12-week trial conducted with 51 patients from 3 hospitals in Taiwan who had chronic stroke ( > 6 months ; Brunnstrom recovery stages III-V ) . Patients and their caregivers in the intervention arm ( n = 25 ) were given weekly personalized CHI trainings design ed by a physical therapist . Patients in the control arm ( n = 26 ) received visits from the therapist without intervention . All were evaluated for physical recovery through the Stroke Impact Scale , Berg Balance Scale , 10-Meter Walk Test , 6-Minute Walk Test , and Barthel Index at baseline and endpoint . Caregivers were evaluated with the Caregiver Burden Scale . Results were analyzed through Mann-Whitney U test . Results . CHI significantly improved scores of the Stroke Impact Scale : strength ( control vs intervention , respectively : 1.4 vs 15.5 ; P = .002 ) , mobility ( –0.5 vs 13.7 ; P < .001 ) , composite physical ( –0.7 vs 11.2 ; P < .001 ) , and general recovery domain ( 0.2 vs 17.4 ; P < .001 ) . CHI also significantly improved free-walking velocity ( –1.4 vs 7.5 cm/s ; P = .006 ) , 6-minute walk distance ( –10.5 vs 15.8 m ; P = .003 ) , Berg Balance Scale score ( –0.8 vs 4.5 ; P = .006 ) , and Barthel Index score ( 0.6 vs 7.2 ; P = .008 ) . CHI did not significantly increase caregiver burden at endpoint . Conclusion . CHI can improve physical functional recovery and , possibly , social participation in patients with chronic stroke AIM AND OBJECTIVE To explore the long-term effects of a discharge-preparation programme targeting Taiwanese family caregivers of older patients with stroke . BACKGROUND Little is known about the effects of interventions for caregivers of patients with stroke in Asian and Chinese families . DESIGN A r and omised experimental design was used . METHOD Participants included 158 older patients with stroke ( 72 in the experimental group and 86 in the control group ) and their family caregivers . A caregiver-oriented intervention programme was design ed to increase caregiver preparedness , to enhance caregiver perception of balance between competing needs and to satisfy specific needs during the transition between hospitalisation and discharge . Long-term outcomes were measured by caregiver 's health-related quality of life , quality of care , stroke patient 's self-care ability , patient 's health-related quality of life and service utilisation . Longitudinal data were analysed by the generalised estimating equation approach . RESULTS During the 12 months following discharge of older patients with stroke , caregivers in the experimental group provided significantly better quality of care ( beta = 0.45 ; p = 0.03 ) than the control group . Between the sixth-twelfth months following discharge , patients in the control group were more likely to be institutionalised than those in the experimental group ( chi(2 ) = 5.11 ; p = 0.03 ) . CONCLUSION Using a sample from Taiwan , this intervention programme succeeded in improving quality of care provided by family caregivers to older patients with stroke and in decreasing the likelihood of their institutionalisation . RELEVANCE TO CLINICAL PRACTICE Older Chinese patients with stroke and their family caregivers can benefit from an individualised programme that prepares caregivers for patient discharge . Similar programmes may be applicable to other countries with Chinese population Objective : An intensified transition concept between neurological inpatient rehabilitation and home care was investigated for effects on the functional status of stroke patients and the physical and emotional health of their carers . Design : Controlled clinical trial allocating patients to intervention group ( intensified transition on ward II ) or control group ( st and ard transition on ward I ) ; patients were allocated to whichever ward had a vacancy . Follow-up assessment was carried out six months after discharge . Subjects : Seventy-one patients and their family carers were included , of which nine cases dropped out . Therefore 62 stroke patients with persisting disability and their family carers were available for assessment at follow-up - 33 patients in the intervention group , 29 patients in the control group . Intervention : The intensified transition concept consisted of therapeutic weekend care , bedside teaching and structured information for relatives during the second phase of the rehabilitation . Main measures : Patients were assessed with the Barthel Index , Functional Independence Measure , Ashworth Spastic Scale , Frenchay Arm Test , and Timed Up and Go Test . The carers completed SF-36 , and were assessed using the Giessen Symptom List , Depression Scale and Burden Scale for Family Caregivers . Results : The intensified transition did not lead to significant change in the functional status of the patients or in the physical and emotional health of the family carers . Within the first four weeks after discharge , the patients in the intervention group had fewer new illnesses . In the observation period the use of outpatient care services was more frequent in the intervention group than in the control group . Conclusion : Even though there are few differences of moderate intensity between the two groups the intensified transition programme does not affect either the functional status of the stroke patients or the health of the carers OBJECTIVE To determine the time course of both neurological and functional recovery from stroke . DESIGN Prospect i ve , consecutive , and community based . SETTING The stroke unit of a hospital in Copenhagen , Denmark . This setting receives all acute stroke patients admitted from a well-defined catchment area of 239,886 inhabitants within the city of Copenhagen . Acute treatment as well as all stages of rehabilitation are cared for within the stroke unit regardless of age , stroke severity , and premorbid condition . PATIENTS 1,197 patients with acute stroke . MAIN OUTCOME MEASURES Weekly examinations of neurological deficits ( using the Sc and inavian Neurological Stroke Scale ) and functional disabilities ( Activity of Daily Living ( ADL ) measured by the Barthel Index ) were performed from the time of acute admission to the end of rehabilitation . These evaluations were repeated 6 months poststroke . Time course of recovery was stratified according to initial stroke severity and disability . RESULTS Functional recovery was completed within 12.5 weeks ( 95 % confidence interval ( CI ) 11.6 to 13.4 ) from stroke onset in 95 % of the patients . However , 80 % of the patients had reached their best ADL function within 6 weeks ( CI 5.3 to 6.7 ) from onset . The time course of functional recovery was strongly related to initial stroke severity . Best ADL function was reached within 8.5 weeks ( CI 8 to 9 ) in patients with initially mild strokes , within 13 weeks ( CI 12 to 14 ) in patients with moderate strokes , within 17 weeks ( CI 15 to 19 ) in patients with severe strokes , and within 20 weeks ( CI 16 to 24 ) in patients with very severe strokes . After these time-points , no significant changes occurred . However , a valid prognosis of functional outcome can be made much earlier . Best ADL function was reached by 80 % of the patients with initially mild strokes within 3 weeks ( CI 2.6 to 3.4 ) , within 7 weeks ( CI 6 to 8) of the patients with moderate strokes , and within 11.5 weeks ( CI 10 to 13 ) of the patients with severe and very severe strokes . The time course of neurological recovery followed a pattern similar to that of functional recovery , but preceeded functional recovery by 2 weeks on average . CONCLUSIONS A reliable prognosis can in all stroke patients be made within 12 weeks from stroke onset . Even in patients with severe and very severe strokes , neurological and functional recovery should not be expected after the first 5 months This study was a preliminary examination of the effect of low-intensity home-based physical therapy on the performance of activities of daily living ( ADL ) and motor function in patients more than 1 year after stroke . Twenty patients were recruited from a community stroke register in Nan-Tou County , Taiwan , to a r and omized , crossover trial comparing intervention by a physical therapist immediately after entry into the trial ( Group I ) or after a delay of 10 weeks ( Group II ) . The intervention consisted of home-based physical therapy once a week for 10 weeks . The Barthel Index ( BI ) and Stroke Rehabilitation Assessment of Movement ( STREAM ) were used as st and ard measures for ADL and motor function . At the first follow-up assessment at 11 weeks , Group I showed greater improvement in lower limb motor function than Group II . At the second follow-up assessment at 22 weeks , Group II showed improvement while Group I had declined . At 22 weeks , the motor function of upper limbs , mobility , and ADL performance in Group II had improved slightly more than in Group I , but the between-group differences were not significant . It appears that low-intensity home-based physical therapy can improve lower limb motor function in chronic stroke survivors . Further studies will be needed to confirm these findings The Berg Balance Scale ( BBS ) was design ed to help determine change in functional st and ing balance over time . The purpose of this paper was to estimate the minimum detectable change score ( MDC ) using the st and ard error of measure ( SEM ) , thereby providing a means to decide if genuine change had occurred . Calculation of the agreement regarding the presence of change as determined by the MDC and clinicians ' perceptions was performed to give an indication of the validity of this criterion value . Forty-eight subjects who were receiving inpatient rehabilitation after stroke were assessed on consecutive days by two raters using the BBS . The MDC analysis suggests that a change of + /- 6 BBS points is necessary to be 90 % confident of genuine change . Only 25/45 subjects showed agreement between the statistically derived presence of change and clinicians ' perceptions of change . The lack of agreement may relate to the validity of the SEM/MDC methodology to determine the criterion BBS value , the heterogeneity of the subjects , or the use of clinician gestalt impressions of change BACKGROUND AND PURPOSE The purpose of this study was to establish the interrater reliability of assessment s made with the Fugl-Meyer evaluation of physical performance in a rehabilitation setting . SUBJECTS Twelve patients ( 7 male , 5 female ) , aged 49 to 86 years ( mean = 66 ) , who had sustained a cerebrovascular accident participated in the study . All patients were admitted consecutively to a rehabilitation center and were between 6 days and 6 months poststroke . METHODS Three physical therapists , each with more than 10 years of experience , assessed the patients in a r and omized and balanced order using this assessment . The therapists st and ardized the assessment approach prior to the study but did not discuss the procedure once the study began . RESULTS The overall reliability was high ( overall intraclass correlation coefficient = .96 ) , and the intraclass correlation coefficients for the subsections of the assessment varied from .61 for pain to .97 for the upper extremity . CONCLUSION AND DISCUSSION The relative merits of using the Fugl-Meyer assessment as a research tool versus a clinical assessment for stroke are discussed 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 AIM This study aims at describing an intervention based on informal caregivers ' skills when taking care of older people after a stroke ( InCARE ) . BACKGROUND Most informal caregivers feel unprepared to deliver assistance in activities of daily living at home . This lack of preparedness can lead to misconceptions , burden and affect their health , which , consequently , may imply hospital readmissions or early institutionalization of the older adults . DESIGN A single blinded r and omised trial . METHODS This study will recruit 198 dyads , comprising old stroke survivors and their caregivers , who will be divided into two groups : intervention and control ( protocol approved in May 2013 ) . INCLUSION CRITERIA ( informal caregivers ) absence of cognitive impairment ; resident in the Cávado Region ; to return the informed consent ( older people ) are over 65 years of age ; have had a first stroke and ; be dependent on at least one of the self-care activities post hospital discharge . PRIMARY OUTCOME informal caregivers ' skills . SECONDARY OUTCOMES include burden and Health Quality of Life in informal caregivers ; functionality , hospital readmission and institutionalization of older people stroke survivors , measured 1 and 3 months after InCARE programme . DISCUSSION The InCARE programme will highlight new ways to underst and the feasibility of a large trial , which supports caregivers who take care of older people after a stroke . It will be expected that the level of burden decreases , thus helping informal caregivers enhance their quality of life . Also , it is expected that older people 's functionality will be improved and that hospital readmission or institutionalization may be avoided AIMS AND OBJECTIVES The aim of the present study was to determine the impact of a nurse-led support and education programme for improving the spouses ' perceived general quality of life , life situation , general well-being and health state . BACKGROUND Stroke is a disease with great consequences for the patients and their families . The spouses often feel obligated to care for the patient , providing psychological and physical support and having to cope with the patient 's physical and cognitive impairments . This might lead to increased problems , as family members struggle to adapt to their new roles and responsibilities . DESIGN AND METHODS Longitudinal , r and omized controlled trial . One hundred spouses were r and omly assigned to intervention or control groups , 50 in each group . The intervention group participated in a support and education programme , six times during six months , led by stroke specialist nurses . Both groups were followed for 12 months . RESULTS No significant differences were found , between intervention and control groups , over time . In the sub analyses , we found that the group attending 5 - 6 times had a significant decrease in negative well-being and increased quality of life over time , while the group attending fewer times had a significant decrease in positive well-being and health state , similar to the control group , which also had a significant decrease in negative and general well-being . CONCLUSIONS A support and education programme might have a positive effect on spouses ' well-being , on condition that they attend at least five times . RELEVANCE TO CLINICAL PRACTICE To facilitate the spouses ' role as informal caregivers to the stroke patients , further development of the support and education programme used in the present study is needed , including empowerment approach and implementation of coping strategies BACKGROUND Most patients who have had a stroke are dependent on informal caregivers for activities of daily living . The TRACS trial investigated a training programme for caregivers ( the London Stroke Carers Training Course , LSCTC ) on physical and psychological outcomes , including cost-effectiveness , for patients and caregivers after a disabling stroke . METHODS We undertook a pragmatic , multicentre , cluster r and omised controlled trial with a parallel cost-effectiveness analysis . Stroke units were eligible if four of five criteria used to define a stroke unit were met , a substantial number of patients on the unit had a diagnosis of stroke , staff were able to deliver the LSCTC , and most patients were discharged to a permanent place of residence . Stroke units were r and omly assigned to either LSCTC or usual care ( control group ) , stratified by geographical region and quality of care , and using blocks of size 2 . Patients with a diagnosis of stroke , likely to return home with residual disability and with a caregiver providing support were eligible . The primary outcome for patients was self-reported extended activities of daily living at 6 months , measured with the Nottingham Extended Activities of Daily Living ( NEADL ) scale . The primary outcome for caregivers was self-reported burden at 6 months , measured with the caregivers burden scale ( CBS ) . We combined patient and caregiver costs with primary outcomes and quality -adjusted life-years ( QALYs ) to assess cost-effectiveness . This trial is registered with controlled-trials.com , number IS RCT N 49208824 . FINDINGS We assessed 49 stroke units for eligibility , of which 36 were r and omly assigned to either the intervention group or the control group . Between Feb 27 , 2008 , and Feb 9 , 2010 , 928 patient and caregiver dyads were registered , of which 450 were in the intervention group , and 478 in the control group . Patients ' self-reported extended activities of daily living did not differ between groups at 6 months ( adjusted mean NEADL score 27·4 in the intervention group versus 27·6 in the control group , difference -0·2 points [ 95 % CI -3·0 to 2·5 ] , p value=0·866 , ICC=0·027 ) . The caregiver burden scale did not differ between groups either ( adjusted mean CBS 45·5 in the intervention group versus 45·0 in the control group , difference 0·5 points [ 95 % CI -1·7 to 2·7 ] , p value=0·660 , ICC=0·013 ) . Patient and caregiver costs were similar in both groups ( length of the initial stroke admission and associated costs were £ 13,127 for the intervention group and £ 12,471 for the control group ; adjusted mean difference £ 1243 [ 95 % CI -1533 to 4019 ] ; p value=0·380 ) . Probabilities of cost-effectiveness based on QALYs were low . INTERPRETATION In a large scale , robust evaluation , results from this study have shown no differences between the LSCTC and usual care on any of the assessed outcomes . The immediate period after stroke might not be the ideal time to deliver structured caregiver training . FUNDING Medical Research Council OBJECTIVE To establish the time course of recovery regarding smoothness of upper limb movements in the first 6 months poststroke . DESIGN Cohort study with 3-dimensional kinematic measurements in weeks 1 , 2 , 3 , 4 , 5 , 8 , 12 , and 26 poststroke . SETTING Onsite 3-dimensional kinematic measurements in stroke units , rehabilitation centers , nursing homes , and patients ' homes . PARTICIPANTS Patients ( N=44 ; 19 women , 25 men ; mean age ± SD , 58±12y ) with a first-ever unilateral ischemic stroke and incomplete upper limb paresis ( 27 left sided , 17 right sided ) were included . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES In each measurement , an electromagnetic motion tracker acquired h and and finger trajectories during a reach-to-grasp task . Movement duration was determined , and smoothness of h and transport and grasp aperture was quantified by normalized jerk . With the use of r and om coefficient analysis , the effect of progress of time on smoothness of h and transport and grasp aperture was investigated . RESULTS During the first 5 weeks poststroke , there was a significant contribution of progress of time to reductions in movement duration and normalized jerk of h and transport and grasp aperture ( P<.01 ) . CONCLUSIONS The present longitudinal 3-dimensional kinematic study showed that smoothness of paretic upper limb movements improves in the first 8 weeks poststroke . This improvement suggests that motor control normalizes in the first 8 weeks poststroke and can be mostly explained by spontaneous neurologic recovery that occurs typically in the first weeks poststroke . Future 3-dimensional kinematic studies should investigate whether therapies starting early after stroke can improve the quality of motor control beyond spontaneous neurologic recovery OBJECTIVE To evaluate the effectiveness of an intervention using video to deliver therapy at home for patients with stroke . DESIGN R and omized controlled trial . SETTING The neurology ward and rehabilitation medicine department of a tertiary hospital . PARTICIPANTS Patients with stroke ( N=90 ) . There were 44 patients in the intervention group and 46 patients in the control group . INTERVENTIONS The intervention group received a combination of at-home rehabilitation guided by a digital videodisk containing therapy techniques and twice-monthly outpatient follow-up for 3 months . The conventional therapy group ( control ) attended weekly outpatient therapy sessions . MAIN OUTCOME MEASURES The primary outcome measure was the modified Barthel Index ( MBI ) score . The secondary measures were the incidence of poststroke complications and the Caregiver Strain Index . RESULTS At 3 months , there were no significant differences with regard to the number of patients with improved MBI score , complication rate , or Caregiver Strain Index score between the 2 groups . Both groups had significant increases in the MBI score at 3 months ( P<.001 for both groups ) . Regression analysis revealed that only stroke severity significantly influenced the MBI score ( P<.001 ) , complication rate ( P<.01 ) , and caregiver stress level ( P<.05 ) . CONCLUSIONS Video-based therapy at home for post-acute stroke patients is safe , does not negatively impact independence , and is not stressful for caregivers BACKGROUND The majority of stroke patients are discharged home dependent on informal caregivers , usually family members , to provide assistance with activities of daily living ( ADL ) , including bathing , dressing and toileting . Many caregivers feel unprepared for this role and this may have a detrimental effect on both the patient and caregiver . OBJECTIVE To evaluate whether or not a structured , competency-based training programme for caregivers [ the London Stroke Carer Training Course ( LSCTC ) ] improved physical and psychological outcomes for patients and their caregivers after disabling stroke , and to determine if such a training programme is cost-effective . DESIGN A pragmatic , multicentre , cluster r and omised controlled trial . SETTING Stratified r and omisation of 36 stroke rehabilitation units ( SRUs ) to the intervention or control group by geographical region and quality of care . PARTICIPANTS A total of 930 stroke patient and caregiver dyads were recruited . Patients were eligible if they had a confirmed diagnosis of stroke , were medically stable , were likely to return home with residual disability at the time of discharge and had a caregiver available , willing and able to provide support after discharge . The caregiver was defined as the main person -- other than health , social or voluntary care provider -- helping with ADL and /or advocating on behalf of the patient . INTERVENTION The intervention ( the LSCTC ) comprised a number of caregiver training sessions and competency assessment delivered by SRU staff while the patient was in the SRU and one recommended follow-up session after discharge . The control group continued to provide usual care according to national guidelines . Recruitment was completed by independent research ers and participants were unaware of the SRUs ' allocation . MAIN OUTCOME MEASURES The primary outcomes were self-reported extended ADL for the patient and caregiver burden measured at 6 months after recruitment . Secondary outcomes included quality of life , mood and cost-effectiveness , with final follow-up at 12 months . RESULTS No differences in primary outcomes were found between the groups at 6 months . Adjusted mean differences were -0.2 points [ 95 % confidence interval ( CI ) -3.0 to 2.5 points ; p = 0.866 ; intracluster correlation coefficient ( ICC ) = 0.027 ] for the patient Nottingham Extended Activities of Daily Living score and 0.5 points ( 95 % CI -1.7 to 2.7 points ; p = 0.660 ; ICC = 0.013 ) for the Caregiver Burden Scale . Furthermore , no differences were detected in any of the secondary outcomes . Intervention compliance varied across the units . Half of the participating centres had a compliance rating of > 60 % . Analysis showed no evidence of higher levels of patient independence or lower levels of caregiver burden in the SRUs with better levels of intervention compliance . The economic evaluation suggests that from a patient and caregiver perspective , health and social care costs , societal costs and outcomes are similar for the intervention and control groups at 6 months , 12 months and over 1 year . CONCLUSIONS We have conducted a robust multicentre , cluster r and omised trial , demonstrating for the first time that this methodology is feasible in stroke rehabilitation research . There was no difference between the LSCTC and usual care with respect to improving stroke patients ' recovery , reducing caregivers ' burden , or improving other physical and psychological outcomes , nor was it cost-effective compared with usual care . Compliance with the intervention varied , but analysis indicated that a dose effect was unlikely . It is possible that the immediate post-stroke period may not be the ideal time for the delivery of structured training . The intervention approach might be more relevant if delivered after discharge by community-based teams . TRIAL REGISTRATION Current Controlled Trials IS RCT N49208824 . FUNDING This project was funded by the MRC and is managed by the NIHR ( project number 09/800/10 ) on behalf of the MRC-NIHR partnership , and will be published in full in Health Technology Assessment ; Vol . 17 , No. 46 . See the NIHR Journals Library website for further project information Rationale The majority of stroke patients are discharged home dependent on informal caregivers , usually family members , to provide assistance with activities of daily living , including bathing , dressing , and toileting . Many caregivers feel unprepared for this role , and this may have a detrimental effect on both the patient and caregiver . Aims To evaluate whether a structured , competency-based training programme for caregivers improves physical and psychological outcomes for patients and their caregivers after disabling stroke , and to determine if such a training programme is cost-effective . Design A cluster r and omized controlled trial . The trial aims to recruit 25 patient and caregiver dyads from each of the 36 participating stroke rehabilitation units . Stroke units have been r and omized to either the intervention or control group with r and omization stratified by geographical region and quality of care . The intervention is the London Stroke Carer Training Course developed and evaluated in a previous single-centre study . The London Stroke Carer Training Course comprises a number of caregiver training sessions and competency assessment delivered while the patient is in the hospital and one follow-up session after discharge . The multidisciplinary teams in the units r and omized to the intervention group have been trained to incorporate delivery of the London Stroke Carer Training Course into ward practice , while those r and omized to the control group have continued to provide usual care according to national guidelines . Study outcomes The primary outcomes are extended activities of daily living for the patient and caregiver burden measured at six-months after recruitment . Secondary outcomes include mood and cost-effectiveness , with final follow-up at 12 months RATIONALE Stroke is a major cause of long-term adult disability with many survivors living in the community relying on family members for on-going support . However , reports of inadequate underst and ing of rehabilitation techniques are common . A self-management DVD-based observational learning tool may help improve functional outcomes for survivors of stroke and reduce caregivers ' burden . AIMS This article describes the methodology of the stroke self-management rehabilitation trial . The overall aim of this pilot trial is to assess the feasibility and preliminary efficacy of a DVD-based intervention for improving functional outcomes of survivors of stroke 2 months postr and omization to inform the design of a full-scale r and omized clinical trial . DESIGN Recruitment of a minimum of 20 survivors of stroke and their informal caregivers ( where available ) in each of the participating centers will occur across multiple international sites . After baseline assessment s , participants will be r and omly assigned to an intervention or st and ard care group . The intervention comprises a structured DVD observation and practice schedule over 8 weeks . All participants will complete follow-up assessment s. STUDY OUTCOMES The outcome measures will include a global shift in the Rankin Scale scores and dichotomized scores , changes in quality of life , general health , depression , and caregiver burden at 2 months postr and omization . A qualitative analysis of the effects of the intervention will also be undertaken . DISCUSSION The results of the pilot study will provide knowledge of whether observational learning techniques delivered via DVD can effectively improve recovery after stroke and reduce caregiver burden |
12,032 | 20,687,092 | Overall , the results demonstrate that outpatient induction of labour is feasible and that important adverse events are rare .
There was no strong evidence that agents used to induce labour in outpatient setting s had an impact ( positive or negative ) on maternal or neonatal health .
There was some evidence that , compared to placebo or no treatment , induction agents reduced the need for further interventions to induce labour , and shortened the interval from intervention to birth .
We were unable to pool results on outcomes relating to progress in labour as studies tended to measure a very broad range of outcomes .There was no evidence that induction agents increased interventions in labour such as operative deliveries .
Only two studies provided information on women 's views about the induction process , and overall there was very little information on the costs to health service providers of different methods of labour induction in outpatient setting s. AUTHORS ' CONCLUSIONS Induction of labour in outpatient setting s appears feasible .
We do not have sufficient evidence to know which induction methods are preferred by women , or the interventions that are most effective and safe to use in outpatient setting | BACKGROUND Induction of labour is carried out for a variety of indications and using a range of pharmacological , mechanical and other methods .
For women at low risk , some methods of induction of labour may be suitable for use in outpatient setting s. OBJECTIVES To examine pharmacological and mechanical interventions to induce labour in outpatient setting s in terms of feasibility , effectiveness , maternal satisfaction , healthcare costs and , where information is available , safety .
The review complements existing review s on labour induction examining effectiveness and safety . | OBJECTIVE To assess the ability of mifepristone to prime the cervix adequately and induce labor in pregnant women at term ; and when mifepristone alone proves insufficient , to determine whether oral misoprostol taken 48 h following mifepristone administration is effective in inducing labor . METHODS In this prospect i ve study 50 pregnant women at term with an unfavorable cervix were given 400 mg of mifepristone orally and allowed to return home . If labor did not start within 48 h , the women were admitted and induction was continued with 50 mug of misoprostol , a prostagl and in ( PG ) E1 analogue , taken orally every 4 h. The 50 controls , who were matched prospect ively for parity and pregnancy duration , underwent labor induction according to the routine administration of 3-mg tablets of PGE2 vaginally . RESULTS In the study group , 66 % of the women entered labor spontaneously or had a sufficiently ripened cervix within 48 h of taking mifepristone . However , there was no difference in time between prostagl and in administration and delivery between the control group and the 34 % of women who required misoprostol in the study group . In the study group , the cesarean section rate was significantly lower among the women whose labor was induced with mifepristone alone than among those who required misoprostol . There were no differences overall in obstetric or neonatal outcomes between the study and control groups . CONCLUSIONS In this pilot sample , 400 mg of mifepristone was effective in inducing cervical changes and labor . Although there were no adverse effects using oral misoprostol in combination with mifepristone , labor was more difficult to induce in the women who did not respond to mifepristone alone , and these women had a higher operative delivery rate The value of gentle , unilateral breast stimulation in the ripening of cervix and induction of labour was studied . Three hundred patients with uncomplicated term pregnancies , ( 38 - 42 weeks ) were recruited into the study , consisting of three separate r and omised double blind prospect i ve trials . The first trial was to evaluate the effectiveness of breast stimulation in ripening the cervices of 200 term primigravid patients . There was a mean change of 3.90 + /- 2.39 points in cervical score among the study group compared to 0.50 + /- 0.67 among the control group . Thirty-three per cent of the study group went into labour when compared with 4 % among the control group . In a second study of cross-over trial involving 78 of the original 200 patients , the study ( ex-control ) group had a mean change in cervical score of 3.84 + /- 2.24 when compared with the control ( ex- study ) group , ( 1.43 + /- 1.08 ) . In a third study involving 100 multiparous patients , a mean change in cervical score of 2.74 + /- 1.16 was observed in the study group when compared with the control group , 0.92 + /- 1.07 . Forty-six per cent of the patients went into labour compared with 12 % in the control group . All findings were highly significant and there were no maternal or fetal side-effects . The study confirmed the efficacy of breast stimulation in cervical ripening and induction of labour Two hundred consecutive women with uncomplicated pregnancies , at or within 4 days of their expected date of confinement , were prospect ively r and omized into 2 groups . One group had expectant management , with twice weekly surveillance tests , while the other group had 3 mg of vaginal prostagl and in E2 as outpatient treatment . There were 104 women in the expectant group and 70 in the induction group ( 26 women allocated to induction preferred no treatment ) . The average number of days to delivery was 1.6 in the induction group and 5.2 in the expectant group ( p < 0.001 ) . While meconium was much less frequent in the induction group ( p < 0.002 ) , all other outcome measures , including cesarean section rates , incidence of macrosomia , and Apgar scores , were similar in the two groups In a prospect i ve r and omized study , pregnancies with unfavorable cervix and well established gestational age of at least 42 weeks were selected for management by either antepartum fetal testing or prostagl and in gel induction of labor . Of the 108 pregnancies studied , 57 ( 53 % ) had labor induced and 51 ( 47 % ) continued without intervention . Comparison of the two groups showed no difference in meconium staining , fetal distress , length of first stage of labor , the need for intervention , or the mode of delivery . In terms of Apgar score the neonatal outcome was not significantly different but a greater proportion of the babies ( 7.8 % versus 1.8 % ) in the noninduced group required intubation . Our data show that there is no particular advantage in letting the pregnancy go beyond 42 completed weeks of gestation especially if prostagl and in is available for induction of labor OBJECTIVE To determine whether outpatient administration of intracervical prostagl and in ( PG ) E2 gel decreases the interval to delivery and duration of labor . METHODS A r and omized , double-blind , placebo-controlled trial compared the intracervical placement of 0.5 mg PGE2 gel with placebo in 61 pregnant women at 38 weeks ' or greater gestation with Bishop scores less than 9 . Transvaginal cervical length , fetal fibronectin , and Bishop score were assessed before gel placement . Subjects were then allowed to go into spontaneous labor unless an indication for induction developed . RESULTS Thirty women were assigned to PGE2 and 31 to placebo . There were no significant demographic differences between the groups and there were no differences in cervical length , fetal fibronectin status , or Bishop scores . Fifteen women in the PGE2 group and five in the placebo group went into labor and delivered within the first 2 days after gel placement ( P = .007 ) . The median interval to delivery was significantly shorter in the PGE2 group , at 2.5 days , compared with placebo , at 7 days ( P = .02 ) . Nulliparas in the PGE2 group had a median interval to delivery of 2 days , compared with 7 days for nulliparas receiving placebo ( P = .03 ) . Active phases of labor were significantly shorter in the PGE2 group and for women with a negative fetal fibronectin test who received PGE2 . CONCLUSION Outpatient administration of intracervical PGE2 gel shortened intervals to delivery and shortened labor Objective To compare the effects of 50 mg or 200 mg of oral mifepristone with placebo on cervical ripening and induction of labor in primigravid women at term with unfavorable cervices . Methods This was a double-blind study in which 80 primigravidae at term with a modified Bishop score of 4 or less were r and omly assigned to one of three treatment groups . They were assessed at 24-hour intervals for 72 hours , after which labor was induced if it had not occurred spon-taneously . Results Two hundred milligrams of mifepristone result ed in a favorable cervix ( with a Bishop score greater than 6 or in spontaneous labor ) in significantly more women than placebo ( P = .01 ) . An improvement in cervical ripening was seen in the group given 50 mg of mifepristone , but this was not statistically significant . There were more cesarean deliveries performed for fetal distress in the group treated with 200 mg of mifepristone than placebo , but this was not statistically significant and was not associated with any differences between groups in terms of neonatal outcome . Conclusion Mifepristone , a progesterone antagonist , is known to cause softening and dilation of the human early pregnant cervix and an increase in uterine activity . It is theoretically attractive for use as an adjunct in cervical priming and labor induction . In this study , 200 mg of mifepristone was significantly more likely to result in a favorable cervix than placebo Background There is increasing interest in carrying out pre-induction cervical ripening on an outpatient basis . However , there are concerns about the use of prostagl and ins , the agents commonly used in hospital setting s for this indication , because prostagl and ins induce uterine contractions that may lead to fetal hypoxia . Indeed , in a recent study we demonstrated abnormalities in 9 % of fetal heart rate tracings performed following prostagl and in induced cervical ripening at term . In contrast , we confirmed in the same study that isosorbide mononitrate ( IMN ) ( administered on an inpatient basis ) was both effective in inducing cervical ripening at term , and was associated with no associated fetal heart rate abnormalities . Methods / design The aim of this study is to determine whether IMN self administered by women on an outpatient basis improves the process of induction of labour . Specifically , we hypothesise that the use of outpatient IMN will result in a shorter inpatient stay before delivery , decreased costs to the health service and greater maternal satisfaction with ripening and induction of labour , compared with placebo treatment . In the study described here ( the " IMOP " study ) , women scheduled for induction of labour at term , and who require pre-induction cervical ripening will be r and omised to self-administer at home either IMN 40 mg , or a placebo , each vaginally , at 48 hours , 32 hours and 16 hours before scheduled hospital admission . After admission to hospital , treatment will revert to the usual induction of labour protocol . We will compare the primary outcomes of the elapsed time interval from hospital admission to vaginal delivery , the costs to the health service of induction of labour , and women 's experience of induction of labour in the two groups . Discussion This trial will provide evidence on the efficacy of outpatient IMN for pre-induction cervical ripening at term . We will study a formulation of IMN which is cheap and widely available . If the treatment is effective , acceptable to women , and cost effective , it could be implemented into obstetric practice worldwide . Trial registration The trial has been registered on the International St and ard R and omised Controlled Trial Number Register ( IS RCT N ) and given the registration number ISRTN39772441 OBJECTIVE Our purpose was to determine whether a protocol for outpatient induction is safe and effective for initiating labor . STUDY DESIGN A r and omized , double-blind , placebo-controlled trial was performed with 100 low-risk patients having well- date d pregnancies . Women with a Bishop score < or = 6 at 38 to 40 weeks ' gestation were administered either 2 mg of intravaginal prostagl and in E2 gel or placebo for 5 consecutive days as out patients while undergoing fetal monitoring . RESULTS The median interval from r and omization to delivery was 4 days in the prostagl and in E2 group ( range 0 to 28 days ) versus 10 days in the placebo group ( range 0 to 26 days , p = 0.002 ) . Twenty-seven of 50 patients ( 54 % ) in the prostagl and in E2 group were admitted for labor during the dosing interval compared with 10 placebo-treated patients ( 20 % , p = 0.001 ) . The mean gestational age at delivery was significantly reduced in the treatment group ( 39.9 + /- 1.0 weeks vs 40.5 + /- 0.99 weeks , p = 0.003 ) as was the incidence of post date s pregnancy ( 40 % vs 66 % , p = 0.016 ) . Hyperstimulation was observed in one prostagl and in E2-treated patient , but no intervention was required . CONCLUSIONS Outpatient low-dose prostagl and in E2 gel administration is effective for initiating labor in patients with an unfavorable cervix and appears safe if performed with adequate monitoring OBJECTIVE Within the obstetric community , several studies suggest that cervical ripening and labor induction after 40 weeks ' gestation leads to improved maternal and neonatal outcomes . The most effective drug regimen to safely promote labor has not been determined . METHOD Forty-nine subjects followed in an outpatient obstetrical clinic with pregnancies of at least 40 weeks ' gestation , and an unfavorable Bishop score were assigned r and omly to receive oral misoprostol 50 or 25 microg every 3 days for a maximum of three doses . RESULTS Twenty-three subjects received misoprostol 25 microg and 26 received 50 microg . The mean interval ( + /-st and ard deviation ) from start of cervical ripening to delivery was 2.4 days + /-0.3 vs. 3.9 days + /-0.7 for the 50 and 25 microg groups ( P<0.05 ) . No adverse events were noted . However , due to small sample size , less frequent adverse events may be missed . Type II errors can not be excluded . CONCLUSION In the prevention of post date pregnancy , out patients use of oral misoprostol 50 microg appears to result in earlier delivery , as compared to 25 microg Abstract Our purpose was to examine the hypothesis that corticosteroids , when administered intramuscularly , can enhance the labor process and reduce the time interval between the induction and the active phase . A r and omized , controlled study was conducted on 66 women with gestational age of 41 weeks and over and favorable cervix ( bishop score ≥ 7 ) . The study group ( n = 32 ) received 10 mg of dexamethasone phosphate intramuscularly in two doses at an interval of 12 hours , and the day after the enrolling administration intravenous oxytocin was given . The control group ( n = 33 ) received only intravenous oxytocin 24 hours after enrolling . The number of patients to enter the active phase of labor was significantly higher in the study group than in the control group ( n = 33 [ 100 % ] vs n = 29 [ 87.9 % ] , p < 0.039 ) . The mean time interval between induction of labor and the active phase was significantly shorter in the study group than in the control group ( 1.7±1.5 hours vs 4±1.7 , P < 0.0001 ) , and the mean of oxytocin dose was significantly lower in the study group ( 1.15±1.5u vs 4.16±2.5u , P < 0.0001 ) . Induction of labor with the use of intramuscularly injected dexamethasone phosphate reduced the time interval between the induction of labor and the active phase A double-blind , placebo-controlled , prospect i ve investigation was undertaken to determine whether the outpatient administration of prostagl and in E2 gel was helpful for ripening the cervix in post date pregnancies . One hundred eighteen women with an uncomplicated pregnancy at or beyond 42 weeks ' gestation with an unripe cervix ( Bishop score less than or equal to 5 ) were r and omly administered a single dose of gel containing either 2.5 mg prostagl and in E2 ( n = 55 ) or a placebo ( n = 63 ) before induction of labor with Pitocin . No side effects were detected in these healthy mothers and fetuses . A distinct change in Bishop score after 12 hours occurred more often in the prostagl and in E2 than in the placebo group ( 42 % versus 6 % , p less than 0.0001 ) . Forty-four women ( 80 % ) who had received prostagl and in E2 were admitted in early labor ; they required little or no oxytocin for augmentation . The duration of labor and maximum dose of oxytocin infused were significantly decreased in the prostagl and in E2 group , and forceps delivery or primary cesarean sections were performed less often when prostagl and in E2 was used ( 24 % versus 44 % , p less than 0.05 ) . The outpatient administration of a single dose of prostagl and in E2 gel is safe in the uncomplicated post date pregnancy and was found to significantly change the unripe cervix , enhance the onset of labor , minimize the need for oxytocin administration , and encourage a spontaneous vaginal delivery Induction of labor is frequently a matter of medical or obstetric necessity . Patients with worsening maternal or fetal problems often have an unfavorable cervix which may preclude successful induction of labor . In a blind , r and omized , controlled trial of breast stimulation to ripen the cervix at term , it was found that breast stimulation was associated with a 45 % incidence of spontaneous labor . When the patient did not go into labor , there was a mean change of 2.4 points in the Bishop score . Both findings are highly significant when compared with the control group Objective To evaluate the efficacy and tolerance of mifepristone in women undergoing induction of labour at term after previous caesarean section Objective : To determine whether weekly outpatient administration of prostagl and in gel or estrogen cream initiated labor in women with an unfavorable cervix . Methods : All uncomplicated pregnancies at term gestation who were c and i date s for a vaginal delivery with a Bishop score of ≤ 6 were r and omly assigned to receive on a weekly basis : prostagl and in E2 gel ( n = 41 ) ; estrogen cream ( n = 44 ) ; or inert lubricant jelly ( n = 43 ) . Results : In the three groups no differences were observed among 128 subjects in the weekly Bishop scores , cervical dilatation or gestational age upon admission to the labor and delivery suite , the percentage of patients presenting with spontaneous labor or ruptured membranes , the number of post- date inductions or neonatal outcome . Conclusions : Weekly out-patient cervical ripening using either prostagl and in gel or estrogen in women with an unfavorable cervix at 37 weeks ' gestation was no more effective than a placebo in Bishop score improvement or in preventing post- date inductions Recent experience has suggested that porcine ovarian relaxin may promote cervical changes . We have performed two double-blind r and omized studies : ( 1 ) comparing cervical changes with relaxin versus placebo during oxytocic labor induction and ( 2 ) as out patients in post date s pregnancies . In the induction study , cervical changes were speeded up by both 2 and 4 mg doses of relaxin , and times to delivery were decreased . In the outpatient study , 2 mg doses of relaxin produced greater cervical changes than did control or 4 mg doses . We conclude that relaxin may have benefit in ripening of the cervix . Since relaxin works directly on the cervix and not through uterine contractions , relaxin may have advantages in cervical ripening of pregnancies in which stress to the fetus is an issue 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 To evaluate the efficacy and safety of three concentrations of prostagl and in E2 ( PGE2 ) gel for preinduction cervical ripening . Two hundred ninety-one patients with an unfavorable cervix scheduled for induction of labor were eligible to participate in a prospect i ve , r and omized , double-blind study of one or two doses of intracervical PGE2 gel . Group 1 received a dose of 0.125 mg/2 ml ; group 2 received 0.25 mg/2 ml ; and group 3 received 0.5 mg/2 ml . Outcome variables included change in Bishop score , uterine tachysystole , oxytocin use , route of delivery , and maternal and neonatal complications . Two hundred twenty-nine patients were included in the study , 79 in group 1 , 70 in group 2 , and 80 in group 3 . Among the three groups , no statistically significant differences were noted for change in Bishop score , uterine tachysystole , oxytocin use , route of delivery , or incidence of maternal or neonatal complications , Subsequent labors were frequently complicated by fetal heart rate abnormalities ( 24.3 % ) and uterine tachysystole ( 9.6 % ) ; 84 ( 38.9 % ) patients were delivered by cesarean section . A dose-dependent influence on outcome variables was not identified . Complications from PGE2-ripening within 4 hours of gel application were not dose dependent and occurred infrequently . This study demonstrates that there is no dose in the range tested that assures an absences of tachysystole , limiting the role of outpatient cervical ripening without some period of observation Objective : To shorten post- date pregnancies in a safe , effective manner by outpatient acceleration of cervical ripening . Methods : Eighty patients with uncomplicated pregnancies at or beyond 41 weeks ' gestation and a cervical Bishop score less than 9 were r and omized to daily self-administered , 2-mg intravaginal prostagl and in E2 ( PGE2 ) or placebo suppositories . Each followed a st and ard post- date antepartum surveillance protocol . Patients were admitted for spontaneous labor or for induction if the Bishop score reached 9 , antepartum testing was nonreassuring , exclusion criteria were fulfilled , or if the gestational age reached 44 weeks . Results : Fewer suppositories were used in the PGE2 group ( four versus seven ; P=.006 ) , result ing in earlier gestational age on admission ( 295 versus 297 days ; P=.021 ) and lower antepartum testing charges ( $ 476.97 versus $ 647.29 ; P=.001 ) . Labor and delivery time was significantly decreased in nulliparas ( 10.7 ± 5.1 versus 15.3 ± 7.6 hours ; P=.035 ) . Conclusions : Daily low-dose , patient-administered PGE2 vaginal suppositories can decrease the gestational length and cost of uncomplicated post- date pregnancies by reducing the time to achieve a favorable cervix , the need for antepartum testing , and , potentially , post- date -related complications OBJECTIVE To evaluate the efficacy of mifepristone in inducing labor in women with an unripe cervix , its effect on the cervix and on the status of the newborn . METHODS In a prospect i ve double-blind study , 36 post-term pregnant women with a Bishop score of 5 or less received either 400 mg mifepristone ( n=24 ) or placebo ( n=12 ) . If , 48 hours after the treatment was started , labor had not begun or the Bishop score was 5 or less , the women were given 0.5 mg prostagl and in E2 intracervically , a treatment which was repeated 12 hours later , if necessary . RESULTS During the first 48 hours following treatment , 19 ( 79.2 % ) of the women treated with mifepristone and two of the women ( 16.7 % ) treated with placebo went into labor . In addition , one and three women , respectively , had a ripe cervix at the end of the 48h period . The overall success rate was thus 83.3 % for mifepristone and 41.7 % for placebo ( p=0.008 ; OR 14.8 ; 95 % CI 2.1 - 107.6 ) . The median time from the start of treatment to delivery was also shorter ( mifepristone 36h23 ' and placebo 53h17 ' ) . Treatment with intracervical PGE2 was needed more often after the placebo . The duration of labor , however , tended to be shorter after placebo than after mifepristone in the women who delivered vaginally . The frequencies of instrumental delivery were similar in both treatment groups . The median Apgar score was slightly lower at 1 minute ( p<0.05 ) following mifepristone treatment , but did not differ at 5 and 10 minutes . There was no difference between the two treatment groups in the umbilical pH at delivery . CONCLUSION The results of the present study show that mifepristone is a simple and effective treatment for inducing labor in post-term women with an unripe cervix Objective . To evaluate the utility of outpatient acupuncture for labor stimulation . Methods . Nulliparous women at 39 4/7 weeks or greater with a singleton gestation and Bishop score of less than 7 were r and omized to usual medical care ( control group ) versus usual care and three outpatient acupuncture treatments ( acupuncture group ) . Each treatment consisted of eight needles applied to bilateral points LI4 , SP6 , UB31 , and UB32 . The primary outcome was time elapsed from the time of r and omization to delivery . Secondary outcomes included rates of cesarean section and induction of labor . Medical records were abstract ed for maternal demographic , medical , and delivery outcome data . A priori sample size calculation revealed that 56 women were required to detect a 72-hour difference in delivery time with a power of 83 % and an alpha of 0.05 . Student 's t-test , Chi-square , and Kaplan – Meier statistics were used to compare groups . Results . Fifty-six women were r and omized and completed the study procedures . Race , age , gestational age , and cervical Bishop score were similar in both groups . Mean time to delivery occurred 21 hours sooner in the acupuncture group , but this difference did not reach statistical significance ( p = 0.36 ) . Compared to controls , women in the acupuncture group tended to be more likely to labor spontaneously ( 70 % vs. 50 % , p = 0.12 ) and less likely to deliver by cesarean section ( 39 % vs. 17 % , p = 0.07 ) . Of women who were not induced , those in the acupuncture group were more likely to be delivered than the controls at any point after enrollment ( p = 0.05 ) . Conclusion . Acupuncture is well tolerated among term nulliparous women and holds promise in reducing interventions that occur in post-term pregnancies Background . Interventions that may help shorten the duration of pregnancy in an African setting where facilities for fetal monitoring in post‐term pregnancy are limited , and induction is not without its hazards , are needed OBJECTIVE To compare the clinical effectiveness and safety of outpatient administration of intracervical prostagl and in ( PG ) E2 gel with expectant treatment for women desiring vaginal births after cesareans . METHODS This was a r and omized , multicenter investigation involving term pregnant women who each had one previous low-transverse cesarean and an unfavorable cervix ( Bishop score no more than 6 ) , and who was a c and i date for vaginal delivery . They were assigned to receive 0.5 mg of PGE2 , ( Prepidil ; Pharmacia-Upjohn , Kalamazoo , MI ) intracervically at 39 weeks ' gestation , repeated at weekly office visits for up to three doses , or expectant treatment . The main outcome variable was vaginal birth . RESULTS Of 294 cases , 143 received gel and 151 were treated expectantly . No differences between groups were found for maternal age , race , or Bishop score . Compared with the expectant treatment group , the PGE2 gel group was not more likely to deliver sooner or vaginally ( 57 % versus 55 % , P = .68 ) . The onset of labor , duration of labor among those delivering vaginally , and 1- and 5-minute Apgar scores were not different between groups . No uterine ruptures occurred , and adverse effects were equally likely in both groups . CONCLUSION Although its safety was confirmed for outpatient use , weekly doses of intracervical PGE2 did not improve the likelihood of vaginal births after cesareans Objective To determine if outpatient cervical ripening using misoprostol can initiate labor within 48 hours of medication administration and to determine if time from medication administration to time of delivery is decreased using outpatient cervical ripening . Methods Uncomplicated singleton , vertex pregnancies at 41 weeks ' gestation or later with Bishop score of 4 or less were eligible for enrollment . Other inclusion criteria included intact membranes , less than eight uterine contractions per hour , a reactive nonstress test , and amniotic fluid index ( AFI ) over 5 cm . After r and omization , 25 μcg of misoprostol or placebo was placed within the posterior vaginal fornix . Patients were continuously monitored for 4 hours , then discharged if not in active labor . Patients returned in 24 hours for a repeat administration of the respective medication . Patients not delivered within 48 hours were admitted for inpatient induction of labor . Statistical analysis was performed with the Fisher , Student t , χ2 , and Mann-Whitney U tests , with P < .05 considered statistically significant . Results Among the 60 patients enrolled , 27 ( 45 % ) received misoprostol and 33 ( 55 % ) received placebo . The majority ( 24 of 27 , 88.9 % ) of study group patients entered active labor within 48 hours after dosing , compared with 16.7 % ( five of 33 ) of placebo group patients ( P < .001 ) . The time from initial dose to delivery was significantly shorter in the misoprostol group ( 36.9 ± 3.8 compared with 61.3 ± 3.8 hours , P < .001 ) . Conclusion Intravaginal misoprostol is effective for outpatient cervical ripening . No adverse effects were encountered , although further study is required to determine the safety of this treatment regimen Objective : To compare the clinical effectiveness and safety of outpatient administration of an intracervical prostagl and in ( PG ) E(2 ) gel with expectant management for women with an unfavorable cervix who wish to attempt a vaginal birth after cesarean section . Study Design : This outpatient study was a r and omized , multicenter investigation involving pregnant women at term with one previous low transverse cesarean section . Each had an unfavorable cervix ( Bishop score < /=4 ) and was a c and i date for vaginal delivery . Those r and omly assigned to receive the gel , rather than expectant management , were given a 0.5 mg dose of PGE(2 ) ( Prepidil ) intracervically at 39 weeks gestation . This cervical ripening treatment was repeated at weekly office visits for up to 3 doses . Results : Of the 294 cases , 143 received the gel while 151 underwent expectant management . No differences between the two groups were found for maternal demographics , race , parity , or predose Bishop score . The rates of repeat cesarean section did not differ ( P = .68 ) with use of the gel ( 61 , 42 % ) or with expectant therapy ( 48 , 45 % ) . The onset of active labor , the duration of labor among those delivering vaginally , and the 1-minute and 5-minute Apgar scores were not different between the two groups . No uterine rupture was apparent , and adverse effects during labor were as likely to occur in the two groups . Conclusions : Although its safety was confirmed for outpatient use and for persons with a prior cesarean delivery , intracervical prostagl and in E(2 ) gel did not improve the chance of a vaginal birth after a cesarean delivery OBJECTIVE Our aim was to examine the efficacy , safety , and acceptability of isosorbide mononitrate for cervical ripening and labor induction in women in an outpatient setting . STUDY DESIGN Two hundred pregnant women of at least 42 weeks ' gestation with an unripe cervix were r and omly selected to receive vaginally either 40 mg isosorbide mononitrate or placebo tablets . RESULTS Twenty-two women treated with isosorbide mononitrate went into labor within 24 hours compared to 8 women in the placebo group ( P < .05 ) . In women who did not go into labor , cervical status was similar in the 2 groups the next day . Headache was a common side effect . No maternal or fetal side effects of clinical importance were registered . CONCLUSION Outpatient cervical ripening and labor induction with isosorbide mononitrate seems to be an effective , safe , and well tolerated procedure . The definitive clinical efficacy and safety needs to be evaluated in larger series of patients OBJECTIVE To investigate the action of intracervical administration of hyaluronidase ( HAase ) as an inductor of cervical ripening on an outpatient basis . METHODS A r and omized double-blind trial was conducted with 168 pregnant women at term , Bishop score (BS)<5 , normal fetal vitality and no uterine contractions . An evaluation was performed at the first visit , when either 20,000 UI of lyophilized HAase ( 5 ml ) or placebo was administered via cervical injection . After 48 h , if the BS remained<5 , a second dose was administered . The primary outcome was the BS after 48 h or 96 h. The outcome was considered positive when BS>/=5 . RESULTS The results indicate that the proportion of positive response for the HAase group ( 55 % ) after 48 h is significantly higher ( p<0.0001 ) than the corresponding proportion for the placebo group ( 7 % ) with an absolute risk reduction ( ARR ) of 48%=55 - 7 % ( 95%CI=40 - 56 % ) . After 96 h , these proportions are 93 % in the Haase group and 22 % in the placebo group ( p<0.0001 , ARR=71 % , 95%CI=61 - 81 % ) . The average duration of labour for the nulliparae in the HAase group ( 6.5h ) is significantly smaller ( p<0.0001 ) than for those under placebo ( 12.0 h ) with an absolute difference of 5.5h ( 95%CI=4.6 - 6.4h ) . For the multiparae , the results are 4.3h for the HAase patients versus 9.5h for the placebo patients ( p<0.0001 ) with an absolute difference of 5.2h ( 95%CI=4.1 - 6.3h ) . The proportion of vaginal deliveries for women who received HAase was 82 % versus 51 % for the placebo group ( p=0.0007 , ARR=31 % , 95%CI=19 - 44 % ) . The proportion of vaginal deliveries for patients with prior cesareans in the HAase group ( 69 % ) was also significantly higher ( p<0.0001 ) than that corresponding to the placebo group ( 13 % ) with ARR=56 % ( 95%CI=26 - 86 % ) . No uterine hyper stimulation occurred in the study . CONCLUSION We detected significant associations between intracervical injection of HAase and ripening of the cervix , as well as with shorter duration of labour and larger chance of vaginal delivery , suggesting that this is a simple , effective and safe method even for women with prior cesarean 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 : To determine whether a single outpatient dose of intravaginal misoprostol ( versus intracervical dinoprostone gel ) reduces the oxytocin use for induction . Despite the numerous trials examining misoprostol for induction , the efficacy of a single outpatient dose of misoprostol followed by oxytocin induction is unknown . METHODS : Patients with a term , vertex , singleton pregnancy and a Bishop score of 6 or less were r and omly assigned to receive misoprostol ( n = 42 , 0.25 μg intravaginally ) or dinoprostone gel ( n = 42 , 0.5 mg intracervically ) the evening before oxytocin induction . Patients were monitored for 3 hours after administration and discharged to home if fetal assessment was reassuring , for readmission the next morning for oxytocin . Primary outcomes were oxytocin dose , time , and dose intensity ( dose divided by duration ) . Secondary outcomes were incidence of labor , uterine hyperstimulation , cesarean delivery , Apgar score . Statistics used were χ2 , Student t test , Mann-Whitney rank sum test , and Fisher exact test . P < .05 was accepted as statistically significant . RESULTS : A single dose of misoprostol significantly decreased the cumulative dose of oxytocin , the cumulative time of oxytocin administration , and the dose intensity of oxytocin ( dose divided by time ) . Data are as follows ( mean ± st and ard error of the mean ) : oxytocin dose — dinoprostone 10,929 ± 219 mU , misoprostol 6,081 ± 170 mU , P = .008 ; oxytocin time — dinoprostone 798 ± 11 minutes , misoprostol 531 ± 11 minutes , P = .009 ; dose intensity — dinoprostone 11.3 ± 0.1 mU/min , misoprostol 7.4 ± 0.2 mU/min , P = .003 . Misoprostol induced labor during the ripening period in 19 of 41 of patients , compared with 6 of 42 after dinoprostone ( P = .002 ) . There was no difference in cesarean delivery ( dinoprostone , 8/42 ; misoprostol , 9/42 ; P = 1.00 ) . There was no difference in short-term neonatal outcome . No patient had hyperstimulation or required cesarean delivery for nonreassuring fetal assessment during the ripening period . CONCLUSION : A single dose of misoprostol administered in the outpatient setting significantly decreases oxytocin use , largely due to labor within the ripening period . LEVEL OF EVIDENCE : A prospect i ve double-blind r and omized study was undertaken to evaluate the use of RU-486 for induction of labor at term with living infants . 120 patients at 37 weeks of pregnancy or over were included . 60 were given 200 mg RU-486 per day for 48 hours and the others were given placebos . The 120 women all had a medical indication for induction of labor . In the RU-486 and placebo groups respectively , 27 and 28 were past term , 10 and 13 had preeclampsia , and 6 and 4 showed signs of intrauterine growth retardation . 75 were primiparas . Pregnancy ages ranged from 37.5 weeks to 41.4 and averaged 39.8 . The uterus was scarred in 30 cases . The 2 groups were homogeneous in maternal age , pregnancy age , average parity , number of primiparas and number of scarred uterus , and average Bishop scores indicating cervical status . 3 patients in the RU-486 and 5 in the placebo group were excluded from the analysis because of deteriorating obstetrical status in the 12 hours after administration of the 1st pill . For all vaginal deliveries , the total dose in international units of oxytocin was lower in the RU-486 group : 2.41 + or- 2.4 international units , vs. 4.48 + or- 2.66 in the placebo group . The difference was also found in women undergoing caesareans , 2.97 + or- 1.82 vs 4.94 + or- 2.41 in the controls . 31 women in the RU-486 group but only 10 in the placebo group underwent spontaneous labor . It was possible to induce labor on the 4th day following administration of the 1st dose of RU-486 or placebo using prostagl and in ( PG ) E1 in 13 patients in each group . 13 patients in the RU-486 group and 32 in the placebo group still had Bishop scores under 4 on the 4th day . For this subgroup of 45 patients , there was no significant difference between the 2 groups in the average dose of PG E2 . Indication of labor with RU-486 alone was especially successful after 40 weeks of gestation . In this series , RU-486 was successful in spontaneously inducing labor in over 80 % of pregnancies around 41 weeks of gestation . There were no significant differences in the RU-486 and placebo groups in the type of delivery , average duration of labor , use of anesthetic , or neonatal condition . Maternal tolerance of RU-486 was good . There were no cases of metrorrhagia . RU-486 was shown to be useful for women with scarred uteri , in whom the use of oxytocin and prostagl and ins for induction of labor remains relatively contraindicated OBJECTIVE The purpose of this study was to compare the efficacy and safety profile of prostagl and in E2 with isosorbide mononitrate for cervical ripening before the induction of labor at term . STUDY DESIGN Primigravid women were assigned r and omly to receive either 40 mg of isosorbide mononitrate or 2 mg of prostagl and in E2 . Efficacy outcomes were the cervical ripening effect of each agent and the time from treatment initiation to delivery . Safety outcomes were the incidence and frequency of maternal side effects and events that would be potentially hazardous for mother and baby during outpatient cervical ripening . RESULTS Prostagl and in E2 was more effective than isosorbide mononitrate in inducing a change in modified Bishop score . Mean duration from treatment initiation to delivery was greater for isosorbide mononitrate than prostagl and in E2 . There were no adverse events in the isosorbide mononitrate group that would contraindicate outpatient treatment . However , in the prostagl and in E2 group , 7 % of the pregnancies had abnormal fetal heart rate patterns ( P = .0002 ) . Maternal satisfaction was significantly higher in the isosorbide mononitrate group . CONCLUSION Although isosorbide mononitrate was less effective , maternal satisfaction was significantly greater . The safety profile of each agent was such that it would be reasonable to give isosorbide mononitrate , but not prostagl and in E2 , on an outpatient basis OBJECTIVE To examine the effectiveness and safety of outpatient vaginal administration of isosorbide mononitrate ( IMN ) to induce cervical ripening . METHODS A prospect i ve , double-blind , placebo-controlled , r and omized clinical trial was conducted on 102 singleton term pregnant women with unfavorable cervices who were r and omly assigned to receive outpatient intravaginal IMN or placebo before admission for induction of labor . The main outcome variable was time from hospital admission to delivery . Secondary outcomes included fetal and maternal morbidity , labor characteristics , and incidence of cesarean delivery . RESULTS The admission-delivery interval was 13.45+/-6.63 and 20.12+/-8.19 h ( P=0.0001 ) for the IMN and placebo groups , respectively . Of the IMN patients 62.75 % needed prostagl and ins for cervical ripening versus 90.2 % with placebo ( P=0.002 ) . The incidence of tachysystole was significantly lower in the IMN group ( P<0.05 ) but there were no significant differences in cesarean delivery rate , neonatal outcomes , and incidence of hyperstimulation . CONCLUSIONS Outpatient use of IMN result ed in shorter admission to delivery interval , and was associated with less prostagl and in use and lower incidence of uterine tachysystole OBJECTIVE To compare the use of vaginally administered misoprostol to placebo for outpatient labor induction in patients with diabetes . STUDY DESIGN In this double-masked , controlled clinical trial , pregnant women with diabetes and gestational age of > 38(1/2 ) weeks were r and omized to receive 25 microg misoprostol or placebo vaginally on days 1 and 4 of a 7-day outpatient cervical ripening period . If necessary , inpatient labor induction was managed by using a st and ard protocol . RESULTS Of 120 women included in the study , 57 received misoprostol and 63 received placebo . Most of the women had been diagnosed with gestational ( Class A ) diabetes . Similar numbers of misoprostol and placebo-treated women delivered within 7 days of the first dose ( 31/57 [ 54 % ] vs 36/63 [ 57 % ] , P = .63 ) . The mean ( + /-SEM ) interval from induction to delivery was similar ( 8530.5 minutes + /-1439.7 minutes vs 6712.5 minutes + /-606.4 minutes , P = .23 ) . CONCLUSION Vaginally administered misoprostol was no more effective than placebo in reducing the need for inpatient labor induction or the induction-delivery interval . Outpatient cervical ripening with use of vaginally administered misoprostol was well tolerated Objective : To determine the efficacy and safety of mifepristone as an induction agent for the initiation of labor or as a cervical ripening agent in women at term . Methods : Our study group contained 120 women at term ( after 37.5 weeks ' amenorrhea ) who had clear clinical indications for labor induction . They were r and omized to receive either 200 mg of mifepristone or placebo on days 1 and 2 of a 4-day observation period , with labor induction planned for day 4 . Eight patients , three treated with mifepristone and five receiving placebo , had to be excluded from the survey because they required cesareans for medical reasons ( fetal distress or maternal complications ) less than 12 hours after taking the first tablet . Results : Forty-one subjects entered spontaneous labor , 31 treated with mifepristone and ten in the control group ( P<.001 ) . Forty-five needed cervical maturation with prostagl and ins on day 4,13 of whom had received mifepristone and 32 of whom had been given placebo ( P<.001 ) . Thirteen women treated with mifepristone and 13 who had taken placebo had mature cervices sufficient for classic labor induction with oxytocin and amniotomy . Patients who delivered vaginally needed a much lower amount of oxytocin when mifepristone had been given , and the mean time interval between day 1 of the survey and the onset of labor was also significantly shorter in this group . Conclusion : Although more studies are needed , we have found mifepristone to be a safe , efficient , and suitable induction agent for initiation of labor in women at term . ( Obstet Gynecol 1992;80:972 - 5 OBJECTIVE Our purpose was to evaluate whether inserting prostagl and in E2 gel at the time of scheduled nonstress tests in patients with post date pregnancies can decrease rates of intervention . STUDY DESIGN A multicenter pilot study enrolled women with post date pregnancies with Bishop score < or = 6 who were undergoing antepartum fetal heart rate testing . Patients were r and omized in a double-blind fashion to receive either a prostagl and in E2 intracervical gel ( Prepidil ) or a placebo gel after each of their scheduled nonstress tests . RESULTS There were no significant differences in the number of antepartum tests , labor inductions , or cesarean sections , the maximum oxytocin dosage , or the interval from admission to delivery in the prostagl and in E2 gel and placebo gel groups ( n = 90 ) . In the subset of patients with a Bishop score between 3 and 6 ( 63 patients ) , there were fewer inductions in the prostagl and in E2 group ( 30 % vs 55 % , P < .05 ) . CONCLUSION Application of prostagl and in E2 gel at the time of scheduled antepartum testing in patients with post date pregnancies with unfavorable cervices decreased the induction rate only among patients with intermediate Bishop scores Post date pregnancy is estimated to occur in 3 % to 12 % of all gestations . Morbidity and mortality rates associated with this common obstetric problem are higher than those with term gestation . The incidence of fetal distress , birth injury , meconium aspiration , congenital malformations , macrosomia , and oligohydramnios is also greater in post date pregnancy . We prospect ively evaluated breast self-stimulation to determine its effect on the incidence of post date pregnancy . Two hundred low-risk patients at 39 weeks ' gestation were r and omly assigned to either a control group or a breast-stimulation group . Results showed that breast stimulation reduced the number of pregnancies managed as post date s from 17 per 100 ( 17 % ) to five per 100 ( 5 % ) ( p less than 0.01 ) , a 70 % reduction . It is concluded that breast stimulation in post date s pregnancies can decrease significantly the number of patients that must be monitored by biochemical or biophysical means OBJECTIVE : To estimate the effect of outpatient administration of a single dose of vaginal misoprostol at term on the interval to delivery in women with unfavorable cervices . METHODS : R and omized , double blind , placebo-controlled trial comparing a single 25-μg outpatient intravaginal dose of misoprostol to placebo in pregnant women with Bishop scores less than 9 at 40 weeks or greater . After placement of the study medication , subjects were permitted to go into spontaneous labor unless an indication for induction developed . Analysis was by intent to treat . The interval to delivery , defined as the time from medication placement to delivery , was compared by Student t test and by survival analysis with the log-rank test . RESULTS : Thirty-three women were r and omly assigned to receive misoprostol , and 35 were assigned to receive placebo . The mean interval to delivery was significantly less in the misoprostol group , 4.2 ± 4.1 compared with 6.1 ± 3.6 days , P = .04 . The interval to delivery for only the nulliparous patients was significantly less in the misoprostol group , 4.2 ± 4.0 compared with 7.2 ± 3.7 days , P = .02 . The survival curves for the interval to delivery were significantly different ( P = .04 by log-rank test ) with 4.1 days median interval to delivery for misoprostol compared with 9.2 days for placebo . There were no adverse outcomes in either group . CONCLUSION : A single 25-μg outpatient intravaginal dose of misoprostol is effective in decreasing the interval to delivery in women with unfavorable cervices at term . LEVEL OF EVIDENCE : OBJECTIVE : To characterize the frequency and timing of cardiotocographic abnormalities associated with the use of 3 commercially available prostagl and in analogues , misoprostol , dinoprostone gel , and dinoprostone pessary , as labor preinduction agents . METHODS : One-hundred and eleven women undergoing induction of labor with an unfavorable cervix were r and omized to receive either misoprostol 50 μg every 6 hours × 2 doses , dinoprostone gel 0.5 mg every 6 hours × 2 doses , or dinoprostone pessary 10 mg × 1 dose for 12 hours intravaginally . Oxytocin induction was initiated per st and ardized protocol . Cardiotocographic tracings were blindly review ed , with abnormalities coded using established definitions . RESULTS : Fifty-five percent of women treated with misoprostol demonstrated an abnormal tracing event within the initial 24 hours of induction , compared with 21.1 % with dinoprostone pessary and 31.4 % with the dinoprostone gel . The mean ( ± st and ard deviation ) number of abnormal events was significantly greater in women treated with misoprostol ( 5.0 ± 5.9 ) versus the dinoprostone pessary ( 1.6 ± 2.5 ) and gel ( 2.2 ± 3.1 ) ( P < .05 ) . In addition , these events occurred earlier after initial misoprostol dosing ( 5.0 ± 4.0 hours ) , compared with the dinoprostone pessary ( 9.4 ± 5.6 hours ) and gel ( 7.7 ± 6.6 ) . Thirty-nine percent of the misoprostol-treated women had abnormal patterns within 6 hours of initial dosing , compared with those treated with the dinoprostone pessary ( 7.9 % ) and gel ( 17.1 % ) . CONCLUSION : Cardiotocographic abnormalities are more frequent after misoprostol administration compared with the dinoprostone analogues . The early onset and frequent nature of the tracing abnormalities associated with misoprostol raises concern for the potential use of misoprostol for outpatient cervical ripening . LEVEL OF EVIDENCE : |
12,033 | 27,578,428 | For induction therapy , no treatment appeared more effective than another in reducing graft loss or mortality .
Compared with placebo/no induction , rATG and BAS appeared more effective in reducing biopsy-proven acute rejection ( BPAR ) and BAS appeared more effective at improving GRF .
For maintenance therapy , no treatment was better for all outcomes and no treatment appeared most effective at reducing graft loss .
BEL + MMF appeared more effective than TAC + MMF and SRL + MMF at reducing mortality .
MMF + CSA ( ciclosporin ) , TAC + MMF , SRL + TAC , TAC + AZA ( azathioprine ) and EVL + CSA appeared more effective than CSA + AZA and EVL + MPS at reducing BPAR .
SRL + AZA , TAC + AZA , TAC + MMF and BEL + MMF appeared to improve GRF compared with CSA + AZA and MMF + CSA .
In the base-case deterministic and probabilistic analyses , BAS , MMF and TAC were predicted to be cost-effective at £ 20,000 and £ 30,000 per quality -adjusted life-year ( QALY ) .
Only a regimen of BAS induction followed by maintenance with TAC and MMF is likely to be cost-effective at £ 20,000 - 30,000 per QALY . | BACKGROUND End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy : kidney transplantation , haemodialysis or peritoneal dialysis . | INTRODUCTION The EuroTransplant " old to old " program establishes that patients older than 60 years can receive offers of organs from donors older than 60 years . The compromised function of these organs makes it a priority to preserve their initial kidney function . HYPOTHESIS Calcineurin-sparing protocol s using anti-IL-2 receptor ( IL-2R ) antibody induction ( Simulect ) may benefit initial kidney function in these patients , as assessed by the rates of delayed graft function and of rejection during the first month after transplant . PATIENTS AND METHODS A cohort of 15 consecutive elderly patients were prospect ively compared with 30 cadaveric kidney transplants in younger recipients . Study patients were induced with Simulect ( 20 mg , 30 minutes before reperfusion and 4 days after transplantation ) and steroids , delaying the introduction of CsA until the serum creatinine was below 3 mg/dL. The other cohort of patients were immunosuppressed with tacrolimus ( trough 8 to 12 ) , mycophenolats mofetil ( MMF , 1 g/d ) , and an identical taper of steroids . The analysis compared donor and recipient ages , mean cold ischemic time , incidence of initial kidney function ( diuresis in the first 24 h ) serum creatinine levels , glomerular filtration rate ( GFR ) , number of dialysis sessions , and rejection rate in the two groups . RESULTS Except for the donor and recipient ages ( 72 vs 54 in donors , and 67 versus 52 years in recipients ) , no significant differences were observed between the groups among the rates of acute rejection ( 6.6 % vs 13.2 % ) , delayed graft function ( 13.2 % required dialysis ) , or infection ( 6.6 % ) . Within 1 month all 45 grafts showed primary function with equal creatinine levels ( mean 1.65 ) . CONCLUSIONS Calcineurin-free protocol s using IL-2 therapy as the initial suppression allow patients in the " old to old " ET program to display equal results to cadaveric kidney transplants with initial treatment with calcineurin antagonists Background . Two open-label studies demonstrated that conversion from mycophenolate mofetil ( MMF ) to enteric-coated mycophenolate sodium ( EC-MPS ) significantly reduces gastrointestinal ( GI ) symptom burden and improves GI-specific health-related quality of life . Using a r and omized design , this study evaluated changes in GI symptoms and health-related quality of life in patients converted from MMF to EC-MPS versus patients who continued with MMF-based treatment . Methods . In this 4-week , multicenter , r and omized , prospect i ve , double-blind , parallel-group trial , renal transplant recipients with GI symptoms receiving MMF plus a calcineurin inhibitor±corticosteroids were r and omized to an equimolar dose of EC-MPS+MMF placebo or continue on their MMF-based regimen+EC-MPS placebo . The primary efficacy outcome was a change from baseline in total Gastrointestinal Symptom Rating Scale score of a minimally important difference of more than or equal to 0.3 . Results . Three hundred ninety-six patients ( EC-MPS group : n=199 ; MMF group : n=197 ) were included . A greater proportion of EC-MPS patients ( 62 % ) reached the primary efficacy outcome compared with MMF patients ( 55 % ) ; however , the difference was not statistically significant ( P=0.15 ) . EC-MPS patients had a significantly greater decrease in the Gastrointestinal Symptom Rating Scale indigestion syndrome dimension versus MMF patients . Within the subgroups of patients with diabetes , patients transplanted 6 to 12 months of study enrollment , and patients on steroids , a statistically significant greater proportion of EC-MPS versus MMF patients reached the primary efficacy outcome . Conclusions . Conversion from MMF to EC-MPS may be associated with improvements in presence and severity of GI symptoms , particularly in patients with indigestion , diabetes , on steroids , and in patients converted between 6 and 12 months posttransplantation This study was design ed to investigate the effect of tacrolimus ( FK506 ) and of cyclosporine ( CsA ) on tubular function in renal graft recipients . Patients were r and omised after renal transplantation to immunosuppressive treatment with FK506 ( n = 8) or CsA ( n = 8) . Patients had a mean age of 45.7 + /- 3.4 yr ; there was no difference in age , sex , HLA status or CMV mismatches . Neither was there any difference in the frequency of episodes of acute kidney failure between the groups , nor was there a significant difference in the frequency of episodes of kidney rejection within the first year . The mean FK506 level at the time lay at 14.7 + /- 14.4 ng/mL whole blood , and the mean CsA level at the time of study was 162 + /- 25 ng/mL whole blood . We performed renal function studies 6 months after transplantation : CIn , CPAH , NaHCO3 loading , and Na2SO4 loading . There was no significant impairment of GFR in patients treated with FK506 with 53.6 + /- 2.5 mL/min as compared to 58 + /- 6 mL in group 2 . Plasma renin activity ( 0.6 + /- 0.4 ng/mL vs 2.3 + /- 3 ; p < 0.01 ) and aldosterone ( 69 + /- 17 vs 157 + /- 28.2 pg/mL ; p < 0.05 ) were significantly decreased during treatment with FK506 . Fractional HCO3 excretion was low in both groups , indicating that bicarbonate reabsorption in the proximal nephron was unimpaired . Distal renal tubular acidosis was demonstrated in 4 patients of group 1 but in only 1 of group 2 . Potassium levels were slightly increased in patients treated with FK506 ( 5.4 + /- 0.2 mmoL/L ) as compared to cyclosporine ( 4.9 + /- 0.3 mmoL/L ; p < 0.05 ) . Distal hydrogen ion secretion , evaluated by the ability to increase urinary pCO2 in a highly alkaline urine , was impaired in patients treated with FK506 ( U-B pCO2 : 16.1 + /- 4 vs 36 + /- 5.8 ; p < 0.05 ) as compared to patients treated with CsA. The maximum acidification capability ( NAE ) was slightly lowered during therapy with FK506 ( 67.5 + /- 11.8 versus 86.6 + /- 16.5 mumoL/min , ns ) . We conclude that FK506 administration results in a decrease in the rate of hydrogen ion secretion by the collecting tubules . This defect was disclosed by the finding of a subnormal pCO2 in a highly alkaline urine . These results show that FK506 is able to induce distal tubular acidosis . Distal tubular acidosis is part of FK506 induced nephrotoxicity , the pathogenesis of this type of hyperkalemic metabolic acidosis found in patients treated with FK506 after renal transplantation has to be further eluci date Acute and chronic lesion scores on renal allograft protocol biopsies may predict long-term graft function . The aim of this study was to compare the effects of tacrolimus ( Tac ) and cyclosporine microemulsion ( CsA ) based immunosuppressive protocol s using protocol biopsies from well-functioning renal allografts . 35 consecutive renal transplant patients were r and omized to Tac ( n : 17 ) versus CsA ( n : 18 ) treatment arms . Patient age and sex , donor type and age , histocompatibility , cold ischemia time and prior delayed graft function were similar between the two groups . Treatment protocol consisted of prednisolone , azathioprine and Tac or CsA. Biopsies performed on the third , sixth and twelfth months were blindly evaluated by the same pathologist . The incidences of acute rejection ( AR ) episodes among CsA vs Tac groups were 33 % vs 29 % , respectively ( NS ) . The Creatinine level was lower in Tac than CsA , although it was not significant ( Table ) . Sub clinical AR and sub clinical chronic allograft nephropathy were detected on protocol biopsies in 3 ( 2 CsA , 1 Tac ) and 12 ( 7 CsA , 5 Tac ) patients , respectively . Acute lesion score at the third month PBx was significantly lower in the Tac group ( p < 0.05 ) . Chronic lesion scores in all biopsies were lower in the Tac group , although not significantly . The protocol biopsy findings suggest that graft injury may be less pronounced among the Tac group Background No study to date has evaluated the efficacy and safety of everolimus with reduced-exposure cyclosporine in Japanese de-novo renal transplant ( RTx ) patients . Methods This 12-month , multicenter , open-label study r and omized ( 1:1 ) 122 Japanese de-novo RTx patients to either an everolimus regimen ( 1.5 mg/day starting dose ( target trough : 3 to 8 ng/ml ) + reduced-dose cyclosporine ) or a mycophenolate mofetil ( MMF ) regimen ( 2 g/day + st and ard dose cyclosporine ) . All patients received basiliximab and corticosteroids . Key endpoints at month 12 were composite efficacy failure ( treated biopsy-proven acute rejection , graft loss , death , or loss to follow-up ) and renal function ( estimated glomerular filtration rate ; Modification of Diet in Renal Disease-4 ) . Results Clear cyclosporine exposure reduction was achieved in the everolimus group throughout the study ( 52 % reduction at month 12 ) . Month 12 efficacy failure rates showed everolimus 1.5 mg to be non-inferior to MMF ( 11.5 % vs. 11.5 % ) . The median estimated glomerular filtration rate at month 12 was 58.00 ml/minute/1.73 m2 in the everolimus group versus 55.25 ml/minute/1.73 m2 in the MMF group ( P = 0.063 ) . Overall , the incidence of adverse events was comparable between the groups with some differences in line with the known safety profile of the treatments . The everolimus group had a higher incidence of wound healing events and edema , whereas a higher rate of cytomegalovirus infections was reported in the MMF group . Conclusions This study confirmed the efficacy of everolimus 1.5 mg/day ( target trough : 3 to 8 ng/ml ) in Japanese RTx patients for preventing acute rejection , while allowing for substantial cyclosporine sparing . Renal function and safety findings were comparable with previous reports from other RTx population s . Trial registration Clinical Trials.gov number : Background The once-daily ( QD ) , prolonged-release formulation of tacrolimus has been shown to improve adherence versus twice-daily ( BD ) tacrolimus . Treatment nonadherence in transplant recipients has been associated with poor graft outcomes . Methods This open-label , parallel-group study r and omized adults with end-stage renal disease undergoing primary kidney transplantation or retransplantation to an initial dose of tacrolimus BD 0.2 mg/kg per day ( Arm 1 ; n=309 ) , QD 0.2 mg/kg per day ( Arm 2 ; n=302 ) , QD 0.3 mg/kg per day ( Arm 3 ; n=304 ) all with mycophenolate mofetil and corticosteroids ( tapered ) over 24 weeks , or tacrolimus QD 0.2 mg/kg per day with mycophenolate mofetil , basiliximab , and corticosteroids given only perioperatively ( Arm 4 ; n=283 ) . The primary composite endpoint ( efficacy failure ; per protocol set ) was defined as graft loss , biopsy-confirmed acute rejection , or graft dysfunction at week 24 . Graft dysfunction was defined as estimated glomerular filtration rate Modification of Diet in Renal Disease-4 formula of less than 40 mL/min/1.73 m2 . The prespecified noninferiority margin was 12.5 % . Results The per protocol set included 976 patients : 237 , 263 , 246 , and 230 patients in Arms 1 to 4 , respectively . Noninferiority of the composite endpoint was demonstrated for Arm 2 versus Arm 1 ; Kaplan – Meier estimates of efficacy failure were 42.2 % and 40.6 % , respectively ( difference , −1.6 % ; 95 % confidence interval [ CI ] , −12.2 % to 9.0 % ) . Noninferiority to Arm 1 was not confirmed for Arm 3 ( difference , −3.5 % ; 95 % CI , −13.6 % to 6.6 % ) or Arm 4 ( difference , −7.1 % ; 95 % CI , −16.1 % to 1.9 % ) . Graft dysfunction ( estimated glomerular filtration rate < 40 mL/min/1.73 m2 ) was the main determinant of composite-endpoint efficacy failure across all arms . Conclusions In patients representative of the European kidney transplant population , tacrolimus QD-based immunosuppression ( 0.2 mg/kg/day ) , without induction , showed similar efficacy to 0.2 mg/kg per day tacrolimus BD BACKGROUND AND OBJECTIVES The optimal maintenance immunosuppressive regimen to improve long-term renal allograft function and graft survival is yet to be determined . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This observational study prospect ively compared tacrolimus/sirolimus with tacrolimus/mycophenolate mofetil in renal transplant recipients using a prednisone-free regimen with over 8.5 years of follow-up . Patients received methylprednisonlone and anti-IL2 receptor antagonist ( Basiliximab ) induction and were blindly r and omized to either the tacrolimus/mycophenolate mofetil ( n=45 ) or tacrolimus/sirolimus ( n=37 ) groups . Outcome measures included patient and renal allograft survival , incidence of acute rejection , and estimated GFR . RESULTS The tacrolimus/mycophenolate mofetil group compared with the tacrolimus/sirolimus group had overall better renal allograft survival ( 91 % versus 70 % , P=0.02 ) ; 13 patients ( 35.1 % ) in the tacrolimus/sirolimus group and 8 patients ( 17.8 % ) in the tacrolimus/mycophenolate mofetil group experienced biopsy-proven acute cellular rejection ( P=0.07 ) . By 3 months post-transplant , estimated GFR was significantly lower in the tacrolimus/sirolimus group compared with the tacrolimus/mycophenolate mofetil group ( 47.7 versus 59.6 ml/min per 1.73 m(2 ) , P=0.0002 ) , and this trend persisted throughout the follow-up period . Also , the slope of decline in the tacrolimus/sirolimus group was significantly steeper than in the tacrolimus/mycophenolate mofetil group . CONCLUSIONS This study shows that , in a prednisone-free immunosuppressive regimen , long-term renal graft survival and function are significantly worse in the tacrolimus/sirolimus group than the tacrolimus/mycophenolate mofetil group . The synergistic nephrotoxic effect and higher acute rejection rates in the tacrolimus/sirolimus compared with the tacrolimus/mycophenolate mofetil group adversely affect graft survival Prospect i ve data are lacking concerning the effect of reduced mycophenolic acid ( MPA ) dosing on efficacy and the influence of concomitant tacrolimus exposure . The Mycophenolic Renal Transplant ( MORE ) Registry is a prospect i ve , observational study of de novo kidney transplant patients receiving MPA therapy under routine management . The effect of MPA dose reduction , interruption , or discontinuation ( dose changes ) was assessed in 870 tacrolimus‐treated patients : 375 ( 43.1 % ) reduced tacrolimus ( ≤7 ng/mL at baseline ) and 495 ( 56.9 % ) st and ard tacrolimus ( > 7 ng/mL ) ; enteric‐coated mycophenolate sodium 589 ( 67.7 % ) and mycophenolate mofetil 281 ( 32.3 % ) . During baseline to month 1 , months 1–3 , months 3–6 , and months 6–12 , 9.3 % ( 78/838 ) , 16.6 % ( 132/794 ) , 20.7 % ( 145/701 ) , and 13.1 % ( 70/535 ) patients , respectively , required MPA dose changes . These patients experienced an increased risk of biopsy‐proven acute rejection at one yr with tacrolimus exposure either included in the model ( hazard ratio [ HR ] 2.60 , 95 % CI 1.28–5.29 , p = 0.008 ) or excluded ( HR 2.58 , 95 % CI 1.28–5.23 , p = 0.008 ) . MPA dose changes were significantly associated with one yr graft failure when tacrolimus exposure was included ( HR 2.23 ; 95 % CI 1.01–4.89 , p = 0.047 ) but not when tacrolimus exposure was excluded ( HR 2.16 ; 95 % CI 0.99–4.79 ; p = 0.054 ) . These results suggest that reducing or discontinuing MPA can adversely affect graft outcomes regardless of tacrolimus trough levels BACKGROUND The economic impact of therapies has increasingly become part of the clinical decision-making process . Costs associated with kidney transplantation are substantial and economic evaluations are useful in identifying immunosuppressive regimens that yield optimal clinical and economic benefits . METHODS Utilisation of health care re sources during the first 6-months after renal transplantation was examined in 557 kidney transplant recipients participating in a European , multicentre , r and omised , parallel group study that compared the efficacy and safety of a tacrolimus-based regimen versus a cyclosporin-microemulsion-based regimen . Cost-minimisation and cost-effectiveness analyses were conducted from an Italian hospital perspective , including direct medical costs only ( e.g. medication , hospitalisation ) . RESULTS The incidence of acute rejection was significantly lower in the tacrolimus group than in the cyclosporin microemulsion ( ME ) group ( 32.5 % versus 51.3 % ; p<0.001 ) . Patient and graft survival were similar in both treatment groups . Renal transplant recipients receiving tacrolimus-based immunosuppression had lower utilisation of health care re sources and lower total costs per patient than cyclosporin-ME treated patients . When surviving patients with a rejection-free graft were analysed , tacrolimus therapy was cost-saving , since it was both more effective ( 18.8 % difference in the incidence of acute rejection ; 95%CI 10.7%-26.8 % ; p<0.001 ) and less costly than cyclosporin-ME based therapy ( cost difference euro9918 ) . The costs per patient with a functioning graft were euro2305 , the costs per surviving patient were euro1892 lower in tacrolimus treated patients . Sensitivity analyses using the key cost-drivers ( hospitalisation , study drug , and concomitant medication ) found the cost advantage of tacrolimus was maintained . CONCLUSION In the first 6 months after renal transplantation , tacrolimus-based therapy was less costly than cyclosporin-ME based therapy . When surviving patients with a rejection-free graft were considered , tacrolimus was the dominant therapy Kidney transplant recipients receiving calcineurin inhibitor-based immunosuppression incur increased long-term risks of cancer and kidney fibrosis . Switch to mammalian target of rapamycin ( mTOR ) inhibitors may reduce these risks . Steroid or Cyclosporin Removal After Transplant using Everolimus ( SOCRATES ) , a 36-month , prospect i ve , multinational , open-label , r and omized controlled trial for de novo kidney transplant recipients , assessed whether everolimus switch could enable elimination of mycophenolate plus either steroids or CNI without compromising efficacy . Patients received cyclosporin , mycophenolate and steroids for the first 14 days then everolimus with mycophenolate and CNIwithdrawal ( CNI-WD ) ; everolimus with mycophenolate and steroid withdrawal ( steroid-WD ) ; or cyclosporin , mycophenolate and steroids ( control ) . 126 patients were r and omized . The steroid WD arm was terminated prematurely because of excess discontinuations . Mean eGFR at month 12 for CNI-WD versus control was 65.1 ml/min/1.73 m2 vs. 67.1 ml/min/1.73 m2 by ITT , which met predefined noninferiority criteria ( P = 0.026 ) . The CNI-WD group experienced a higher rate of BPAR(31 % vs. control 13 % , P = 0.048 ) and showed a trend towards higher composite treatment failure ( BPAR , graft loss , death , loss to follow-up ) . The 12 month results from SOCRATES show noninferiority in eGFR , but a significant excess of acute rejection when everolimus was commenced at week 2 to enable a progressive withdrawal of mycophenolate and cyclosporin in kidney transplant recipients Background . Our single-center , open-labeled r and omized trial of 150 adult , primary kidney transplant recipients receiving 2 g mycophenolate mofetil ( group A , n=75 ) versus 1.440 g enteric-coated mycophenolate sodium ( group B , n=75 ) , with reduced maintenance tacrolimus dosing , steroid elimination at 1 week , and combined rabbit antithymocyte globulin/daclizumab induction , previously showed at 1 year posttransplant low biopsy-proven acute rejection ( BPAR ) , acceptably high renal function , and no differences in incidence of symptomatic gastrointestinal ( GI ) side effects between the two groups . This report includes 3 additional years of follow-up with similar endpoints as in the original study . Methods . Rates of developing first BPAR , graft failure ( death censored and uncensored ) , death , and adverse events ( GI toxicity , infections requiring hospitalization , and new onset diabetes mellitus after transplantation ) during the first 48 months posttransplant were compared between the two groups using an intent-to-treat approach . Results . At 48 months posttransplant , patient/graft survival in groups A and B was 97%/90 % vs. 96%/86 % , respectively ( not significant [ NS ] ) . Twenty-seven patients experienced BPAR ( including borderline ) , with actuarial 19 % ( 14/75 ) vs. 18 % ( 13/75 ) in groups A and B , respectively ( NS ) . Geometric mean*/st and ard error serum creatinine level and arithmetic mean calculated glomerular filtration rate ( ±st and ard error ) at 48 months in groups A and B , respectively , were 1.25*/1.06 and 69.2±3.9 vs. 1.20*/1.05 and 71.2±3.2 ( NS ) . Incidence of new onset diabetes mellitus after transplantation ( 22 % vs. 15 % ) , infections requiring hospitalization ( 31 % vs. 39 % ) , and GI side effects ( 45 % vs. 52 % ) seemed equivalent . Conclusions . This is the first long-term , r and omized trial comparing enteric-coated mycophenolate sodium versus mycophenolate mofetil along with reduced maintenance tacrolimus dosing and steroid avoidance , which result ed in similarly low-BPAR rates , acceptably high renal function at 48 months , and an equivalent side effect profile BACKGROUND Non-nephrotoxic immunosuppressive strategies that allow reduction of calcineurin-inhibitor exposure without compromising safety or efficacy remain a goal in kidney transplantation . Immunosuppression based on the mammalian-target-of-rapamycin inhibitor everolimus was assessed as a strategy for elimination of calcineurin-inhibitor exposure and optimisation of renal-graft function while maintaining efficacy . METHODS In the ZEUS multicentre , open-label study , 503 patients ( aged 18 - 65 years ) who had received de-novo kidney transplants were enrolled . After initial treatment with ciclosporin , based on trough concentrations , and enteric-coated mycophenolate sodium ( 1440 mg/day , orally ) , corticosteroids ( ≥5 mg/day prednisolone or equivalent , orally ) , and basiliximab induction ( 20 mg , intravenously , on day 0 [ 2 h before transplantation ] , and on day 4 ) , 300 ( 60 % ) patients were r and omly assigned at 4·5 months in a 1:1 ratio to undergo calcineurin-inhibitor elimination ( everolimus-based regimen that was based on trough concentrations [ 6 - 10 ng/mL ] and enteric-coated mycophenolate sodium [ 1440 mg/day ] with corticosteroids ) , or continue st and ard ciclosporin-based treatment . R and omisation was done by use of a central , vali date d system that automated the r and om assignment of treatment groups to r and omisation numbers . The primary objective was to show better renal function ( glomerular filtration rate [ GFR ] ; Nankivell formula ) with the calcineurin-inhibitor-free everolimus regimen at 12 months after transplantation . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00154310 . FINDINGS 118 ( 76 % ) of 155 everolimus-treated patients and 117 ( 81 % ) of 145 ciclosporin-treated patients completed treatment with study drug up to 12 months after transplantation . At this timepoint , the everolimus regimen was associated with a significant improvement in GFR versus the ciclosporin regimen ( 71·8 mL/min per 1·73 m(2 ) vs 61·9 mL/min per 1·73 m(2 ) , respectively ; mean difference 9·8 mL/min per 1·73 m(2 ) , 95 % CI -12·2 to -7·5 ) . Rates of biopsy-proven acute rejection were higher in the everolimus group than in the ciclosporin group after r and omisation ( 15 [ 10 % ] of 154 vs five [ 3 % ] of 146 ; p = 0·036 ) , but similar for the full study period ( 23 [ 15 % ] vs 22 [ 15 % ] ) . Compared with the ciclosporin regimen , higher mean lipid concentrations , slightly increased urinary protein excretion , and lower haemoglobin concentrations were noted with the everolimus regimen ; thrombocytopenia , aphthous stomatitis , and diarrhoea also occurred more often in the everolimus group . A higher incidence of hyperuricaemia was noted with ciclosporin . INTERPRETATION Early elimination of calcineurin inhibitor by use of everolimus-based immunosuppression improved renal function at 12 months while maintaining efficacy and safety , indicating that this strategy may facilitate improved long-term outcomes in selected patients . FUNDING Novartis Pharma Purpose : We sought to compare directly elicited valuations for EQ-5D health states between the US and UK general adult population s. Methods : We analyzed data from 2 EQ-5D valuation studies where , using similar time trade-off protocol s , values for 42 common health states were elicited from representative sample s of the US and UK general adult population s. First , US and UK population mean valuations were estimated and compared for each health state . Second , r and om-effect models were used to compare the US and UK valuations while adjusting for known predictors of EQ-5D valuations ( ie , age , sex , health state descriptors ) and to investigate whether and how the valuations differ . Results : Population mean valuations of the 42 health states ranged from −0.38 to 0.88 for the United States and from −0.54 to 0.88 for the United Kingdom , with the US mean scores being numerically higher than the UK for 39 health states ( mean difference : 0.11 ; range : −0.01 to 0.25 ) . After adjusting for the main effects of known predictors , the average difference in valuations was 0.10 ( P < 0.001 ) . The magnitude of the difference in the US and UK valuations was not constant across EQ-5D health states ; greater differences in valuations were present in health states characterized by extreme problems . Conclusions : Meaningful differences exist in directly elicited TTO valuations of EQ-5D health states between the US and UK general population s. Therefore , EQ-5D index scores generated using valuations from the US general population should be used for studies aim ing to reflect health state preferences of the US general public We performed a prospect i ve r and omized trial comparing sirolimus/mycophenolate mofetil (MMF)/prednisone to cyclosporine/MMF/prednisone and selected induction therapy with basiliximab . Twenty patients received sirolimus ( 10 mg loading dose followed by 3 mg/m body surface area/day , keeping 24-hr trough levels at 10 - 15 ng/mL for six months and 5 - 10 ng/mL thereafter . Twenty-one patients began cyclosporine ( 4 to 8 mg/kg/day , keeping 12-hour trough levels at 150 - 300 ng/mL for 6 months and 100 - 200 ng/mL afterwards ) . Mean follow up was 15.8 months . One-year patient and graft survival was similar in both groups ( > 90 % ) . Acute rejection rate was 16.6 % in the sirolimus group and 5.2 % in the cyclosporine group ( P = NS ) . There were no differences in mean serum creatinine between groups . No patients who received basiliximab and had sirolimus target levels suffered acute rejection at one year . The sirolimus group had significantly higher cholesterol and triglycerides . A calcineurin inhibitor-free regimen using sirolimus produces comparable one-year transplant outcomes in living related kidney transplants compared to a calcineurin inhibitor regimen Calcineurin inhibitors have decreased acute rejection and improved early renal allograft survival , but their use has been implicated in the development of chronic nephrotoxicity . We performed a prospect i ve , r and omized trial in kidney transplantation comparing sirolimus‐MMF‐prednisone to tacrolimus‐MMF‐prednisone . Eighty‐one patients in the sirolimus group and 84 patients in the tacrolimus group were enrolled ( mean follow‐up = 33 months ; range 13–47 months ) . At 1 year , patient survival was similar in the groups ( 98 % with sirolimus , 96 % with tacrolimus ; p = 0.42 ) as was graft survival ( 94 % sirolimus vs. 92 % tacrolimus , p = 0.95 ) . The incidence of clinical acute rejection was 10 % in the tacrolimus group and 13 % in the sirolimus group ( p = 0.58 ) . There was no difference in mean GFR measured by iothalamate clearance between the tacrolimus and sirolimus groups at 1 year ( 61 ± 19 mL/min vs. 63 ± 18 mL/min , p = 0.57 ) or 2 years ( 61 ± 17 mL/min vs. 61 ± 19 mL/min , p = 0.84 ) . At 1 year , chronicity using the Banff schema showed no difference in interstitial , tubular or glomerular changes , but fewer chronic vascular changes in the sirolimus group . This study shows that a CNI‐free regimen using sirolimus‐MMF‐prednisone produces similar acute rejection rates , graft survival and renal function 1–2 years after transplantation compared to tacrolimus‐MMF‐prednisone Planned conversion from tacrolimus to sirolimus was evaluated in de novo kidney transplant recipients . In this multicenter , r and omized , open‐label study , 297 patients were initially treated with tacrolimus , mycophenolate sodium and prednisone . Of the 283 patients reaching 3 months , 97 were converted to sirolimus ( SRL ) , 107 were maintained on tacrolimus ( TAC ) and 79 were patients receiving TAC without criteria to undergo intervention at month 3 ( TACex ) . The primary objective was to show superior estimated glomerular filtration rate ( eGFR ) in the SRL group at month 24 . Of the 258 patients who completed 24 months , 91 ( 94 % ) were in the SRL group , 101 ( 94 % ) in the TAC group and 66 ( 84 % ) in the TACex group . In the intention‐to‐treat population there were no differences in eGFR ( 66.2 ± 25.3 vs. 70.7 ± 25.1 , p = 0.817 ) or in the severity of chronic sclerosing lesions scores in 24‐month protocol biopsies . Higher mean urinary protein‐to‐creatinine ratio ( 0.36 ± 0.69 vs. 0.15 ± 0.53 , p = 0.03 ) and higher incidence of treated acute rejection between months 3–24 ( 13.4 % vs. 4.7 % , p = 0.047 ) were observed in SRL compared to TAC group . In this population planned conversion from TAC to SRL 3 months after kidney transplantation was not associated with improved renal function at 24 months Current immunosuppressive regimens in renal transplantation typically include calcineurin inhibitors ( CNIs ) and corticosteroids , both of which have toxicities that can impair recipient and allograft health . This 1‐year , r and omized , controlled , open‐label , exploratory study assessed two belatacept‐based regimens compared to a tacrolimus (TAC)‐based , steroid‐avoiding regimen . Recipients of living and deceased donor renal allografts were r and omized 1:1:1 to receive belatacept‐mycophenolate mofetil ( MMF ) , belatacept‐sirolimus ( SRL ) , or TAC‐MMF . All patients received induction with 4 doses of Thymoglobulin ( 6 mg/kg maximum ) and an associated short course of corticosteroids . Eighty‐nine patients were r and omized and transplanted . Acute rejection occurred in 4 , 1 and 1 patient in the belatacept‐MMF , belatacept‐SRL and TAC‐MMF groups , respectively , by Month 6 ; most acute rejection occurred in the first 3 months . More than two‐thirds of patients in the belatacept groups remained on CNI‐ and steroid‐free regimens at 12 months and the calculated glomerular filtration rate was 8–10 mL/min higher with either belatacept regimen than with TAC‐MMF . Overall safety was comparable between groups . In conclusion , primary immunosuppression with belatacept may enable the simultaneous avoidance of both CNIs and corticosteroids in recipients of living and deceased st and ard criteria donor kidneys , with acceptable rates of acute rejection and improved renal function relative to a TAC‐based regimen BACKGROUND A double-blind , placebo-controlled phase III study was performed to assess whether basiliximab , a chimeric anti-interleukin-2 receptor monoclonal antibody , reduced the incidence of acute rejection episodes in renal allograft recipients . METHODS A total of 348 patients were r and omized into two demographically matched , equally sized groups treated with either basiliximab or placebo . The dose of basiliximab-20-mg infusions on day 0 and day 4-was selected to block detection of interleukin-2 receptor on 97 % of peripheral blood lymphocytes for 30 - 45 days . All patients received immunosuppressive therapy with cyclosporine microemulsion ( Neoral ) and steroids . An intent-to-treat analysis of 1-year data assessed the incidence of posttransplant acute rejection episodes , patient and graft survival rates , and the safety and tolerability of basiliximab . RESULTS Among the eligible 346 patients equally divided into the two treatment groups , basiliximab reduced the proportion of patients who experienced biopsy-confirmed acute rejection episodes by 28 % : 61 ( 35.3 % ) basiliximab vs. 85 ( 49.1 % ) placebo ( P=0.009 ) . Graft losses occurred in 9 ( 5.2 % ) basiliximab-treated and 12 ( 6.9 % ) placebo-treated patients . Five ( 2.9 % ) deaths in the basiliximab group and seven ( 4.0 % ) in the placebo group occurred . Compared with placebo , a higher fraction of basiliximab patients produced urine in the operating room , and a significantly lower fraction had renal dysfunction in the first month ( serum creatinine > or = 5 mg(dl ) and between 1 and 12 months ( serum creatinine > or =3 mg/dl ) . During the first 12 months , 94 ( 54 % ) basiliximab-treated patients experienced serious adverse events , compared with 106 ( 61 % ) who received placebo . CONCLUSIONS Prophylactic basiliximab therapy is well tolerated , has an adverse event profile comparable to placebo , and significantly reduces the number of acute rejection episodes in renal allograft patients within the first year after transplantation This study attempted to establish whether a calcineurin inhibitor (CNI)-free immunosuppressant regimen based on sirolimus ( SRL ) is associated with a preservation of conduit arteries endothelial function in kidney recipients or not . Twenty-nine kidney recipients were r and omized to receive since transplantation SRL ( n=15 ) or cyclosporin A ( CsA , n=14 ) associated with mycophenolate mofetil ( MMF ) and steroids ( 6months ) in a parallel prospect i ve study . Systolic , diastolic blood pressures , glomerular filtration rate ( GFR ) and radial artery flow-mediated dilatation ( FMD ) induced by postischaemic hyperaemia were assessed in a blind manner at one ( M1 ) and 7months ( M7 ) after transplantation . Endothelium-independent dilatation was assessed by glyceryl trinitrate spray . There was no difference between the groups for all vascular parameters at M1 . At M7 , systolic blood pressure was lower ( SRL : 119±3 vs. CsA : 138±4mmHg , P<0.05 ) and FMD was higher in SRL compared with CsA ( SRL : 13.1±0.9 vs. CsA : 9.9±0.9 % , P<0.05 ) without any difference for hyperaemia , endothelium-independent dilatation and GFR ( SRL : 66.7±1.05 vs. CsA : 67.5±1.22ml/min ) . Our results demonstrate that a CNI-free regimen based on SRL and MMF prevents conduit artery endothelial dysfunction compared with CsA and MMF in kidney recipients suggesting a beneficial arterial wall effect that may also contribute to the decrease in systolic blood pressure Background . Clinical data are lacking concerning concomitant administration of everolimus and tacrolimus in renal transplant recipients . Methods . In a prospect i ve , multicenter , open-label , exploratory , r and omized , 6-month study , 92 de novo renal transplant patients received everolimus , steroids , and basiliximab with low or st and ard tacrolimus exposure . The primary objective was to compare renal function at 6 months after transplant . Results . Mean 6-month serum creatinine ( primary safety variable ) was 112±31 & mgr;mol/L ( 1.26±0.35 mg/dL ) and 127±50 & mgr;mol/L ( 1.44±0.57 mg/dL ) in the low and st and ard tacrolimus groups , respectively , ( n.s . ) ; mean estimated GFR ( Nankivell ) was 75.3±16.6 mL/min and 72.5±15.2 mL/min ( n.s . ) . Biopsy-proven acute rejection occurred in 13 patients : seven ( 14 % ) in the low tacrolimus group and six ( 14 % ) in the st and ard tacrolimus group , n.s . One graft was lost in the st and ard tacrolimus group . No patients died . Conclusions . Tacrolimus exposure reduction in the presence of everolimus , steroids and basiliximab induction results in good efficacy in de novo renal transplant recipients with very well-preserved renal function . Additional studies are warranted because between-group comparisons were limited by the relatively small differences in tacrolimus exposure in the 2 arms ; trough levels were toward the upper end of the low-exposure ranges and toward the bottom of the st and ard-exposure ranges Calcineurin inhibitor ( CNI ) nephrotoxicity is a major concern after renal transplantation . To investigate the safety and efficacy of a CNI-free immunosuppressive regimen , 132 live-donor renal transplant recipients were included in a prospect i ve , r and omized controlled trial . All patients received induction therapy with basiliximab and steroids . The patients were r and omized to a maintenance immunosuppression regimen that included steroids , sirolimus , and either low-dose tacrolimus or mycophenolate mofetil ( MMF ) . Over a mean follow-up period of approximately 5 yr , patient and graft survival did not significantly differ between the two maintenance regimens . Patient survival was 93.8 % and 98.5 % in the tacrolimus/sirolimus and MMF/sirolimus groups , respectively , and graft survival was 83 % and 88 % , respectively . However , the MMF/sirolimus group had significantly better renal function , calculated by Cockcroft-Gault , from the second year post-transplant until the last follow-up . In addition , this group was less likely to require a change in their primary immunosuppression regimen than the tacrolimus/sirolimus group ( 20.8 % versus 53.8 % , P = 0.001 ) . The safety profile was similar between groups . In summary , after long-term follow-up , a CNI-free maintenance regimen consisting of sirolimus , MMF , and steroids was both safe and efficacious among low to moderate immunologic risk renal transplant recipients OBJECTIVES Recent evidence of a high incidence of proteinuria among de novo sirolimus-based regimens has been reported among renal transplant patients at short-term follow-up . We report on long-term evaluation of proteinuria among patients maintained on such regimen . MATERIAL S AND METHODS Between May 2001 and January 2003 , 132 patients received a renal allograft from a living donor and were r and omized to 2 groups ( steroids/sirolimus/tacrolimus , n=65 ) and ( steroids/sirolimus/mycophenolate mofetil , n=67 ) : Both received basiliximab induction . Retrospective review of those patients was performed , 5 years posttransplant with particular emphasis on the incidence of proteinuria . RESULTS The 5-year incidence of proteinuria was 29.2 % and 38.8 % among sirolimus/tacrolimus and sirolimus/mycophenolate mofetil group . Single DR-matched patients ( P = .016 ) and the incidence of acute rejection ( P = .039 ) were associated with significantly higher incidence of proteinuria . Moreover , the presence of mesangial matrix increased ( P = .015 ) , and glomerulosclerosis ( P = .014 ) , in 1-year protocol biopsies , was found to have a positive predictive value for current and future incidences of proteinuria . Proteinuria was found to be associated with significant inferior graft outcome . Recurrent original kidney disease , de novo glomerulopathy , and acute transplant glomerulopathy were responsible for early cases of nephrotic range proteinuria ( first 2 years ) , while cases presented later were attributed to chronic allograft nephropathy . CONCLUSIONS Proteinuria has become a recognized , serious event of primarily sirolimus-treated renal transplants patients , which is most probably of glomerular origin . It has been shown that proteinuria exerts a bad prognostic effect upon graft function and subsequent graft survival at 5-year follow-up Recipients of extended criteria donor ( ECD ) kidneys are at increased risk for graft dysfunction/loss , and may benefit from immunosuppression that avoids calcineurin inhibitor ( CNI ) nephrotoxicity . Belatacept , a selective costimulation blocker , may preserve renal function and improve long‐term outcomes versus CNIs . BENEFIT‐EXT ( Belatacept Evaluation of Nephroprotection and Efficacy as First‐line Immunosuppression Trial — EXTended criteria donors ) is a 3‐year , Phase III study that assessed a more ( MI ) or less intensive ( LI ) regimen of belatacept versus cyclosporine in adult ECD kidney transplant recipients . The co primary endpoints at 12 months were composite patient/graft survival and a composite renal impairment endpoint . Patient/graft survival with belatacept was similar to cyclosporine ( 86 % MI , 89 % LI , 85 % cyclosporine ) at 12 months . Fewer belatacept patients reached the composite renal impairment endpoint versus cyclosporine ( 71 % MI , 77 % LI , 85 % cyclosporine ; p = 0.002 MI vs. cyclosporine ; p = 0.06 LI vs. cyclosporine ) . The mean measured glomerular filtration rate was 4–7 mL/min higher on belatacept versus cyclosporine ( p = 0.008 MI vs. cyclosporine ; p = 0.1039 LI vs. cyclosporine ) , and the overall cardiovascular/metabolic profile was better on belatacept versus cyclosporine . The incidence of acute rejection was similar across groups ( 18 % MI ; 18 % LI ; 14 % cyclosporine ) . Overall rates of infection and malignancy were similar between groups ; however , more cases of posttransplant lymphoproliferative disorder ( PTLD ) occurred in the CNS on belatacept . ECD kidney transplant recipients treated with belatacept‐based immunosuppression achieved similar patient/graft survival , better renal function , had an increased incidence of PTLD , and exhibited improvement in the cardiovascular/metabolic risk profile versus cyclosporine‐treated patients BACKGROUND Non-adherence to immunosuppressants is a major cause of renal transplant failure . Interventions to improve adherence need to target modifiable risk factors . METHODS Adherence was measured using the ' gold st and ard ' measure of electronic monitoring in 58 adult renal transplant recipients from a UK transplant unit . Subjects were identified from a stratified r and om sample of 153 recipients recruited to a larger cross-sectional study comparing different measures of adherence . Inclusion criteria included age over 18 years and a functioning renal transplant , transplanted 6 - 63 months previously . Exclusion criteria included residence outside the region served by the unit and inability to give informed consent . Health beliefs , depression and functional status were measured using st and ardized question naires ( Beliefs about Medicines Question naire , Illness Perception Question naire , Revised Clinical Interview Schedule and SF-36 ) and semi-structured interview . Transplant and demographic details were collected from the notes . RESULTS Seven [ 12 % , 95 % confidence interval ( CI ) 4 - 20 % ] subjects missed at least 20 % of days medication and 15 ( 26 % , 15 - 37 % ) missed at least 10 % of days . Lower belief in the need for medication and having a transplant from a live donor were the major factors associated with non-adherence . Depression was common , although not strongly associated with non-adherence . CONCLUSIONS Beliefs about medication are a promising target for interventions design ed to improve adherence . The lower adherence in recipients of transplants from live donors needs confirming but may be clinical ly important in light of the drive to increase live donation Nonadherence to immunosuppressive medications may partly explain the worse allograft outcomes among black recipients of renal transplants . In a prospect i ve cohort study of recipients of deceased donor renal transplants , microelectronic cap monitors were placed on bottles of one immunosuppressive medication to ( 1 ) measure average daily percentage adherence during the first posttransplantation year and ( 2 ) determine the factors associated with adherence . A total of 278 transplant recipients who provided sufficient microelectronic adherence data were grouped into four categories of average daily percentage adherence : 95 to 100 % adherence ( 41.0 % of patients ) , 80 to 95 % adherence ( 32.4 % ) , 50 to 80 % adherence ( 12.9 % ) , and 0 to 50 % adherence ( 13.7 % ) . In the unadjusted ordinal logistic regression model , black race was associated with decreased adherence ( odds ratio [ OR ] , 0.43 ; 95 % confidence interval [ CI ] , 0.26 to 0.72 ; P = 0.001 ) . Cause of renal disease , Powerful Others health locus of control , transplant center , and dosing frequency were also associated with adherence . After adjustment for transplant center and dosing frequency , the association between black race and decreased adherence was substantially attenuated ( OR , 0.65 ; 95 % CI , 0.38 to 1.14 , P = 0.13 ) . Transplant center ( P = 0.003 ) and increased dosing frequency ( OR , 0.43 ; 95 % CI , 0.22 to 0.86 , for three or four times per day dosing ; OR , 2.35 ; 95 % CI , 1.01 to 5.45 , for daily dosing ; versus two times per day dosing ; P = 0.003 ) remained independently associated with adherence . Other baseline demographic , socioeconomic , medical , surgical , and psychosocial characteristics were not associated with adherence . The transplant center and dosing frequencies of immunosuppressive medications are associated with adherence and explain a substantial proportion of the race-adherence relationship BACKGROUND Various preparations of ALG/ATG have been used in clinical transplantation for more than 30 years . In recent years the number of high immunological risk patients has increased and biological agents are being used as induction therapy . The aim of this prospect i ve , r and omized study was to asses the safety and efficacy of a single high dose of antithymocyte globulin ( 9 mg/kg ATG Fresenius S ) in cadaveric renal transplantation . The maintenance immunosuppressive regimen consisted of steroids , mycophenolate mofetil ( converted after the fourth month to azathioprine ) , and cyclosporine . MATERIAL / METHODS Between November 1997 and April 1999 , 79 recipients were included into the study . Patients were r and omized to ATG ( n=40 ) or the st and ard treatment group ( n=39 ) with a follow up period of 5 years . RESULTS The incidence of acute rejection was lower in the ATG group--9 patients ( 22.5 % ) compared to 14 in the control group ( 35.9 % ) ( p = NS ) . The total number of all acute rejections episodes in the ATG group was 11 and 23 in the control group . Steroid resistant rejections occurred in 4 ( 10 % ) and 8 ( 20.5 % ) patients respectively . The number of infectious complications was similar in both groups ( 65 % - ATG , 67.5 % - control , p = NS ) . Graft survival was 70 % for the ATG and 69.23 % for the control group . Death censored graft survival was 85 % in the ATG and 74.43 % in the control group ( p = NS ) . CONCLUSIONS Induction Therapy with high single dose of ATG seems to be safe and efficacious in kidney transplantation Abstract .An economic evaluation was undertaken alongside a multicentre international trial of basiliximab . Re source usage within the trial was assessed , and the cost implication s of using basiliximab evaluated . Recipients of a primary cadaveric kidney transplant were recruited into a double-blind trial and received either placebo ( n=186 ) or basiliximab ( n=190 ) . Clinical outcomes and re source usage were monitored in the 12 months following transplantation . Local unit costs were obtained , and global analysis was undertaken using health sector purchasing-power parity rates . No statistically significant differences were found in the mean cost of treatment per patient . The mean cost of treatment was $ 47,940 for basiliximab patients and $ 46,280 for placebo patients , a mean difference of $ 1,660 ( 95 % confidence interval ( CI ) : –$4,150 , $ 7,360 ; P=0.58 ) . Basiliximab produces clinical benefit in terms of preventing episodes of acute rejection , whilst the difference in the total re source usage and cost of treatment is not statistically significant Once‐daily tacrolimus extended‐release formulation ( Prograf XL , formerly referred to as MR or MR4 ) was compared with the twice‐a‐day tacrolimus formulation ( TAC ) and cyclosporine microemulsion ( CsA ) , all administered in combination with mycophenolate mofetil ( MMF ) , corticosteroids and basiliximab induction , in a phase 3 , r and omized ( 1:1:1 ) , open‐label trial in 638 de novo kidney transplant recipients . In combination with MMF and corticosteroids , XL had an efficacy profile comparable to TAC and CsA. XL/MMF and TAC/MMF were statistically noninferior at 1‐year posttransplantation to CsA/MMF for the primary efficacy endpoint , efficacy failure ( death , graft loss , biopsy‐confirmed acute rejection ( BCAR ) or lost to follow‐up ) . One‐year patient and graft survival were 98.6 % and 96.7 % in the XL/MMF group , 95.7 % and 92.9 % in TAC/MMF group and 97.6 % and 95.7 % in CsA/MMF group . The safety profile of XL in comparison with CsA was similar to that observed with TAC in this study and consistent with previously published reports of TAC in comparison with CsA. The results support the safety and efficacy of tacrolimus in combination with MMF , corticosteroids and basiliximab induction , as well as XL as a safe and effective once‐daily dosing alternative AIMS The aim of this study was to examine the glomerular filtration rate ( GFR ) and tubular function at three months after renal transplantation in two groups of patients receiving cyclosporine A associated with either sirolimus ( SRL ) ( n = 18 ) or everolimus ( RAD ) ( n = 12 ) , two structurally similar immunosuppressant drugs . RESULTS Donors ' and recipients ' characteristics and mean cyclosporine A trough levels were similar in the two groups . The mean sirolimus trough level was 12.01 + /- 1.6 ng/ml whereas the mean everolimus trough level was 4.23 + /- 0.36 ng/ml . GFR , equated by the clearance of inulin , was higher in RAD patients ( 64 + /- 4 ml . min- 1.1.73 m(-2 ) ) than in SRL patients ( 49 + /- 4 ml.min(-1 ) .1.73 m(-2 ) ) ( p < 0.05 ) . The significant difference in GFR between the groups was not affected by differences in mean arterial blood pressures , or by differences in daily prednisone dosages , cyclosporine trough levels , or SRL and RAD trough levels . Phosphatemia , renal phosphate threshold ( TmPO4/ GFR ratio ) and uric acid clearance were significantly lower in the SRL than in the RAD group , despite similar levels of parathyroid hormone . Finally , urinary acid excretion was significantly lower in the RAD group . CONCLUSION In conclusion , regarding nephrotoxicity , our preliminary data suggest that it seems to be preferable to combine cyclosporine with RAD rather than with sirolimus in renal transplant patients . However , long-term renal effects of this combination are still to be determined in a larger cohort The proliferation signal inhibitor everolimus ( Certican ) , has demonstrated efficacy with full-dose cyclosporine ( CsA ) ( Neoral ) . Two multicenter r and omized controlled studies were performed to compare 12-month efficacy and safety of everolimus 1.5 and 3.0 mg/day with reduced-dose CsA. Study 1 enrolled 237 de novo renal allograft recipients , r and omizing 222 nonblack patients to either everolimus 1.5 or 3.0 mg/day , with the Neoral ) dose guided by C(2 ) ( monitoring of CsA concentration 2 h after dosing ) . Study 2 had a similar protocol , with basiliximab included , enrolling 256 recipients and r and omizing 243 nonblack patients . In Study 1 , there was a lower incidence of acute rejection in nonblack patients on 3 mg/day ( 16.4 % ) compared with 1.5 mg/day ( 25.9 % ) , P = 0.08 . In Study 2 , the inclusion of basiliximab lowered the overall incidence of acute rejection ; 14.3 % of nonblack patients ( 3 mg/day ) and 13.6 % of nonblack patients ( 1.5 mg/day ) had acute rejection by 12 months ( P = 0.891 ) . Renal function was preserved throughout the study , with no differences observed between groups within studies . Everolimus was well tolerated with no significant differences between doses . Everolimus , in combination with reduced-dose Neoral ) , demonstrated efficacy and was well tolerated . Basiliximab allows for utilization of lower doses of everolimus with reduced dosing of Neoral ) Background A prolonged-release formulation of tacrolimus ( Tacrolimus QD ) was developed to allow once-daily dosing and to have similar safety and efficacy profiles to twice-daily tacrolimus ( Tacrolimus BID ) . This study compared the pharmacokinetics ( PK ) and renal pathology by protocol biopsy in de novo living kidney transplant recipients treated with either low-dose Tacrolimus QD or Tacrolimus BID . Methods Between November 2009 and January 2011 , 102 consecutive adult patients were r and omized to receive either low-dose Tacrolimus QD or Tacrolimus BID . All patients underwent PK study and protocol biopsy on postoperative day 14 . Additional protocol biopsies were performed between 6 and 12 months after renal transplantation . Results During the 1-year follow up , the incidence of biopsy-proven acute rejection and toxic tubulopathy was low and similar in both groups . Twenty-four hours area under the curve ( AUC0–24 ) was not different in both groups ( 285±78.7 and 281±62.4 ng hr/mL in Tacrolimus QD and Tacrolimus BID , respectively ) . C0 was well correlated with AUC0–24 in both groups and AUC0–24 between 260 and 280 in the Tacrolimus QD group was achieved by 6 to 8 ng/mL of C0 . Acute nephrotoxicity was less than 10 % in both groups without any clinical manifestation . Conclusion Clinical efficacy , safety , and PK profile of Tacrolimus QD is same as those of Tacrolimus BID Few studies used paired kidneys for comparison between tacrolimus and cyclosporine in renal transplantation . Most of the published data used whole blood trough levels for drug monitoring . However , the use of limited sampling strategy and abbreviated formula to estimate the 12-h area under concentration-time curve ( AUC(0 - 12 ) ) allowed better prediction of drug exposure . Sixty-six first cadaveric renal transplant recipients receiving paired kidneys were r and omized to receive either tacrolimus-based ( n = 33 ) or cyclosporine microemulsion (Neoral)-based therapies ( n = 33 ) . Abbreviated AUC(0 - 12 ) was used for drug monitoring and dose titration . Mean follow-up duration was 2.8 + /- 2 years . The patient and graft survival were comparable . Fewer incidence of acute rejection was observed in tacrolimus group ( 15 % vs. 27.3 % ) though the difference was not significant ( P = 0.23 ) . The absolute value and the rate of decline of creatinine clearance were both significantly better in tacrolimus-treated patients . Prevalence of hypertension , post-transplant diabetes mellitus , infection , and malignancy were similar in both groups . Prevalence of hypercholesterolemia ( 11/33 vs. 4/33 ) and gum hypertrophy ( 6/33 vs. 1/33 ) was more common in cyclosporine-treated patients ( P = 0.04 in both parameters ) . This was the first prospect i ve , r and omized study with paired kidney analysis showing the renal function was significantly better in tacrolimus-treated patients than in cyclosporine-treated patients Purpose The purpose of this study was to compare once-daily tacrolimus with twice-daily tacrolimus in terms of safety , efficacy , and patient satisfaction . Material s and Methods This prospect i ve , r and omized , open-label , multicenter study was conducted at three institutes . Patients in the investigational group were converted from tacrolimus twice daily to the same dose of extended-release tacrolimus once daily at 1 month post-transplantation , while patients in the control group were maintained on tacrolimus twice daily . The efficacies , safeties , and patient satisfaction for the two drugs at 6 months post-transplantation were compared . Results Sixty patients were enrolled and r and omized to the investigational group ( 28 of 29 patients completed the study ) or the control group ( 26 of 31 patients completed the study ) . At 6 months post-transplantation , composite efficacy failure rates including the incidences of biopsy-confirmed acute rejection in the investigational and control groups were 0 % and 10.7 % , respectively ; patient survival was 100 % in each group . No difference in estimated glomerular filtration rate values were observed at 6 months post-transplantation ( p=0.97 ) . The safety and satisfaction profile ( immunosuppressant therapy barrier scale ) of once-daily tacrolimus was comparable with that of twice-daily tacrolimus ( p=0.35 ) . Conclusion Conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation is safe and effective Background . Mycophenolate mofetil ( MMF ) , compared to azathioprine ( AZA ) , reduces acute rejection and treatment failure in cyclosporine ( CsA ) and steroid regimens , but its effect on graft survival is unproven from prospect i ve studies and prolonged use is costly . This study evaluated the efficacy and tolerability of replacing MMF by AZA after 3 months . Methods . This 28 center , prospect i ve , 12-month , parallel group , open-label study , r and omized patients to three groups with microemulsion formulation of CsA ( ME-CsA ) and steroids as baseline therapy . Group 1 ( n=158 ) received MMF for 3 months , replaced by AZA for 9 months ; group 2 ( n=162 ) received MMF for 12 months ; and group 3 ( n=157 ) received AZA for 12 months . Results . Treatment failure and the cumulative rate of acute rejection were significantly lower in the MMF groups compared with the AZA group ( P = 0.007 and P = 0.03 , respectively ) . Graft loss , death , and safety profiles of all three treatments were similar over 12 months , as were mean serum creatinine levels . Switching from MMF to AZA did not affect treatment failure . No patient in group 1 experienced a recurrent rejection after month 3 , one patient died , and nine patients experienced first rejection episodes . Most rejections ( 6/9 ) were steroid-sensitive and histologically mild . Conclusions . Replacement of MMF by AZA after 3 months of therapy with ME-CsA and steroids provides comparable efficacy and safety profiles to continuous MMF over 12 months . Although apparently a cost-effective option , long-term studies are required to assess the benefit/risk ratio of this therapy switch in different patient sub population Background . Chronic steroid therapy in kidney transplantation has myriad side effects and steroid avoidance has become feasible . This prospect i ve study compared the safety and efficacy of steroid avoidance in tacrolimus (TAC)/mycophenolate mofetil ( MMF ) and TAC/sirolimus ( SRL ) combinations in kidney transplantation . Methods . In all , 150 kidney recipients were analyzed : 75 each in TAC/MMF and TAC/SRL groups . The primary endpoint was acute rejection . Surveillance biopsies were completed to analyze sub clinical acute rejection ( SCAR ) and chronic allograft nephropathy ( CAN ) . Acute rejection and SCAR were treated by methylprednisolone . Two-year patient and graft survival , renal function , and adverse effects were monitored . Results . Acute rejection was seen in 12 % of TAC/MMF and 8 % of TAC/SRL patients . Two-year actuarial patient survival was 95 % and 97 % , and graft survival 90 % and 90 % in TAC/MMF and TAC/SRL groups , respectively . Surveillance biopsy showed cumulative incidence of SCAR was 27 % in TAC/MMF and 16 % in TAC/SRL groups at 2 years ( P=0.04 ) . Overall , 33 % of recipients in TAC/MMF and 20 % in TAC/SRL received methylprednisolone for acute rejection/SCAR . Moderate/severe CAN was 10 % in TAC/SRL group and 22 % in TAC/MMF group(P=0.06 ) . New-onset diabetes mellitus ( NODM ) was 4 % each in both groups . All recipients remain free of maintenance steroid therapy . Conclusions . Steroid avoidance in tacrolimus-based immunosuppression with MMF or SRL provides equivalent 2-year patient and graft survival with a low incidence of acute rejection and NODM . SCAR and CAN are lower in TAC/SRL compared to TAC/MMF group . The impact of decreased SCAR and CAN in TAC/SRL group on longer-term graft survival and function is to be evaluated Acute graft rejection remains a major problem in renal transplant recipients , and there is no consensus on the optimal immunosuppressive strategy . Immunoprophylaxis with Thymoglobulin ® or basiliximab has significantly reduced the incidence of acute rejection episodes and graft loss following kidney transplantation . This open , r and omized , multicenter study investigated the efficacy and tolerability of basiliximab ( 20 mg day 0– day 4 ) plus early cyclosporine from day 0 ( n = 50 ) compared with Thymoglobulin ® plus delayed cyclosporine ( n = 50 ) in adult kidney transplant patients . In addition , all patients received steroids and mycophenolate mofetil ( MMF ) at st and ard doses from day 0 . Patient and graft survival rates at 12 months were 98 and 94 % in the basiliximab group , respectively , compared with 100 and 96 % in the Thymoglobulin ® group . The incidences of biopsy‐confirmed acute rejection ( 8.0 % in each group ) and treatment failure ( 14 % in the basiliximab group vs. 8 % in the Thymoglobulin group ) were comparable in the two groups . There was a nonsignificant tendency to more dialysis ( 14 vs. 6 % ) , and fewer cytomegalovirus ( CMV ) infections ( p = 0.005 ) in the basiliximab group , but the percentage of clinical CMV was not different between the two groups ( 6 vs. 12 % ) . Both strategies give excellent results , despite the differences in patterns , in nonhyperimmunized patients receiving their first cadaveric renal allograft Background s. Variability of blood trough concentration ( C0 ) in immunosuppressant leads to rejection and graft loss after kidney transplantation . Methods . The aim of this study is to prospect ively investigate the change of within-patient variability among stable kidney transplant recipients with conversion from twice-daily Prograf to the same milligram-for-milligram daily dose of once-daily Advagraf . Results . The mean age of 129 patients was 51.3±12.1 years . The conversion to Advagraf was administrated at 6.3±4.8 years after transplantation . The daily dose was changed from 4.7±2.0 mg to 4.9±2.1 mg after conversion . Only six patients increased daily dose by 16.7 % to 25 % to maintain target levels . The whole blood C0 of tacrolimus before conversion was 5.9±1.7 ng/mL. The mean C0 was significantly reduced after conversion to Advagraf ; it was 4.9±1.5 ng/mL on the seventh day ( P<0.001 ) and 5.4 to 5.5 ng/mL at 1 to 6 months ( P<0.05 ) . Forty-one ( 31.8 % ) patients have reduced C0 of more than 25 % on the seventh day . The percent coefficient of variation of tacrolimus C0 more than 22.5 % before conversion is associated with higher risk of reduced C0 after conversion ( P<0.05 ) . Compared with before conversion , less kidney transplant recipients have percent coefficient of variation more than 22.5 % after conversion ( 3.1 % vs. 17.4 % with P<0.01 ) . Conclusions . The results support that conversion from Prograf to Advagraf among kidney transplant recipient leads to a significantly lower C0 and within-patient variability of tacrolimus C0 . The within-patient variability of C0 before conversion influences C0 on the sevent day after conversion to Advagraf Delayed graft function ( DGF ) has long been identified as one of the main correlates of poor graft survival in cadaveric renal transplantation , but the factors that affect its onset and duration are not fully eluci date d. The impact of two immunosuppressive protocol s on the incidence and length of DGF among kidney transplant recipients of a suboptimal organ was evaluated . Patients were r and omly treated with corticosteroids ( CS ) ; low-dose cyclosporine ( CsA ) and sirolimus ( SRL ; group 1 ; n = 42 ) ; or CS , full-dose CsA , and mycophenolate mofetil ( group 2 ; n = 48 ) . All recipients received immunoprophylaxis with basiliximab . After 3 mo , group 1 discontinued CsA and continued with SRL , whereas group 2 continued the same treatment . The incidence of DGF was similar in the two groups ( group 1 = 52.4 % ; group 2 = 58.3 % ) , whereas its duration was significantly higher in the group 1 ( 19.0 + /- 6.0 versus 10.3 + /- 3.2 d ; P = 0.001 ) . Both groups showed 100 % actuarial graft and patient survival at 1-yr . Among DGF patients , serum creatinine ( sCr ) at discharge was significantly worse in group 1 ( sCr , 3.0 + /- 1.0 versus 1.5 + /- 0.2 mg/dl ; calculated creatinine clearance , 31.2 + /- 9.3 versus 61.1 + /- 10 ml/min ; P = 0.001 ) . During the first year , the former group displayed a significant improvement of graft function , such that at 1-yr , no difference could be measured between groups ( sCr , 1.8 + /- 0.5 versus 1.7 + /- 0.4 mg/dl ; calculated creatinine clearance , 51.5 + /- 10.2 versus 53.3 + /- 9.4 ml/min ) . In conclusion , in de novo renal transplanted patients , the administration of SRL , in combination with low-dose CsA , is associated with a delayed recovery from DGF but does not worsen 1-yr graft function AIMS Restoration of renal function after kidney transplantation ( KT ) is expected to improve oxidative stress ( OS ) . However , little is known about the influence of calcineurin inhibitors on oxidized low-density lipoproteins ( ox-LDL ) after KT . The aim of this study was to evaluate ox-LDLs and related markers of OS , advanced oxidation protein products ( AOPP ) and total antioxidant status ( TAS ) in patients after KT on either cyclosporin A ( CyA ) or tacrolimus ( Tac ) treatment . METHODS This was a prospect i ve , r and omized , single-center 12 month study evaluating time-dependent changes in biomarkers of OS before and after KT . Twenty nine patients ( mean age 54.4 ± 11.1 ; 55 % male and 45 % female ) were treated with CyA ( Group A ) and twenty four patients ( mean age 52.9 ± 9.9 ; 75 % male and 25 % female ) were treated with Tac ( Group B ) . The ox-LDL , AOPP , TAS , lipid metabolism parameters , creatinine and glomerular filtration were assessed on day 1 before KT and on days 1 and 7 , and in months 1 , 3 , 6 and 12 after KT . RESULTS Over the 12 months , the ox-LDL for group A changed from 69.2±32.9 to 65.1±17.1 U/L ( P=0.665 ) , while AOPP significantly decreased from 233.0±159.6 to 156.5±90.1 μmol/L ( P=0.025 ) and TAS from 1.87±0.31 to 1.68±0.20 mmol/L ( P=0.030 ) . For group B the ox-LDL changed from 62.9±29.7 to ± 61.4±14.6 U/L ( P=0.168 ) and TAS from 1.87±0.51 to 1.68±0.20 mmol/L ( P=0.168 ) , while AOPP significantly decreased from 180.5±90.0 to 123.9±37.7 μmol/L ( P=0.019 ) . CONCLUSION AOPP is more sensitive than ox-LDL for assessing OS after KT . TAS values appear to be insufficiently sensitive for monitoring OS in patients after KT BACKGROUND Comparison studies of calcineurin inhibitors as cornerstone immunosuppressants in renal transplantation have demonstrated that tacrolimus consistently reduces acute rejection rates and , in some studies , also improves long-term renal outcome in comparison to cyclosporin A ( CsA ) . The aim of the present 2 year follow-up of the European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was to investigate long-term clinical outcome in terms of rate of acute rejection , graft and patient survival and graft function . METHODS The European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was a r and omized , comparative 6 month trial of the calcineurin inhibitors tacrolimus and CsA in combination with both azathioprine and steroids . The intent-to-treat population ( ITT ) consisted of 286 patients in the tacrolimus arm and 271 in the CsA microemulsion ( CsA-ME ) arm . Whereas whole blood level targets were 10 - 20 and 5 - 15 ng/ml for tacrolimus and 100 - 400 and 100 - 200 ng/ml for CsA during months 0 - 3 and 4 - 6 , respectively , during the investigator-driven follow-up after termination of the main study ( months 7 - 24 ) no specific calcineurin inhibitor target levels were required . Follow-up data were collected at 2 years post-transplantation from 237 ( 82.9 % of the ITT population ) patients who received tacrolimus and 222 ( 81.9 % of the ITT population ) patients who received CsA-ME . RESULTS Calculated on ITT population s , mortality ( 2.0 % vs 3.3 % ; P<0.05 in Kaplan-Meier analysis ) was lower , but rate of graft loss ( 9.3 % vs 11.2 % ; P = 0.12 in Kaplan-Meier analysis ) was not significantly different after 2 years with tacrolimus- vs CsA-ME-based immunosuppression . Biopsy-proven acute rejection was significantly lower ( 19.6 % ) with tacrolimus than with CsA-ME ( 37.3 % ) during months 0 - 6 ( P<0.0001 ) , but was not significantly different during months 7 - 12 and 13 - 24 of follow-up ( 1.7 % and 0.8 % with tacrolimus and 4.7 % and 0.9 % with CsA-ME , respectively ) . A composite endpoint consisting of graft loss , patient death and biopsy-proven acute rejection occurred significantly more frequently in CsA-ME patients than in tacrolimus patients ( 42.8 % vs 25.9 % ; P<0.001 ) during 24 months follow-up . Renal function 2 years post-transplant , measured by serum creatinine concentrations , was significantly better in tacrolimus-based compared with CsA-ME-based immunosuppression ( 136.9 vs 161.6 micromol/l ; P<0.01 ) . Cornerstone immunosuppression remained unchanged in 82.5 % and 66.2 % of patients treated with tacrolimus and CsA-ME , respectively . At 2 years , more patients in the tacrolimus arm were off steroids and received calcineurin inhibitor monotherapy , and fewer tacrolimus patients remained on a triple immunosuppressive regimen . The cardiovascular risk profile was affected favourably in the tacrolimus arm , with lower cholesterol and triglyceride concentrations ( despite less use of cholesterol-lowering drugs ) ; no significant difference in requirement for antidiabetic medication was noted . CONCLUSIONS The 2 year study results confirm that tacrolimus is a highly efficacious cornerstone immunosuppressant in kidney transplantation . Tacrolimus-based immunosuppression may induce long-term benefits with regard to graft function and graft survival . The overall side-effect profile is considered to be favourable In a multicenter trial , renal transplant recipients were r and omized to tacrolimus with fixed-dose sirolimus ( Tac/SRL , N = 318 ) or tacrolimus with MMF ( Tac/MMF , N = 316 ) . Targeted tacrolimus trough levels were lower in the Tac/SRL group after day 14 . The primary endpoint was renal function at 6 months using creatinine clearance ( Cockcroft-Gault ) and was comparable at 66.4 mL/min ( SE 1.4 ) with Tac/SRL and at 65.2mL/min ( SE 1.3 ) with Tac/MMF ( completers ) . Biopsy-confirmed acute rejection was 15.1 % ( Tac/SRL ) and 12.3 % ( Tac/MMF ) . In both groups , graft survival was 93 % and patient survival was 99.0 % . Premature withdrawal due to an adverse event was twice as high in the Tac/SRL group , 15.1 % versus 6.3 % . Hypercholesterolemia incidence was higher with Tac/SRL ( P < .05 ) while CMV , leukopenia , and diarrhea incidences were higher with Tac/MMF ( P < .05 ) . The incidence of any antidiabetic treatment for > 30 consecutive days in previously nondiabetic patients was 17.8 % , Tac/SRL , and 24.8 % , Tac/MMF . Evaluation at 6 months showed comparable renal function using tacrolimus/sirolimus and tacrolimus/MMF regimens Immunological monitoring for chronic allograft nephropathy ( CAN ) is of great potential interest . We assessed serum soluble CD30 ( sCD30 ) together with in vitro Th2‐type responses ( IL‐4 , IL‐10 , CD4 helper activity ) and neopterin in a prospect i ve study of 84 renal transplant recipients with 2‐year follow‐up . Patients were r and omized to CsA/Aza , CsA/MMF and Tacr/Aza , respectively , to analyze the effect of immunosuppression on posttransplant sCD30 and neopterin . ATG induction and acute rejections did not alter sCD30 levels whereas CMV disease was associated with transient upregulation of sCD30 ( p = 0.003 at 4 months ) and sustained upregulation of neopterin ( corrected for graft function ( Neo/CR ) p = 0.005 at 2 years ) . Tacr versus CsA treatment proved to be an independent variable associated with downregulation of 1‐year sCD30 , which was positively related to Neo/CR ( p = 0.007 and 0.01 , respectively ; logistic regression ) . Importantly , increased 1‐year sCD30 and Neo/CR were associated with decreased glomerular filtration rate at 2 years ( p = 0.02 and p < 0.0005 , respectively ) and evidence of CAN ( p < 0.0005 ) . High 1‐year sCD30 could not be attributed to enhanced Th2‐type responses and was not associated with HLA antibody formation . Our data suggest that elevated sCD30 and neopterin predict graft deterioration by CAN . Tacr effectively downregulates these responses and might be of advantage in patients with elevated sCD30 or neopterin OBJECTIVE This study examines the outcomes of de novo kidney transplants treated by a sequential protocol , design ed to target the succession of immunologic events following engraftment . SUBJECTS A total of 113 sequential live-donor recipients were r and omized into 2 arms . Patients in arm A received prednisolone , cyclosporine , and sirolimus for 3 months ( phase 1 ) , followed by replacement of cyclosporine with mycophenolate mofetil ( phase 2 ) . Those in arm B ( controls ) received prednisolone/cyclosporine/mycophenolate mofetil throughout the study . The primary endpoints were patient and graft survival rates at 2 years . Secondary endpoints included biopsy-proven acute rejection , early and late graft function , hypertension , and adverse reactions . RESULTS The 2-year intent-to-treat patient and graft survival rates ( 95.8 % vs 91.4 % and 94.6 % vs 90.2 % ) were numerically but not significantly higher in arm A. The overall incidence of biopsy-proven acute rejection was numerically lower ( 13.5 % vs 18.9 % ) , yet it occurred exclusively with cyclosporine C2 levels below 770 ng/mL ( P = .28 ) . Mean time for serum creatinine to reach 132 micromol/L was significantly longer in arm A ( 7.3 vs 2.9 days ) . Graft function at 2 years ( eGFR , 70.2 vs 55.9 mL/min ) and number of drugs needed to control blood pressure ( mean 1.7 vs 2.25 ) were significantly more favorable in group A. Significant adverse effects for patients in arm A included proteinuria ( 36.8 % vs 18.6 % ) , hyperlipidemia ( peak cholesterol > 7.75 mmol/L in 32.9 % vs 23.7 % of patients ) and thrombocytopenia ( platelet count < 100 x 109/L in 32.9 % vs 13.5 % of patients ) . CONCLUSIONS The described protocol reduced the incidence of biopsy-proven acute rejection in patients after kidney transplant , particularly in those with adequate cyclosporine blood levels . Despite the significantly higher incidence of certain adverse effects ( ie , delayed graft function , proteinuria , hyperlipidemia , and transient thrombocytopenia ) , patient and graft survival rates at 2 years were numerically , though not statistically , improved in patients in arm A. At 2-year analysis , compared with patients in the control arm ( arm B ) , graft function significantly improved in patients in arm A , and the number of drugs needed to control blood pressure was significantly lower Our purpose s were to determine the incidence of BK viruria , viremia or nephropathy with tacrolimus ( FK506 ) versus cyclosporine ( CyA ) and whether intensive monitoring and discontinuation of mycophenolate ( MMF ) or azathioprine ( AZA ) , upon detection of BK viremia , could prevent BK nephropathy Everolimus allows calcineurin‐inhibitor reduction without loss of efficacy and may improve renal‐transplant outcomes . In a 24‐month , open‐label study , 833 de novo renal‐transplant recipients were r and omized to everolimus 1.5 or 3.0 mg/day ( target troughs 3–8 and 6–12 ng/mL , respectively ) with reduced‐exposure CsA , or mycophenolic acid ( MPA ) 1.44 g/day plus st and ard‐exposure CsA. Patients received basiliximab ± corticosteroids . The primary endpoint was composite efficacy failure ( treated biopsy‐proven acute rejection , graft loss , death or loss to follow‐up ) and the main safety endpoint was renal function ( estimated glomerular filtration rate [ eGFR ] , by Modification of Diet in Renal Disease [ MDRD ] ) at Month 12 ( last‐observation‐carried‐forward analyses ) . Month 12 efficacy failure rates were noninferior in the everolimus 1.5 mg ( 25.3 % ) and 3.0 mg ( 21.9 % ) versus MPA ( 24.2 % ) groups . Mean eGFR at Month 12 was noninferior in the everolimus groups versus the MPA group ( 54.6 and 51.3 vs 52.2 mL/min/1.73 m2 in the everolimus 1.5 mg , 3.0 mg and MPA groups , respectively ; 95 % confidence intervals for everolimus 1.5 mg and 3.0 mg vs MPA : −1.7 , 6.4 and −5.0 , 3.2 , respectively ) . The overall incidence of adverse events was comparable between groups . The use of everolimus with progressive reduction in CsA exposure , up to 60 % at 1 year , result ed in similar efficacy and renal function compared with st and ard‐exposure CsA plus MPA BACKGROUND Exposure to mycophenolic acid ( MPA ) , the primary active metabolite of mycophenolate mofetil ( MMF ) , is correlated with therapeutic efficacy of MMF but varies depending on the concomitantly administered immunosuppressive drugs . METHODS A 3-month pharmacokinetic sub study of the prospect i ve , r and omized , multicentre , open-label Symphony study was performed . Eighty-three adult renal transplant patients received st and ard-dose cyclosporine , MMF 2 g/day and corticosteroids , or daclizumab induction , MMF 2 g/day and corticosteroids plus low-dose cyclosporine , low-dose tacrolimus or low-dose sirolimus . The area under the concentration-time curve ( AUC(0 - 12 ) ) of MPA and its metabolites between treatment groups was compared . Pharmacokinetic sampling was performed before MMF administration and at 20 , 40 , 75 min ; 2 , 3 , 6 , 8 , 10 and 12 h post-dose on Day 7 and Months 1 and 3 . RESULTS Compared with st and ard-dose cyclosporine , patients receiving low-dose tacrolimus or low-dose sirolimus had significantly higher AUC(0 - 12 ) values for MPA at Day 7 and Month 1 and for free MPA at Day 7 , and significantly lower AUC(0 - 12 ) values for 7-O-MPA-glucuronide ( MPAG ) at Month 1 and for acyl-glucuronide at Months 1 and 3 ( P < 0.05 ) . AUC(0 - 12 ) of MPA and free MPA was significantly greater with low-dose tacrolimus and low-dose sirolimus than with low-dose cyclosporine in the first month ( P < 0.05 ) . The ratio of MPA to MPAG exposure was significantly higher in the three low-dose groups than in the st and ard-dose cyclosporine group ( P < 0.05 ) . CONCLUSIONS St and ard- and low-dose cyclosporine reduces the exposure of MPA and free MPA compared to low-dose tacrolimus or low-dose sirolimus in patients given the same dose of MMF INTRODUCTION Sirolimus is the one of new immunosuppressants that may be a substitute to traditional drugs such as cyclosporine . We present our investigation on sirolimus-based immunosuppression in kidney transplant recipients as compared with cyclosporine-based immunosuppression . MATERIAL S AND METHODS We enrolled 100 patients in an open-labeled r and omized clinical trial at Shahid Labbafinejad Medical Center . The patients were assigned to one of the immunosuppressive groups to receive either sirolimus or cyclosporine in combination with mycophenolate mofetil and steroids . All kidney transplant recipients were followed up by for serum creatinine and glomerular filtration rate for 4 years . RESULTS There was no significant differences between the two groups regarding serum creatinine level and GFR until for years posttransplant ; however , serum creatinine levels were significantly lower and the GFRs were higher in the sirolimus group after 3 and 4 years . The mean serum creatinine was 1.24 ± 0.28 mg/dL in the sirolimus group and 1.57 ± 0.33 mg/dL in the cyclosporine group at 4 years posttransplant ( P = .02 ) . Also , GFR was 79.8 ± 22.3 mL/min/1.73 m2 in the sirolimus group and 70.3 ± 23.6 mL/min/1.73 m2 in the cyclosporine group B ( P = .04 ) . Acute rejection was 1.7-fold higher in the cyclosporine group than in the sirolimus group . CONCLUSIONS Our study demonstrated that sirolimus in the immunosuppressive regimen of kidney transplant recipients had better outcomes regarding graft and patient survival . The effectiveness of sirolimus for kidney allograft recipients should be further assessed to be implemented from the first day after transplantation BACKGROUND Induction immunosuppression is perceived as an expensive therapy , so is often given only to select patients . This study evaluated the cost-effectiveness of antibody induction comparing interleukin-2 receptor antagonists ( IL2Ra ) to st and ard therapy with no induction or induction with polyclonal antibodies . METHODS A Markov model was developed to estimate costs and health outcomes [ survival ( life years saved , LYS ) and quality -adjusted survival ( QALYs ) ] for the alternative strategies . Outcome data were obtained from a meta- analysis of r and omized trials and large-scale renal registries . RESULTS IL2Ra offers improved survival of 0.21 LYS ( 2.5 months ) and 1.42 QALYs compared with no induction , with a cost saving over 20 years of $ 79,302 per patient treated regardless of risk profile . The incremental benefits of IL2Ra compared with polyclonal antibody induction therapy were 0.35 LYS ( 4.3 months ) and 0.20 QALYs , with an incremental cost of $ 5144 per patient . The incremental cost-effectiveness ratio ( ICER ) of IL2Ra compared to polyclonal induction was $ 14,803 per LYS and $ 25,928 per QALY . Sensitivity analyses showed that IL2Ra remained more effective and less expensive than no induction . When IL2Ra was compared to polyclonal induction , the model was sensitive to changes in the cost of induction and the probability of malignancy . Over the range of all other variables tested , IL2Ra was cost-effective compared to polyclonal induction . CONCLUSIONS Adopting IL2Ra as induction immunosuppression for kidney transplant recipients improves survival and QALYs and is less costly than no induction . It also represents good value for money compared to polyclonal induction Pharmacokinetic analyses comparing generic tacrolimus preparations versus the reference drug in kidney transplant patients are lacking . A prospect i ve , multicenter , open‐label , r and omized , two‐period ( 14 days per period ) , two‐sequence , crossover and steady‐state pharmacokinetic study was undertaken to compare twice‐daily generic tacrolimus ( S and oz ) versus reference tacrolimus ( Prograf ® ) in stable renal transplant patients . AUC0–12h and peak concentration ( Cmax ) were calculated from 12 h pharmacokinetic profiles at the end of each period ( days 14 and 28 ) . Of 71 patients enrolled , 68 provided evaluable pharmacokinetic data . The ratios of geometric means were 1.02 ( 90 % CI 97–108 % , p = 0.486 ) for AUC0–12h and 1.09 ( 90 % CI 101–118 % , p = 0.057 ) for Cmax . Mean ( SD ) C0 was 7.3(1.8 ) ng/mL for generic tacrolimus versus 7.0(2.1 ) ng/mL for reference tacrolimus based on data from days 14 and 28 . Correlations between 12 h trough levels and AUC were r = 0.917 for generic tacrolimus and r = 0.887 for reference drug at day 28 . These data indicate that generic tacrolimus ( S and oz ) has a similar pharmacokinetic profile to the reference drug and is bioequivalent in kidney transplant recipients according to US Food and Drug Administration and European Medicines Agency guidelines Background Old studies reported a worse outcome for second transplant recipient ( STR ) than for first transplant recipient ( FTR ) mainly due to non-comparable population s with numbers confounding factors . More recent analysis , based on improved methodology by using multivariate regressions , challenged this generally accepted idea : the poor prognosis for STR is still under debate . Methodology To assess the long-term patient- and -graft survival of STR compared to FTR , we performed an observational study based on the French DIVAT prospect i ve cohort between 1996 and 2010 ( N = 3103 including 641 STR ) . All patients were treated with a CNI , an mTOR inhibitor or belatacept in addition to steroids and mycophenolate mofetil for maintenance therapy . Patient- and -graft survival and acute rejection episode ( ARE ) were analyzed using Cox models adjusted for all potential confounding factors such as pre-transplant anti-HLA immunization . Results We showed that STR have a higher risk of graft failure than FTR ( HR = 2.18 , p = 0.0013 ) but that this excess risk was observed after few years of transplantation . There was no significant difference between STR and FTR in the occurrence of either overall ARE ( HR = 1.01 , p = 0.9675 ) or steroid-resistant ARE ( HR = 1.27 , p = 0.4087 ) . Conclusions The risk of graft failure following second transplantation remained consistently higher than that observed in first transplantation after adjusting for confounding factors . The rarely performed time-dependent statistical modeling may explain the heterogeneous conclusions of the literature concerning second transplantation outcomes . In clinical practice , physicians should not consider STR and FTR equally It is reported that a conversion from mycophenolate mofetil ( MMF ) to enteric-coated mycophenolate sodium ( EC-MPS ) relieves gastrointestinal ( GI ) symptom burden and improves health-related quality of life ( HRQoL ) . However , it is unclear whether renal transplant recipients using tacrolimus receive the same benefit from the conversion . In this prospect i ve , multi-center , open-label trial , patients were categorized into two groups by their GI symptom screening . Equimolar EC-MPS ( n=175 ) was prescribed for patients with GI burdens ; those with no complaints remained on MMF ( n=83 ) . Gastrointestinal Symptom Rating Scale ( GSRS ) and Gastrointestinal Quality of Life Index ( GIQLI ) were evaluated at baseline and after one month . Patients and physicians completed Overall Treatment Effect ( OTE ) at one month . EC-MPS-converted patients had worse GSRS and GIQLI scores at baseline than MMF-continued patients ( all P<0.001 ) . Significant improvements in GSRS and GIQLI scores were observed for EC-MPS-converted patients at one month , but MMF-continued patients showed worsened GSRS scores ( all P<0.05 ) . OTE scale indicated that EC-MPS patients improved in overall GI symptoms and HRQoL more than MMF patients did ( P<0.001 ) . In tacrolimus-treated renal transplant recipients with GI burdens , a conversion from MMF to EC-MPS improves GI-related symptoms and Background . Long-term success of renal transplantation depends upon the quality of the donor organ , avoidance of peritransplant and early posttransplant damage ( rejection ) , and optimal maintenance of graft function after the first 6–12 months . Glomerular filtration rate ( GFR ) at 1 year is a st and ard way to evaluate short-term success , whereas calculated GFR at 5 years gives a better appreciation of long-term outcomes . The objective of this study was to assess the effect of various demographic and transplant-related parameters on renal function via GFR at 1 year and 5 years post transplantation , using univariate and multivariate data analysis . Methods . Data on 1-year GFR were available from 10,397 patients , whereas 2,889 patients provided data on both 1-year and 5-year GFR . All patients were enrolled in the Neoral Multinational Observational Study in Transplantation ( Neoral-MOST ) , an ongoing , prospect i ve , observational study of adult renal transplant recipients . Results . One-year GFR was the most relevant predictor for 5-year GFR . In a multifactorial analysis ( ANCOVA ) using 1-year GFR as a continuous variable , the effects of several highly relevant parameters from univariate analysis ( such as acute rejection and delayed graft function ) on 5-year GFR appeared to be fully mediated by their influence on 1-year GFR , whereas immunological risk factors like HLA match or previous transplantation had an ongoing effect on graft function beyond year 1 . Conclusions . The findings of this study corroborate and augment data from previous registry surveys , and confirm the importance of observational studies in investigating the role of peritransplant parameters on long-term graft outcome Background . The Symphony study compared four immunosuppressant regimens , defined by protocol -specified target drug concentrations . This sub analysis examines actual drug levels and the implication s on the interpretation of results . Methods . De novo renal transplant patients ( n=1645 ) were r and omized to receive mycophenolate mofetil ( 2 g/day ) and corticosteroids in combination with st and ard-dose cyclosporine A ( CsA ; 150–300 ng/mL for 3 months then 100–200 ng/mL ) , or daclizumab induction and low-dose CsA ( 50–100 ng/mL ) , low-dose tacrolimus ( Tac ; 3–7 ng/mL ) , or low-dose sirolimus ( SRL ; 4–8 ng/mL ) . Results . Low-dose Tac was significantly superior for renal function , acute rejection , and graft survival at 12 months . Median trough levels of CsA , Tac , or SRL were toward the high end of target ranges in all groups , and 50 % to 60 % were within target . During weeks 1 to 8 , only 6.5 % to 11.0 % of patients were consistently within target . At week 8 , the range of concentrations encompassing 75 % of patients on st and ard-dose CsA was 141 to 321 ng/mL ; for low-dose CsA , 62 to 159 ng/mL ; for low-dose Tac , 4.3 to 10.0 ng/mL , and for low-dose SRL , 4.4 to 11.2 ng/mL. The protocol -defined target levels were approximately , but not fully achieved . Conclusions . To replicate the Symphony study results in clinical practice , the protocol -defined drug concentration targets should be aim ed for , but the concentrations actually achieved may be regarded as acceptable . Future clinical studies should include measures of how well target drug levels were achieved to better guide further attempts to develop new regimens design ed to reduce or eliminate calcineurin inhibitors Background . Everolimus is a proliferation inhibitor design ed to target chronic rejection , including prevention of acute rejection . Everolimus blocks growth factor-mediated transduction signals , preventing organ rejection by a mechanism different than that of calcineurin inhibitors and of mycophenolate mofetil ( MMF ) . Methods . Everolimus ( 1.5 mg or 3 mg daily ) was compared with MMF ( 2 g daily ) in a r and omized , multicenter , multinational , 12-month double-blind , double-dummy and 2-year open-label , phase 3 trial in de novo renal allograft recipients ( n=588 ) who also received cyclosporine and corticosteroids as part of a triple immunosuppressive regimen . Results . At 12 months , there were no statistically significant differences between doses of 1.5 and 3 mg/day everolimus and MMF ( 2 g/day ) in incidence of biopsy-proven acute rejection ( 23.2 % , 19.7 % , and 24.0 % , respectively ) , graft loss ( 4.6 % , 10.6 % , and 9.2 % ) , or death ( 5.2 % , 4.0 % , and 2.6 % ) , respectively . Everolimus 1.5 mg/day and MMF were generally equally well tolerated . Both were better tolerated than everolimus 3 mg/day . The incidence of cytomegalovirus infection was significantly lower in patients receiving either 1.5 or 3 mg/day everolimus than in those receiving MMF ( 5.2 % and 7.6 % vs. 19.4 % , respectively ) ( P=.001 ) . Conclusions . Everolimus is effective in preventing acute rejection and graft loss in de novo renal allograft recipients receiving a triple immunosuppressive regimen . Prevention of acute rejection , along with reduction in cytomegalovirus infection , addresses two factors known to contribute to chronic rejection in such patients Background . This 36-month , r and omized , parallel-group study compared safety and efficacy of two doses of everolimus with mycophenolate mofetil ( MMF ) in de novo renal-transplant recipients . Methods . Renal-allograft recipients received 1.5 mg/day or 3 mg/day of everolimus or 2 g/day of MMF , plus full-dose cyclosporine ( CsA ) and corticosteroids after r and omization . For at least their first year , patients received study medication according to a double-blinded , double-dummy design . Concerns over nephrotoxicity led to a protocol amendment to an open-label design with reduced CsA troughs . Results . Incidences of primary efficacy failure at 36 months ( biopsy-proven acute rejection , graft loss , death , or loss to follow-up ) were everolimus 1.5 mg/day , 33.7 % ( 65/193 ) ; everolimus 3 mg/day , 34.0 % ( 66/194 ) ; and MMF , 31.1 % ( 61/196 ) ( P=0.810 ) . Antibody-treated acute rejection at 36 months was significantly lower with everolimus 1.5 mg ( 9.8 % ) than MMF ( 18.4 % , P=0.014 ) . Discontinuation for adverse events was more frequent with everolimus and hemolytic uremic syndrome , lymphoproliferative disease , and proteinuria , and higher serum creatinine occurred at increased frequency relative to the MMF arm . Creatinine levels in the everolimus arms were stable in follow-up : the mean rise in creatinine over the first 6 months of the open-label phase was 3 & mgr;mol/L or greater with everolimus and 7 & mgr;mol/L with MMF . However , serum creatinine levels were lower in the MMF group throughout . Death and graft loss were higher in the everolimus arms ( not significant ) . Conclusions . As part of triple-drug immunosuppression , everolimus ( 1.5 or 3 mg/day ) was as efficacious as MMF , although the side-effect profile featured increased adverse events . Nephrotoxicity/calcineurin – inhibitor-related adverse events will require judicious lowering of CsA exposure with monitoring of everolimus troughs Background . To define the role of mammalian target of rapamycin inhibitors in kidney transplantation , we compared efficacy and safety of two immunosuppressive regimens — a calcineurin inhibitor-free regimen with depletive induction versus a calcineurin inhibitor-based regimen . Methods . De novo renal allograft recipients were r and omized before transplantation to receive sirolimus ( SRL ; n=71 , group A ) or tacrolimus ( n=70 , group B ) . All patients received mycophenolate mofetil and corticosteroids . In group A , patients received rabbit antithymocyte globulin induction . In group B , antithymocyte globulin therapy could be given in case of delayed graft function . The estimated glomerular filtration rate ( GFR ) ( Nankivell 's formula ) at month 12 was the primary endpoint . Results . GFR showed no significant difference at month 12 , with 56.1 in group A versus 58.4 mL/min/1.73 m2 in group B. In functioning grafts , renal function was significantly better in the SRL group , with higher GFR values at months 1 , 2 , 3 , 6 , and 9 ( P<0.05 ) . At month 12 , patient survival and incidence of biopsy-proven rejection were not different between groups ( 95.8 % vs. 97.1 % , and 16.9 % vs. 12.9 % , respectively ) . However , proportion of graft loss was higher with SRL at months 6 and 12 ( 11.3 % vs. 0.0 % , P=0.004 ; 14.1 % vs. 4.3 % , P=0.044 , respectively ) . Adverse events and premature withdrawals were more frequent with SRL ( P<0.001 and P<0.05 , respectively ) , whereas cytomegalovirus infections were more frequent with tacrolimus ( P<0.001 ) . Conclusion . Patients treated with induction plus SRL , mycophenolate mofetil , and corticosteroids may obtain good renal function but have a higher risk of adverse events , drug withdrawal , and graft loss Background . Progressive nephrotoxicity caused by calcineurin inhibitor drugs contributes to the long-term decline in renal function in kidney transplant patients . Methods . We conducted a r and omized , prospect i ve trial of calcineurin inhibitor drug avoidance in 61 adult primary kidney transplant recipients . Each patient received induction therapy with 20 mg basiliximab on days 0 and 4 , and maintenance therapy with mycophenolate mofetil 1 g two times per day and steroids . Thirty-one patients received sirolimus , 5 mg daily after a 15-mg loading dose . Doses were then concentration-controlled to keep 24-hr trough levels at 10 to 12 ng/mL for 6 months and 5 to 10 ng/mL thereafter . Thirty patients began cyclosporine therapy at 6 to 8 mg/kg per day in divided doses and were then concentration-controlled to keep 12-hr troughs of 200 to 250 ng/mL. Results . Mean follow-up is 18.1 months ( range , 12–26 months ) . The percentages of 1-year patient survival , graft survival , and biopsy-confirmed acute rejection rates were not significantly different between the sirolimus-treated patients ( 96.7 % , 96.7 % , and 6.4 % , respectively ) and the cyclosporine-treated patients ( 100 % , 95.4 % , and 16.6 % , respectively ) . At 6 and 12 months , respectively , the sirolimus-treated patients enjoyed significantly better ( P = 0.008 and P = 0.004 ) mean serum creatinine levels ( 1.29 and 1.32 mg/dL ) and calculated creatinine clearances ( 77.8 and 81.1 mL/min ) than cyclosporine-treated patients ( 1.74 and 1.78 mg/dL , and 64.1 and 61.1 mL/min , respectively ) . Sirolimus-treated recipients have significantly ( P = 0.001 ) higher 1-year trough levels of mycophenolic acid ( 4.16 ng/mL ) than cyclosporine-treated patients ( 1.93 ng/mL ) . Sirolimus also delays the re population of basiliximab-depleted CD25 + T cells compared with cyclosporine . Conclusions . Calcineurin inhibitor drug avoidance with basiliximab induction and sirolimus provides comparable 1-year transplant outcomes , with significantly better renal function in primary renal allograft recipients To evaluate the efficacy and tolerance of a calcineurin inhibitor (CNI)‐free regimen , 145 renal recipients were prospect ively r and omized to receive either sirolimus ( n = 71 ) or cyclosporine ( CsA ; n = 74 ) . All patients received polyclonal antilymphocyte antibodies , mycophenolate mofetil ( MMF ) and steroids ( 6 months ) . The primary endpoint , estimated glomerular filtration rate ( eGFR ) was not significantly different at 12 months comparing sirolimus‐ and CsA‐treated patients ( 60 ± 27 vs. 57 ± 21 mL/min ) . At 12 months , patient and graft survival , incidence of biopsy‐proven rejection and rates of steroid withdrawal were not statistically different ( 97 % vs. 97 % ; 90 % vs. 93 % ; 14.3 % vs. 8.6 % and 82.8 % vs. 84.1 % , respectively ) . Delayed and slow graft function ( SGF ) was not significantly different ( 18.6 % vs. 12.3 % and 11.4 % vs. 13.7 % , respectively ) . In patients who remained on treatment according to protocol at 12 months , eGFR was significantly higher with sirolimus ( 69 ± 19 vs. 60 ± 14 mL/min , p = 0.01 ) . Overall study drug discontinuation rates were 28.2 % with sirolimus and 14.9 % with CsA. Adverse events ( wound complications , mouth ulcers , diarrhea , hypokalemia , bronchopneumonia ) and proteinuria > 0.5 g/24h ( 38.8 % vs. 5.6 % , p < 0.001 ) were significantly more frequent in sirolimus‐treated patients . Cytomegalovirus ( CMV ) infections were significantly less frequent with sirolimus ( 6 % vs. 23 % , p < 0.01 ) . A CNI‐free regimen using sirolimus‐MMF can achieve excellent renal function , but patients on sirolimus experienced a high rate of adverse events and study drug discontinuation We performed a r and omized prospect i ve trial comparing calcineurin inhibitor (CNI)‐free to CNI‐based immunosuppression to determine the impact on renal function , structure and gene expression . Sixty‐one kidney recipients treated with basiliximab mycophenolate mofetil ( MMF ) and prednisone ( P ) were r and omly assigned to concentration‐controlled sirolimus or cyclosporine . Two years post‐transplant 55 patients underwent renal function studies , 48 ( 87 % ) underwent transplant biopsies ; all classified by Banff scoring and 41 by DNA microarrays . Comparing sirolimus/MMF/P to cyclosporine/MMF/P there was a significantly lower serum creatinine ( 1.35 vs. 1.81 mg/dL ; p = 0.008 ) , higher Cockroft‐Gault glomerular filtration rate ( GFR ) ( 80.4 vs. 63.4 mL/min ; p = 0.008 ) , iothalamate GFR ( 60.6 vs. 49.2 mL/min ; p = 0.018 ) and Banff 0 ( normal ) biopsies ( 66.6 vs. 20.8 % ; p = 0.013 ) . Regression analysis of calculated GFRs from 1 to 36 months yielded a positive slope for sirolimus of 3.36 mL/min/year , and a negative slope for cyclosporine of −1.58 mL/min/year ( p = 0.008 ) . Gene expression profiles from kidneys with higher Banff chronic allograft nephropathy ( CAN ) scores confirmed significant up‐regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling . At 2 years the sirolimus‐treated recipients have better renal function , a diminished prevalence of CAN and down‐regulated expression of genes responsible for progression of CAN . All may provide for an alternative natural history with improved graft survival There is increasing interest in tacrolimus-minimization regimens . ASSET was an open-label , r and omized , 12-month study of everolimus plus tacrolimus in de-novo renal-transplant recipients . Everolimus trough targets were 3 - 8 ng/ml throughout the study . Tacrolimus trough targets were 4 - 7 ng/ml during the first 3 months and 1.5 - 3 ng/ml ( n = 107 ) or 4 - 7 ng/ml ( n = 117 ) from Month 4 . All patients received basiliximab induction and corticosteroids . The primary objective was to demonstrate superior estimated glomerular filtration rate ( eGFR ; MDRD-4 ) at Month 12 in the tacrolimus 1.5 - 3 ng/ml versus the 4 - 7 ng/ml group . Secondary endpoints included incidence of biopsy-proven acute rejection ( BPAR ; Months 4 - 12 ) and serious adverse events ( SAEs ; Months 0 - 12 ) . Statistical significance was not achieved for the primary endpoint ( mean eGFR : 57.1 vs. 51.7 ml/min/1.73 m(2 ) ) , potentially due to overlapping of achieved tacrolimus exposure levels ( Month 12 mean ± SD , tacrolimus 1.5 - 3 ng/ml : 3.4 ± 1.4 ; tacrolimus 4 - 7 ng/ml : 5.5 ± 2.0 ng/ml ) . BPAR ( months 4 - 12 ) and SAE rates were comparable between groups ( 2.7 % vs. 1.1 % and 58.7 % vs. 51.3 % ; respectively ) . Everolimus-facilitated tacrolimus minimization , to levels lower than previously investigated , achieved good renal function , low BPAR and graft-loss rates , and an acceptable safety profile in renal transplantation over 12 months although statistically superior renal function of the 1.5 - 3 ng/ml tacrolimus group was not achieved Background . This is the 1-year report of a r and omized , multicenter , clinical trial comparing the combination of sirolimus or mycophenolate mofetil ( MMF ) with tacrolimus-based immunosuppression in kidney transplantation . Methods . Prior to transplantation , recipients were r and omized to receive tacrolimus plus corticosteroids with either sirolimus ( n=185 ) or MMF ( n=176 ) . The incidence of biopsy-confirmed acute rejection at 6 months was the primary endpoint of the study . Patient and graft survival , renal function , study drug dosing and discontinuations were evaluated at 1 year . Results . At 1 year , there was no difference in patient survival ( 95.7 % sirolimus vs. 97.2 % MMF ; P=0.45 ) or graft survival ( 90.8 % sirolimus vs. 94.3 % MMF ; P=0.22 ) . Patients without delayed graft function ( DGF ) receiving MMF had significantly better graft survival ( 99 % vs. 93 % ; P=0.01 ) . Patients receiving a transplant from a live donor had a trend towards better graft survival with MMF as compared to sirolimus ( 98 % vs. 91 % ; P=0.07 ) . Patients receiving sirolimus had a significantly higher incidence of study drug discontinuation ( 26.5 % vs. 14.8 % MMF ; P=0.006 ) . Patients receiving MMF had significantly better renal function as shown by median serum creatinine levels ( 1.3 mg/dL vs. 1.5 mg/dL ; P=0.03 ) and a trend towards higher calculated creatinine clearance ( CrCl ) , ( 58.4 ml/min vs. 54.3 ml/min ; P=0.06 ) . More patients in the sirolimus group had a serum creatinine > 2.0 mg/dL , ( 20.4 % vs. 11.0 % ; P=0.02 ) . Conclusions . Tacrolimus is safe and effective in live and deceased donor kidney transplantation when given in combination with sirolimus or MMF . Patient and graft survival were excellent in both arms . Renal function is superior for patients treated with tacrolimus + MMF combination BACKGROUND Induction therapy reduces the frequency of acute rejection and delayed graft function after transplantation . A rabbit antithymocyte polyclonal antibody or basiliximab , an interleukin-2 receptor monoclonal antibody , is most commonly used for induction . METHODS In this prospect i ve , r and omized , international study , we compared short courses of antithymocyte globulin and basiliximab in patients at high risk for acute rejection or delayed graft function who received a renal transplant from a deceased donor . Patients taking cyclosporine , mycophenolate mofetil , and prednisone were r and omly assigned to receive either rabbit antithymocyte globulin ( 1.5 mg per kilogram of body weight daily , 141 patients ) during transplantation ( day 0 ) and on days 1 through 4 or basiliximab ( 20 mg , 137 patients ) on days 0 and 4 . The primary end point was a composite of acute rejection , delayed graft function , graft loss , and death . RESULTS At 12 months , the incidence of the composite end point was similar in the two groups ( P=0.34 ) . The antithymocyte globulin group , as compared with the basiliximab group , had lower incidences of acute rejection ( 15.6 % vs. 25.5 % , P=0.02 ) and of acute rejection that required treatment with antibody ( 1.4 % vs. 8.0 % , P=0.005 ) . The antithymocyte globulin group and the basiliximab group had similar incidences of graft loss ( 9.2 % and 10.2 % , respectively ) , delayed graft function ( 40.4 % and 44.5 % ) , and death ( 4.3 % and 4.4 % ) . Though the incidences of all adverse events , serious adverse events , and cancers were also similar between the two groups , patients receiving antithymocyte globulin had a greater incidence of infection ( 85.8 % vs. 75.2 % , P=0.03 ) but a lower incidence of cytomegalovirus disease ( 7.8 % vs. 17.5 % , P=0.02 ) . CONCLUSIONS Among patients at high risk for acute rejection or delayed graft function who received a renal transplant from a deceased donor , induction therapy consisting of a 5-day course of antithymocyte globulin , as compared with basiliximab , reduced the incidence and severity of acute rejection but not the incidence of delayed graft function . Patient and graft survival were similar in the two groups . ( Clinical Trials.gov number , NCT00235300 [ Clinical Trials.gov ] . ) Regional transplant practice s may affect clinical outcomes within multinational studies . This study evaluated whether the overall results from the Symphony study can be generalized to the participating countries . De novo adult renal transplant recipients ( n = 1645 ) were r and omized to receive st and ard-dose cyclosporine , or daclizumab induction plus low-dose cyclosporine , low-dose tacrolimus , or low-dose sirolimus , all in addition to mycophenolate mofetil and steroids . Data for the highest patient-recruiting countries , Spain ( n = 275),Germany ( n = 316 ) and Turkey ( n = 258 ) , were compared . Patient transplant characteristics were different among the country subsets ; only deceased donors in Spain , more exp and ed criteria donors in Germany , and mainly living donors in Turkey . Efficacy results for the three countries were consistent with that of the overall study - renal function and biopsy-proven acute rejection (BPAR)rates were superior with low-dose tacrolimus . Turkey had higher mean calculated glomerular filtration rate across all treatment groups ( 60.6 - 72.2 ml/min)compared with that of Spain ( 51.1 - 57.5 ml/min ) and Germany ( 51.3 - 62.9 ml/min ) . Spain and Turkey had lower BPAR rates across the four treatment groups compared with the overall study ; Germany had much higher rates(21.0 - 54.2 % ) . These findings confirm the general applicability of the Symphony study results and highlight the importance of inclusion of patients from different geographic origins in r and omized clinical trials The clinical profile of belatacept in kidney transplant recipients was evaluated to determine if earlier results in the BENEFIT study were sustained at 3 years . BENEFIT is a r and omized 3 year , phase III study in adults receiving a kidney transplant from a living or st and ard criteria deceased donor . Patients were r and omized to a more ( MI ) or less intensive ( LI ) regimen of belatacept , or cyclosporine . 471/666 patients completed ≥3 years of therapy . A total of 92 % ( MI ) , 92 % ( LI ) , and 89 % ( cyclosporine ) of patients survived with a functioning graft . The mean calculated GFR ( cGFR ) was ∼21 mL/min/1.73 m2 higher in the belatacept groups versus cyclosporine at year 3 . From month 3 to month 36 , the mean cGFR increased in the belatacept groups by + 1.0 mL/min/1.73 m2/year ( MI ) and + 1.2 mL/min/1.73 m2/year ( LI ) versus a decline of −2.0 mL/min/1.73 m2/year ( cyclosporine ) . One cyclosporine‐treated patient experienced acute rejection between year 2 and year 3 . There were no new safety signals and no new posttransplant lymphoproliferative disorder ( PTLD ) cases after month 18 . Belatacept‐treated patients maintained a high rate of patient and graft survival that was comparable to cyclosporine‐treated patients , despite an early increased occurrence of acute rejection and PTLD Abstract Objective : To compare re source use and costs in renal transplant recipients treated with basiliximab or placebo plus triple immunosuppressive therapy . Design : International r and omised , double-blind , placebo-controlled trial ; economic evaluation undertaken alongside the efficacy trial . The economic evaluation was performed from a UK National Health Service hospital perspective . Setting : 31 centres in 12 countries . Participants : 345 renal transplant recipients were enrolled ; 340 were r and omised ( basiliximab 168 ; placebo 172 ) and included in the intention-to-treat analysis . Intervention : Treatment with placebo or basiliximab ( 20 mg intravenous bolus ) on day 0 and day 4 after transplantation Main outcome measures : Re source utilisation in multiple categories and treatment costs for basiliximab and placebo-treated patients during the 6-month post-transplantation period . Results : No statistically significant differences were found in any of the economically important categories of re source use or in the mean cost of treatment per person across the whole trial . The mean cost of treatment , including the cost of basiliximab , was £ 16 095 for basiliximab recipients and £ 15 864 ( 1997/1998 costs ) for placebo recipients , a mean difference of £ 231 ( 95%CI : −£1983 to £ 2446 ) , which was not significant . Basiliximab treatment led to a significant reduction in acute rejection episodes ( basiliximab 20.8 % ; placebo 34.9 % ; p = 0.005 ) . Conclusions : Basiliximab therapy confers a significant clinical benefit to renal transplant recipients without increasing overall treatment costs Tacrolimus combined with mycophenolate mofetil ( MMF ) is an effective regimen in kidney transplantation . This study compared the efficacy of combining tacrolimus and two different dosages of sirolimus with an established tacrolimus‐MMF regimen . Each day in addition to tacrolimus , 325 patients received 2 mg sirolimus ( TAC‐SRL2 mg ) , 325 patients received 0.5 mg sirolimus ( TAC‐SRL0.5 mg ) and 327 patients 1 g MMF ( TAC‐MMF ) . The initial tacrolimus dose was 0.2 mg/kg/day . Sirolimus patients received loading doses of 6 or 1.5 mg , and daily doses of 2 or 0.5 mg thereafter . Steroid administration was identical for all groups . The incidence of biopsy‐proven acute rejection was lower in the TAC‐SRL2 mg group ( 15.7 % ) compared with the TAC‐SRL0.5 mg ( 25.2 % , p = 0.003 ) and the TAC‐MMF groups ( 22.3 % , p = 0.036 ) . Six‐month graft survival was 91.0 % ( TAC‐SRL2 mg ) , 92.6 % ( TAC‐SRL0.5 mg ) and 92.4 % ( TAC‐MMF ) ; the respective values for patient survival were 98.1 % , 97.8 % and 97.9 % . Thirty‐four patients ( 10.5 % ) , 19 patients ( 5.8 % ) and 16 patients ( 4.9 % ) in the TAC‐SRL2 mg , TAC‐SRL0.5 mg and TAC‐MMF groups , respectively , discontinued the study because of adverse events . Hyperlipemia was reported more often in the TAC‐SRL2 mg group ( 24.0 % ) compared with 19.4 % ( TAC‐SRL0.5 mg ) and 11.0 % ( TAC‐MMF ; p < 0.05 ) . Combining 2 mg sirolimus/day with tacrolimus results in lower rates of acute rejection , but a higher incidence of adverse events FK 506 was compared with cyclosporin in a r and omised trial in good-risk cadaveric renal transplant recipients . The objective was to evaluate whether oral FK 506 dosing was viable and whether blood concentrations in the range 10 - 20 ng/ml would prove to be practical . Thirty-one adult patients were r and omised to FK 506 and 16 to cyclosporin . Both groups received an identical regimen of azathioprine and corticosteroids . Serum creatinine concentrations decreased rapidly in both groups with mean values below 200 mumol/l within 2 weeks . One graft in the cyclosporin group was lost due to renal vein thrombosis . During the 6-week study period , 19.4 % of patients on FK 506 and 31.3 % on cyclosporin experienced acute rejection . One patient in each group experienced corticosteroid-resistant rejection that responded to anti-lymphocyte therapy . Infections were reported in 51.6 % of the FK 506 group compared with 37.5 % of the cyclosporin group . The spectrum of adverse events was similar in both groups . However , minor neurological disorders were more common in the FK 506 group ( 54.8 % versus 6.3 % ) whereas hypertension was less common ( 48.8 % versus 75.0 % ) . The results indicate that oral FK 506 rapidly achieves therapeutic blood concentrations and is an effective immunosuppressant for the initial treatment of renal allograft recipients Background With effective agents available to prevent posttransplantation acute organ rejection , medication adherence becomes a key factor for successful treatment outcomes after renal transplantation . A once-daily , modified-release oral formulation of tacrolimus has been developed to simplify dosing and improve medication adherence . Methods Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograft to Advagraf is a r and omized multicenter controlled trial to evaluate adherence between a tacrolimus once-daily regimen and a tacrolimus twice-daily regimen using an electronic monitor to document drug intake . After enrolment , all patients continued the twice-daily regimen for 3 months and then were r and omized 2:1 between the two formulations and followed for 6 months . Adherence was decomposed into patients ’ persistence and implementation of each regimen . Results Two hundred nineteen patients ( 45 % male ; 3±2 years after transplantation ) were analyzed ( 145 once daily and 74 twice daily ) . At 6 months after r and omization , 81.5 % of the once-daily group and 71.9 % of the twice-daily group remained persistent with the treatment ( P=0.0824 ) . Among patients who remained engaged with the regimen , 88.2 % of the once-daily group and 78.8 % of the twice-daily group ( P=0.0009 ) took the prescribed number of daily doses . When the patients took the twice-daily regimen , the average percentage of missed doses was 11.7 % in the morning and 14.2 % in the evening ( P=0.0035 ) . Conclusions Regimen implementation of tacrolimus once daily is significantly superior to the twice-daily regimen . There was a residual prevalence of suboptimal adherence that will have to be countered by means other than reformulation and regimen simplification . Electronically compiled dosing histories provide detailed data on patient adherence that can be used for efficient medication management A 6-month , open-label , multicenter prospect i ve pilot study was conducted to evaluate the effects of sirolimus ( SRL ) versus cyclosporine ( CsA ) in recipients of kidneys from exp and ed criteria donors . All patients also received antithymocyte globulins induction , mycophenolate mofetil , and steroids . Sixty-nine patients ( 33 SRL , 36 CsA ) were r and omized . More patient were withdrawn in the SRL group ( 16 vs. 6 , P<0.01 ) , because of delayed graft function and surgical complications . Delayed graft function tended to be more frequent with SRL than with CsA ( 45.4 % vs. 30.6 % , P=0.22 ) . Graft survival was numerically lower in the SRL group ( 87.5 % vs. 97 % , P=0.19 ) . At 6 months , there were no significant differences in biopsy-proven acute rejection or calculated creatinine clearance ( SRL 12.1 % vs. CsA 8.3 % ; P=0.7 and 44.7±16.6 vs. 41.9±15.2 mL/min ; P=0.54 respectively ) . These results do not support the use of SRL immediately after transplantation in exp and ed criteria donor recipients BACKGROUND Optimal immunosuppression is essential to maintain kidney allograft viability but minimizing toxicity is also fundamental . OBJECTIVE This article compares immunosuppressants , corticosteroids , cyclosporine , tacrolimus , and basiliximab , which are used in the treatment regimens for renal transplantation . The analyses evaluated their effectiveness to prevent acute rejection episodes and to reduce the appearance of other complications , mainly infectious disease complications . METHODS Ninety-five patients were analysed during the first year after primary renal transplantation . These patients were included in a r and om way in 3 different groups according to the immunosuppressant drug therapy : Group I ( 35 patients ) received corticosteroids + CsA ; Group II ( 35 patients ) received corticosteroids + CsA + Basiliximab ; Group III ( 25 patients ) received corticosteroids + Tacrolimus + Basiliximab . RESULTS Among the 95 patients , 9 presented with an acute rejection episode in Group I. None in Group II , and one in group III . With reference to the infectious disease complications , the incidence of oral herpes was one case in Group I , 4 cases in Group II , and 2 cases in group III . CONCLUSIONS Treatment with Basiliximab produced a significantly lower incidence of acute rejection cases and an increase in infectious disease complications , such as lip herpes Morbidity and mortality due to cardiovascular disease are major problems after renal transplantation . The effects of three immunosuppressive protocol s on cardiovascular end points were investigated in a single-center , r and omized , parallel ( 1 - 1 - 1 ) group . Acute rejection was a secondary safety endpoint . Groups were as follows : group one , tacrolimus+sirolimus ; group two , tacrolimus+mycophenolate mofetil ( MMF ) ; group three , sirolimus+MMF+daclizumab . All groups received two days methylprednisolone only . The Ethical Committee dem and ed an interim analysis when 50 % of the patients were included . In this analysis , 54 patients with a median follow-up of 9.2 months were studied . The Kaplan-Meyer analysis showed a difference in rejection free survival between group one ( 82 % ) and group three ( 34 % , P=0.03 ) and between groups one and two ( tacrolimus-based , 76 % ) and group three ( calcineurin-free , 34 % , P=0.04 ) . Calcineurin-free immunosuppression with two days of steroids only showed an unacceptable high incidence of acute rejection and re-rejection , and the study had to be stopped BACKGROUND Mycophenolate mofetil has replaced azathioprine in immunosuppression regimens worldwide to prevent graft rejection . However , evidence that its antirejection activity is better than that of azathioprine has been provided only by registration trials with an old formulation of ciclosporin and steroid . We aim ed to compare the antirejection activity of these two drugs with a new formulation of ciclosporin . METHODS The mycophenolate steroids sparing multicentre , prospect i ve , r and omised , parallel-group trial compared acute rejections and adverse events in recipients of cadaver-kidney transplants over 6-month treatment with mycophenolate mofetil or azathioprine along with ciclosporin microemulsion ( Neoral ) and steroids ( phase A ) , and over 15 more months without steroids ( phase B ) . The primary endpoint was occurrence of acute rejection episodes . Analysis was by intention to treat . FINDINGS 168 patients per group entered phase A. 56 ( 34 % ) assigned mycophenolate mofetil and 58 ( 35 % ) assigned azathioprine had clinical rejections ( risk reduction [ RR ] on mycophenolate mofetil compared with azathioprine 13.7 % [ 95 % CI -25.7 % to 40.7 % ] , p=0.44 ) . 88 patients in the mycophenolate mofetil group and 89 in the azathioprine group entered phase B. 14 ( 16 % ) taking mycophenolate mofetil and 11 ( 12 % ) taking azathioprine had clinical rejections ( RR -16.2 % , [ -157.5 % to 47.5 % ] , p=0.71 ) . Average per-patient costs of mycophenolate mofetil treatment greatly exceeded those of azathioprine ( phase A 2665 Euros [ SD 586 ] vs Euros 184 [ 62 ] ; phase B 5095 Euros [ 2658 ] vs 322 Euros [ 170 ] , p<0.0001 for both ) . INTERPRETATION In recipients of cadaver kidney-transplants given ciclosporin microemulsion , mycophenolate mofetil offers no advantages over azathioprine in preventing acute rejections and is about 15 times more expensive . St and ard immunosuppression regimens for transplantation should perhaps include azathioprine rather than mycophenolate mofetil , at least for kidney grafts BACKGROUND AND OBJECTIVES Development of new therapeutic strategies to improve long-term transplant outcomes requires improved underst and ing of the mechanisms by which these complications limit long-term transplant survival . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The association of acute rejection and new-onset diabetes was determined in the first posttransplantation year with the outcomes of transplant failure from any cause , death-censored graft loss , and death with a functioning graft in 27,707 adult recipients of first kidney-only transplants , with graft survival of at least 1 yr , performed between 1995 and 2002 in the United States . RESULTS In multivariate analyses , patients who developed acute rejection or new-onset diabetes had a similar risk for transplant failure from any cause , but the mechanisms of transplant failure were different : Acute rejection was associated with death-censored graft loss but only weakly associated with death with a functioning graft . In contrast new-onset diabetes was not associated with death-censored graft loss but was associated with an increased risk for death with a functioning graft . CONCLUSIONS Acute rejection and new-onset diabetes have a similar impact on long-term transplant survival but lead to transplant failure through different mechanisms . The mechanisms by which new-onset diabetes leads to transplant failure should be prospect ively studied . Targeted therapeutic strategies to minimize the impact of various early posttransplantation complications may lead to improved long-term outcomes In an open‐label , multicenter trial , de novo kidney transplant recipients at low to medium immunological risk were r and omized at week 7 posttransplant to remain on CsA ( n = 100 , controls ) or convert to everolimus ( n = 102 ) , both with enteric‐coated mycophenolate sodium and corticosteroids . The primary endpoint , change in measured GFR ( mGFR ) from week 7 to month 12 , was significantly greater with everolimus than controls : 4.9 ( 11.8 ) mL/min versus 0.0 ( 12.9 ) mL/min ( p = 0.012 ; analysis of covariance [ ANCOVA ] ) . Per protocol analysis demonstrated a more marked difference : an increase of 8.7 ( 11.2 ) mL/min with everolimus versus a decrease of 0.4 ( 12.0 ) mL/min in controls ( p < 0.001 ; ANCOVA ) . There were no differences in graft or patient survival . The 12‐month incidence of biopsy‐proven acute rejection ( BPAR ) was 27.5 % ( n = 28 ) with everolimus and 11.0 % ( n = 11 ) in controls ( p = 0.004 ) . All but two episodes of BPAR in each group were mild . Adverse events occurred in 95.1 % of everolimus patients and 90.0 % controls ( p = 0.19 ) , with serious adverse events in 53.9 % and 38.0 % , respectively ( p = 0.025 ) . Discontinuation because of adverse events was more frequent with everolimus ( 25.5 % ) than controls ( 3.0 % ; p = 0.030 ) . In conclusion , conversion from CsA to everolimus at week 7 after kidney transplantation was associated with a greater improvement in mGFR at month 12 versus CNI‐treated controls but discontinuations and BPAR were more frequent BACKGROUND Evidence -based health policy is urgently needed to meet the increasing dem and for health services among elderly people , particularly for expensive technologies such as renal-replacement therapy . Age has been used to ration dialysis , although not always explicitly , despite the lack of rigorous empirical evidence about how elderly people fare on dialysis . We undertook a comprehensive assessment of outcomes in patients 70 years or over . METHODS We did a 12-month prospect i ve cohort study of outcomes in 221 patients with end-stage renal failure aged 70 years or over recruited from four hospital-based renal units . We assessed 1-year survival in 125 incident patients ( 70 - 86 years ) and disease burden ( hospital admissions , quality of life , costs ) in 174 prevalent patients ( 70 - 93 years ) . FINDINGS 1-year survival rates were : 71 % overall ; 80 % , 69 % , and 54 % in patients 70 - 74 years , 75 - 79 years , and 80 years and older , respectively ( p=0.008 ) ; and 88 % , 71 % , and 64 % in patients with no , one , or two or more comorbid conditions , respectively ( p=0.056 ) . Cox regression analyses showed that mortality was significantly associated with age 80 years and older ( relative risk 2.79 [ 95 % CI 1.28 - 6.93 ] ) and peripheral vascular disease ( 2.83 [ 1.29 - 6.17 ] ) , but not with diabetes , ischaemic heart disease , cerebrovascular disease , chronic obstructive airways disease , sex , or treatment method . In terms of disease burden , hospital admissions represent a low proportion of costs and was not required by a third of patients , mental quality of life in elderly dialysis patients was similar to that of elderly people in the general population , and the average annual cost per patient of 20802 ( US$ 31200 ) ( 68 % dialysis treatment , 1 % transport , 19 % inpatient hospital admissions , 12 % medications ) was within the range of other life-extending interventions . INTERPRETATION Our results suggest that age alone should not be used as a barrier to referral and treatment and emphasise the need to consider the benefits of dialysis in elderly people . Indicators of the ability to benefit from treatment , rather than chronological age , should be used to develop policies that ensure equal access to care for all Objective : To study the efficacy and safety profile of Simulect , anti-IL-2R monoclonal antibody , and prevent the acute rejection in renal allograft recipients . Methods : 46 patients were treated with Neoral-based immunosuppressive agents combined with or without Simulect in March 1999-October 2002 in our organ transplant center . The 46 patients were classified into two groups , group Simulect and group control r and omly . The all patients in both groups received Neoral , Azatheoprine and steroid conventionally , but the patients in group Simulect were given Simulect additionally with the first dose of Simulect 20mg,2 hours preoperatively and the second dose of 20 mg 4 days postoperatively . Thereafter , acute rejection , dosage of Neoral , steroids and Azatheoprine as well as the toxicity of these agents and Simulect were closely monitored . In addition , the trough level of CsA in whole blood , liver and renal functions were also monitored . Results : In 8 weeks post-transplantation,3 cases of group control recipients experienced 4 episodes of acute allograft rejection , but none of group Simulect recipients had it(P0.01).No patients in both groups were associate with toxicity , such as cytokin release syndrome , CMV infection and post-transplantation lymphoproliferative disorders(PTLD ) and so on . No significant difference of dosage of Neoral and trough level of CsA were found in the patients in both groups . The total dosage of corticosteroids in the patients of the group control was higher than group Simulect because of acute rejection(P0.05 ) . Conclusions : Simulect prevented the recipients of kidney transplantation from acute rejection effectively , with a simple administration , short course and very well safety profile.kidney transplantation;graft The long‐term effect of conversion from calcineurin inhibitor ( CNI ) therapy to an mTOR inhibitor requires clarification . Following completion of the 12‐month , open‐label , multicenter ZEUS study , in which 300 kidney transplant recipients were r and omized to continue cyclosporine ( CsA ) or convert to everolimus at 4.5 months posttransplant , outcomes were assessed at month 36 ( n = 284 ; 94.7 % ) . CNI therapy was reintroduced in 28.4 % of everolimus patients by month 36 . The primary efficacy endpoint , estimated glomerular filtration rate ( Nankivell , ANCOVA ) was significantly higher with everolimus versus the CsA group at month 24 ( 7.6 mL/min/1.73 m2 , 95%CI 4.3 , 11.0 mL/min/1.73 m2 ; p < 0.001 ) and month 36 ( 7.5 mL/min/1.73 m2 , 95%CI 3.6 , 11.4 mL/min/1.73 m2 ; p < 0.001 ) . The incidence of biopsy‐proven acute rejection from r and omization to month 36 was 13.0 % in the everolimus arm and 4.8 % in the CsA arm ( p = 0.015 ) . Patient and graft survival , as well as incidences of malignancy , severe infections and hospitalization , were similar between groups . Kidney transplant patients who are converted from CsA to everolimus at month 4.5 and who remain on everolimus thereafter may achieve a significant improvement in renal function that is maintained to 3 years . There was a significantly higher rate of rejection in the everolimus arm but this did not exert a deleterious effect by 3 years posttransplant Background . Sequential anti-thymocyte globulins (ATG)/cyclosporine immunosuppression has two main advantages : delayed introduction of the nephrotoxic drug cyclosporine and prevention of acute rejection . Basiliximab , a recently developed chimeric monoclonal antibody that selectively depletes the minor sub population of activated T lymphocytes , has been shown to reduce the incidence of acute rejection when used with cyclosporine introduced on day 1 . Methods . This open , r and omized , multicenter study was undertaken to compare the safety and efficacy of ATG versus basiliximab induction therapy ( IT ) with delayed introduction of cyclosporine for microemulsion ( Neoral ) in 105 low immunologic risk renal-transplant patients receiving mycophenolate mofetil and steroids . Results . One-year patient and graft survival rates were 98.1 % and 94.2 % , respectively , in the basiliximab group ( n=52 ) , and 98.1 % and 96.2 % in the ATG group ( n=53 ) . The incidence of biopsy-confirmed acute rejection was comparable ( basiliximab 9.6 % , ATG 9.4 % ) , as were key parameters of renal function , notably serum creatinine levels , time-to-nadir serum creatinine , and the number of patients requiring posttransplantation dialysis ( basiliximab 28.8 % , ATG 30.2 % ) . However , significantly fewer patients in the basiliximab group experienced cytomegalovirus ( CMV ) infection , leukopenia , and thrombocytopenia , and this without any significant difference in any other key safety parameters ( including the incidences of serum sickness , fever , lymphoma , and infections in general ) . Conclusions . Both ATG and basiliximab , when used for IT in a sequential protocol , are equally effective in terms of graft and patient survival as well as at preventing acute rejection . However , basiliximab is associated with a lower incidence of certain key adverse events , namely CMV infection , leukopenia , and thrombocytopenia Despite the potential tolerability advantage of enteric-coated mycophenolate sodium ( EC-MPS ) , no prospect i ve , r and omized trial has evaluated whether conversion from mycophenolate mofetil ( MMF ) to EC-MPS permits mycophenolic acid dose to be increased or gastrointestinal side-effects to be ameliorated . In a r and omized , multicenter , open-label trial , kidney transplant recipients experiencing gastrointestinal side-effects either remained on MMF or switched to an equimolar dose of EC-MPS , adjusted 2 weeks subsequently to target the highest tolerated dose up to 1440 mg/day ( EC-MPS ) or 2000 mg/day ( MMF ) . Patients were followed up to 12 weeks postr and omization . One hundred and thirty-four patients were r and omized . The primary efficacy endpoint , the proportion of patients receiving a higher mycophenolic acid ( MPA ) dose at week 12 than at r and omization , was significantly greater in the EC-MPS arm ( 32/68 , 47.1 % ) than the MMF arm ( 10/61 , 16.4 % ; P < 0.001 ) . At the final visit , 50.0 % ( 34/68 ) of EC-MPS patients were receiving the maximum recommended dose versus 26.2 % ( 16/61 ) of MMF patients ( P = 0.007 ) . Kidney transplant patients receiving reduced-dose MMF because of gastrointestinal side-effects can tolerate a significant increase in MPA dose after conversion to EC-MPS . Patient-reported gastrointestinal outcomes with higher doses of EC-MPS remained at least as good as in MMF-treated controls BACKGROUND Sirolimus ( rapamycin ) is a potent immunosuppressant with a mechanism of action different from cyclosporine ( CsA ) or tacrolimus . METHODS In 11 European centers , first cadaveric renal allograft recipients were r and omized to CsA ( n=42 ) or sirolimus ( n=41 ) . Dosing of these agents was concentration-controlled and open-labeled . All patients received corticosteroids and azathioprine . RESULTS At 12 months , graft survival ( 98 % sirolimus vs. 90 % CsA ) , patient survival ( 100 % vs. 98 % ) , and incidence of biopsy-confirmed acute rejection ( 41 % vs. 38 % ) were similar . Serum creatinine was lower with sirolimus , significantly ( P < or = 0.05 ) so at 3 and 4 months , and serum uric acid and magnesium were normal . Laboratory abnormalities reported significantly more often with sirolimus included hypertriglyceridemia ( 51 % vs. 12 % ) , hypercholesterolemia ( 44 % vs. 14 % ) , thrombocytopenia ( 37 % vs. 0 % ) , leukopenia ( 39 % vs. 14 % ) , and , of lesser importance , increased liver enzymes and hypokalemia . These abnormalities improved 2 months after transplantation when the sirolimus target trough level was lowered from 30 to 15 ng/ml . Occurrence of cytomegalovirus was comparable ( 14 % vs. 12 % ) ; incidences of herpes simplex ( 24 % vs. 10 % , P=0.08 ) and pneumonia ( 17 % vs. 2 % , P=0.03 ) were higher with sirolimus . No gingival hyperplasia was seen with sirolimus , tremor was rare , and hypertension was less frequent ( 17 % vs. 33 % ) . Two malignancies were observed with CsA and none with sirolimus . CONCLUSIONS Results at 12 months suggest that sirolimus can be used as base therapy in the prophylaxis of acute renal transplant rejection , and has a safety profile that differs from INTRODUCTION A previous trial in renal transplantation comparing sirolimus ( rapamycin ) to cyclosporine ( CsA ) in a triple-drug therapy regimen with azathioprine and corticosteroids found that the incidence of acute rejection was similar ( approximately 40 % ) with a trend for better renal function with sirolimus . METHODS In 14 European centers , first cadaveric renal allograft recipients were r and omized to receive sirolimus ( n = 40 ) or CsA ( n = 38 ) in an open-label design . All patients received corticosteroids and mycophenolate mofetil 2 g/day . Sirolimus and CsA were concentration controlled ; trough levels of mycophenolic acid and prednisolone were also measured . RESULTS At 12 months , graft survival ( 92.5 % sirolimus vs. 89.5 % CsA ) , patient survival ( 97.5 % sirolimus vs. 94.7 % CsA ) , and the incidence of biopsy-proven acute rejection ( 27.5 % sirolimus vs. 18.4 % CsA ) were not statistically different . The use of antibodies to treat suspected rejection episodes was also similar ( 7.5 % sirolimus vs. 5.3 % CsA ) . More sirolimus patients received bolus steroid therapy ( 20 vs. 11 , P = 0.068 ) . From month 2 onward , the calculated glomerular filtration rate was consistently higher in sirolimus-treated patients . The adverse events reported more frequently with sirolimus were thrombocytopenia ( 45 % vs. 8 % ) and diarrhea ( 38 % vs. 11 % ) . In the CsA group , increased creatinine ( 18 % vs. 39 % ) , hyperuricemia ( 3 % vs. 18 % ) , cytomegalovirus infection ( 5 % vs. 21 % ) , and tremor ( 5 % vs. 21 % ) were observed significantly more often . DISCUSSION Patient and graft survival and the incidence of biopsy-proven acute rejection at 12 months were comparable between sirolimus and CsA , whereas safety profiles were different . These data suggest that sirolimus may be used as primary therapy for the prevention of acute rejection BACKGROUND Our clinical trial was design ed to investigate the optimal combination of immunosuppressants for renal transplantation . METHODS A r and omized three-arm , parallel group , open label , prospect i ve study was performed at 15 North American centers to compare three immunosuppressive regimens : tacrolimus + azathioprine ( AZA ) versus cyclosporine ( Neoral ) + mycophenolate mofetil ( MMF ) versus tacrolimus + MMF . All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen . Only patients with delayed graft function ( 32 % ) received antilymphocyte induction . A total of 223 patients were r and omized , transplanted , and followed for 1 year . RESULTS There were no significant differences in baseline demography between the three treatment groups . At 1 year the results are as follows : acute rejection 17 % ( 95 % confidence interval 9 % , 26 % ) in tacrolimus + AZA ; 20 % ( confidence interval 11 % , 29 % ) in cyclosporine + MMF ; and 15 % ( confidence interval 7 % , 24 % ) in tacrolimus + MMF . The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12 % in the tacrolimus + AZA group , 11 % in the cyclosporine + MMF group , and 4 % in the tacrolimus + MMF group . There were no significant differences in overall patient or graft survival . Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant . The incidence of posttransplant diabetes mellitus requiring insulin was 14 % in the tacrolimus + AZA group , 7 % in the cyclosporine + MMF and 7 % in the tacrolimus + MMF groups . CONCLUSIONS All regimens yielded similar acute rejection rates and graft survival , but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy The effects of the calcineurin inhibitors tacrolimus ( FK506 ) and cyclosporine ( Neoral ) on graft survival , function , and metabolic profile were evaluated in 69 patients receiving Neoral ( group 1 ) and 54 patients receiving FK506 ( group 2 ) for maintenance immunosuppression following kidney transplantation . Recipient and donor demographics and induction therapy were comparable , except for a higher number of sensitized patients in group 2 ( n = 13 ) . Acute rejection timing , severity , and infection rates and types were similar in both groups . During hospitalization , at 6 months , and at 1 year following transplantation , no significant differences were noted between groups in fasting glucose , serum cholesterol levels , triglyceride levels , or need for insulin or antihypertensive therapy . Mean serum creatinine levels on discharge ( 1.42 mg/dL + /- 0.14 vs 1.68 mg/dL + /- 0.3 ) , at 1 month ( 1.45 mg/dL + /- 0.1 vs 1.39 mg/dL + /- 0.11 ) , 3 months ( 1.46 mg/dL + /- 0.09 vs 1.32 mg/dL + /- 0.14 ) , and 1 year ( 1.29 mg/dL + /- 0.08 vs 1.19 mg/dL + /- 0.09 ) , but not at 6 months ( 1.42 + /- 0.37 vs 1.10 + /- 0.07 ; P = .001 ) , were comparable between groups . The 1-year patient and graft survival rates were 98.3 % for group 1 and 94.5 % for group 2 . When evaluated for acute rejection , infection , and metabolic differences , we conclude that both tacrolimus and cyclosporine are effective and safe calcineurin inhibitors for short-term use in kidney transplantation . A similar study is proposed to evaluate the long-term effects of both agents INTRODUCTION The aim of the study was to compare efficacy of cyclosporine ( CsA ) very low exposure with everolimus high exposure , with respect to CsA st and ard exposure with enteric-coated mycophenolate sodium ( EC-MPS ) therapy . METHODS In a r and omized , prospect i ve , single-center , open-label study , patients were enrolled to receive either everolimus ( C0 ( trough level ) 8 - 12 ng/mL ) + CsA ( C2 ( CsA level 2 hours after drug administration ) 250 - 300 ng/mL ) + steroids , or EC-MPS ( 1,440 mg/day ) + CsA ( C2 500 - 700 ng/mL ) + steroids . Fifty-six patients were enrolled in the everolimus group , 50 in the EC-MPS group . Efficacy was evaluated at 3 and 12 months . RESULTS Characteristics of groups were similar . Biopsy-proven acute rejection ( BPAR ) rates were similar in both groups ( everolimus 18.8 % vs. EC-MPS 18.2 % ) . Everolimus patients had a lower incidence of delayed graft function ( DGF ) than EC-MPS patients ( 22.6 % vs. 40.9 % ; p<0.05 ; relative risk [ RR ] = 0.65 ) . One-year graft survival was 95 % in the everolimus group and 88 % in the EC-MPS group ( p = NS ) . CsA dose at 1 year was lower in the everolimus group ( 1.52 ± 0.67 vs. 2.55 ± 0.79 mg/kg ; p<0.0001 ) . Estimated glomerular filtration rate ( eGFR ; Cockcroft-Gault ) was higher in the everolimus group ( 81.64 ± 32.67 vs. 62.62 ± 22.81 ml/min ; p<0.001 ) . Systolic blood pressure was lower in the everolimus group ( 124.9 ± 14.64 mm Hg vs. 131.1 ± 13.23 mm Hg ; p=0.03 ) . Hemoglobin blood levels were slightly lower in the everolimus group ( 12.62 ± 1.42 vs. 13.01 ± 1.3 g/L ; p = NS ; for anemia , RR=1.302 ) . Serum cholesterol was similar in both groups ( everolimus 219.1 ± 47.20 vs. EC-MPS 207.2 ± 38.8 mg/dL ; p = NS ) , but everolimus patients used more statins ( RR=1.49 ) . Twenty-four-hour proteinuria was higher in the everolimus group ( 519.7 ± 77.31 vs. 296.7 ± 33.42 mg/24 hours ; p=0.01 ) . CONCLUSIONS Everolimus regimen compared with EC-MPS regimen is associated with lower incidence of DGF , slightly better 1-year graft survival rate , a significantly higher GFR and lower systolic blood pressure Background . The benefit of converting renal transplant recipients with gastrointestinal ( GI ) complaints from mycophenolate mofetil ( MMF ) to enteric-coated mycophenolate sodium ( EC-MPS ) has not been evaluated using patient-reported outcomes . Methods . A multicenter , open-label , prospect i ve study was undertaken in MMF-treated renal transplant patients . Patients experiencing GI complaints were converted to equimolar EC-MPS ( Cohort A ) . Patients without GI complaints remained on MMF ( Cohort B ) . At baseline and Visit 2 ( 4–6 weeks postbaseline ) , patients completed the Gastrointestinal Symptom Rating Scale ( GSRS ) , Gastrointestinal Quality of Life Index ( GIQLI ) and Psychological General Well-being Index ( PGWBI ) . At Visit 2 , patients and physicians completed the Overall Treatment Effect ( OTE ) scale for GI symptoms . Additionally , patients completed the OTE for health-related quality of life ( HRQoL ) . Minimal important difference ( MID ) was calculated for GSRS and GIQLI based on patients ’ and physicians ’ OTE evaluation . Results . Of 328 patients enrolled ( i.e. the intent-to-treat and safety population s ) , 278 formed the per- protocol population ( Cohort A , n=177 ; Cohort B , n=101 ) . At baseline , Cohort A had significantly worse scores on all GSRS , GIQLI and PGWBI subscales compared to Cohort B ( all P<0.0001 ) . All GSRS , GIQLI and PGWBI subscale scores improved significantly in Cohort A between baseline and Visit 2 ( all P<0.0001 ) . Mean improvements in all GSRS subscales and most GIQLI subscores exceeded the calculated MID . GSRS , GIQLI and PGWBI subscales remained stable in Cohort B. Conclusion . This first exploratory study indicates that converting patients with mild , moderate or severe GI complaints from MMF to EC-MPS significantly reduces GI-related symptom burden and improves patient functioning and well-being Background . De novo sirolimus in calcineurin inhibitor-free regimens , although potentially useful to improve early renal function , are complicated by various drug-related side effects . Methods . We report a prospect i ve open-label , multicenter , r and omized trial to evaluate early conversion from a CsA-based to a sirolimus (SRL)-based regimen 10 to 24 days after renal transplantation . Of the 196 patients , 141 patients with a low-to-moderate immunological risk were eligible to be converted to SRL or to continue CsA. All patients received antithymocyte globulin-F single-bolus induction , mycophenolate mofetil , and steroids . Results . The primary endpoint , renal function determined by S-creatinine and estimated glomerular filtration rate calculated by Nankivell formula at 12 months was significantly better in the SRL group ( 1.51±0.59 vs. 1.87±0.98 mg/dL or 64.5±25.2 vs. 53.4±18.0 mL/min/1.73 m2 ) . Patient survival , graft survival , and incidence of biopsy-proven acute rejection after conversion were not statistically different . Drug discontinuations were significantly higher in the SRL group ( 36.2 % vs. 19.7 % ) . Significantly , more patients in the SRL group reported acne , aphtous , and temporary hyperlipidemia , whereas cytomegalovirus viremia was significantly decreased ( 7.3 % vs. 28.2 % ) . Conclusions . Early conversion to a calcineurin inhibitor-free regimen with SRL in combination with mycophenolate mofetil may be a useful strategy to improve renal function . The identification of appropriate c and i date s and safe management of SRL-related adverse events will be a key to avoid the high rate of dropouts , which currently limit the broad applicability of this protocol Patients undergoing primary cadaveric kidney transplantation were followed for 1 year as part of a phase II , multicenter , open-label concentration-ranging trial of FK506 and cyclosporine . One hundred twenty patients were r and omly assigned to a cyclosporine-based regimen or one of three FK506-based regimens design ed to achieve low ( 5 - 14 ng/ml ) , medium ( 15 - 25 ng/ml ) , or high ( 26 - 40 ng/ml ) trough whole blood levels . Corresponding initial doses of FK506 were 0.2 , 0.3 , or 0.4 mg(kg/day , respectively . Patients with toxicity to FK506 had their target concentration reduced by lowering the dose of FK506 . Ninety-two patients completed a 1-year follow-up to determine patient and graft survival and long-term safety . At 1-year , the patient survival rate was 98 % for FK506 and 92 % for cyclosporine , and the graft survival rate was 93 % and 89 % in the FK506 and cyclosporine groups , respectively . The incidence of acute rejection was significantly lower ( 14 % FK506 , 32 % cyclosporine , P=0.048 ) at day 42 after transplantation . However , the incidence of rejection episodes requiring treatment at 1 year was similar in both groups ( 33 % for FK506 and 32 % for cyclosporine ) . Nephrotoxicity occurred with a similar frequency with FK506 and cyclosporine , but the incidence of neurotoxic events and the incidence of new insulin use were higher among FK506-treated patients . The target range of whole blood levels that optimizes efficacy and minimizes toxicity seems to be 5 - 15 ng/ml . The corresponding recommended initial dose of FK506 for kidney transplant recipients is 0.2 mg/kg/day . These results indicate that the efficacy and safety of FK506 were comparable to that for cyclosporine for primary immunosuppression in patients undergoing cadaveric kidney transplantation Background . The aim of this prospect i ve r and omized study was to examine the effect of induction immunosuppression and low initial cyclosporine ( CsA ) on the onset of graft function and its long-term consequences . Methods . During 1999–2001 , 155 patients were r and omized to single 9 mg/kg dose antithymocyte globulin (ATG)-Fresenius ( group A ) or two 20-mg doses of basiliximab ( group B ) with reduced dose CsA or conventional CsA triple therapy without induction ( group C ) . Results . Delayed function ( DGF ) was lower in group A than in groups B or C ( 5.7 % vs. 24.1 % and 15.9 % , P<0.025 ) and need of dialysis was less in groups A and B compared to C ( 10.3 and 10.4 vs. 20.0 days , P<0.05 ) . Acute rejections occurred in 11.3 % , 12.1 % and 20.5 % , and the mean ( median ) time to rejection was 16 ( 13 ) , 97 ( 46 ) and 101 ( 35 ) days in groups A , B , and C , respectively ( P<0.005 ) . One- and 5-year graft survivals ( GS ) were 98.1 % and 90.6 % ( group A ) , 96.6 % and 96.6 % ( group B ) , and 93.2 % and 84.1 % ( group C ) . Five-year GS was significantly better in group B than in group C ( P<0.05 ) . The death censored 5-year GS in groups A , B , and C were 94.3 % , 96.6 % , and 90.0 % ( P = NS ) . Single high-dose ATG induction was associated with hemodynamic and pulmonary disturbances without , however , serious or long-term consequences . Conclusions . ATG induction significantly reduced DGF . Both induction regimens together with low initial CsA led to significantly less posttransplant dialysis and excellent survival . The high dose ATG was associated with significant hemodynamic and pulmonary side effects during drug infusion Purpose : The EQ-5D is a brief , multiattribute , preference-based health status measure . This article describes the development of a statistical model for generating US population -based EQ-5D preference weights . Methods : A multistage probability sample was selected from the US adult civilian noninstitutional population . Respondents valued 13 of 243 EQ-5D health states using the time trade-off ( TTO ) method . Data for 12 states were used in econometric modeling . The TTO valuations were linearly transformed to lie on the interval [ −1 , 1 ] . Methods were investigated to account for interaction effects caused by having problems in multiple EQ-5D dimensions . Several alternative model specifications ( eg , pooled least squares , r and om effects ) also were considered . A modified split- sample approach was used to evaluate the predictive accuracy of the models . All statistical analyses took into account the clustering and disproportionate selection probabilities inherent in our sampling design . Results : Our D1 model for the EQ-5D included ordinal terms to capture the effect of departures from perfect health as well as interaction effects . A r and om effects specification of the D1 model yielded a good fit for the observed TTO data , with an overall R2 of 0.38 , a mean absolute error of 0.025 , and 7 prediction errors exceeding 0.05 in absolute magnitude . Conclusions : The D1 model best predicts the values for observed health states . The result ing preference weight estimates represent a significant enhancement of the EQ-5D 's utility for health status assessment and economic analysis in the US BACKGROUND Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30 % to 50 % of these patients . In the phase III study described here we assessed the ability of basiliximab , a chimeric interleukin (IL)-2 receptor monoclonal antibody , to prevent acute-rejection episodes in renal allograft recipients . METHODS 380 adult recipients of a primary cadaveric kidney transplant were r and omly allocated , in this double-blind trial , to receive a 20 mg infusion of basiliximab on day 0 ( day of surgery ) and on day 4 , to provide IL-2-receptor suppression for 4 - 6 weeks ( n=193 ) , or to receive placebo ( n=187 ) . Both groups received baseline dual immunosuppressive therapy with cyclosporin and steroids throughout the study . The primary outcome measure was incidence of acute-rejection episodes during the 6 months after transplantation . Safety and tolerability were monitored over the 12 months of the study . FINDINGS 376 patients were eligible for intention-to-treat analysis ( basiliximab , n=190 ; placebo , n=186 ) . No significant differences in patient characteristics were apparent . The incidence of biopsy-confirmed acute rejection 6 months after transplantation was 51 ( 29.8 % ) of 171 in the basiliximab group compared with 73 ( 44.0 % ) of 166 in the placebo group ( 32 % reduction ; 14.2 % difference [ 95 % Kaplan-Meier CIs 3 % to 24 % ] , p=0.012 ) . The incidence of steroid-resistant first rejection episodes that required antibody therapy was significantly lower in the basiliximab group ( 10 % vs 23.1 % , 13.1 % difference [ 5.4 % to 20.8 % ] , p<0.001 ) . At weeks 2 and 4 post-transplantation , the mean daily dose of steroids was significantly higher in the placebo group ( p<0.001 with one-way analysis of variance ) . The incidence of graft loss at 12 months post-transplantation was 23 ( 12.1 % ) of 190 in the basiliximab group and 25 ( 13.4 % ) of 186 in the placebo group ( 1.3 % difference [ -5 % to 9 % ] , p=0.591 ) . The incidence of infection and other adverse events was similar in the two treatment groups . The acute tolerability of basiliximab was excellent , with no evidence of cytokine-release syndrome . 14 deaths ( basiliximab n=9 ; placebo n=5 ; -2.0 % difference [ -6 % to 2 % ] , p=0.293 ) occurred during the 12-month study and a further three deaths ( basiliximab n=1 ; placebo n=2 ) occurred within the 380-day cut-off period . One post-transplantation lymphoproliferative disorder was recorded in each group . INTERPRETATION Prophylaxis with 40 mg basiliximab reduces the incidence of acute rejection episodes significantly , with no clinical ly relevant safety or tolerability concerns Background . To reduce long-term nephrotoxic calcineurin inhibitor dosage , adjunctive sirolimus or mycophenolate mofetil ( MMF ) was used in a 150-patient , r and omized , three-armed trial in cadaveric or human leukocyte antigen non-identical living-donor first renal transplant recipients ( n=50/group ) . Methods . Group A received tacrolimus and sirolimus . Target tacrolimus trough levels postoperatively were 10 , 8 , and 6 ng/mL at 1 month , 6 months , and 1 year , respectively . Group B received tacrolimus and MMF . Target tacrolimus trough levels were 10 and 8 ng/mL at 1 month and 1 year , with a targeted dose of MMF of 1 g twice daily . Group C received cyclosporine A ( CsA ) ( Neoral , Novartis , Basel , Switzerl and ) and sirolimus with target CsA trough levels of 225 and 175 ng/mL at 1 month and 1 year . Maintenance sirolimus target trough levels were 8 ng/mL in groups A and C. Each group received daclizumab induction and methylprednisolone maintenance . This first of two companion 1-year reports details demographics , drug-dosing interactions , and rejection . Results . There were no notable differences in group demographics , but a somewhat less favorable course occurred in group C , despite higher bioavailability of sirolimus in group C versus group A ( P < 0.001 ) . Acute rejection rates were lower in groups A ( 4 % ) and B ( 4 % ) combined versus group C ( 14 % ) ( P = 0.03 ) . Histopathologic findings were supported by comparing perioperative with 1-year postoperative protocol biopsies . Conclusions . This 1-year interim analysis indicates that a decreasing dosage of tacrolimus with either adjunctive sirolimus or MMF may optimize future graft survival versus a less favorable outcome using a similar algorithm with CsA and sirolimus Background . Immunosuppressive regimens based on low doses of cyclosporine A ( CsA ) or tacrolimus ( TAC ) may improve short-term outcome after kidney transplantation ( KT ) , but the optimal immunosuppressive protocol is currently unknown . Methods . This study compared the 24-month efficacy and safety of two immunosuppressive regimens using reduced calcineurin inhibitors ( CNIs ) exposure with st and ard dosage of CsA in 240 patients who were r and omized into three groups : group A ( n=80 ) : Thymoglobulin , CsA ( 4 mg/kg twice daily ) plus azathioprine ( 1.5 mg/kg once daily ) ; group B ( n=80 ) : basiliximab , CsA ( 2 mg/kg/ twice daily ) plus mycophenolate mofetil ( MMF ; 1 g twice daily ) ; and group C ( n=80 ) : basiliximab , TAC ( 0.05 mg/kg/ twice daily ) plus MMF ( 1 g twice daily ) . Steroid administration was identical for all groups . Results . A significantly better creatinine clearance at 12 months , estimated by Cockcroft-Gault ( 57±12 , 65.2±20 , 73.5±27 ml/min , P=0.044 ) , the Jelliffe-2 ( 51.5±16 , 56±19 , 59.4±19 ml/min/1.73 m2 , P=0.041 ) and the Modification of Diet in Renal Disease equations ( 53±17 , 58.5±20 , 61.6±22 ml/min/1.73 m2 , P=0.035 ) , was observed in group C compared with group A. No significant differences were observed between groups B and C. The incidence of biopsy-proven acute rejection was similar between groups ( 15 % , 13.8 % , and 16.3 % ) . In addition , patient and graft survival at 24 months were not different between groups . Adverse effects were similar among groups , but cytomegalovirus infections was significantly higher in group A ( 41 % vs. 20 % vs. 25 % ; P=0.008 ) . Conclusions . Immunosuppressive regimens with reduced CNI exposure provide similar preservation of renal function compared with st and ard dose of CsA after KT and do not lead to underimmunosuppression Background . Induction therapy with antithymocyte globulin ( ATG ) reduces the incidence of acute rejection after transplantation . A study was undertaken to assess the efficacy and safety of ATG induction on tacrolimus-based and cyclosporine A (CsA)-based therapies compared with immediate tacrolimus triple therapy in kidney transplant recipients . Methods . In a 6-month , open-label , r and omized , prospect i ve study conducted in 30 European centers , 555 renal transplant patients were r and omly assigned to tacrolimus triple therapy ( Tac triple , n=185 ) , ATG induction with tacrolimus ( ATG-Tac , n=186 ) , or ATG induction with CsA microemulsion ( ATG-CsA , n=184 ) ; all were combined with azathioprine and corticosteroids . The primary endpoint was incidence and time to first acute rejection episode confirmed by biopsy . Results . Patient demographics and clinical parameters at baseline were similar . Patient and graft survival rates were similar in all groups . The incidence of clinical ly apparent acute rejection was significantly higher ( P = 0.003 ) for Tac triple ( 33.0 % ) compared with ATG-Tac ( 22.6 % ) and the incidence for ATG-Tac was significantly lower ( P = 0.004 ) than for ATG-CsA ( 37.0 % ) . The incidences of acute rejection confirmed by biopsy ( primary endpoint ) were 25.4 % , 15.1 % , and 21.2 % for Tac triple , ATG-Tac , and ATG-CsA , respectively ( Tac triple vs. ATG-Tac , P = 0.004 ) . The incidences of corticosteroid-resistant acute rejection were 7.0 % ( Tac triple ) , 4.8 % ( ATG-Tac ) , and 10.9 % ( ATG-CsA ) ( ATG-Tac vs. ATG-CsA , P = 0.038 ) . In the ATG groups , the incidences of leukopenia , thrombocytopenia , serum sickness , fever , and cytomegalovirus infection were significantly higher ( P < 0.05 ) . Conclusions . Acute rejection was significantly lower in the ATG-Tac group compared with the ATG-CsA and Tac triple groups . Significantly more hematologic and infectious adverse events were observed in both ATG induction groups Enteric-coated mycophenolate sodium ( EC-MPS ) is an enteric-coated formulation of mycophenolic acid . A 12-month , multicenter , double-blind , r and omized clinical study demonstrated that converting maintenance renal transplant patients from mycophenolate mofetil ( MMF ) to EC-MPS is safe and does not affect efficacy . In an open-label study extension , 130 patients initially r and omized to MMF were converted to EC-MPS ( newly exposed ) ; 130 initially r and omized to EC-MPS continued on EC-MPS ( EC-MPS long-term ) . A composite endpoint of biopsy-proven acute rejection ( BPAR ) , graft loss , or death occurred in 3 ( 2.3 % ) newly exposed and 2 ( 1.5 % ) EC-MPS long-term patients during the extension phase . One patient died and one lost his graft . BPAR occurred in 3 ( 2.3 % ) newly exposed patients and 1 ( 0.8 % ) EC-MPS long-term patient . During the first 12 months of the extension phase , incidence and type of adverse events was similar in both groups and comparable to that seen in the core study . Nine cases of malignancy were reported , mainly nonmelanoma skin cancers . EC-MPS dose adjustments for adverse events were required in < 12 % of patients . At the end of the 12-month extension , 58 ( 44.6 % ) and 64 ( 49.2 % ) newly exposed and EC-MPS long-term patients , respectively , had reported at least one gastrointestinal adverse event . Mean serum creatinine remained stable at the 12-month visit of the extension study ( 137 micromol/L in the newly exposed and 142 micromol/L in the EC-MPS long-term groups ) . The results of this study demonstrate the long-term safety of EC-MPS and reconfirm the safety of converting MMF maintenance renal transplant patients to EC-MPS Abstract This prospect i ve study investigated hypertension and renal vasoconstriction developing during the 1st year after renal transplantation in patients r and omly allocated to treatment with FK 506 ( n = 28 ) or CyA ( n = 13 ) . Starting doses were 0.2–0.3 mg/kg per day for FK 506 and 5–8 mg/kg per day for CyA ; doses were subsequently adjusted to trough levels ( 5–15 ng/ml for FK 506 and 100–150 ng/ml for CyA ) . We compared 24-h ambulatory blood pressure measurement , antihypertensive treatment , serum creatinine , and resistance index ( RI ) , measured by Doppler ultrasound at the level of the interlobar artery . Until month 2 of treatment , FK 506-treated patients had a significantly lower RI ( 8 % ) and better renal graft function , as evidence d by significantly lower serum creatinine values . Some 13 % of FK 506-treated patients , compared to 70 % of CyA-treated patients ( P < 0.01 ) , needed additional antihypertensive drugs after transplantation to keep blood pressure stable . FK 506 treatment , at the above-mentioned dosages , was associated with a significantly higher number of infections ( urinary tract infection , pyelonephritis , and pneumonia ) . We conclude that CyA produces greater renal vasoconstriction and systemic hypertension than FK 506 , as reflected in higher renal interlobar artery RI values and a greater need for antihypertensive treatment . After 2 months of treatment and a reduction in CyA trough levels , the renal effects ( i. e. , lower RI and lower creatinine values ) , but not the systemic hypertensive effects , disappear The aim of this study was to compare the effect of Neoral ® cyclosporin‐ and tacrolimus‐based therapy on the development of renal allograft fibrosis ( chronic allograft nephropathy ; CAN ) in a prospect i ve r and omized trial It is not known how different steroid‐free immunosuppressive combinations affect renal graft survival and long‐term kidney transplant function . Here we sought to compare the impact on graft survival and long‐term graft function of two tacrolimus (Tac)‐based , prednisone‐free maintenance immunosuppressive protocol s : Tac/Mycophenolate Mofetil ( MMF ) vs. Tac/Sirolimus ( SRL ) . Renal transplant patients given induction therapy with IL2‐RA and methylprednisolone on days 0 , 1 and 2 post‐transplant were prospect ively r and omized to two maintenance immunosuppressive regimens with Tac/MMF ( n = 45 ) or Tac/SRL ( n = 37 ) . During the 3‐year follow‐up the following data were collected : patient survival , renal allograft survival , incidence of acute rejection and glomerular filtration rate ( GFR ) at different time‐points post‐transplant . Cumulative graft survival was significantly different in the two groups : one kidney loss in the Tac/MMF vs. six kidney losses in the Tac/SRL ( log‐rank test p = 0.04 ) . GFR at different time‐points post‐transplant was consistently and statistically better in the Tac/MMF than in the Tac/SRL group . The slope of GFR decline per month was flatter in the Tac/MMF than in the Tac/SRL group . This study showed that renal graft survival and graft function were significantly lower in the combination of Tac/SRL than Tac/MMF Interstitial fibrosis is the main characteristic of chronic allograft nephropathy and long-term graft failure . Cyclosporin ( CsA ) is thought to be more fibrogenic than tacrolimus . In a prospect i ve , r and omized , multicenter trial using a calcineurin-sparing regimen , renal interstitial volume was compared in CsA- and tacrolimus-treated renal transplant recipients by image analysis of Sirius red (SR)-stained cortical areas in protocol biopsies obtained at 6 mo ( n = 94 ) and 12 mo ( n = 97 ) after transplantation . Immunosuppression consisted of CsA or tacrolimus , CD25 mAb , mycophenolate mofetil , and prednisolone . CsA therapy increased the 6-mo risk for sub clinical rejection . The prevalence of sub clinical rejection was 38.8 % in the CsA-treated and 15.2 % in the tacrolimus-treated patient group ( P = 0.012 ) . Strikingly , no difference in the degree of interstitial SR-stained area was detectable between the two treatment groups . In particular , previous sub clinical rejection episodes did not influence the degree of interstitial volume . Also , no difference in GFR occurred at 1 yr , when the mean GFR mounted 63 ml/min . No significant differences in the degree of interstitial SR-stained area could be observed at 6 and 12 mo between CsA- and tacrolimus-treated renal transplant recipients . Although CsA-treated patients developed significantly more sub clinical rejections at 6 mo , this did not influence the degree of SR staining or the change in renal function at 1 yr Background / Aims The long-term evaluation of single bolus high dose antithymocyte globulin ( ATG ) induction therapy has not been adequately studied . We aim ed to evaluate its long-term effects in the living related donor kidney transplantation . Methods Eighty adult recipients with their first kidney allograft were r and omized into two equal treatment groups , one group received intraoperative single bolus rabbit ATG in a dose of 9 mg/kg and the second group served as a control . All patients were maintained on triple immunosuppressive therapy ( steroids , calcineurin inhibitor and antiproliferative agent ) . We followed them thoroughly for minimum of 5 years . Results ATG significantly reduced the proportion of patients who experienced acute rejection episodes in the first year ( 9/40 ) when compared to the control group ( 26/40 ) and in 5 years ( 11/40 ) when compared to ( 30/40 ) in controls . The cumulative steroid dose used throughout the study was significantly lower in the ATG group . The overall incidence of post-transplant complications was comparable among the two treatment groups . There was no significant difference in patient and graft survival : 5 year survival was 100 % and 85 % for the ATG group , and 95 % and 92.5 % in the control group , respectively . Conclusion Although routine single bolus ATG induction significantly reduces the incidence of acute rejection , its long-term beneficial effects on graft function and patient and graft survival are not evident BACKGROUND We performed a prospect i ve r and omized trial to compare the efficacy and safety of tacrolimus ( FK506 ) versus cyclosporine ( CSA ) in black primary cadaveric renal transplant ( CRT ) recipients . METHODS Between December 1994 and February 1997 , 35 black primary CRT recipients were enrolled in this trial . All patients received 7 days of induction therapy with OKT3 . Fourteen patients received FK506 and prednisone only . Twenty-one patients received CSA , azathioprine , and prednisone . The two groups were comparable in terms of age , gender , plasma renin activity , human leukocyte antigen mismatches , and cause of renal failure . RESULTS Patient and graft survival were 12 of 14 ( 86 % ) for the FK506 group and 20 of 21 ( 95 % ) for the CSA group ( P = 0.71 ) . Three patients died owing to cardiac events with functioning grafts . Acute rejection was 2 of 14 ( 14 % ) for the FK506 and 8 of 21 ( 38 % ) for the CSA group ( P = 0.25 ) . Two other patients on CSA were converted to FK506 as rescue for OKT3-resistant rejection . Mean serum cholesterol at 1 year was 198 + /- 45 mg/dL for the FK506 group and 244 + /- 49 mg/dL for the CSA group ( P = 0.03 ) . Mean serum creatinine at 1 year was 1.39 + /- 0.38 mg/dL for the FK506 group and 1.94 + /- 0.64 mg/dL for the CSA group ( P = 0.02 ) . CONCLUSION Patient and graft survival were similar in both groups at 1 year posttransplant . Although statistically not significant , the incidence of acute rejection was lower in the FK506 group . Furthermore , FK506-treated patients had significantly lower serum creatinine and cholesterol levels at 1 year posttransplant With the objective of enhancing upper gastrointestinal ( GI ) tolerability , enteric‐coated mycophenolate sodium ( EC‐MPS , myfortic ® , Novartis Pharma AG , Basel , Switzerl and ) has been developed . This double‐blinded , 12‐month study investigated whether renal transplant patients taking mycophenolate mofetil ( MMF ) can be safely converted to EC‐MPS . Stable kidney transplant patients were r and omized to receive EC‐MPS ( 720 mg b.i.d . ; n = 159 ) or continue receiving MMF ( 1000 mg b.i.d . ; n = 163 ) . The incidence of GI adverse events ( AEs ) was similar at 3 months ( primary endpoint : EC‐MPS 26.4 % ; MMF 20.9 % ; p = NS ) and at 12 months ( EC‐MPS 29.6 % ; MMF 24.5 % ; p = NS ) . The increase from baseline in mean GI AE severity score , adjusted for duration , tended to be lower in EC‐MPS patients ( 3 months : 0.15 vs. 0.20 ; 12 months : 0.23 vs. 0.47 ; p = NS ) . Neutropenia ( < 1500 cells/mm3 ) within the first 3 months ( co primary endpoint ) was low in both groups ( EC‐MPS 0.6 % ; MMF 3.1 % ; p = NS ) . Although the overall incidence of infections was similar , the number of serious infections was significantly lower in EC‐MPS patients ( 8.8 % vs. 16.0 % ; p < 0.05 ) . Similar rates of efficacy failure ( EC‐MPS 2.5 % ; MMF 6.1 % ; p = NS ) , biopsy‐proven acute rejection ( EC‐MPS 1.3 % ; MMF 3.1 % ; p = NS ) and biopsy‐proven chronic rejection ( EC‐MPS 3.8 % ; MMF 4.9 % ; p = NS ) were observed in both groups . In conclusion , renal maintenance patients can be converted from MMF to EC‐MPS without compromising the safety and efficacy profile associated with MMF This was a multicenter , open-label , concentration-ranging trial of FK506 and cyclosporine in 120 patients undergoing primary cadaveric kidney transplant . Patients were r and omized to a cyclosporine-based regimen or to one of three FK506-based regimens design ed to achieve low ( 5 - 14 ng/ml ) , medium ( 15 - 25 ng/ml ) , or high ( 26 - 40 ng/ml ) trough whole blood levels . Corresponding initial doses of FK506 were 0.2 , 0.3 , and 0.4 mg/kg/day . Patients were evaluated at 42 days after transplant for the occurrence of the first episode of acute rejection or toxicity , necessitating a dosage reduction . There was no significant difference among the three FK506-based regimens and the cyclosporine-based regimen for rejection or toxicity at 42 days . However , the incidence of acute rejection was significantly lower ( 14 % for FK506 and 32 % for cyclosporine ; P=0.048 ) for the aggregate of all FK506-treated patients versus cyclosporine . The incidence of neurotoxic and gastrointestinal events was higher among FK506-treated patients during the first month after transplant . A significant trend was observed for increasing toxicity with increasing maximum trough FK506 concentrations ( P=0.01 ) and for decreasing rates of rejection with increasing minimum trough FK506 concentrations ( P=0.021 ) . FK506 was effective in preventing early rejection in kidney transplant recipients . The target range of whole blood levels that optimizes efficacy and minimizes toxicity seems to be 5 - 15 ng/ml . The corresponding recommended initial dose of FK506 for kidney transplant recipients seems to be 0.2 mg/kg/day Background . The best immunosuppressive regimen in benefit-risk ratio in renal transplantation is debated . Nowadays , tacrolimus ( Tac ) and mycophenolate mofetil ( MMF ) are considered more efficient than cyclosporine A ( CsA ) and MMF , but recent studies have challenged this assumption . Methods . We conducted a monocentric , prospect i ve , open-labeled , r and omized , and controlled trial comparing CsA/azathioprine ( Aza ) versus Tac/MMF in 289 kidney transplant recipients treated with antithymocyte globulins and prednisone . Primary outcome was the number of patients with clinical ly suspected acute rejection at 1 year . Secondary outcomes were the number of patients with biopsy-proven acute rejection ( BPAR ) , estimated glomerular filtration rate ( eGFR ) , patient and graft survivals , and adverse events at 1 and 3 years . Results . During the first year , 21 patients had clinical ly suspected acute rejection with CsA/Aza ( 14.4 % ) vs. 11 ( 7.7 % ) with Tac/MMF ( P=0.07 ) . BPAR , including borderline , was more frequent in the CsA/Aza group ( 14.4 % ) than in the Tac/MMF group ( 5.6 % ; P=0.013 ) . At 1 year , patient and graft survivals were not different , and eGFR was 48±1 in the CsA/Aza group and 53±1 mL/min/1.73 m2 in the Tac/MMF group ( P=0.007 ) . There was no significant difference in diabetes after transplantation ( 16.8 % and 18.8 % , respectively ) . Conclusions . With antithymocyte globulins and steroids , clinical ly suspected acute rejections did not differ between CsA/Aza and Tac/MMF arms . Analysis of secondary endpoints showed a lower rate of BPAR , including border line , and a higher eGFR in the Tac/MMF group . CsA/Aza allowed a low acute rejection rate , but Tac/MMF seemed as a better regimen regarding severe secondary outcomes Aims /hypothesisThis study estimated the economic efficiency ( 1 ) of intensive blood glucose control and tight blood pressure control in patients with type 2 diabetes who also had hypertension , and ( 2 ) of metformin therapy in type 2 diabetic patients who were overweight . Methods We conducted cost-utility analysis based on patient-level data from a r and omised clinical controlled trial involving 4,209 patients with newly diagnosed type 2 diabetes conducted in 23 hospital-based clinics in Engl and , Scotl and and Northern Irel and as part of the UK Prospect i ve Diabetes Study ( UKPDS ) . Three different policies were evaluated : intensive blood glucose control with sulphonylurea/insulin ; intensive blood glucose control with metformin for overweight patients ; and tight blood pressure control of hypertensive patients . Incremental cost : effectiveness ratios were calculated based on the net cost of healthcare re sources associated with these policies and on effectiveness in terms of quality -adjusted life years gained , estimated over a lifetime from within-trial effects using the UKPDS Outcomes Model . Results The incremental cost per quality -adjusted life years gained ( in year 2004 UK prices ) for intensive blood glucose control was £ 6,028 , and for blood pressure control was £ 369 . Metformin therapy was cost-saving and increased quality -adjusted life expectancy . Conclusions /interpretationEach of the three policies evaluated has a lower cost per quality -adjusted life year gained than that of many other accepted uses of healthcare re sources . The results provide an economic rationale for ensuring that care of patients with type 2 diabetes corresponds at least to the levels of these interventions AIM A 12-month multicenter , double-blind trial in which maintenance renal transplant patients were r and omized to remain on mycophenolate mofetil ( MMF ) or convert to enteric-coated mycophenolate sodium ( EC-MPS , myfortic ) has demonstrated that conversion from MMF to EC-MPS is safe . Patients completing the study were invited to enter an open-label extension . Upon entry to the extension , patients who had received MMF during the r and omized phase were converted to EC-MPS ( " newly-exposed EC-MPS " group ) and were monitored separately from those who had been r and omized to EC-MPS ( " long-term EC-MPS " group ) . The aim of the extension study was to collect long-term safety and efficacy data on EC-MPS , and to confirm the safety of conversion from MMF to EC-MPS in a larger patient population . METHODS All patients received EC-MPS 720 mg b.i.d . with cyclosporine microemulsion and corticosteroids per local practice . Data derived from the analysis of the first 24 months of the extension phase are presented . RESULTS Of the 297 patients who completed the core study , 260 ( 88 % ) entered the extension ; 195 ( 75 % ) completed the 24-month extension visit . For on-treatment patients > 95 % of the planned daily dose of EC-MPS was administered , and < 13 % of patients in both groups had discontinued EC-MPS due to adverse events by 24 months . The overall incidence of adverse events during the extension phase , including infections and hematological abnormalities , was comparable to that seen in the core study , with a similar safety profile in the newly-exposed and long-term EC-MPS groups . There were 3 deaths during the first 24 months of the extension , and 2 graft failures in both the " newly-exposed " and " long-term " EC-MPS groups . CONCLUSIONS These data demonstrate that long-term use of EC-MPS is effective and has an acceptable tolerability profile in renal transplant patients , and confirm that conversion of maintenance renal transplant patients from MMF to EC-MPS is a safe therapeutic option Background . Registry data can provide valuable information about possible treatment effects ; however , pretreatment differences in patient characteristics may influence treatment assignment . Careful analysis must therefore be undertaken when evaluating treatment differences in the context of nonr and omized studies so that the impact of treatment selection bias is minimized . Methods . A multivariable risk factor analysis of adult patients registered in the US Renal Data System who received a primary renal allograft during 1995 to 1998 was undertaken to compare 3-year graft survival using tacrolimus or Neoral with mycophenolate mofetil ( MMF ) and steroids . Results . In total , 9,449 patients were included ( cadaveric donor n=6,011 ; living donor n=3,438 ) . Patients ( 2,130 ) received tacrolimus , and 7,319 received Neoral . At 3 years posttransplant , the proportion of cadaveric donor recipients experiencing all causes of graft loss was 10.0 % for tacrolimus and 10.6 % for Neoral ; for living donor recipients these figures were 6.5 % and 6.7 % , respectively ( unadjusted Kaplan-Meier analysis ) . The incidence of graft failure excluding death was also similar between the two groups . With Cox proportional hazards modeling , the adjusted relative hazard of 3-year graft failure for cadaveric donor patients taking tacrolimus versus Neoral was 1.02 ( 95 % confidence interval [ CI ] 0.8–1.3 ) , and for living-donor recipients it was 1.15 ( 95 % CI 0.8–1.8 ) . Conclusions . These results indicate excellent 3-year graft survival for both cadaveric and living-donor renal-transplant patients receiving either Neoral or tacrolimus with MMF and steroids , with no significant differences between treatment groups . On the basis of these results , relative cost-effectiveness may become increasingly important in selection of tacrolimus or Neoral as primary immunosuppressant for renal-transplant patients Abstract Background and aims : R and omized controlled trials have shown that a once-daily prolonged-release ( PR ) tacrolimus formulation ( PR tacrolimus ; Advagraf ) , is non-inferior to a twice-daily immediate-release ( IR ) tacrolimus formulation ( IR tacrolimus ; Prograf ) in terms of biopsy-proven acute rejection , graft failure and mortality in renal transplant recipients . However , relative to IR tacrolimus , PR tacrolimus exhibits reduced tacrolimus trough concentration variability , which has been associated with reduced graft failure . Based on these data , the present study evaluated the cost of switching UK renal transplant patients from IR tacrolimus to PR tacrolimus . Methods : UK-specific data on acute rejection , graft failure , and mortality were used to construct a budget impact model to assess the costs of switching from IR tacrolimus to PR tacrolimus on a 1:1 mg : mg basis . The model assumed that 3.1 % of patients on PR tacrolimus had high tacrolimus trough concentration variability compared with 17.4 % on IR tacrolimus , based on a study comparing PR tacrolimus and IR tacrolimus pharmacokinetics . A relative graft failure risk of 2.38 was applied to high variability patients based on data from a tacrolimus variability study in which 10/148 patients with low variability experienced graft failure , compared with 24/149 in the high variability group . Cost data were taken from the British National Formulary and 2012–2013 NHS tariff information . Results : The mean per-patient cost ( including tacrolimus , concomitant immunosuppressive medications , dialysis after graft failure , and treatment for acute rejection ) was GBP 26,941 ( st and ard deviation [ SD ] = GBP 2765 ) with PR tacrolimus vs GBP 30,356 ( SD = GBP 3085 ) for IR tacrolimus over a 5-year period , corresponding to a saving of GBP 3415 ( SD = GBP 516 ) per patient or GBP 341,500 in a hypothetical 100-patient transplant center . Cost savings were driven primarily by lower dialysis costs result ing from the lower proportion of PR tacrolimus patients with high tacrolimus trough concentration variability ( leading to lower graft failure risk ) . Limitations : The main limitation of the study was the use of heterogeneous data sources to capture the effect of within-patient variability on graft failure . The most important difference between the studies was the definition of the threshold between low and high within-patient variability . This was explored in sensitivity analyses in which the inter-arm difference in the inter-arm proportions of patients with high and low variability was abolished . Conclusions : Converting UK renal transplant recipients from IR tacrolimus to PR tacrolimus was associated with lower pharmacy and dialysis costs Abstract Introduction and objective : In 1983 , the launch of cyclosporin was a significant clinical advance for organ transplant recipients . Subsequent drug research led to further advances with the introduction of cyclosporin microemulsion ( cyclosporin ME ) and tacrolimus . This paper presents the results from a long-term model comparing the clinical and economic outcomes associated with cyclosporin ME and tacrolimus immunosuppression for the prevention of graft rejection following renal transplantation . Study design : A model was developed to project the costs and outcomes over a 10-year period following transplantation . The model was based on the results of a prospect i ve , r and omised study of 179 renal transplantation recipients receiving either cyclosporin ME or tacrolimus , which was conducted by the Welsh Transplantation Research Group ( median follow-up : 2.7 years ) . Methods : The short-term costs and outcomes were the averages from the actual head-to-head trial data . From this , the long-term costs and outcomes were extrapolated based on the rate of change in patient and graft survival at 3 , 5 and 10 years post transplant , as reported in the 1995 United Kingdom Transplant Support Service Authority Renal Transplant Audit . Perspective and year of cost data : The analysis was conducted from the perspective of a UK transplant unit . Costs were at 1999 prices ( £ 1 = $ US1.42 = € 1.5 ) and costs and outcomes were discounted at 6 % and 1.5 % , respectively . Results : The model estimated that 10 years after transplantation , the proportion of patients surviving was 56 % of the cyclosporin ME cohort and 64 % of the tacrolimus cohort . The cumulative cost of maintenance therapy at 10 years was £ 23 204 per patient maintained on cyclosporin ME versus £ 23 803 per patient on tacrolimus . The cost per survivor at 10 years was £ 37 000 ( tacrolimus ) versus £ 41 000 ( cyclosporin ME ) and the cost per patient with a functioning graft was £ 39 000 versus £ 45 000 . A Monte Carlo simulation of the model ( 10 000 simulations ) gave an average cost at 10 years of £ 23 279 ( SD £ 3457 ) for cyclosporin ME and £ 22 841 ( SD £ 3590 ) for tacrolimus . A ( second order ) probabilistic sensitivity analysis was also performed . The average cost at 10 years from a simulated cohort of 1000 was £ 23 473 ( SD £ 2154 ) for cyclosporin ME and £ 24 087 ( SD £ 2025 ) for tacrolimus . Conclusion : Renal transplant recipients maintained on tacrolimus have better short- and long-term outcomes than patients maintained on cyclosporin ME . The long-term use of tacrolimus is a more cost-effective solution in terms of the number of survivors , patients with a functioning graft and rejection-free patients Background . The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients . In this study we compared two corticosteroid-free tacrolimus-based regimens with a st and ard triple therapy . Methods . This was a 6-month , phase III , open-label , parallel-group , multicenter study . The total analysis set comprised 451 patients , r and omized ( 1:1:1 ) to receive tacrolimus ( Tac ) monotherapy following basiliximab ( Bas ) administration ( n=153 ) , Tac/mycophenolate mofetil ( MMF ) ( n=151 ) , or , Tac/MMF/corticosteroids triple therapy as a control ( n=147 ) . Results . The study was completed by 91.2 % ( triple therapy ) , 94.7 % ( Tac/MMF ) , and 82.4 % ( Bas/Tac ) of patients . Patient baseline characteristics were similar in all groups . The incidences of biopsy-proven acute rejection were 8.2 % ( triple therapy ) , 30.5 % ( Tac/MMF ) , and 26.1 % ( Bas/Tac ) , p<0.001 ( multiple test for comparison with triple therapy ) ; Bas/Tac vs. Tac/MMF , p = ns . The incidences of corticosteroid-resistant acute rejection were 2.0 % , 4.0 % , and 5.2 % , p = ns . Graft survival ( 95.9 % , 96.7 % , and 94.7 % , p = ns ) and patient survival ( 100 % , 99.3 % , and 99.3 % , p = ns ) were similar in all groups . Median serum creatinine at month 6 was 123.0 & mgr;mol/L ( triple therapy ) , 134.7 & mgr;mol/L ( Tac/MMF ) and 135.8 & mgr;mol/L ( Bas/Tac ) . The overall safety profiles were similar ; differences ( p<0.05 ) were reported for anaemia ( 24.5 % vs. 12.6 % vs. 14.5 % ) , diarrhoea ( 12.9 % vs. 17.9 % vs. 5.9 % ) , and leukopenia ( 7.5 % vs. 18.5 % vs. 5.9 % ) for the triple therapy , Tac/MMF , and Bas/Tac group , respectively . The incidences of new-onset diabetes mellitus were 4.6 % , 7.1 % , and 1.4 % , respectively . Conclusion . Corticosteroid-free immunosuppression was feasible with the Bas/Tac and the Tac/MMF regimens . Both corticosteroid-free regimens were equally effective in preventing acute rejection , with the Bas/Tac therapy offering some safety benefits This multicenter , 1:1‐r and omized , parallel‐group , noninferiority study compared the efficacy and safety of twice‐daily tacrolimus ( Tacrolimus BID ; Prograf ) and once‐daily tacrolimus prolonged release ( Tacrolimus QD ; Advagraf ) , combined with steroids and low‐dose mycophenolate mofetil without antibody induction , in 667 de novo kidney transplant recipients . A double‐blind , double‐dummy 24‐week period was followed by an open extension of up to 12 months posttransplant . Biopsy‐proven acute rejection rate at 24 weeks ( primary endpoint , per‐ protocol analysis ) was 15.8 % for Tacrolimus BID versus 20.4 % for Tacrolimus QD ( p = 0.182 ; treatment difference 4.5 % , 95 % confidence interval—1.8 % , 10.9 % , just outside the prespecified 10 % noninferiority margin ) . Kaplan – Meier 12‐month patient and graft survival rates were 97.5 % and 92.8 % for Tacrolimus BID and 96.9 % and 91.5 % for QD . Both treatment groups showed equally well‐maintained renal function at 12 months ( mean creatinine clearance approximately 67 mL/min ) and similar adverse event profiles . Overall results obtained with either Tacrolimus QD or BID , without antibody induction , were good , supporting use of the once‐daily formulation as an effective alternative to the established twice‐daily formulation Tacrolimus , a cornerstone immunosuppressant , is widely available as a twice‐daily formulation ( Tacrolimus BID ) . A once‐daily prolonged‐release formulation ( Tacrolimus QD ) has been developed that may improve adherence and impart long‐lasting graft protection . This study compared the pharmacokinetics ( PK ) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID . A 6‐week , open‐label , r and omized comparative study was conducted in centers in Europe and Australia . Eligible patients received Tacrolimus QD or Tacrolimus BID . PK profiles were obtained following the first tacrolimus dose ( day 1 ) , and twice under steady‐state conditions . As secondary objectives , efficacy and safety parameters were also evaluated . Sixty‐six patients completed all PK profiles ( 34 Tacrolimus QD , 32 Tacrolimus BID ) . Mean AUC0–24 of tacrolimus on day 1 was approximately 30 % lower for Tacrolimus QD than Tacrolimus BID ( 232 and 361 ng.h/mL , respectively ) , but was comparable by day 4 . There was a good correlation and a similar relationship between AUC0–24 and Cmin for both formulations . Efficacy and safety data were also comparable over the 6‐week period . Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID BACKGROUND To date , there are no data on long-term use of enteric-coated mycophenolate sodium ( EC-MPS ; myfortic ) from time of renal transplantation . We report the first long-term safety and efficacy data on EC-MPS when administered for up to 3 years post transplant . METHODS De novo renal transplant recipients completing 1 year of treatment in a multicenter , r and omized , double-blind trial of EC-MPS versus mycophenolate mofetil ( MMF ) were invited to take part in an open-label extension during which all patients received EC-MPS 720 mg b.i.d . Results from the period 12 - 36 months post transplant were compared to comparable data from MMF-treated patients taking part in two studies of everolimus versus MMF ( RAD 201 and RAD 251 ) . RESULTS Of 367 patients completing the blinded core study , 247(62 % ) entered the open-label extension phase . During the first 24 months of the extension , the incidence , type and severity of adverse events were comparable between the newly-exposed and long-term EC-MPS patients . There were 2 deaths in the newly-exposed group and 4 among long-term EC-MPS patients , with 1 and 2 graft losses , respectively . Six patients ( 5 % ) in the newly-exposed group and 4 ( 3 % ) in the long-term EC-MPS group experienced biopsy-proven acute rejection . Cross- study comparisons indicated that the tolerability profile of EC-MPS was similar to MMF , including the incidence of adverse events , infections and malignancies , as was the incidence of efficacy events . CONCLUSION These results demonstrate that EC-MPS with cyclosporine and steroids provides good long-term efficacy and tolerability , and confirm the safety of converting renal transplant patients from MMF to EC-MPS Traditionally , chronic calcineurin inhibitor ( CNI ) nephrotoxicity has been considered to be one of the main nonimmune mechanisms causing chronic renal allograft dysfunction . CNI minimization and withdrawal strategies have yielded inconsistent results . Few studies address the feasibility of CNI elimination in a prednisone‐free regimen . We report a prospect i ve , r and omized trial in 200 patients evaluating the impact on renal function and incidence of acute rejection after conversion from tacrolimus ( Tac ) to sirolimus ( SRL ) . Patients with recent ( <3 months ) acute rejection episodes or with > 0.5 g/day of proteinuria were excluded . All were induced with alemtuzumab , underwent rapid steroid elimination and were maintained on mycophenolate mofetil and Tac . At 12 months posttransplant , patients were r and omized 2:1 to SRL ( n = 123 ) or maintained on Tac ( n = 64 ) . Mean follow‐up was 41.1 ± 15.8 months in the SRL group and 40.7 ± 14.4 months in the Tac group . Biopsy‐proven acute rejection at 24 months postr and omization was similar between the groups . Patient survival , graft survival and estimated GFR were also not statistically different . Our study demonstrates that in a prednisone‐free immunosuppressive regimen , conversion from Tac to SRL at 12 months posttransplantation is not associated with increased rates of acute rejection and graft loss . However , despite CNI elimination , renal allograft function is equally maintained in both groups The Belatacept Evaluation of Nephroprotection and Efficacy as First‐line Immunosuppression Trial r and omized patients receiving a living or st and ard criteria deceased donor kidney transplant to a more ( MI ) or less intensive ( LI ) regimen of belatacept or cyclosporine A ( CsA ) . The 5‐year results of the long‐term extension ( LTE ) cohort are reported . A total of 456 ( 68.5 % of intent‐to‐treat ) patients entered the LTE at 36 months ; 406 patients ( 89 % ) completed 60 months . Between Months 36 and 60 , death occurred in 2 % , 1 % and 5 % of belatacept MI , belatacept LI and CsA patients , respectively ; graft loss occurred in 0 % belatacept and 2 % of CsA patients . Acute rejection between Months 36 and 60 was rare : zero belatacept MI , one belatacept LI and one CsA. Rates for infections and malignancies for Months 36–60 were generally similar across belatacept groups and CsA , respectively : fungal infections ( 14 % , 15 % , 12 % ) , viral infections ( 21 % , 18 % , 16 % ) and malignancies ( 6 % , 6 % , 9 % ) . No new posttransplant lymphoproliferative disorder cases occurred after 36 months . Mean calculated GFR ( MDRD , mL/min/1.73 m2 ) at Month 60 was 74 for belatacept MI , 76 for belatacept LI and 53 for CsA. These results show that the renal function benefit and safety profile observed in belatacept‐treated patients in the early posttransplant period was sustained through 5 years In transplant recipients , Epstein-Barr virus ( EBV ) infection may be related to posttransplantation lymphoproliferative disorders ( PTLD ) , the most important risk factors for which are the patient 's serostatus before transplantation and the level of immunosuppression . Herein , we have evaluated the impact of EBV in adult kidney transplant recipients by prospect ively investigating its molecular epidemiology in 855 consecutive whole blood sample s obtained from 290 patients . EBV-DNA monitoring by real-time polymerase chain reaction ( PCR ) was performed at 3-month intervals in the first year after transplantation and subsequently once a year . Moreover , we studied 55 healthy , non-transplant recipient , blood donors . PCR for EBV-DNA results were positive in 99/855 sample s ( 11.6 % ) obtained from 72/290 patients ( 24.8 % ) versus none from healthy control subjects ( P < .05 ) . There were no differences in the prevalence of EBV-DNA positivity regarding demographic characteristics , underlying pathology leading to transplantation , renal function , and immunosuppressive protocol . Only 4 patients showed a viral load of > 2,000 genome equivalents/mL whole blood at > 12 months ; no patient developed PTLD . In conclusion , although the occurrence of EBV-DNA positivity was frequent , it was usually at low levels of viral load , confirming that adult kidney graft recipients are at a low risk of developing PTLD Background . The first generic tacrolimus product gained Food and Drug Administration approval in August 2009 . This prospect i ve , observational trial sought to determine the need for dose titrations and measure drug cost savings on conversion to generic tacrolimus . Methods . Transplant recipients on stable tacrolimus doses were converted from br and to generic tacrolimus on a mg : mg basis . Data were collected at the time of generic conversion ( study arm ) and at a time point exactly 6 months before conversion ( control arm ) for all subjects . Results . Seventy conversions from four centers are reported . Subjects were a mean of 70 months after kidney ( n=37 ) , liver ( n=28 ) , or multiorgan ( n=5 ) transplant . In the study arm , mean tacrolimus doses were 4.4 and 4.5 mg/d and mean tacrolimus trough concentrations were 5.8 and 5.9 ng/mL before and after conversion , respectively . In the control arm , mean tacrolimus doses were 4.6 and 4.6 mg/d and mean tacrolimus trough concentrations were 6.1 and 5.9 ng/mL before and after the control time point , respectively . Dose titrations occurred in five patients ( 7 % ) in the control arm and 15 patients ( 21 % ) in the study arm ( P=0.028 ) . Mean monthly drug costs were $ 645 for br and , $ 593 for generic , and $ 595 for generic after dose titrations . Mean monthly patient copays were $ 38 for br and and $ 15 for generic . Conclusions . These cumulative data show that dose requirements and trough levels are similar between br and and generic tacrolimus and that generic substitution allows for savings . However , postconversion monitoring is prudent as patients may require dose titration BACKGROUND Reducing side effects of immunosuppressive regimens has become a priority in transplantation medicine because of the large number of patients and grafts that succumb to infection in the short term and cardiovascular disease in the long term . The Symphony study was a 12-month prospect i ve , r and omized , open-label , multi-centre , four parallel arm study that aim ed to evaluate the safety and efficacy of low-dose immunosuppressive regimens compared with a st and ard-dose regimen in renal transplant recipients . This sub- analysis focuses on specific toxicities observed with the low-dose regimens . METHODS Adult patients ( n = 1645 ) scheduled to undergo renal transplantation received low-dose cyclosporine ( CsA ) , tacrolimus ( Tac ) or sirolimus ( SRL ) in addition to daclizumab induction or st and ard-dose cyclosporine without induction . All patients received mycophenolate mofetil and corticosteroids . We evaluated the incidence of adverse events ( AEs ) , tested specific group differences and assessed the relationship of selected AEs with drug levels . RESULTS The four arms had similar incidences of AEs , but serious AEs were more common with low-dose SRL and led to more discontinuations . Infections were the most common AEs , with the highest incidence in the st and ard-dose CsA group , in particular , cytomegalovirus ( CMV ) infections . Low-dose Tac had the most reports of new-onset diabetes , leucopenia and diarrhoea . Low-dose SRL negatively influenced triglycerides , wound healing , lymphocele and anaemia . We found only weak relationships between specific AEs and drug levels . CONCLUSIONS Despite the low doses , CsA , Tac and SRL retained distinct and different toxicity profiles . These findings may be of relevance for tailoring specific immunosuppressive regimens to patients with particular needs BACKGROUND / PURPOSE Combined therapy of sirolimus and cyclosporine has been found to exacerbate cyclosporine-related nephrotoxicity and to imperil graft renal function . We hypothesized that tacrolimus could bring about better renal function than cyclosporine when used in combination with sirolimus and corticosteroids for de novo renal transplantation . METHODS A two-arm r and omized study was conducted to test the hypothesis . Patients who gave written informed consent and received renal transplantation were r and omized to take sirolimus in combination with either tacrolimus or cyclosporine . The primary endpoint of this study was renal function , and the secondary endpoints were acute rejection , graft and patient survival , metabolic side effects and infectious complications . RESULTS A total of 41 Taiwanese renal transplant patients were r and omized to receive cyclosporine ( CsA group , n = 20 ) or tacrolimus ( TAC group , n = 21 ) in combination with sirolimus and corticosteroids . The average estimated glomerular filtration rate ( eGFR ) was 52.77 + /- 3.86 mL per minute for the TAC group at 6 months , and 46.42 + /- 3.95 mL per minute for the CsA group ( p > 0.05 ) . At 12 months , the average eGFR was 52.04 + /- 4.38 mL per minute for the TAC group , and 46.79 + /- 4.38 mL per minute for the CsA group ( p > 0.05 ) . The biopsy-proven acute rejection rate of the TAC group was 4.76 % ( 1/21 ) , and that of the CsA group was 5.00 % ( 1/20 ) at 12 months . The 12-month graft survival rates for the TAC and CsA groups were 100 % and 90 % ( p = 0.142 ) , respectively . CONCLUSION Our study demonstrated that concomitant tacrolimus and sirolimus therapy result ed in a favorable outcome in Taiwanese renal transplant patients at 12 months . Large-scale clinical trials will be needed to further address the issue of which calcineurin inhibitor , cyclosporine or tacrolimus , provides better renal function and graft survival for renal transplant patients Background . Although conversion from calcineurin inhibitors to mammalian target of rapamycin inhibitors proved to be effective in regressing left ventricular hypertrophy ( LVH ) in renal transplant recipients ( RTRs ) with chronic allograft dysfunction , there are currently no reports of r and omized trials on this issue involving de novo RTRs administered everolimus ( EVL ) . Methods . This r and omized , open-label , controlled trial evaluated the effect of EVL on the left ventricular mass index ( LVMi ) of 30 nondiabetic RTRs ( 21 men ; age 28–65 years ) . Ten were allocated to EVL plus reduced-exposure cyclosporine A ( CsA ) , and 20 to st and ard dose CsA. LVMi was assessed by echocardiography both at baseline and 1 year later . Blood pressure ( BP ) , hemoglobin , serum creatinine , lipids , trough levels of immunosuppressive drugs , and daily proteinuria were also evaluated twice monthly . Antihypertensive therapy that did not include renin-angiotensin system blockers was administered to achieve BP less than or equal to 130/80 mm Hg . Results . Changes in BP were similar in the two groups ( between group difference 1.2±5.7 mm Hg , P=0.84 for systolic , and −1.5±3.7 , P=0.69 , for diastolic BP ) , whereas LVMi significantly decreased in the EVL group alone ( between group difference 9.2±3.1 g/m2.7 , P=0.005 ) , due to a reduction in both the interventricular septum and the left ventricular posterior wall thickness . EVL therapy together with baseline LVMi were the only significant predictors of LVH regression according to a multivariate model that explained 49 % of the total LVMi variance ( P=0.0015 ) . Conclusions . An immunosuppressive regimen consisting of EVL plus reduced exposure CsA proved to be effective in regressing LVH in RTRs regardless of BP , mainly by reducing left ventricular wall thickness The natural history for patients with de novo donor‐specific antibodies ( dnDSA ) and the risk factors for its development have not been well defined . Furthermore , clinical and histologic correlation with serologic data is limited . We studied 315 consecutive renal transplants without pretransplant DSA , with a mean follow‐up of 6.2 ± 2.9 years . Protocol ( n = 215 ) and for cause ( n = 163 ) biopsies were analyzed . Solid phase assays were used to screen for dnDSA posttransplant . A total of 47 out of 315 ( 15 % ) patients developed dnDSA at a mean of 4.6 ± 3.0 years posttransplant . Independent predictors of dnDSA were HLA‐DRβ1 MM > 0 ( OR 5.66 , p < 0.006 ) ; and nonadherence ( OR 8.75 , p < 0.001 ) ; with a strong trend toward clinical rejection episodes preceding dnDSA ( OR 1.57 per rejection episode , p = 0.061 ) . The median 10‐year graft survival for those with dnDSA was lower than the No dnDSA group ( 57 % vs. 96 % , p < 0.0001 ) . Pathology consistent with antibody‐mediated injury can occur and progress in patients with dnDSA in the absence of graft dysfunction and furthermore , nonadherence and cellular rejection contribute to dnDSA development and progression to graft loss Conversion from cyclosporine ( CsA ) to sirolimus at week 12 after kidney transplantation is associated with a significant improvement in renal function . The aim of this analysis was to investigate the effect of this conversion on interstitial fibrosis ( IF ) , a hallmark of chronic allograft injury , in patients taking part in the CONCEPT trial . This multicenter , prospect i ve , trial included 193 renal recipients r and omized at week 12 to switch from CsA to sirolimus or to continue CsA , with mycophenolate mofetil . Routine biopsy with automated , quantified assessment of IF by a program of color segmentation was performed at 1 year in 121 patients . At 1 year , renal function was significantly improved in the conversion group as assessed by estimated GFR ( MDRD ) and measured GFR . Biopsy results , however , showed no between‐group difference in percentage of IF . Calculated GFR at 1 year was significantly associated with the percentage of IF ( p = 0.004 , R2= 0.07 ) . By multivariate analysis diabetic patients had more fibrosis than non‐diabetic patients . In conclusion , although kidney transplant patients converted from CsA to sirolimus showed significant improvement in renal function , we found no difference of IF on 1‐year biopsies Background . In kidney transplant recipients with alemtuzumab induction maintained on mycophenolate mofetil ( MMF ) immunosuppression , sirolimus ( SRL ) promotes significant expansion of circulating CD4+CD25high regulatory T cells ( Treg ) . This might translate into more effective protection against chronic graft injury compared to cyclosporin A ( CsA ) , which , in the same clinical setting , does not affect Treg . Methods . To assess this hypothesis , in the extension of a single-center , prospect i ve , r and omized , open , blind endpoint study aim ed to assess the effect of low-dose SRL or CsA on circulating Treg , we compared the outcomes of renal transplant recipients on SRL ( n=11 ) or CsA ( n=10 ) by per- protocol biopsies and serial measurements of glomerular filtration rate ( GFR ) , renal plasma flow ( RPF ) , and 24-hour proteinuria over 30 months posttransplant . Results . Despite 4-fold higher CD4+CD25high Treg counts ( 22.1±12.2 % vs. 5.7±4.2 % of CD3+CD4 + T cells ) , SRL-treated patients , compared to CsA-treated patients , had a significantly higher tubular C4d staining score ( 1.1±0.6 vs. 0.2±0.3 , P<0.01 ) , with nonsignificant trends to higher chronic allograft damage index score ( 5.6±2.4 vs. 3.7±3.3 ) , faster GFR ( −2.92±0.33 vs. −0.28±0.44 ml/min/1.73m2 per year ) , and RPF ( −10.80±5.45 vs. −1.86±3.09 ml/min/1.73 m2 per year ) decline , and more clinical proteinuria ( n=6 vs. 4 ) . There was no significant correlation between Treg counts and any considered outcome variable in the study group as a whole and within each cohort . Conclusions . These data suggest that , despite enhanced Treg expression , low-dose SRL combined to alemtuzumab induction and MMF-based steroid-free maintenance therapy , does not appreciably protect renal transplant recipients from chronic allograft injury and dysfunction Background . Basiliximab ( Simulect ) , a high-affinity chimeric , monoclonal antibody directed against the alpha chain of human interleukin-2 receptor ( CD25 ) , reduces the incidence of acute renal allograft rejection when used in combination with cyclosporine ( Neoral ) and steroids . This study was design ed to compare the safety and efficacy of basiliximab to polyclonal anti-T-cell ( ATGAM ) therapy for the prevention of acute rejection in de novo renal transplant recipients . Methods . This 1-year , open-label , r and omized trial was conducted in recipients of cadaveric or living-related donor renal transplants . All patients received cyclosporine ( Neoral ) , mycophenolate mofetil ( CellCept , MMF ) , and corticosteroids . Patients who were r and omized to basiliximab therapy received a 20 mg i.v . bolus dose on days 0 and 4 , and the majority of patients were initiated on cyclosporine within 48 hr of transplantation . Patients who were r and omized to antithymocyte globulin therapy ( ATGAM , ATG ) received 15 mg/day i.v . within 48 hr of transplant and continued treatment for up to 14 days ; ATG was stopped once therapeutic cyclosporine blood levels were achieved . The initiation of cyclosporine use was delayed in the ATG group until renal function was established ( serum creatinine < 3.0 mg/dl or 50 % fall from baseline ) . Results . Of the 138 r and omized patients , 135 received at least 1 dose of study medication ( 70 patients , basiliximab ; 65 patients , ATG ) . Demographic characteristics were similar between the basiliximab and ATG-treatment groups . At 12 months , the rate of biopsy-proven acute rejection was 19 % and 20 % , respectively , in the basiliximab and ATG groups . Although the overall profile of adverse events was similar between basiliximab- and ATG-treated patients , adverse events considered by the investigators to be associated with the study drug occurred more often among patients receiving ATG ( 42 % vs. 11 % with basiliximab ) . Conclusions . Basiliximab combined with early initiation of cyclosporine therapy result ed in low acute rejection rates similar to those achieved with ATG combined with delayed cyclosporine . Basiliximab therapy showed an excellent safety profile , with no increases in malignancies , infections , or deaths . Based on its convenient two-dose , body-weight independent regimen and comparable effectiveness to ATG , basiliximab is an attractive choice for the prevention of acute rejection episodes in renal transplant patients Background . This is the first report of a r and omized , multicenter , clinical trial comparing the combination of sirolimus or mycophenolate mofetil ( MMF ) with tacrolimus-based immunosuppression in kidney transplantation . Results at 6 months of follow-up are presented . Methods . Before transplantation , patients were r and omized to receive tacrolimus plus corticosteroids with sirolimus ( n=185 ) or MMF ( n=176 ) . The primary endpoint of the study was the incidence of biopsy-confirmed acute rejection . Patient and graft survival , renal function , and composite endpoints also were evaluated . Safety was assessed by monitoring laboratory parameters and adverse events . Results . By 6 months of follow-up , the incidence of biopsy-confirmed acute rejection was similar in both treatment groups ( 13.0 % tacrolimus+sirolimus vs. 11.4 % tacrolimus+MMF;P = 0.64 log-rank ) . Patient survival ( 97.3 % tacrolimus+sirolimus vs. 97.7 % tacrolimus+MMF ) and graft survival ( 93.0 % tacrolimus+sirolimus vs. 95.5 % tacrolimus+MMF ) were equivalent ( P = 0.53 , overall survival log-rank ) . There was a significantly higher incidence of study drug discontinuation in patients receiving sirolimus ( 21.1 % vs. 10.8%;P = 0.008 ) . Renal function was significantly better in the MMF-treatment group ( serum creatinine 1.44±0.45 mg/dL vs. 1.77±1.42 mg/dL;P = 0.018 ) . Hyperlipidemia was significantly more prevalent in the sirolimus-treatment group . Diastolic blood pressure was significantly higher in sirolimus-treated patients . There were significantly more leukopenia and gastrointestinal adverse events in the MMF-treatment group . The incidence of posttransplant diabetes mellitus was 7.6 % in the sirolimus group and 7.7 % in the MMF group . Conclusion . Tacrolimus is equally effective in renal transplantation when combined with sirolimus or MMF . The tacrolimus-MMF combination may be superior in terms of improved renal function and improved cardiovascular risk factors including hyperlipidemia and hypertension Background . Chronic allograft nephropathy ( CAN ) represents the most common cause of late graft loss . Nephrotoxicity from chronic use of calcineurin inhibitors ( CNI ) has the potential to contribute to CAN . The present investigation aim ed to evaluate the impact of early CNI withdrawal on kidney graft function and structure at 1 year in sirolimus (SRL)-treated patients . Methods . Forty consecutive kidney transplant recipients were initially treated with corticosteroids , cyclosporine A ( CsA ) , and SRL ( 2 mg/day ) . After 3 months , patients were r and omly assigned to either continue the same treatment ( group I ) or to withdraw CsA and continue SRL ( group II ) . All patients underwent kidney graft biopsy immediately after graft reperfusion ( 0-hr biopsy ) and 12 months after engraftment . Results . Baseline graft biopsy showed a higher degree of renal damage in group II patients ( total score , 4±1.6 vs. 2±0.9;P < 0.05 ) . Twelve months after engraftment , CAN was diagnosed in 55 % of all patients , of whom 64 % were in group I and 36 % in group II . CAN lesions were scored as moderate to severe in 90 % of group I patients but only 32 % of group II patients ( P < 0.05 ) . A vascular score greater than or equal to 2 occurred in 90 % of group I patients and in 38 % of group II patients ( P < 0.05 ) . At 1 year , group I patients showed a significantly worse kidney graft function ( serum creatinine , 2.0±0.3 vs. 1.3±0.3 mg/dL ; creatinine clearance , 54±14 vs. 66±17 mL/min ; both P < 0.002 ) . Conclusions . These results suggest that early withdrawal of CsA is a safe option , which allows a significant reduction of chronic histologic damage , particularly vascular injury , of cadaveric kidney allografts Background . Registry data bases offer the statistical power to analyze differences in graft survival rates that may not be detected in r and omized clinical trials . This study analyses 2‐year graft survival using tacrolimus ( tac ) or cyclosporine ( CsA ) with mycophenolate mofetil ( MMF ) and steroids . Methods . Data reported to the United Network for Organ Sharing Renal Transplant Registry for livingdonor kidney patients receiving a transplant during 1998 to 1999 were included . The primary end point was graft survival after adjustment for confounding variables . A Cox model multivariate analysis was used to adjust for potential confounding factors . Results . Patients receiving CsA‐MMF ( n=4,686 ) and tac‐MMF ( n=2,393 ) were included . Unadjusted allcause 2‐year graft survival rate was significantly higher with CsA‐MMF than tac‐MMF ( 94.3 % vs. 92.2 % , P=0.0006 ) . After adjustment for potential confounding factors , risk of graft failure at 2 years was significantly higher in patients receiving tac‐MMF versus CsA‐MMF for both all‐cause graft failure ( hazards ratio [ HR ] 1.28 , 95 % confidence interval [ CI ] 1.09‐1.49 , P=0.002 ) and death‐censored graft failure ( HR 1.25 , 95 % CI 1.05‐1.49 , P=0.013 ) . Other independent risk factors for graft failure were recipient or donor age greater than 55 years , female sex , pretransplant blood transfusions , one or two haplotype mismatches compared with zero haplotype mismatch , and panel reactive antibody ( PRA ) greater than 30 % . Conclusions . Our findings demonstrate that 2‐year renal allograft survival is significantly higher in living‐donor recipients receiving CsA compared with tac as initial immunosuppression in combination with MMF BACKGROUND A double-blind , placebo-controlled , r and omized study was performed to assess whether immunoprophylaxis with basiliximab ( Simulect ) could reduce the incidence of acute rejection in kidney transplant recipients treated with cyclosporine ( Neoral ) , steroids , and azathioprine . METHODS Three hundred forty patients received either placebo or basiliximab at a dose of 20 mg , given intravenously on days 0 and 4 . All patients received cyclosporine , steroids , and azathioprine . The primary endpoint was the incidence of acute rejection at 6 months . Secondary endpoints included the safety and tolerability of basiliximab and placebo , 1-year patient and graft survival , and significant medical events up to 12 months . RESULTS During the first 6 months posttransplantation , acute rejection occurred in 20.8 % of patients given basiliximab versus 34.9 % of patients administered placebo ( P=0.005 ) . Similarly , there was a reduction in biopsy-proven acute rejection at 6 months in the patients receiving basiliximab ( P=0.023 ) . One-year patient survival was 97.6 % with basiliximab and 97.1 % with placebo , graft survival was 91.5 % versus 88.4 % , respectively ( NS ) . The adverse-events profile of patients treated with basiliximab was indistinguishable from that of patients treated with placebo . The number of patients with infections was similar ( 65.5 % for basiliximab vs. 65.7 % for placebo ) , including cytomegalovirus infections ( 17.3 % vs. 14.5 % , P=0.245 ) . Nine neoplasms ( three in the basiliximab group , six in the placebo arm ) were recorded up to 1 year from transplantation . CONCLUSIONS Basiliximab in combination with cyclosporine , steroids , and azathioprine triple therapy was highly effective in reducing the incidence of acute renal allograft rejection without increasing the incidence of infections and other side effects Background . In renal transplant ( RT ) recipients , treatment with enteric-coated mycophenolate sodium ( EC-MPS ) improves gastrointestinal ( GI ) tolerability compared with mycophenolate mofetil ( MMF ) . The impact of conversion from MMF to EC-MPS on patient 's health-related quality of life ( HRQoL ) using GI-specific instruments has been scarcely evaluated in r and omized trials . Methods . The present r and omized , multicenter , open-labeled , 12-week study included RT recipients experiencing GI adverse events due to MMF treatment . Patients were r and omized to continue with MMF ( n=54 ) or change to EC-MPS ( n=59 ) . Patients were converted at equimolar doses , and dose was optimized between weeks 2 and 6 to achieve maximum tolerated dose . Results . Incidence of GI complications ( particularly diarrhea ) was significantly lower in the EC-MPS group ( 67.8 % vs. 87.0 % , P=0.015 ) . The baseline-adjusted mean global scores at 12 weeks in GI quality of life index were significantly higher in the EC-MPS group versus MMF ( P=0.014 ) . Results at 12 weeks for all secondary scales indicated better HRQoL in the EC-MPS group compared with the MMF group ( Gastrointestinal Symptom Rating Scale , Psychological General Well-Being Index , and overall treatment effect ) . In the EC-MPS group , a higher percentage of patients were receiving intermediate doses of mycophenolic acid ( 720 mg/day ) at 12 weeks compared with MMF ( 55.4 % vs. 27.4 % , P=0.003 ) , whereas no differences were observed for high doses ( > 720 mg/day ) . Conclusions . In RT patients with GI undesirable effects due to MMF , switching from MMF to EC-MPS may enable an increase in the maximum tolerated dose of mycophenolic acid and reduce GI complications , thus enhancing patients ' GI MYCOPHENOLIC acid ( MPA ) is a potent , selective , non-competitive , reversible inhibitor of inosine mono phosphate dehydrogenase . However , use of immunosuppressive agents containing MPA as the active compound , such as mycophenolate mofetil ( MMF ) , may be limited by various side effects . These include hematological adverse events such as anemia , thrombocytopenia , and leucopenia , increased risk of cytomegalovirus ( CMV ) and opportunistic infections and gastrointestinal ( GI ) disorders , such as nausea , vomiting , diarrhea , gastritis , ulcers , and abdominal pain , which may be associated with CMV infection Background . Chronic steroid therapy in spite of myriad side effects is widely used in kidney transplantation . This prospect i ve controlled study evaluated safety and efficacy of steroid withdrawal at 2 days in kidney recipients monitored by surveillance biopsy . Methods . In all , 300 kidney recipients were studied ; 150 in second-day steroid withdrawal group and 150 in steroid treated group ( control group ) . Immunosuppression was basiliximab induction and maintenance was a calcineurin inhibitor and mycophenolate mofetil or sirolimus . Biopsy-proven acute rejection ( BPAR ) was treated by methylpredisolone . Surveillance biopsies were completed to evaluate sub clinical acute rejection ( SCAR ) and chronic allograft nephropathy ( CAN ) . Primary end point was acute rejection . Three-year patient and graft survival , new onset diabetes mellitus ( NODM ) , serum creatinine and creatinine clearance were evaluated . Results . Acute rejection was diagnosed in 14 % in control group and 16 % in steroid withdrawal group . Three-year patient and graft survival was 89 % and 79 % in control and 91 % and 78 % in steroid withdrawal group . Serum creatinine and creatinine clearance was 1.9±0.8 and 59±11 in control group and 1.8±0.9 mg/dl and 61±10 mls/minute in steroid withdrawal group . Incidence of SCAR and progression of CAN were comparable in the 2 groups . At 3-years NODM was diagnosed in 21 % in control group and 4 % in steroid withdrawal group ( P<0.01 ) . Conclusions . Two-day steroid withdrawal in kidney transplant recipients did not affect BPAR , SCAR , CAN , graft function and patient and graft survival compared to control group up to 3 years . NODM was significantly less in steroid withdrawal group . Two-day steroid withdrawal is safe and beneficial in kidney transplant recipients Induction and maintenance immunosuppression protocol s with or without long-term steroid therapy in kidney transplant recipients are variable and are transplant center-specific . The aim of this prospect i ve r and omized pilot study was to compare 5-year outcomes in kidney recipients maintained on 4 different calcineurin inhibitor (CNI)-based immunosuppression protocol s without long-term steroid therapy . Two hundred consenting patients who received kidney transplants between June 2000 and October 2004 were enrolled in 4 immunosuppression protocol groups , with 50 patients in each group : cyclosporine (CSA)/mycophenolate mofetil ( MMF ) , CSA/sirolimus ( SRL ) , tacrolimus (TAC)/MMF , and TAC/SRL . Induction therapy was done with basiliximab and methylprednisolone . Steroids were withdrawn on post-transplant day 2 , and long-term steroid therapy was not used . Demographic characteristics among the four groups were comparable ; approximately 50 % of the recipients were African American and > or = 80 % of the kidneys transplanted were from deceased donors . Clinical acute rejection ( CAR ) was confirmed by biopsy and treated with intravenous pulse steroid therapy . Steroid-unresponsive CAR was treated with Thymoglobulin . Surveillance biopsies were performed at 1 , 6 , 12 , 24 , 36 , 48 , and 60 months to evaluate sub clinical acute rejection ( SCAR ) , chronic allograft injury ( CAI ) , and other pathological changes per the Banff 2005 schema . The primary end point was CAR , and secondary end points were 5-year patient and graft survival rates , renal function , SCAR , CAI , and adverse events . In the first year post-transplant , the incidence of CAR was 18 % in the CSA/MMF group , 8 % in the CSA/SRL group , 14 % in the TAC/MMF group , and 4 % in the TAC/SRL group ( CSA/MMF vs. TAC/SRL ; p=0.05 ) . The incidence of SCAR was 22 % in the CSA/MMF group , 8 % in the CSA/SRL group , 16 % in the TAC/MMF group , and 6 % in the TAC/SRL group ( CSA/MMF vs. CSA/SRL and TAC/SRL ; p=0.05 ) . After the first year , the incidences of CAR and SCAR decreased and were comparable in all 4 groups . At 5 years post-transplant , cumulative CAI due to interstitial fibrosis/tubular atrophy ( IF/TA ) , hypertension ( HTN ) , and chronic calcineurin inhibitor ( CNI ) toxicity was observed in 54 % , 48 % , and 8 % of the CSA/MMF group vs. 16 % , 36 % , and 12 % of the CSA/SRL group vs. 38 % , 24 % and 6 % of the TAC/MMF group vs. 14 % , 25 % and 12 % of the TAC/SLR group ( IF/TA : CSA/MMF vs. CSA/SRL and TAC/SRL ; p=0.04 , HTN : CSA/MMF vs. TAC/MMF and TAC/SRL ; p=0.05 , CNI toxicity : TAC/SRL and CSA/SRL vs. TAC/MMF ; p=0.05 ) . Five-year patient and graft survival rates were 82 % and 60 % in the CSA/MMF group , 82 % and 60 % in the CSA/SRL group , 84 % and 62 % in the TAC/MMF group , and 82 % and 64 % in the TAC/SRL group ( p=0.9 ) . Serum creatinine levels and creatinine clearances at 5 years were comparable among the groups . Our data show that the rates of CAR and SCAR in the first year post-transplant were significantly lower in the CSA/SRL and TAC/SRL groups and that cumulative CAI rates due to IF/TA and HTN at 5 years were significantly lower in the TAC/MMF , TAC/SRL , and CSA/SRL groups than in the CSA/MMF group . Despite significant differences in the incidences of CAR and SCAR and prevalence of different types of CAI at 5 years , renal function and patient and graft survival rates at 5 years were comparable among kidney recipients maintained on 4 different immunosuppression protocol s without long-term steroid therapy OBJECTIVE The aim of this study in renal transplant recipients was to compare a tacrolimus plus mycophenolate mofetil ( MMF ) immunosuppressive regimen with a combination of low dose of cyclosporine and everolimus . PATIENTS AND METHODS Sixty consecutive patients were prospect ively assigned to receive tacrolimus and MMF ( TAC ; n = 30 ) or everolimus and low-dose cyclosporine ( EVL ; n = 30 ) . Tacrolimus was dosed seeking a trough blood level of 8 to 10 ng/mL by month 3 and 5 to 8 ng/mL thereafter . Everolimus was dosed seeking a trough blood level of 3 to 8 ng/mL by day 7 . Cyclosporine was dosed aim ing at a C2 blood level of 350 to 700 ng/mL in the first week and 150 to 400 ng/mL thereafter . All patients received induction with basiliximab and maintenance treatment with corticosteroids . RESULTS At 6-months follow-up , patient survival rates ( TAC 100 % vs EVL 100 % ) and graft survival rates ( TAC 96.7 % vs EVL 93.3 % ) were not significantly different between the groups . Patients in the EVL group showed more acute rejection episodes , but serum creatinine concentrations and creatinine clearances were not significantly different from the TAC group . Among the observed side effects , hypercholesterolemia was significantly higher in the EVL group ( total cholesterol : TAC 206 + /- 38 vs EVL 250 + /- 55 mg/dL ; P < .003 ) . CONCLUSIONS This study showed that the immunosuppressive association of tacrolimus and MMF produced similar acute rejection episodes , graft survivals , and renal function at 6 months after renal transplantation compared with an immunosuppressive combination of everolimus and low-dose cyclosporine . Dyslipidemia was significantly greater among patients who received everolimus The introduction of mycophenolate mofetil ( MMF ) represented a major advance in transplant medicine , although optimal use may be limited by gastrointestinal ( GI ) side‐effects . An enteric‐coated formulation of mycophenolate sodium ( EC‐MPS ; myfortic ® ) has been developed with the aim of improving the upper GI tolerability of mycophenolic acid . Therapeutic equivalence of EC‐MPS ( 720 mg b.i.d . ) and MMF ( 1000 mg MMF b.i.d . ) , with concomitant cyclosporine microemulsion ( Neoral ® ) and corticosteroids , was assessed in 423 de novo kidney transplant patients recruited to a 12‐month , double‐blind study . Efficacy failure ( biopsy‐proven acute rejection [ BPAR ] , graft loss , death or loss to follow up ) at 6 months ( EC‐MPS 25.8 % vs. MMF 26.2 % ; 95 % CI : [ −8.7 , + 8.0 ] ) demonstrated therapeutic equivalence . At 12 months , the incidence of BPAR , graft loss or death was 26.3 % and 28.1 % , and of BPAR alone was 22.5 % and 24.3 % for EC‐MPS and MMF , respectively . Among those with BPAR , the incidence of severe acute rejection was 2.1 % with EC‐MPS and 9.8 % with MMF ( p = ns ) . The safety profile and incidence of GI adverse events were similar for both groups . Within 12 months , 15.0 % of EC‐MPS patients and 19.5 % of MMF patients required dose changes for GI adverse events ( p = ns ) . Enteric‐coated‐MPS 720 mg b.i.d . is therapeutically equivalent to MMF 1000 mg b.i.d . with a comparable safety profile Background . The use of calcineurin inhibitors is associated with chronic nephrotoxicity and lower glomerular filtration rate ( GFR ) . As a result , one strategy of transplant immunosuppression is calcineurin inhibitor elimination . Methods . The aim of this study was to determine the outcome of a prospect i ve r and omized trial of kidney transplant recipients receiving rapid corticosteroid withdrawal , tacrolimus and mycophenolate mofetil ( MMF ) for 1 month followed by r and omization to switch to sirolimus-MMF or to stay on tacrolimus-MMF . The primary outcome was the difference in measured GFR at 1 year using intention-to-treat analysis . Results . Sixty patients were r and omized to stay on tacrolimus-MMF and 62 to sirolimus-MMF . Actual graft survival ( including death ) at 2 years was 98.4 % in the sirolimus group , 96.7 % in the tacrolimus group . Sixty-three percentage of the patients in the sirolimus group withdrew during the 2-year period of the study compared with 18 % of the tacrolimus group ( P<0.0001 ) , primarily related to rejection or medication side effects . Rejection during the first year occurred in 5 % of the tacrolimus group and 13 % of the sirolimus group ( P=0.15 ) . Measured GFR at 1 year ( mean±SD ) was 57.4±20.7 mL/min/1.73 m2 in the sirolimus group and 62.7±26.5 mL/min/1.73 m2 in the tacrolimus group ( 95 % CI of difference −3.7–14.4 ) . Conclusions . We conclude that conversion from tacrolimus-MMF to sirolimus-MMF at 1 month posttransplant in kidney recipients on rapid steroid withdrawal is poorly tolerated and does not improve GFR at 1 year AIMS To estimate the immediate and long-term inpatient and non-inpatient costs for Type 2 diabetes-related complications . METHODS The costs of all consultations , visits , admissions and procedures associated with diabetes-related complications during UK Prospect i ve Diabetes Study post-trial monitoring in the period 1997 - 2007 were estimated using hospitalization records for 2791 patients in Engl and and re source use question naires that were administered to 3589 patients across the UK . RESULTS The estimated ( 95 % CI ) inpatient care costs ( in 2012 pounds sterling ) in the event year for the example of a 60-year-old man were : non-fatal ischaemic heart disease £ 9767 ( £ 7038-£12 696 ) ; amputation £ 9546 ( £ 6416-£13 463 ) ; non-fatal stroke £ 6805 ( £ 3856-£10 278 ) ; non-fatal myocardial infa rct ion £ 6379 ( £ 4290-£8339 ) ; fatal stroke £ 3954 ( £ 2012-£6428 ) ; fatal ischaemic heart disease £ 3766 ( £ 746-£5512 ) ; heart failure £ 3191 ( £ 1678 - 4903 ) ; fatal myocardial infa rct ion £ 1521 ( £ 647-£2670 ) ; and blindness in one eye £ 1355 ( £ 415-£2655 ) . In subsequent years , estimated ( 95 % CI ) costs ranged from £ 1792 ( £ 1060-£2943 ) for amputations to £ 453 ( £ 315-£691 ) for blindness in one eye . Costs of non-inpatient healthcare in the event year were : amputation £ 2699 ( £ 1409-£4126 ) ; blindness in one eye £ 1790 ( £ 878-£3056 ) ; non-fatal stroke £ 1019 ( £ 770-£1499 ) ; nonfatal myocardial infa rct ion £ 1963 ( £ 794-£1157 ) ; heart failure £ 979 ( £ 708-£1344 ) ; non-fatal ischaemic heart disease £ 864 ( £ 718-£1014 ) ; and cataract extraction £ 700 ( £ 619-£780 ) . In each subsequent year , non-inpatient costs ranged from £ 1611 ( £ 1193-£2116 ) for amputations to £ 654 ( £ 572-£799 ) for ischaemic heart disease . CONCLUSIONS Diabetic complications are associated with substantial immediate and long-term healthcare costs . Our comprehensive new estimates of these costs , derived from detailed recent UK Prospect i ve Diabetes Study post-trial data , should aid research ers and health policy analyses The ideal immunosuppressive treatment for African-American kidney transplant recipients has not been established . We performed a long-term prospect i ve r and omized trial comparing the results of tacrolimus ( TAC ) and cyclosporine ( CSA ) in the African-American population . Thirty-five African-American primary cadaveric renal transplant ( CRT ) recipients were enrolled in the study . Group I ( n = 14 ) received TAC and group II ( n = 21 ) received CSA ; mean follow up was 78 months . We found no difference in patient/graft survival rates between the groups . Twelve patients in the CSA group were converted to TAC , mostly because of hypercholesterolemia or as a rescue for an acute rejection episode . Significant lower creatinine and cholesterol levels were seen at 1 year post-transplant , but this difference lost significance at 3 and 5 years , possibly because of conversion of most patients from CSA to TAC . In conclusion , African-American recipients of primary CRTs can achieve excellent long-term results with TAC-based immunosuppression OBJECTIVES This prospect i ve , r and omized , multicentre study investigated the efficacy and safety of two tacrolimus-based regimens and their potential to withdraw steroids . METHODS In total 489 patients were r and omised to receive either tacrolimus and MMF ( n = 243 ) or tacrolimus and azathioprine ( n = 246 ) concomitantly with steroids in both treatment groups . The initial oral dose of tacrolimus was 0.2 mg/kg/day , MMF dose was 1 g/day , azathioprine was administered at 1 - 2 mg/day . Steroids were tapered from 20 mg/day to 5 mg/day . From month 3 onwards , steroids were withdrawn in patients who were free from steroid-resistant rejection and who had serum creatinine concentrations < 160 mumol/L. Study duration was 6 months . RESULTS Patient survival at month 6 was 98.3 % ( Tac/MMF/S ) and 98.4 % ( Tac/Aza/S ) , graft survival at 6 month was 95.0 % ( Tac/MMF/S ) and 93.5 % ( Tac/Aza/S ) . The 6-month incidences of biopsy-proven acute rejection were 18.9 % ( Tac/MMF/S ) compared with 26.8 % ( Tac/Aza/S ) , p = 0.038 . The 6-month incidences of steroid-resistant acute rejection were 2.1 % ( Tac/MMF/S ) and 4.9 % ( Tac/Aza/S ) , p = ns . At the end of month 3 , steroid withdrawal was performed in 60.5 % ( Tac/MMF/S ) and 48.8 % ( Tac/Aza/S ) of patients , p < 0.01 . During months 4 - 6 , 2.7 % of patients in the Tac/MMF group had a biopsy-confirmed acute rejection compared with 0.8 % of patients in the Tac/Aza group . In patients who continued to receive steroids , the incidences of biopsy-proven acute rejections during months 4 - 6 were 3.5 % ( Tac/MMF/S ) and 7.1 % ( Tac/Aza/S ) . At study end , the steroid-free patients had an excellent kidney function , the median serum creatinine concentration was 119.5 mumol/L ( Tac/MMF ) and 115.1 mumol/L ( Tac/Aza ) ; the median serum creatinine of the total study group was 130.5 mumol/L ( Tac/MMF/S ) and 132.8 mumol/L ( Tac/Aza/S ) . CONCLUSION Both tacrolimus regimens are efficacious and safe . The combination of Tacrolimus and MMF achieved a lower rejection rate and permitted a higher proportion of steroid-free patients . The overall incidence of acute rejection was low and kidney function was good Background . To date , the clinical trials of tacrolimus ( TAC ) versus cyclosporine modified ( CsA ) , have not defined which agent is more cost-effective for immunosuppression in renal transplant recipients especially in a quadruple immunosuppressive regimen . Methods . The objective of this r and omized , prospect i ve study was to compare the clinical and economic outcomes of TAC versus CsA , in a regimen that consisted of Thymoglobulin induction , an antimetabolite , and prednisone . Between December 2000 and October 2002 , 200 patients were enrolled and r and omized in a 2:1 fashion ( TAC n=134 , CsA n=66 ) . Results . At 1 year , acute rejection ( 4 % TAC vs. 6 % CsA ) , patient survival ( TAC 99 % vs. CsA 100 % ) , and graft survival ( 95 % TAC versus 100 % CsA , P=0.059 ) were similar . Serum creatinine levels were lower in the TAC group compared with the CsA group ( 1.3±0.3 vs. 1.6±0.7 mg/dL , P=0.03 ) . The incidence of CMV infection was similar between the groups and two patients , both in the TAC arm , developed malignancy . Anti-hypertensive requirement ( 32 % TAC vs. 32 % CsA ) and the incidence of posttransplant diabetes mellitus ( 4 % TAC vs. 2 % CsA ) were similar . Pretransplant , fewer TAC patients received dyslipidemia treatment ( 40 % TAC vs. 67 % CsA , P=0.0005 ) , while more CsA patients were able to discontinue these medications posttransplant ( absolute change 25 % TAC vs. 47 % CsA ) . Total 12-month medication costs were similar ( $ 17,723±11,647 TAC vs. $ 16,515±10,189 CsA ) . Conclusions . When combined with Thymoglobulin induction , an antimetabolite , and corticosteroids , TAC and CsA are comparable in safety , efficacy , and cost in renal transplantation Recipients of extended‐ criteria donor ( ECD ) kidneys have poorer long‐term outcomes compared to st and ard‐ criteria donor kidney recipients . We report 3‐year outcomes from a r and omized , phase III study in recipients of de novo ECD kidneys ( n = 543 ) assigned ( 1:1:1 ) to either a more intensive ( MI ) or less intensive ( LI ) belatacept regimen , or cyclosporine . Three hundred twenty‐three patients completed treatment by year 3 . Patient survival with a functioning graft was comparable between groups ( 80 % in MI , 82 % in LI , 80 % in cyclosporine ) . Mean calculated GFR ( cGFR ) was 11 mL/min higher in belatacept‐treated versus cyclosporine‐treated patients ( 42.7 in MI , 42.2 in LI , 31.5 mL/min in cyclosporine ) . More cyclosporine‐treated patients ( 44 % ) progressed to GFR < 30 mL/min ( chronic kidney disease [ CKD ] stage 4/5 ) than belatacept‐treated patients ( 27–30 % ) . Acute rejection rates were similar between groups . Posttransplant lymphoproliferative disorder ( PTLD ) occurrence was higher in belatacept‐treated patients ( two in MI , three in LI ) , most of which occurred during the first 18 months ; four additional cases ( 3 in LI , 1 in cyclosporine ) occurred after 3 years . Tuberculosis was reported in two MI , four LI and no cyclosporine patients . In conclusion , at 3 years after transplantation , immunosuppression with belatacept result ed in similar patient survival , graft survival and acute rejection , with better renal function compared with cyclosporine . As previously reported , PTLD and tuberculosis were the principal safety findings associated with belatacept in this study population In 11 European centers , first cadaveric renal allograft recipients were r and omized to CsA ( n = 42 ) or sirolimus ( n = 41 ) . Dosing of these agents was concentration-controlled and open-labeled . All patients received corticosteroids and azathioprine . At 12 months , graft survival ( 98 % sirolimus vs 93 % CsA ) , patient survival ( 100 % vs 98 % ) , and incidence of biopsy-confirmed acute rejection ( 41 % vs 38 % ) were similar . Serum creatinine was lower with sirolimus , significantly ( P < /=.05 ) so at 3 and 4 months , and serum uric acid and magnesium were normal . Laboratory abnormalities were reported significantly more often with sirolimus , which included hypertriglyceridemia ( 51 % vs 12 % ) , hypercholesterolemia ( 44 % vs 14 % ) , thrombocytopenia ( 37 % vs 0 % ) , leukopenia ( 39 % vs 14 % ) , and , of lesser importance , increased liver enzymes and hypokalemia . These abnormalities improved 2 months after transplantation when the sirolimus target trough level was lowered from 30 to 15 ng/mL. Occurrence of cytomegalovirus was comparable ( 14 % vs 12 % ) , but incidence of herpes simplex ( 24 % vs 10 % , P = .08 ) and pneumonia ( 17 % vs 2 % , P = .03 ) were higher with sirolimus . No gingival hyperplasia was seen with sirolimus , tremor was rare , and hypertension was less frequent ( 17 % vs 33 % ) . Two malignancies were observed with CsA , none with sirolimus . Results at 12 months suggest that sirolimus can be used as base therapy in the prophylaxis of acute renal transplant rejection , and has a safety profile that differs from that of BACKGROUND Acute rejection remains a major problem in renal transplantation . Immunoprophylaxis with basiliximab ( Simulect ) has achieved significant reductions in acute rejection episodes in renal allograft recipients receiving dual immunosuppression . This study explored the tolerability and cumulative benefit of combining basiliximab with triple-drug therapy-cyclosporine ( USP Modified , Neoral ) , mycophenolate mofetil , and steroids . METHODS In a r and omized , double-blind , placebo-controlled , multicenter study , 123 kidney transplant recipients received either basiliximab at 20 mg before transplantation ( day 0 ) and 20 mg on day 4 ( n=59 ) , or placebo ( n=64 ) . All received triple-drug immunosuppression and were followed for 6 months . RESULTS Tolerability of basiliximab was equivalent to placebo , with no increase in serious adverse events , infection , malignancy , or posttransplant lymphoproliferative disorder . At 6 months , there were trends in favor of basiliximab over placebo in the incidences of first biopsy-confirmed acute rejection ( 15.3 % vs. 26.6 % , P = NS ) and of acute rejection treated with antibody ( 5.1 % vs. 15.6 % , P = NS ) . Kaplan-Meier estimates at 4 weeks and 6 months were significantly in favor of basiliximab treatment for first acute rejection , biopsy-confirmed rejection , rejection episodes treated with antibody therapy , and treatment failure . Renal function improved more rapidly in the basiliximab group , with mean creatinine clearance at week 2 being 54.7 mL/min versus 43.2 mL/min for placebo ( P=0.034 ) . At 12 months , patient survival was 100 % in both groups ; graft survival was 94.9 % with basiliximab and 92.2 % with placebo . CONCLUSIONS Basiliximab immunoprophylaxis is safe , well tolerated , and shows a trend toward reduction in number of acute rejection episodes in renal transplant patients receiving cyclosporine , mycophenolate mofetil , and steroids BACKGROUND Chronic allograft nephropathy is an important cause of graft failure . Many donor and recipient factors contribute to its development . Prospect i ve analysis of these factors has been hindered by the lack of sensitive and specific indicators of renal injury . As a consequence protocol biopsies have been increasingly used in the assessment of renal allograft injury . We performed protocol renal allograft biopsies to prospect ively examine the role of important determinants and mediators of chronic allograft nephropathy . METHODS A total of 51 consecutive cadaveric renal transplant recipients entered a r and omized prospect i ve study of tacrolimus ( Tac ) versus cyclosporine ( CsA ) microemulsion based immunosuppression . Study patients underwent protocol renal allograft biopsies at the time of engraftment and at 3 , 6 and 12 months post-transplantation . Biopsies were analyzed by quantitative polymerase chain reaction ( PCR ) for mRNA for transforming growth factor-beta ( TGF-beta ) , thrombospondin , and fibronectin . Measurements of renal structural injury were estimated by quantitative assessment of interstitial fibrosis and glomerulosclerosis . Changes in profibrotic growth factors and renal structural injury were related to donor and recipient determinants by stepwise regression analysis . RESULTS Longitudinal assessment of renal injury demonstrated an early and progressive increase in mRNA for TGF-beta , thrombospondin ( TSP ) and fibronectin ( FBN ) : TGF-beta baseline , 1.9 + /- 0.2 log copies ; TGF-beta 6 months , 2.5 + /- 0.2 log copies , P < 0.05 6 months vs. baseline ; TSP baseline , 1.9 + /- 0.2 log copies ; TSP 6 months , 2.4 + /- 0.2 log copies , P < 0.05 6 months vs. baseline ; FBN baseline , 2.0 + /- 0.2 log copies ; FBN 12 months , 2.3 + /- 0.2 log copies , P < 0.05 12 months vs. baseline . This increase in profibrotic growth factors within the allograft was associated with a significant increase in interstitial fibrosis ( Vvi ) on renal biopsies : Vvi baseline , 13 + /- 1 % ; Vvi 3 months , 18 + /- 1 % ; Vvi 6 months , 28 + /- 2 % ; Vvi 12 months , 34 + /- 2 % ; P < 0.05 3 , 6 , and 12 months vs. baseline . Histological analysis demonstrated chronic allograft nephropathy in 4 % biopsies at 3 months , 12 % at 6 months and in 49 % at 12 months . These changes in renal structure were not associated with any change in creatinine clearance ( CCr ) : CCr 3 months , 56 + /- 2 mL/min , CCr 24 months , 56 + /- 2 mL/min ; P = NS . Stepwise regression analysis of key donor and recipient determinants of chronic renal injury identified calcineurin inhibitors and acute rejection episodes as important factors involved in the development of chronic renal injury . In particular , the use of cyclosporine compared to tacrolimus was associated with a tenfold increase in TGF-beta mRNA ( TGF-beta mRNA at 6 months , CsA vs. Tac , 3 + /- 0.3 vs. 2 + /- 0.3 log copies , P < 0.05 ) , interstitial fibrosis ( Vvi at 6 months , CsA vs. Tac , 33 + /- 4 % vs. 24 + /- 2 % , P < 0.05 ) . Changes in growth factors and renal structure predicted impaired renal function ( CCr at 12 months , CsA vs. Tac , 53 + /- 4 mL/min vs. 62 + /- 2 mL/min , P < 0.05 ) . Similarly , acute rejection episodes were associated with an accelerated development of interstitial fibrosis ( Vvi at 6 months , acute rejection vs. no rejection , 34 + /- 3 % vs. 25 + /- 2 % ; P < 0.05 ) , but not with changes in TGF-beta , thrombospondin or fibronectin expression . CONCLUSION Our results suggest that structural injury develops early in the natural history of the renal allograft and is mediated , in part , by the early up-regulation of profibrotic growth factors . We have determined that calcineurin inhibitors , in particular cyclosporine , and acute rejection episodes are key factors in the development of renal structural injury We examined short-term outcomes and posttransplant medical complications under three different immunosuppressive regimens at a single center . The study design was a r and omized , prospect i ve , open-label trial comparing a calcineurin inhibitor-free ( CNI ) protocol to st and ard triple therapy with tacrolimus , prednisone , and mycophenolate mofetil . They were also compared to a concurrent but nonr and omized third cohort treated with a prednisone-free protocol . All three groups had excellent early outcomes with no significant difference in patient or graft survival or biopsy-proven acute rejection . Serum creatinine was significantly lower in the CNI-free recipients . Lipid panels and posttransplant diabetes mellitus were significantly lower in the prednisone-free patients . Prednisone-free kidney transplant recipients have improved early glucose metabolism and hyperlipidemia compared to CNI-free or st and ard triple therapy recipients with comparable rejection and graft survival rates We performed a pilot study in which 22 kidney recipients ( 14 LD : 8 DCD ) were given alemtuzumab induction ( 30 mg day 0 and 1 ) , steroids ( 500 mg mp day 0 and 1 , none thereafter ) , mycophenolate mofetil ( MMF ) maintenance ( 500 mg b.i.d ) and sirolimus ( concentration controlled 8–12 ng/mL ) . With a mean follow‐up of 15.9 months , patient survival is ( 21/22 ) 96 % and graft survival ( 19/22 ) 87 % . Acute rejections occurred in ( 8) 36.3 % ( two humoral ) . Of 19 surviving grafts , 18 ( 95 % ) remain steroid and 15 ( 79 % ) CNI‐free . At 1 year , mean creatinine was 1.43 mg/dL. Overall infection rates were low , but 2 patients developed severe acute respiratory distress syndrome ( ARDS ) at month 3 and 7 , respectively , result ing in mortality in one and a graft loss in the other . No cancer or PTLD was observed . Leukopenia was common and MMF dose was reduced or eliminated in 6/22 ( 27 % ) patients . The reported higher than expected rate of acute rejection , leukopenia and possible pulmonary toxicity suggests excessive morbidity . Modifications such as an initial period of CNI use should be considered Background Kidney transplantation from DCD now represents a significant part of the overall transplant activity in the UK . Outcome of different induction immunosuppression regimes and related cost benefit analysis has been reported by very few studies . This is a single centre study on frequency-matched patients who received a DCD kidney transplant between August 2007 and August 2009 . Methods Data on 45 patients divided in 2 groups were collected prospect ively and analyzed retrospectively . Group A ( 24 patients ) received IL2Mab and Group B ( 21 patients ) ATG as induction immunosuppression . Patient and graft survival were similar in both groups . Results In the ATG-induced group , there was a significant lower rate of DGF , BPAR , and infections requiring readmission . A cost analysis was performed including all immunosuppression-related costs , and it has shown remarkable savings in the ATG-induced group . Conclusion Considering that the number of DCD kidney transplants is destined to rise in the UK , we believe that ATG is a valid option to continue optimizing outcomes of DCD kidney transplant . In our experience , ATG proved to be safe , effective , and contributed to significant cost savings The 6 month prospect i ve , r and omized study compared the steroid-sparing potential of two tacrolimus-based regimens after renal transplantation . A total of 489 patients were r and omized ( 1:1 ) to receive tacrolimus/mycophenolate mofetil (MMF)/steroids ( n = 243 ; group Tac/MMF/S ) or tacrolimus/azathioprine/steroids ( n = 246 ; group Tac/Aza/S ) . At 3 months , steroids were tapered off in 267 ( 54.6 % ) patients free from steroid-resistant acute rejection and with serum creatinine concentrations < 160 micromol/l . The incidence of biopsy-confirmed acute rejection at month 3 was lower in group Tac/MMF/S compared with group Tac/Aza/S ( 18.1 % vs. 26.0%,P = 0.035 ) . Moreover , more patients in the Tac/MMF/S group met the criteria for steroid withdrawal than in the Tac/Aza/S group ( 60.5 % vs. 48.8 % ; P < 0.01 ) . The incidence of acute rejection during months 4 - 6 was low in all groups , both for patients on steroid-free dual therapy ( Tac/MMF : 2.7 % , Tac/Aza : 0.8 % ) and for patients who continued steroid maintenance therapy ( Tac/MMF/S : 3.5 % , Tac/Aza/S : 7.1 % ) . Moreover , kidney function was well preserved in steroid-free patients with month 6 median serum creatinine levels of 119.5 micromol/l ( Tac/MMF ) , and 115.1 micromol/l ( Tac/Aza ) . For patients who continued to receive steroids , month 6 median creatinine levels were 130.5 micromol/l ( Tac/MMF/S ) and 132.8 micromol/l ( Tac/Aza/S ) . The criteria for the selection of patients to discontinue steroids were adequate . Both tacrolimus-based regimens allowed the safe discontinuation of steroids in low-risk patients at month 3 . The Tac/MMF combination was superior in the prevention of acute rejections and more patients met the chosen criteria for steroid withdrawal Background The use of mycophenolate mofetil ( MMF ) is associated with less acute rejection than azathioprine ( AZA ) early after kidney transplantation . However , the long-term impact of MMF versus AZA is less well studied . Methods The Tricontinental Mycophenolate Mofetil Renal Transplantation Study was a double-blind r and omized placebo-controlled trial of MMF versus AZA , together with cyclosporine and steroids , first reported in 1996 . We analyzed the long-term outcomes of the Australian cohort of patients enrolled in this study using follow-up data from the Australia and New Zeal and Dialysis and Transplant Registry . Patient and graft survival , cancer incidence , and estimated kidney function were compared on an intention-to-treat basis . Results A total of 133 Australian patients participated in the study : 45 were r and omized to AZA , 44 were r and omized to MMF 2 g/d , and 44 were r and omized to MMF 3 g/d . Baseline characteristics were similar between the groups . Median follow-up was 13.8 years , during which there were 97 graft failures , 75 deaths , and 1 lost to follow-up . There were no statistically significant differences between the groups in long-term patient or graft survival , cancer incidence , or kidney function . Death-censored graft survival was best in the group with 3 g/d MMF and worst in the group with 2 g/d MMF . By 5 years , 42 % of the MMF group had switched permanently to AZA , whereas crossover from AZA to MMF was rare . Conclusions This long-term examination , although limited by small numbers , found little evidence for the superiority of MMF over AZA BACKGROUND The aim of this work was to investigate the benefit of basiliximab induction therapy in living-related-donor kidney transplantation . METHODS One hundred adult recipients of a first kidney allograft were r and omized into two treatment groups , one to receive basiliximab and the second as a control . All patients received maintenance triple immunosuppressive therapy ( steroids , cyclosporine microemulsion and azathioprine ) . The patients were followed up for a minimum of three years . The end points for evaluation included the incidence of acute rejection episodes , severity of rejection , cumulative steroid dose , patients ' and graft survival . RESULTS Basiliximab significantly reduced the proportion of patients who experienced an acute rejection in the first year ( 18/50 ) compared to the control group ( 31/50 ) . At three years there were 26 acute rejections in the basiliximab group and 36 in control group . The cumulative steroid dose at three and 12 months was significantly lower in the basiliximab group . The overall incidence of post-transplant complications was comparable in the two groups . CONCLUSIONS Prophylactic basiliximab is well tolerated and significantly reduces the incidence of acute rejection episodes in living-related-donor kidney transplantation Vascular disease and chronic allograft nephropathy have prompted re-evaluation of steroids and calcineurin inhibitors ( CNIs ) in renal transplantation . Sirolimus ( SRL ) can facilitate early CNI withdrawal . We report on the Early CNI and Steroid Elimination in Leeds ( ECSEL ) study , which was terminated early due to poor tolerability of SRL . Basiliximab/methylprednisolone induction was used , then 2 months of tacrolimus ( TAC ) and mycophenolate mofetil ( MMF ) treatment . A total of 51 patients were r and omized to continue TAC/MMF or switch to SRL/MMF . In ECSEL1 , patients were switched at 2 months ( n=10 ) . In ECSEL2 , SRL was introduced at months 4–6 and TAC was tapered ( n=13 ) . Median overall follow up was 701 days . All 10 ECSEL1 and 10 of 13 ( 77 % ) ECSEL2 patients discontinued SRL due to adverse events , including leucopenia , rash , mucosal ulceration , arthralgia , and possible pneumonitis . Mean end-of- study creatinine was comparable in all groups . Sirolimus should be used with caution in complete CNI and steroid withdrawal , due to the result ant intolerable adverse event profile An exploratory , post hoc analysis was performed using data from a prospect i ve , multicenter , open‐label , r and omized , two‐period ( 14 d per period ) , two‐sequence , crossover , steady‐state pharmacokinetic study comparing generic tacrolimus ( S and oz ) vs. reference tacrolimus in stable renal transplant patients receiving their pre‐ study twice‐daily dose . Pharmacokinetic parameters were compared in 68 patients according to gender , African American ethnicity , the presence or absence of diabetes , and use of steroids . The ratios of tacrolimus AUC0–12 h , Cmax , and C12 with generic vs. reference tacrolimus were calculated using the geometric mean ( GM ) of dose‐normalized values at days 14 and 28 . Mean ( SD ) tacrolimus dose at baseline was 5.7 ( 4.2 ) mg/d . There were no consistent differences in dose‐normalized AUC0–12 h , C12 , Cmax , or tmax between the generic and reference preparations within sub population s. The 90 % confidence intervals ( CI ) for the ratios of dose‐normalized AUC0–12 h and C12 with generic vs. reference tacrolimus were within 80–125 % for all sub population s , as were 90 % CIs for Cmax other than for females , African Americans , and non‐diabetics , which is not unexpected given the wide variability of tacrolimus Cmax and the small sub population sizes . These exploratory results suggest that this generic tacrolimus preparation would be expected to offer comparable bioavailability to the reference drug in these patient sub population Despite reduced risk of acute rejection and increased 1-year graft survival with modern immunosuppressive regimens , chronic allograft nephropathy and death with a functioning graft remain major causes of allograft loss beyond the first year post-transplant . Anti-rejection agents may influence renal transplant outcome not solely through their immunosuppressive activity but also through their effects on other prognostic risk factors . We have analysed 6-year follow-up data from 232 renal transplant recipients r and omized to treatment with tacrolimus or cyclosporin microemulsion at the University Hospital of Wales , Cardiff . Tacrolimus-based therapy was associated with a more favourable cardiovascular risk profile than therapy with cyclosporin microemulsion , with an improved lipid profile , lower arterial blood pressure and lower homocysteine levels . Renal function at 1-year post-transplant is probably the most significant factor influencing long-term graft survival . In our analyses , renal function determined by the glomerular filtration rate was significantly better in tacrolimus-treated patients from month 3 post-transplant . Moreover , normal renal function was maintained throughout a 5-year follow-up in a significantly higher proportion of non-rejecting patients treated with tacrolimus than with cyclosporin microemulsion ( 58 versus 10 % , respectively , at 5 years ; P=0.002 ) . Morphometric analysis of protocol biopsies revealed that the degree of interstitial fibrosis , similar in both treatment groups at baseline , was significantly greater in the cyclosporin microemulsion group over 12 months . Importantly , patients receiving tacrolimus had significantly greater 6-year graft survival ( 81 versus 60 % , P=0.0496 ) and a higher projected graft half-life ( 15 versus 10 years ) than those receiving cyclosporin microemulsion . Tacrolimus treatment is associated with a significantly better cardiovascular risk profile and superior renal function compared with cyclosporin microemulsion treatment , which appears to translate into improved long-term graft survival Between May 2001 and January 2003 , 132 live donor renal allotransplant recipients were included in a prospect i ve , r and omized controlled trial where they were divided into two groups . All patients received steroids and basiliximab induction therapy . For maintenance immunosuppression , tacrolimus and sirolimus were used in group A. In group B , mycophenolate mofetil ( MMF ) and sirolimus were utilized . Patients were followed up for a minimum of 24 months . One‐year patient and graft survival rates were not significantly different between group A ( 96.9 % , 92.3 % ) and group B ( 100 % , 98.4 % ) , respectively . However , the incidence of biopsy‐proven acute rejection was less in group B but the difference was not statistically significant ( 13.5 % vs. 18.5 % in group A ) . Statistically significant better renal function was encountered among group B patients at two years post‐transplantation as measured by serum creatinine ( 1.25 vs. 1.43 mg/dl ; P = 0.017 ) and calculated glomerular filtration rate ( GFR ) ( 94.9 vs. 79.6 ml/min ; P = 0.005 ) . One year protocol biopsies showed insignificant differences relative to chronic allograft damage index ( CADI ) between either group ( Group A : 2.41 vs. Group B : 2.69 ; P = 0.436 ) . Conclusion : Similar outcome was noted among patients in whom calcineurin inhibitors were not included in their immunosuppressive regimen . The long term impact of this observation on graft survival and function needs longer follow up OBJECTIVE In spite of increases in short-term kidney transplant survival rates and reductions in acute rejection rates , increasing long-term graft survival rates remains a major challenge . The objective here was to project long-term graft- and survival-related outcomes occurring among renal transplant recipients based on short-term outcomes including acute rejection and estimated glomerular filtration rates observed in r and omized trials . METHODS We developed a two-phase decision model including a trial phase and a Markov state transition phase to project long-term outcomes over the lifetimes of hypothetical renal graft recipients who survived the trial period with a functioning graft . Health states included functioning graft stratified by level of renal function , failed graft , functioning regraft , and death . Transitions between health states were predicted using statistical models that accounted for renal function , acute rejection , and new-onset diabetes after transplant and for donor and recipient predictors of long-term graft and patient survival . Models were estimated using data from 38,015 renal transplant recipients from the United States Renal Data System . The model was populated with data from a 3-year , r and omized phase III trial comparing belatacept to cyclosporine . RESULTS The decision model was well calibrated with data from the United States Renal Data System . Long-term extrapolation of Belatacept Evaluation of Nephroprotection and Efficacy as Firstline Immunosuppression Trial was projected to yield a 1.9-year increase in time alive with a functioning graft and a 1.2 life-year increase over a 20-year time horizon . CONCLUSIONS This is the first long-term follow-up model of renal transplant patients to be based on renal function , acute rejection , and new-onset diabetes . It is a useful tool for undertaking comparative effectiveness and cost-effectiveness studies of immunosuppressive medications Introduction . This study examines the efficacy and toxicity of sirolimus used as primary immunosuppression in combination with reduced dose tacrolimus ( calcineurin inhibitor [CI]-sparing regimen ) or mycophenolate mofetil ( CI-free regimen ) in high-risk cadaveric renal transplantation . Methods . Seventy subjects were treated in a quadruple sequential protocol in which 41 were treated with a CI-sparing regimen and 29 were treated with a CI-free regimen . The efficacy and toxicity profiles of these regimens were prospect ively monitored and compared . Results . The study consisted of African Americans ( 71 % ) , cadaveric donors ( 100 % ) , donors aged more than 50 years ( 30 % ) , and patients with delayed graft function ( 47 % ) . At 1 year , patient survival , graft survival , and incidence of biopsy-proven acute rejection were 98 % , 80 % , and 10 % , respectively , in the CI-sparing group and 100 % , 89 % , and 7 % , respectively , in the CI-free group . Three-month protocol biopsies were performed in 41 % ( 17/41 ) and 67 % ( 20/29 ) of the subjects in the CI-sparing and CI-free groups , respectively . Sub clinical rejection was detected in 6 % ( 1/17 ) and 15 % ( 3/20 ) of the subjects in the CI-sparing and CI-free groups , respectively . Histologic evidence of chronic allograft nephropathy was more prevalent in the CI-sparing group . At 1 year , the mean estimated creatinine clearance was higher in the CI-free group than in the CI-sparing group ( 72.4±20.0 mL/min vs. 50.5±20.8 mL/min , P < 0.01 ) . The two regimens had similar toxicity profiles ( hospital readmission , infection , wound complications , and metabolic complications ) . Conclusions . Both sirolimus-based CI-sparing and CI-free regimens are safe and effective in a population with high immunologic risk . The CI-free regimen is associated with better renal function at 1 year post-transplant . Long-term follow-up will aid in determining the risk and benefit ratio of these regimens Everolimus 1.5 or 3 mg/day was compared with mycophenolate mofetil ( MMF ) 2 g/day in a r and omized , multicenter 36‐month trial in de novo renal allograft recipients ( n = 588 ) receiving cyclosporine microemulsion ( CsA ) and corticosteroids . The study was double‐blind until all patients had completed 12 months , then open‐label . By 36 months , graft loss occurred in 7.2 , 16.7 and 10.7 % of patients in the everolimus 1.5 , 3 mg/day , and MMF groups , respectively ( p = 0.0048 for everolimus 1.5 mg/day vs. 3 mg/day ) ; efficacy failure ( biopsy‐proven acute rejection ( BPAR ) , graft loss , death or lost to follow‐up ) occurred in 33.0 , 38.9 and 37.2 % of patients ( p = 0.455 overall ) , respectively . Mortality and incidence of BPAR were comparable in all groups . Creatinine values were higher in everolimus groups , requiring a protocol amendment that recommended lower CsA exposure . Diarrhea , lymphocele , peripheral edema and hyperlipidemia were more common among everolimus‐treated patients , whereas viral infections , particularly cytomegalovirus infection , increased in the MMF group . Overall safety and tolerability were better with MMF and everolimus 1.5 mg/day than with everolimus 3 mg/day . In conclusion , at 36 months , an immunosuppressive regimen containing everolimus 1.5 mg/day had equivalent patient , and graft survival and rejection rates compared with MMF in de novo renal transplant recipients , whereas everolimus 3 mg/day had inferior graft survival . Renal dysfunction in everolimus cohorts necessitates close monitoring Mycophenolate mofetil ( MMF ) , a new immunosuppressant that selectively inhibits proliferation of T and B lymphocytes , may reduce the frequency and severity of acute graft rejection . Acute graft rejection is the leading cause of graft loss in cadaveric renal transplantation . The purpose of this r and omized , double-blind , multicenter study was to evaluate the efficacy and safety of MMF for the prevention of acute rejection episodes in adult patients during the first 6 months after renal transplantation . A total of 499 patients who were to receive a primary cadaveric renal allograft as their first transplant were r and omized to receive MMF 1.0 g b.i.d . ( MMF 2 g treatment group ) , MMF 1.5 g b.i.d . ( MMF 3 g treatment group ) , or azathioprine 1 - 2 mg/kg/day . CsA , corticosteroids , and antithymocyte globulin ( ATGAM ) were administered as part of a quadruple sequential induction protocol . The primary efficacy endpoint was biopsy-proven rejection or treatment failure ( defined as graft loss , death , or premature withdrawal from the study for any reason ) during the first 6 months after transplant . All enrolled patients were included in the primary analyses of efficacy on the basis of intent to treat . The 495 patients who received study drug were included in the safety and secondary efficacy analyses . Biopsy-proven acute rejection episodes or treatment failure occurred in 47.6 % of patients in the azathioprine group compared with 31.1 % ( P = 0.0015 ) and 31.3 % ( P = 0.0021 ) of patients in the MMF 2 g and 3 g treatment groups , respectively . Time to first biopsy-proven rejection episode or treatment failure was significantly longer for MMF 2 g versus azathioprine ( P = 0.0036 ) and MMF 3 g versus azathioprine ( P = 0.0006 ) . First biopsy-proven rejection alone occurred in 38.0 % of patients who received azathioprine compared with 19.8 % and 17.5 % of patients who received MMF 2 g and 3 g , respectively . Patients in the azathioprine group received a greater number of full courses of antirejection treatment as compared with the MMF 2 g and MMF 3 g groups ( 44.5 % , 24.8 % , and 21.1 % , respectively ) . The use of antilymphocyte agents to treat rejection was greater in the azathioprine group ( 20.1 % ) compared with the MMF 2 g group ( 10.3 % ) and the MMF 3 g group ( 5.4 % ) . At 6 months after transplant , graft and patient survival were similar in all 3 treatment groups . ( ABSTRACT TRUNCATED AT 400 WORDS Chronic allograft nephropathy ( CAN ) is the main cause of graft failure after the first year of transplantation Calcineurin inhibitors improve acute rejection rates and short‐term graft survival in renal transplantation , but their continuous use may be deleterious . We evaluated the 5‐year outcomes of sirolimus ( SRL ) versus cyclosporine ( CsA ) immunosuppressive treatment . This observational study was an extension of the SPIESSER study where deceased donor kidney transplant recipients were r and omized before transplantation to a SRL‐ or CsA‐based regimen and followed up 1 year . Data from 131 ( 63 SRL , 68 CsA ) out of 133 patients living with a functional graft at 1 year were collected retrospectively at 5 years posttransplant . Seventy percent of CsA patients versus 54 % of SRL patients were still on the allocated treatment at 5 years ( p = 0.091 ) , most discontinuations in each group being due to safety issues . In intent‐to‐treat , mean MDRD eGFR was higher with SRL : 54.2 versus 45.3 mL/min with CsA ( p = 0.019 ) ; SRL advantage was greater in on‐treatment analyses . There were no differences for patient survival ( p = 0.873 ) , graft survival ( p = 0.121 ) and acute rejection ( p = 0.284 ) . Adverse events were more frequent with SRL ( 80 % vs. 60 % , p = 0.015 ) . Results confirmed the high SRL discontinuation rate due to adverse events . Nevertheless , a benefit was evidence d on renal function in patients ( more than 50 % ) still on treatment at 5 years Background . We report the 5-year outcomes from a r and omized prospect i ve trial in primary adult renal allograft recipients , design ed to evaluate calcineurin inhibitor (CNI)-free immunosuppression on kidney transplant function . Methods . Sixty-one patients were r and omized to either sirolimus ( n=31 ) or cyclosporine ( n=30 ) after basiliximab induction and mycophenolate mofetil ( MMF ) with steroids . Sirolimus was concentration controlled at 10–12 ng/mL for at least 6 months . Results . After 5 years , sirolimus-MMF-steroids compared to cyclosporine-MMF-steroids provides similar patient survival ( 87.1 vs. 90 % , P=0.681 ) , acute rejection rates ( 12.9 vs. 23.3 % , P=0.22 ) , total cholesterol ( 209.1 vs. 204.3 mg/dL , P=0.973 ) , urine protein/creatinine ratios ( 0.398 vs. 0.478 mg/dL , P=0.72 ) , and overall medical and surgical morbidity ( P = NS ) . Although unadjusted patient survival was similar , sirolimus based CNI-free patients had longer death censored graft survival ( 96.4 vs. 76.7 % , P=0.0265 ) , higher glomerular filtration rate ( GFR ) by the abbreviated Modified Diet in Renal Disease ( 66.7 vs. 50.7 cc/min , P=0.0075 ) , and fewer graft losses from chronic allograft nephropathy . The Banff chronic scores at two years were strong predictors of 5-year GFR . At 5 years , there were six de novo ( three solid organ , three skin ) cancers in the CNI group and only two de novo ( one skin , one leukemia , no solid organ ) cancers in the sirolimus group ( P = NS ) . Conclusions . This study of low to moderate risk patients demonstrates that excellent 5-year kidney transplant outcomes can be achieved without CNI drugs , when therapeutic drug monitoring of sirolimus is employed . The application of CNI drug avoidance protocol s to high-risk recipients ( retransplants , highly sensitized , etc . ) , extrarenal allograft recipients , or alternative drug regimens such as steroid or MMF elimination should be subjected to controlled trials High pretransplantation sCD30 levels have been shown to be associated with lower 5-year kidney graft survival in mainly Cyclosporine A (CsA)-treated recipients ( Collaborative Transplant Study data base ) . To analyze the effect of different immunosupressive regimens ( CsA/Azathioprine [ Aza ] , CsA/Mycophenolate Mofetil [ MMF ] , Tacrolimus [Tacr]/Aza ) on sCD30 , we assessed serum sCD30 and neopterin together with in vitro cytokine responses in a prospect i ve r and omized study of 84 renal transplant recipients before , 4 months , and 1 year after transplantation . Panel-reactive antibody ( PRA ) formation , HLA matching , ATG induction therapy , and acute rejections had no impact on sCD30 levels , whereas cytomegalovirus ( CMV ) infections induced an up-regulation of sCD30 4 months posttransplantation ( P = .003 ) . Whereas MMF showed no effect on sCD30 compared with Aza therapy , we found a significant impact of Tacr versus CsA treatment ( 1-year sCD30 > or = 60 U/mL : 14/42 ( 33 % ) , CsA ; 1/38 ( 3 % ) , Tacr ; P < .0005 ) . Chronic rejection 2 years posttransplantation was associated with elevated 1-year sCD30 ( P = .001 ) and neopterin levels ( P = .006 ) . Our data indicate that the Th2 activation marker sCD30 provides a risk factor for chronic rejection independent of classical immunological risk factors and may be down-regulated using Tacr treatment Introduction . This study evaluated whether cyclosporine ( CsA ) could be eliminated from a sirolimus ( Rapamune , rapamycin , SRL)-CsA-steroid ( ST ) regimen at 3 months . Methods . This was an open-label study conducted in Europe , Australia , and Canada . Upon enrollment , 525 primary ( 90 % ) or secondary ( 10 % ) renal allograft recipients with cadaveric ( 89 % ) or living ( 11 % ) donors received 2 mg of sirolimus ( troughs>5 ng/ml ) , CsA , and steroids . At 3 months±2 weeks , eligible patients were r and omized ( 1:1 ) to remain on SRL-CsA-ST or to have CsA withdrawn and therapy continued with SRL ( troughs 20–30 ng/ml)-ST . Results . At 12 months , overall graft and patient survival were 89.1 % and 94.9 % , respectively . In the 430 ( 82 % ) r and omized patients , there was no difference in graft survival ( 95.8 % vs. 97.2 % , SRL-CsA-ST vs. SRL-ST ) or patient survival ( 97.2 % vs. 98.1 % , respectively ) . The incidence of biopsy-confirmed primary acute rejection was 13.1 % during the prer and omization period . After r and omization , the acute rejection rates were 4.2 % and 9.8 % for SRL-CsA-ST and SRL-ST , respectively ( P = 0.035 ) . Renal function ( calculated glomerular filtration rate , 57 vs. 63 ml/min , P < 0.001 ) and blood pressure significantly improved when CsA was withdrawn . Hypertension , CsA nephrotoxicity , hyperuricemia , and Herpes zoster occurred statistically more frequently in patients remaining on CsA , whereas thrombocytopenia , abnormal liver function tests , and hypokalemia were reported more often for SRL-ST therapy . Conclusion . Sirolimus , CsA , and steroids for 3 months posttransplant , followed by elimination of CsA , is a safe and effective alternative to continuous therapy with sirolimus , CsA , and steroids that can result in better renal function and lower blood pressure Background Strategies allowing calcineurin inhibitor minimization while maintaining efficacy may improve renal transplant outcomes . Methods A2309 was a 24-month , phase IIIb , open-label trial of 833 de novo renal transplant recipients r and omized to everolimus , targeting trough concentrations of 3–8 or 6–12 ng/mL plus reduced-exposure cyclosporine A ( CsA ) or to mycophenolic acid ( MPA ) 1.44 g per day plus st and ard-exposure CsA. All patients received basiliximab±corticosteroids . The incidence of the primary composite efficacy endpoint and its components ( treated biopsy-proven acute rejection , graft loss , death , or loss to follow-up ) , renal function ( serum creatinine and estimated glomerular filtration rate ) , and adverse events ( AEs ) were compared at 24 months ; as per the protocol , these analyses were not noninferiority . Results Composite efficacy failure rates ( 95 % confidence interval for difference vs. MPA ) were 32.9 % ( −2.2 % , 13.0 % ) , 26.9 % ( −7.9 % , 6.8 % ) , and 27.4 % at month 24 in the everolimus 3–8 and 6–12 ng/mL and MPA groups , respectively . Mean estimated glomerular filtration rate ( Modification of Diet in Renal Disease ) at month 24 was 52.2 ( −2.1 , 5.5 mL/min/1.73 m2 ) , 49.4 ( −4.8 , 2.7 mL/min/1.73 m2 ) , and 50.5 mL/min/1.73 m2 , respectively . AEs were generally mild to moderate in severity and comparable between the groups . AEs leading to discontinuation were reported in 28.5 % ( P=0.03 vs. MPA ) , 30.6 % ( P=0.007 vs. MPA ) , and 20.5 % of patients receiving everolimus 3–8 and 6–12 ng/mL and MPA , respectively . Conclusions Everolimus trough concentrations targeted to 3–8 ng/mL , along with a greater than 60 % reduction in CsA exposure , was associated with comparable efficacy and renal function versus MPA plus st and ard-exposure CsA over the 2-year period . A significantly higher incidence of AEs led to discontinuation in the everolimus groups compared with the MPA group BACKGROUND To confirm the results of a number of studies conducted in Europe , the United States , and Japan , this multicenter , r and omized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection . METHODS A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus ( n=303 ) or cyclosporine ( n=145 ) in conjunction with azathioprine and low-dose corticosteroids . RESULTS At 12 months after transplantation , tacrolimus therapy was associated with a significant reduction in the frequency of both acute ( tacrolimus 25.9 % vs. cyclosporine 45.7 % ; P<0.001 [ absolute difference : 19.8 % , 95 % confidence interval : 10.0 - 29.6 % ] ) and corticosteroid-resistant rejection ( 11.3 % vs. 21.6 % ; P=0.001 [ absolute difference : 10.3 % , 95 % confidence interval : 2.5 - 18.2 % ] ) . Actuarial 1-year patient ( tacrolimus 93.0 % vs. cyclosporine 96.5 % ; P=0.140 ) and graft survival rates ( 82.5 % vs. 86.2 % ; P=0.380 ) did not differ significantly between the two treatment groups . Overall , the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable . Infections , renal impairment , neurological complications , and gastrointestinal complaints were frequently reported but were mostly reversible in both groups . Higher incidences of elevated serum creatinine , tremor , diarrhea , hyperglycemia , diabetes mellitus , and angina pectoris were reported in the tacrolimus treatment group , whereas acne , arrhythmia , gingival hyperplasia , and hirsutism were more frequent with cyclosporine treatment . CONCLUSIONS The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implication s given the prognostic influence of rejection on graft survival The Mycophenolate Steroids Sparing ( MYSS ) study found that in renal transplant recipients who were on immunosuppressive therapy with the cyclosporine microemulsion Neoral , mycophenolate mofetil ( MMF ) was not better than azathioprine in preventing acute rejection at 21 mo after transplantation and was 15 times more expensive . The MYSS Follow-up Study , an extension of MYSS , was aim ed at comparing long-term outcome of 248 MYSS patients according to their original r and omization to MMF ( 1 g twice daily ) or azathioprine ( 75 to 100 mg/d ) . Primary outcome was estimated GFR at 5 yr after transplantation . Mean 5-yr GFR difference between azathioprine and mycophenolate was 4.67 ml/min per 1.73 m(2 ) ( 95 % confidence interval [ CI ] -0.43 to 9.77 ml/min per 1.73 m(2 ) ; P = 0.07 ) . GFR from month 6 ( mean + /- SEM : 54.3 + /- 1.6 versus 53.9 + /- 1.5 ml/min per 1.73 m(2 ) ; P = 0.83 ) to month 72 after transplantation ( 49.5 + /- 2.2 versus 47.3 + /- 2.4 ml/min per 1.73 m(2 ) ; P = 0.50 ) ; GFR slopes ( mean + /- SEM : -1.10 + /- 0.56 versus -1.23 + /- 0.31 ml/min per 1.73 m(2 ) per year ; P = 0.83 ) ; and 72-mo patient mortality ( 4.0 versus 4.0 % [ P = 0.95 ] ; HR 0.96 ; 95 % CI 0.28 to 3.31 ; P = 0.95 ) , graft loss ( 6.8 versus 6.1 % [ P = 0.82 ] ; HR 0.89 ; 95 % CI 0.32 to 2.46 ; P = 0.83 ) , incidence of persistent proteinuria ( 25.0 versus 27.4 % ; P = 0.72 ) , late ( > 6 mo after transplantation ) rejections ( 25.3 versus 21.2 % ; P = 0.53 ) , and adverse events were similar on azathioprine ( n = 124 ) and MMF ( n = 124 ) , respectively . Outcomes in the two groups were comparable also among patients with or without steroid therapy , considered separately . In kidney transplantation , the long-term risk/benefit profile of MMF and azathioprine therapy in combination with cyclosporine Neoral is similar . In view of the cost , st and ard immunosuppression regimens for kidney transplantation should perhaps include azathioprine rather than MMF BACKGROUND The 1-year results of the Phase III U.S. Multicenter Trial comparing tacrolimus (FK506)- and cyclosporine (CsA)-based immunosuppressive therapy in kidney transplantation revealed a significant reduction in the incidence and severity of acute rejection episodes among patients maintained on tacrolimus . The present report at 5 years of follow-up focuses on the long-term impact of tacrolimus treatment on kidney allograft outcome . METHODS The study protocol permitted crossover of patients to the alternate treatment arm under stringent conditions . The effect of crossover on graft survival was analyzed . Cardiovascular risk factors and serious adverse events were also monitored over 5 years . RESULTS Intent-to-treat analysis revealed equivalent patient and graft survival between treatment arms at 5 years of follow-up ( 79.1 % vs. 81.4 % ; P=0.472 and 64.3 % vs. 61.6 % ; P=0.558 among tacrolimus and CsA-treated patients , respectively ) . However , the rate of crossover was significantly higher among patients r and omized to receive CsA-based therapy ( 27.5 % vs. 9.3 % ; P<0.001 ) . The incidence of treatment failure ( 43.8 % vs. 56.3 % ; P=0.008 ) was significantly lower among tacrolimus-treated patients . Graft survival was significantly improved in the tacrolimus treatment arm when crossover due to rejection was counted as graft failure ( 63.8 % vs. 53.8 % ; P=0.014 ) . Tacrolimus therapy was also associated with a significantly reduced requirement for medications to control hypertension and hyperlipidemia . There was a substantial rate of reversal of tacrolimus-associated insulin dependence . CONCLUSION Tacrolimus-based therapy result ed in significantly reduced risk of graft failure , without an increase in the incidence of adverse events associated with long-term immunosuppression Background . Calcineurin-inhibitor therapy is a contributing factor to the origin of interstitial fibrosis and tubular atrophy ( IFTA ) . Methods . We conducted a prospect i ve r and omized trial of conversion of tacrolimus to sirolimus at 1-month posttransplant in kidney transplant recipients on rapid steroid withdrawal . We compared the chronic changes ( IFTA and sum of Banff chronic scores — Total Score ) on protocol biopsies at 1 month , 1 year , and 2 years in all r and omized patients . We compared the outcomes between treatment groups and analyzed the impact of previous rejection on the chronic changes . Results . We r and omized 122 patients , 62 to sirolimus and 60 to tacrolimus . The 1-year biopsy was performed in 54 patients ( 90 % ) of the tacrolimus group and 56 patients ( 90 % ) of the sirolimus group . The proportion of biopsies with IFTA more than or equal to 2 and the Total Score more than 2 increased over the 2 years but were not different between the study groups at any time point . On the 1-year biopsy , there was more IFTA , and the fraction with Total Score more than 2 was higher in the tacrolimus group with previous rejection . In the cohort without rejection , there was a significant progression of the IFTA and Total Score between 1 and 2 years in both the sirolimus and tacrolimus groups . Conclusion . Conversion from tacrolimus to sirolimus at 1-month posttransplant in kidney transplant recipients on rapid steroid withdrawal does not decrease the progression of chronic changes on protocol biopsies during the first 2 years even in those patients without previous acute rejection INTRODUCTION With the introduction of new immunosuppressive medicines , it has become possible to determine the extent to which nephrotoxic medicines contribute to CAN . The aim of this study is to compare the safety and efficacy of calcineurin inhibitor ( CI ) free immunosuppression in a prospect i ve , r and omized trial comparing sirolimus-mycophenolate mofetil (MMF)-prednisone to tacrolimus- MMF-prednisone . METHODS Patients are r and omized at the time of transplant to receive either tacrolimus ( target level 12 to 15 ng/mL in the first month ) or sirolimus ( target level 12 to 18 ng/mL in the first month ) . All patients also receive MMF ( 750 mg bid ) and prednisone tapered to 10 mg/d by 3 months and thymoglobulin induction ( 1.5 mg/kg/d on days 0 , 1 , 2 , 4 and 6 ) . RESULTS At this point we have 4-month follow-up in 85 patients . The acute rejection rate is 7.5 % ( 3/40 ) in the tacrolimus group and 6.7 % ( 3/45 ) in the sirolimus group . We have discontinued sirolimus in eight patients so far , with wound complications being the most common indication . Renal function appears to be better in the sirolimus group at 1 month after transplantation , but the difference is not statistically significant . CONCLUSIONS While longer follow-up is needed , these results demonstrate that total avoidance of CI can be achieved with extremely low acute cellular rejection rates using sirolimus-based immunosuppression in combination with thymoglobulin , MMF , and prednisone In cyclosporine-based protocol s , everolimus is more effective than azathioprine to reduce acute rejection . Ketoconazole may reduce cyclosporine and everolimus requirements . We compared kidney transplant patients treated with everolimus or azathioprine in a ketoconazole- and cyclosporine-based immunosuppressive regimen . This open-label , prospect i ve trial of low immunologic risk patients . Included one group ( n = 11 ) who received everolimus ( target blood level , 3 - 8 ng/mL ) and the other ( n = 11 ) azathioprine ( 2.0 - 2.5 mg/kg/d ) . Both received steroids , ketoconazole , and cyclosporine with C(0 ) targets ( ng/mL ) in the everolimus group of 200 - 250 , 100 - 125 , and 50 - 65 for months 1 and 2 and thereafter and in the azathioprine group of 250 - 300 in month 1 , 200 - 250 in month 2 , 180 - 200 until month 6 , and 100 - 125 thereafter . Their baseline characteristics were similar . Two biopsy-proven acute rejections occurred in each group . Three-year graft and patient survival in both groups was 100 % . Creatinine clearances at months 6 , 12 , 24 , and 36 were 63.7 + /- 25.4 , 58.9 + /- 24.9 , 56.0 + /- 22.9 , and 57.0 + /- 27.6 in the everolimus group versus 72.6 + /- 20 , 68.6 + /- 21.3 , 71.4 + /- 23.2 , and 68.4 + /- 19.2 in the azathioprine group ( NS for every comparison ) . Major complications were rare and similar in both groups . Five patients in the everolimus group received simvastatin versus 4 in the azathioprine cohort ( P = .53 ) . The average cyclosporine doses to achieve targets were 0.8 - 1.2 mg/kg in the everolimus group and 1.6 - 2.2 mg/kg in the azathioprine group . The average everolimus dose after month 2 was 0.75 - 0.9 mg/d . We concluded that with cyclosporine , ketoconazole , and steroids , everolimus was as effective and safe as azathioprine . Cyclosporine reduction with everolimus did not influence graft survival or function at 3 years Safety and efficacy of two sirolimus (SRL)‐based regimens were compared with tacrolimus ( TAC ) and mycophenolate mofetil ( MMF ) . Renal transplantation recipients were r and omized to Group 1 ( SRL+TAC ; week 13 TAC elimination [ n = 152 ] ) , Group 2 ( SRL + MMF [ n = 152 ] ) or Group 3 ( TAC + MMF [ n = 139 ] ) . Group 2 , with higher‐than‐expected biopsy‐confirmed acute rejections ( BCARs ) , was sponsor‐terminated ; therefore , Group 2 two‐year data were limited . At 1 and 2 years , respectively , graft ( Group 1 : 92.8 % , 88.5 % ; Group 2 : 90.6 % , 89.9 % ; Group 3 : 96.2 % , 95.4 % ) and patient ( Group 1 : 97.3 % , 94.4 % ; Group 2 : 95.2 % , 94.5 % ; Group 3 : 97.0 % , 97.0 % ) survival rates were similar . One‐ and 2‐year BCAR incidence was : Group 1 , 15.2 % , 17.4 % ; Group 2 , 31.3 % , 32.8 % ; Group 3 , 8.2 % , 12.3 % ( Group 2 vs. 3 , p < 0.001 ) . Mean 1‐ and 2‐year modified intent‐to‐treat glomerular filtration rates ( mL/min ) were similar . Primary reason for discontinuation was adverse events ( Group 1 , 34.2 % ; Group 2 , 33.6 % ; Group 3 , 22.3 % ; p < 0.05 ) . In Groups 1 and 2 , delayed wound healing and hyperlipidemia were more frequent . One‐year post hoc analysis of new‐onset diabetes posttransplantation was greater in TAC recipients ( Groups 1 and 3 vs. 2 , 17 % vs. 6 % ; p = 0.004 ) . Between‐group malignancy rates were similar . The SRL‐based regimens were not associated with improved outcomes for kidney transplantation patients The safety and efficacy of concentration-controlled use of sirolimus ( SRL ) and cyclosporine ( CsA ) followed by CsA minimization ( CsAm ) or elimination ( CsAe ) beginning at week 13 was compared in a phase 4 , open-label , r and omized ( 1:1 ) trial of renal transplant recipients enrolled between March 2004 and November 2005 . The primary endpoint was renal function , measured at 12 months using the Nankivell formula , in patients remaining on therapy . Though a total enrollment of 140 patients in each group was planned to provide an 80 % power to detect a difference in means , only 207 subjects were enrolled in this study . Demographic characteristics were similar between groups , with 98.1 % recipients of first grafts , 69.1 % from living donors , and 7.2 % diabetics . At 12 months , there were no differences in renal function ( 61.08 vs 65.24 mL/min , P = .132 ) ; incidence of biopsy-confirmed acute rejection ( 14.3 % vs 22.5 % , P = .152 ) ; and patient ( 89.5 % vs 92.2 % , P = .632 ) , graft ( 87.6 % vs 88.2 % , P = .999 ) , and death-censored graft ( 98.1 % vs 94.1 % , P = .166 ) survivals between CsAm and CsAe groups , respectively . There were no differences in the overall rate of study -drug discontinuation ( 32.4 % vs 36.3 % , P = .562 ) but more patients discontinued because of lack of efficacy/graft loss in the CsAe group ( 4.8 % vs 14.7 % , P = .018 ) . This study was underpowered to demonstrate the superiority of one regimen over the other . In summary , SRL immunotherapy combined with CsA minimization or elimination showed comparative safety and efficacy . Both regimens offer potential treatment options for de novo renal allograft recipients Sirolimus ( SRL ) allows to minimize the use of cyclosporine ( CsA ) , but de novo administration after transplantation is associated with various complications . We report a prospect i ve , open‐label , multicenter r and omized study to evaluate conversion from a CsA‐based regimen to a SRL‐based regimen 3 months after transplantation . One hundred ninety‐two of a total of 237 patients were eligible at 3 months to be converted to SRL ( n = 95 ) or to continue CsA ( n = 97 ) . All patients were also given mycophenolate mofetil ( MMF ) and oral steroids , planned to be discontinued at month 8 . The primary endpoint , the clearance estimated according to Cockcroft and Gault at week 52 , was significantly better in the SRL group ( 68.9 vs. 64.4 mL/min , p = 0.017 ) . Patient and graft survival were not statistically different . The incidence of acute rejection episodes , mainly occurring after withdrawal of steroids , was numerically but not statistically higher in the SRL group ( 17 % vs. 8 % , p = 0.071 ) . Sixteen patients discontinued SRL , mainly for adverse events ( n = 11 ) , and seven patients discontinued CsA for renal failure or acute rejection . Significantly , more patients in the SRL group reported aphthous , diarrhea , acne and high triglyceride levels . Conversion CsA to SRL 3 months after transplantation combined with MMF is associated with improvement in renal function Whether or not a cyclosporine A (CsA)‐free immunosuppressant regimen based on sirolimus ( SRL ) prevents aortic stiffening and improves central hemodynamics in renal recipients remains unknown . Forty‐four patients ( 48 ± 2 years ) enrolled in the CONCEPT trial were r and omized at week 12 ( W12 ) to continue CsA or switch to SRL , both associated with mycophenolate mofetil . Carotid systolic blood pressure ( cSBP ) , pulse pressure ( cPP ) , central pressure wave reflection ( augmentation index , AIx ) and carotid‐to‐femoral pulse‐wave velocity ( PWV : aortic stiffness ) were blindly assessed at W12 , W26 and W52 together with plasma endothelin‐1 ( ET‐1 ) , thiobarbituric acid‐reactive substances ( TBARS ) and superoxide dismutase ( SOD ) and catalase erythrocyte activities . At W12 , there was no difference between groups . At follow‐up , PWV , cSBP , cPP and AIx were lower in the SRL group . The difference in PWV remained significant after adjustment for blood pressure and eGFR . In parallel , ET‐1 decreased in the SRL group , while TBARS , SOD and catalase erythrocyte activities increased in both groups but to a lesser extent in the SRL group . Our results demonstrate that a CsA‐free regimen based on SRL reduces aortic stiffness , plasma endothelin‐1 and oxidative stress in renal recipients suggesting a protective effect on the arterial wall that may be translated into cardiovascular risk reduction Background . It was of interest to compare enteric-coated mycophenolate sodium ( EC-MPS ) versus mycophenolate mofetil ( MMF ) among renal transplant recipients receiving a tacrolimus-based immunosuppressive regimen . Methods . Between December 2004 and February 2006 , a single-center , open-label r and omized trial of MMF ( group A , n=75 ) versus EC-MPS ( group B , n=75 ) was performed in primary renal transplant recipients receiving combined thymoglobulin/daclizumab induction along with reduced tacrolimus dosing and elimination of corticosteroids 1 week postoperatively . The primary endpoint was the incidence rate of acute rejection ( AR ) during the first 12 months posttransplant ; secondary aims were to compare graft and patient survival , renal function , drug dosing and monitoring , gastrointestinal side effects , and other adverse events at 12 months of follow-up . Results . Patient/graft survival in groups A and B were 100%/96 % versus 99%/96 % , respectively ( N.S. ) . At 12 months , a total of nine patients ( 6 % ) experienced biopsy-proven AR , 3 % ( 2/75 ) vs. 9 % ( 7/75 ) in the MMF and EC-MPS arms , respectively ( N.S. ) . At 12 months , the geometric mean*/SE serum creatinine concentration and arithmetic mean±SE calculated glomerular filtration rate in groups A and B , respectively , were 1.30*/1.03 and 61.4±2.0 vs. 1.26*/1.03 and 66.0±2.1 ( N.S. ) . Incidence of new onset diabetes mellitus ( 11 % vs. 11 % ) , infections requiring hospitalization ( 13 % vs. 15 % ) , and gastrointestinal side effects ( 36 % vs. 32 % ) appeared equivalent ( N.S. ) . Conclusions . Early efficacy and toxicity were equivalent between the two study arms . Optimizing either MMF or EC-MPS along with a combined thymoglobulin/daclizumab induction , low tacrolimus dosing and steroid avoidance result ed in a low AR rate and an acceptably high renal function at 12 months Abstract Objective : To compare the cost-utility of exenatide once weekly ( EQW ) and insulin glargine in patients with type 2 diabetes in the United Kingdom ( UK ) . Research design and methods : The IMS CORE Diabetes Model was used to project clinical and economic outcomes for patients with type 2 diabetes treated with EQW or insulin glargine . Treatment effects and patient baseline characteristics ( mean age : 58 years , mean glycohaemoglobin : 8.3 % ) were taken from the DURATION -3 study . Unit costs and health state utility values were derived from published sources . As the price of EQW is not yet known , the prices of two currently available glucagon-like peptide-1 products were used as benchmarks . To reflect diabetes progression , patients started on EQW switched to insulin glargine after 5 years . The analysis was conducted from the perspective of the UK National Health Service over a time horizon of 50 years with costs and outcomes discounted at 3.5 % . Sensitivity analyses explored the impact of changes in input data and assumptions and investigated the cost utility of EQW in specific body mass index ( BMI ) subgroups . Main outcome measures : Incremental cost-effectiveness ratio ( ICER ) for EQW compared with insulin glargine . Results : At a price equivalent to liraglutide 1.2 mg , EQW was more effective and more costly than insulin glargine , with a base case ICER of £ 10,597 per quality -adjusted life-year ( QALY ) gained . EQW was associated with an increased time to development of any diabetes-related complication of 0.21 years , compared with insulin glargine . Three BMI subgroups investigated ( < 30 , 30–35 and > 35 kg/m2 ) reported ICERs for EQW compared with insulin glargine ranging from £ 9425 to £ 12,956 per QALY gained . Conclusions : At the prices investigated , the cost per QALY gained for EQW when compared with insulin glargine in type 2 diabetes in the UK setting , was within the range normally considered cost effective by NICE . Cost effectiveness in practice will depend on the final price of EQW and the extent to which benefits observed in short-term r and omised trials are replicated in long-term use |
12,034 | 30,526,532 | Conclusion A decreased pretreatment haemoglobin level among patients with lung cancer is a prognostic factor of poor survival that can serve as an important indicator in survival prediction , risk stratification and treatment selection . | Background Many studies have reported the prognostic value of haemoglobin level for cancers .
Whereas the prognostic impact of decreased pretreatment haemoglobin level on the survival of patients with lung cancer remains controversial , herein , a systematic review and meta- analysis were conducted to investigate whether a decreased haemoglobin level before treatment is a significant predictor of survival in patients with lung cancer .
Methods We performed a systematic review and meta- analysis of observational studies to evaluate the prognostic impact of a decreased haemoglobin level on the survival of patients with lung cancer . | OBJECTIVES Blood transfusion has been shown to have deleterious effect on lung cancer survival , but little data are available that assess whether leukocyte-depleted ( LD ) blood has a similar adverse effect . Our institution has been using LD red cells since 2001 . We sought to determine whether LD blood has an effect on survival after resection of early-stage lung cancer . METHODS From a prospect i ve data base , we evaluated all patients with pathologic stage I non-small cell lung cancer . Patients receiving LD blood were compared with those receiving no transfusion . Survival was estimated using the Kaplan-Meier method and compared using the log-rank test . Multivariate analysis by Cox regression was used to identify independent risk factors affecting survival . RESULTS From 2001 to 2009 , 361 patients were evaluated ; 63 received LD red cell cell transfusion and 298 received no transfusion . Median follow-up was 48 months . Disease-free survival ( P < .001 ) and overall survival ( P < .001 ) were worse in patients receiving LD blood . Stratifying for stage , disease-free survival continued to be worse with transfusion for stage IA ( P = .002 ) and IB ( P = .002 ) . Similarly , overall survival continued to be worse with transfusion for stage IA ( P < .001 ) and IB ( P < .001 ) . For disease-free and overall survival , univariate analysis revealed increased age , male gender , anemia , transfusion , and higher stage to be adverse factors , with transfusion and higher stage continuing to be significant adverse factors after multivariate analysis . CONCLUSIONS Our data suggest that transfusion of LD blood is associated with a worse disease-free and overall survival in patients with resected stage I non-small cell lung cancer Background Little is known about prognosis of metastatic patients after receiving a first-line treatment and failure . Our group already showed in pre-treated patients enrolled in phase I clinical trials that a performance status ( PS ) > 2 and an LDH > 600 UI/L were independent prognostic factors . In this prospect i ve study , which included 45 patients , we identified clinical and biological variables as outcome predictors in metastatic Non-Small Cell lung cancer after first line chemotherapy were identified . Findings Forty-five patients that were previously treated for metastatic disease from 12/2000 to 11/2005 in the comprehensive cancer centre ( Centre Léon Bérard ) . Clinical assessment and blood parameters were recorded and considered . Patient prognostic factors for overall survival ( OS ) with a 0.05- significance level in univariate analysis were entered in a multivariate Cox model for further analysis . Patients ' median age was 58.5 years ( range : 37 - 76 ) . Sixty two percent of the patients were PS = 0 or 1 . After inclusion , nine patients received second-line ( 22.5 % ) , and two received third-line chemotherapy ( 5 % ) . Univariate analysis showed that the factors associated with reduced OS were : PS > 2 , weight loss > 10 % , more than one line of chemotherapy treatment and abnormal blood parameters ( hemoglobin ( Hb ) , platelet and neutrophils counts ) . Multiple regression analysis confirmed that PS > 2 and abnormal hemoglobin were independent predictors for low overall survival . According to the presence of none ( 33 % ) , 1 ( 37 % ) and 2 ( 30 % ) prognostic factors , median OS were 12 , 5 and 2 months respectively . Conclusion From this prospect i ve study , both PS and anemia were found as independent determinants of survival , we found that both PS and anemia were independent determinants of survival . The combination of poor PS and anemia is an effective strategy to predict survival in the case of patients with metastatic NSCLC receiving further treatment after the first line Purpose To evaluate the efficacy of concurrent radiochemotherapy in patients with stage III non-small cell lung cancer ( NSCLC ) , and to examine the effect of hemoglobin levels on survival of those patients . The negative impact of anemia on survival has been noticed for other cancer sites including the head and neck , and the uterine cervix , but it has been rarely described in NSCLC cancer patients treated with radiotherapy . Methods From April 1995 through March 2002 , 56 patients with inoperable stage III non-small lung cancer were treated with radiotherapy consisting of 60 Gy ( 50 Gy+10 Gy boost ) given in 30 fractions of 2 Gy daily , 5 days a week , over a period of 6 weeks , and concurrent low-dose daily chemotherapy ( CHT ) consisting of 6 mg/m2 of cisplatin given Mondays – Fridays during weeks 1–2 and 5–6 . All patients had stage III disease and ages ranged from 39 to 81 years old ( median 63.9 years ) . Results The 2-year and 3-year survival rates were 34 % and 16 % , respectively . Patients with a pretreatment hemoglobin level superior or equal to 11.6 g/dl had a 2-year survival rate of 52 % as compared to 15.5 % for patients with a pretreatment hemoglobin level inferior to 11.6 g/dl ( p=0.0075 ) . Patients with higher KI ( > 70 % ) showed better survival rates than those with lower KI . Surprisingly , patients in stage IIIA did not survive significantly longer than those in stage IIIB . Hematological toxicity ( grade ≥2 ) prevailed ( 25 % ) , followed by esophageal ( 5.4 % ) and bronchopulmonary ( 2 % ) toxicity . Only three patients experienced acute grade 3 hematological toxicity . Because of acute toxic effects , irradiation was interrupted in 8 patients ( 14.3 % ) for 7–13 days ( median 7.5 days ) . Late high- grade ( ≥3 ) toxicity was not found . No grade 4 toxicity or treatment-related deaths were observed during this study . Conclusion Our data show that concurrent radiotherapy with daily low dose cisplatin is well tolerated , and shows survival rates comparable to more aggressive treatment regimens . A combination of this chemotherapy with accelerated hyperfractionated radiotherapy might improve the results in the future . Furthermore , we could show that the hemoglobin levels prior to therapy have an influence on the prognosis , where lower levels were associated with worse outcome . Further trials should consider supplementation with erythropoietin BACKGROUND : According to the literature , performance status , stage-tumor dimension and nodal status , weight loss , were the most important prognostic factors for survival in patients with locally advanced non-small cell lung cancer . AIM : To evaluate the treatment results and the prognostic variables in our patients treated with sequential and concurrent chemoradiotherapy . MATERIAL AND METHODS : In the study 85 patients were r and omly assigned to one of the two treatment arms . In the sequential arm , 45 patients had previously received sequential chemotherapy with 4 cycles of and etoposide followed by conformal radiotherapy ( RT ) . In the second concurrent group , 40 patients received concomitant chemotherapy of cisplatine and etoposide and conformal RT , followed by two cycles of consolidation chemotherapy of carboplatine and etoposide . We described all phases of the conformal three dimensional ( 3-D ) RT . RESULTS : From October 2005 to March 2008 , 93 patients were enrolled . Eight patients were not eligible , seven had stage IV and one patient had pleural effusion . They were all initially considered to have stage IIIB disease . The median survival was 13 months for the patients in the sequential arm and 19 months for those in the concurrent treatment arm . The differences were statistically significant ( log-rank test p=0.0039 ) . The disease-free survival was 9 months in the sequential arm and 16 months in the concurrent treatment group . The differences were statistically significant ( log-rank test p=0.0023 ) . We found that the following prognostic factors significantly influenced the survival in lung cancer patients treated with conservative method : - age , p<0.05 ; - performant status , p<0.001 ; - weight loss , p<0.001 ; tumor dimension , p<0.05 ; and - nodal involvement , p<0.05 . CONCLUSION : In our study , the dose-limiting toxicity , esophagitis was reduced by performing conformal radiotherapy . Conformal thoracic radiotherapy and new radiotherapy technics , such as respiratory gated radiotherapy , allow dose escalating and may probably improve survival and local control in lung cancer patients Introduction : BR.21 demonstrated significant survival benefit for non-small cell lung cancer patients receiving erlotinib compared with placebo . We undertook to characterize , by exploratory subset analysis , patients less likely to benefit from erlotinib . Methods : Using stratification and potential prognostic factors , Cox regression with stepwise selection with minimum Akaike Information Criteria was used to separate erlotinib patients into risk categories based on 10th , 50th , and 90th percentiles of prognostic index scores . The hypothesis was that characteristics of treated patients in the highest risk group would be predictive of lack of benefit from erlotinib when comparing erlotinib to placebo patients in the same risk group . Results : Ten factors ( smoking history , performance status , weight loss , anemia , lactic dehydrogenase , response to prior chemotherapy , time from diagnosis , number of prior regimens , epidermal growth factor receptor copy , and ethnicity ) were predictive of overall survival for erlotinib-treated patients and were used in the final model . Four risk groups were derived from the index score of the Prognostic Model : Low Risk ( HR = 0.34 , p < 0.001 ) , Intermediate Low and Intermediate High Risk ( HR 0.76 , p = 0.05 ; HR 0.92 ; p = 0.51 ) and High Risk ( HR 1.07 ; p = 0.78 ) . Median survivals for erlotinib ( placebo ) patients in each group were 20.6 ( 8.9 ) , 10.4 ( 7.6 ) , 4.0 ( 4.1 ) , 1.9 ( 2.3 ) months . The trend test showed that higher risk was associated with shorter survival ( p < 0.001 ) and less treatment effect ( p = 0.03 ) . Conclusions : By establishing a prognostic model , we identified a small group of patients who did not seem to benefit from erlotinib in this study . This model requires prospect i ve validation to confirm that it is both prognostic and predictive of outcome We have evaluated the prognostic value of 22 pretreatment attributes in 436 small cell lung cancer ( SCLC ) patients included in a prospect i ve multicenter study with a minimum 5-year follow-up . Pretreatment clinical and laboratory parameters were registered . Possible prognostic factors were evaluated by univariate analysis ( log rank test ) and by the Cox multivariate regression model . In the univariate analysis of all patients , only age , nodal metastasis , and skin metastasis were not associated with survival . The multivariate Cox model identified gender , extent of disease , performance status ( PS ) , weight loss , platelet count , LDH , and NSE as independent prognostic factors . In subset multivariate analyses according to extent of disease , we found haemoglobin level , PS , NSE , and total WBC as significant prognostic indicators for survival in limited-stage disease ( LD-SCLC ) , while PS , weight loss , LDH , number of metastases , liver metastases , and brain metastases were identified as independent prognostic factors in extensive-stage disease ( ED-SCLC ) . There was a significant correlation between serum LDH and NSE levels . In conclusion , gender , extent of disease , PS , weight loss , haemoglobin , WBC count , platelet count , LDH , and NSE were all found to be independent prognostic factors for SCLC survival . However , the prognostic value of these factors depends highly on whether all or subsets of SCLC patients are studied PURPOSE The aim of this study was to analyze prognostic variables associated with long-term survival in patients with stage III non-small-cell lung cancer enrolled in a Spanish Lung Cancer Group ( SLCG ) phase II trial . PATIENTS AND METHODS Between May 2001 and June 2006 , 139 patients were enrolled . The initial design included 3 arms : sequential chemotherapy ( CT ) followed by st and ard thoracic radiation therapy ( TRT ; RT ) , concomitant CT/TRT followed by consolidation CT , or induction CT followed by CT/TRT . Based on the results of the Radiation Therapy Oncology Group 9410 trial , the sequential arm was closed . Induction or consolidation therapy comprised docetaxel plus gemcitabine . Concomitant treatment comprised docetaxel plus carboplatin plus 60 Gy TRT . A univariate and a Cox proportional hazard regression analysis of the following 11 variables were performed : age , sex , Eastern Cooperative Oncology Group performance status ( PS ) , histology , forced expiratory volume in 1 second , disease stage , nodal status , hemoglobin level , completion of RT treatment , completion of induction or consolidation plus concomitant treatment , and RT delay . RESULTS With a median follow-up of 23 months for living patients , median survival was 13.07 months for the consolidation arm and 14.65 months for the induction arm . The 4-year survival rates were 25.37 % and 32.35 % , respectively . Only RT treatment completion ( P < .0001 ) and induction or consolidation plus concomitant treatment completion ( P < .0001 ) were associated with longer survival . CONCLUSION Based on this retrospective analysis of patients enrolled in the SLCG 0008 r and omized phase II study , age , sex , PS , and clinical parameters are not good predictors of overall survival ; however , completion of treatment is needed to achieve long-term results BACKGROUND Lung cancer is one of the most common types of cancer causing high morbidity and mortality worldwide . An increasing incidence of lung cancer has been observed in India . OBJECTIVES To evaluate the clinic- pathological profile and haematological abnormalities associated with lung cancer in Bangalore , India . MATERIAL S AND METHODS This prospect i ve study was carried out over a period of 2 years . A total of 96 newly diagnosed and histopathologically confirmed cases of lung cancer were included in the study . RESULTS Our lung cancer cases had a male to female ratio of 3:1 . Distribution of age varied from 40 to 90 years , with a major contribution in the age group between 61 and 80 years ( 55.2 % ) . Smoking was the commonest risk factor found in 69.7 % of patients . The most frequent symptom was cough ( 86.4 % ) followed by loss of weight and appetite ( 65.6 % ) and dyspnea ( 64.5 % ) . The most common radiological presentation was a mass lesion ( 55 % ) . The most common histopathological type was squamous cell carcinoma ( 47.9 % ) , followed by adenocarcinoma ( 28.1 % ) and small cell carcinoma ( 12.5 % ) . Distant metastasis at presentation was seen in 53.1 % patients . Among the haematological abnormalities , anaemia was seen in 61.4 % of patients , leucocytosis in 36.4 % , thrombocytosis in 14.5 % and eosinophilia in 19.7 % of patients . Haematological abnormalities were more commonly seen in non small cell lung cancer . CONCLUSIONS Squamous cell carcinoma was found to be the most common histopathological type and smoking still remains the major risk factor for lung cancer . Haematological abnormalities are frequently observed in lung cancer patients , anaemia being the commonest of all Background : The aim of the present study was to investigate any prognostic value of pre-treatment anemia , leukocytosis and thrombocytosis in patients with advanced pretreated NSCLC . Methods : A r and omized , multicenter phase II study comparing the IGF-1R modulator AXL with st and ard docetaxel in the treatment of previously treated stage IIIB or IV NSCLC patients was conducted in 2011 - 2013 . Clinical and laboratory data were collected , including serum values for hemoglobin ( Hgb ) , white blood cells ( WBC ) and platelets ( Plt ) at baseline . These hematological parameters were studied in relation to overall survival using Kaplan – Meier product-limit estimates and multivariate Cox proportional hazards regression models . Results : The median overall survival for all patients was 8.9 months . Patients with leukocytosis ( WBC > 9 x 109/L ) had a significantly shorter median overall survival ( 4.2 months ) as compared with those with a WBC ≤ 9 x 109/L at baseline ( 12.3 months ) with a corresponding of HR 2.10 ( 95 % CI : 1.29 - 3.43 ) . Patients with anemia ( Hgb < 110 g/L ) had a non-significant ( p = 0.097 ) shorter median overall survival ( 6.1 months ) as compared with their counterparts with Hgb ≥ 110 g/L at baseline ( 9.4 months ) . As for thrombocytosis ( Plt > 350 x 109/L ) , there was no statistically significant impact on overall survival . Leukocytosis retained its prognostic significance in a multivariate model where other clinical factors such as age , sex and WHO performance status were taken into consideration ( HR : 1.83 , 95 % CI : 1.06 - 3.13 , p = 0.029 ) . Conclusion : Pre-treatment leukocytosis is a strong and independent prognostic marker for shorter overall survival in previously treated stage IIIB or IV NSCLC patients receiving docetaxel or AXL1717 . Combined use of pre-treatment leukocytosis assessment s together with established prognostic factors such as performance status could be of help when making treatment decisions in this clinical setting It has been postulated that transfusions have immunosuppressive effects that promote tumor growth and metastasis . Moreover perioperative anemia is considered an independent prognostic factor on outcome in patients operated for malignancy . We evaluated the influence of red blood cell ( RBC ) transfusions and perioperative anemia on survival in non-small cell lung carcinoma ( NSCLC ) patients . From 1999 through 2005 , 331 consecutive patients , male/female=295/36 ( mean age 64+/-9 years ) , who underwent radical surgery for NSCLC were prospect ively enrolled in this cohort and followed up for a mean of 27.2 months . The overall survival of patients was analyzed in relation to RBC transfusions and perioperative anemia . These parameters were analyzed in the whole cohort of patients and separately for stage I patients . Patients were divided according to perioperative transfusion , into Group A ( transfused ) and Group B ( non-transfused ) and according to the preoperative haemoglobin ( Hb ) level into Group 1(Hb<12g/dl ) and Group 2(Hb > or = 12g/dl ) , respectively . The overall transfusion rate was 25.7 % . Univariate analysis showed that in the whole cohort of patients overall survival was significantly shorter in Group A ( mean 33.6 months , 5-year survival 25.1 % ) compared to Group B ( mean 48.0 months , 5-year survival 37.3 % ) ( p=0.001 ) . It also showed that patients with preoperative Hb level < 12g/dl ( Group 1 ) , ( mean of 33.0 months , 5-year survival 21.3 % ) had shorter survival compared to Group 2 patients ( mean 49.3 months and 5-year survival 40.0 % ) , respectively ( p=0.002 ) . Multivariate analysis in the whole cohort of patients showed that preoperative anemia was an independent risk factor for survival while RBC transfusion was not . In particular for stage I patients , it was shown that RBC transfusion was an independent prognostic factor for long-term survival as detected by multivariate analysis ( p=0.043 ) , while anemia was not . RBC transfusions affect adversely the survival of stage I NSCLC patients , while do not exert any effect on survival of patients with surgically resectable more advanced disease , where preoperative anemia is an independent negative prognostic factor . These findings indicate that RBC transfusion might exert an immunomodulatory effect on patients with early disease while in more advanced stages this effect is not apparent The objective of this retrospective study was to investigate prognostic factors associated with survival of patients with extensive stage small cell lung cancer ( ES-SCLC ) . Included were 200 patients admitted to the Liberation Army General Hospital with a diagnosis of ES-SCLC . The demographics of patients , disease characteristics , pre-treatment biochemical parameters and therapeutic plan were assessed or evaluated . Univariate analysis found that second-line chemotherapy , radiotherapy , and no liver metastasis were associated with improved survival . Tumor response to first-line chemotherapy and normal initial hemoglobin levels were also associated with a survival benefit ( all P-values ≤ 0.0369 ) . Multivariate Cox regression analysis indicated that liver metastasis and the total number of all chemotherapy cycles were independent prognostic factors of survival . The morbidity risk in patients with liver metastasis was 2.52-fold higher than that in patients without liver metastasis ( hazard ratio (HR)=2.52 ( 1.69 - 3.76 ) ; P<0.0001 ) . However , one unit increase in the total number of chemotherapy cycles decreased the risk of death by 0.86-fold ( HR=0.86 ( 0.80 - 0.92 ) ; P<0.0001 ) . Absence of liver metastasis and ability of a patient to receive and tolerate multiple lines of chemotherapy were associated with longer survival BACKGROUND Cisplatin-induced anemia may correlate with adverse events , poor quality of life ( QoL ) , decreased adjuvant chemotherapy ( ACT ) dose intensity , shorter relapse-free survival ( RFS ) or overall survival ( OS ) . METHODS The JBR.10 trial demonstrated significantly longer survival with adjuvant cisplatin and vinorelbine ( n=242 ) compared to observation ( n=240 ) in patients with resected NSCLC [ Winton T , Livingston R , Johnson D , Rigas J , Johnston M , Butts C , et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer . N Engl J Med 2005;352(25):2640 - 2 ] . This exploratory analysis evaluates the predictive value of baseline ( in all patients ) and during-treatment ( in ACT arm only ) hemoglobin ( Hb ) levels on OS and RFS when adjusted for prognostic factors . Baseline ( in all patients ) and during treatment ( in ACT arm only ) Hb levels were also correlated with adverse events , QoL , morbidity and ACT dose intensity . RESULTS Baseline Hb did not predict RFS or OS . However , there was a trend to shorter OS ( p=0.1 ) when baseline Hb was < 120g/L. Lower baseline Hb predicted increased hospitalization ( p=0.04 ) and worse QoL ( SOB item , p=0.03 ) but had no impact on adverse events or dose intensity . There was a trend to longer RFS ( p=0.08 ) in patients with lower nadir during-treatment Hb and to longer OS ( p=0.06 ) and RFS ( p=0.08 ) in patients with maximum during-treatment Hb drop > 30 % that was not maintained when ACT dose intensity was included in the model . Maximum during-treatment Hb drop > 30 % correlated with increased lethargy ( p=0.003 ) and worse QoL ( fatigue item , p=0.07 ) . CONCLUSIONS Lower baseline and during-treatment Hb levels seem associated with poorer QoL , fatigue and increased hospitalization . There is a trend for shorter OS in patients with lower baseline Hb levels PURPOSE The aim of this study is to present an analysis investigating the association of patient characteristics with overall survival ( OS ) in individuals with stage III non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Ten prognostic factors were analyzed in 203 patients with NSCLC who were enrolled in a phase III trial conducted by the Hoosier Oncology Group and US Oncology between 2002 and 2006 . Eligible patients had untreated stage III NSCLC , forced expiratory volume in one second ( FEV(1 ) ) > or = 1 liter , baseline performance status of 0/1 , and weight loss < 5 % in 3 months preceding the trial . Univariate analysis , Cox proportional hazards regression , and parametric accelerated failure time models were performed to identify the factors that affected survival duration . Variables analyzed included age ( < 70 years vs. > or = 70 years ) , sex , ethnicity , body mass index , performance status ( 0 vs. 1 ) , FEV(1 ) ( > 2 L vs. 1 - 2 L ) , smoking status ( current vs. never/former ) , hemoglobin ( Hb ) level , use of positron emission tomography scan in staging , and stage ( IIIA vs. IIIB ) . RESULTS Median follow-up was 25.6 months and the median OS was 21.2 months . The univariate analysis showed that Hb levels > or = 12 were associated with an improved survival ( P = .033 ) . The multivariable parametric accelerated failure time model demonstrated the association of FEV(1 ) > 2 L ( P = .014 ) , and higher pretreatment Hb values ( P = .007 ) as independent prognostic factors for OS . Similarly in the Cox regression , survival was influenced by Hb and FEV(1 ) > 2 L. CONCLUSION This analysis suggests that FEV(1 ) > 2 L and higher pretreatment Hb values are associated with improved OS in patients with stage III NSCLC . These factors can be useful in predicting for more favorable outcomes in patients with stage III NSCLC and provide additional information when design ing future studies Predictive models for survival prediction in individual cancer patients following the tumor , node , and metastasis ( TNM ) staging system are limited . The survival rates of patients who share TNM stage diseases are diversified . Therefore , we established a nomogram in which hematological biomarkers and clinical characteristics for predicting the overall survival ( OS ) of nasopharyngeal carcinoma ( NPC ) patients were incorporated . The clinicopathological and follow-up data of 690 NPC patients who were histologically diagnosed histologically at the Sun Yat-sen University Cancer Center between July 2007 and December 2011 were retrospectively review ed . Data was r and omly divided into primary ( n = 460 ) and validation groups ( n = 230 ) . Cox regression analysis was used to identify prognostic factors for building the nomogram in primary cohorts . The predictive accuracy and discriminative ability of the nomogram were measured by the concordance index ( C-index ) and decision curve , and were compared with the TNM staging system , Epstein-Barr virus DNA copy numbers ( EBV DNA ) , or TMN stage plus EBV DNA . The results were internally vali date d by assessment of discrimination and calibration using the validation cohorts at the same institution . Independent factors selected into the nomogram for OS included age [ hazard ratio ( HR ) : 1.765 ; 95 % confidence interval ( CI ) : 1.008 - 3.090 ) ] , TNM stage ( HR : 1.899 ; 95 % CI : 1.023 - 3.525 ) , EBV DNA ( HR : 1.322 ; 95 % CI : 1.087 - 1.607 ) , lactate dehydrogenase level ( LDH ) ( HR : 1.784 ; 95 % CI : 1.032 - 3.086 ) , high sensitivity C-reactive protein ( hs-CRP ) ( HR : 1.840 ; 95 % CI : 1.039 - 3.258 ) , high-density lipoprotein cholesterol ( HDL-C ) ( HR : 0.503 ; 95 % CI : 0.282 - 0.896 ) , hemoglobin ( HGB ) ( HR : 0.539 ; 95 % CI : 0.309 - 0.939 ) and lymphocyte to lymphocyte ratio ( LMR ) ( HR:0.531 ; 95 % CI : 0.293 - 0.962 ) . The C-index in the primary cohort and validation cohort were 0.800 and 0.831 , respectively , and were statistically higher when compared to C-index values for TNM stage ( 0.672 and 0 . 716 ) , EBV DNA ( 0.668 and 0.688 ) , and TNM stage+ EBV DNA ( 0 . 732 and 0 . 760 ) , P < 0.001 for all . Moreover , the decision curve analyses demonstrated that the nomogram model had a higher overall net benefit compared to the TNM staging system , EBV DNA and TNM stage+ EBV DNA . Next , patients were divided into three distinct risk groups for OS based on total points ( TPs ) of the nomogram : a low-risk group ( TPs ≤ 19.0 ) , an intermediate risk group ( 19.0 < TPs ≤ 25.5 ) and a high risk group ( TPs > 25.5 ) , respectively . The nomogram predicting prognosis generated for NPC patients had a higher predictive power compared to the TNM staging system , EBV DNA , and TNM stage+ EBV DNA |
12,035 | 29,318,283 | There was no evidence on the effect of AIS screening on adult health outcomes .
Conclusions and Relevance Screening can detect AIS .
Bracing and possibly exercise treatment can interrupt or slow progression of curvature in adolescence .
However , there is little or no evidence on long-term outcomes for AIS treated in adolescence , the association between curvature at skeletal maturity and adult health outcomes , the harms of AIS screening or treatment , or the effect of AIS screening on adult health outcomes | Importance Adolescent idiopathic scoliosis ( AIS ) , a spinal curvature of 10 ° or more , is the most common form of scoliosis , with a prevalence of 1 % to 3 % .
Curves progress in approximately two-thirds of patients with AIS before skeletal maturity , and large curves ( > 50 ° ) may be associated with adverse health outcomes .
Objective To systematic ally review evidence on benefits and harms of AIS screening for the US Preventive Services Task Force ( USPSTF ) . | Background The effectiveness of bracing patients with IS has not yet been convincingly established due to a lack of RCTs . Some authors suggest that their results confirm that bracing is effective ; others conclude that the effectiveness of bracing is doubtful or recommend a RCT . The aim of this study was to establish whether bracing patients with idiopathic scoliosis ( IS ) in an early stage will result in at least 5 degrees less mean progression of the curvature compared to the control group after two years of follow-up . Methods A r and omized controlled trial was design ed . Eligible patients are girls and boys in the age group 8–15 years whose diagnosis of IS has been established by an orthopedic surgeon , who have not yet been treated by bracing or surgery , and for whom further growth of physical height is still expected based on medical examination and maturation characteristics ( Risser ≤ 2 ) . The Cobb angle of the eligible patient should either be minimally 22 and maximally 29 degrees with established progression of more than 5 degrees , or should be minimally 30 and maximally 35 degrees ; established progression for the latter is not necessary . A total of 100 patients will be included in this trial . The intervention group will be treated with full-time Boston brace wear ; the control group will not be braced . Every four months , each patient will have a physical and an X-ray examination . The main outcomes will be the Cobb angle two years after inclusion and health-related quality of life . Discussion The results of this trial will be of great importance for the discussion on early treatment for scoliosis . Furthermore , the result will also be important for screening for scoliosis policies . Trial registration Nederl and s Trialregister IS RCT Study Design . A consecutive series of female patients with adolescent idiopathic scoliosis treated between 1968 and 1977 , either with distraction and fusion using Harrington rods ( n = 145 ) or with a brace ( n = 122 ) , were followed for at least 20 years after completion of the treatment . Objectives . To determine the long-term outcomes of childbearing and sexual life in women treated for adolescent idiopathic scoliosis , as compared with matched control subjects who did not have scoliosis . Summary of Background Data . The effect of pregnancy on curve progression is not established , and results are contradictory . Few reports exist on the social life ( marriage , childbearing , and sexual function ) of formerly treated individuals with scoliosis . Methods . In this study , 136 surgically treated women ( 94 % ) and 111 brace-treated women ( 91 % ) completed the Scoliosis Research Society (SRS)/MODEM ’s question naire concerning childbearing and sexual life as a part of an unbiased personal follow-up examination . Of these , 129 surgically treated and 105 brace-treated women also underwent a radiographic examination . The Cobb method was used to measure curve size in present and earlier examinations . An age-matched control group of 90 women was r and omly selected and subjected to the same examinations . Results . The mean age for all the groups was 40 years . Of the surgically treated and brace-treated women , 85 % were or had been married , as compared with 82 % of the control women . In the total cohort , 628 pregnancies had occurred . No significant mean difference existed between the groups in the number of children born ( 1.8 for the surgically treated , 1.9 for the brace-treated , and 2 for the control women ) ( P = 0.25 ) . The patients in the brace-treated group had a significantly higher mean age at first pregnancy ( 28 years ) than the control subjects ( 25.9 years ) ( P = 0.011 ) , whereas the age for the surgically treated women ( 26.6 years ) did not differ significantly from that for the brace-treated women . There were no significant differences between the groups in rates for low back pain ( 35 % for the surgically treated , 43 % for the brace-treated , and 28 % for the control group ) or for cesarean section ( 19 % for the surgically treated , 14 % for the brace-treated , and 18 % for the control group ) during the first pregnancy . The rate of vacuum extraction s was higher in the surgically treated group ( 16 % ) than in thecontrol group ( 5 % ) ( P = 0.036 ) or the brace-treated group(8 % ) . Limitation of sexual function from the back was admitted by 33 % of the surgically treated , 28 % of the brace-treated , and 15 % of the control women : surgically treated vs control subjects ( P = 0.0042 ) , brace-treated vs control subjects ( P = 0.026 ) , and brace-treated vs surgically treated subjects ( P = 0.57 , a nonsignificant difference ) . These limitations were largely because of difficulties participating physically in activities or self-consciousness about appearance . Pain was a minor reason for limitation . There was no correlation between progression of the major or lumbar curve and number of pregnancies , or between curve progression and age at first pregnancy . Conclusions . Patients treated for adolescent idiopathic scoliosis appeared to function well with regard to marital status and number of children . The scoliotic curve did not seem to increase as a result of childbearing . Minor problems occurred during pregnancy and delivery . Some patients , however , experienced a slight negative effect in their sexual life Abstract In a 5-year prospect i ve study on idiopathic scoliosis , an attempt was made to eluci date the natural history of the disease and to determine which factors contribute to curve progression . A total of 85,622 children were examined for scoliosis in a prospect i ve school screening study carried out in northwestern and central Greece . Curve progression was studied in 839 of the 1,436 children with idiopathic scoliosis of at least 10 ° detected from the school screening program . Each child was followed clinical ly and roentgenographically for one to four follow-up visits for a mean of 3.2 years . Progression of the scoliotic curve was recorded in 14.7 % of the children . Spontaneous improvement of at least 5 ° was observed in 27.4 % of them , with 80 children ( 9.5 % ) demonstrating complete spontaneous resolution . Eighteen percent of the patients remained stable , while the remaining patients demonstrated nonsignificant changes of less than 5 ° in curve magnitude . A strong association was observed between the incidence of progression and the sex of the child , curve pattern , maturity , and to a lesser extent age and curve magnitude . More specifically , the following were associated with a high risk of curve progression : sex ( girls ) ; curve pattern ( right thoracic and double curves in girls , and right lumbar curves in boys ) ; maturity ( girls before the onset of menses ) ; age ( time of pubertal growth spurt ) ; and curve magnitude ( ≥ 30 ° ) . On the other h and , left thoracic curves showed a weak tendency for progression . In conclusion , the findings of the present study strongly suggest that only a small percentage of scoliotic curves will undergo progression . The pattern of the curve according to curve direction and sex of the child was found to be a key indicator of which curves will progress BACKGROUND CONTEXT The value of scoliosis screening has been recently shown in a multicenter r and omized controlled trial . However , the long-term sustainability of the clinical effectiveness of scoliosis screening as a routine health service remains unknown . PURPOSE The aim of this study was to assess the sustainability of the clinical effectiveness of school scoliosis screening . STUDY DESIGN / SETTING A large population -based cohort study with a 10-year follow-up was conducted . PATIENT SAMPLE A total of 394,401 students who were in the fifth grade during the five academic years from 1995/1996 to 1999/2000 formed five consecutive annual cohorts . The students were eligible for the Hong Kong scoliosis screening program , with their screening history and medical records until their nineteenth birthdays being assessed . OUTCOME MEASURES The outcome measures considered in the study were development of adolescent idiopathic scoliosis by the 19 years of age and the Cobb angle . METHODS The clinical effectiveness of scoliosis screening was assessed by referral rate for radiographic diagnosis , sensitivity , specificity , and predictive values . RESULTS A total of 306,144 students ( 78 % ) participated in scoliosis screening , which used a two-tier system . The prevalence of curves of 20 ° or greater was 1.8 % ( 95 % confidence interval [ CI ] , 1.7 - 1.8 % ) , whereas the referral rate for radiography , the sensitivity , and the positive predictive value ( PPV ) for curves of 20 ° or greater were 4.1 % ( 95 % CI , 4.0 - 4.2 % ) , 91 % ( 95 % CI , 90 - 92 % ) , and 40 % ( 95 % CI , 39 - 41 % ) , respectively . Across the five consecutive annual cohorts , the prevalence and sensitivity for curves of 20 ° or greater increased by 0.23 % ( 95 % CI , 0.21 - 0.25 % ; p<.001 ) and 0.76 % ( 95 % CI , 0.43 - 1.04 % ; p<.001 ) per year , respectively ; however , the PPV was reduced by 1.71 % ( 95 % CI , 1.09 - 2.33 % ; p<.001 ) per year . CONCLUSIONS This report describes the first large population -based study with a long-term follow-up indicating that a scoliosis screening program can have sustained clinical effectiveness in identifying patients with adolescent idiopathic scoliosis needing clinical observation . As the prevalence of adolescent idiopathic scoliosis increases , scoliosis screening should be continued as a routine health service in schools or by general practitioners if there is no scoliosis screening policy Abstract . No results on long-term outcome in terms of health-related quality of life ( HRQL ) have previously been presented for patients treated for adolescent idiopathic scoliosis . A consecutive series of patients with adolescent idiopathic scoliosis , treated between 1968 and 1977 before the age of 21 , either with distraction and fusion using Harrington rods [ surgical treatment group ( ST ) , n=156 ; 145 females and 11 males ] or with a brace [ brace treatment group ( BT ) , n=127 ; 122 females and 5 males ] were followed at least 20 years after completion of the treatment . Ninety-four percent of ST and 91 % of BT patients filled in a question naire comprising the SF-36 , Psychological General Well-Being Index ( PGWB ) , Oswestry Disability Back Pain Question naire , parts of SRS/MODEM 'S question naire and study -specific questions concerning the treatment , as a part of an unbiased personal follow-up examination including radiography and clinical examination . An age- and sex-matched control group of 100 persons was r and omly selected and subjected to the same examinations . The results showed no differences in terms of sociodemographic data between the groups . Both ST and BT patients had a slightly , but significantly , reduced physical function using the SF-36 subscales , SF-36/Physical Component Summary ( PCS ) score as well as the Oswestry Disability Back Pain Question naire compared to the controls . Neither the mental subscales and the Mental Component Summary ( MCS ) score of SF-36 nor the PGWB index showed any significant difference between the groups . Forty-nine percent of ST , 34 % of BT and 15 % of controls admitted limitation of social activities due to their back [ P<0.001 ST vs controls , P=0.0010 BT vs controls , and n.s . ( P=0.024 ) ST vs BT ] , mostly due to difficulties with physical participation in activities or self-consciousness about appearance . Pain was a minor reason for limitation . No correlation was found between the outcome scores and curve size after treatment , curve type , total treatment time or age at completed treatment . Patients treated for adolescent idiopathic scoliosis were found to have approximately the same HRQL as the general population . A minority of the patients ( 4 % ) had a severely decreased psychological well-being , and a few ( 1.5 % ) were severely physically disabled due to the back In a study conducted by the Scoliosis Research Society , 159 girls with a mean age of thirteen years ( range , ten to fifteen years ) who had adolescent idiopathic scoliosis were followed prospect ively until skeletal maturity or until the curve had increased 6 degrees or more . All patients had had an initial curve of 25 to 35 degrees and an apical level between the eighth thoracic and first lumbar vertebrae , inclusive . Of the 159 patients , 120 were observed without treatment and thirty-nine were managed with lateral electrical surface stimulation . The curve progressed at least 6 degrees in eighty patients . There was no apparent difference in the outcome between the patients who were managed with observation only and those who were given electrical stimulation . Logistic regression analysis was performed to determine which of eleven factors were predictive of progression of the scoliotic curve . A Risser sign of 0 or 1 , an apical level cephalad to the twelfth thoracic vertebra , and an imbalance of ten millimeters or less were found to be independently prognostic of progression of more than 6 degrees . A prognostic model that included these three factors and chronological age allowed correct classification of the curve as either progressive or non-progressive in 81 per cent of these patients who had a thoracic or thoracolumbar adolescent idiopathic scoliosis . The positive predictive value was 82 per cent , the negative predictive value was 80 per cent , and the sensitivity and specificity were each 81 per cent AIM The purpose of this r and omized controlled trial was to evaluate the efficacy of the Dynamic SpineCor brace for early idiopathic scoliosis ( 15 ° -30 ° ) compared to the natural evolution of the disease . 68 patients participated in this study ( 32 treated and 36 controls ) with at least 5 years follow-up . METHODS The inclusion criteria were : 1 ) high risk of evolution : family history and /or proven progressive ; 2 ) no significant pathological malformation of the spine ; 3 ) initial Cobb angle between 15 ° and 30 ° ; 4 ) risser 0 , 1 or 2 . Assessment of brace efficacy included the percentage of patients who have 5º or less curve progression and the percentage of patients who have 6º or more progression at skeletal maturity . RESULTS At five-year follow-up a correction was achieved in 50 % of treated patient and only in 9.5 % of controls , stabilization in 42.3 % treated and 47.7 % in controls and progression in 26.9 % for the treated group and 42.8 % for controls . For the control patients we considered as a failure if the Cobb angle worsened by more then 5 ° from the original angle and the patient then received treatment . CONCLUSION The results 5 years after the treatment suggested that the SpineCor brace reduced the probability of the progression of early idiopathic scoliosis comparing with its natural history . Moreover , the positive outcome appears to be maintained in the long term Background : Spinal bracing is widely utilized in patients with moderate severity adolescent idiopathic scoliosis with the goal of preventing curve progression and therefore preventing the need for surgical correction . Bracing is typically initiated in patients with a primary curve angle between 25 and 40 degrees , who are Risser sign 0 to 2 and < 1-year postmenarchal . The purpose of this study is to determine whether nighttime bracing using a Charleston bending brace is effective in preventing progression of smaller curves ( 15 to 25 degrees ) in skeletally immature , premenarchal female patients relative to current st and ard of care ( observation for curves < 25 degrees ) . Methods : Premenarchal , Risser 0 female patients presenting to 2 pediatric orthopaedic specialty practice s for evaluation of idiopathic scoliosis with Cobb angle measurements between 15 and 25 degrees were selected . They were r and omized by location to receive nighttime bending brace treatment or observation . Patients in the observation group were converted to fulltime TLSO wear if they progressed to > 25 degrees primary curve Cobb angle . Curve progression was monitored with minimum 2-year follow-up . Results : Sixteen patients in the observation group and 21 patients in the bracing group completed 2-year follow-up . All patients in the observation group progressed to fulltime bracing threshold . In the nighttime bracing group , 29 % of the patients did not progress to 25 degrees primary curve magnitude . Rate of progression to surgical magnitude was similar in the 2 groups . Conclusions : Risser 0 patients presenting with mild idiopathic scoliosis are at high risk for progression to > 25 degrees primary curve magnitude . Treatment with the Charleston nighttime bending brace may reduce progression to full-time bracing threshold . No difference in progression to surgical intervention was shown between nighttime bracing and observation for small curves . Level of Evidence : Level II — therapeutic study ( prospect i ve comparative study ) Trials often do not succeed in including as many patients as anticipated beforeh and . The aim of this paper was to describe why we were not able to include more than a few patients in our r and omized controlled treatment trial on the effectiveness of bracing patients with idiopathic scoliosis , and to describe which lessons can be learnt . A pilot study on the willingness to participate in such a trial was conducted amongst 21 patients and their parents . A description of how we prepared and design ed this trial , the problems we faced and how we tried to improve the inclusion are given . A total of four patients were included , and 14 refused to participate in an 18-month period . There were a lot less eligible patients than anticipated ( 40 instead of 100 per year ) , and the patients ’ participation rate was much lower than we had found in our pilot study ( 21 % instead of 70 % ) . The trial failed to include more than a few patients because of an overestimation of the number of eligible patients and because a lot less eligible patients were willing to participate compared to our pilot study . One reason for a low participation rate could be that this trial evaluated a frequently used existing treatment instead of a new treatment , and patients and parents might be afraid of not being treated ( despite an intensive secure system for the control arm ) Purpose To evaluate the effect of a programme of active self-correction and task-oriented exercises on spinal deformities and health-related quality of life ( HRQL ) in patients with mild adolescent idiopathic scoliosis ( AIS ) ( Cobb angle < 25 ° ) . Methods This was a parallel-group , r and omised , superiority-controlled study in which 110 patients were r and omly assigned to a rehabilitation programme consisting of active self-correction , task-oriented spinal exercises and education ( experimental group , 55 subjects ) or traditional spinal exercises ( control group , 55 subjects ) . Before treatment , at the end of treatment ( analysis at skeletal maturity ) , and 12 months later ( follow-up ) , all of the patients underwent radiological deformity ( Cobb angle ) , surface deformity ( angle of trunk rotation ) and HRQL evaluations ( SRS-22 question naire ) . A linear mixed model for repeated measures was used for each outcome measure . Results There were main effects of time ( p < 0.001 ) , group ( p < 0.001 ) and time by group interaction ( p < 0.001 ) on radiological deformity : training in the experimental group led to a significant improvement ( decrease in Cobb angle of > 5 ° ) , whereas the control group remained stable . Analysis of all of the secondary outcome measures revealed significant effects of time , group and time by group interaction in favour of the experimental group . Conclusions The programme of active self-correction and task-oriented exercises was superior to traditional exercises in reducing spinal deformities and enhancing the HRQL in patients with mild AIS . The effects lasted for at least 1 year after the intervention ended OBJECTIVE To compare the effect of Scientific Exercises Approach to Scoliosis ( SEAS ) exercises with " usual care " rehabilitation programmes in terms of the avoidance of brace prescription and prevention of curve progression in adolescent idiopathic scoliosis . DESIGN Prospect i ve controlled cohort observational study . PATIENTS Seventy-four consecutive out patients with adolescent idiopathic scoliosis , mean 15 degrees ( st and ard deviation 6 ) Cobb angle , 12.4 ( st and ard deviation 2.2 ) years old , at risk of bracing who had not been treated previously . METHODS Thirty-five patients were included in the SEAS exercises group and 39 in the usual physiotherapy group . The primary outcome included the number of braced patients , Cobb angle and the angle of trunk rotation . RESULTS There were 6.1 % braced patients in the SEAS exercises group vs 25.0 % in the usual physiotherapy group . Failures of treatment in the worst-case analysis were 11.5 % and 30.8 % , respectively . In both cases the differences were statistically significant . Cobb angle improved in the SEAS exercises group , but worsened in the usual physiotherapy group . In the SEAS exercises group , 23.5 % of patients improved and 11.8 % worsened , while in the usual physiotherapy group 11.1 % improved and 13.9 % worsened . CONCLUSION These data confirm the effectiveness of exercises in patients with scoliosis who are at high risk of progression . Compared with non-adapted exercises , a specific and personalized treatment ( SEAS ) appears to be more effective A two-year prospect i ve study was done to assess the prevalence and distribution of various parameters associated with scoliosis in schoolchildren in northwestern and central Greece . A total of 82,901 children ( 41,939 boys and 40,962 girls ) who were nine to fourteen years old were screened for scoliosis . Five thous and eight hundred and three children had clinical signs of scoliosis and , of these , 4185 were referred for posteroanterior radiographs ( to be made with the patient st and ing ) because they had a positive result on the forward-bending test ( a difference of more than five millimeters between the two sides of the torso as measured in the thoracic or thoracolumbar region with use of a ruler and a level plane ) at the time of a second screening . The prevalence of scoliosis ( defined as a curve of 10 degrees or more ) was 1.7 per cent ( 1436 of 82,901 children ) , and most of the curves ( 1255 ; prevalence , 1.5 per cent ) were small ( 10 to 19 degrees ) . The ratio of boys to girls was 1:2.1 over-all but varied according to the magnitude of the curve ( 1:1.5 for curves of less than 10 degrees , 1:2.7 for curves of 10 to 19 degrees , 1:7.5 for curves of 20 to 29 degrees , 1:5.5 for curves of 30 to 39 degrees , and 1:1.2 for curves of 40 degrees or more ) . Thoracolumbar curves were the most common type of curve identified , followed by lumbar curves ; specifically , of the 1436 children who had a curve of at least 10 degrees , 493 ( 34.3 per cent ) had a thoracolumbar curve , 475 ( 33.1 per cent ) had a lumbar curve , 261 ( 18.2 per cent ) had a thoracic curve , and 207 ( 14.4 per cent ) had a double curve . Although most ( 753 ) of these curves were to the left , the left : right ratio varied according to the location of the apex of the curve ( 1:3.1 for thoracic curves , 2.0:1 for thoracolumbar curves , and 3.2:1 for lumbar curves ) . The cost of the screening process was negligible ( estimated at thirty cents per child ) ; however , the decreased number of operative procedures performed in children from the geographical area of our University Hospital , the identification of a large number of previously undiagnosed curves ( eleven of which were treated operatively and 170 of which were treated with a brace ) , and the identification of children who were at high risk for progression were considered important benefits of the school-screening program STUDY DESIGN This study is a follow-up investigation for a consecutive series of patients with adolescent idiopathic scoliosis treated between 1968 and 1977 . In this series , 156 patients underwent surgery with distraction and fusion using Harrington rods , and 127 were treated with brace . OBJECTIVES To determine the long-term outcome in terms of radiologic findings and curve progression at least 20 years after completion of the treatment . SUMMARY OF BACKGROUND DATA Radiologic appearance is important in comparing the outcome of different treatment options and in evaluating clinical results . Earlier studies have shown a slight increase of the Cobb angle in brace-treated patients with time , but not in fused patients . METHODS Of 283 patients , 252 attended a clinical and radiologic follow-up assessment by an unbiased observer ( 91 % of the surgically treated and 87 % of the brace-treated patients ) . This evaluation included chart review s , vali date d question naires , clinical examination , and full-length st and ing frontal and lateral roentgenographs . Curve size was measured by the Cobb method on anteroposterior roentgenograms as well as by sagittal contour and balance on lateral films . The occurrence of any degenerative changes or other complications was noted . An age- and gender-matched control group of 100 individuals was r and omly selected and subjected to the same examinations . RESULTS The mean follow-up times were 23 years for surgically treated group and 22 years for brace-treated group . The deterioration of the curves was 3.5 degrees for all the surgically treated curves and 7.9 degrees for all the brace-treated curves ( P < 0.001 ) . Five patients , all brace-treated , had a curve increase of 20 degrees or more . The overall complication rate after surgery was low : Pseudarthrosis occurred in three patients , and flat back syndrome developed in four patients . Eight of the patients treated with fusion ( 5.1 % ) had undergone some additional curve-related surgical procedure . The lumbar lordosis was less in the surgically treated than in the brace-treated patients or the control group ( mean , 33 degrees vs 45 degrees and 44 degrees , respectively ) . Both surgically treated and brace-treated patients had more degenerative disc changes than the control participants ( P < 0.001 ) , but no significant differences were found between the scoliosis groups . No statistically significant difference in terms of radiographically detectable degenerative changes in the unfused lumbar discs was found between patients fused below L3 or those fused to L3 and above ( P = 0.22 ) . A study on intra- and interobserver measurements of kyphosis , lordosis , and sagittal vertical axis on two films for each patient demonstrated that the repeatability of measuring sagittal plumbline on two different lateral radiographs , with patients moving between radiograms , was unreliable for comparison . CONCLUSIONS Although more than 20 years had passed since completion of the treatment , most of the curves did not increase . The surgical complication rate was low . Degenerative disc changes were more common in both patient groups than in the control group Study Design . A point prevalence survey of 72,699 schoolchildren in four age groups was performed . Objectives . To determine the prevalence rates of idiopathic scoliosis and to compare with a previous prevalence study done 15 years earlier . Summary of Background Data . Prevalence rates for idiopathic scoliosis of 5 ° or more in schoolchildren were established in a study performed in 1982 . There have been no previous data on prevalence rate changes over time . Methods . A total of 35,558 boys and 37,141 girls from r and omly selected schools were screened for scoliosis . Those with scoliometer readings of more than 5 ° underwent radiographic evaluation . Prevalence rates were calculated for scoliosis at a predefined Cobb angle of 10 ° and 5 ° , the latter for comparison with the previous prevalence study . Curve type and distribution , pubertal status , and symptoms were correlated with the prevalence data . Results . Prevalence rates were 0.05 % for girls and 0.02 % for boys at 6 to 7 years of age , 0.24 % for girls and 0.15 % for boys at 9 to 10 years of age , 1.37 % for girls and 0.21 % for boys at 11 to 12 years of age , and 2.22 % and 0.66 % , respectively , for girls and boys at 13 to 14 years of age . The ratio of girls to boys increased from 1.6 at 9 to 10 years of age to 6.4 at 11 to 12 years of age . Thoracolumbar curves were the most common ( 40.1 % ) , followed by thoracic curves ( 33.3 % ) , double/triple curves ( 18.7 % ) , and lumbar curves ( 7.9 % ) . Older children had greater proportions of larger curves . Compared with the previous prevalence study in 1982 , there was a significant increase in the prevalence rate in girls 11 to 12 years of age . Screening of 11- to 12- and 13- to 14-year-old girls detected curves in the range suitable for bracing , with nearly 96 % and 32 % of the age groups , respectively , still amenarche or within a year of menarche , and 57 % and 34 % of the age groups , respectively , having low Risser grade s of 0 , 1 , and 2 . Conclusions . The overall prevalence rate of idiopathic scoliosis in our school population in 1997 was 0.93 % in girls and 0.25 % in boys . The prevalence rates were low at 6 to 7 and 9 to 10 years of age but increased rapidly to 1.37 % and 2.22 % for girls at 11 to 12 and 13 to 14 years ofage , respectively . The prevalence rate increased significantly in 11- to 12-year-old girls over a 15-year period from 1982 to 1997 . Screening of 11- to 12- and 13- to 14-year-old girls identified a significant number who could benefit from brace treatment Thirty-two adolescent girls braced for late onset idiopathic scoliosis at Children 's Hospital , Boston were compared with thirty-two untreated girls from Our Lady 's Hospital for Sick Children , Dublin , Irel and paired on the basis of curve size and site and age at diagnosis . All were Risser 0 at diagnosis . Study period for the braced group was from brace initiation to part-time brace wearing and , for the controls , from diagnosis to last review . There was no statistically significant difference between the groups on any parameter of curve progression . This study raises questions about the efficacy of spinal orthoses in modifying the natural history of late-onset idiopathic scoliosis and removes the ethical problems inherent in a prospect i ve trial in which the only treatment permitted to the control group is surgery A total of 187 r and om cases of untreated idiopathic scoliosis , seen from a minimum of 15 to a maximum of 47 years after the end of growth , were review ed . All curves increased after skeletal maturity ( average progression : 0.4 ° per year ) . Thoracic curves tend to progress more than lumbar , lumbar more than thoracolumbar , and thoracolumbar more than double major curves . Pain was present in 114 cases ( 61 % ) and appeared more frequently in women , after pregnancies , and with fatigue . Cardiopulmonary symptoms were present in 42 patients ( 22 % ) , especially those with thoracic and thoracolumbar curves greater than 40 ° . Psychologic disturbances were found in 35 cases ( 19 % ) , mostly female patients with thoracic curves greater than 40 ° . The cosmetic appearance of these patients at long-term follow-up was better compared with that at the end of growth , even though the curves progressed . Patients with decompensation of the trunk at the end of growth seemed to improve with time . In an unselected group of patients with severe curves a mortality rate of 17 % was found , twice as much as in the Italian general population BACKGROUND The role of bracing in patients with adolescent idiopathic scoliosis who are at risk for curve progression and eventual surgery is controversial . METHODS We conducted a multicenter study that included patients with typical indications for bracing due to their age , skeletal immaturity , and degree of scoliosis . Both a r and omized cohort and a preference cohort were enrolled . Of 242 patients included in the analysis , 116 were r and omly assigned to bracing or observation , and 126 chose between bracing and observation . Patients in the bracing group were instructed to wear the brace at least 18 hours per day . The primary outcomes were curve progression to 50 degrees or more ( treatment failure ) and skeletal maturity without this degree of curve progression ( treatment success ) . RESULTS The trial was stopped early owing to the efficacy of bracing . In an analysis that included both the r and omized and preference cohorts , the rate of treatment success was 72 % after bracing , as compared with 48 % after observation ( propensity-score-adjusted odds ratio for treatment success , 1.93 ; 95 % confidence interval [ CI ] , 1.08 to 3.46 ) . In the intention-to-treat analysis , the rate of treatment success was 75 % among patients r and omly assigned to bracing , as compared with 42 % among those r and omly assigned to observation ( odds ratio , 4.11 ; 95 % CI , 1.85 to 9.16 ) . There was a significant positive association between hours of brace wear and rate of treatment success ( P<0.001 ) . CONCLUSIONS Bracing significantly decreased the progression of high-risk curves to the threshold for surgery in patients with adolescent idiopathic scoliosis . The benefit increased with longer hours of brace wear . ( Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and others ; BRAIST Clinical Trials.gov number , NCT00448448 . ) |
12,036 | 28,580,841 | The pooled toxicity analysis showed that Ofatumumab-based therapy was associated with an increased risk of infusion-related reaction but decreased risk of thrombocytopenia and anemia compared with non-Ofatumumab-based therapy .
Moreover , infections , and infusion-related reaction occurred more frequently in participants with single Ofatumumab studies .
Discussion : Our analysis showed PFS was statistically significantly improved with Ofatumumab-based treatments ( including Ofatumumab alone , Ofatumumab plus chemotherapy ) for CLL compared with observation or chemotherapy-based regimen groups .
Ofatumumab had no statistically significant improvement on the OS of patients with CLL .
The Ofatumumab-based therapy could generally decrease the risk of adverse effects except infusion-related reaction and infections | ABSTRACT Objectives : Increasing numbers of clinical studies have been carried out to investigate the therapeutic effect of Ofatumumab for patients with chronic lymphocytic leukemia ( CLL ) but no studies have yet reported a pooled estimate of the treatment effect .
We performed a meta- analysis of evidence from 13 clinical trials to assess effectiveness and safety of Ofatumumab-based therapy in patients with CLL . | This open-label , phase 1 study evaluated the effects of ofatumumab on QTc intervals , safety , efficacy , B-cell and neutrophil counts , complement levels , and cytokine and chemokine concentrations . Fourteen patients with fludarabine-refractory chronic lymphocytic leukemia received 12 ofatumumab infusions . A higher maximum infusion rate of 400 mL/h was tested at the first two doses and was well tolerated . The 43 % overall response rate was similar to previous data ( 42–51 % ) . B-cell depletion was observed along with complement consumption ; median C2 and CH50 levels appeared lower during monthly dosing in patients who responded . Responding patients appeared to have higher median levels of certain pro-inflammatory cytokines and lower median levels of certain immunotolerant cytokines than patients who did not respond . Ofatumumab-induced complement-dependent cytotoxicity activity can be detected clinical ly by measuring complement and may be associated with clinical activity . The potential relationship between changes in complement or cytokines and clinical response to ofatumumab warrants further study We report the largest retrospective , phase IV non-interventional , observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia . Total number of patients was 103 ; median age was 65 years ( range 39–85 ) . Median number of prior lines of therapy was 4 ( range 1–13 ) , including , in most cases , rituximab- , fludarabine- and alemtuzumab-based regimens ; 13 patients had been allografted . Of 113 adverse events , 28 ( 29 % ) were considered to be directly related to ofatumumab . Grade 3–4 toxicities included neutropenia ( 10 % ) , thrombocytopenia ( 5 % ) , anemia ( 3 % ) , pneumonia ( 17 % ) , and fever ( 3 % ) . Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy . On an intention-to-treat analysis , the overall response rate was 22 % ( 3 complete response , 1 incomplete complete response ) . Median progression-free and overall survival times were 5 and 11 months , respectively . This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia . The complete response rate , however , was low . Therefore , treatment with ofatumumab should be moved to earlier phases of the disease . Ideally , this should be done in combination with other agents , as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine . This study is registered at clinical trials.gov identifier:01453062 There are limited data on retreatment with monoclonal antibodies ( mAb ) in patients with chronic lymphocytic leukaemia ( CLL ) . In a pivotal study , ofatumumab ( human anti‐CD20 mAb ) monotherapy demonstrated a 47 % objective response rate ( ORR ) in fludarabine refractory CLL patients . From this study , a subset of 29 patients who had at least stable disease and then progressed were retreated with eight weekly ofatumumab infusions ( induction treatment period ) , followed by monthly infusions for up to 2 years ( maintenance treatment period ) . The ORR after 8 weeks of induction retreatment was 45 % and 24 % had continued disease control after maintenance at 52 weeks . Efficacy and safety of the retreated patients were compared with their initial results in the pivotal study . Response duration was 24·1 months vs. 6·8 months ; time to next therapy was 14·8 months vs. 12·3 months ; and progression‐free survival was 7·4 months vs. 7·9 months ( medians ) . Upon retreatment , 72 % had infusion reactions , mostly Grade 1–2 . Three patients had fatal infections . In summary , ofatumumab retreatment and maintenance therapy was feasible in patients with heavily pretreated CLL and appeared to result in more durable disease control than initial ofatumumab treatment in this subset of patients who may have a more favourable disease profile Objectives Ofatumumab is a human IgG1κ monoclonal antibody that targets a membrane proximal epitope encompassing the small and large loops of CD20 . This Phase I study evaluated the safety , tolerability , efficacy and pharmacokinetics of ofatumumab monotherapy in Japanese patients with relapsed/refractory B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma . Methods Ofatumumab was administered intravenously weekly for a total of eight doses ( dose escalation : 500 and 1000 mg ) . Six patients ( two chronic lymphocytic leukemia and four small lymphocytic lymphoma ) were enrolled into two dose cohorts ( 500 mg , three patients ; 1000 mg , three patients ) . All six patients received 300 mg ofatumumab at the first infusion and either 500 or 1000 mg at seven subsequent weekly infusions . Results No dose-limiting toxicities or serious adverse events were observed . Grade 3–4 adverse events observed were grade 3 lymphocytopenia ( n = 1 ) and neutropenia ( n = 1 ) . Grade 1–2 infusion-related adverse events leading to temporary interruption of ofatumumab infusion were observed in all six patients on the first infusion day , and all patients completed the planned eight infusions . The overall response rate was 50 % ( 3/6 ) . Conclusions Ofatumumab was well tolerated at doses up to 1000 mg and showed preliminary evidence of activity in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma , warranting further investigations . This study was registered at Clinical Trials.gov ( NCT00742144 ) Despite the recent advances in treatment of CLL with targeted agents such as ibrutinib , availability of nonchemotherapy based therapies is desired . Given the 58 % response rate ( 1996 NCI‐WG criteria ) of single agent ofatumumab in CLL refractory to fludarabine and alemtuzumab , we initiated a phase II trial examining response , safety , and progression‐free survival ( PFS ) of ofatumumab as front‐line monotherapy . Patients enrolled included untreated , symptomatic CLL patients over the age of 65 or those who were inappropriate/did not desire chemotherapy . Two cohorts were enrolled sequentially examining either 1 g ( 33 patients ) or 2 g ( 44 patients ) weekly for 8 weeks followed by maintenance dosing every 2 months for a total of 24 months . Patients receiving 1 g were older than those receiving 2 g , but there were no significant differences in other clinical characteristics . The best overall response rates in the 1 and 2 g patient cohorts were 72 and 89 % ( 1996 NCI‐WG criteria ) , respectively ( 54 and 68 % , respectively , using 2008 IWCLL criteria ) . All but two responses were partial . The 24‐month estimated PFS rates were 46 and 78 % , respectively . Response and PFS was lower in del(17p ) and del(11q ) CLL patients . Differences in PFS between dose cohorts were statistically significant and remained so when adjusting for age or high‐risk cytogenetics . Toxicity of this treatment was mild with only six patients not completing therapy due to toxicity . Ofatumumab induction followed by maintenance therapy in untreated CLL represents a well‐tolerated and active regimen , particularly with the 2 g of ofatumumab . Am . J. Hematol . 91:1020–1025 , 2016 . © 2016 Wiley Periodicals , 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 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 BACKGROUND Ofatumumab is a human anti-CD20 monoclonal antibody that has proven efficacy as monotherapy in refractory chronic lymphocytic leukaemia . We assessed the efficacy and safety of ofatumumab maintenance treatment versus observation for patients in remission after re-induction treatment for relapsed chronic lymphocytic leukaemia . METHODS This open-label , multicentre , r and omised phase 3 study enrolled patients aged 18 years or older from 130 centres in 24 countries who had chronic lymphocytic leukaemia in complete or partial remission after second-line or third-line treatment . Eligible patients had a WHO performance status of 0 - 2 , had a response assessment within the previous 3 months , did not have refractory disease , autoimmune haemolytic anaemia requiring treatment , chronic or active infection requiring treatment , and had not previously received maintenance treatment or autologous or allogeneic stem-cell transplant . Using a r and omisation list generated by a central computerised system and an interactive voice recognition system , we r and omly assigned ( 1:1 ) patients to receive ofatumumab ( 300 mg followed by 1000 mg 1 week later and every 8 weeks for up to 2 years ) or undergo observation . R and omisation was stratified by number and type of previous treatment and remission status after induction treatment ( block size of four ) . Treatment assignment was open label . The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population . We report the results of a prespecified interim analysis after two-thirds of the planned study events ( disease progression or death ) had happened . This trial is closed to accrual but follow-up is ongoing . This trial is registered with Clinical Trials.gov , number NCT00802737 . FINDINGS Between May 6 , 2010 , and June 19 , 2014 , we enrolled 474 patients : 238 patients were r and omly assigned to receive ofatumumab maintenance treatment and 236 to undergo observation . One ( < 1 % ) patient in the ofatumumab group did not receive the allocated intervention ( withdrawal of consent ) . The median follow-up was 19·1 months ( IQR 10·3 - 28·8 ) . Progression-free survival was improved in patients assigned to the ofatumumab group ( 29·4 months , 95 % CI 26·2 - 34·2 ) compared with those assigned to observation ( 15·2 months , 11·8 - 18·8 ; hazard ratio 0·50 , 95 % CI 0·38 - 0·66 ; p<0·0001 ) . The most common grade 3 or higher adverse events up to 60 days after last treatment were neutropenia ( 56 [ 24 % ] of 237 patients in the ofatumumab group vs 23 [ 10 % ] of 237 in the observation group ) and infections ( 31 [ 13 % ] vs 20 [ 8 % ] ) . 20 ( 8 % ) of 237 patients in the ofatumumab group and three ( 1 % ) of 237 patients in the observation group had adverse events that led to permanent discontinuation of treatment . Up to 60 days after last treatment , two deaths related to adverse events occurred in the ofatumumab treatment group and five deaths related to adverse events occurred in the observation group ; no deaths were attributed to the study drug . INTERPRETATION These data are important for the development of optimum maintenance strategies in patients with relapsed chronic lymphocytic leukaemia , notably in the present era of targeted drugs , many of which are to be used until progression The tolerability , efficacy , safety and pharmacokinetic profile of a human anti-CD20 monoclonal antibody , ofatumumab , was evaluated in this phase I/II study in patients with relapsed or refractory B-cell chronic lymphocytic leukemia ( B-CLL ) . This study consisted of two parts . Tolerability was assessed in phase I ( Part A ) , while the overall response rate ( ORR ) was assessed in phase II ( comprising Parts A and B ) . Three patients were enrolled in Part A , and another seven patients were enrolled in Part B. Ofatumumab 300 mg was given at the first infusion , followed by seven weekly and four monthly infusions of 2000 mg . No patients experienced dose-limiting toxicity , and tolerability was confirmed . The ORR was 70 % . The most commonly reported adverse events ( AEs ) were leukopenia , neutropenia , and lymphopenia . No patients discontinued the study due to AEs . Plasma concentrations of ofatumumab prior to the next weekly dose increased steadily over the 8 weeks and did not reach steady state ; with monthly dosing , pre-dose ofatumumab concentrations decreased . Inter-patient variability of pharmacokinetic parameters was larger after the first dose than after the later dose . In conclusion , this phase I/II study suggests that ofatumumab provides favorable safety and efficacy in Japanese/Korean patients with relapsed or refractory B-CLL BACKGROUND Treatment for patients with chronic lymphocytic leukaemia who are elderly or who have comorbidities is challenging because fludarabine-based chemoimmunotherapies are mostly not suitable . Chlorambucil remains the st and ard of care in many countries . We aim ed to investigate whether the addition of ofatumumab to chlorambucil could lead to better clinical outcomes than does treatment with chlorambucil alone , while also being tolerable for patients who have few treatment options . METHODS We carried out a r and omised , open-label , phase 3 trial for treatment-naive patients with chronic lymphocytic leukaemia in 109 centres in 16 countries . We included patients who had active disease needing treatment , but in whom fludarabine-based treatment was not possible . We r and omly assigned patients ( 1:1 ) to receive oral chlorambucil ( 10 mg/m(2 ) ) on days 1 - 7 of a 28 day treatment course or to receive chlorambucil by this schedule plus intravenous ofatumumab ( cycle 1 : 300 mg on day 1 and 1000 mg on day 8 ; subsequent cycles : 1000 mg on day 1 ) for three to 12 cycles . Assignment was done with a r and omisation list that was computer generated at GlaxoSmithKline , and was stratified , in a block size of two , by age , disease stage , and performance status . The primary endpoint was progression-free survival in the intention-to-treat population and assessment was done by an independent review committee that was masked to group assignment . The study is registered with Clinical Trials.gov , number NCT00748189 . FINDINGS We enrolled 447 patients , median age 69 years ( range 35 - 92 ) . Between Dec 22 , 2008 , and May 26 , 2011 , we r and omly assigned 221 patients to chlorambucil plus ofatumumab and 226 patients to chlorambucil alone . Median progression-free survival was 22·4 months ( 95 % CI 19·0 - 25·2 ) in the group assigned to chlorambucil plus ofatumumab compared with 13·1 months ( 10·6 - 13·8 ) in the group assigned to chlorambucil only ( hazard ratio 0·57 , 95 % CI 0·45 - 0·72 ; p<0·0001 ) . Grade 3 or greater adverse events were more common in the chlorambucil plus ofatumumab group ( 109 [ 50 % ] patients ; vs 98 [ 43 % ] given chlorambucil alone ) , with neutropenia being the most common event ( 56 [ 26 % ] vs 32 [ 14 % ] ) . Grade 3 or greater infections had similar frequency in both groups . Grade 3 or greater infusion-related adverse events were reported in 22 ( 10 % ) patients given chlorambucil plus ofatumumab . Five ( 2 % ) patients died during treatment in each group . INTERPRETATION Addition of ofatumumab to chlorambucil led to clinical ly important improvements with a manageable side-effect profile in treatment-naive patients with chronic lymphocytic leukaemia who were elderly or had comorbidities . Chlorambucil plus ofatumumab is therefore an important treatment option for these patients who can not tolerate more intensive therapy . FUNDING GlaxoSmithKline , Genmab BACKGROUND In patients with chronic lymphoid leukemia ( CLL ) or small lymphocytic lymphoma ( SLL ) , a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome . We evaluated the efficacy of ibrutinib , a covalent inhibitor of Bruton 's tyrosine kinase , in patients at risk for a poor outcome . METHODS In this multicenter , open-label , phase 3 study , we r and omly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab . The primary end point was the duration of progression-free survival , with the duration of overall survival and the overall response rate as secondary end points . RESULTS At a median follow-up of 9.4 months , ibrutinib significantly improved progression-free survival ; the median duration was not reached in the ibrutinib group ( with a rate of progression-free survival of 88 % at 6 months ) , as compared with a median of 8.1 months in the ofatumumab group ( hazard ratio for progression or death in the ibrutinib group , 0.22 ; P<0.001 ) . Ibrutinib also significantly improved overall survival ( hazard ratio for death , 0.43 ; P=0.005 ) . At 12 months , the overall survival rate was 90 % in the ibrutinib group and 81 % in the ofatumumab group . The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group ( 42.6 % vs. 4.1 % , P<0.001 ) . An additional 20 % of ibrutinib-treated patients had a partial response with lymphocytosis . Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues . The most frequent nonhematologic adverse events were diarrhea , fatigue , pyrexia , and nausea in the ibrutinib group and fatigue , infusion-related reactions , and cough in the ofatumumab group . CONCLUSIONS Ibrutinib , as compared with ofatumumab , significantly improved progression-free survival , overall survival , and response rate among patients with previously treated CLL or SLL . ( Funded by Pharmacyclics and Janssen ; RESONATE Clinical Trials.gov number , NCT01578707 . ) Abstract In this multicenter , open-label , phase III study , patients with relapsed chronic lymphocytic leukemia ( CLL ) were r and omized ( 1:1 ) to receive ofatumumab plus fludarabine and cyclophosphamide ( OFA + FC ) or FC alone ; the primary endpoint being progression-free survival ( PFS ) assessed by an independent review committee ( IRC ) . Between March 2009 and January 2012 , 365 patients were r and omized ( OFA + FC : n = 183 ; FC : n = 182 ) . Median IRC-assessed PFS was 28.9 months with OFA + FC versus 18.8 months with FC ( hazard ratio = 0.67 ; 95 % confidence interval , 0.51–0.88 ; p = .0032 ) . Grade ≥3 adverse events ( ≤60 days after last dose ) were reported in 134 ( 74 % ) OFA + FC-treated patients compared with 123 ( 69 % ) FC-treated patients . Of these , neutropenia was the most common ( 89 [ 49 % ] vs. 64 [ 36 % ] ) . OFA + FC improved PFS with manageable safety for patients with relapsed CLL compared with FC alone , thus providing an alternative treatment option for patients with relapsed CLL . Trial registration : www . clinical trials.gov ( NCT00824265 ) Ofatumumab , the human CD20 monoclonal antibody that binds a distinct epitope from rituximab , has demonstrated clinical benefit as monotherapy for patients with chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab ( FA-ref ) and patients refractory to fludarabine with bulky ( > 5 cm ) lymph nodes ( BF-ref ) . To potentially gain insight into outcomes in patients previously treated with or refractory to rituximab , we performed an ad hoc retrospective analysis in the final 96 FA-ref and 111 BF-ref patients . There were 117 patients previously treated with rituximab ( 98 rituximab-refractory ) ; 89 patients were rituximab-naive . For rituximab-treated , rituximab-refractory , and rituximab-naive patients , overall response rate was 43 % , 44 % , and 53 % ; median progression-free survival was 5.3 , 5.5 , and 5.6 months ; and median overall survival was 15.5 , 15.5 , and 20.2 months . There were no significant differences in ofatumumab-related infusion reactions , or hematologic or infectious adverse events between subgroups . In summary , ofatumumab monotherapy was effective and well tolerated in patients with fludarabine-refractory chronic lymphocytic leukemia , including in patients with previous rituximab exposure . This trial was registered at www . clinical trials.gov as # NCT00349349 |
12,037 | 32,200,440 | Our meta- analysis showed a modest but a significant reduction in SBP and DBP in patients with hypertension , particularly in those with diabetes mellitus , following probiotic supplementation .
This effect was associated with treatment duration , dosage , and the age of subject but was not associated with single or multiple strains usage .
Additionally , probiotic supplement had a beneficial effect in reducing BMI and blood glucose | This meta- analysis and systematic review was conducted to evaluate the effect of probiotics on blood pressure , body mass index ( BMI ) , and blood glucose changes in patients with hypertension . | BACKGROUND Hypercholesterolemia is a major risk factor for cardiovascular disease . Not all patients respond well to traditional cholesterol lowering medications . Probiotics have been evaluated for their cholesterol-lowering effects in humans with variable results . This study was performed to evaluate the efficacy of two probiotics in lowering the serum cholesterol of hypercholesterolemic patients . MATERIAL S AND METHODS A r and omized double-blind controlled trial was conducted comparing placebo to Lactobacillus acidophilus plus Bifidobacterium bifidum in patients diagnosed with hypercholesterolemia . Placebo or probiotic capsules were taken three times daily for six weeks . Pre- and post-treatment total cholesterol ( TC ) , HDL-cholesterol ( HDL-C ) , LDL-cholesterol ( LDL-C ) and triglyceride ( TG ) levels and demographic parameters of the two groups were compared . From a total of 70 participants , 64 completed the assigned treatment ( 31 in probiotics group and 33 in the control group).The two treatment groups were matched for age , sex , weight , height , BMI , waist and hip circumferences , and blood pressure . RESULTS Baseline evaluation revealed no difference between the probiotics group and control group levels of TC , HDL-C , LDL-C and TG . TC levels in the probiotics group decreased during treatment ( 237.2 vs. 212.7 mg/dL , p<0.05 ) . TC and LDL-C levels in the control group increased significantly from their baseline levels during treatment . TC ( 212.7 vs 252.8 mg/dL , p<0.001 ) , HDL-C ( 52.0 vs 59.1 mg/dL , p=0.04 ) and LDL-C ( 153.9 vs 182.1 mg/dL , p<0.01 ) levels in the probiotics group were significantly lower at the end of treatment than the corresponding levels in the control group . CONCLUSION A combination of Lactobacillus acidophilus and Bifidobacterium bifidum decreased serum total cholesterol , LDL-cholesterol and HDL-cholesterol levels in hypercholesterolemic patients over a six week period . There was no effect on serum triglyceride or fasting blood glucose levels BACKGROUND The short-chain fatty acids formed in the human colon by the bacterial fermentation of fiber may have an antiinflammatory effect , may reduce insulin production , and may improve lipid metabolism . We previously showed in hypercholesterolemic patients that supplementation with the probiotic bacteria Lactobacillus plantarum 299v significantly lowers concentrations of LDL cholesterol and fibrinogen . OBJECTIVE We determined the influence of a functional food product containing L. plantarum 299v on lipid profiles , inflammatory markers , and monocyte function in heavy smokers . DESIGN Thirty-six healthy volunteers ( 18 women and 18 men ) aged 35 - 45 y participated in a controlled , r and omized , double-blind trial . The experimental group drank 400 mL/d of a rose-hip drink containing L. plantarum 299v ( 5 x 10(7 ) colony-forming units/mL ) ; the control group consumed the same volume of product without bacteria . The experiment lasted 6 wk and entailed no changes in lifestyle . RESULTS Significant decreases in systolic blood pressure ( P < 0.000 ) , leptin ( P < 0.000 ) , and fibrinogen ( P < 0.001 ) were recorded in the experimental group . No such changes were observed in the control group . Decreases in F(2)-isoprostanes ( 37 % ) and interleukin 6 ( 42 % ) were also noted in the experimental group in comparison with baseline . Monocytes isolated from subjects treated with L. plantarum showed significantly reduced adhesion ( P < 0.001 ) to native and stimulated human umbilical vein endothelial cells . CONCLUSION L. plantarum administration leads to a reduction in cardiovascular disease risk factors and could be useful as a protective agent in the primary prevention of atherosclerosis in smokers Aim Evidence of a possible connection between gut microbiota and several physiological processes linked to type 2 diabetes is increasing . However , the effect of multi-strain probiotics in people with type 2 diabetes remains unclear . This study investigated the effect of multi-strain microbial cell preparation — also refers to multi-strain probiotics — on glycemic control and other diabetes-related outcomes in people with type 2 diabetes . Design A r and omized , double-blind , parallel-group , controlled clinical trial . Setting Diabetes clinic of a teaching hospital in Kuala Lumpur , Malaysia . Participants A total of 136 participants with type 2 diabetes , aged 30–70 years , were recruited and r and omly assigned to receive either probiotics ( n = 68 ) or placebo ( n = 68 ) for 12 weeks . Outcomes Primary outcomes were glycemic control-related parameters , and secondary outcomes were anthropomorphic variables , lipid profile , blood pressure and high-sensitivity C-reactive protein . The Lactobacillus and Bifidobacterium quantities were measured before and after intervention as an indicator of successful passage of the supplement through gastrointestinal tract . Statistical analysis Intention-to-treat ( ITT ) analysis was performed on all participants , while per- protocol ( PP ) analysis was performed on those participants who had successfully completed the trial with good compliance rate . Results With respect to primary outcomes , glycated hemoglobin decreased by 0.14 % in the probiotics and increased by 0.02 % in the placebo group in PP analysis ( p < 0.05 , small effect size of 0.050 ) , while these changes were not significant in ITT analysis . Fasting insulin increased by 1.8 µU/mL in placebo group and decreased by 2.9 µU/mL in probiotics group in PP analysis . These changes were significant between groups at both analyses ( p < 0.05 , medium effect size of 0.062 in PP analysis and small effect size of 0.033 in ITT analysis ) . Secondary outcomes did not change significantly . Probiotics successfully passed through the gastrointestinal tract . Conclusion Probiotics modestly improved HbA1c and fasting insulin in people with type 2 diabetes Background Gut lactobacilli can affect the metabolic functions of healthy humans . We tested whether a 1500 kcal/d diet supplemented with cheese containing the probiotic Lactobacillus plantarum TENSIA ( Deutsche Sammlung für Mikroorganismen , DSM 21380 ) could reduce some symptoms of metabolic syndrome in Russian adults with obesity and hypertension . Methods In this 3-week , r and omized , double-blind , placebo-controlled , parallel pilot study , 25 subjects ingested probiotic cheese and 15 ingested control cheese . Fifty grams of each cheese provided 175 kcal of energy . Blood pressure ( BP ) , anthropometric characteristics , markers of liver and kidney function , metabolic indices ( plasma glucose , lipids , and cholesterol ) , and urine polyamines were measured . Counts of fecal lactobacilli and L. plantarum TENSIA were evaluated using molecular methods . The data were analyzed by t-test for independent sample s and Spearman ’s partial correlation analysis . Results The probiotic L. plantarum TENSIA was present in variable amounts ( 529.6 ± 232.5 gene copies ) in 16/25 ( 64 % ) study subjects . Body mass index ( BMI ) was significantly reduced ( p = 0.031 ) in the probiotic cheese group versus the control cheese group . The changes in BMI were closely associated with the water content of the body ( r = 0.570 , p = 0.0007 ) when adjusted for sex and age . Higher values of intestinal lactobacilli after probiotic cheese consumption were associated with higher BMI ( r = 0.383 , p = 0.0305 ) and urinary putrescine content ( r = 0.475 , p = 0.006 ) . In patients simultaneously treated with BP-lowering drugs , similar reductions of BP were observed in both groups . A positive association was detected between TENSIA colonization and the extent of change of morning diastolic BP ( r = 0.617 , p = 0.0248 ) and a trend toward lower values of morning systolic BP ( r = −0.527 , p = 0.0640 ) at the end of the study after adjusting for BMI , age , and sex . Conclusion In a pilot study of obese hypertensive patients , a hypocaloric diet supplemented with a probiotic cheese helps to reduce BMI and arterial BP values , recognized symptoms of metabolic syndrome . Trial registration Current Controlled Trials IS RCT Objective : Two tripeptides ( Val-Pro-Pro and Ile-Pro-Pro ) that have inhibitory activities for angiotensin I-converting enzyme are produced in milk fermented with Lactobacillus helveticus . In this study we evaluated the effect and safety of powdered fermented milk with L. helveticus CM4 on subjects with high-normal blood pressure or mild hypertension . Methods : A r and omized , placebo-controlled , double-blind study was conducted using 40 subjects with high-normal blood pressure ( HN group ) and 40 subjects with mild hypertension ( MH group ) . Each subject ingested 6 test tablets ( 12 g ) containing powdered fermented milk with L. helveticus CM4 daily for 4 weeks ( test group ) or the same amount of placebo tablets for 4 weeks ( placebo group ) . Results : During treatment , the decrease in systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) in the test group tended to be greater than in the placebo group for both blood pressure groups . At the end of treatment ( week 4 ) , a significant decrease in DBP in the HN group was observed ( i.e. 5.0 mm Hg ( 0.1 , 9.9 ; p = 0.04 ) compared with the placebo group ) . There was no significant change in SBP ( 3.2 mm Hg ( 95 % CI −2.6 , 8.9 ; p = 0.27 ) . In the MH group , SBP decreased by 11.2 mm Hg ( 4.0 , 18.4 ; p = 0.003 ) and there was a statistically non-significant decrease in DBP of 6.5 mm Hg ( −0.1 , 13.0 ; p = 0.055 ) compared with the placebo group . No marked changes were observed in other indexes , including pulse rate , body weight and blood serum variables , and no adverse effects attributed to the treatment was found in each group . Conclusions : Daily ingestion of the tablets containing powdered fermented milk with L. helveticus CM4 in subjects with high-normal blood pressure or mild hypertension reduces elevated blood pressure without any adverse effects BACKGROUND AND AIMS Despite strong mechanistic data , and promising results from in vitro and animal studies , the ability of probiotic bacteria to improve blood pressure and serum lipid concentrations in humans remains uncertain . The aim of this study was to determine the effect of Lactobacillus acidophilus La5 and Bifidobacterium animalis subsp lactis Bb12 , provided in either yoghurt or capsule form , on home blood pressure and serum lipid profile . METHODS AND RESULTS Following a 3-week washout period , 156 overweight men and women over 55 y were r and omized to a 6-week double-blinded , factorial , parallel study . The four intervention groups were : A ) probiotic yoghurt plus probiotic capsules ; B ) probiotic yoghurt plus placebo capsules ; C ) control milk plus probiotic capsules ; and D ) control milk plus placebo capsules . Each probiotic test article provided a minimum L. acidophilus La5 and B. animalis subsp . lactis Bb12 dose of 3.0 × 10⁹ CFU/d . Home blood pressure monitoring , consisting of 7-day bi-daily repeat measurements , were collected at baseline and week 6 . Fasting total cholesterol , low density lipoprotein cholesterol ( LDLC ) , high density lipoprotein cholesterol ( HDLC ) , and serum triglyceride were performed at baseline and week 6 . When compared to control milk , probiotic yoghurt did not significantly alter blood pressure , heart rate or serum lipid concentrations ( P > 0.05 ) . Similarly , when compared to placebo capsules , supplementation with probiotic capsules did not alter blood pressure or concentrations of total cholesterol LDLC , HDLC , or triglycerides ( P > 0.05 ) . CONCLUSIONS The probiotic strains L. acidophilus La5 and B. animalis subsp . lactis Bb12 did not improve cardiovascular risk factors The blood pressure-lowering effect of dairy products holds the potential to decrease the risk of cardiovascular disease ( CVD ) . An open question is if the successful expression of functional properties of the probiotic strain depends on host biomarkers and /or food matrix properties . The probiotic Lactobacillus plantarum strain TENSIA ® ( DSM 21380 ) is a novel microorganism with antimicrobial and antihypertensive functional properties . The aim of this study was to characterise the functional properties of the probiotic L. plantarum TENSIA and compare its effects on host anthropometric , clinical , and blood biomarkers when consumed with cheese or yoghurt . This study involved two double-blinded r and omised placebo-controlled exploratory trials ( IS RCT N15061552 and IS RCT N79645828 ) of healthy adults over a three-week period . The three-week consumption of probiotic L. plantarum TENSIA in a daily dose of 1 × 1010 cfu in probiotic cheese or a daily dose of 6 × 109 cfu in yoghurt with different content of carbohydrates , proteins , and lipids did not significantly change the body mass index ( BMI ) , plasma glucose and lipid levels , or inflammatory markers in the blood . Reduced lowered systolic and diastolic blood pressure values were detected , regardless of food matrix or baseline values for blood pressure and BMI . In conclusion , our study showed that three-week consumption of the probiotic L. plantarum TENSIA either in cheese or yoghurt lowered diastolic and systolic blood pressure regardless of food matrix and baseline values of blood pressure and BMI , confirming the impact of the functional properties of the probiotic strain in decreasing CVD risk Objectives : To our knowledge , no reports are available indicating the effects of synbiotic bread consumption on nitric oxide ( NO ) , biomarkers of oxidative stress , and liver enzymes among patients with type 2 diabetes mellitus ( T2DM ) . This study was performed to determine the effects of the daily consumption of synbiotic bread on NO , biomarkers of oxidative stress , and liver enzymes in patients with T2DM . Methods : This r and omized , double-blind , placebo-controlled trial was performed among 81 patients with diabetes , aged 35–70 years old . After a 2-week run-in period , patients were r and omly divided into 3 groups : group A ( n = 27 ) received synbiotic bread containing viable and the heat-resistant probiotic Lactobacillus sporogenes ( 1 × 108 CFU ) and 0.07 g inulin per 1 g , group B ( n = 27 ) received probiotic bread containing Lactobacillus sporogenes ( 1 × 108 CFU ) , and group C ( n = 27 ) received control bread for 8 weeks . Patients were asked to consume the synbiotic , probiotic , or control breads 3 times a day in 40 g packages for a total of 120 g/day . Fasting blood sample s were taken at baseline and after an 8-week intervention for quantificationof related markers . Results : After 8 weeks , the consumption of synbiotic bread compared to the probiotic and control breads result ed in a significant rise in plasma NO ( 40.6 ± 34.4 vs 18.5 ± 36.2 and −0.8 ± 24.5 µmol/L , respectively , p < 0.001 ) and a significant reduction in malondialdehyde ( MDA ) levels ( −0.7 ± 0.7 vs 0.6 ± 1.7 and 0.5 ± 1.5 µmol/L , respectively , p = 0.001 ) . We did not find any significant effect of the synbiotic bread consumption on plasma total antioxidant capacity ( TAC ) , plasma glutathione ( GSH ) , catalase , serum liver enzymes , calcium , iron , magnesium levels , and blood pressure compared to the probiotic and control breads . Conclusion : In conclusion , consumption of the synbiotic bread for 8 weeks among patients with T2DM had beneficial effects on plasma NO and MDA levels ; however , it did not affect plasma TAC , GSH , catalase levels , serum liver enzymes , calcium , iron , magnesium levels , and blood pressure Obesity in the postmenopausal period is associated with an increased risk of cardiovascular diseases in women . One of the key drivers of cardiovascular risk is endothelial dysfunction ; thus , this is also a crucial point for studies on new therapeutic methods of cardioprotective properties . The aim of the current study was to evaluate the effect of two doses of multispecies probiotic Ecologic ® Barrier supplement on functional ( primary endpoint ) and biochemical parameters ( secondary endpoint ) of endothelial dysfunction in obese postmenopausal women in a 12-week r and omized , placebo-controlled clinical trial . A total of 81 obese Caucasian women participated in the trial . The subjects were r and omly assigned to three groups that received a placebo , a low dose ( LD ) ( 2.5 × 109 colony forming units ( CFU ) per day ) , or a high dose ( HD ) ( 1 × 1010 CFU per day ) of lyophilisate powder containing live multispecies probiotic bacteria . The probiotic supplement was administered each day for 12 weeks in two equal portions . A high dose probiotic supplementation for 12 weeks decreased systolic blood pressure , vascular endothelial growth factor , pulse wave analysis systolic pressure , pulse wave analysis pulse pressure , pulse wave analysis augmentation index , pulse wave velocity , interleukin-6 , tumor necrosis factor alpha , and thrombomodulin . Low doses of probiotic supplementation decreased the systolic blood pressure and interleukin-6 levels . The mean changes in the estimated parameters , compared among the three groups , revealed significant differences in the vascular endothelial growth factor , the pulse wave analysis systolic pressure , the pulse wave analysis augmentation index , the pulse wave velocity , the tumor necrosis factor alpha , and thrombomodulin . The post hoc tests showed significant differences for all parameters between HD and the placebo group , and HD and LD ( besides pulse wave analysis augmentation index ) . We show for the first time that supplementation with multispecies probiotic Ecologic ® Barrier favorably modifies both functional and biochemical markers of vascular dysfunction in obese postmenopausal women Probiotics have been reported to ameliorate symptoms of type 2 diabetes mellitus ( T2DM ) in animal models and human studies . We previously demonstrated that oral administration of Lactobacillus reuteri ADR-3 reduced insulin resistance in high-fructose-fed ( HFD ) rats . In the present study , we first identified another L. reuteri strain , ADR-1 , which displayed anti-diabetes activity that reduced the levels of serum HbA1c and cholesterol and that increased antioxidant proteins in HFD rats . We further performed a r and omized , double-blinded , placebo-controlled trial with a total of 68 T2DM patients to examine the beneficial effects of oral consumption of L. reuteri strains ADR-1 and ADR-3 and to investigate the associated changes in intestinal flora using a quantitative PCR method to analyze 16 S rRNA in fecal specimens . Significant reductions in HbA1c and serum cholesterol were observed in participants in the live ADR-1 consumption group ( n = 22 ) after 3 months of intake when compared with those in the placebo group ( n = 22 ) . Although there was no significant difference in the HbA1c serum level among participants who consumed heat-killed ADR-3 ( n = 24 ) , the systolic blood pressure and mean blood pressure were significantly decreased after 6 months of intake . There was no obvious change in serum inflammatory cytokines or antioxidant proteins in participants after intaking ADR-1 or ADR-3 , except for a reduction in IL-1β in the ADR-3 consumption group after 6 months of intake . With the analysis of fecal microflora , we found that L. reuteri or Bifidobacterium spp . were significantly increased in the ADR-1 and ADR-3 consumption groups , respectively , after 6 months of intake . Interestingly , a significant reduction in HbA1c was observed in the ADR-1 and ADR-3 consumption participants who displayed at least an 8-fold increase in fecal L. reuteri . We also observed that there was a significantly positive correlation between Bifidobacterium spp . and Lactobacillus spp . in participants with increased levels of fecal L. reuteri . In the ADR-1 intake group , the fecal Lactobacillus spp . level displayed a positive correlation with Bifidobacterium spp . but was negatively correlated with Bacteroidetes . The total level of fecal L. reuteri in participants in the ADR-3 consumption group was positively correlated with Firmicutes . In conclusion , L. reuteri strains ADR-1 and ADR-3 have beneficial effects on T2DM patients , and the consumption of different strains of L. reuteri may influence changes in intestinal flora , which may lead to different outcomes after probiotic intake Gut microbiota may influence blood pressure ( BP ) , namely via end products of carbohydrate fermentation . After informed consent , male volunteers were prospect ively categorized into 3 groups upon European Society of Hypertension criteria based on 24-hour ambulatory BP measurements : ( 1 ) hypertension , ( 2 ) borderline hypertension , and ( 3 ) normotension . Stool , urine and serum sample s were collected in fasting conditions . Gut microbiota was characterized by 16S amplicon sequencing . Metabolomics , including quantification of short-chain fatty acids , was conducted using nuclear magnetic resonance . Two-way ANOVA combined with Tukey post hoc test , as well as multiple permutation test and Benjamini-Hochberg-Yekutieli false discovery rate procedure , was used . The cohort included 54 males : 38 hypertensive ( including 21 under treatment ) , 7 borderline , and 9 normotensive . No significant difference was observed between groups concerning age , body mass index , smoking habits , and weekly alcohol consumption . The genus Clostridium sensu stricto 1 positively correlated with BP levels in nontreated patients ( n=33 ) . This correlation was significant after multiple permutation tests but was not substantiated following false discovery rate adjustment . Short-chain fatty acid levels were significantly different among groups , with higher stool levels of acetate , butyrate , and propionate in hypertensive versus normotensive individuals . No difference was observed in serum and urine metabolomes . Correlation between stool metabolome and 24-hour BP levels was evidence d , with R2 reaching 0.9 . Our pilot study based on 24-hour ambulatory BP measurements , 16S amplicon sequencing , and metabolomics supports an association between gut microbiota and BP homeostasis , with changes in stool abundance of short-chain fatty acids Purpose Polycystic ovarian syndrome ( PCOS ) is one of the most common metabolic and endocrine disorders . Functional foods like pomegranate and probiotics are those that are considered to have beneficial effects on metabolic diseases beyond their basic nutritional value . So , we aim ed to evaluate the effect of synbiotic pomegranate juice ( SPJ ) on cardiovascular risk factors on PCOS patients . Methods This was a r and omized , triple-blinded , 8-week trial . Participants were r and omly assigned to receive 300 mL/day of pomegranate juice ( PJ ) , synbiotic beverage ( SB ) , synbiotic pomegranate juice ( SPJ ) , or placebo beverage ( PB ) . Biochemical indices ( lipid profile , Total Antioxidant Capacity ( TAC ) , Malondialdehyde ( MDA ) , high sensitive C-Reactive Protein ( hs-CRP ) ) and blood pressure were assessed before and after the intervention . Results Participants in the PJ , SB , and SPJ groups experienced improvement in their lipid profile , oxidative stress , inflammation , and blood pressure during the time . Compared to placebo , Total Cholesterol ( TC ) was lower in the SB group ( P < 0.01 ) , LDL-c was lower in the SPJ and SB groups ( P < 0.01 ) , and HDL-c was higher in the SPJ and PJ groups ( P < 0.01 ) . With regards to oxidative stress and inflammation , when compared with placebo , MDA was lower in the SPJ , SB , and PJ groups ( P < 0.001 ) , TAC was increased in the SPJ and PJ groups ( P $ $ < $ $ < 0.001 ) , and hs-CRP was decreased in the PJ group ( P = 0.02 ) . Blood pressure ( BP ) was lower in the SPJ and PJ groups compared to placebo ( P < 0.001 ; P < 0.01 , respectively ) . Conclusions Consuming daily SPJ for 8 weeks improved metabolic , oxidative , inflammatory , and BP outcomes in females with PCOS . This trial was registered in the Iranian Registry of Clinical Trials ( I RCT 20170207032439N2 ) |
12,038 | 17,702,723 | Treatment of lupus nephritis with mycophenolate mofetil compared with cyclophosphamide reduces the risk for failure to induce remission during induction therapy and may reduce the risk for death or end-stage renal disease .
Mycophenolate mofetil may be considered as a first-line induction therapy for the treatment of lupus nephritis in patients without severe renal dysfunction | BACKGROUND AND OBJECTIVES Although the accepted st and ard of care for induction of lupus nephritis has been cyclophosphamide , recent trials suggest that mycophenolate mofetil may be as or more effective and less toxic . | The treatment of patients with severe lupus nephritis remains controversial . Comparison of treatment outcomes from existing controlled trials is hampered by the heterogeneity of the patient groups with their different intrinsic disease progression . Corticosteroids with cyclophosphamide or azathioprine remain the mainstay of treatment , although meta- analysis has failed to show the superiority of cyclophosphamide over the less toxic azathioprine . The development of safer alternative treatments for the induction of remission of nephritis , long term maintenance , and the management of patient groups refractory to current therapies remains the goal . Mycophenolate mofetil ( MMF ) is one of a number of newer therapies , including ̄udarabine , CTLA4-Ig and anti-C5b under evaluation in lupus nephritis . MMF may potentially offer an alternative for the induction of remission , treatment of refractory , and maintenance of severe lupus nephritis . Controlled trials in renal transplantation have found that MMF reduces the incidence of acute rejection , and is superior to azathioprine when combined with cyclosporin and prednisolone for this indication . The role of MMF in chronic allograft nephropathy is less certain but recently retrospective analysis of data from the US Renal Transplant Registry has shown that MMF decreases the risk of developing chronic allograft failure . This was found to be partly due to MMF decreasing the incidence of acute rejection , but was also caused by an effect independent of acute rejection . The success of MMF in allotransplantation has led to its use in a number of autoimmune diseases and there have been published case series examining its use in Takaysau 's arteritis , refractory uveitis , psoriasis and Crohn 's disease . Recently , reports of MMF in lupus nephritis apparently refractory to cyclophosphamide have been published with encouraging results . The role of MMF for remission induction in severe biopsy proven lupus nephritis , in patients without previous cytotoxic exposure is the subject of several ongoing prospect i ve studies Controlled clinical trials in renal transplantation have demonstrated that mycophenolate mofetil is well tolerated and has lower renal transplant rejection rates than azathioprine regimens . This study reports on the clinical experiences at two institutions with mycophenolate mofetil ( MMF ) for severe lupus nephritis . Twelve patients with relapsing or resistant nephritis previously treated with cyclophosphamide therapy and one patient who refused cyclophosphamide as initial therapy for diffuse proliferative nephritis but accepted MMF were included . During combined MMF/prednisone therapy , serum creatinine values remained normal or declined from elevated values : mean change in serum creatinine was -0.26+/-0.46 microM/L , P = 0.039 . Proteinuria significantly decreased : mean change in urine protein-to-creatinine ratios was -2.53+/-3.76 , P = 0.039 . Decreased serum complement component C3 and elevated anti-double-str and ed DNA antibody levels at baseline improved in some , but not all , patients . The mean initial dose of MMF was 0.92 g/d ( range , 0.5 to 2 g/d ) . The mean duration of therapy was 12.9 mo ( range , 3 to 24 mo ) . Adverse events included herpes simplex stomatitis associated with severe leukopenia ( n = 1 ) , asymptomatic leukopenia ( n = 2 ) , nausea/ diarrhea ( n = 2 ) , thinning of scalp hair ( n = 1 ) , pancreatitis ( n = 1 ) , and pneumonia without leukopenia ( n = 1 ) . Recurrence of the pancreatitis led to discontinuation of MMF in this patient ; all other adverse events resolved with dose reduction . It is concluded that MMF is well tolerated and has possible efficacy in controlling major renal manifestations of systemic lupus erythematosus . Controlled clinical trials are needed to define the role of MMF in the management of lupus nephritis Pulse cyclophosphamide is more effective than prednisone alone in preventing renal failure in lupus nephritis . We undertook a r and omised , controlled trial to find out whether pulse methylprednisolone could equal pulse cyclophosphamide in preserving renal function in patients with lupus nephritis , and whether there was a difference between long and short courses of pulse cyclophosphamide in preventing exacerbations . 65 patients ( 60 female , 5 male ; median [ range ] age 29 [ 10 - 48 ] years ) with severe lupus nephritis were assigned r and omly to monthly pulse methylprednisolone for 6 months ( 25 patients ) , monthly pulse cyclophosphamide for 6 months ( 20 ) , or monthly cyclophosphamide for 6 months followed by quarterly pulse cyclophosphamide for 2 additional years ( 20 ) . Patients treated with pulse methylprednisolone had a higher probability of doubling serum creatinine than those treated with long-course cyclophosphamide ( p less than 0.04 ) . Risk of doubling creatinine was not significantly different between short and long course cyclophosphamide . However , patients treated with short-course cyclophosphamide had a higher probability of exacerbations than those treated with long-course cyclophosphamide ( p less than 0.01 ) . An extended course of pulse cyclophosphamide is more effective than 6 months of pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis . Addition of a quarterly maintenance regimen to monthly pulse cyclophosphamide reduces the rate of exacerbations BACKGROUND The aim of the present study was to evaluate the efficacy of mycophenolate mofetil in the induction therapy of proliferative lupus nephritis . METHODS Forty-four patients from eight centres with newly diagnosed lupus nephritis World Health Organization class III or IV were r and omly assigned to either mycophenolate mofetil ( MMF ) 2 g/day for 6 months or intravenous cyclophosphamide ( IVC ) 0.75 - 1 g/m(2 ) monthly for 6 months in addition to corticosteroids . RESULTS Remission occurred in 13 out of 25 patients ( 52 % ) in the IVC group and 11 out of 19 patients ( 58 % ) in the MMF group ( P = 0.70 ) . There were 12 % in the IVC group and 26 % in the MMF group that achieved complete remission ( P = 0.22 ) . Improvements in haemoglobin , the erythrocyte sedimentation rate , serum albumin , serum complement , proteinuria , urinary activity , renal function and the Systemic Lupus Erythematosus Disease Activity Index score were similar in both groups . Twenty-four follow-up renal biopsies at the end of therapy showed a significant reduction in the activity score in both groups . The chronicity index increased in both groups but was only significant in the IVC group . Adverse events were similar . Major infections occurred in three patients in each group . There was no difference in gastrointestinal side-effects . CONCLUSIONS MMF in combination with corticosteroids is an effective induction therapy for moderately severe proliferative lupus nephritis Mycophenolate mofetil ( MMF ) and the sequential use of cyclophosphamide followed by azathioprine ( CTX-AZA ) demonstrate similar short-term efficacy in the treatment of diffuse proliferative lupus nephritis ( DPLN ) , but MMF is associated with less drug toxicity . Results from an extended long-term study , with median follow-up of 63 mo , that investigated the role of MMF as continuous induction-maintenance treatment for DPLN are presented . Thirty-three patients were r and omized to receive MMF , and 31 were r and omized to the CTX-AZA treatment arm , both in combination with prednisolone . More than 90 % in each group responded favorably ( complete or partial remission ) to induction treatment . Serum creatinine in both groups remained stable and comparable over time . Creatinine clearance increased significantly in the MMF group , but the between-group difference was insignificant . Improvements in serology and proteinuria were comparable between the two groups . A total of 6.3 % in the MMF group and 10.0 % of CTX-AZA-treated patients showed doubling of baseline creatinine during follow-up ( P = 0.667 ) . Both the relapse-free survival and the hazard ratio for relapse were similar between MMF- and CTX-AZA-treated patients ( 11 and nine patients relapsed , respectively ) and between those with MMF treatment for 12 or > /=24 mo . MMF treatment was associated with fewer infections and infections that required hospitalization ( P = 0.013 and 0.014 , respectively ) . Four patients in the CTX-AZA group but none in the MMF group reached the composite end point of end-stage renal failure or death ( P = 0.062 by survival analysis ) . It is concluded that MMF and prednisolone constitute an effective continuous induction-maintenance treatment for DPLN in Chinese patients The Phase III Aspreva Lupus Management Study ( ALMS ) will investigate mycophenolate mofetil ( MMF ) therapy for lupus nephritis ( LN ) . Eligibility criteria include : 12—75 years of age ; diagnosis of systemic lupus erythematosus according to revised American College of Rheumatology criteria ; and biopsy-demonstrated LN ( Class III — V ) . R and omized patients will receive open-label induction therapy with MMF or cyclophosphamide in combination with corticosteroids for 24 weeks . The primary efficacy endpoint is treatment response [ decreased proteinuria and stabilized ( within 25 % of baseline ) or improved serum creatinine level ] . Patients achieving response or complete remission ( normalization of all parameters ) will be rer and omized to double-blind , placebo-controlled maintenance treatment with MMF or azathioprine , both plus corticosteroids . The maintenance phase primary endpoint is time to treatment failure . To detect a 15 % rate improvement in the MMF group compared with cyclophosphamide , and to provide 90 % power , a total of 358 patients will be required for the induction phase . On the basis of a projected 278 rer and omized patients , the maintenance phase will have 90 % power to detect a difference between treatment groups assuming azathioprine and MMF three-year failure rates of 59.5 % and 40.7 % , respectively . Aspreva Lupus Management Study may provide invaluable comparative data on the efficacy and safety of MMF as LN induction and maintenance therapy . Lupus ( 2007 ) 16 , 972—980 OBJECTIVE To make an open label prospect i ve trial for comparing the therapeutic effects of mycophenolate mofetil ( MMF ) vs cyclophosphamide ( CYC ) pulse therapy on patients with diffuse proliferative lupus nephritis ( DPLN ) . METHODS Forty-six patients with biopsy proven active DPLN were enrolled in this study . Twenty-three patients were given MMF orally at a dosage of 1.0 - 1.5 g/d ( MMF Group ) . Another 23 cases received conventional intermittent CYC pulse therapy ( CYC Group ) . Supplemental steroid treatment was offered in the same manner to both groups . The age , sex distribution and severity of renal damage were matched in two groups . Therapeutic effects were evaluated at the end of six-month treatment . Fifteen patients in the MMF Group and 12 patients in the CYC Group had repeated renal biopsy at that time . RESULTS MMF therapy was more effective in reducing proteinuria and hematuria . A 50 % reduction of urinary protein and urinary red blood cell excretion from baseline value in 69.6 % and 91.3 % patients in the MMF Group , while only 47.8 % and 65.2 % in the CYC Group . MMF was more effective in inhibiting autoantibody production ( especially anti-dsDNA antibody ) and in decreasing serum cryoglobulin levels . Pathologically , the MMF group showed more markedly reduction in glomerular immune deposits with less glomerular necrosis , and less microthrombi , less crescent formation and vascular changes in the repeated renal biopsy as compared with the CYC group . Adverse reactions related to the treatment included gastrointestinal symptoms 26.1 % and 43.5 % in the MMF and CYC Groups respectively , infection 17.4 % in the MMF group and 30.4 % in the CYC group . CONCLUSION MMF was more effective in controlling the clinical activity of DPLN and renal vascular lesions as compared with CYC pulse therapy in a 6 month follow-up study Table . Drugs and Abbreviation Ovarian toxicity is an important consideration before the use of cyclophosphamide therapy in premenopausal women [ 1 ] . The deleterious effects of cyclophosphamide on ovarian function were noted in patients with rheumatoid arthritis treated with daily oral cyclophosphamide [ 2 ] . These preliminary observations have been confirmed and extended by subsequent studies in patients with various immune-mediated diseases including rheumatoid arthritis [ 3 ] , systemic lupus erythematosus [ 4 - 6 ] , renal diseases [ 3 , 4 , 6 , 7 ] , and multiple sclerosis [ 8 ] . In these studies , 50 % to 70 % of women receiving regimens of daily oral cyclophosphamide for 6 to 48 months developed amenorrhea . Studies mainly in cancer patients have suggested that ovarian toxicity from cyclophosphamide is related to dosage and patient age [ 9 - 13 ] . Intermittent pulse cyclophosphamide is widely used in renal [ 6 , 14 - 17 ] and major extrarenal complications of lupus erythematosus [ 18 - 20 ] . Because of its more favorable balance of efficacy and toxicity , intermittent pulse cyclophosphamide therapy is considered an acceptable alternative to daily oral cyclophosphamide for the treatment of proliferative lupus nephritis . In addition to lupus , pulse cyclophosphamide therapy has been used with variable results for the treatment of various immune-mediated rheumatic [ 21 - 28 ] , renal [ 29 - 31 ] , neurologic [ 32 , 33 ] , and hematologic diseases [ 34 ] or their complications ( review ed in [ 20 ] ) . Because pulse cyclophosphamide therapy is used for women of child-bearing age who have immunologically mediated diseases , accurate information about ovarian toxicity rates with this therapy is critical . Even though several studies exist of the gonadal toxicity of alkylating agents in patients with malignancy and autoimmune diseases , the doses and treatment schedules in these studies [ 3 - 13 ] differ from those of pulse cyclophosphamide as currently used in immunologically mediated disorders [ 14 - 34 ] . Moreover , the concomitant use of adjunctive oncologic therapies that may be toxic to the ovaries also limits the applicability of some of these data [ 9 - 13 ] to patients with autoimmune diseases . To address some of these issues more directly , we evaluated the risk for amenorrhea in women with systemic lupus erythematosus treated with pulses of cyclophosphamide according to duration of treatment ( number of doses ) and the age at the initiation of therapy . Our data suggest that intermittent pulse cyclophosphamide therapy is associated with secondary amenorrhea and that duration of therapy and age are independent risk factors . The toxicity rates provided by our study should be useful to physicians and patients before they decide whether to use pulse cyclophosphamide therapy . Methods Selection of Patients For the purpose of this study , we defined a short course of cyclophosphamide ( Cytoxan , Bristol Myers Oncology , Princeton , New Jersey ) as 7 monthly pulses of intravenous cyclophosphamide ( short-CY ) and a long course as 15 or more pulses ( long-CY ) . Criteria for eligibility included women who were 40 years old or younger . Patients with other causes of secondary amenorrhea ( including end-stage renal disease ) were excluded from the analysis . Amenorrhea was defined as lack of menses for at least 4 months . Sustained amenorrhea was defined as amenorrhea not resolving within 12 months after cessation of pulse cyclophosphamide therapy . Patients included in this analysis participated in two different prospect i ve therapeutic trials for lupus nephritis at the National Institutes of Health from 1973 to 1990 [ 6 , 17 ] and in a retrospective study for neuropsychiatric lupus [ 19 ] . For the first protocol , patients with severe proliferative nephritis [ defined as impaired renal function alone , very active renal histology , or both ] were r and omly assigned to one of the following three treatment groups : 1 ) methylprednisolone pulses at 1.0 g/m2 of body surface area , monthly for 6 months [ total of nine doses , n = 25 ] ; 2 ) a short course of cyclophosphamide pulses ( short-CY ) at 0.5 to 1.0 g/m2 , monthly for 6 months only [ total of seven doses , n = 20 ] ; or 3 ) a long course of cyclophosphamide pulses ( long-CY ) given monthly for 6 months followed by quarterly pulses for an additional 2 years ( total of 15 doses , n = 20 ) . Sixteen patients from the methylprednisolone ( Medrol , The Upjohn Company , Kalamazoo , Michigan ) group ; 13 patients from the short-CY group ; and 14 patients from the long-CY group were eligible by age , sex , and renal function criteria for our analysis . In the second protocol [ 6 ] , one group of patients with active lupus nephritis was r and omly assigned to receive quarterly pulse cyclophosphamide ( 0.5 to 1.0 g/m2 [ n = 20 ] ) . Patients from this protocol who received at least 15 doses ( range , 15 to 24 doses ) of cyclophosphamide were included in our analysis ( n = 9 ) . Finally , three patients with neuropsychiatric lupus treated with a short course of cyclophosphamide [ 19 ] , analogous to the protocol of short-CY for lupus nephritis , were included . Patients were followed for at least 4 years after the cessation of therapy . All patients had a thorough gynecologic evaluation after the occurrence of amenorrhea . Serum gonadotrophin levels were available for 7 of 11 patients who developed sustained amenorrhea . Statistical Analysis The distribution of clinical features among the treatment groups at study entry was analyzed using the Kruskal-Wallis and chi-square tests . Two-tailed tests were used to estimate the P values . The proportion of patients developing sustained amenorrhea was compared according to duration of cyclophosphamide therapy and patient age at study entry . For these comparisons , statistical analysis was done using the Fisher exact test and the chi-square test for trend where appropriate . Results Pertinent data on the patients evaluated for amenorrhea are shown in Table 1 . The distributions of demographic and laboratory features were not statistically different among the methylprednisolone and cyclophosphamide treatment groups . Table 1 . Characteristics of Patients with Systemic Lupus Erythematosus in this Study The rates of sustained amenorrhea according to age and duration of treatment are shown in Table 2 . Eleven patients had sustained ( 28 % ) and three patients had temporary ( 8 % ) amenorrhea of the 39 patients treated with pulse cyclophosphamide . Patients treated with 15 or more doses of cyclophosphamide ( long-CY ) were more likely to develop sustained amenorrhea than patients receiving 7 doses ( short-CY ) ( 39 % compared with 12 % ) ( the Fisher exact test , P = 0.07 ) . No patients treated with methylprednisolone ( the control group ) had amenorrhea . Seven of 14 patients who developed amenorrhea did so within the first seven doses of pulse cyclophosphamide . Older patients tended to develop amenorrhea earlier . Three patients ( all in the Short-CY group ) developed temporary amenorrhea that resolved within 12 months after cessation of therapy . Table 2 . Rate of Sustained Amenorrhea in Patients Treated with Pulse Cyclophosphamide according to Age and Duration of Therapy In addition to the number of doses , age seemed to contribute to the risk for permanent amenorrhea ( Table 2 ) . Of 16 patients younger than 25 years , only 2 developed amenorrhea ( 12 % ) . Both patients ( ages 22 years ) belonged to the Long-CY group and had received 20 and 24 doses of cyclophosphamide , respectively . Among the 8 patients who were 31 years old or older , 5 ( 62 % ) developed amenorrhea compared with 12 % in the youngest age group . Patients who were 26 to 30 years old had an intermediate rate ( 27 % ) of amenorrhea ( chi-square test for trend , P = 0.04 ) . The risk for sustained amenorrhea among patients treated with Long-CY was most evident in patients older than 25 years ( Table 2 ) . Among patients 26 years of age or older , 2 of 12 treated with Short-CY developed sustained amenorrhea , whereas 7 of 11 patients treated with Long-CY developed sustained amenorrhea ( the Fisher exact test , P = 0.03 ) . Discussion Patients with systemic lupus erythematosus now survive longer . With the decreased morbidity and longer life expectancy of these patients , gonadal toxicity is becoming a problem . Our study addresses the ovarian toxicity of pulse cyclophosphamide therapy , a commonly used intensive therapy for the major manifestations of lupus and other immune-mediated diseases . Ovarian Toxicity The mechanism of ovarian toxicity from cyclophosphamide has been studied in animal models [ 35 - 38 ] . A single intraperitoneal injection of 100 mg/kg of cyclophosphamide decreases the number of small follicles in ovaries of mice by about 63 % [ 35 ] . The pool of growing follicles ( medium to large ) appears to be more vulnerable to the cytotoxic effect of cyclophosphamide than the small follicles [ 37 ] . After intraperitoneal injections of cyclophosphamide in immature rats primed with pregnant mare gonadotrophins , serum estradiol levels and the number of granulosa cells expressed from each ovary were decreased [ 37 ] . Cross-links in DNA in granulosa cells continue up to and probably beyond 24 hours , suggesting that the effects of cyclophosphamide on granulosa cells are prolonged . In addition to DNA , other macromolecules ( enzymes , proteins ) in the granulosa cells may be alkylated by cyclophosphamide metabolites . Decreased serum estrogen levels lead to up-regulation of follicle-stimulating hormone secretion , thus accelerating further follicular recruitment into the developing cyclophosphamide-sensitive pool of follicles . This mechanism perpetuates a vicious cycle , whereby cyclophosphamide destroys the developing follicles by attacking rapidly dividing granulosa cells , reducing their steroid secretion , and leading to increased pituitary gonadotrophin production , which enhances further recruitment of follicles into the pool of maturing follicles susceptible to cyclophosphamide [ 37 ] . These early events eventually result in accelerated depletion of ovarian follicles as shown in histologic sections Objective : To investigate the effectiveness and safety of mycophenolate mofetil in patients with systemic lupus erythematosus who were inadequately controlled with corticosteroids , antimalarials , and other immunosuppresive agents . Methods : Ten patients with systemic lupus erythematosus ( SLE ) were treated with 1500 - 2000 mg mycophenolae mofetil ( MMF ) daily for a median observation time of 11.2 ± 2.4 ( 8 - 16 ) months in an open clinical trial . The effectiveness and safety of treatment were analyzed using an established disease activity score , clinical status , and laboratory parameters . Results : All patients improved under treatment with no or only minor side effects . The disease activity score ( SLAM ) decreased statistically significantly from a median of 15.6 ± 5.5 to 9.9 ± 4.1 after three months ( P < 0.01 ) and to 8.0 ± 3.3 after six months ( P < 0.01 ) . Hematologic parameters did not change significantly whereas a reduction of inflammatory markers was observed . Four patients with SLE-nephritis already treated with cyclophosphamide pulse therapy continuously showed a slight improvement of renal function . Prednisolone dosages could be reduced significantly from a median level of 10.0 + 5.1 mg/d before treatment to 4.6 ±3.5 mg/d after six months ( P < 0.01 ) . Conclusion : Mycophenolate mofetil is a promising option in immunosuppressive treatment of patients with moderate and severe systemic lupus erythematosus who did not show a satisfactory response to other immunosuppressives Therapy for patients with life-threatening systemic lupus erythematosus has included high doses of corticosteroids and cytotoxic or cytostatic drugs [ 1 - 20 ] . Cyclophosphamide , given in intermittent intravenous boluses , has been widely used to treat renal [ 1 - 68 , 15 , 21 ] and central nervous system disease [ 2 , 3 , 6 , 7 , 19 - 21 ] , but this therapy is sometimes withheld in the hope that disease might be controlled with corticosteroids or other immunosuppressive drugs . Moreover , some patients do not respond adequately to therapy with intermittent boluses of cyclophosphamide , and these patients might benefit from more intensive therapy . In a previous study [ 3 ] , monthly administration of methylprednisolone ( 1.0 g/m2 body surface area ) was less effective than bolus therapy with cyclophosphamide . However , the limited duration of the methylprednisolone regimen [ 6 months ] might have been insufficient to treat lupus nephritis . To address this concern , we evaluated patients receiving methylprednisolone once a month for 1 year ; additional boluses were given as needed to control disease . We compared these patients with patients receiving our st and ard therapy : intermittent boluses of cyclophosphamide . A group of patients r and omly assigned to receive both cyclophosphamide and methylprednisolone was also included for three major reasons : 1 ) some patients with lupus nephritis respond inadequately to boluses of cyclophosphamide , 2 ) anecdotal experience had suggested that cyclophosphamide therapy might be more effective for all patients when given with substantial doses of corticosteroids , and 3 ) animal studies had shown the advantage of combined chemotherapy for lupus nephritis [ 22 , 23 ] . Our study design was modified from previous design s so that therapy could be intensified for patients with refractory or relapsing disease . Methods Patient Selection We enrolled 82 patients with lupus nephritis into this r and omized , parallel study at the Clinical Center of the National Institutes of Health ( Bethesda , Maryl and ) between 1986 and 1990 . To enter the study , patients had to have both glomerulonephritis and a diagnosis of systemic lupus erythematosus [ 24 ] . Glomerulonephritis was defined as a sediment on two or more urinalyses that showed either 10 or more erythrocytes per high-power field or erythrocyte or leukocyte casts ( without evidence of infection ) or both , plus histologic evidence of active proliferative lupus glomerulonephritis on a renal biopsy specimen obtained within 3 months of study entry ( provided that a biopsy could be done safely ) . Scores for renal histologic activity and chronicity were assessed as reported elsewhere [ 25 ] . All eligible patients were invited to participate . Exclusion criteria were 1 ) receipt of cytotoxic drug treatment for more than 2 weeks during the 6 weeks before study entry or receipt of cyclophosphamide therapy for more than 10 weeks at any time ; 2 ) receipt of pulse therapy with corticosteroids during the 6 weeks before study entry ; 3 ) need [ at the time of study entry ] for oral corticosteroids in dosages greater than 0.5 mg of a prednisone equivalent per kilogram of body weight per day to control extrarenal disease ; 4 ) active or chronic infection ; 5 ) pregnancy ; 6 ) the presence of only one kidney ; 7 ) insulin-dependent diabetes mellitus ; and 8) allergy to methylprednisolone or cyclophosphamide . Study Design The protocol that we used was approved by the NIDDK/NIAMS ( National Institute of Diabetes and Digestive and Kidney Diseases/National Institute of Arthritis and Musculoskeletal and Skin Diseases ) Institutional Review Board [ 86-AR-0189 ] . After giving signed , written informed consent , patients were r and omly assigned to one of three treatment groups by drawing from a masked card sequence arranged from a table of r and om numbers . Each group received one of the following regimens : 1 ) intravenous methylprednisolone [ 1 g/m2 body surface area ] , given as boluses over 60 minutes on 3 consecutive days followed by at least 12 consecutive monthly single infusions ; 2 ) intravenous cyclophosphamide , given as boluses once a month for 6 consecutive months and then once every 3 months for at least 2 more years ; and 3 ) the combination of these two regimens . After a patient completed 1 year of study , a decision about whether therapy would be modified was made on the basis of the patient 's renal status at that time ( Figure 1 ) . In patients receiving methylprednisolone , therapy was discontinued if urine studies showed that renal remission had occurred . Renal remission was defined as the presence of fewer than 10 dysmorphic erythrocytes per high-power field , the absence of cellular casts , and excretion of less than 1 g of protein per day . If a renal remission was not evident , the patient continued to receive methylprednisolone every month for 6 more months . After the additional 6 months , if renal remission was still not evident , the patient received treatment for another 6 months . Therapy with methylprednisolone was limited to a maximum of 36 monthly boluses . Figure 1 . Treatment regimens and decision pathways used in this clinical trial for lupus nephritis . At 1 year , patients who had been receiving cyclophosphamide alone or in combination with methylprednisolone continued to receive or began to receive cyclophosphamide alone , once every 3 months , if the results of urine studies were substantially improved . Substantial improvement was defined as a reduction of at least 50 % in 1 ) the number of dysmorphic erythrocytes seen in urine sample s , 2 ) the number of cellular casts , and 3 ) proteinuria , without a mmol of the serum creatinine level . Quarterly administration of cyclophosphamide was continued for 2 years after renal remission occurred , after which time therapy was stopped . After the first year of the study , patients in any treatment group who were no longer receiving monthly therapy but who had evidence of the reactivation of glomerular disease had their originally assigned regimens reinstituted as if they were beginning therapy from enrollment . Reactivation of glomerular disease was defined as new active nephritis with an increase of at least 50 % ( relative to the lowest reproducible values obtained during the study ) in at least two of the following : number of dysmorphic erythrocytes ( 10 per high-power field ) , number of cellular casts , proteinuria ( 1 g of protein per day ) , or serum creatinine level . One year after the reinstitution of therapy , patients were again evaluated for evidence of active glomerulonephritis ( as described above ) . As before , patients could be withdrawn from therapy , could restart treatment , or could continue to receive cyclophosphamide every 3 months . Patients could restart therapy no more than twice ; if therapy failed more than three times , patients were declared to be nonresponders . Treatment and Follow-up Cyclophosphamide was infused for 60 minutes at an initial dose of 0.75 g/m2 body surface area . If the leukocyte nadir was greater than 3000 cells/mm3 , the cyclophosphamide dose was increased by 25 % , to a maximum of 1 g/m2 body surface area . The dose was reduced by 25 % for leukocyte counts less than 1500 cells/mm3 . Patients with a creatinine clearance of less than 30 mL/min received an initial dose of 0.5 g/m2 body surface area , and subsequent doses were adjusted on the basis of the lowest leukocyte count . Patients treated with cyclophosphamide were hydrated , and diuretics were used to maintain neutral fluid balance . Thiethylperazine , 10 mg , with 25 mg of diphenhydramine or 0.25 mg of lorazepam , was administered orally or intravenously every 6 hours for nausea . After the middle of 1990 , patients were treated in a day hospital setting , where they received intravenous saline , 200 mL per hour for 10 hours . Mesna ( 2-mercaptoethanesulfonate ) , at 20 % of the cyclophosphamide dose , was infused intravenously for 10 minutes before cyclophosphamide was administered and every 3 hours thereafter , for a total of four doses . Ondansetron , 8 mg , was given every 4 hours beginning 4 hours after infusion of cyclophosphamide , for a total of three doses . Dexamethasone , 10 mg , was given 4 hours after administration of cyclophosphamide [ 26 ] . Patients were instructed to continue oral hydration after discharge from the day hospital to maintain a dilute and frequent diuresis for at least 24 hours after infusion of cyclophosphamide . All patients were initially given oral prednisone , 0.5 mg/kg per day for 4 weeks . The prednisone dose was then tapered by 5 mg every other day each week to the minimal dose required to control extrarenal disease or 0.25 mg/kg every other day , whichever was greater . For severe extrarenal flares of lupus , patients were permitted to receive prednisone , 1.0 mg/kg per day for 2 weeks . Blood pressure was closely monitored and was maintained within 110 to 130/70 to 85 mm Hg with antihypertensive therapy . The intervals at which patients were followed were dictated by the activity of lupus and nephritis . In general , all patients were seen monthly during the first year of the study and every 3 months thereafter . At each study visit , patients were question ed about and examined for adverse events . Outcome Measures The primary study outcome was the response to the study drugs as defined by 1 ) the percentage of patients who achieved renal remission , 2 ) the number of nonresponders ( nonresponse was defined as 10 erythrocytes per high-power field , cellular casts , proteinuria [ > 1 g of protein per day ] , and doubling of the serum creatinine level ) , and 3 ) the percentage of adverse events . The outcome data , with the exception of data on adverse events , were collected in a blinded manner on 1 May 1995 , 5 years after the last patient was enrolled in the study . Secondary outcome measures were renal failure that required dialysis ( end-stage renal disease ) , stable doubling of the serum creatinine level , and number of renal relapses ( renal relapse was defined as a reactivation of renal disease after 6 or more months of BACKGROUND Since anecdotal series and small , prospect i ve , controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis , larger trials are desirable . METHODS We conducted a 24-week r and omized , open-label , noninferiority trial comparing oral mycophenolate mofetil ( initial dose , 1000 mg per day , increased to 3000 mg per day ) with monthly intravenous cyclophosphamide ( 0.5 g per square meter of body-surface area , increased to 1.0 g per square meter ) as induction therapy for active lupus nephritis . A change to the alternative regimen was allowed at 12 weeks in patients who did not have an early response . The study protocol specified adjunctive care and the use and tapering of corticosteroids . The primary end point was complete remission at 24 weeks ( normalization of abnormal renal measurements and maintenance of baseline normal measurements ) . A secondary end point was partial remission at 24 weeks . RESULTS Of 140 patients recruited , 71 were r and omly assigned to receive mycophenolate mofetil and 69 were r and omly assigned to receive cyclophosphamide . At 12 weeks , 56 patients receiving mycophenolate mofetil and 42 receiving cyclophosphamide had satisfactory early responses . In the intention-to-treat analysis , 16 of the 71 patients ( 22.5 percent ) receiving mycophenolate mofetil and 4 of the 69 patients receiving cyclophosphamide ( 5.8 percent ) had complete remission , for an absolute difference of 16.7 percentage points ( 95 percent confidence interval , 5.6 to 27.9 percentage points ; P=0.005 ) , meeting the prespecified criteria for noninferiority and demonstrating the superiority of mycophenolate mofetil to cyclophosphamide . Partial remission occurred in 21 of the 71 patients ( 29.6 percent ) and 17 of the 69 patients ( 24.6 percent ) , respectively ( P=0.51 ) . Three patients assigned to cyclophosphamide died , two during protocol therapy . Fewer severe infections and hospitalizations but more diarrhea occurred among those receiving mycophenolate . CONCLUSIONS In this 24-week trial , mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile |
12,039 | 28,947,911 | The spatial variable approach was most common and involved st and ard statistical analysis of distance measurements .
Studies tended to demonstrate the importance of accounting for location and distribution of observations in estimating unbiased effects . | Background Cluster r and omised trials ( CRTs ) often use geographical areas as the unit of r and omisation , however explicit consideration of the location and spatial distribution of observations is rare .
In many trials , the location of participants will have little importance , however in some , especially against infectious diseases , spillover effects due to participants being located close together may affect trial results .
This review aims to identify spatial analysis methods used in CRTs and improve underst and ing of the impact of spatial effects on trial results . | Background Typical advice on the design and analysis of cluster r and omized trials ( C- RCTs ) focuses on allowance for the clustering at the level of the unit of allocation . However often C- RCTs are also organised spatially as may occur in the fields of Public Health and Primary Care where population s may even overlap . Methods We allowed for spatial effects on the error variance by a multiple membership model . These are a form of hierarchical model in which each lower level unit is a member of more than one higher level unit . Membership may be determined through adjacency or through Euclidean distance of centroids or in other ways such as the proportion of overlapping population . Such models may be estimated for Normal , binary and Poisson responses in Stata ( v10 or above ) as well as in WinBUGS or MLWin . We used this to analyse a dummy trial and two real , previously published cluster-allocated studies ( one allocating general practice s within one City and the other allocating general practice s within one County ) to investigate the extent to which ignoring spatial effects affected the estimate of treatment effect , using different methods for defining membership with Akaike 's Information Criterion to determine the " best " model . Results The best fitting model included both a fixed North-South gradient and a r and om cluster effect for the dummy RCT . For one of the real RCTs the best fitting model included both a r and om practice effect plus a multiple membership spatial term , while for the other RCT the best fitting model ignored the clustering but included a fixed North-South gradient . Alternative models which fitted only slightly less well all included spatial effects in one form or another , with some variation in parameter estimates ( greater when less well fitting models were included ) . Conclusions These particular results are only illustrative . However , we believe when design ing C- RCTs in a primary care setting the possibility of spatial effects should be considered in relation to the intervention and response , as well as any explanatory effect of fixed covariates , together with any implication s for sample size and methods for planned analyses Spatial analyses of the effect of insecticide (permethrin)-treated bed nets ( ITNs ) on nearby households both with and without ITNs was performed in the context of a large-scale , group-r and omized , controlled mortality trial in Asembo , western Kenya . Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality , moderate anemia , high-density parasitemia , and hemoglobin levels . This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs . This implies that in areas with intense malaria transmission with high ITN coverage , the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not , as commonly supposed , by simple imposition of a physical barrier protecting individuals from biting . The strength of the community effect depended upon the proportion of nearby compounds with treated nets . To maximize their public health impact , high coverage with treated nets is essential Research is needed to help identify interventions that will improve the capacity or functioning of health systems and thereby contribute to achieving global health goals . Well conducted , r and omized controlled trials ( RCTs ) , insofar as they reduce bias and confounding , provide the strongest evidence for identifying which interventions delivered directly to individuals are safe and effective . When ethically feasible , they can also help reduce bias and confounding when assessing interventions targeting entire health systems . However , additional challenges emerge when research focuses on interventions that target the multiple units of organization found within health systems . Hence , one can not complacently assume that r and omization can reduce or eliminate bias and confounding to the same degree in every instance . While others have articulated arguments in favour of alternative design s , this paper is intended to help people underst and why the potential value afforded by RCTs may be threatened . Specifically , it suggests six points to be borne in mind when exploring the challenges entailed in design ing or evaluating RCTs on health system interventions : ( i ) the number of units available for r and omization ; ( ii ) the complexity of the organizational unit under study ; ( iii ) the complexity of the intervention ; ( iv ) the complexity of the cause-effect pathway , ( v ) contamination ; and ( vi ) outcome heterogeneity . The authors suggest that the latter may be informative and that the reasons behind it should be explored and not ignored . Based on improved underst and ing of the value and possible limitations of RCTs on health system interventions , the authors show why we need broader platforms of research to complement RCTs Abstract Objectives To measure the impact on the dengue vector population ( Aedes aegypti ) and disease transmission of window curtains and water container covers treated with insecticide . Design Cluster r and omised controlled trial based on entomological surveys and , for Trujillo only , serological survey . In addition , each site had a non-r and omised external control . Setting 18 urban sectors in Veracruz ( Mexico ) and 18 in Trujillo ( Venezuela ) . Participants 4743 inhabitants ( 1095 houses ) in Veracruz and 5306 inhabitants ( 1122 houses ) in Trujillo . Intervention Sectors were paired according to entomological indices , and one sector in each pair was r and omly allocated to receive treatment . In Veracruz , the intervention comprised curtains treated with lambdacyhalothrin and water treatment with pyriproxyfen chips ( an insect growth regulator ) . In Trujillo , the intervention comprised curtains treated with longlasting deltamethrin ( PermaNet ) plus water jar covers of the same material . Follow-up surveys were conducted at intervals , with the final survey after 12 months in Veracruz and nine months in Trujillo . Main outcome measures Reduction in entomological indices , specifically the Breteau and house indices . Results In both study sites , indices at the end of the trial were significantly lower than those at baseline , though with no significant differences between control and intervention arms . The mean Breteau index dropped from 60 % ( intervention clusters ) and 113 % ( control ) to 7 % ( intervention ) and 12 % ( control ) in Veracruz and from 38 % to 11 % ( intervention ) and from 34 % to 17 % ( control ) in Trujillo . The pupae per person and container indices showed similar patterns . In contrast , in nearby communities not in the trial the entomological indices followed the rainfall pattern . The intervention reduced mosquito population s in neighbouring control clusters ( spill-over effect ) ; and houses closer to treated houses were less likely to have infestations than those further away . This created a community effect whereby mosquito numbers were reduced throughout the study site . The observed effects were probably associated with the use of material s treated with insecticide at both sites because in Veracruz , people did not accept and use the pyriproxyfen chips . Conclusion Window curtains and domestic water container covers treated with insecticide can reduce densities of dengue vectors to low levels and potentially affect dengue transmission SUMMARY An individual 's risk of infection from an infectious agent can depend on both the individual 's own risk and protective factors and those of individuals in the same community . We hypothesize that an individual 's exposure to an infectious agent is associated with the risks of infection of those living nearby , whether their risks are modified by pharmaceutical interventions or by other factors , because of the potential for transmission from them . For example , unvaccinated individuals living in a highly vaccinated community can benefit from indirect protection , or living near more children in a typhoid-endemic region ( where children are at highest risk ) might result in more exposure to typhoid . We tested this hypothesis using data from a cluster-r and omized typhoid vaccine trial . We first estimated each individual 's relative risk of confirmed typhoid outcome using their vaccination status and age . We defined a new covariate , potential exposure , to be the sum of the relative risks of all who live within 100 m of each person . We found that potential exposure was significantly associated with an individual 's typhoid outcome , and adjusting for potential exposure affected estimates of vaccine efficacy . We suggest that it is useful and feasible to adjust for spatially heterogeneous distributions of individual-level risk factors , but further work is required to develop and test such approaches OBJECTIVES Insecticide-treated bednets ( ITNs ) are effective in preventing nocturnally transmitted vector-borne diseases , but their effect on diurnally active dengue vectors has never been studied . We investigated the efficacy of ITNs in reducing Aedes aegypti population s and dengue transmission . METHODS A cluster-r and omized trial was carried out in Leogane , Haiti between July 2003 and July 2004 . The study area ( 1017 houses ) was divided into 18 sectors ( clusters ) : nine received ITNs ( Olyset(R ) long-lasting insecticidal bednets ) and nine were untreated controls . Entomological surveys [ measuring Breteau ( BI ) , house ( HI ) , container ( CI ) and pupae per person ( PPI ) indices and oviposition activity ] were undertaken at baseline and at 1 and 5 months post-intervention . All houses were georeferenced to enable spatial analysis . Control sectors received ITNs at 6 months , and a final entomological and attitudinal survey was undertaken at 12 months after baseline . Anti-dengue IgM seropositivity rates were measured at baseline and after 12 months . Efficacy of ITNs was assessed by WHO cone bioassays . RESULTS At 1-month post-intervention , entomological indices fell in all sectors , with HI and BI in the bednet sectors reduced by 6.7 ( 95 % CI -10.6 , -2.7 ; P < 0.01 ) and 8.4 ( 95 % CI -14.1 , -2.6 ; P < 0.01 ) respectively . Moreover at 1 month , ovitraps in control sectors were significantly more likely to be positive than in bednet sectors ( P < 0.01 ) . By 5 months , all indices remained low and HI , CI and BI were also significantly lower than that of baseline in the control arm . Curiously , at 5 months , HI , CI and BI were lower in the control arm than that in the bednet arm . A final survey , 12 months after the initial baseline study ( 5 months after bednets had been given to all households ) indicated that all indices were significantly lower than that at baseline ( P < 0.001 ) . Control houses located within 50 m of a bednet house had significantly lower CI ( Z = -2.67 , P = 0.008 ) and PPI ( Z = -2.19 , P = 0.028 ) at 1 month , an effect that extended to 100 m by 5 months ( Z = -2.03 , P = 0.042 and Z = -2.37 , P = 0.018 respectively ) , suggesting a spill-over effect of the bednets . An IgM serosurvey showed a 15.3 % decrease ( 95 % CI 5.0 - 25.5 % , P < 0.01 ) in the number of IgM-positive individuals from baseline to12 months later . CONCLUSIONS Insecticide-treated bednets had an immediate effect on dengue vector population s after their introduction , and over the next 5 - 12 months , the presence of ITNs may have continued to affect vector population s and dengue transmission This paper identifies spatial patterns and predictors of vaccine uptake in a cluster-r and omized controlled trial in Hue , Vietnam . Data for this study result from the integration of demographic surveillance , vaccine record , and geographic data of the study area . A multi-level cross-classified ( non-hierarchical ) model was used for analyzing the non-nested nature of individual 's ecological data . Vaccine uptake was unevenly distributed in space and there was spatial variability among predictors of vaccine uptake . Vaccine uptake was higher among students with younger , male , or not literate family heads . Students from households with higher per-capita income were less likely to participate in the trial . Residency south of the river or further from a hospital/polyclinic was associated with higher vaccine uptake . Younger students were more likely to be vaccinated than older students in high- or low-risk areas , but not in the entire study area . The findings are important for the management of vaccine campaigns during a trial and for interpretation of disease patterns during vaccine-efficacy evaluation Effects of the distribution in space of permethrin (insecticide)-impregnated bed nets ( IIBNS ) on child mortality were studied in a r and omized controlled trial of IIBNs in a an area highly endemic for Plasmodium falciparum malaria in rural northern Ghana . Eight hundred sixty-two deaths occurred among children 6 - 59 months of age during 16,841 child-years-at-risk . Mortality increased with the distance from health facilities but not with proximity to identifiable anopheline breeding sites ( reservoirs ) . The efficacy of IIBNs was independent of these distances . Mortality in users of IIBNs was independent of the proximity of nonusers , and mortality rates of nonusers and users living close to each other were similar . Poisson regression estimated a 6.7 % increase in mortality among nonusers with each 100-m shift away from the nearest compound with IIBNS , indicating that the insecticide protects nearby nonusers . High coverage of IIBNs achieves maximum impact , but users of IIBNs offer some protection to less fortunate neighbors if coverage is incomplete The effect of insecticide (permethrin)-treated bed nets ( ITNs ) on the spatial distribution of malaria vectors in neighboring villages lacking ITNs was studied during a r and omized controlled trial of ITNs in western Kenya . There was a trend of decreased abundance of Anopheles gambiae with decreasing distance from intervention villages both before ( P = 0.027 ) and after ( P = 0.002 ) introduction of ITNs , but this trend was significantly stronger after ITNs were introduced ( P = 0.05 ) . For An . funestus , no pre-intervention trend was observed ( P = 0.373 ) , but after the intervention , a trend of decreased abundance with closer proximity to intervention compounds developed ( P = 0.027 ) . Reduction in mosquito population s in villages lacking ITNs was most apparent in compounds located within 600 meters of intervention villages . Sporozoite infection rates decreased in control areas following the introduction of ITNs ( P < 0.001 for both species ) , but no spatial association was detected between sporozoite rates and distance to nearest intervention village . We conclude that high coverage of ITNs is associated with a community-wide suppression of mosquito population s that is detectable in neighboring villages lacking ITNs , thereby affording individuals residing in these villages some protection against malaria |
12,040 | 27,776,567 | In total , we ended up with 18 articles for our purpose s. RESULTS The combination of depression and DM may be harmful as depression has a strong impact on psychosocial and medical outcomes in patients with DM .
It showed that depression improvement had a favourable effect on glycaemic control that was weight independent .
Bear in mind that there is a possible risk of hypoglycemia when using SSRIs . | OBJECTIVE Depression may be difficult to treat and with comorbid diabetes mellitus ( DM ) it is an even bigger challenge .
This article aims to evaluate antidepressants most suitable for patients with depression and comorbid DM . | Objective : The presence of co-morbid depressive symptoms may have a negative impact on the management of diabetes mellitus . Moreover , some antidepressants may adversely affect glycemic control . Selective serotonin reuptake inhibitors ( SSRIs ) may improve glycemic control and may be beneficial for patients with co-morbid depression and diabetes . We examined the safety and efficacy of s-citalopram therapy in patients with co-morbid depression and diabetes , and its ability to improve glycemic control . Research Design and Methods : 17 patients were enrolled into the trial and 14 patients received open-label s-citalopram therapy for up to 16 weeks . Clinical outcome measures included the 17-item Hamilton depression rating ( HAM-D 17 ) and the clinical global impressions severity ( CGI/S ) and change ( CGI/C ) ratings . In addition , fasting glucose , fructosamine , and glycosylated hemoglobin-A1C measures were obtained before and during s-citalopram therapy . Results : We observed a significant reduction in mean HAM-D 17 ( p < 0.001 ) , CGI/S ( p = 0.001 ) and CGI/C ( p = 0.001 ) ratings during s-citalopram therapy . We also observed a modest , non-significant reduction in fasting glucose , fructosamine , and glycosylated hemoglobin-A1C levels during s-citalopram therapy . Limitation : Limitations of this study include a modest patient sample size and a 16-week treatment duration which may have been insufficient to demonstrate the full effect of SSRI therapy on glycemic control . Conclusion : We observed a significant reduction in depressive symptoms and modest , non-significant reductions in fasting glucose , fructosamine , and glycosylated hemoglobin-A1C levels during SSRI therapy of co-morbid depression and diabetes To evaluate the efficacy and safety of oral magnesium supplementation , with magnesium chloride ( MgCl2 ) , in the treatment of newly diagnosed depression in the elderly with type 2 diabetes and hypomagnesemia . Twenty-three elderly patients with type 2 diabetes and hypomagnesemia were enrolled and r and omly allocated to receive either 50 mL of MgCl2 5 % solution equivalent to 450 mg of elemental magnesium or Imipramine 50 mg daily during 12 weeks . Widowhood or divorce in the last six months , alcoholism , degenerative illnesses of the nervous central system , recent diagnosis of diabetes , previous or current treatment with antidepressants , chronic diarrhea , use of diuretics , and reduced renal function were exclusion criteria . Hypomagnesemia was defined by serum magnesium levels < 1.8 mg/dL and depression by Yasavage and Brink score > or = 11 points . The primary trial end point was the improvement of depression symptoms . At baseline , there were no differences by age ( 69 + /- 5.9 and 66.4 + /- 6.1 years , p = 0.39 ) , duration of diabetes ( 11.8 + /- 7.9 and 8.6 + /- 5.7 years , p = 0.33 ) , serum magnesium levels ( 1.3 + /- 0.04 and 1.4 + /- 0.04 mg/dL , p = 0.09 ) , and Yasavage and Brink Score ( 17.9 + /- 3.9 and 16.1 + /- 4.5 point , p = 0.34 ) in the groups with MgCl2 and imipramine , respectively . At end of follow-up , there were no significant differences in the Yasavage and Brink score ( 11.4 + /- 3.8 and 10.9 + /- 4.3 , p = 0.27 ) between the groups in study ; whereas serum magnesium levels were significantly higher in the group with MgCl2 ( 2.1 + /- 0.08 mg/dL ) than in the subjects with imipramine ( 1.5 + /- 0.07 mg/dL ) , p < 0.0005 . In conclusion , MgCl2 is as effective in the treatment of depressed elderly type 2 diabetics with hypomagnesemia as imipramine 50 mg daily CONTEXT In patients with diabetes mellitus , depression is a prevalent and recurrent problem that adversely affects the medical prognosis . OBJECTIVE To determine whether maintenance therapy with sertraline hydrochloride prevents recurrence of major depression in patients with diabetes . DESIGN A r and omized , double-blind , placebo-controlled , maintenance treatment trial . Patients who recovered from depression during open-label sertraline treatment continued to receive sertraline ( n = 79 ) or placebo ( n = 73 ) and were followed up for up to 52 weeks or until depression recurred . SETTING Outpatient clinics at Washington University , St Louis , MO , the University of Washington , Seattle , and the University of Arizona , Tucson . PATIENTS One hundred fifty-two patients with diabetes ( mean age , 52.8 years ; 59.9 % female ; 82.9 % with type 2 diabetes ) who recovered from major depression ( 43.3 % of those initially assigned ) during 16 weeks of open-label treatment with sertraline ( mean dose , 117.9 mg/d ) . INTERVENTION Sertraline continued at recovery dose or identical-appearing placebo . MAIN OUTCOME MEASURES The primary outcome was length of time ( measured as the number of days after r and omization ) to recurrence of major depression as defined in DSM-IV . The secondary outcome was glycemic control , which was assessed via serial determinations of glycosylated hemoglobin levels . RESULTS Sertraline conferred significantly greater prophylaxis against depression recurrence than did placebo ( hazard ratio = 0.51 ; 95 % confidence interval , 0.31 - 0.85 ; P = .02 ) . Elapsed time before major depression recurred in one third of the patients increased from 57 days in patients who received placebo to 226 days in patients treated with sertraline . Glycosylated hemoglobin levels decreased during the open treatment phase ( mean + /- SD glycosylated hemoglobin level reduction , -0.4 % + /- 1.4 % ; P = .002 ) . Glycosylated hemoglobin levels remained significantly lower than baseline during depression-free maintenance ( P = .002 ) and did not differ between treatment groups ( P = .90 ) . CONCLUSIONS In patients with diabetes , maintenance therapy with sertraline prolongs the depression-free interval following recovery from major depression . Depression recovery with sertraline as well as sustained remission with or without treatment are associated with improvements in glycosylated hemoglobin levels for at least 1 year BACKGROUND This study aims to investigate the efficacy of fluoxetine and paroxetine on the levels of depression-anxiety , quality of life , disability , and metabolic control in type II diabetes mellitus ( DM ) patients . METHODS The patients were first applied the Hospital Anxiety-Depression Scale ( HADS ) . After a psychiatric interview with patients who had scores above the cut-off point , those who were diagnosed as having a major depressive disorder according to DSM-IV criteria were applied the Hamilton Depression Rating Scale ( HDRS ) and the Hamilton Anxiety Rating Scale ( HARS ) . Twenty three patients who scored 16 or above on the HDRS were included in the study and given the Short Form-36 ( SF-36 ) , and the Brief Disability Question naire ( BDQ ) and HbA1c levels were measured . Patients were r and omized on 20 mg/day fluoxetine or 20 mg/day paroxetine treatment . The patients were evaluated with the same scales at the 2(nd ) , 4(th ) , 6(th ) , and the 12(th ) weeks . RESULTS Both groups showed a statistically significant decrease in HDRS , HARS , and BDQ scores with comparison to the index assessment . At the end of treatment , though not statistically significant , a decrease was observed in HbA1c values of the fluoxetine-administered group . CONCLUSIONS Fluoxetine and paroxetine effectively reduce the severity of major depressive disorder in type II DM patients . There is need for further and longer-lasting monitoring studies with more patients in order to determine whether there is any difference in terms of their effects on glycemic control OBJECTIVE To determine whether pharmacological treatment of depression in low-income minorities with diabetes improves A1C and quality of life ( QOL ) . RESEARCH DESIGN AND METHODS This was a 6-month , r and omized , double-blind , placebo-controlled trial . Patients were screened for depression using Whooley 's two- question tool at a county diabetes clinic . Depression was confirmed ( or not ) with the Computerized Diagnostic Interview Survey ( CDIS ) software program , and the severity of depression was assessed monthly by the Hamilton Depression Scale ( HAM-D ) . Depressed subjects with A1C levels ≥8.0 % were r and omly assigned to receive either sertraline or placebo . Diabetes care was provided by nurses following detailed treatment algorithms who were unaware of therapy for depression . RESULTS A total of 150 subjects answered positively to at least one question on Whooley 's question naire . The positive predictive value for depression diagnosed by CDIS was 69 , 67 , and 84 % for positive answers to question 1 only , question 2 only , or both , respectively . Of the 89 subjects who entered the study , 75 completed . An intention-to-treat analysis revealed significant differences between baseline and 6 months in HAM-D and pain scores , QOL , and A1C and systolic blood pressure levels in both groups , with no differences between groups for the first three but a significantly greater decrease with sertraline in A1C and systolic blood pressure levels . Changes in HAM-D scores and A1C levels were significantly correlated in all subjects ( P = 0.45 [ P < 10−6 ] ) . CONCLUSIONS In this low-income minority population , pharmacological treatment of depression significantly improved A1C and systolic blood pressure levels compared with placebo OBJECTIVE Depression is prevalent in patients with diabetes . It is associated with poor glycemic control and is linked to an increased risk for diabetic complications . In this study , we assessed the efficacy of fluoxetine for depression in patients with diabetes . RESEARCH DESIGN AND METHODS Sixty patients with diabetes ( type 1 , n = 26 ; type 2 , n = 34 ) and major depressive disorder entered an 8-week r and omized placebo-controlled double-blind trial . Patients were given daily doses of fluoxetine ( up to 40 mg/day ) . The Beck Depression Inventory ( BDI ) and Hamilton Rating Scale for Depression ( HAMD ) were used to measure the severity of depression and to determine the percentage of patients who achieved substantial improvement or complete remission . GHb levels were obtained to monitor glycemic control . RESULTS Reduction in depression symptoms was significantly greater in patients treated with fluoxetine compared with those receiving placebo ( BDI , -14.0 vs. -8.8 , P = 0.03 ; HAMD , -10.7 vs. -5.2 , P = 0.01 ) . The percentage of patients achieving a significant improvement in depression per the BDI was also higher in the fluoxetine group ( 66.7 vs. 37.0 % , P = 0.03 ) . Additionally , trends toward a greater rate of depression remission ( 48.1 vs. 25.9 % , P = 0.09 per the HAMD ) and greater reduction in GHb ( -0.40 vs. -0.07 % , P = 0.13 ) were observed in the fluoxetine group . CONCLUSIONS Fluoxetine effectively reduces the severity of depression in diabetic patients . Our study demonstrated that after only 8 weeks , this treatment also produced a trend toward better glycemic control OBJECTIVES Depression is prevalent in patients with type 2 diabetes and affects quality of life . The prevalence of depression in the sample of Croatian patients with diabetes is 32.2 % . The main aim of the investigation was to evaluate the effect of antidepressant treatment on quality of life and metabolic control in depressed diabetic patients . DESIGN AND METHODS In the sample we r and omized 60 diabetic out patients with optimally controlled diabetes and with depression . The efficacy of 50 mg sertraline per day treatment was tested by the MADRAS question naire in a 24-week period , where the patients controlled themselves . Changes in the quality of life as the consequences of treatment of depression were tested by the QLSQ question naire for the quality of life follow-up . RESULTS The MADRAS scale results , measuring the changes in the degree of depression , showed substantial improvement of condition throughout the whole treatment . The first eight weeks of treatment presented statistically high significance in examinees in all the groups of chronic somatic diseases . The QLSQ scale results for measuring the quality of life showed marked improvement . Statistically significant changes occurred during the first eight weeks of treatment . Two patients withdrew their consent before starting medication and 13 dropped out later in the study . Treatment of depression with sertraline in chronic somatic patients did not induce changes in the HbA1c . CONCLUSION that the prevalence of depression in patients with somatic diseases is several times higher than in general population . Treatment of depression with antidepressants from the group of selective serotonin reuptake inhibitors ( sertraline ) causes improvement of depressive symptoms and increases the quality of life in diabetic patients . Treatment of depression has no impact upon the values control parameters in these patients As many as 25 percent of patients with diabetes mellitus may also have depressive symptoms . Tricyclic antidepressants ( TCAs ) may produce increased appetite and weight gain with adverse consequences for diabetes . The selective serotonin reuptake inhibitors ( SSRIs ) , however , may improve fasting blood sugar in laboratory studies . In an initial application , sertraline was administered at a dose of 50 mg/day in a 10-week open study to 28 non-insulin-dependent diabetes mellitus ( NIDDM ) patients with DSM-III-R major depression after a 2-week single-blind placebo washout period with a minimum 17-Item Hamilton Rating Scale for Depression ( HAM-D ) score of 18 . The patient group included 16 males and 12 females with a mean age of 54.2 + /- 8.8 years . Results indicated ( 1 ) significant improvement in mean HAM-D ( 22.6 + /- 3.4 to 4.9 + /- 5.9 , p < .001 ) and in mean Beck Depression Inventory ( BDI ) scores ( 21.9 + /- 10.5 to 12.7 + /- 8.3 , p < .001 ) ; ( 2 ) fall in platelet serotonin ( 5-HT ) content ( 79.7 + /- 22.5 to 13.6 + /- 12.7 ng/10(8 ) platelets , p < .001 ) ; ( 3 ) correlation of baseline platelet 5-HT content with response to sertraline by BDI scores ( r = 0.51 , p < .05 ) ; ( 4 ) improved dietary compliance for those with baseline value below 70 percent ( 59.7 % to 69.1 % , p < .005 ) ; and ( 5 ) 13 of 17 patients with baseline glycosylated hemoglobin A ( HbA1c ) levels greater than 8.0 , showed a reduction ( p = .018 ) . Sertraline may be an effective antidepressant in patients with diabetes mellitus and response may be predictable by higher baseline platelet 5-HT content , with the potential to improve dietary compliance and reduce HbA1c measures . As with all open studies , replication is essential OBJECTIVE Depression is a common disorder among diabetic patients and affects negatively the treatment of their basic disease . The aim of the study was to assess , whether antidepressant medication could positively influence glycemic control of diabetes type 1 in depressive or anxious patients . METHODS A six-month , double-blinded , r and omized , placebo-controlled study was performed to investigate the reaction of type 1diabetic patients ( n=21 ) to treatment of depression and anxiety symptoms using antidepressant drug sertraline . The patients were given sertraline ( 100 mg/day ) or placebo . The evolution of mental change was assessed using Zung Self-Rating Depression Scale ( SDS ) , Hamilton Anxiety Rating Scale ( HAMA ) and Hamilton Depression Rating Scale ( HAMD ) along with development of somatic parameters commonly assessed in diabetic patients , especially glycosylated hemoglobin , insulin dose and body weight . The level of active substance in serum of the patients was also measured . RESULTS Mental state improved at the level of statistical significance of p<0.001 in both patients using antidepressant and placebo . From somatic parameters , body weight and systolic blood pressure increased statistically significantly also in both groups of patients . CONCLUSIONS The mental state of most patients who successfully completed the study improved regardless of the fact if they were using antidepressant or placebo . No statistically significant connections between the mental and somatic changes were found . This finding points out to the placebo effect of the medication , to the importance of a contact with patients , but also to the need to concentrate on their mental state INTRODUCTION The presence of depression in patients with diabetes mellitus is reported to be associated with poor glycemic control and an increased risk of diabetic complications . Treatment of depression with selective serotonin reuptake inhibitors ( SSRIs ) may improve glycemic control and may be beneficial for patients with comorbid depression and diabetes . AIMS AND OBJECTIVE To study the effect of Escitalopram ( SSRI ) in patients with diabetes mellitus with comorbid depression and the relationship of treatment response for depression and glycemic control . RESEARCH DESIGN AND METHODS 40 patients received open-label Escitalopram therapy for up to 12 weeks . Clinical outcome measures included Hamilton Depression rating scale ( HAM-D ) assessment at 3 , 6 , and 12 weeks . In addition , fasting and post-pr and ial plasma glucose level , weight and waist circumference , glycosylated hemoglobin level ( HbA1C ) , lipid profile , renal function test and fundus examination were done before and during Escitalopram therapy . RESULTS A significant decline in mean HAM-D scores was observed 3 weeks onwards till the end of the study during Escitalopram therapy . There was a corresponding decline in mean fasting and post-pr and ial plasma glucose level at 6 and 12 weeks respectively and glycosylated hemoglobin level at 12 weeks was observed . CONCLUSION Escitalopram is effective in treating depression in patients with diabetes mellitus , and has beneficial effects on glycemic control Abstract : This study was design ed to compare the effects of fluoxetine and imipramine on fasting blood glucose ( FBG ) in patients with major depressive disorder . Sixty nondiabetic patients with major depressive disorder ( based on Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria ) entered this r and omized , double-blind study . Patients did not receive any medication affecting serum FBG levels for at least 2 weeks before the initiation of the study . Patients were assigned to receive 20 to 40 mg/d of fluoxetine or 75 to 200 mg/d of imipramine for 8 weeks . Pregnant women and patients with diabetes mellitus and a history of any major heart disease were excluded from this study . Additionally , none of the patients should have received electroconvulsive therapy within 6 months before the initiation of the antidepressants . FBG levels were measured at the initiation , as well as 4 and 8 weeks after starting antidepressants . Nineteen patients in the fluoxetine and 24 patients in the imipramine groups completed the study . In the fluoxetine group , FBG level was decreased from 88.5 mg/dL ( baseline ) to 85.0 mg/dL at week 4 ( P = 0.73 ) , and to 79.8 mg/dL at week 8 ( P < 0.001 ) . On the other h and , in the imipramine group , FBG level was increased from 86.96 mg/dL ( baseline ) to 89.71 mg/dL at week 4 ( P = 0.079 ) , and to 96.90 mg/dL at week 8 ( P < 0.001 ) . This 8-week study showed that FBG levels may decrease in depressive patients receiving fluoxetine and may increase in those patients treated with imipramine . Therefore , it is suggested to measure and monitor FBG before initiation and during treatment with fluoxetine and imipramine OBJECTIVE There is substantial evidence that depression constitutes a risk factor for type 2 diabetes mellitus . A recent study has shown that high salivary cortisol levels are associated with decreased insulin sensitivity in unmedicated , depressed patients . Further , antidepressive treatment might have differential effects on hypothalamus-pituitary-adrenal ( HPA ) system activity . Therefore , the aim of the present study was to examine whether insulin sensitivity improves during anti-depressive treatment in depressed patients with declining HPA system activity . METHOD Eighty in patients with an episode of major depressive disorder ( DSM-IV criteria ) were treated in a double-blind , r and omized protocol with either amitriptyline or paroxetine over a period of 5 weeks . After 6 drug-free days , an oral glucose tolerance test was performed on day 1 and again 35 days after antidepressive treatment . For quantification of free cortisol levels , saliva was obtained daily at 8:00 a.m. during weeks -1 ( washout ) and 5 . The study was conducted from May 2005 to December 2005 . RESULTS The insulin sensitivity index(Matsuda ) increased in only those patients who remitted from major depressive disorder as a result of treatment with either antidepressant ( F = 7.0 , df = 1,74 ; p < .01 ) , while correcting for body mass index . Further , cortisol concentrations declined in remitters and responders to amitriptyline ( F = 2.1 , df = 1,70 ; p < .05 ) , but not in any other subgroup . CONCLUSION Successful antidepressive treatment with either a selective serotonin reuptake inhibitor or a tricyclic substance increases the sensitivity to insulin in nondiabetic depressed patients . The herein presented longitudinal data do not exclude the HPA system as a major contributor to insulin resistance in depressed patients , but underscore the assumption of additional factors Objective Depression is a prevalent and chronic condition in diabetes and is associated with poor glucose regulation and poor compliance with diabetes treatment . This investigation evaluated the effects of nortriptyline on depression and glycemic control to see whether depression in diabetes is treatable and whether restoring mental health contributes to improved medical outcome . Method : Sixty-eight diabetic patients with poor glycemic control , 28 of whom had active major depression ( DSM-IIIR ) , completed a r and omized , placebo-controlled , double-blind trial involving 8 weeks of treatment with nortriptyline targeted to therapeutic plasma levels ( 50 - 150 ng/ml ) . Depression improvement was determined with the Beck Depression Inventory ; glucose control was measured by glycated hemoglobin levels . Compliance behavior was assessed using medication dispensing devices and glucometers equipped with electronic memory . Results : The reduction in depression symptoms was significantly greater in depressed patients treated with nortriptyline compared with those receiving placebo ( -10.2 vs -5.8 , p = .03 ) . Nortriptyline was not statistically superior to placebo in reducing glycated hemoglobin of the depressed subjects ( p = .5 ) . However , path analysis indicated that the direct effect of nortriptyline was to worsen glycemic control whereas depression improvement had an independent beneficial effect on glycated hemoglobin . These findings were not explained by the relationships of nortriptyline treatment to weight change ( r = -0.21 , p = .31 ) or depression improvement to compliance with the protocol for self-monitoring of blood glucose ( r = 0.01 , p = .97 ) . Conclusions : Major depression in diabetic patients can be effectively treated with nortriptyline at the expense of a direct hyperglycemic effect . Path analysis demonstrated a treatment-independent effect of depression improvement on glycemic control , suggesting that a more ideal antidepressant agent may both restore mental health and improve medical outcome OBJECTIVE The present study compared the efficacy of agomelatine and sertraline in the treatment of symptoms of depression/anxiety , diabetes self-care and metabolic control in a sample of depressed patients with non-optimally controlled type 2 diabetes mellitus ( DM ) . METHOD This was an observational open label study of 40 depressed patients with DM who were r and omly assigned to receive either agomelatine or sertraline , and were assessed over a 4-month period for depression , anxiety , self-care , fasting plasma glucose , haemoglobin A1c and body weight . RESULTS Lower anxiety and depression scores as well as higher self-care scores were measured in the agomelatine group compared with the sertraline group after 4 months of treatment . Although the main effects of treatment on final body weight and fasting plasma glucose were not significant , significantly lower final haemoglobin A1c levels were measured in the agomelatine group compared with the sertraline group . Both antidepressants were well tolerated and none of the patients dropped-out of the study . CONCLUSION The main finding of the present small pilot study was that agomelatine may be a promising agent in the treatment of symptoms of depression and anxiety as well as in the improvement of health-related behaviours , in depressed patients with type 2 DM possibly offering some advantages over sertraline . However , the lack of a placebo control group limits the generalisability of the findings and warrants further studies |
12,041 | 22,392,396 | RESULT The search showed that studies in this area were published recently and that the neuroanatomic substrate of SP has not yet been consoli date d. CONCLUSION In spite of method ological differences among studies , results converge to a greater activation in the insula , anterior cingulate cortex , amygdala , and prefrontal and orbitofrontal cortex of patients exposed to phobia-related situations compared to controls .
These findings support the hypotheses of the hyperactivation of a neuroanatomic structural network involved in SP | OBJECTIVE Specific phobia ( SP ) is characterized by irrational fear associated with avoidance of specific stimuli .
In recent years , neuroimaging techniques have been used in an attempt to better underst and the neurobiology of anxiety disorders .
The objective of this study was to perform a systematic review of articles that used neuroimaging techniques to study SP . | Little is known about the effects of successful psychotherapy on brain function in subjects with anxiety disorders . The present study aim ed to identify changes in brain activation following cognitive-behavioral therapy ( CBT ) in subjects suffering from specific phobia . Using functional magnetic resonance imaging ( fMRI ) , brain activation to spider videos was measured in 28 spider phobic and 14 healthy control subjects . Phobics were r and omly assigned to a therapy-group ( TG ) and a waiting-list control group ( WG ) . Both groups of phobics were scanned twice . Between scanning sessions , CBT was given to the TG . Before therapy , brain activation did not differ between both groups of phobics . As compared to control subjects , phobics showed greater responses to spider vs. control videos in the insula and anterior cingulate cortex ( ACC ) . CBT strongly reduced phobic symptoms in the TG while the WG remained behaviorally unchanged . In the second scanning session , a significant reduction of hyperactivity in the insula and ACC was found in the TG compared to the WG . These results propose that increased activation in the insula and ACC is associated with specific phobia , whereas an attenuation of these brain responses correlates with successful therapeutic intervention BACKGROUND Animal studies demonstrate that stress and negative affect enhance the release of the neuropeptide substance P ( SP ) , which binds to the neurokinin 1 ( NK1 ) receptor . This positron emission tomography ( PET ) study evaluated how the activity in the SP-NK1 receptor system in the amygdala was affected by fear provocation in subjects with specific phobia . METHODS Sixteen adult women with DSM-IV-defined specific phobia for either snakes or spiders but not both viewed pictures of feared and non-feared animals while being PET-scanned for 60 min with the highly specific NK1 receptor antagonist [(11)C]GR205171 as the labeled PET tracer . RESULTS The uptake of the labeled NK1 receptor antagonist was significantly reduced in the right amygdala during phobic stimulation . In the left amygdala no significant differences were found between phobic and non-phobic conditions . There was a negative correlation in the right , but not left , amygdala between subjective anxiety ratings and NK1 tracer binding . CONCLUSIONS Fear provocation affects the SP-NK1 receptor system in the right amygdala . This reflects reduced NK1 receptor availability during fear and could mirror an increased release of endogenous substance Neurofunctional mechanisms underlying cognitive behavior therapy ( CBT ) are still not clearly understood . This functional magnetic resonance imaging ( fMRI ) study focused on changes in brain activation as a result of one-session CBT in patients suffering from spider phobia . Twenty-six female spider phobics and 25 non-phobic subjects were presented with spider pictures , generally disgust-inducing , generally fear-inducing and affectively neutral scenes in an initial fMRI session . Afterwards , the patients were r and omly assigned to either a therapy group ( TG ) or a waiting list group ( WG ) . The scans were repeated one week after the treatment or after a one-week waiting period . Relative to the non-phobic participants , the patients displayed increased activation in the amygdala and the fusiform gyrus as well as decreased activation in the medial orbitofrontal cortex ( OFC ) during the first exposure . The therapy effect consisted of increased medial OFC activity in the TG relative to the WG . Further , therapy-related reductions in experienced somatic anxiety symptoms were positively correlated with activation decreases in the amygdala and the insula . We conclude that successful treatment of spider phobia is primarily accompanied by functional changes of the medial OFC . This brain region is crucial for the self-regulation of emotions and the relearning of stimulus-reinforcement associations Forty-six patients with spider phobia , fulfilling the DSM-IV criteria for specific phobia , were assessed with behavioral , physiological and self-report measures . They were r and omly assigned to three group treatment conditions : ( 1 ) direct treatment ; ( 2 ) direct observation ; and ( 3 ) indirect observation . All treatments were carried out in large groups of eight patients , and consisted of one 3 hr session of massed exposure and modelling . The results showed that on the behavioral test , measures and the specific self-report measures of spider phobia the direct treatment was significantly better than direct observation and indirect observation , which did not differ . On the physiological measures and the psychopathology self-report measures there were significant pre-post improvements , but no differences between the groups . The effects were maintained or furthered at the one year follow-up assessment . The proportion of clinical ly significantly improved patients were , at post-treatment , 75 % in the direct treatment , 7 % in the direct observation , and 31 % in the indirect observation group . At follow-up , the corresponding figures were 75 , 14 , and 44 % , respectively . The conclusion that can be drawn is that direct treatment is the treatment of choice BACKGROUND Exposure-based therapy for anxiety disorders is believed to operate on the basis of fear extinction . Studies have shown acute administration of D-cycloserine ( DCS ) enhances fear extinction in animals and facilitates exposure therapy in humans , but the neural mechanisms are not completely understood . To date , no study has examined neural effects of acute DCS in anxiety-disordered population s. METHODS Two hours prior to functional magnetic resonance imaging scanning , 23 spider-phobic and 23 non-phobic participants were r and omized to receive DCS 100 mg or placebo . During scanning , participants viewed spider , butterfly , and Gaussian-blurred baseline images in a block- design paradigm . Diagnostic and treatment groups were compared regarding differential activations to spider versus butterfly stimuli . RESULTS In the phobic group , DCS enhanced prefrontal ( PFC ) , dorsal anterior cingulate ( ACC ) , and insula activations . For controls , DCS enhanced ventral ACC and cau date activations . There was a positive correlation between lateral PFC and amygdala activation for the placebo-phobic group . Reported distress during symptom provocation was correlated with amygdala activation in the placebo-phobic group and orbitofrontal cortex activation in the DCS-phobic group . CONCLUSIONS Results suggest that during initial phobic symptom provocation DCS enhances activation in regions involved in cognitive control and interoceptive integration , including the PFC , ACC , and insular cortices for phobic participants BACKGROUND The study aim ed to identify brain activation during direct and automatic processing of phobogenic stimuli in specific phobia . METHODS Responses to phobia-related and neutral pictures ( spiders and mushrooms ) were measured by means of event-related functional magnetic resonance imaging during two different tasks . In the identification task , subjects were asked to identify the object ( spider or mushroom ) . In a dem and ing distraction task , subjects had to match geometric figures displayed in the foreground of the pictures . RESULTS Phobics showed greater responses to spiders versus mushrooms in the left amygdala , left insula , left anterior cingulate gyrus ( ACC ) , and left dorsomedial prefrontal cortex ( DMPFC ) during the identification task and in the left and right amygdala during the distraction task . All of these activations were also significantly increased compared to control subjects who did not show stronger brain activation to spiders versus mushrooms under any task condition . CONCLUSIONS Our findings propose specific neural correlates of automatic versus direct evaluation of phobia-relevant threat . While the amygdala , especially the right amygdala , seems to be crucially involved in automatic stimuli processing , activation of areas such as the insula , ACC and DMPFC is rather associated with direct threat evaluation and requires sufficient attentional re sources Previous imaging studies of obsessive-compulsive symptom states have implicated frontal-striatal and limbic regions in the pathophysiology of obsessive-compulsive disorder ( OCD ) . Functional imaging studies , however , have yielded inconsistent results , presumably due to method ological differences ( patient inclusion criteria , stimulus paradigm , imaging technique , and absence of control groups ) . In the present study , r and omized presentation of contamination-related and neutral visual stimuli was used to investigate the neurophysiological correlates of contamination fear in a group of medication-free OCD patients with washing behaviors and healthy controls . A total of 21 subjects ( 11 OCD patients and 10 healthy controls ) were scanned using H(2)(15)O positron emission tomography ( PET ) . Subjects were presented with pictures of clean and dirty surroundings and were requested to make indoor/outdoor decisions to control for attention differences . State anxiety and obsessionality were rated after each scan using visual analogue scales . Main effects of stimulus type ( contamination vs. neutral ) were found in bilateral occipital cortex in both groups . A significant group interaction effect was observed in the left amygdala reflecting enhanced activity in response to contamination stimuli in OCD patients . Sensitization effects were observed in the right amygdala in the OCD group ; these paralleled an increase in levels of distress and obsessionality as well as a decrease in dorsolateral prefrontal activity . The findings of the present study are consistent with the hypothesis of decreased frontal-striatal control of limbic structures , specifically the amygdala , result ing in an inadequate fear response in OCD patients with contamination fear This study evaluated the efficacy of behavioral and cognitive-behavioral one-session exposure treatment procedures with and without programmed generalization for participants with small animal phobias . Forty participants were r and omly assigned to the treatment and generalization conditions . Both treatments produced significant improvements from pre-test to post-test and these results were maintained for 1 year . The treatment effect sizes ranged from large to very large across behavioral , self-report , and subjectively rated measures . Participants in the behavioral treatment condition reported that the treatment was significantly more intrusive than participants in the cognitive-behavioral treatment group . The programmed generalization condition did not produce additional measured benefit . The results are discussed in terms of the overall effectiveness of one-session exposure treatment components for small animal phobias OBJECTIVE This study investigated the neural substrates of implicit sequence learning in subjects with and without small animal phobia , in a follow-up to analogous studies of obsessive-compulsive disorder ( OCD ) . METHOD Ten subjects with specific phobia and 10 healthy comparison subjects were studied by using a serial reaction time task paradigm and functional magnetic resonance imaging . RESULTS A main effect of condition ( implicit sequence learning versus r and om sequence ) was observed across diagnostic groups in the right striatum , as well as in other regions . In the striatum , the a priori region of interest , there were no significant effects of diagnosis or the interaction of diagnosis and condition . CONCLUSIONS Brain activation in the striatum of subjects with specific phobia does not significantly differ from that of normal comparison subjects during implicit sequence learning . This suggests different pathophysiological mechanisms for specific phobia in contrast to OCD , in which deficient striatal recruitment has been reproducibly found with this paradigm . This approach offers promise for demonstrating diagnostic specificity across different neuropsychiatric disorders based on the presence or absence of deficient striatal activation We investigated central nervous system correlates of simple phobic fear . Regional cerebral blood flow ( rCBF ) was measured using positron emission tomography ( PET ) in eight volunteers with symptomatic spider phobia that were exposed to visual phobogenic and neutral stimuli . Diazepam ( 0.1 mg/kg body weight i.v . ) or placebo was administered under double-blind conditions after initial PET scans . The PET scans were then repeated . The presence of fear was confirmed by rating procedures and increased number of nonspecific electrodermal fluctuations and by higher heart rate during phobic than during neutral stimulation . Phobic as compared to neutral stimulation elevated the regional to whole brain ( relative ) CBF in the secondary visual cortex but reduced relative rCBF in the hippocampus , prefrontal , orbitofrontal , temporopolar , and posterior cingulate cortex . Diazepam treatment did not affect the relative rCBF or the subjective or physiological fear indices . The observed rCBF pattern replicates our previous findings in snake phobics ( M. Fredrikson et al. [ 1993 ] Psychophysiology , 30 , 127 - 131 ; G. Wik et al. [ 1993 ] Psychiatry Research ( Neuroimaging ) , 50 , 15 - 24 ) and indicates that fear and anxiety affect cortical areas outside the classic limbic system areas Positron emission tomography was employed to contrast the brain activation pattern in patients with obsessive-compulsive disorder ( OCD ) to that of matched control subjects while they performed an implicit learning task . Although patients and control subjects evidence d comparable learning , imaging data from control subjects indicated bilateral inferior striatal activation , whereas OCD patients did not activate right or left inferior striatum and instead showed bilateral medial temporal activation . The findings further implicate corticostriatal dysfunction in obsessive-compulsive disorder . Furthermore , when OCD patients are confronted with stimuli that call for recruitment of corticostriatal systems , they instead appear to access brain regions normally associated with explicit ( conscious ) information processing Fifty-two patients with spider phobia , fulfilling the DSM-III-R criteria for simple phobia , were assessed with behavioral , physiological and self-report measures . They were r and omly assigned to five different treatment conditions : ( 1 ) one session therapist-directed exposure ( maximum 3 hours ) , ( 2 ) specific manual-based treatment in the home , ( 3 ) specific manual-based treatment at the clinic , ( 4 ) general manual-based treatment in the home and ( 5 ) general manual-based treatment at the clinic . The results show that therapist-directed one-session treatment was significantly more effective than three of the manual-based treatments , both at the post-treatment and follow-up stages . Specific manual-based treatment at the clinic was significantly more successful than the other manual-based treatments , but only at follow-up . The proportion of clinical ly significant improved patients at follow-up was 80 % in the therapist-directed group compared to 63 % for the specific manual-based treatment at the clinic , 10 % for specific manual-based treatment in the home , 9 % for general manual-based treatment in the home , and 10 % for general manual-based treatment at the clinic . The conclusion that can be drawn is that one-session therapist-directed treatment is the treatment of choice for spider phobia but manual-based treatment is a good alternative in some cases Behavioural studies suggest that phobic subjects are hypersensitive in the processing of phobia-related linguistic stimuli . We used functional magnetic resonance imaging ( fMRI ) to investigate blood oxygen level dependent ( BOLD ) brain activation to phobia-relevant words in spider phobic and non-phobic subjects . Phobia-related versus phobia-unrelated words elicited increased activation in prefrontal cortex , insula , and posterior cingulate cortex in spider phobics , while these effects were absent in controls . Furthermore , between-group comparisons confirmed that differential activations within these brain regions were specifically due to increased responses to phobia-related stimuli in phobics . Our results provide first insights into brain activation patterns when phobics are confronted with phobia-specific linguistic information und suggest a neural network for the processing of these threatening stimuli BACKGROUND The amygdala is implicated as a key brain structure in fear processing . Studies exploring this process using the paradigm of fear conditioning have implicated the amygdala in fear acquisition and in generating behavioral fear responses . As such , fear extinction could be expected to induce a reduction in amygdala activity . However , exposure in specific phobia has never been shown persistently to reduce amygdala activity . METHODS By means of event-related functional magnetic resonance imaging , responses to phobia-related , general threat , and neutral pictures were measured before and 2 weeks after an intensive exposure session in 20 subjects with specific phobia for spiders and compared with healthy control subjects . RESULTS Phobic subjects showed increased amygdala activity at baseline . This hyperactivity was significantly reduced 2 weeks after exposure therapy . Furthermore , a significant reduction of hyperactivity in anterior cingulate cortex and insula was found postexposure . CONCLUSIONS To our knowledge , this is the first study demonstrating the effect of exposure on the amygdala in specific phobia . Our findings suggest that exposure therapy can have an effect on subcortical structures |
12,042 | 28,502,603 | Alcohol consumption mostly deteriorated the following performance outcomes in descending order : SDSD , LPSD , speed , MLPD , LC and NA .
Alcohol consumption may decrease simulated driving performance in alcohol consumed people compared with non-alcohol consumed people via changes in SDSD , LPSD , speed , MLPD , LC and NA . | PURPOSE Alcohol consumption can lead to risky driving and increase the frequency of traffic accidents , injuries and mortalities .
The main purpose of our study was to compare simulated driving performance between two groups of drivers , one consumed alcohol and the other not consumed , using a systematic review . | The aim of this study was to determine the association between drug type and arrest for driving under the influence of drugs ( DUID ) by calculating odds ratios ( ORs ) using a case-control design . A DUID arrest is in most cases related to aberrant or risky driving and might therefore be regarded as a proxy for a drug related traffic crash . The ' cases ' were 2738 drivers arrested on suspicion of drugged driving from April 2008 to March 2009 with blood alcohol concentrations below the legal limit of 0.2g/L ; 794 were arrested due to involvement in road traffic crashes , whereas 1944 were arrested for other reasons , mainly dangerous driving , suspected impairment when stopped in traffic controls , or because of phone calls to the police from other road users or observers . The ' controls ' were 9375 r and om drivers in normal traffic , also with alcohol concentrations below this limit . Blood sample s from ' cases ' and oral fluid sample s from ' controls ' were analyzed for 15 drugs that have legislative concentration limits in Norway , in addition to two other commonly detected psychoactive drugs . The most prevalent illicit drug in the control group was tetrahydrocannabinol ( THC ; 0.58 % ) , which was also commonly found in sample s from drivers arrested due to road crash ( 15.6 % ) or arrested for other reasons ( 21.8 % ) . Amphetamine/methamphetamine was most prevalent among arrested drivers involved in crashes ( 30.6 % ) and drivers arrested for other reasons ( 56.9 % ) , whereas only 0.18 % of the control group was positive for amphetamine/methamphetamine . The single-use substances which gave highest OR for police arrest were amphetamine/methamphetamine , alprazolam , clonazepam and oxazepam . The majority of the alprazolam and clonazepam findings were probably due to non-therapeutic use of medicinal drugs purchased on the illegal market . Combinations of two or more drugs yielded higher ORs than the use of single substances ; combinations of amphetamine/methamphetamine and benzodiazepines gave the highest risk Rationale In party circuits dexamphetamine is frequently used in combination with alcohol . It is hypothesized that co-administration of dexamphetamine to alcohol might reduce the sedative effects of alcohol , but may potentiate risk-taking behaviour . Objectives The study was aim ed at assessing the effects of alcohol , dexamphetamine and the combination of both on simulated driving and cognitive performance . Method Eighteen subjects participated in a r and omized , crossover , placebo-controlled study employing four conditions : 10 mg dexamphetamine , 0.8 g/kg alcohol , 10 mg dexamphetamine + 0.8 g/kg alcohol , and placebo . Fundamental driving skills and risk-taking behaviour were assessed in a driving simulator . Subjects also completed vigilance and divided attention tasks , and subjective ratings . Results Mean BAC levels during simulated driving were between 0.91‰ and 0.64‰. Subjects using alcohol showed a significantly larger mean st and ard deviation of lateral position and shorter accepted gap time and distance . Use of alcohol or dexamphetamine + alcohol was associated with a higher frequency of red light running and collisions than the dexamphetamine or placebo conditions . Performance of vigilance and divided attention tasks was significantly impaired in the alcohol condition and , to a lesser degree , in the dexamphetamine + alcohol condition . ConclusionS ingle doses of 0.8 g/kg alcohol increased risk-taking behaviours and impaired tracking , attention and reaction time during a 3-h period after drinking when BACs declined from 0.9 to 0.2 mg/ml . The stimulatory effects of co-administration of dexamphetamine 10 mg were not sufficient to overcome the impairing effects of alcohol on skills related to driving Using a cover story of the effects of alcohol on perceptual and motor abilities , two levels of alcohol consumed ( moderate and none ) , two levels of alcohol expectancy ( moderate and none ) , and two levels of sensation seeking ( high and low ) were combined to determine their effect on risk taking in a driving simulator . Ninety-six subjects were r and omly assigned to eight conditions . Dependent variables were lane changes-cars passed and time at maximum speed . Results on lane-changes-cars passed indicated greater risk-taking in driving by high sensation seekers . Interaction of alcohol expectancy and sensation seeking indicated high sensation seekers took more risks when they believed they had consumed alcohol . Low sensation seekers became more cautious in driving when they believed they had consumed alcohol . Alcohol consumed did not produce a significant main effect or interaction The present investigation employed a balanced placebo design to examine the effects of alcohol versus the belief that one has consumed alcohol , i.e. alcohol expectancy , on error production while operating a driving simulator . The male subjects employed were social drinkers , having no history of alcohol abuse . The alcoholic beverage consisted of vodka and tonic in the ratio of 1:5 , result ing in a mean blood alcohol level of .064 % . The placebo beverage consisted of water and tonic , also in the ration 1:5 . Principal findings were that alcohol ingestion had a debilitating effect on certain measures of driving behavior ( operation of brakes , steering ) , whereas the belief that one had consumed alcohol had no discernable effects . The results are discussed in relation to other findings using the balanced placebo design . It was concluded that reckless driving under the influence of alcohol , is at least partly a result of the pharmological effects of ethanol Rationale The driving simulator provides a safe and controlled environment for testing driving behaviour efficiently . The question is whether it is sensitive to detect drug-induced effects . Objective The primary aim of the current study was to investigate the sensitivity of the driving simulator for detecting drug effects . As a case in point , we investigated the dose-related effects of oral ∆9-tetrahydrocannabinol ( THC ) , i.e. dronabinol , on simulator and on-the-road driving performance in equally dem and ing driving tasks . Method Twenty-four experienced driver participants were treated with dronabinol ( Marinol ® ; 10 and 20 mg ) and placebo . Dose-related effects of the drug on the ability to keep a vehicle in lane ( weaving ) and to follow the speed changes of a lead car ( car following ) were compared within subjects for on-the-road versus in-simulator driving . Additionally , the outcomes of equivalence testing to alcohol-induced effects were investigated . Results Treatment effects found on weaving when driving in the simulator were comparable to treatment effects found when driving on the road . The effect after 10 mg dronabinol was however less strong in the simulator than on the road and inter-individual variance seemed higher in the simulator . There was , however , a differential treatment effect of dronabinol on reactions to speed changes of a lead car ( car following ) when driving on the road versus when driving in the simulator . Conclusion The driving simulator was proven to be sensitive for demonstrating dronabinol-induced effects particularly at higher doses . Treatment effects of dronabinol on weaving were comparable with driving on the road but inter-individual variability seemed higher in the simulator than on the road which may have potential effects on the clinical inferences made from simulator driving . Car following on the road and in the simulator were , however , not comparable The Lane Change Task was developed to provide an objective safety criterion for the assessment of driver distraction by in-vehicle information systems ( IVIS ) . It consists of two basic driving tasks , namely lane keeping and lane changes . The LCT has been shown to reliably detect distraction from driving . As this test becomes increasingly important for the assessment of safety the validity of the LCT is crucial . In order to examine this further , the effect of an alcohol intoxication of 0.08 g/dl on the performance in the LCT was examined in the present study as the negative effects of alcohol on driving are well known . Twenty-three participants were tested under alcohol and placebo in a cross-over design measuring different performance indicators in the LCT . There were significant effects of alcohol during the lane keeping phase . However , these were much smaller than those typically found with distracting secondary tasks . The lane change phase was only marginally affected by alcohol . This result gives rise to some caution for interpreting effects in the LCT . The LCT is well able to detect distraction , as other studies have shown . However , our study with intoxicated participants shows that a small effect in the LCT does not necessarily mean that this condition does not impair driving AIMS Marketing that promotes mixing caffeinated ' energy ' drinks with alcoholic beverages ( e.g. Red Bull with vodka ) targets young drinkers and conveys the expectation that caffeine will offset the sedating effects of alcohol and enhance alertness . Such beliefs could result in unwarranted risk taking ( e.g. driving while intoxicated ) . The aim of this study was to assess the acute effects of caffeinated versus non-caffeinated alcoholic beverages on a simulated driving task and attention/reaction time . DESIGN We conducted a 2 × 2 between-groups r and omized trial in which participants were r and omized to one of four conditions : beer and non-alcoholic beer , with and without caffeine added . Caffeine was added in the same proportion as found in a commercially available caffeinated beer ( 69 mg/12 oz of beer at 4.8 % alc . by vol ) . PARTICIPANTS Participants were 127 non-dependent , heavy episodic , young adult drinkers ( age 21 - 30 ) who were college students or recent graduates . The target breath alcohol level was 0.12 g% . MEASURES Driving performance was assessed with a driving simulator ; sustained attention/reaction with the Psychomotor Vigilance Task ( PVT ) . FINDINGS Across the driving and attention/reaction time we found main effects for alcohol , with alcohol significantly impairing driving and sustained attention/reaction time , with mainly large statistical effects ; however , the addition of caffeine had no main or interaction effects on performance . CONCLUSION The addition of caffeine to alcohol does not appear to enhance driving or sustained attention/reaction time performance relative to alcohol alone Both driving speed and speed of detection of potentially hazardous events while driving have been found to correlate positively with accident rates across individuals . Alcohol ingestion is also known to increase risk of a traffic accident . This paper reports two double-blind , placebo-controlled studies : one on the effect of alcohol on driving speed and the other on the effect of alcohol on time taken to detect potential traffic hazards . Moderate drinkers aged between 30 and 55 took part . Each subject underwent three experimental conditions on separate days : no alcohol , low alcohol ( 0.025 % BAC ) and moderate alcohol ( 0.05 % BAC ) . The order of conditions was counterbalanced . The moderate alcohol dose increased mean time taken to respond to hazards ( 2.5 s in no alcohol condition compared with 3.2 s in moderate alcohol condition ) but did not affect mean driving speed ( indexed by time taken to travel sections of a fixed route ; 19.3 s in no alcohol compared with 19.0 s in moderate alcohol ) . The results support the view that at least part of the excess risk of accident associated with alcohol ingestion is attributable to an increase in the time taken to respond to traffic hazards High rates of binge drinking and alcohol-related problems , including drinking and driving , occur among college students . Underlying reasons for the heightened impaired driving rates in this demographic group are not known . The authors hypothesized that acute tolerance to the interoceptive cues of intoxication may contribute to these maladaptive decisions to drive in binge drinkers . Groups of binge-drinking and non-binge-drinking college students ( N = 28 ) attended sessions during which they received a moderate dose of alcohol ( 0.65 g/kg ) or a placebo . The development of acute tolerance to subjective ratings of intoxication and simulated driving performance was assessed by comparing measures taken during the ascending phase and descending phases of the blood alcohol curve . Compared with placebo , alcohol increased ratings of intoxication and impaired multiple aspects of simulated driving performance in both binge and non-binge drinkers . During the descending phase of the blood alcohol curve , binge drinkers showed acute tolerance to alcohol 's effect on subjective intoxication , and this effect was accompanied by an increased rating of willingness to drive . By contrast , non-binge drinkers showed no acute tolerance Changes in drivers , vehicles , and roadways pose substantial challenges to the transportation safety community . Crash records and naturalistic driving data are useful for examining the influence of past or existing technology on drivers , and the associations between risk factors and crashes . However , they are limited because causation can not be established and technology not yet installed in production vehicles can not be assessed . Driving simulators have become an increasingly widespread tool to underst and evolving and novel technologies . The ability to manipulate independent variables in a r and omized , controlled setting also provides the added benefit of identifying causal links . This paper introduces a special issue on simulator-based safety studies . The special issue comprises 25 papers that demonstrate the use of driving simulators to address pressing transportation safety problems and includes topics as diverse as neurological dysfunction , work zone design , and driver distraction This study presents an investigation of the effects of peer attitude , gender , and blood alcohol level on driving performance using a driving simulator . The subjects were 18 male and 18 female social drinkers from the general population , aged 18 - 25 , and holding a current drivers ' licence . Subjects were r and omly assigned to pro or against drinking driving conditions and tested at different blood alcohol levels . The results revealed that subjects in the for drinking driving condition perceived themselves to be more capable than they actually were and drove increasingly faster and made more mistakes than subjects in the against drinking driving condition when under the influence of alcohol . Significant sex differences were observed only for performance on the driving simulator . Males , in the main , engaged in more dangerous driving and risk taking in simulated driving conditions than females |
12,043 | 22,233,833 | Training of providers alone ( even in a specific interventional method ) did not result in improved patient outcomes .
The additional implementation of guidelines and the use of more complex interventions in primary care yield a significant reduction in depressive symptomatology .
Provider training by itself does not seem to improve depression care ; however , if combined with additional guidelines implementation , results are promising for new-onset depression patient sample s. Additional organizational structure changes in form of collaborative care models are more likely to show effects on depression care | Background Primary care practice s provide a gate-keeping function in many health care systems .
Since depressive disorders are highly prevalent in primary care setting s , reliable detection and diagnoses are a first step to enhance depression care for patients .
Provider training is a self-evident approach to enhance detection , diagnoses and treatment options and might even lead to improved patient outcomes . | Abstract OBJECTIVE : To determine the incremental cost-effectiveness of a quality improvement depression intervention ( enhanced care ) in primary care setting s relative to usual care . DESIGN : Following stratification , we r and omized 12 primary care practice s to enhanced or usual care conditions and followed patients for 12 months . SETTING : Primary care practice s located in 10 states across the United States . PATIENTS / PARTICIPANTS : Two hundred eleven patients beginning a new treatment episode for major depression . INTERVENTIONS : Training the primary care team to assess , educate , and monitor depressed patients during the acute and continuation stages of their depression treatment episode over 1 year . MEASUREMENTS AND MAIN RESULTS : Cost-effectiveness was measured by calculating incremental ( enhanced minus usual care ) costs and quality -adjusted life years ( QALYs ) derived from SF-36 data . The mean incremental cost-effectiveness ratio in the main analysis was $ 15,463 per QALY . The mean incremental cost-effectiveness ratios for the sensitivity analyses ranged from $ 11,341 ( using geographic block variables to control for pre-intervention service utilization ) to $ 19,976 ( increasing the cost estimates by 50 % ) per QALY . CONCLUSIONS : This quality improvement depression intervention was cost-effective relative to usual care compared to cost-effectiveness ratios for common primary care interventions and commonly cited cost-effectiveness ratio thresholds for intervention implementation Abstract BACKGROUND : Major depression is common in older adults and is associated with increased health care costs . Depression often remains unrecognized in older adults , especially in primary care . OBJECTIVE : To evaluate the cost-effectiveness of a disease management program for major depression in elderly primary care patients compared with usual care . DESIGN : Economic evaluation alongside a cluster r and omized-controlled trial . PARTICIPANTS : Consecutive patients of 55 years and older were screened for depression using the Geriatric Depression Scale and the PRIME-MD was used for diagnosis . INTERVENTIONS : General practitioners in the intervention group received training on how to implement the disease management program consisting of screening , patient education , drug therapy with paroxetine , and supportive contacts . General practitioners in the usual care group were blind to the screening results . Treatment in this group was not restricted in any way . MEASUREMENTS : Severity of depression , recovery from depression , and quality of life . Re source use measured over a 12-month period using interviews and valued using st and ard costs . RESULTS : Differences in clinical outcomes between the intervention and usual care group were small and statistically insignificant . Total costs were $ 2,123 in the intervention and $ 2,259 in the usual care group ( mean difference −$136 , 95 % confidence interval : −$1,194 ; $ 1,110 ) . Cost-effectiveness planes indicated that there were no statistically significant differences in cost-effectiveness between the 2 groups . CONCLUSIONS : This disease management program for major depression in elderly primary care patients had no statistically significant relationship with clinical outcomes , costs , and cost-effectiveness . Therefore , based on these results , continuing usual care is recommended BACKGROUND General practitioners ( GPs ) can be provided with effective training in the skills to manage depression . However , it remains uncertain whether such training achieves health gain for their patients . METHOD The study aim ed to measure the health gain from training GPs in skills for the assessment and management of depression . The study design was a cluster r and omized controlled trial . GP participants were assessed for recognition of psychological disorders , attitudes to depression , prescribing patterns and experience of psychiatry and communication skills training . They were then r and omized to receive training at baseline or the end of the study . Patients selected by GPs were assessed at baseline , 3 and 12 months . The primary outcome was depression status , measured by HAM-D. Secondary outcomes were psychiatric symptoms ( GHQ-12 ) quality of life ( SF-36 ) , satisfaction with consultations , and health service use and costs . RESULTS Thirty-eight GPs were recruited and 36 ( 95 % ) completed the study . They selected 318 patients , of whom 189 ( 59 % ) were successfully recruited . At 3 months there were no significant differences between intervention and control patients on HAM-D , GHQ-12 or SF-36 . At 12 months there was a positive training effect in two domains of the SF-36 , but no differences in HAM-D , GHQ-12 or health care costs . Patients reported trained GPs as somewhat better at listening and underst and ing but not in the other aspects of satisfaction . CONCLUSIONS Although training programmes may improve GPs ' skills in managing depression , this does not appear to translate into health gain for depressed patients or the health service Abstract Objective : To assess the effectiveness of teaching general practitioners skills in brief cognitive behaviour therapy . Design : Parallel group , cluster r and omised , controlled trial of an educational package on cognitive behaviour therapy . Setting : General practice s in north London . Participants : 84 general practitioner principals and 272 patients attending their practice s who scored above the threshold for psychological distress on the hospital anxiety and depression scale . Intervention : A training package of four half days on brief cognitive behaviour therapy . Main outcome measures : Scores on the depression attitude question naire ( general practitioners ) and the Beck depression inventory ( patients ) . Results : Doctors ' knowledge of depression and attitudes towards its treatment showed no major difference between intervention and control groups after 6 months . The training had no discernible impact on patients ' outcomes . Conclusion : General practitioners may require more training and support than a basic educational package on brief cognitive behaviour therapy to acquire skills to help patients with depression . What is already known on this topic Trained professionals can deliver effective cognitive behaviour therapy to depressed patients presenting to general practitioners Limited evidence shows that cognitive behaviour therapy is effective when delivered by general practitioners who have received extensive instruction Most doctors do not have the time or inclination to carry out such comprehensive training What this study adds Basic training in brief cognitive behaviour therapy has little effect on general practitioners ' attitudes to the identification and treatment of depression or the outcome of their patients with emotional problems General practitioners may require more extensive training and support if they are to acquire skills in brief cognitive behaviour therapy that will have a positive impact on their Objectives : Screening is advocated to improve the recognition of patients with major depression in primary care . Furthermore , disease management programmes are advocated to improve the quality of care and outcome for these patients . But is screening and the subsequent implementation of a disease management programme more effective than usual care ? Methods : Review of the literature on the effects of disease management programmes that include screening for major depression in general practice . Results : Six r and omised controlled trials were identified in which the effectiveness of disease management programmes were studied in patients with major depression in primary care and compared with usual care . The majority of these , and especially the largest , showed positive effects on the recognition , diagnosis , treatment and outcome of patients . Population s in the US seem to benefit most . Conclusion : The results of disease management programmes for depression in primary care that include screening are positive and are more effective than usual care . Therefore , if preceded by screening , attention to the whole process of care for patients with major depression instead of paying attention to isolated elements of the process is justified Complex interventions , which have been shown to improve primary care depression outcomes , are difficult to disseminate to routine practice setting s. To address this problem , we developed a brief intervention to train primary care physicians and nurses employed by the practice to improve the detection and management of major depression . Before recruitment began , the research team conducted academic detailing conference calls with primary care physicians and nurses , and provided in-person training with nurses and administrative staff . Administrative staff screened over 11,000 patients before their visits to identify those with probable major depression . Primary care physicians delegated increased responsibility to office nurses , who educated over 90 % of patients about effective depression treatment and systematic ally monitored their progress over time . Early results demonstrate that community primary care practice s can rebundle traditional team roles over the short-term to provide more systematic mental health treatment without adding additional personnel . A rigorous evaluation of this effort will reduce time-consuming , expensive , and often unsuccessful efforts to " translate " research intervention findings into everyday practice Abstract Objective : To evaluate the effectiveness of a population based , multifaceted shared care intervention for late life depression in residential care . Design : R and omised controlled trial , with control and intervention groups studied one after the other and blind follow up after 9.5 months . Setting : Population of residential facility in Sydney living in self care units and hostels . Participants : 220 depressed residents aged ≥65 without severe cognitive impairment . Intervention : The shared care intervention included : ( a ) multidisciplinary consultation and collaboration , ( b ) training of general practitioners and carers in detection and management of depression , and (c)depression related health education and activity programmes for residents . The control group received routine care . Main outcome measure : Geriatric depression scale . Results : Intention to treat analysis was used . There was significantly more movement to “ less depressed ” levels of depression at follow up in the intervention than control group ( Mantel-Haenszel stratification test , P=0.0125 ) . Multiple linear regression analysis found a significant intervention effect after controlling for possible confounders , with the intervention group showing an average improvement of 1.87 points on the geriatric depression scale compared with the control group ( 95 % confidence interval 0.76 to 2.97 , P=0.0011 ) . Conclusions : The outcome of depression among elderly people in residential care can be improved by multidisciplinary collaboration , by enhancing the clinical skills of general practitioners and care staff , and by providing depression related health education and activity programmes for residents . Key messages Large numbers of depressed elderly people live in residential care but few receive appropriate management A population based , multifaceted shared care intervention for late life depression was more effective than routine care in improving depression outcome The outcome of late life depression can be improved by enhancing the clinical skills of general practitioners and care staff and by providing depression related health education and activity programmes for residents The intervention needs further refining and evaluation to improve its effectiveness and to determine how best to implement it in other residential care setting BACKGROUND Depression , a common disorder often treated by family physicians , may be both underdiagnosed and undertreated . The objective of this study was to determine whether the diagnosis and treatment of depression by family physicians could be improved through an educational strategy . METHODS In this study , conducted between July and December 1997 , 42 family physicians in Newfoundl and were r and omly assigned to an intervention group ( 3-hour case-based educational session on clinical practice guidelines [ CPGs ] for depression and access to a psychiatrist for consultation ) or to a control group ( receipt of CPGs without educational session or access to the psychiatrist ) . Physicians were asked to keep a log of patients with newly diagnosed depression and to record information on severity of depression , medications and referrals to mental health professionals . Patients were asked to complete the Centre for Epidemiologic Studies Depression ( CES-D ) scale before treatment and after 6 months of follow-up . The primary outcome measure was the " gain " score ( difference between first and last CES-D scores ) . RESULTS During the study period physicians in the intervention group diagnosed 91 new cases of depression ( mean 4.1 per physician ) and those in the control group diagnosed 56 ( mean 2.8 per physician ) ; the difference was not significant . Most patients ( 91.2 % in the intervention group and 89.3 % in the control group received a prescription for an antidepressant on their first visit . Similar proportions ( 46.2 % in the intervention group and 37.5 % in the control group ) took their medication for the full 6 months ; however , significantly more patients in the intervention group were taking an antidepressant at the 6-month follow-up ( 56 % v. 39.3 % , p = 0.02 ) . The mean number of visits per patient was similar in the 2 groups ( 7.7 in the intervention group and 7.6 in the control group ) . Physicians in the intervention group consulted the psychiatrist 9 times . The overall rate of referrals to psychiatrists and other mental health professionals was 10.9 % ; however , referrals were significantly higher in the intervention group ( 15.4 % v. 3.5 % , p = 0.05 ) . After 6 months of follow-up , a significant difference in gain scores was detected between the intervention and control groups for both the patient 's self-rated CES-D scores ( mean gain score 19.3 v. 15.5 respectively , p = 0.04 ) and the physicians ' ratings of depression severity before treatment and at 6 months ( mean gain 1.1 v. 0.7 respectively , p = 0.02 ) . INTERPRETATION The educational strategy had a modest beneficial effect on the outcomes of patients with depression , but there are still concerns regarding the low rates of drug treatment and referral to mental health professionals by family physicians PURPOSE Although potentially costly , enhancing primary care depression management on an ongoing basis results in substantial long-term treatment effectiveness . The purpose of this article is to compare the cost-effectiveness of this approach with that of usual care . METHODS The study was conducted in 12 community primary care practice s r and omized to enhanced or usual care after stratification by baseline practice patterns . Practice s assigned to enhanced care encouraged depressed patients to engage in active treatment , using practice nurses to provide regularly scheduled care management during the course of 24 months . We analyze outcomes for 211 adults ( 73.4 % of potential eligible patients ) beginning a new treatment episode for major depression determined by previsit screening . Outcomes included blinded estimates of days free of depression impairment as well as health care costs for 2 years . RESULTS Enhanced care significantly increased the number of days free of depression impairment for 2 years when compared with usual care ( 647.6 days vs 588.2 days , P < .01 ) . The incremental cost-effectiveness ratio for enhanced care ranged from $ 9,592 to $ 14,306 per quality -adjusted life-year ( QALY ) . The number of incremental days free of depression impairment increased between the first year and the second year ( 23.0 vs 36.4 , respectively , P < .001 ) while incremental health plan costs decreased significantly ( $ 568 vs -$12 , P < .001 ) . CONCLUSIONS Enhancing primary care depression management on an ongoing basis should be considered for adoption by policy and health plan leaders Abstract OBJECTIVE : To determine whether redefining primary care team roles would improve outcomes for patients beginning a new treatment episode for major depression . DESIGN : Following stratification , 6 of 12 practice s were r and omly assigned to the intervention condition . Intervention effectiveness was evaluated by patient reports of 6-month change in 100-point depression symptom and functional status scales . SETTING : Twelve community primary care practice s across the country employing no onsite mental health professional . PATIENTS : Using two-stage screening , practice s enrolled 479 depressed adult patients ( 73.4 % of those eligible ) ; 90.2 % completed six-month follow-up . INTERVENTION : Two primary care physicians , one nurse , and one administrative staff member in each intervention practice received brief training to improve the detection and management of major depression . MAIN RESULTS : In patients beginning a new treatment episode , the intervention improved depression symptoms by 8.2 points ( 95 % confidence interval [ CI ] , 0.2 to 16.1 ; P=.04 ) . Within this group , the intervention improved depression symptoms by 16.2 points ( 95 % CI , 4.5 to 27.9 ; P=.007 ) , physical role functioning by 14.1 points ( 95 % CI , 1.1 to 29.2 ; P=.07 ) , and satisfaction with care ( P=.02 ) for patients who reported antidepressant medication was an acceptable treatment at baseline . Patients already in treatment at enrollment did not benefit from the intervention . CONCLUSIONS : In practice s without onsite mental health professionals , brief interventions training primary care teams to assume redefined roles can significantly improve depression outcomes in patients beginning a new treatment episode . Such interventions should target patients who report that antidepressant medication is an acceptable treatment for their condition . More research is needed to determine how primary care teams can best sustain these redefined roles over time BACKGROUND Various methods are available for implementing change in the clinical behaviour of general practitioners ( GPs ) . Although passive dissemination of information is generally ineffective , other methods can be variably effective . Few studies have investigated the impact of tailored methods . AIM To determine whether methods tailored to overcome obstacles to change using psychological theories are more effective than dissemination alone in the implementation of guidelines for depression among GPs . DESIGN OF STUDY R and omised controlled trial . SETTING Sixty general practice s in Engl and ; 30 GPs in the control group , 34 in the intervention group . METHOD Practitioners identified patients presenting with depression before and after the implementation of guidelines ( control group n = 192 in the first data collection , n = 181 in the second ; intervention group n = 210 in the first data collection and n = 197 in the second ) . The main outcome measures were : record of adherence to guideline recommendations in clinical records ; proportion of patients with Beck Depression Inventory ( BDI ) score less than 11 at 16 weeks after diagnosis . RESULTS In comparison with the control group , in the group of GPs receiving tailored implementation , there were increases in the proportions of patients assessed for suicide risk . In the intervention group , the proportion of patients with BDI scores of less than 11 at 16 weeks increased . CONCLUSION Obstacles to implementation can be identified and strategies tailored to address them . The findings indicate a new approach for research to underst and and develop methods of implementation Abstract Objectives : To assess the extent to which the outcome of depression among primary care attenders may be affected by medical diagnosis or by feedback of question naire results in unrecognised cases . Design : Prospect i ve 12 month study including a r and omised controlled trial of the effects of disclosure , with data on depression status and clinical management collected by question naire and interview . Setting : Two group practice s in north Liverpool . Subjects : 1099/1444 ( 76 % ) consecutive adult attenders completed the Beck depression inventory , of whom 179 with scores of at least 14 were followed up . Interventions : Disclosure of a r and om 45 % ( 52/116 ) of depression scores to general practitioners for subjects whose depression was undetected . Main outcome measures : Depression status estimated by depression score at start of study and at six and 12 months , with sub sample validation against ICD−10 criteria . Results : Question naire response rates were 76 % ( 136/179 ) at six months and 68 % ( 122/179 ) at 12 months and were higher for women than men . The median depression score was 19 ( interquartile range 15 to 22 ) initially , decreasing to 16 ( 11 to 23 ) at 12 months . The median depression score decreased significantly ( two sided test , P=0.019 ) in subjects whose depression was unrecognised at the index consultation but increased in those whose depression had been detected by their general practitioners . Disclosure of cases of unrecognised depression to general practitioners had no effect on outcome . Intention to treat was associated with a worse prognosis , although only a minority of subjects received adequate treatment . Conclusions : Disclosure of undetected depression did not improve prognosis . A diagnosis of depression in general practice should be considered simply as a marker of its severity This study set out to assess the effects on diagnosis and management of providing general practitioners with feedback of patients ' scores on a depression screening instrument . One hundred and sixteen general practice attenders aged 16 - 64 with undetected depression were identified using the Beck Depression Inventory ( BDI ) . The BDI scores of a r and om 45 % were disclosed to the general practitioners . Subjects and medical casenotes were review ed over 12 months . Thirty-one ( 27 % ) of subjects were later diagnosed as depressed . Rates of diagnosis were higher in the disclosed group , but only after six months . Rates of intention to treat were low , but were marginally higher for the disclosed group ; they were much higher for patients diagnosed by the doctors themselves . Feedback of screening question naire results appears to be of limited value in enhancing general practitioners ' detection or management of depression Records of patients included in a trial of educating practice teams about the management of depression were examined to determine changes in the process of care . There were no significant differences in the proportions recognised or treated for depression . Only 15 % of those with possible , and 26 % of those with probable , major depressive disorder were prescribed recommended doses and duration of antidepressants . The education apparently delayed a switch away from tricyclics while achieving a similar outcome . However health service costs were mainly non-psychiatric , and there were no significant savings as a result |
12,044 | 24,606,191 | There was no difference in the prevalence of ureteral strictures or vesicoureteral reflux between the various techniques .
Of the three most frequently used ureterovesical anastomotic techniques , the LG technique results in fewer urological complications than the PL and U techniques | No consensus exists about which ureterovesical anastomosis technique to use for kidney transplantation .
The aim of this systematic review was to compare the existing techniques in relation to the risk of urological complications . | We carried out a trial to evaluate the complication rate of intravesical ( LP ) versus extravesical ( Lich ) ureteroneocystostomy in recipients of renal transplantation . Ureteric stenosis was the predominant complication in the LP technique , which was more difficult to correct . Complications by the Lich technique were urinary leaks , which were managed successfully by prolonged bladder drainage . We conclude that the Lich technique is simpler to perform and avoids the complication of ureteric stenosis , and should therefore be the procedure of choice for ureteric implantation in recipients of renal transplants AIM To compare urological infections in patients with or without stents following transplantation and to determine the effect of such infections on graft function . METHODS All 285 recipients of kidney transplantation at our centre between 2006 and 2010 were included in the study . Detailed information including stent use and transplant function was collected prospect ively and analysed retrospectively . The diagnosis of urinary tract infection was made on the basis of compatible symptoms supported by urinalysis and /or microbiological culture . Graft function , estimated glomerular filtration rate and creatinine at 6 mo and 12 mo , immediate graft function and infection rates were compared between those with a stent or without a stent . RESULTS Overall , 196 ( 183 during initial procedure , 13 at reoperation ) patients were stented following transplantation . The overall urine leak rate was 4.3 % ( 12/277 ) with no difference between those with or without stents - 7/183 vs 5/102 , P = 0.746 . Overall , 54 % ( 99/183 ) of stented patients developed a urological infection compared to 38.1 % ( 32/84 ) of those without stents ( P = 0.0151 ) . All 18 major urological infections occurred in those with stents . The use of stent ( Wald χ(2 ) = 5.505 , P = 0.019 ) and diabetes mellitus ( Wald χ(2 ) = 5.197 , P = 0.023 ) were found to have significant influence on urological infection rates on multivariate analysis . There were no deaths or graft losses due to infection . Stenting was associated with poorer transplant function at 12 mo . CONCLUSION Stents increase the risks of urological infections and have a detrimental effect on early to medium term renal transplant function OBJECTIVE To determine whether the change from the Leadbetter-Politano technique to a stented extravesical technique for the vesico-ureteric anastomosis in renal transplantation has altered the incidence of urological complications . PATIENTS AND METHODS Data were retrieved from a prospect i ve computerized data base and by case-note review on 248 consecutive renal transplants performed between January 1990 and June 1996 . The characteristics of the donor . recipient and organ were noted , together with the technique used for the vesicoureteric anastomosis and the occurrence of major and minor urological complications . RESULTS The Leadbetter-Politano technique was used in 140 transplants and the stented extravesical technique in 108 . There were no significant differences in the donor , recipient or organ characteristics between the groups . The stented extravesical technique was associated with a significantly lower rate of major complications ( < 2 % ) and clinical ly significant haematuria than with the Leadbetter-Politano technique . CONCLUSION Changing from the Leadbetter-Politano technique to a stented extravesical technique for the vesico-ureteric anastomosis has been a major factor in reducing the incidence of urological complications in our transplant practice OBJECTIVES To evaluate the impact of the routine use of double-J stents in live-donor renal transplantation at a single institute from a prospect i ve r and omized study . METHODS A total of 100 patients were prospect ively r and omized into two groups of 50 patients each . Group 1 received a routine double-J silicone ureteral stent and group 2 did not . A st and ard Lich-Gregoir ureteroneocystostomy was performed in both groups . In group 1 , the patients were scheduled for stent removal after 2 weeks . RESULTS Both groups were comparable in terms of age , sex , ischemia time , number of renal arteries , and time to diuresis . In group 1 , two grafts were lost in the early postoperative period and those patients were excluded from the final analysis . None of our patients in either group had developed a ureteral stricture at a mean follow-up of 10.8 + /- 3.6 months . In the stented group , 2 patients developed a urinary leak , but no leakage was reported in the nonstented group ( P = 0.14 ) . Although 19 patients in group 1 ( 39.6 % ) had a urinary tract infection , only 9 in group 2 ( 18 % ) showed evidence of a positive urine culture ( P = 0.02 ) . The presence of a ureteral stent and female sex were the independent predictors of postoperative urinary tract infection on multivariate analysis . The mean serum creatinine at discharge was 1.2 + /- 0.3 mg% and 1.2 + /- 0.4 mg% in groups 1 and 2 , respectively ( P = 0.2 ) . CONCLUSIONS The results of our study have shown that routine ureteral stent insertion has no impact on the rate of vesicoureteral leakage or obstruction in live-donor renal transplantation , whereas it is significantly associated with an increased incidence of urinary tract infection . Stenting should be limited to patients with a pathologic and /or defunctionalized bladder Taguchi technique of ureteral implantation was used in 22 kidney transplant patients ( group T ) . Group T was compared with 25 patients who were treated using Lich-Gregoir technique ( group LG ) . Immunosuppression , incidence of biopsy evidence d acute cellular rejection ( ACR ) , haematuria rate and ureteral complications ( stricture , reflux ) were assessed in both groups . The immunosuppression used was based on cyclosporin A ( 63.6 % ) , tacrolimus ( 27.3 % ) and sirolimus ( 8.1 % ) in T group . Cyclosporin A ( 72 % ) , tacrolimus ( 20 % ) and sirolimus ( 8 % ) were used in LG group . No induction was used . The incidence of ACR was similar in both groups – T resp . LG was 50 % resp . 52 % . Haematuria after operation was on average 4.0 days in the T group and on average 3.1 in the LG group . Ureteral complications were observed in 18.2 % of cases in T group and in 16 % of cases in LG group . No reflux was evidence d in any group . Taguchi technique is fast and very easy to do . A slightly higher incidence of ureteral complications and a longer period of postoperative haematuria were observed in T group . Taguchi technique is very easily performed with a shorter operating time . We advocate it as a method of ureteral implantation on the thin-wall urinary bladder . The results were very good in these cases Abstract The incidence of urologic complications was studied in 131 patients with cadaver renal allografts allocated r and omly to undergo either the Politano-Leadbetter or end-to-side ureteroneocystostomy . Obstruction occurred in 6 per cent of patients with end-to-side versus 0 per cent of those with Politano-Leadbetter reconstructions ( p less than 0.05 ) . Complications of leakage , infection and graft loss were comparable in the 2 groups Background . Whether routine ureteric stenting in low-urological-risk patients reduces the risk of urological complications in kidney transplantation is not established . Methods . Eligible patients were recipients of single-organ renal transplants with normal lower urinary tracts . Patients were r and omized intraoperatively to receive either routine stenting or stenting only in the event of technical difficulties with the anastomosis . All patients underwent Lich-Gregoire ureteroneocystostomy . Results . Between June 1994 and December 1997 , 331 kidney transplants were performed at a single center , 305 patients were eligible , and 280 patients were enrolled and r and omized . Donor and recipient age , sex , donor source , whether first or subsequent grafts , ureteric length , native renal disease , and immunosuppression were similar in each group . In the no-routine-stenting group 6 of 137 patients ( 4.4 % ) received stents after r and omization for intraoperative events that in the surgeon ’s opinion required use of a stent . In an intention-to-treat analysis there was no difference between groups in the primary outcome cluster of obstruction or leak [ routine stenting 5 of 143 ( 3.5 % ) vs. no routine stenting 9 of 137 (6.6%);P = 0.23 ] , or in either of these complications analyzed separately . All urological complications were successfully managed without major morbidity . Living donor organs and shorter ureteric length ( after trimming ) were univariate risk factors for leaks , although increasing donor age was associated with obstruction . Conclusions . Routine ureteric stenting is unnecessary in kidney transplantation in patients at low risk for urological complications . Careful surgical technique with selective stenting of problematic anastomoses yields similar results |
12,045 | 24,727,433 | Our review found that αTF exerted beneficial , harmful or null effects on bone formation cells .
Animal studies generally showed positive effects of αTF supplementation on bone in various models of osteoporosis .
However , high-dose αTF was possibly detrimental to bone in normal animals .
Three possible reasons high dosage of αTF can be detrimental to bone include its interference with Vitamin K function on bone , the blocking of the entry of other Vitamin E isomers beneficial to bone , and the role of αTF as a prooxidant .
However , these adverse effects have not been shown in human studies .
In conclusion , αTF may have a dual role in bone health , whereby in the appropriate doses it is beneficial but in high doses it may be harmful to bone | Recent studies have found conflicting evidence on the role of α-tocopherol ( αTF ) on bone health .
This non systematic review aim ed to summarize the current evidence on the effects of αTF on bone health from cell culture , animal , and human studies in order to clarify the role of αTF on bone health . | BACKGROUND Antioxidant defenses are one possible mechanism for decreasing oxidative damage and its potentially negative effects on age-related bone mass . OBJECTIVE This study cross-sectionally examined whether higher dietary intakes , total intakes , and serum concentrations of antioxidants may be associated with higher bone mineral density ( BMD ) . DESIGN Total hip ( and subregions ) , spine , and total-body BMDs were measured in 11,068 women aged 50 - 79 y enrolled in the Women 's Health Initiative Observational Study and Clinical Trial at 3 clinics . Antioxidant intakes from diet ( vitamin A , retinol , beta-carotene , vitamin C , vitamin E , and selenium ) were estimated by using a self-reported food-frequency question naire . Antioxidants from supplements were estimated with an interviewer-administered question naire . A r and om subset ( n = 379 ) had serum concentrations of retinol , carotenoids , and tocopherols measured . RESULTS After adjustment for important BMD-related covariates , increasing intakes of antioxidants were not independently associated with BMD . A significant interaction effect was observed between intake of total vitamin C ( lower three-fourths compared with highest one-fourth ) and use of hormone therapy ( HT ) ( P < 0.01 ) . The beneficial effect of current HT use on femoral neck BMD appeared to be greater in women with higher concentrations of total vitamin C. This interaction was also significant for total-body ( P < 0.045 ) , spine ( P = 0.03 ) , and total-hip BMDs ( P = 0.029 ) . CONCLUSIONS Our results do not support independent associations between dietary intake , total intake , or serum concentrations of antioxidants and BMD in women participating in the Women 's Health Initiative . The extent to which HT use may interact with vitamin C intake and BMD warrants further exploration BACKGROUND Cases of enhanced anticoagulant effect in response to high-dose vitamin E supplementation have been reported among patients taking oral anticoagulants . Although a vitamin E-vitamin K interaction was proposed to underlie this effect , it has not been systematic ally investigated in adults with normal baseline coagulation status . OBJECTIVE The objective was to study the effect of 12 wk of supplementation with 1000 IU RRR-alpha-tocopherol/d on biochemical measures of vitamin K status in men and women not taking oral anticoagulants . DESIGN Vitamin K status , which was assessed with the use of plasma phylloquinone concentrations , the degree of under-gamma-carboxylation of prothrombin ( proteins induced by vitamin K absence-factor II , PIVKA-II ) , and the percentage of undercarboxylated osteocalcin ( ucOC ) , was determined in 38 men and women with rheumatoid arthritis ( study A ) and in 32 healthy men ( study B ) participating in 2 independent , 12-wk r and omized clinical trials of vitamin E supplementation ( 1000 IU/d ) . RESULTS Mean ( + /- SD ) PIVKA-II increased from 1.7 + /- 1.7 to 11.9 + /- 16.1 ng/mL ( P < 0.001 ) in study A and from 1.8 + /- 0.6 to 5.3 + /- 3.9 ng/mL ( P < 0.001 ) in study B in response to 12 wk of vitamin E supplementation . An increase in PIVKA-II is indicative of poor vitamin K status . In contrast , the other measures of vitamin K status ( ie , plasma phylloquinone concentration and percentage of ucOC ) did not change significantly in response to the supplementation . CONCLUSIONS High-dose vitamin E supplementation increased PIVKA-II in adults not receiving oral anticoagulant therapy . The clinical significance of these changes warrants further investigation , but high doses of vitamin E may antagonize vitamin K. Whether such an interaction is potentially beneficial or harmful remains to be determined Postmenopausal osteoporotic bone loss occurs mainly due to cessation of ovarian function , a condition associated with increased free radicals . Vitamin E , a lipid-soluble vitamin , is a potent antioxidant which can scavenge free radicals in the body . In this study , we investigated the effects of alpha-tocopherol and pure tocotrienol on bone microarchitecture and cellular parameters in ovariectomized rats . Three-month-old female Wistar rats were r and omly divided into ovariectomized control , sham-operated , and ovariectomized rats treated with either alpha-tocopherol or tocotrienol . Their femurs were taken at the end of the four-week study period for bone histomorphometric analysis . Ovariectomy causes bone loss in the control group as shown by reduction in both trabecular volume ( BV/TV ) and trabecular number ( Tb . N ) and an increase in trabecular separation ( Tb . S ) . The increase in osteoclast surface ( Oc . S ) and osteoblast surface ( Ob . S ) in ovariectomy indicates an increase in bone turnover rate . Treatment with either alpha-tocopherol or tocotrienol prevents the reduction in BV/TV and Tb . N as well as the increase in Tb . S , while reducing the Oc . S and increasing the Ob . S. In conclusion , the two forms of vitamin E were able to prevent bone loss due to ovariectomy . Both tocotrienol and alpha-tocopherol exert similar effects in preserving bone microarchitecture in estrogen-deficient rat model Vitamin E absorption requires the presence of fat ; however , limited information exists on the influence of fat quantity on optimal absorption . In the present study we compared the absorption of stable-isotope-labelled vitamin E following meals of varying fat content and source . In a r and omised four-way cross-over study , eight healthy individuals consumed a capsule containing 150 mg (2)H-labelled RRR-alpha-tocopheryl acetate with a test meal of toast with butter ( 17.5 g fat ) , cereal with full-fat milk ( 17.5 g fat ) , cereal with semi-skimmed milk ( 2.7 g fat ) and water ( 0 g fat ) . Blood was taken at 0 , 0.5 , 1 , 1.5 , 2 , 3 , 6 and 9 h following ingestion , chylomicrons were isolated , and (2)H-labelled alpha-tocopherol was analysed in the chylomicron and plasma sample s. There was a significant time ( P<0.001 ) and treatment effect ( P<0.001 ) in (2)H-labelled alpha-tocopherol concentration in both chylomicrons and plasma between the test meals . (2)H-labelled alpha-tocopherol concentration was significantly greater with the higher-fat toast and butter meal compared with the low-fat cereal meal or water ( P<0.001 ) , and a trend towards greater concentration compared with the high-fat cereal meal ( P=0.065 ) . There was significantly greater (2)H-labelled alpha-tocopherol concentration with the high-fat cereal meal compared with the low-fat cereal meal ( P<0.05 ) . The (2)H-labelled alpha-tocopherol concentration following either the low-fat cereal meal or water was low . These results demonstrate that both the amount of fat and the food matrix influence vitamin E absorption . These factors should be considered by consumers and for future vitamin E intervention studies It has been reported that vitamin K supplementation effectively prevents fractures and sustains bone mineral density in osteoporosis . However , there are only limited reported data concerning the association between vitamin K nutritional status and bone mineral density ( BMD ) or fractures in Japan . The objectives were to evaluate the association between plasma phylloquinone ( K1 ) or menaquinone ( MK-4 and MK-7 ) concentration and BMD or fracture in Japanese women prospect ively . A total of 379 healthy women aged 30–88 years ( mean age , 63.0 years ) were consecutively enrolled . Plasma K1 , MK-4 , MK-7 , and serum undercarboxylated osteocalcin ( ucOC ) concentrations , BMD , and incidence of vertebral fractures were evaluated . In stepwise multiple linear regression analyses , L2–4 BMD and a bone turnover marker , log K1 , concentrations were independently correlated with vertebral fracture incidence . When subjects were divided into low and high K1 groups by plasma K1 concentration , the incidence of vertebral fracture in the low K1 group ( 14.4 % ) was significantly higher than that in the high K1 group ( 4.2 % ) , and its age-adjusted RR was 3.58 ( 95 % CI , 3.26–3.93 ) . L2–4 BMD was not different between the two groups . These results suggest that subjects with vitamin K1 insufficiency in bone have increased susceptibility for vertebral fracture independently from BMD Smoking increases the concentrations of free radicals , which have been suggested to be involved in bone resorption . We examined whether the dietary intake of antioxidant vitamins may modify the increased hip fracture risk associated with smoking . We prospect ively studied 66,651 women who were 40 - 76 years of age . Forty-four of the cohort members who sustained a first hip fracture within 2 - 64 months of follow-up ( n = 247 ) and 93 out of 873 age-matched controls were current smokers . Information on diet was obtained by a vali date d food-frequency question naire . The relative risk of hip fracture for current versus never smokers was analyzed in relation to the dietary intake of antioxidant vitamins stratified into two categories ( low/high ) , where median intakes among the controls were used as cut-off points . After adjustment for major osteoporosis risk factors , the odds ratio ( OR ) for hip fracture among current smokers with a low intake of vitamin E was 3.0 ( 95 % confidence interval 1.6 - 5.4 ) and of vitamin C 3.0 ( 1.6 - 5.6 ) . In contrast , the OR decreased to 1.1 ( 0.5 - 2.4 ) and 1.4 ( 0.7 - 3.0 ) with high intakes of vitamin E and C , respectively . This effect was not seen for beta-carotene , selenium , calcium , or vitamin B6 . In current smokers with a low intake of both vitamins E and C , the OR increased to 4.9 ( 2.2 - 11.0 ) . The influence of the intake of these two antioxidant vitamins on hip fracture risk was less pronounced in former smokers . Our results suggest a role for oxidant stress in the adverse effects on the skeleton of smoking , and that an insufficient dietary intake of vitamin E and C may substantially increase the risk of hip fracture in current smokers , whereas a more adequate intake seems to be protective Recent studies have shown that estrogen ( E ) likely plays a dominant role in inhibiting bone resorption in normal elderly men . Because both E and T inhibit osteoclast development and activity , stimulate osteoclast apoptosis , and inhibit osteoblast production of IL-6 , it is unclear why T is less potent than E in inhibiting bone resorption in vivo . Osteoprotegerin ( OPG ) binds to and inactivates RANKL , the final mediator of osteoclastogenesis . In vitro , OPG production is stimulated by E , and preliminary data suggest that T has the opposite effect . Thus , we analyzed serum for OPG levels from a study in which 59 elderly men ( mean age , 68 yr ) were made acutely hypogonadal using a GnRH agonist and were also placed on an aromatase inhibitor to block conversion of and rogens to estrogens . They were studied first under conditions of physiologic E and T replacement , and then r and omized to no replacement , replacement with E alone , T alone , or both E and T. E alone result ed in an 18.6 + /- 7.9 % ( mean + /- SEM ) increase in serum OPG levels ( P < 0.05 ) , whereas T alone tended to decrease OPG levels ( by 10.0 + /- 8.5 % ; P < 0.05 compared with E alone ) . Using a two-factor ANOVA model , there was a highly significant T effect ( P = 0.006 ) on decreasing serum OPG levels . Serum TNF-alpha , IL-6 , and IL-6 soluble receptor levels increased significantly in the men who had both E and T withdrawn , and the increases in TNF-alpha and IL-6sR were absent in the men treated with either E or T. However , due to the variability in these cytokine measurements , the ANOVA models were not significant for E or T effects . Taken together , these data suggest that in vivo , T decreases OPG levels , whereas E tends to have the opposite effect . These differential effects of E vs. T on OPG production may explain , at least in part , why T has weaker effects than E on inhibiting bone resorption in vivo in humans |
12,046 | 27,153,743 | Studies did not find increased odds of VTE with POPs for contraceptive purpose s , implants or LNG-IUDs nor were there increased odds of stroke or AMI with any POCs .
CONCLUSION The majority of evidence identified by this systematic review did not suggest an increase in odds for venous or arterial events with use of most POCs .
Any increase in risk likely translates to a small increase in absolute numbers of thrombotic events at the population level | BACKGROUND Women with medical conditions associated with increased risk for thrombosis generally should not use estrogen-containing contraceptives ; however , less is known about progestin-only contraceptives ( POCs ) and thrombosis risk .
OBJECTIVES The objective was to identify evidence regarding the risk of venous thromboembolism ( VTE ) or arterial thromboembolism [ stroke or acute myocardial infa rct ion ( AMI ) ] among women using POCs . | The objective of this study was to assess the influence of oral contraceptives ( OCs ) on the risk of venous thromboembolism ( VTE ) in young women . A 5-year case-control study including all Danish hospitals was conducted . All women 15 - 44 years old , suffering a first ever deep venous thrombosis or a first pulmonary embolism ( PE ) during the period January 1 , 1994 , to December 30 , 1998 , were included . Controls were selected annually , 600 per year in 1994 - 1995 and 1200 per year 1996 - 1998 . Response rates for cases and controls were 87.2 % and 89.7 % , respectively . After exclusion of nonvalid diagnoses , pregnant women , and women with previous thrombotic disease , 987 cases and 4054 controls were available for analysis . A multivariate , matched analysis was performed . Controls were matched to cases within 1-year age b and s. Adjustment was made for confounding influence ( if any ) from the following variables : age , year , body mass index , length of OC use , family history of VTE , cerebral thrombosis or myocardial infa rct ion , coagulopathies , diabetes , years of schooling , and previous birth . The risk of VTE among current users of OCs was primarily influenced by duration of use , with significantly decreasing odds ratios ( OR ) over time : < 1 year , 7.0 ( 5.1 - 9.6 ) ; 1 - 5 years , 3.6 ( 2.7 - 4.8 ) ; and > 5 years , 3.1 ( 2.5 - 3.8 ) , all compared with nonusers of OCs . After adjustment for confounders , current use of OCs with second- ( levonorgestrel or norgestimate ) and third- ( desogestrel or gestodene ) generation progestins when compared with nonuse result ed in ORs for VTE of 2.9 ( 2.2 - 3.8 ) and 4.0 ( 3.2 - 4.9 ) , respectively . After adjusting for progestin types and length of use , the risk decreased significantly with decreasing estrogen dose . With 30 - 40 microg as reference , 20 and 50 microg products implied ORs of 0.6 ( 0.4 - 0.9 ) and 1.6 ( 0.9 - 2.8 ) , respectively ( p(trend ) = 0.02 ) . After correction for duration of use and differences in estrogen dose , the third/second-generation risk ratio was 1.3 ( 1.0 - 1.8 ; p < 0.05 ) . In conclusion , use of OCs was associated significantly to the risk of VTE . The risk among current users was reduced by more than 50 % during the first years of use . The risk increased more than 100 % with increasing estrogen dose , and the difference in risk between users of third- and second-generation OCs , after correction for length of use and estrogen dose , was 33 % To test the efficacy and tolerance of progestagens as contraceptives in systemic lupus erythematosus ( SLE ) , 200 mg IM norethisterone enanthate was administered to 10 patients , 0.03 mg/day oral levonorgestrel to 15 patients and they were compared with 18 control patients . There were 4 episodes of active SLE in 48 patient-months on norethisterone enantate and 6 episodes in 122 patient-months on levonorgestrel as compared with 9 episodes of active disease in 298 control patient-months ( p = ns ) . There were no pregnancies and intermenstrual bleeding led to discontinuation of medication in 30 % of patients . Progestagens may be an alternative contraceptive method in SLE Epidemiologic studies conducted in the 1960s and 1970s [ 1 - 4 ] showed an increased risk for stroke as well as myocardial infa rct ion and venoocclusive disease in women who used oral contraceptives containing more than 50 g of ethinyl estradiol . These reports spurred the development of oral contraceptive pills containing less than 50 g of ethinyl estradiol . Initial studies of cerebrovascular risk in users of low-dose oral contraceptives produced conflicting results : Some investigators found increased risks [ 5 , 6 ] , and others found no increased risk [ 7 ] . In addition , few data are available on whether the risk for stroke associated with use of low-dose oral contraceptives is influenced by the type of progestin present in these medications . In the United States , most currently available low-dose oral contraceptives contain either norethindrone-type progestins ( norethindrone , norethindrone acetate , ethynodiol diacetate , or norethynodrel ) or norgestrel-type progestins ( norgestrel or levonorgestrel ) . It has been proposed that the levonorgestrel component of oral contraceptives may offset the cardiovascular benefits that arise from the use of low doses of estrogen [ 8 , 9 ] , but little empirical research has addressed this hypothesis . A recent study [ 10 ] conducted among the members of the Northern and Southern California Kaiser Permanente medical care programs reported that the use of low-dose oral contraceptives available in the United States was not associated with an increased risk for either hemorrhagic or ischemic stroke , regardless of progestin type . In that study , past users of oral contraceptives were at reduced risk for ischemic stroke but not hemorrhagic stroke ; this finding was consistent with findings from an earlier study of cerebral thromboembolic attack [ 5 ] but differed from those in a previous study of subarachnoid hemorrhage [ 7 ] . To provide information on the occurrence of stroke among oral contraceptive users in a U.S. community , we report the results of a population -based casecontrol study done in a defined geographic region of western Washington State . Methods The source population for our study was women 18 to 44 years of age residing in King , Pierce , or Snohomish counties , Washington , between 1 July 1991 and 28 February 1995 . This represented approximately 2.2 million women-years at risk , according to population estimates provided by the State of Washington Office of Financial Management . Definition and Ascertainment of Case- Patients and Controls Eligible case- patients were women in the source population with a first diagnosis of fatal or nonfatal stroke and without a history of major coronary heart disease , such as myocardial infa rct ion , angina , or congestive heart failure . We identified potential case- patients through regular review and abstract ion of 1 ) medical records containing cerebrovascular disease discharge diagnoses at all 34 acute care hospitals within the study region and 2 ) death certificates filed at county health departments . These sources were supplemented with monthly letters sent to all neurologists , neurosurgeons , and physiatrists in the region . We defined stroke as the new , rapid onset of symptoms and signs consistent with loss of cerebral function that lasted at least 24 hours and could not be ascribed to subdural hematoma ; brain tumor ; infection ; seizure ; or other neurologic disease , such as multiple sclerosis . A neurologist review ed the records to confirm the diagnosis of stroke and to classify confirmed strokes as either arterial or venous in origin . Arterial strokes were further classified as hemorrhages , ischemic events , or other [ a category that included arterial dissections ] . Aneurysmal bleeding was defined as a hemorrhagic stroke in which the diagnostic workup or autopsy showed 1 ) blood in the subarachnoid space with or without a demonstrated aneurysm and no evidence of arteriovenous malformation or 2 ) an aneurysm with blood in other locations , such as the parenchyma or ventricles , and no evidence of arteriovenous malformation . Eligible controls were women 18 to 44 years of age who were residents of King , Pierce , or Snohomish counties during the case-diagnosis period and had no history of major coronary or cerebrovascular disease . We identified a sample of these women by using r and om-digit dialing [ 11 ] . Data Collection Participating case- patients and controls were interviewed in person by trained female interviewers who used a structured question naire that elicited information about cardiovascular risk factors . We used the reproductive calendar method and color photographs of all oral contraceptive pills marketed in the United States to help women recall date s and specific br and s of oral contraceptives used . All interview questions elicited information about the time period before each participant 's reference date , which was the date of stroke for a case-patient and a date assigned at r and om from among the potential stroke occurrence date s for a control . We also sought in-person interviews with proxy respondents for case- patients who had died or were mentally impaired . To evaluate the quality of information received from proxy respondents , we did in-person interviews with proxy respondents for case- patients who had not died and who were not mentally impaired and for a r and om one third of controls [ 12 ] . The interviews with proxy respondents contained the same questions asked of the case- patients and controls . Proxy respondents and participants were not interviewed in each other 's presence . Statistical Analysis A woman was considered to be a current user of oral contraceptives if she or her proxy reported that she had been taking these pills within a month of her reference date . She was considered to be a past user if she had used oral contraceptives but was not using them at that time . The remaining women were classified as having never used oral contraceptives . We classified current users of oral contraceptives according to whether the pill was a low-dose ( < 50 g of ethinyl estradiol ) or a high-dose ( 50 g of ethinyl estradiol ) formulation . No women reported current use of pills containing more than 50 g of ethinyl estradiol . We used unconditional logistic regression models to compute estimated odds ratios and 95 % CIs [ 13 ] . We excluded from all analyses women who were pregnant at the reference date ( 5 case- patients , 14 controls ) and women for whom information on use of oral contraceptives was missing ( 6 case- patients , 24 controls ) . Thus , 173 case- patients and 485 controls were included in the analysis . Of the case- patients , 102 were classified as having had hemorrhagic stroke , 60 were classified as having had ischemic stroke , and 11 were classified as having had other types of stroke . Sixty-nine of the hemorrhagic strokes were classified as cases of aneurysmal bleeding . In all analyses , we examined the potential confounding effect of known or suspected cerebrovascular risk factors . We initially adjusted all odds ratios for age ( in years ) , race , treated hypertension , and cigarette smoking ; we then examined whether further adjustment for other characteristics changed the estimates of association . We also conducted subanalyses in which case- patients who did not have residential telephones were excluded . To determine whether the risk for total stroke associated with oral contraceptive use varied according to other cardiovascular risk factors , we estimated odds ratios separately by age , cigarette smoking status , obesity ( body mass index 27.3 kg/m2 or < 27.3 kg/m2 ) , and among women not receiving treatment for hypertension . Results Case- Patients and Controls We identified 249 women who met the eligibility criteria for stroke : One hundred forty-one were classified as having had hemorrhagic stroke , 95 as having had ischemic stroke , 10 as having had arterial dissection , and 3 as having had venous stroke . The results of computed tomography , magnetic resonance imaging , or both were available for 92 % of patients with stroke diagnoses . Ninety-one of the 141 patients with hemorrhagic strokes were further classified as having had strokes as a result of aneurysms . Of the 198 patients who were alive and not mentally impaired as a result of their strokes , 149 ( 75.3 % ) participated in the study . Most nonparticipation was due to patient refusal ( n = 30 ) or inability to locate the patient ( n = 13 ) . For the 51 eligible patients with stroke who died or were mentally impaired as a result of the stroke , we attempted to identify and recruit proxy respondents . Through r and om-digit dialing , we completed a household census for 94.9 % of the residences contacted . Among the eligible women identified , we attempted to recruit 691 who were similar in age to the patients with stroke . Six of the potential controls were excluded because of a history of major coronary heart disease or stroke , and one was excluded because she was unable to communicate in English . Of the remaining 684 women , 526 were recruited into the study , for an estimated overall response rate of 73.0 % ( 526 684 0.949 ) . Proxy Respondents We recruited proxy respondents for 34 of the 51 patients with stroke who had died or were mentally impaired , 106 of the 149 patients with stroke who had not died and were not mentally impaired , and 160 of the 273 controls whom we had selected at r and om . Approximately 80 % of the proxy respondents for both case- patients and controls were spouses or sexual partners ( 54.3 % of proxy respondents for case- patients ; 64.4 % of proxy respondents for controls ) , mothers ( 15.7 % of proxy respondents for case- patients ; 10.0 % of proxy respondents for controls ) , or roommates or close friends ( 10.7 % of proxy respondents for case- patients ; 8.1 % of proxy respondents for controls ) of the participants . Because data for approximately 18 % of the case- patients were obtained through proxy respondents , we used proxy respondent data rather than control respondent data for 93 of the controls selected . The distribution of proxy types ( spouse Objective To determine the relationship between the use of low-dose ( less than 50 μg estrogen ) oral contraceptives ( OC ) and myocardial infa rct ion . Methods In this population -based case-control study , all incident myocardial infa rct ions in women , ages 15–44 years who were members of the Kaiser Permanente Medical Care Program , Northern and Southern California regions were ascertained during a 39-month period from 1991 through 1994 . For each woman with myocardial infa rct ion , up to three age- and facility-matched controls were chosen at r and om from female members . Information about OC use ( predominantly low-dose preparations ) was obtained in face-to-face interviews . Results There were 187 incident cases of myocardial infa rct ion during 3.6 million woman-years of observation ( incidence rate , 5.2 per 100,000 woman-years ) . The prevalence of several risk factors for myocardial infa rct ion was lower in controls who were current users of OCs than in controls who were noncurrent ( past and never ) users . The odds ratio for myocardial infa rct ion in current OC users compared with noncurrent users was 1.65 ( 95 % confidence interval 0.45 , 6.06 ) after adjustment for major risk factors and for race and ethnicity , corresponding to an excess risk of less than one case per 100,000 woman-years . The study had 80 % power to detect a relative risk of 2.3 ( one-sided test , α = .05 ) . The odds ratio of myocardial infa rct ion in past OC users was not elevated . Conclusion With respect to myocardial infa rct ion , low-dose oral contraceptives can be used safely by women who lack risk factors for coronary heart disease The objective of the study was to evaluate the venous impact of a progestogen-only contraception on women at high risk of venous thromboembolism ( VTE ) . In this retrospective cohort study , 204 consecutive women at high risk of VTE were recruited between January 1992 and June 1997 and were prospect ively followed . Women using chlormadinone acetate ( CMA ) at antigonadotropic doses ( n=102 ) were matched by age and date of referral and history of venous thrombosis with women who had no hormonal contraception ( n=102 ) . During follow-up ( mean of 33 months ) , nine episodes of VTE were observed : three in women receiving CMA and six in nontreated women . Using the Cox model to adjust for confounding variables such as age , thrombophilia and body mass index , the relative risk of VTE associated with the use of CMA was not significant [ relative risk : 0.8 ( 0.2 - 3.9 ) ] . These reassuring results need to be confirmed in other prospect i ve studies Abstract Objective : To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of venous thromboembolism . Design : Matched case-control study . Setting : 10 centres in Germany and United Kingdom . Subjects : Cases were 471 women aged 16 - 44 who had a venous thromboembolism . Controls were 1772 women ( at least 3 controls per case ) unaffected by venous thromboembolism who were matched with corresponding case for age and for hospital or community setting . Main outcome measures : Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables . Results : Odds ratios ( 95 % confidence intervals ) for venous thromboembolism were : for any oral contraceptives versus no use , 4.0 ( 3.1 to 5.3 ) ; for second generation products ( low dose ethinyloestradiol , no gestodene or desogestrel ) versus no use , 3.2 ( 2.3 to 4.3 ) ; for third generation products ( low dose ethinyloestradiol , gestodene or desogestrel ) versus no use , 4.8 ( 3.4 to 6.7 ) ; for third generation products versus second generation products , 1.5 ( 1.1 to 2.1 ) ; for products containing gestodene versus second generation products , 1.5 ( 1.0 to 2.2 ) ; and for products containing desogestrel versus second generation products , 1.5 ( 1.1 to 2.2 ) . Probability of death due to venous thromboembolism for women using third generation products is about 20 per million users per year , for women using second generation products it is about 14 per million users per year , and for non-users it is five per million per year . Conclusions : Risk of venous thromboembolism was slightly increased in users of third generation oral contraceptives compared with users of second generation products . Key messages Key messages This case-control study examined risk of venous thromboembolism associated with different types of oral contraceptive Overall , there was a fourfold higher relative risk of thromboembolism associated with current use of any oral contraceptive versus no current use The risk of thromboembolism was 1.5 times higher for third generation contraceptives compared with second generation products Our data indicate the need for clinical prudence but allow doctors and women seeking contraception to exercise informed UNLABELLED BACKGROUND The risk of recurrent venous thrombosis is higher in men than in women , and this is so far unexplained . We set out to determine the influence of age , time between first and second event , type of first event , oral contraception , pregnancy and surgery . METHODS We performed a prospect i ve follow-up study of 474 patients with a first objective diagnosis of deep vein thrombosis , aged 18 - 70 years ( Leiden Thrombophilia Study cohort ) . RESULTS During 3477 person-years of follow-up , 90 recurrences occurred . The overall incidence rates of recurrence ( IRs ) were 40.9 per 1000 person-years in men and 15.8 per 1000 person-years in women . Men with an unprovoked first event had the highest risk of recurrence , with almost one-third experiencing a second unprovoked event within 8 years ( IR 41.2 per 1000 person-years ) . This risk was three-fold lower in women [ IR 14.2 per 1000 person-years ; hazard ratio 2.8 ( 95 % confidence interval 1.4 - 5.7 ) ] . Age at diagnosis had little effect on recurrence rate , and nor had time elapsed since the first event . In women , almost half of the recurrences were provoked and were mainly related to oral contraceptive use or pregnancy . CONCLUSIONS The higher recurrence rate in men than in women is not the result of differences in the environmental or transient risk factors that we studied . The risk profile for a second thrombotic event is clearly different from that of a first The object of this study was to assess the influence of oral contraceptives ( OCs ) on the risk of cerebral thromboembolic attacks ( CTA ) including thrombotic stroke and transitory cerebral ischemic attacks . A 5-year case-control study including all Danish hospitals was conducted . All women 15 - 44 years old suffering a first ever CTA during the period January 1 , 1994 to December 31 , 1998 , were included . Controls were selected annually , 600 per year in 1994 - 1995 , 1200 per year 1996 - 1998 . Response rates for cases and controls were 88 % and 90 % , respectively . After exclusion of nonvalid diagnoses , pregnant women , and women with previous thrombotic diseases , 626 cases and 4054 controls were available for analysis . A multivariate matched analysis was performed . Controls were matched to cases within 1-year age b and s. Adjustments were made for the following potential confounders : year , length of OC use , smoking , hypertension , migraine , family CTA , and years of schooling . There were 212 and 1208 current users of OCs among cases and controls , respectively . The risk of CTA among current users of OCs decreased significantly with decreasing estrogen dose ( nonusers reference ) : OCs with 50 microg , 30 - 40 microg , 20 microg ethinyl estradiol ( EE ) and progestin-only pills implied adjusted odds ratios ( ORs ) ( 95 % CI ) of 4.5 ( 2.6 - 7.7 ) , 1.6 ( 1.3 - 2.0 ) , 1.7 ( 1.0 - 3.1 ) , and 1.0 ( 0.3 - 3.0 ) , respectively . Current users of OCs with second- ( levonorgestrel or norgestimate ) and third- ( desogestrel or gestodene ) generation progestins combined with 20 - 30 microg EE had ORs of CTA of 2.2 ( 1.6 - 3.0 ) and 1.4 ( 1.0 - 1.9 ) , respectively . After correction for differences in estrogen dose , the third- to second-generation risk ratio was 0.6 ( 0.4 - 0.9 ; p = 0.01 ) . In conclusion , high dose OCs and OCs with second-generation progestins were associated with the risk of CTA . The risk increased 2.5 times with estrogen dose increasing from 20 to 50 microg EE , and users of low-dose OCs with second-generation progestins had a 61 % higher risk-association of CTA than users of OCs with third-generation progestins INTRODUCTION Hemostasis in women is affected by changes of estrogen levels . The role of endogenous estrogens on risk of venous thromboembolism ( VTE ) remains unclear . The aim of this study was to investigate the importance of acquired and genetic risk factors for VTE in pre- and postmenopausal women . METHOD In a nationwide case-control study we included as cases 1470 women , 18 to 64years of age with a first time VTE . The 1590 controls were r and omly selected and matched by age to the cases . Information on risk factors was obtained by interviews and DNA-analyses . We used unconditional logistic regression to calculate odds ratios ( ORs ) with 95 % confidence intervals ( CIs ) . RESULTS The ORs were generally of similar magnitude in pre- and postmenopausal women . The highest risk was for the combination of surgery and cast ( adjusted OR 54.12 , 95 % CI 16.62 - 176.19 ) in postmenopausal women . The adjusted OR for use of menopausal hormone therapy was 3.73 ( 95 % CI 1.86 - 7.50 ) in premenopausal and 2.22 ( 95 % CI 1.54 - 3.19 ) in postmenopausal women . Overweight was linked to an increased risk and exercise to a decreased risk , regardless of menopausal status . CONCLUSION Menopausal status had only minor influence on the risk levels . Acquired transient risk factors conveyed the highest risks for VTE Abstract Objective : To determine whether migraine is a risk factor for ischaemic stroke in young women . Design : A case-control study . Setting : Five hospitals in Paris and suburbs . Subjects : 72 women aged under 45 with ischaemic stroke and 173 controls r and omly selected from women hospitalised in the same centres . Main outcome measures : Ischaemic stroke confirmed by cerebral computerised tomography or magnetic resonance imaging ; history of headache recorded with structured interview , and diagnosis of migraine assessed by reproducibility study . Results : Ischaemic stroke was strongly associated with migraine , both migraine without aura ( odds ratio 3.0 ( 95 % confidence interval 1.5 to 5.8 ) ) and migraine with aura ( odds ratio 6.2 ( 2.1 to 18.0 ) ) . The risk of ischaemic stroke was substantially increased for migrainous women who were using oral contraceptives ( odds ratio 13.9 ) or who were heavy smokers ( > /=20 cigarettes/day ) ( odds ratio 10.2 ) . Conclusions : These results indicate an independent association between migraine and the risk of ischaemic stroke in young women . Although the absolute risk of ischaemic stroke in young women with migraine is low , the reduction of known risk factors for stroke , in particular smoking and use of oral contraceptives , should be considered in this group |
12,047 | 20,556,746 | While programs which offer additional support during pregnancy are unlikely to prevent the pregnancy from result ing in a low birthweight or preterm baby , they may be helpful in reducing the likelihood of antenatal hospital admission and caesarean birth | BACKGROUND Studies consistently show a relationship between social disadvantage and low birthweight .
Many countries have programs offering special assistance to women thought to be at risk for giving birth to a low birthweight infant .
These programs may include advice and counseling ( about nutrition , rest , stress management , alcohol , and recreational drug use ) , tangible assistance ( e.g. , transportation to clinic appointments , household help ) , and emotional support .
The programs may be delivered by multidisciplinary teams of health professionals , specially trained lay workers , or combination of lay and professional workers .
OBJECTIVES The primary objective was to assess effects of programs offering additional social support compared with routine care , for pregnant women believed at high risk for giving birth to babies that are either preterm or weigh less than 2500 gm , or both , at birth .
Secondary objectives were to determine whether effectiveness of support was mediated by timing of onset ( early versus later in pregnancy ) or type of provider ( healthcare professional or lay woman ) . | BACKGROUND The goal of our study was to measure the effectiveness of a home-based intervention for prevention of low birth weight with 154 high-risk , low-income black women attending a prenatal clinic in Clevel and . METHODS Based on previous research , risk was defined by clinic registration between the 17th and 28th weeks of gestation , low family functioning score , and experience of at least one stressful life event prior to registration . Optional factors included being a smoker , a low maternal weight-height ratio , being age 27 or older , and a previous premature birth . A 21-item family function screen previously vali date d in a similar population was the primary determinant of psychosocial risk . Low birth weight was defined as weight less than 2,500 g regardless of gestational age . RESULTS There was no decrease in the rate of low birth weight for women who received four home visits focusing on smoking , drug and nutrition education , support , and links with community services , compared to women who received no visits . The number of prenatal visits was significantly higher in the intervention group , but an increased number of prenatal visits did not correlate with a reduced rate of low birth weight . Despite previous research , the family function screen was not an effective predictor of low birth weight in our study . A revised equation involving a history of previous premature birth , smoking , and a low maternal weight-height ratio did predict low birth weight . CONCLUSIONS These findings question the utility of short-term psychosocial interventions for influencing low birth-weight rates in low-income black clinic population s. The family function screen was not cross vali date d. Integration of any psychosocial intervention with the routine prenatal care occurring in the obstetrical clinic is suggested for future research We assessed the effectiveness of the home-visiting system in reducing the care provided in maternity units , especially hospitalization , and attempted to establish whether this system increases women 's satisfaction with medical care . The trial involved 158 women and was conducted in four maternity units in Paris . A policy of one or two weekly visits by domiciliary midwives was compared with the usual policy of the hospitals . The study was restricted to women with moderate threatened preterm labor between 26 and 36 weeks of gestation . No decrease in the number of women hospitalized or the number of days spent in hospital was observed in the intervention group , but the number of prenatal visits to outpatient clinics was significantly smaller in the intervention than control group . Satisfaction with medical care during the episode of threatened preterm labor was much greater in the intervention group . Home visits by a midwife were considered by the women to be a better care system than numerous outpatient visits or hospitalization . Our results for medical care suggest that the introduction of the home-visiting system did not greatly alter medical practice in the maternity units , although this system had been design ed to avoid or reduce hospitalization We conducted a health technology assessment of the care of women with high-risk pregnancies in the South Wales valleys . Women in the control arm were intended to receive conventional care with st and ard midwifery visits . Women in the intervention arm received additional or longer visits and domiciliary fetal heart rate telemonitoring . Eighty-one mothers were r and omized . There were significant differences in midwifery intervention re sources between domiciliary and control groups , with the former receiving a mean of 3.7 visits lasting 33.5 min , compared with 1.4 visits lasting 12.8 min for the latter . There were slightly more spontaneous labours and fewer Caesarean sections in the domiciliary group . Maternal satisfaction and anxiety were high in both groups . Domiciliary care increased the service costs by 21.02 per woman in terms of extra midwife travel and visiting time , and by a further £ 18.38 per woman in home monitoring equipment costs . This , however , was more than offset by health service savings from fewer clinic visits ( £ 35.60 ) and fewer clinic ultrasound scans ( £ 9.01 ) . Adding the reductions in lost productivity to women and their partners ( £ 34.51 ) suggests that domiciliary care was cheaper than conventional care , even if it did not greatly reduce inpatient days ( a reduction nonetheless saving £ 184.24 ) . While clinical processes were similar in both groups , there were useful practical advantages and savings for patients and the health service from the domiciliary intervention This article presents the methodology and baseline findings of a large multicenter trial involving four countries from Latin America ( Argentina , Brazil , Cuba , and Mexico ) . The study was a r and omized , controlled , single-masked trial to investigate the impact of social support during pregnancy on perinatal outcomes . Pregnant women with gestational ages between 15 and 22 weeks were screened in health facilities in the four countries . Those presenting with one or more risk factors for having a low-birthweight baby were invited to join the trial . A total of 2235 women -- between 500 and 600 in each country -- were r and omized into an intervention ( n = 1110 ) or a control ( n = 1125 ) group . Both groups were comparable in terms of nearly all baseline variables . The intervention group received a minimum of four visits at home by a trained health worker who provided direct emotional support , health education , and an attempt to enhance the woman 's social support network . Over 90 % of all women were evaluated at 36 weeks of pregnancy and soon after delivery , and 85 % at the 40th day postpartum . The outcomes under study included intrauterine growth retardation , gestational age , perinatal and maternal morbidity and mortality , labor interventions , psychological distress and characteristics of the social support network , among others . This trial showed that it was possible to select , screen , r and omize , visit , and evaluate a large number of women in four Latin American countries using a st and ardized methodology This study examines whether an integrated behavioral intervention with proven efficacy in reducing psycho-behavioral risks ( smoking , environmental tobacco smoke exposure ( ETSE ) , depression , and intimate partner violence ( IPV ) ) in African-Americans is associated with improved pregnancy outcomes . A r and omized controlled trial targeting risks during pregnancy was conducted in the District of Columbia . African-American women were recruited if reporting at least one of the risks mentioned above . R and omization to intervention or usual care was site and risk specific . Sociodemographic , health risk and pregnancy outcome data were collected . Data on 819 women , and their singleton live born infants were analyzed using an intent-to-treat approach . Bivariate analyses preceded a reduced logistical model approach to eluci date the effect of the intervention on the reduction of prematurity and low birth weight . The incidence of low birthweight ( LBW ) was 12 % and very low birthweight ( VLBW ) was 1.6 % . Multivariate logistic regression results showed that depression was associated with LBW ( OR = 1.71 , 95 % CI = 1.12–2.62 ) . IPV was associated with preterm birth ( PTB ) and very preterm birth ( VPTB ) ( OR 1.64 , 95 % CI = 1.07–2.51 , OR = 2.94 , 95 % CI = 1.40–6.16 , respectively ) . The occurrence of VPTB was significantly reduced in the intervention compared to the usual care group ( OR = 0.42 , 95 % CI = 0.19 - 0.93 ) . Our study confirms the significant associations between multiple psycho-behavioral risks and poor pregnancy outcomes , including LBW and PTB . Our behavioral intervention with demonstrated efficacy in addressing multiple risk factors simultaneously reduced VPTB within an urban minority population A r and omized controlled trial including 2235 women at high risk of low birthweight was conducted in four Latin American institutions . The objective of this trial was to evaluate a psychosocial support intervention during pregnancy aim ed at improving perinatal health and mothers ' psychosocial conditions . The core of the intervention was four to six home visits where emotional support , counseling and strengthening of the woman 's social network was provided . Outcomes were measured at 36 weeks of pregnancy , post-partum and 40 days after delivery . The intervention was not successful in either altering women 's perception of social support and satisfaction with the reproductive experience , as well as maternal and newborn 's health care . It is concluded that although high levels of psychosocial distress during pregnancy may play an independent role in determining adverse pregnancy outcomes , this adverse effect does not appear to be ameliorated by psychosocial interventions conducted only during pregnancy , particularly those of a magnitude that can be realistically implemented ( in content and frequency ) at public care services in most developing countries OBJECTIVE : To determine whether group prenatal care improves pregnancy outcomes , psychosocial function , and patient satisfaction and to examine potential cost differences . METHODS : A multisite r and omized controlled trial was conducted at two university-affiliated hospital prenatal clinics . Pregnant women aged 14–25 years ( n=1,047 ) were r and omly assigned to either st and ard or group care . Women with medical conditions requiring individualized care were excluded from r and omization . Group participants received care in a group setting with women having the same expected delivery month . Timing and content of visits followed obstetric guidelines from week 18 through delivery . Each 2-hour prenatal care session included physical assessment , education and skills building , and support through facilitated group discussion . Structured interviews were conducted at study entry , during the third trimester , and postpartum . RESULTS : Mean age of participants was 20.4 years ; 80 % were African American . Using intent-to-treat analyses , women assigned to group care were significantly less likely to have preterm births compared with those in st and ard care : 9.8 % compared with 13.8 % , with no differences in age , parity , education , or income between study conditions . This is equivalent to a risk reduction of 33 % ( odds ratio 0.67 , 95 % confidence interval 0.44–0.99 , P=.045 ) , or 40 per 1,000 births . Effects were strengthened for African-American women : 10.0 % compared with 15.8 % ( odds ratio 0.59 , 95 % confidence interval 0.38–0.92 , P=.02 ) . Women in group sessions were less likely to have suboptimal prenatal care ( P<.01 ) , had significantly better prenatal knowledge ( P<.001 ) , felt more ready for labor and delivery ( P<.001 ) , and had greater satisfaction with care ( P<.001 ) . Breastfeeding initiation was higher in group care : 66.5 % compared with 54.6 % , P<.001 . There were no differences in birth weight nor in costs associated with prenatal care or delivery . CONCLUSION : Group prenatal care result ed in equal or improved perinatal outcomes at no added cost . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00271960 LEVEL OF EVIDENCE : OBJECTIVE To examine prenatal , maternal , and infant outcomes and costs through 1 year after delivery using a model of prenatal care for women at high risk of delivering low-birth-weight infants in which half of the prenatal care was provided in women 's homes by nurse specialists with master 's degrees . STUDY DESIGN R and omized clinical trial . PATIENTS AND METHODS A sample of 173 women ( and 194 infants ) with high-risk pregnancies ( gestational or pregestational diabetes mellitus , chronic hypertension , preterm labor , or high risk of preterm labor ) were r and omly assigned to the intervention group ( 85 women and 94 infants ) or the control group ( 88 women and 100 infants ) . Control women received usual prenatal care . Intervention women received half of their prenatal care in their homes , with teaching , counseling , telephone outreach , daily telephone availability , and a postpartum home visit by nurse specialists with physician backup . RESULTS For the full sample , mean maternal age was 27 years ; 85.5 % of women were single mothers , 36.4 % had less than a high school education , 93.6 % were African American , and 93.6 % had public health insurance , with no differences between groups on these variables . The intervention group had lower fetal/infant mortality vs the control group ( 2 vs 9 ) , 11 fewer preterm infants , more twin pregnancies carried to term ( 77.7 % vs 33.3 % ) , fewer prenatal hospitalizations ( 41 vs 49 ) , fewer infant rehospitalizations ( 18 vs 24 ) , and a savings of more than 750 total hospital days and $ 2,496,145 [ corrected ] . CONCLUSION This model of care provides a reasoned solution to improving pregnancy and infant outcomes while reducing healthcare costs OBJECTIVE : Examine frequency , timing , and reasons for maternal postpartum rehospitalizations and acute care visits 1 year postpartum after a high-risk pregnancy . STUDY DESIGN : Secondary analysis of data collected during a r and omized clinical trial of advanced practice nurses gives transitional care for women with high-risk pregnancies . The 171 women were primarily African American , never married , Medicaid eligible , diagnosed with pregestational diabetes ( 20 ) , gestational diabetes ( 23 ) , either diagnosed ( 48 ) or at risk ( 44 ) for preterm labor , and chronic hypertension ( 36 ) . RESULTS : Of the total rehospitalizations ( 17 % ) and acute care visits ( 32 % ) , over one third occurred in the first 8 weeks postpartum . Chronic hypertensives and gestational diabetics had the highest rate of rehospitalization and proportion of acute care visits . Six women were rehospitalized for subsequent pregnancies . CONCLUSION : Women with high-risk pregnancies have continued high health care re source use over the first postpartum year demonstrating the need for more intensive patient education and follow-up to improve outcomes and reduce re source use OBJECTIVES We evaluated the efficacy of a primary care intervention targeting pregnant African American women and focusing on psychosocial and behavioral risk factors for poor reproductive outcomes ( cigarette smoking , secondh and smoke exposure , depression , and intimate partner violence ) . METHODS Pregnant African American women ( N = 1044 ) were r and omized to an intervention or usual care group . Clinic-based , individually tailored counseling sessions were adapted from evidence -based interventions . Follow-up data were obtained for 850 women . Multiple imputation methodology was used to estimate missing data . Outcome measures were number of risks at baseline , first follow-up , and second follow-up and within-person changes in risk from baseline to the second follow-up . RESULTS Number of risks did not differ between the intervention and usual care groups at baseline , the second trimester , or the third trimester . Women in the intervention group more frequently resolved some or all of their risks than did women in the usual care group ( odds ratio = 1.61 ; 95 % confidence interval = 1.08 , 2.39 ; P = .021 ) . CONCLUSIONS In comparison with usual care , a clinic-based behavioral intervention significantly reduced psychosocial and behavioral pregnancy risk factors among high-risk African American women receiving prenatal care OBJECTIVE To ascertain the role of low birth weight ( LBW ) in neonatal mortality in a periurban setting in Bangladesh . METHODS LBW neonates were recruited prospect ively and followed up at one month of age . The cohort of neonates were recruited after delivery in a hospital in Dhaka , Bangladesh , and 776 were successfully followed up either at home or , in the event of early death , in hospital . FINDINGS The neonatal mortality rate ( NMR ) for these infants was 133 per 1000 live births ( 95 % confidence interval : 110 - 159 ) . The corresponding NMRs ( and confidence intervals ) for early and late neonates were 112 ( 91 - 136 ) and 21 ( 12 - 33 ) per thous and live births , respectively . The NMR for infants born after fewer than 32 weeks of gestation was 769 ( 563 - 910 ) ; and was 780 ( 640 - 885 ) for infants whose birth weights were under 1500 g. Eighty-four per cent of neonatal deaths occurred in the first seven days ; half within 48 hours . Preterm delivery was implicated in three-quarters of neonatal deaths , but was associated with only one-third of LBW neonates . CONCLUSION Policy-relevant findings were : that LBW approximately doubles the NMR in a periurban setting in Bangladesh ; that neonatal mortality tends to occur early ; and that preterm delivery is the most important contributor to the NMR . The group of infants most likely to benefit from improvements in low-cost essential care for the newborn accounted for almost 61 % of neonatal mortalities in the cohort BACKGROUND Poor birth outcomes increase the risk of infant mortality and morbidity , developmental delays , and child maltreatment . This study assessed the effectiveness of a prenatal home-visitation program in reducing adverse birth outcomes among socially disadvantaged pregnant women and adolescents . DESIGN As part of a larger RCT , this study examined the effects of home-visitation services on low birth weight ( LBW ) deliveries . SETTING / PARTICIPANTS Pregnant women and adolescents eligible for Healthy Families New York ( HFNY ) were recruited in three communities . Eligibility was based on socioeconomic factors such as poverty , teen pregnancy , and the risk of child maltreatment . Two thirds of the participants were black or Hispanic , and 90 % were unmarried . INTERVENTION Pregnant women and adolescents were r and omized to either an intervention group that received bi-weekly home-visitation services ( n=236 ) or to a control group ( n=265 ) . Home visitors encouraged healthy prenatal behavior , offered social support , and provided a linkage to medical and other community services . Services were tailored to individual needs . MAIN OUTCOME MEASURE An LBW of < 2500 grams on birth certificate files . Baseline and birth interviews were conducted from 2000 to 2002 , and birth records were collected in 2007 . Analyses were done from 2007 to 2008 . RESULTS The risk of delivering an LBW baby was significantly lower for the HFNY group ( 5.1 % ) than for the control group ( 9.8 % ; AOR=0.43 ; 95 % CI=0.21 , 0.89 ) . The risk was further reduced for mothers who were exposed to HFNY at a gestational age of < or=24 weeks ( AOR=0.32 ; 95 % CI=0.14 , 0.74 ) . CONCLUSIONS A prenatal home-visitation program with focus on social support , health education , and access to services holds promise for reducing LBW deliveries among at-risk women and adolescents Background In the 1980s there was substantial interest in early pregnancy and pre-pregnancy interventions to increase birth weight and reduce preterm birth . We developed an inter-pregnancy intervention , implemented in a r and omised controlled trial , to be provided by midwives at home soon after women 's first birth . Methods MCH nurses invited women to take part during their home visit to new mothers . Women 's contact details , with their permission , were passed to the study midwife . She had a r and omisation schedule to which women 's names were added before she met the women or their partners . All women recruited had a home visit from the study midwife with a discussion of their first pregnancy , labour and birth and the postpartum experience . Women in the intervention arm received in addition a pre-pregnancy intervention with discussion of social , health or lifestyle problems , preparation and timing for pregnancy , family history , rubella immunisation , referrals for health problems , and a reminder card . The primary outcome was defined as a birth weight difference in the second birth of 100 g ( one-sided ) in favour of the intervention . Additional data collected were gestational age , perinatal deaths and birth defects . Analyses used EPI-INFO and STATA . Results Intervention and comparison groups were comparable on socioeconomic factors , prior reproductive history and first birth outcomes . Infant birth weight in the second birth was lower ( -97.4 g , ) ) among infants in the intervention arm . There were no significant differences between intervention and comparison arms in the proportion of women having a preterm birth , an infant with low birthweight , or an infant with a birth weight < 10th percentile . There were more adverse outcomes in the intervention arm : ten births < 32 weeks ) , compared with one in st and ard care , and more infants with a birth weight < 2000 g , 16 compared with two in st and ard care Conclusion As the primary outcome was envisaged to be either improved birth weight or no effect , the study was not design ed to identify the alternative outcome with confidence . Despite widespread support for pre-pregnancy interventions to improve maternal and perinatal health , this first r and omised controlled trial of a multi-component intervention provided at home , did not have a beneficial outcome Perinatal health problems are a public health priority in Latin America . Among the identified risk factors , psychological and social conditions play a crucial role . However , care during pregnancy and delivery in the region is usually hospital-centered and does not address women 's psychological and social conditions . The preeminence of research on perinatal health , along with the necessity for testing interventions that represent alternative models to improve women 's health , gave the Latin American Network for Perinatal and Reproductive Research grounds to develop a multicenter r and omized controlled trial to evaluate a program of social support and health education during pregnancy . The conceptual framework for this study was based on an ecological model of social support , i.e. a model in which social support and health education play a synergistic role and are meant to modify stressful situations and negative health-related behaviors . The target population consisted of women attending obstetric hospitals before the 22nd gestational week , at high psychological and social risk ( n = 2236 ) . The intervention consisted of four to six home visits , carried out by social workers , and had four main components : the reinforcement of pregnant women 's social support network , emotional support , health education , and the improvement of health services utilization . The main foci of the intervention were determined after an ethnographic study was carried out to identify stress-producing situations and needs for support during pregnancy . Besides the home visits , the program also offered a hot-line , an office in the hospital , a specially design ed poster and booklet , and a ' guided tour ' of the health institution . Since this was a multicenter trial , the program 's st and ardization was a crucial method ological aspect that was achieved through the training course for the home-visitors team . Biological and psychosocial outcomes were measured in both experimental and control groups at the 36th week of gestational age , post-partum and at the 40th day after delivery . The attributes of the multicenter population showed an important variability , reflecting differences in the countries or hospitals ' population prevalent attributes . The results of the program 's implementation were analyzed , demonstrating that home visitors adapted topics discussed during the interviews to the women 's conditions and the stage of pregnancy during which the visit took place . ( ABSTRACT TRUNCATED AT 400 WORDS BACKGROUND Preterm labour occurs in about 10 % of all pregnancies and is the most important cause of premature birth . Women with preterm labour are admitted to hospital to have the contractions stopped . Thereafter , many women remain in hospital until delivery . We conducted a r and omized clinical trial to compare hospital care with home care of women who had been admitted to hospital for preterm labour . METHODS After they had received treatment for an acute episode of premature labour , women at 2 regional perinatal centres associated with teaching hospitals were r and omly assigned to home care or hospital care . Eligible women ( n = 250 ) were aged 18 years or older , lived within 50 km of the hospital , had a gestational age between 20 and 35 weeks , had no prior preterm delivery and were experiencing their first episode of preterm labour and first admission to hospital for preterm labour . Analysis was by intention to treat . RESULTS There were no significant differences between the 2 groups in mean gestational age at delivery ( home : 37.52 weeks , hospital : 37.50 weeks ) or in mean birth weight ( home : 2974 g , hospital : 3020 g ) . There were no significant differences between the 2 groups with respect to the proportions of babies born before term or the mean duration of neonatal hospital stay , neonatal intensive care unit stay and intermediate care nursery stay . The mean duration of the first stay in hospital for the women in the home group ( 3.8 days ) was significantly shorter than the mean duration for women in the hospital group ( 6.1 days ) . In addition , the mean duration of all maternal stays in hospital was significantly shorter for the women in the home group ( 3.7 days ) than in the hospital group ( 5.0 days ) . INTERPRETATION Home care management is an efficient and acceptable alternative to hospital care for women experiencing preterm labour The Cardiff Integrated Antenatal Care Scheme ( CIACS ) places emphasis on home-centred care for selected women with a high-risk pregnancy . The Scheme is intended to make better use of midwifery and obstetric re sources , and it provides a new type of care where close surveillance is required . A r and omised controlled trial was undertaken in which anxiety levels were compared between two groups of women with an identified high-risk pregnancy . Sixty-five women were eligible for entry to the study . Five refused r and omisation and 60 were r and omised 2:1 either to care under the CIAC Scheme ( domiciliary group n = 40 ) or to conventional hospital antenatal care ( conventional group n = 17 ) . Zung depression and STAI ' trait ' levels conducted at weekly intervals were similar in both groups whilst ' state ' levels were 34.05 ( SD 9.24 ) in the domiciliary group and 41.05 ( SD 9.93 ) in the conventional care group ( P less than 0.01 ) . It is suggested that the observed difference is due to the greater security provided by the home environment coupled with individual support from a midwife Prenatal hospitalisation has not been shown to reduce perinatal morbidity and mortality , yet it is still the treatment of choice for women who experience preterm labour . Home care management may be an alternative means of delivering safe , efficacious and care for these women . The objectives of this controlled clinical trial were to examine differences in neonate 's gestational age and birthweight , and antenatal stress , social support satisfaction , and family functioning among pregnant women receiving home care and those receiving hospital care management . Pregnant women experiencing preterm labour ( N=250 ) were r and omly assigned to home care management ( the experimental group [ EG ] ) or hospital care management ( the control group [ CG ] ) . A Perinatal Information Form was used to collect data on sociodemographic and pregnancy variables . The High-Risk Pregnancy Stress Scale , Brown 's Social Behaviors Inventory , and the Family Assessment Measure III Dyadic Relationships Scale were administered to the women at r and omisation ( T1 ) and at 1-week ( T2 ) and 2-weeks ( T3 ) after r and omisation . Gestational age and birthweight were similar in the two groups of neonates . Women in the EG reported that antenatal stress was significantly lower at T3 than at T1 and T2 , while for those in the CG , antenatal stress was significantly lower at T3 than at T1 , and significantly lower at T2 than at T1 . Women in the EG were more satisfied with support from the male partner at T3 than women in the CG . There was no significant difference between the two groups in family functioning at T1 , T2 and T3 . These findings indicate that home care management is a safe and efficacious mode of health care delivery for women experiencing preterm labour Objective : To examine the cost‐effectiveness of the West Los Angeles Preterm Birth Prevention Project . Methods : Maternal and neonatal care data were collected on all preterm deliveries ( 150 ) and a r and om sample of term deliveries ( 140 ) from high‐risk patients at both experimental and control clinic sites . Costs were determined for prenatal care , inpatient preterm labor , delivery and postpartum care , and newborn care . Cost calculations , weighted by the actual proportions of term and preterm births , were confirmed with square‐root transformation and trimmed mean ( 2 % ) values . Results : When compared to control clinic high‐risk patients , experimental clinic high‐risk patients had an average cost savings of $ 2196 for newborn care ( P = .02 ) , result ing in a net savings of $ 1768 per high‐risk mother‐infant pair . Births before 32 weeks ' gestation accounted for the greatest mean cost . Conclusion : Programs of comprehensive prenatal care and patient education may be highly cost‐effective for prevention of prematurity . ( Obstet Gynecol 1994;83:506‐11 Women 's feelings and beliefs about low birth weight ( LBW ) were obtained by postal question naire completed postnatally by 467 women who had participated in a r and omised controlled trial of social support in pregnancy . All the women in the study had previously given birth to a LBW baby . Differences were found between beliefs about causes of LBW in general and in the women 's explanations for their own LBW baby . These ambiguities were particularly noticeable in relation to smoking beliefs . The women 's views on medical care ; the practical and emotional problems of low birth weight ; and the solutions to some of those problems are discussed . The need for more support from health professionals was given top priority . The main needs of women with a ' high risk ' pregnancy were more reassurance and information , recognition of the economic hardships that can be caused , and more attention to their feelings and opinions The effect of telephonic nursing case management on patient satisfaction in a predominantly non-Caucasian low-income , high-risk pregnancy population was studied . Patient satisfaction of care was significantly higher for treatment group participants than for controls on 9 of 10 items measuring satisfaction . The satisfaction score of the treatment patients , constructed by summing scores for each item , averaged 8 points higher than the control group 's score . Demographics made little difference . Telephonic case management was the strongest predictor of satisfaction in a multiple regression analysis . Satisfaction was unrelated to mode of delivery , infant birth weight , or gestational age . The satisfaction levels of treatment patients were high , whether or not they had outpatient charges . Participants rated the program highly for the nurses ' ability to answer questions , overall program experience , the opportunity to ask the nurses questions , health teachings and instructions received , and confidence in the nurse coordinating their care or their child 's care About one-third of adolescent mothers receive inadequate prenatal care , and babies born to young mothers are more likely to be of low birth weight . The objective of this study is to evaluate a peer-centered prenatal care program for adolescent mothers . Pregnant adolescents were r and omly assigned to an experimental or control group in a mastery modeling peer-support intervention design ed to improve long- and short-term perinatal outcomes . A sample of 282 urban pregnant adolescents ( 94 % African American , 4 % Caucasian , 2 % other ) participated in the study . Participants were recruited from five clinics located mainly in Detroit , Michigan . Participants in the experimental group received care in a small group setting and learned to perform critical measurements with a peer partner during prenatal visits . Participants in the control group received individual prenatal care in the same clinics . Outcome measures included birth weight , years of schooling completed at one year postpartum , planned and unplanned pregnancy at one year postpartum , and employment and school attendance at one year postpartum . Mothers in the experimental group had a lower rate of low birth weight ( 6.6 % vs. 12.5 % , p=0.08 ) . The rate of unplanned pregnancy was also lower for adolescents in the experimental group ( 13.4 % vs. 15.9 % ) , although this difference was not statistically significant . Adolescents who participated in the intervention were more likely to have continued their education during the pregnancy and the postpartum year . The mastery modeling , peer-centered , prenatal care program produced some positive pregnancy outcomes for adolescent mothers OBJECTIVES : To pilot-test a visual aid developed to help counsel pregnant women . METHODS : After agreeing to participate , pregnant women at > 28 weeks of gestation were assigned r and omly to counseling with or without a visual aid . The visual aid contained pictures , graphics , and short messages about delivery room resuscitation , chances of survival , anticipated neonatal course , and long-term neurodevelopmental disabilities . A neonatal fellow performed counseling with a st and ardized script for an anticipated delivery at 23 weeks of gestation . In precounseling and postcounseling sessions , women were given a structured interview to assess their knowledge of chances of survival and disability and attitudes toward resuscitation . RESULTS : Of the 89 women who participated , 76 % were black and 59 % read below a 9th- grade level . Compared with the no – visual aid group , women in the visual aid group recalled more disabilities and predicted longer neonatal stays ( P = .01 ) . For both groups , mothers ' perceptions of the chances of survival were lower after counseling ; the decrease was greater in the visual aid group ( P = .03 ) . The majority of women in each group opted for resuscitation , which was not affected by counseling . In multivariate analyses , use of the visual aid was a significant independent factor in explaining before/after differences in survival chances and recall of a long NICU stay and number of disabilities ; higher literacy levels also were significant for recalling the number of disabilities . CONCLUSIONS : Use of a visual aid improved mothers ' knowledge and showed promise as a decision aid for counseling at the threshold of viability OBJECTIVE The primary objective of this prospect i ve study was to test whether preterm birth prevention education plus increased clinic visits and selected prophylactic interventions reduce preterm birth . STUDY DESIGN Eight West Los Angeles prenatal county clinics , comparable with respect to selected demographics , were r and omized to be either experimental or control clinics . High-risk patients in all clinics were identified with a risk scoring system derived from a similar population . High-risk patients ( N = 1774 ) in experimental clinics were offered a program of education and more frequent visits and were r and omized to receive various secondary intervention protocol s in addition to the basic interventions of education and more frequent visits . Control clinic patients ( N = 880 ) received st and ard county care . RESULTS Preterm birth rates were 19 % lower among the experimental high-risk patients ( 7.4 % vs 9.1 % ) , and differences were significant ( p < 0.05 ) when preterm risk was taken into account . There was no evidence to suggest that the secondary interventions provided added benefit over the primary intervention protocol of preterm birth prevention education and increased visits . CONCLUSION The 19 % reduction in preterm birth rate observed in the experimental clinics suggest an overall program benefit from a protocol that offered education , more frequent visits , and greater attention given to patients while the selected interventions were applied OBJECTIVES This project investigated whether augmented prenatal care for high-risk African American women would improve pregnancy outcomes and patients ' knowledge of risks , satisfaction with care , and behavior . METHODS The women enrolled were African American , were eligible for Medicaid , had scored 10 or higher on a risk assessment scale , were 16 years or older , and had no major medical complications . They were r and omly assigned to augmented care ( n = 318 ) or usual care ( n = 301 ) . Augmented care included educationally oriented peer groups , additional appointments , extended time with clinicians , and other supports . RESULTS Women in augmented care rated their care as more helpful , knew more about their risk conditions , and spent more time with their nurse-providers than did women in usual care . More smokers in augmented care quit smoking . Pregnancy outcomes did not differ significantly between the groups ; however , among patients in augmented care , rates of preterm births were lower and cesarean deliveries and stays in neonatal intensive care units occurred in smaller proportions . Both groups had lower-than-predicted rates of low birthweight . CONCLUSIONS High- quality prenatal care , emphasizing education , health promotion , and social support , significantly increased women 's satisfaction , knowledge of risk conditions , and perceived mastery in their lives , but it did not reduce low birthweight CONTEXT A home visitation program using nurses to improve maternal and child outcomes had favorable results in a r and omized trial with a primarily white , semirural population . Many of the short-term findings have been replicated with urban blacks , but whether the program will continue to demonstrate effectiveness after its conclusion is uncertain . OBJECTIVE To determine the effectiveness of a prenatal and infancy home visitation program on the maternal life course of women in an urban environment 3 years after the program ended . DESIGN AND SETTING Three-year follow-up of a r and omized controlled trial of women seen consecutively between June 1990 and August 1991 at an obstetrical clinic in Memphis , Tenn , who were enrolled in a visitation program for 2 years after the birth of their first child . PARTICIPANTS A cohort of 743 women who were primarily black , were pregnant for less than 29 weeks , had no previous live births , and had at least 2 sociodemographic risk factors ( unmarried , < 12 years of education , or unemployed ) . INTERVENTION An average of 7 ( range , 0 - 18 ) home visits during pregnancy and 26 ( range , 0 - 71 ) from birth to the child 's second birthday . MAIN OUTCOME MEASURES Rate of subsequent pregnancy , mean interval between first and second birth , and mean number of months of welfare use . RESULTS Compared with the control group , women who received home visits by nurses had fewer subsequent pregnancies ( 1.15 vs 1.34 ; P=.03 ) , fewer closely spaced subsequent pregnancies ( 0.22 vs 0.32 ; P=.03 ) , longer intervals between the birth of the first and second child ( 30.25 vs 26.60 months ; P=.004 ) , and fewer months of using Aid to Families with Dependent Children ( 32.55 vs 36.19 ; P=.01 ) and food stamps ( 41.57 vs 45.04 ; P=.005 ) . Compared with the effect of the program while the program was in operation , the effect after it ended was essentially equal for Aid to Families with Dependent Children , greater for food stamps , greater for rates of closely spaced subsequent pregnancies , and smaller for rates of subsequent pregnancy overall . CONCLUSIONS We found enduring effects of a home visitation program on the lives of black women living in an urban setting . While these results were smaller in magnitude than those achieved in a previous trial with white women living in a semirural setting , the direction of the effects was consistent across the 2 studies The purpose of this study was to investigate the effect of applied relaxation training on reducing anxiety and perceived stress among pregnant women . A r and omized controlled trial with a prospect i ve pretest-posttest experimental design was used . One hundred ten primigravid women ( mean age = 23.8 years ) in their second trimester ( mean of gestational age = 17.8 weeks ) were r and omly assigned into experimental and control groups . The experimental group received routine prenatal care with applied relaxation training , and the control group received only routine prenatal care . State/trait anxiety was measured with the Spielberger State-Trait Anxiety Inventory , and perceived stress was measured with the Cohen Perceived Stress Scale . There were significant reductions in state/trait anxiety and perceived stress for the experimental group compared with the control group after the intervention . The findings suggest beneficial effects of relaxation on reducing anxiety and perceived stress in pregnant women . Teaching relaxation techniques could serve as a re source for improving maternal psychological health A preliminary r and omized study has been made of a domiciliary management scheme which incorporates telephonic fetal heart rate monitoring for women with high‐risk pregnancies . In this paper we report effects of the scheme on the pattern of hospital admissions . Sixty women were r and omized 2:1 for domiciliary surveillance or for conventional hospital care , with 40 and 17 records finally available for analysis . The groups were well matched for maternal , obstetric and socio‐economic characteristics . In the domiciliary group , 21 ( 53 % ) of the women avoided hospital admission altogether , the admission rate was more than halved , and the mean proportion of the time spent in hospital was reduced from 50 % to 16 % of the observation period . The women who received domiciliary care were generally satisfied with the scheme . Our study confirms expectations that carefully planned domiciliary surveillance can reduce the number and duration of hospital admissions Maternal anxiety and stress are found to be predictors of adverse pregnancy outcomes , including low birth weight and prematurity . Objective The aim of the study was to determine whether relaxation education in anxious pregnant Iranian women in their first pregnancy affects selected pregnancy outcomes , including birth weight , preterm birth , and surgical delivery rate . Subjects A total of 110 obstetrically and medically low-risk primigravid women in Iran with a high anxiety level demonstrated by Spielberger 's State-Trait Anxiety Inventory were r and omly assigned into experimental and control groups . Method In this r and omized controlled trial , the experimental group received routine prenatal care along with 7-week applied relaxation training sessions , while the control group received only routine prenatal care . Anxiety and perceived stress were measured by preeducational and posteducational intervention . Data related to pregnancy outcomes include birth weight , gestational age at birth , and type of delivery . Results Significant reductions in low birth weight , cesarean section , and /or instrumental extraction were found in the experimental group compared with the control group . No significant differences were found in the rate of preterm birth . Conclusion The findings suggest beneficial effects of nurse-led relaxation education sessions during the prenatal period . This intervention could serve as a re source for improving pregnancy outcomes in women with high anxiety Prospect i ve repeated measures were used to examine attachment , social support , life stress , anxiety , and psychological wellbeing among low-income women in early and late pregnancy and the relationships of these variables to prenatal , intrapartum , and neonatal complications . One hundred and eleven medically healthy , low-income , Medicaid-eligible women ages 18 - 35 years , between 14 and 22 weeks of pregnancy were recruited from prenatal clinics . Self-report question naires and hospital records were used to collect data . Discriminant analysis was performed . The most important discriminating factors for prenatal complications were state anxiety and total functional social support . The factors for neonatal complications were negative life events and the interaction of emotional support with negative life events OBJECTIVE : We tested the efficacy of a cognitive-behavioral intervention in reducing environmental tobacco smoke exposure ( ETSE ) and improving pregnancy outcomes among black women . METHODS : We recruited 1044 women to a r and omized , controlled trial during 2001–2004 in Washington , DC . Data on 691 women with self-reported ETSE were analyzed . A subset of 520 women with ETSE and salivary cotinine levels ( SCLs ) of < 20 ng/mL were also analyzed . Individually tailored counseling sessions , adapted from evidence -based interventions for ETSE and other risks , were delivered to the intervention group . The usual-care group received routine prenatal care as determined by their provider . Logistic regression models were used to predict ETSE before delivery and adverse pregnancy outcomes . RESULTS : Women in the intervention were less likely to self-report ETSE before delivery when controlling for other covariates ( odds ratio [ OR ] : 0.50 [ 95 % confidence interval ( CI ) : 0.35–0.71 ] ) . Medicaid recipients were more likely to have ETSE ( OR : 1.97 [ 95 % CI : 1.31–2.96 ] ) . With advancing maternal age , the likelihood of ETSE was less ( OR : 0.96 [ 95 % CI : 0.93–0.99 ] ) . For women in the intervention , the rates of very low birth weight ( VLBW ) and very preterm birth ( VPTB ) were significantly improved ( OR : 0.11 [ 95 % CI : 0.01–0.86 ] and OR : 0.22 [ 95 % CI : 0.07–0.68 ] , respectively ) . For women with an SCL of < 20 ng/mL , maternal age was not significant . Intimate partner violence at baseline significantly increased the chances of VLBW and VPTB ( OR : 3.75 [ 95 % CI : 1.02–13.81 ] and 2.71 [ 95 % CI : 1.11–6.62 ] , respectively ) . These results were true for mothers who reported ETSE overall and for those with an SCL of < 20 ng/mL. CONCLUSIONS : This is the first r and omized clinical trial demonstrating efficacy of a cognitive-behavioral intervention targeting ETSE in pregnancy . We significantly reduced ETSE as well as VPTB and VLBW , leading causes of neonatal mortality and morbidity in minority population s. This intervention may reduce health disparities in reproductive outcomes The effects of telephonic nursing case management and st and ard care in a low-income , high-risk pregnancy population , controlling for gestational age at referral and risk factors ( medical , demographic , and behavioral ) were compared . The hypothesis was that a program of telephonic perinatal nursing care coordination and case management would increase mean gestational ages and mean birth weights and would reduce clinical re source utilization , compared with st and ard nursing care . The methods focused on a telephonic model developed during the past 16 years that included risk assessment , patient education , coordination of care for home services and clinic appointments , coordination of interventions requested by care providers , and patient advocacy . The patient population , primarily of minority cultural and racial background s , obtained prenatal care from two large obstetric clinics and delivered at a level-3 tertiary care center . They were r and omly assigned to treatment ( N = 61 ) and control ( N = 50 ) conditions . Interpreters were used for any contacts with non-English-speaking patients . The results demonstrated increased mean birth weights for the treatment group when intervening variables were controlled . Mean gestational age at delivery was not significantly different between groups . Telephonic case management saved an average of 501.31 dollars per patient in inpatient and outpatient costs combined . In the treatment group , for every dollar spent on case management costs , the savings were 4.08 dollars A completed series of reports on a r and omized trial ( N=400 ) indicated that , in contrast to comparison services , prenatal and infancy nurse home visitation improved a wide range of maternal and child health outcomes among poor , unmarried , and teenaged women bearing first children in a semirural county in upstate New York . Eighty-nine percent of the sample was white , and all analyses focused on this group . In this article , an analysis of the net cost of the home-visitation program from the perspective of government spending is presented . The average per-family cost of the program in 1980 dollars was $ 3,246 for the sample as a whole , and $ 3,133 for low-income families . Treatment differences in government expenditures for Aid to Families with Dependent Children , Food Stamps , Medicaid , and Child Protective Services , minus tax revenues due to maternal employment ( also expressed in 1980 dollars ) , were conceived as government savings . By the time the children were 4 years of age , government savings were $ 1,772 ( 95 % confidence interval [ CI ] : -$557 , $ 4,102 ) for the sample as a whole , and $ 3,498 ( 95 % CI : $ 569 , $ 6,427 ) for low-income families . Within 2 years after the program ended , after discounting , the net cost of the program ( program costs minus savings ) for the sample as a whole was $ 1,582 per family . For low-income families , the cost of the program was recovered with a dividend of $ 180 per family OBJECTIVE Improve pregnancy outcomes in first-time Hispanic adolescent mothers and their infants . SETTING Urban communities in Orange County , California . DESIGN AND METHODS A comparison of the Nurse-Family Partnership pilot study home visitation program with traditional Public Health Field Nursing ( PHFN ) home visitation . PARTICIPANTS Two hundred twenty-five Hispanic adolescent mothers and their infants . INTERVENTIONS Participants in the control group received the traditional PHFN services ; the intervention group received interventions from advanced trained public health nurses The control group received a minimum of three home visits : one initial client assessment and family profile , one antepartum visit , and one postpartum visit , including newborn assessment . Participants in the intervention group received weekly home visits for the first 4 weeks , followed by visits every other week until delivery , weekly visits for the next 6 weeks , visits every other week until the child was 20 months , and monthly visits until the child was 24 months of age . RESULTS Preliminary results indicate that home visitation by public health nurses ( PHNs ) positively affected the health of adolescents mothers and their infants . The incidence of premature births to adolescent mothers in the intervention group was lower than that found in the California population of adolescent mothers . CONCLUSION Preliminary results from this program showed that PHN home visitation ( control and intervention groups ) positively affects the birth outcomes of adolescent mothers and their infants Data relating to infant feeding practice s were obtained by a 6 week postnatal question naire from 459 women who participated in a r and omised controlled trial of social support in pregnancy . They represented a 90 % response rate from 507 women with a past history of a low birth weight baby before the index pregnancy . Thirty-nine per cent of the babies weighing more than 2500 g were breast fed completely . Women who experienced a delay of more than half an hour between birth and first suckling , and those who were given pethidine during labour breast fed for a shorter period , as did those who gave complementary bottle feeds . By considering the women 's reasons for discontinuing or not initiating breast feeding , this paper suggests that improved social support from health professionals and others in the postnatal period can increase breast feeding success rates BACKGROUND Adolescent pregnancy and parenting remain a major public concern because of their impact on maternal-child health and on the social and economic well-being of the nation . Federal welfare reform legislation has created an urgent need for community-based nursing intervention programs to improve health and social outcomes for disadvantaged adolescent mothers and to promote their self-sufficiency . OBJECTIVE To evaluate the effects of an early intervention program ( EIP ) that uses a public health nursing model on health and social outcomes of adolescent mothers and their children and on the quality of mother-child interaction . METHODS Pregnant adolescents referred to a county health department were r and omly assigned to an experimental ( EIP ) or control ( traditional public health nursing [ TPHN ] ) group . The sample included 121 adolescents from predominantly minority and impoverished background s who were followed from pregnancy through 6 weeks postpartum . Intense and comprehensive home visitation by public health nurses and preparation-for-motherhood classes were provided to adolescents in the EIP . Health outcomes were determined on the basis of medical record data . Other measures included maternal self-report on selected behaviors , nurse interviews , and the Nursing Child Assessment Teaching Scale ( NCATS ) . RESULTS Early findings indicate reduced premature birth and low-birth-weight ( LBW ) rates for young mothers receiving both forms of public health nursing care . No significant differences between groups were found for infant birth weight or type of delivery . Infants in the EIP had significantly fewer total days of birth-related hospitalization and rehospitalization than those in the TPHN group during the first 6 weeks of life ( chi2(1 ) = 6.41 ; p = 0.01 ) . Adolescents in the EIP demonstrated significantly more positive educational outcomes ( e.g. , lower school dropout rates ) than those in the TPHN group ( chi2(1 ) = 6.76 ; p < 0.009 ) . CONCLUSIONS The early findings of this study demonstrate that pregnant adolescents benefit from both traditional and more intense public health nursing care in terms of prenatal and perinatal outcomes . The EIP was associated with decreased infant morbidity during the first 6 weeks of life and decreased maternal school dropout . Long-term outcomes for the EIP are being evaluated AIM The aim of the study was to test the psychosocial benefits of a telephone support program for pregnant women . METHOD R and omised controlled trial . The study sample were women recruited from an antenatal clinic and general practice surgeries who were less than 20 weeks gestation and either single or in a relationship where the partner was unemployed . Women in the intervention group received weekly telephone calls throughout their pregnancy . All women were interviewed initially and at 34 weeks gestation . There were 66 women in the control group and 65 women in the intervention group . RESULTS The intervention and control groups did not differ significantly on the psychosocial measures at baseline . Comparisons at 34 weeks were made by analysis of covariance using the baseline scores . The intervention group at 34 weeks had lower stress scores than the control group ( means 16.5 vs 18.4 , p = 0.02 ) , lower trait anxiety ( means 35.2 vs 39.4 , p = 0.04 ) and less depressed mood ( means 6.6 vs 8.1 , p = 0.02 ) . Self esteem was higher for the intervention group ( means 34.9 vs 32.5 , p = 0.008 ) . The intervention failed to alter smoking but the intervention women did report more use of community re sources ( p = 0.02 ) and were less likely to skip meals ( p = 0.03 ) . CONCLUSION A low cost health promotion program of telephone support during pregnancy can significantly improve a woman 's psychosocial status during pregnancy We evaluated a comprehensive program of prenatal and postpartum nurse home visitation for socially disadvantaged women bearing first children . Eighty-five per cent of the participating women were either teenagers ( less than 19 years at registration ) , unmarried , or of low socioeconomic status . Women were r and omly assigned to either nurse home visitation or comparison services ( free transportation for prenatal and well-child care and /or sensory and developmental screening for the child ) . During the first four years after delivery of their first child , in contrast to their counterparts in the comparison group , nurse-visited White women who had not graduated from high school when they registered in the study returned to school more rapidly ; nurse-visited , poor , unmarried White women showed an 82 per cent increase in the number of months they were employed , had 43 per cent fewer subsequent pregnancies , and postponed the birth of second children an average of 12 months longer Objective To test the effect of telephone calls from registered nurses to low-income pregnant women on the rates of low birth weight ( LBW ) and preterm births . Methods A total of 1554 women receiving prenatal care in a public clinic who met study criteria and who consented were assigned r and omly to intervention and control groups . Women in the intervention group received telephone calls from a registered nurse , one or two times weekly from 24 weeks ' through 37 weeks ' gestation . Relative risks ( RRs ) and 95 % confidence intervals ( CIs ) were calculated . Results Low birth weight rates were 10.9 % in the intervention group and 14.0 % in the control group ( RR 0.75 ; 95 % CI 0.55 , 1.03 ; P = .072 ) . For gestational age less than 37 weeks , rates were 9.7 in the intervention group and 11.0 in the control group ( RR .87 ; 95 % CI 0.62 , 1.22 ; P = .415 ) . In the subgroup of low-income black women 19 years of age and older , a statistically significant difference was found in preterm birth rates before 37 weeks ( 8.7 % in the intervention group versus 15.4 % in the controls [ RR 0.56 ; 95 % CI 0.38 , 0.84 ; P = .004 ] ) . Conclusion There was no difference in LBW or preterm births between intervention and control groups in the total sample . In a secondary analysis of black subjects 19 years of age and older , there was a significant difference in preterm birth rates BACKGROUND A cost-benefit analysis was performed to estimate the cost-savings obtained from a nursing telephone intervention delivered to pregnant women identified as being at risk for preterm or low-birthweight births . METHODS After being screened for eligibility , a total of 1,554 women receiving prenatal care in a clinic located in Winston-Salem , North Carolina were r and omized to intervention and control groups . Women in the intervention group received telephone calls from a registered nurse one or two times each week from the 24th through the 37th week of gestation . RESULTS No clinical benefits were realized by Caucasian participants . The intervention reduced preterm and low-birthweight births , and result ed in cost savings , for African-American mothers ages 19 and over . No significant differences were seen in the rates of low-birthweight or preterm births and no cost savings were realized from intervention with women ages 18 and younger . CONCLUSIONS A prenatal nursing support intervention in a clinic population of pregnant African American women was cost-beneficial for these adults ( < or = 19 years of age ) Previous clinical trials of social support interventions to reduce low birthweight ( LBW ) have not fully capitalized on findings from social science research , and therefore have not used empirically-derived criteria to define a low social support population or to develop the intervention . To overcome limitations of previous studies , this r and omized clinical trial tested the hypothesis that an empirically-derived social support intervention would reduce LBW among African American women . Based on prior work , African American women were identified as at-risk for LBW due to inadequate social support if they lacked support from their mothers or male partners . Focus groups were used in this study to develop a culturally-relevant intervention . Adult low-income African American pregnant women ( n = 319 ) were tested for inadequate social support in mid-pregnancy . Of these , 114 ( 36 % ) low-support women were identified and r and omly assigned to the intervention group ( n = 56 ) or control group ( n = 58 ) . The intervention was design ed to provide the support usually provided by the pregnant woman 's mother or male partner . It consisted of four st and ardized face-to-face sessions at two week intervals and telephone contact in the intervening weeks . Birthweight was obtained blinded from charts or birth certificates , with 99 % follow-up . The rate of LBW ( below 2500 grams ) was 9.1 % in the intervention group compared to 22.4 % in the control group ( P < 0.05 ) . Contrary to previous studies , this social support intervention was effective in reducing the rate of LBW . It is promising that this intervention was successful for African Americans because the rate of LBW is twice as high among African Americans than among Caucasians Objective — To test the effect of a programme of additional antenatal social support on the occurrence of preterm birth ( a birth from 20 to 36 weeks gestation ) in women at risk of preterm birth A pilot scheme was introduced in Manchester to provide additional social support to pregnant women at above average risk of giving birth to a low‐birthweight baby . The help of lay workers , known as family workers , was made available to eligible women . The effect on infant birthweight of offering the help of a family worker was assessed by a r and omized controlled trial . No significant differences were observed between the experimental and control group , but on a number of grounds the interpretation of this finding is not straightforward , and further research is recommended From 2009 to 2010 , an experiment was conducted to increase response rates among African American mothers in the Wisconsin Pregnancy Risk Assessment Monitoring System ( PRAMS ) . Sample members were r and omly assigned to groups that received a prepaid , cash incentive of $ 5 ( n = 219 ) ; a coupon for diapers valued at $ 6 ( n = 210 ) ; or no incentive ( n = 209 ) . Incentives were included with the question naire , which was mailed to respondents . We examined the effects of the incentives on several outcomes , including response rates , cost effectiveness , survey response distributions , and item nonresponse . Response rates were significantly higher for the cash group than for the coupon ( 42.5 vs. 32.4 % , P < .05 ) or no incentive group ( 42.5 vs. 30.1 % , P < .01 ) ; the coupon and no incentive groups performed similarly . While absolute costs were the highest for the cash group , the cost per completed survey was the lowest . The incentives had limited effects on response distributions for specific survey questions . Although respondents completing the survey by mail in the cash and coupon groups exhibited a trend toward being less likely to have missing data , the effect was not significant . Compared to a coupon or no incentive , a small cash incentive significantly improved response rates and was cost effective among African American respondents in Wisconsin PRAMS . Incentives had only limited effects , however , on survey response distributions , and no significant effects on item nonresponse BACKGROUND The addition of supplementary prenatal support may improve the health and well-being of high-risk women and families . The objective of this r and omized controlled trial was to examine the impact of supplementary prenatal care on re source use among a community-based population of pregnant women . METHODS Pregnant women from three urban maternity clinics were r and omized ( a ) to current st and ard of physician care , ( b ) to current st and ard of care plus consultation with a nurse , or ( c ) to ( b ) plus consultation with a home visitor . Participants were 1,352 women who received 3 telephone interviews . The primary outcome was re source use ( e.g. , attended prenatal classes , used nutritional counseling ) . RESULTS Overall , those in the nurse intervention group were more likely to attend an " Early Bird " prenatal class and parenting classes , and to use nutrition counseling and agencies that assist with child care . Women provided with extra nursing and home visitation supports were more likely to use a written re source guide , nutrition counseling , and agencies that assist with child care . Among women at higher risk ( e.g. , language barriers , young maternal age , low income ) , the nurse intervention significantly increased use of early prenatal classes , whereas the nurse and home visitor intervention significantly increased use of the written re source guide and nutrition counseling . The intervention substantially increased the amount of information received on numerous pregnancy-related topics but had little impact on re source use for mental health and poverty-related needs . Among those with added support , re source use among low-risk women was generally greater than among high-risk women . CONCLUSIONS Additional support provided by nurses , or nurses and home visitors , can successfully address informational needs and increase the likelihood that women will use existing community-based re sources . This finding was true even for high-risk women , although this intervention did not reduce the difference in re source use between high- and low-risk women The effect of comprehensive prenatal care on birth weight was examined using a prospect i ve r and omized design . A total of 428 pregnant women were r and omly assigned to comprehensive prenatal care ( n = 217 ) or st and ard prenatal care ( n = 211 ) . Comprehensive care was provided by a multidisciplinary team of nurse-midwives , social workers , a nutritionist , paraprofessional home visitors , and a psychologist . St and ard prenatal care consisted of medical care provided by obstetric residents . Multiple regression analysis using behavioral , demographic , and medical variables showed a strong relationship between the set of predictors and birth weight . Comprehensive care was related to higher birth weights for primiparous but not multiparous mothers . Separate analyses of variance for primiparas and multiparas similarly showed a favorable effect of comprehensive care on birth weight for primiparous but not multiparous mothers In a previous study we showed that moderate to severe stress during pregnancy was inversely related to infant birth weight . Using the same criteria for stress ( according to the Social Readjustment Rating Scale of Holmes and Rahe ) , we studied 86 white mothers with singleton pregnancies and with no known medical or obstetric risk factors for reduced birth weight . After strict r and omization , data were analyzed for 43 mothers who received psychosocial support between enrollment at + /- 20 weeks and delivery at + /- 38 weeks and for 43 control mothers who received st and ard care at the antenatal clinic . In the supported group seven infants weighed less than 3000 gm at birth versus 18 control infants ( p = 0.008 ) , and analysis revealed that this effect was more the result of improved intrauterine growth than of prolongation of pregnancy . These findings are of little clinical relevance as far as the neonate is concerned , but they do indicate that psychosocial support has a significant effect on birth weight . It is possible that previous studies that have looked only for an effect on low- or very-low-birth-weight rates might have missed this clinical ly measurable benefit of counseling Objective The purpose of this study was to examine if depressive symptomatology in pregnancy is associated with adverse obstetric and neonatal outcomes . Method In a prospect i ve observational study , 959 women were followed up longitudinally from early pregnancy to postpartum . The level of depression was measured at baseline ( first antepartum visit ) and in late pregnancy using the Beck Depression Inventory ( BDI ) . Adverse obstetric and neonatal outcomes were recorded at delivery . Results Depression in late pregnancy was associated with increased risk of epidural analgesia ( 33 % vs. 19 % , p = .01 , adjusted RR = 2.56 , 95 % CI 1.24–5.30 ) , operative deliveries ( caesarean sections and instrumental vaginal deliveries ) ( 39 % vs. 27 % , p = .02 , adjusted RR = 2.28 , 95 % CI 1.15–4.53 ) , and admission to neonatal care unit ( 24 % vs. 19 % , p = .03 , adjusted RR = 2.18 , 95 % CI 1.02–4.66 ) . These effects remained significant even when controlled for potential confounders , such as antepartum complications . Conclusion Previous studies have shown that antepartum anxiety or stress was associated with growth retardation , premature delivery , and epidural analgesia . Our findings add to this body of evidence , which together suggest an adverse impact of antepartum psychological morbidity on maternal and neonatal well-being BACKGROUND It is often suggested that psychological and social support and health education for women at high risk for delivering a low-birth-weight infant can improve the outcomes of pregnancy , but the evidence is inconclusive . We undertook this prospect i ve trial to evaluate a program of home visits design ed to provide psychosocial support during pregnancy . METHODS At four centers in Latin America , 2235 women at higher-than-average risk for delivering a low-birth-weight infant were recruited before the 20th week of pregnancy . The women were r and omly assigned either to an intervention group ( n = 1115 ) that received four to six home visits from a nurse or social worker in addition to routine prenatal care or to a control group ( n = 1120 ) that received only routine prenatal care ( with a mean of eight prenatal visits ) . The principal measures of outcome were low birth weight ( < 2500 g ) , preterm delivery ( < 37 weeks of gestation ) , and specified categories of maternal and neonatal morbidity . RESULTS The women who received the home visits as well as routine prenatal care had outcomes that differed little from those of the women who received only routine care . The risks of low birth weight ( odds ratio for the intervention group as compared with the control group , 0.93 ; 95 percent confidence interval , 0.68 to 1.28 ) , preterm delivery ( odds ratio , 0.88 ; 95 percent confidence interval , 0.67 to 1.16 ) , and intrauterine growth retardation ( odds ratio , 1.08 ; 95 percent confidence interval , 0.83 to 1.40 ) were similar in the two groups . There was no evidence that the intervention had any significant effect on the type of delivery , the length of hospital stay , perinatal mortality , or neonatal morbidity in the first 40 days . There was no protective effect of the psychosocial-support program even among the mothers at highest risk . CONCLUSIONS Interventions design ed to provide psychosocial support and health education during high-risk pregnancies are unlikely to improve maternal health or to reduce the incidence of low birth weight among infants OBJECTIVE To compare the effectiveness of routine management of patients at high risk for preterm delivery to the effectiveness of routine management in combination with daily telephone nursing contact . STUDY DESIGN The control group , 1 ( n = 21 ) , had education and frequent prenatal visits and cervical examinations . The study group , 2 ( n = 21 ) , had education , frequent prenatal visits and cervical examination , and daily telephone contact . Group 3 ( n = 22 ) received education but refused to participate . RESULTS There were no significant differences ( SD ) between groups in race , smoking , age , multiple gestation , visits , diagnosis of premature labor , mean days gained after diagnosis of premature labor , tocolytic use or bed rest . There was also no SD in preterm birth rate , mode of delivery , number of maternal or neonatal hospital days , mean neonatal weight or gestational age at delivery between groups . While not reducing the overall incidence of preterm birth , this management for all groups result ed in a more advanced gestational age at the time of delivery ( mean change = 7.5 weeks , P < .0001 ) when compared to the patient 's first preterm birth . CONCLUSION This study indicated that daily contact , while providing reassurance and support , did not change the outcome when the study group was compared to women managed similarly but without daily contact We evaluated a comprehensive program of prenatal and postpartum nurse home visitation . The program was design ed to prevent a wide range of health and developmental problems in children born to primiparous women who were either teenagers , unmarried , or of low socioeconomic status . During pregnancy , women who were visited by nurses , compared with women r and omly assigned to comparison groups , became aware of more community services ; attended childbirth classes more frequently ; made more extensive use of the nutritional supplementation program for women , infants , and children ; made greater dietary improvements ; reported that their babies ' fathers became more interested in their pregnancies ; were accompanied to the hospital by a support person during labor more frequently ; reported talking more frequently to family members , friends , and service providers about their pregnancies and personal problems ; and had fewer kidney infections . Positive effects of the program on birth weight and length of gestation were present for the offspring of young adolescents ( less than 17 years of age ) and smokers . In contrast to their comparison-group counterparts , young adolescents who were visited by nurses gave birth to newborns who were an average of 395 g heavier , and women who smoked and were visited by nurses exhibited a 75 % reduction in the incidence of preterm delivery . ( P less than or equal to .05 for all findings . A program of prenatal and infancy home visitation by nurses was tested as a method of preventing a wide range of health and developmental problems in children born to primiparas who were either teenagers , unmarried , or of low socioeconomic status . Among the women at highest risk for care-giving dysfunction , those who were visited by a nurse had fewer instances of verified child abuse and neglect during the first 2 years of their children 's lives ( P = .07 ) ; they were observed in their homes to restrict and punish their children less frequently , and they provided more appropriate play material s ; their babies were seen in the emergency room less frequently during the first year of life . During the second year of life , the babies of all nurse-visited women , regardless of the families ' risk status , were seen in the emergency room fewer times , and they were seen by physicians less frequently for accidents and poisonings than comparison group babies ( P less than or equal to .05 for all findings , except where indicated . ) Treatment differences for child abuse and neglect and emergency room visits were more significant among women who had a lower sense of control over their lives In order to evaluate the effectiveness of domiciliary care of pathological pregnancies by midwives a comparative study was carried out on two groups of pregnant women , the one group being treated by this new method of caring fort them , the other by traditional care . There was r and om selection for the two groups . The results of this comparative controlled study show that when midwives care for these patients at home once a pathological condition has become established premature labour and admission to hospital is not avoided . A more preventive attitude developed . This implies that they intervene very early in pregnancy as soon as risk factors for pathological conditions appear without waiting for the pathological conditions themselves to develop |
12,048 | 20,687,095 | In other words , it appears that doses > 50mg/day do not produce further reductions in either SBP or DBP .
From the limited available evidence , spironolactone appears to lower blood pressure compared to placebo to a similar degree in patients with primary ( essential ) hypertension when doses of 100 - 500 mg/day are given .
A dose of 25 mg/day did not statistically significantly reduce systolic or diastolic blood pressure , compared to placebo .
Given the lack of a dose-response , coupled with a possible increased risk in adverse events with higher doses , doses of 25 to 100 mg/day are reasonable .
There is no evidence of the effect of spironolactone on clinical outcomes in hypertensive patients | BACKGROUND Spironolactone is an aldosterone antagonist , considered fourth line therapy for hypertension in patients already treated with multiple medications .
OBJECTIVES Primary : to determine the effect of spironolactone on patient mortality , morbidity , and to quantify the magnitude of blood pressure lowering effect of spironolactone monotherapy .
Secondary : to determine the prevalence of adverse reactions observed with spironolactone monotherapy and to determine if there is a blood-pressure lowering dose response with spironolactone . | Background —Specific treatments targeting the pathophysiology of hypertensive heart disease are lacking . As aldosterone has been implicated in the genesis of myocardial fibrosis , hypertrophy , and dysfunction , we sought to determine the effects of aldosterone antagonism on myocardial function in hypertensive patients with suspected diastolic heart failure by using sensitive quantitative echocardiographic techniques in a r and omized , double-blinded , placebo-controlled study . Methods and Results —Thirty medically treated ambulatory hypertensive patients ( 19 women , age 62±6 years ) with exertional dyspnea , ejection fraction > 50 % , and diastolic dysfunction ( E/A < 1 , E deceleration time > 250m/sec ) and without ischemia were r and omized to spironolactone 25 mg/d or placebo for 6 months . Patients were overweight ( 31±5 kg/m2 ) with reduced treadmill exercise capacity ( 6.7±2.1 METS ) . Long-axis strain rate ( SR ) , peak systolic strain , and cyclic variation of integrated backscatter ( CVIB ) were averaged from 6 walls in 3 st and ard apical views . Mean 24-hour ambulatory blood pressure at baseline ( 133±17/80±7 mm Hg ) did not change in either group . Values for SR , peak systolic strain , and CVIB were similar between groups at baseline and remained unchanged with placebo . Spironolactone therapy was associated with increases in SR ( baseline : −1.57±0.46 s−1 versus 6-months : −1.91±0.36 s−1 , P<0.01 ) , peak systolic strain ( −20.3±5.0 % versus −26.9±4.3 % , P<0.001 ) , and CVIB ( 7.4±1.7dB versus 8.6±1.7 dB , P=0.08 ) . Each parameter was significantly greater in the spironolactone group compared with placebo at 6 months ( P=0.05 , P=0.02 , and P=0.02 , respectively ) , and the increases remained significant after adjusting for baseline differences . The increase in strain was independent of changes in blood pressure with intervention . The spironolactone group also exhibited reduction in posterior wall thickness ( P=0.04 ) and a trend to reduced left atrial area ( P=0.09 ) . Conclusions —Aldosterone antagonism improves myocardial function in hypertensive heart disease Summary Since there is only scanty , indirect information about the mechanism of the hypotensive effect of spironolactone , 9 patients with essential hypertension were studied according to a r and omised double-blind , cross-over protocol . Spironolactone 100 mg b.i.d . and placebo were each given for one month and the following parameters were studied : blood pressure , heart rate , response to cold pressure and h and -grip tests , as well as blood flow in the calf and finger vessels . Flow in the calf and fingers representing muscle and skin arteries , respectively , was measured semicontinuously with an ECG-triggered venous occlusion plethysmograph . After spironolactone there was a significant decrease in the systolic and diastolic blood pressures in the supine , sitting and st and ing positions ; the sitting systolic and diastolic blood pressure decreased by ( mean ± SE ) 27±4 mm Hg ( p<0.001 ) and 11±4 mm Hg ( p<0.02 ) , respectively . No orthostatic response was observed . Heart rate remained unchanged . Blood flow through muscle and skin vessels increased in 6 out of 9 patients , and in these patients calculated vascular resistance in these areas decreased . Spironolactone did not significantly change the response of systemic blood pressure to the h and grip and cold pressure tests . The present data confirm the hypotensive properties of spironolactone and show that this effect is associated with dilatation of muscle and skin arteries in many but not in all the patients . The data do not support the hypothesis that spironolactone decreases the responsiveness of systemic blood pressure to orthosympathetic stimulation The relative blood pressure response and side effects of spironolactone ( S ) , 400 mg/day , and hydrochlorothiazide ( H ) , 100 mg/day , were evaluated in a double‐masked crossed comparison . Subjects were 24 essential hypertensives , 13 normal and 11 with low renin activity . Upright renin levels were determined in the am after 3 days of moderately low sodium diet ( < 100 mEq/day ) and at the end of each drug treatment period . The values were not revealed to one investigator until completion of the study . After 4‐week placebo control periods , either S or H was given in divided doses for 6 weeks . Blood pressure measurements and side effects were evaluated at biweekly intervals . The fall in blood pressure from control was the same for each drug and was independent of renin activity . Side effects occurred more often in patients treated with S , and H was judged superior by risk/benefit analysis . We conclude that S is no more beneficial than H in hypertensive patients with either low or normal renin activity but induces a higher incidence of adverse effects in the dose used in this study . We found no evidence for a greater effectiveness of S in low‐renin essential hypertension The effects of inhibiting angiotensin converting enzyme with perindopril and aldosterone with spironolactone were tested in hypertensive patients over fifty . Accordingly , 75 patients with mild hypertension aged 50 to 70 were r and omly divided into three groups for a double-blind 8 week comparison of the actions of placebo , 4 to 8 mg/day perindopril , and 37.5 to 75 mg/day spironolactone . Side-effects caused one patient to withdraw from placebo and one from spironolactone treatment . Mean blood pressure rose by 2.4 mm Hg after placebo but dropped by 7.4 and 8.6 after perindopril and spironolactone ( P less than .01 ) . Placebo , perindopril , and spironolactone did not alter blood glucose or plasma potassium , but induced , respectively , variations of -0.09 , 0 , and + 0.34 mmol/L in cholesterol ( P = .04 ) , and -0.02 , -0.05 , and + 0.27 mmol/L in triglycerides ( P less than .01 ) . After the three treatments , changes in angiotensin converting enzyme activity averaged -1 , -6 , and -1 mU/mL ( P less than .01 ) , in active renin -2 , + 18 , and + 28 pg/mL ( P less than .01 ) , and in aldosterone , + 15 , + 8 , and + 95 pg/mL ( P less than .01 ) . Placebo , perindopril , and spironolactone did not alter microalbuminuria , but reduced urinary kallikrein activity by 0.9 , 1.8 , and 5.4 mU/mmol creatinine ( P = .04 ) . Although short-term administration of spironolactone raised renin and aldosterone markedly and lipids moderately ( possibly because of volume contraction ) , the present results show that perindopril and spironolactone are both safe and effective for treating hypertension at the age of 50 or older Twenty-seven patients with hypertension were r and omly allocated to a 10 month crossover study . Treatment consisted of spironolactone ( 200 mg/day for 2 months ) , propranolol ( 320 mg/day for 2 months ) and combined administration of both drugs at half the dosage . Between treatment periods placebo was given for 2 months . Fourteen patients were previously untreated . The average pretreatment blood pressure for the entire group was 188/114 + /- 16/7(mean + /- st and ard deviation ) mm Hg supine and 188/118 + /- 20/9 mm Hg st and ing . Both spironolactone and propranolol reduced blood pressure significantly in both the supine and st and ing positions . Upright plasma renin activity was determined by radioimmunoassay of angiotensin I. The average initial level was 1.9 + /- 1.2 ( range 0.4 to 5.0 ) ng/ml/hr . There was a close correlation between plasma renin activity and the effects of the drugs : With increasing renin level the response to propranolol was better whereas the opposite was true for spironolactone . The combination of spironolactone and propranolol decreased the blood pressure still further in the supine and st and ing positions , irrespective of initial plasma renin activity . All patients achieved a normal supine pressure . Blood pressure and plasma renin activity returned toward pretreatment values during placebo administration . It is concluded that pretreatment levels of plasma renin activity can predict the antihypertensive response to propranolol and spironolactone . The combination of the two drugs , which have different modes of action , will effectively reduce blood pressure in hypertension . The results support the concept that the renin-angiotensin-aldo-sterone system may be involved in primary hypertension In a prospect i ve , double-blind , intraindividual , cross-over , placebo-controlled multicenter study , clinical and biochemical effects of once daily postpr and ial dose regimens of 50 , 100 , and 200 mg spironolactone were investigated in 45 out patients with primary hypertension , WHO ( World Health Organization ) Stage I-II . Each of the three active therapy periods , which were r and omly allocated to patients , were of 2 months ' duration , with intervening placebo periods , Clinical and biochemical parameters , including furosemide-stimulated plasma renin activity ( PRA ) , were recorded at regular intervals . All three spironolactone doses result ed in statistically significant blood pressure ( BP ) reductions independent of initial pretreatment levels and yielded satisfactory BP control in more than half of the patients . The 200 mg daily dose of spironolactone was found to be more effective than 50 but not 100 mg . When , correlating blood pressure response ( delta MAP ) to PRA , the profiling for positive spironolactone responders was characterized by high age and low PRA , irrespective of sex . Spironolactone therapy result ed in decreased serum sodium and magnesium values ; potassium , creatinine , urate , and triglyceride levels were increased . However , all treatment values were within normal ranges . Side effects were infrequent and mainly of endocrine nature In a crossover study 32 patients with hypertension were r and omly allocated to treatment with spironolactone 200 mg/day for two months , propranolol 320 mg/day for two months , and a combination of both drugs at half the dose . Between the treatments placebo was given for two months . Both spironolactone and propranolol lowered the blood pressure significantly in both positions . The initial plasma renin activity ( PRA ) levels ranged from 0 - 4 to 5 - 0 mug angiotensin I l-1 h-1 , and there was a close correlation between these levels and the effects of the drugs : with increasing PRA the response to propranolol was better while the opposite was true for spironolactone . Spironolactone reduced the blood pressure more at eight than at four weeks , while no such difference could be shown for propranolol . Spironolactone and propranolol together decreased the blood pressure still further irrespective of the initial PRA . All patients achieved a normal supine blood pressure Aims /hypothesisAldosterone antagonism improves endothelial function ( and reduces deaths ) in chronic heart failure . It is not known whether similar effects occur in other high-risk groups such as patients with diabetes and hypertension . We therefore assessed the full effects of aldosterone blockade in poorly controlled hypertensive patients with type 2 diabetes , focussing on blood pressure , endothelial function , glycaemic control and key hormones . Methods We performed a r and omised , placebo-controlled , double-blind , crossover study on 50 patients with type 2 diabetes and treated but poorly controlled hypertension , comparing spironolactone versus placebo . Patients had their endothelial function assessed by st and ard forearm venous occlusion plethysmography . Results There was no significant improvement in endothelium-dependent vasodilatation in response to acetylcholine , despite highly significant reductions in systolic and diastolic blood pressure . However , spironolactone significantly worsened glycaemic control , plasma angiotensin II and cortisol . Conclusions /interpretationSpironolactone is highly effective in lowering blood pressure in patients with type 2 diabetes and poorly controlled hypertension on st and ard treatment , but does not improve vascular endothelial function in this group . We speculate that any tendency for the spironolactone-induced lowering of blood pressure to improve endothelial function is offset by its tendency to worsen glycaemic control and increase the levels of angiotensin II and even possibly cortisol . Trials Registry no. : IS RCT N The long-term efficacy and tolerance of spironolactone in essential hypertension was evaluated among 20,812 patients referred to the Broussais and St. Joseph systemic hypertension clinics between 1976 and 1985 by using information prospect ively collected in the computerized ARTEMIS data bank . In 182 patients ( 51 men , 131 women ) treated with spironolactone alone during a mean follow-up period of 23 months , a mean dose of 96.5 mg decreased systolic and diastolic blood pressure ( BP ) by 18 and 10 mm Hg , respectively , below pretherapeutic levels . The BP decrease was greater with doses of 75 to 100 mg ( 12.4 % and 12.2 % ) than with doses of 25 to 50 mg ( 5.3 and 6.5 % , p less than 0.001 ) , but no additional decrease was found with doses above 150 mg . Plasma creatinine level increased modestly ( 8.3 mumol/liters ) , as did plasma potassium level ( 0.6 mmol/liters ) ( both p less than 0.001 ) ; uric acid level increased , but not significantly ( 10.5 mumol/liter ) . Fasting blood glucose and total cholesterol levels did not change , triglyceride levels increased slightly ( 0.1 mmol/liter , p less than 0.05 ) . These changes were similar in both sexes and were not influenced by length of follow-up . Among the 699 men prescribed spironolactone alone or in association with another antihypertensive treatment , 91 cases of gynecomastia developed ( 13 % ) . Gynecomastia was reversible and dose-related ; at doses of 50 mg or less the incidence was 6.9 % , but 52.2 % for doses of 150 mg or higher . Despite limitations inherent in the interpretation of data banks , it is concluded that spironolactone administered in daily practice reduced BP without inducing adverse metabolic adverse effects and that in patients with essential hypertension , doses should be kept below 100 mg BACKGROUND Several medical reports showed an increased risk of stomach and duodenum bleeding associated with the use of spironolactone . The objective of this work is to examine the association between upper gastrointestinal ( UGI ) bleeding and exposure to spironolactone , using a population -based cohort design . METHODS Using the pharmaceutical prescriptions from 2000 to 2006 , a cohort was identified of residents in Milan ( Italy ) with chronic exposure to spironolactone or other diuretic drugs . The main outcome was defined as the hospital admission for UGI bleeding or ulcers . To control for potential bias related to spironolactone use , the propensity score was estimated . Then , each patient treated with spironolactone was r and omly matched with one treated with other diuretics and having the same propensity score using the caliper matching method . Proportional hazard models were fitted by computing hazard ratios ( HR ) and the corresponding 95 % confidence intervals ( 95%CI ) . RESULTS A total of 53 550 unexposed and 10 564 exposed to spironolactone were identified . Overall in the study period , 174 patients ( 3.2 % ) developed UGI bleeding in the unexposed and 51 ( 4.8 % ) in the exposed group . HR for UGI bleeding for the spironolactone exposed group was 1.94 ( 95%CI 1.42 - 2.65 ) . The sensitivity analysis based on the matched design using the propensity score showed a statistically significant twofold increase of gastrointestinal bleeding only among subjects exposed to high spironolactone dose ( HR 2.50 ; 95%CI 1.08 - 5.79 ) . CONCLUSIONS Results from a large population based study confirm that spironolactone increases the risk of UGI bleeding The blood pressure lowering effects of spironolactone have been studied in 40 subjects with benign essential hypertension in an attempt to determine the optimum starting dose for the drug . The trial was carried out by the double blind method . In almost all patients 100 - 400 mg spironolactone caused a signnificant decrease in diastolic and systolic arterial pressure . Present findings indicate that 100 - 200 mg spironolactone represents the optimum attack dose . The medication caused a significant rise in serum potassium . Other parameters were not affected by the treatment . In conclusion , it would appear that spironolactone -- in association with other antihypertensive regiments -- may improve the treatment of essential hypertension , especially in patients showing a tendency to hypokalemia and uricemia , and may offer an additional possibility or alternative in the therapy of hypertensive diseases A double-blind study of patients with essential hypertension was performed in order to determine which dosage of spironolactone ( 25 mg , 100 mg , or 200 mg daily ) , with or without hydrochlorothiazide , had the optimum hypotensive effect . The data were analyzed by two different statistical methods , in each of which multivariate analysis of variance was used . Both methods led to the conclusion that the most efficacious treatment regimen tested was spironolactone at a daily dosage of 100 mg , without hydrochlorothiazide Nineteen patients with uncomplicated essential hypertension and low activity of plasma renin in response to a change from recumbency to an upright posture along with furosemide administration were given spironolactone , 400 mg/d , or chlorthalidone , 100mg/d , in a double-blind , r and om-sequence , crossover trial . The sequence of treatments was placebo for 2 months , one active drug for 2 months , placebo again for 1 month and the other active drug for 2 months . With both active treatments the average systolic , diastolic and mean arterial pressures decreased significantly . The two agents were equally efficacious in lowering the blood pressure regardless of the severity of hypertension during placebo treatment . Body weight , 24 - -hour urinary excretion of sodium , the plasma renin activity and the plasma aldosterone level at the end of the initial placebo period did not allow us to predict the response to either drug . Both drugs reduced the body weight and increased the stimulated plasma renin level activity . Chlorthalidone significantly increased the serum uric acid level and significantly reduced the serum potassium level . Three patients experienced orthostatic dizziness during spironolactone therapy , but no adverse symptoms were observed with chlorthalidone therapy . Thus , spironolactone is an effective alternative to thiazide-type drugs in patients with low-renin essential hypertension AIMS To assess whether spironolactone has beneficial effects on blood pressure ( BP ) , N-terminal propeptide of type III procollagen ( PIIINP ) and pulse wave velocity ( PWV ) in hypertensive , type II diabetics . METHODS Ten patients with type II diabetes and hypertension were enrolled in a r and omized , double-blind crossover study comparing 4 months ' treatment with spironolactone and placebo with a 4-week washout phase . BP , PIIINP and carotid-radial PWV were measured at the end of each treatment phase . RESULTS Compared with placebo , spironolactone reduced systolic BP by 15.6 + /- 46.1 mmHg ( P = 0.005 , 95 % CI 2.7 - 28.5 mmHg ) , PIIINP by 0.6 + /- 0.3 microg l(-1 ) ( P = 0.04 , 95 % CI 0.02 - 1.1 microg l(-1 ) ) and PWV by 0.6 + /- 0.2 m s(-1 ) ( P = 0.008 , 95 % CI 0.18 - 1.02 m s(-1 ) ) . CONCLUSIONS Spironolactone is effective at reducing systolic BP and brachial artery stiffness as indicated by PWV . It also reduces PIIINP in type II diabetic patients with hypertension 1 . Although it is now easy to treat most patients with hypertension without producing troublesome side effects , a few patients remain refractory to conventional methods of treatment . These patients will progress to die of renal failure unless the blood pressure is controlled . 2 . Thiazides potentiate the effect of other hypotensive agents and this potentiation is probably independent of their diuretic action . Diazoxide actually produces salt and water retention at the same time as marked decrease in the blood pressure . Spirono-lactone in a dose of 400 mg daily produced a highly significant reduction in blood pressure in an unselected group of patients with severe refractory hypertension . 3 . β-Adrenergic blocking agents either alone or in combination with other drugs may be useful in the control of severe hypertension . An increasing effect on the blood pressure was demonstrated with doses between 1 and 2 g per day . 4 . A new drug , prazosin hydrochloride , with properties somewhat similar to hydrallazine but with few side effects promises to be useful in the control of severe refractory hypertension particularly in combination with β-adrenergic blocking drugs BACKGROUND Some 10 % to 15 % of hypertensive patients have hyperaldosteronism , an increased ambulant aldosterone-to-renin ratio . As aldosterone reduces arterial compliance , we examined the relationship between aldosterone-to-renin ratio , aortic blood pressure ( BP ) , arterial stiffness , and the effect of spironolactone in a hypertensive population . METHODS In 24 untreated patients ( mean age 51 + /- 2 years , 10 women ) , we assessed arterial stiffness by augmentation index-height of the late systolic peak in the aorta , pulse pressure ( Sphygmocor ) , and aortic pulse wave velocity ( Complior ) . RESULTS There were significant positive correlations between the aldosterone-to-renin ratio and aortic systolic pressure , aortic pulse pressure , and augmentation index and negative correlations with pulse pressure amplification , but none with brachial BP or pulse wave velocity . After r and omization in a cross-over design to 50 mg of spironolactone or 2.5 mg of bendroflumetazide for 4 weeks with washout period of 1 month , both drugs significantly reduced brachial BP , but only spironolactone reduced ( P < .001 ) pulse wave velocity and augmentation index , which remained significant when corrected for its greater reduction in mean BP . There were significant ( P < .001 ) positive correlations between the ratio and decrease in aortic systolic ( r = 0.78 ) , mean ( r = 0.75 ) , diastolic BP ( r = 0.66 ) , aortic pulse pressure ( r = 0.69 , augmentation index ( r = 0.64 ) and with , brachial systolic pressure ( r = 0.66 ) , brachial pulse pressure ( r = 0.44 , P < .05 ) and pulse pressure amplification ( r = 0.46 , P < .05 ) . Such relationships were not found with pulse wave velocity . CONCLUSIONS The aldosterone-to-renin ratio may have an important role in determining arterial stiffness , particularly wave reflection and aortic systolic pressure and is of predictive value for the responsiveness to spironolactone . Aldosterone antagonism has BP-independent effects on arterial stiffness Once-a-day therapy with spironolactone has been compared with a twice-a-day regimen in an open crossover trial in patients with essential hypertension . When compared with placebo , both treatments significantly lowered blood pressure . Twice-a-day therapy provided slightly better blood pressure control than the once-a-day dosing schedule . There were only minor differences in biochemical findings between the two regimens . Three of the 17 patients developed reversible gynaecomastia BACKGROUND Through its actions on nonepithelial tissues , including brain , blood vessels , and heart , aldosterone may mediate hypertension , cardiac hypertrophy , and fibrosis . Whether aldosterone has a direct pathogenic role in the development of cardiovascular complications in patients with end-stage renal disease is unknown . Oligo-anuric dialysis patients provide a clinical setting to study the effects of the mineralocorticoid receptor blocker spironolactone that are independent of the diuretic properties of the drug . We performed a r and omized , double-blinded , placebo-controlled , crossover study to assess the effect of spironolactone on blood pressure and the renin-angiotensin-aldosterone system in oligo-anuric hemodialysis patients . METHODS Eight hemodialysis patients were administered either spironolactone , 50 mg , or placebo orally twice daily for 2 weeks , followed by a 3-week washout period , after which patients crossed over in their treatment arms for 2 more weeks . RESULTS Administration of spironolactone for 2 weeks decreased predialysis systolic blood pressure from 142.0 + /- 19.6 to 131.4 + /- 18.2 mm Hg ( P < 0.05 ) . Compared with placebo , a 2-week course of spironolactone had no effect on predialysis and postdialysis plasma potassium or aldosterone concentrations or renin activity . CONCLUSION When administered for 2 weeks , spironolactone , 50 mg twice daily , reduced predialysis systolic blood pressure , but did not produce hyperkalemia in oligo-anuric hemodialysis patients The relation between vasodilation and the blood pressure-reducing action of spironolactone was studied in a r and omized , placebo-controlled , double-blind , crossover study using 9 patients with essential hypertension . Vasodilation was studied by measuring blood flow in finger and calf ( representative of skin and muscle circulation ) by an electrocardiographic-triggered venous-occlusion plethysmograph . Treatment with spironolactone ( 100 mg twice daily for 4 weeks ) produced significant decreases in systolic and diastolic blood pressure without significantly affecting heart rate . Blood flow through finger and calf increased , sometimes markedly , in 6 of the 9 patients , while vascular resistance decreased . This study confirms that the antihypertensive action of spironolactone is associated with vasodilation in many patients Hydrochlorothiazide in a daily dose of 150 mg and spironolactone in a daily dose of 400 mg ( 100 mg of the currently available preparation ) were found to have equivalent antihypertensive effects — reducing basal blood pressure , decreasing the pressor response to levarterenol bitartrate ( norepinephrine ) and angiotensin amide , and increasing the depressor response to a ganglion-blocking agent , trimethaphan camsylate — in a double-blind study of 11 hypertensive patients . The two diuretics , when given together , appear to act independently and additively in their antihypertensive effects . Serum potassium level , lowered by hydrochlorothiazide , was in the normal range during administration of spironolactone alone or in combination with hydrochlorothiazide . Spironolactone can thus be a useful substitute for a benzothiadiazine derivative in the treatment of hypertension . The administration of a combination of these diuretics , a thiazide and an aldosterone antagonist , can render hypertension more readily manageable Ten patients with low-renin hypertension were treated with high doses of a diuretic and a mineralocorticoid antagonist in a double-blind crossover study . Hydrochlorothiazide-induced volume depletion had a beneficial hypotensive response . However , despite comparable diuretic response , the hypotensive response observed with spironolactone was significantly greater . Renin responsiveness was seen to increase — but to submaximal levels — with thiazide therapy ; while spironolactone therapy restored normal renin responsiveness . The differential response to thiazide and spironolactone is similar to the response observed when these agents are used in primary aldosteronism , a hypertensive disease where mineralocorticoid excess is clearly identified as the cause of both the hypertension and low plasma renin activity . The fact that mineralocorticoid blockade induced by spironolactone corrects the hypertension and restores normal renin responsiveness suggests that mineralocorticoid excess may be responsible for the hypertension and low plasma renin activity We examined the predictive value of plasma renin activity ( PRA ) in ambulatory patients in the selection of hypertensive patients for treatment with spironolactone . The patients were classified as frusemide responders or non-responders according to their PRA response to 80 mg frusemide orally . After an initial 4 weeks placebo period forty-five patients with the clinical diagnosis of benign hypertension ( WHO stage I-II ) entered a 4 X 4 week double blind treatment period during which they received spironolactone ( Aldactone ) 400 , 300 , 200 and 100 mg/day , respectively . Five out of the forty-five patients who started the trial were withdrawn on account of side-effects and five patients for other reasons . Of the thirty-five patients who completed the study eighteen belonged to the group of non-responders to frusemide , seventeen to the responders . A gradual and significant decrease in mean blood pressure occurred during the period with the high doses of spironolactone , without any significant difference between the groups . The blood pressure lowering effect obtained with the initial high doses was maintained during the consecutive periods when the doses was reduced to a half or even a fourth , in both groups . We conclude that PRA measurement in ambulatory patients is of little , if any , value for the selection of hypertensives for spironolactone treatment ; this in contrast to similar selection s performed on hospitalized patients BACKGROUND Previous reports have demonstrated the antihypertensive efficacy of high doses of spironolactone in subjects with primary aldosteronism and , to a lesser degree , subjects with resistant hypertension . METHODS In current analysis , we examined the antihypertensive benefit of adding low-dose spironolactone to multidrug regimens that included a diuretic and an angiotensin-converting enzyme ( ACE ) inhibitor or angiotensin receptor blocker ( ARB ) in subjects with resistant hypertension with and without primary aldosteronism . Subjects referred for resistant hypertension were evaluated with an early morning plasma renin activity , 24-h urinary aldosterone and sodium during a high dietary salt ingestion . The diagnosis of primary aldosteronism was confirmed with a renin activity < 1.0 ng/mL/h , urinary aldosterone > 12 mug/24 h and urinary sodium > 200 mEq/24 h. After biochemical evaluation , spironolactone ( 12.5 to 25 mg/d ) was added to each subject 's antihypertensive regimen . If blood pressure ( BP ) remained uncontrolled , the dose of spironolactone was titrated up to 50 mg/d . Follow-up BP was determined at 6 weeks , 3 months , and 6 months . RESULTS A total number of 76 subjects were included in the analysis , 34 of whom had biochemical primary aldosteronism . Low-dose spironolactone was associated with an additional mean decrease in BP of 21 + /- 21/10 + /- 14 mm Hg at 6 weeks and 25 + /- 20/12 + /- 12 mm Hg at 6-month follow-up . The BP reduction was similar in subjects with and without primary aldosteronism and was additive to the use of ACE inhibitors , ARBs , and diuretics . CONCLUSIONS We conclude that low-dose spironolactone provides significant additive BP reduction in African American and white subjects with resistant hypertension with and without primary aldosteronism BACKGROUND AND METHODS Aldosterone is important in the pathophysiology of heart failure . In a doubleblind study , we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting-enzyme inhibitor , a loop diuretic , and in most cases digoxin . A total of 822 patients were r and omly assigned to receive 25 mg of spironolactone daily , and 841 to receive placebo . The primary end point was death from all causes . RESULTS The trial was discontinued early , after a mean follow-up period of 24 months , because an interim analysis determined that spironolactone was efficacious . There were 386 deaths in the placebo group ( 46 percent ) and 284 in the spironolactone group ( 35 percent ; relative risk of death , 0.70 ; 95 percent confidence interval , 0.60 to 0.82 ; P<0.001 ) . This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes . The frequency of hospitalization for worsening heart failure was 35 percent lower in the spironolactone group than in the placebo group ( relative risk of hospitalization , 0.65 ; 95 percent confidence interval , 0.54 to 0.77 ; P<0.001 ) . In addition , patients who received spironolactone had a significant improvement in the symptoms of heart failure , as assessed on the basis of the New York Heart Association functional class ( P<0.001 ) . Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone , as compared with 1 percent of men in the placebo group ( P<0.001 ) . The incidence of serious hyperkalemia was minimal in both groups of patients . CONCLUSIONS Blockade of aldosterone receptors by spironolactone , in addition to st and ard therapy , substantially reduces the risk of both morbidity and death among patients with severe heart failure The effect on BP of 100 and 200 mg spironolactone/day has been compared with that of methyl-dopa , 750 mg/day , and with combined treatment with both drugs in 32 patients with essential hypertension . The 28 patients who completed the entire investigation were treated for 30 weeks , divided into 4 treatment periods and 4 placebo periods of equal duration . BP did not fall significantly during the initial placebo period , and at the end of each of the intervening placebo periods it rose to pretreatment levels . A signifcant decrease in mean BP was found during the 4 treatment periods . A fall exceeding 14 % was registered in 32 % of the patients after methyldopa , 750 mg/day , in 50 % of the patients after spironolactone , 200 mg/day , in 89 % after combined treatment with both drugs , and in 29 % after spironolactone , 100 mg/day . Low renin hypertension was found in 9 of the 28 patients . The average decrease in mean BP after sironolactone , 200 mg/day , methyldopa , 750 mg/day , and after combined treatment did not differ significantly between the low and the normal renin group . The rationale for using diuretics such as spironolactone or thiazide as the basic therapy in essential hypertension is discussed . It is concluded that both are useful in the treatment of essential hypertension and might be used alone or in combination |
12,049 | 30,121,682 | Barriers to mammogram screening were lack of knowledge , embarrassment , fear of cancer diagnosis , perception that breast screening was unnecessary , lack of coping skills and pain during procedure .
Mammogram screening uptake among women in selected communities were generally low . | INTRODUCTION This review aim ed to summarise the trend of mammogram screening uptake published in local studies between years 2006 and 2015 among the Malaysian women aged 40 years and above , and identify the associated factors and barriers , as well as discuss limitations of the studies and research gaps . | Objective To evaluate the effectiveness of contemporary mammography screening using individual information about screening history and breast cancer mortality from public screening programmes . Design Prospect i ve cohort study of Norwegian women who were followed between 1986 and 2009 . Within that period ( 1995 - 2005 ) , a national mammography screening programme was gradually implemented , with biennial invitations sent to women aged 50 - 69 years . Participants All Norwegian women aged 50 - 79 between 1986 and 2009 . Main outcome measures Multiple Poisson regression analysis was used to estimate breast cancer mortality rate ratios comparing women who were invited to screening ( intention to screen ) with women who were not invited , with a clear distinction between cases of breast cancer diagnosed before ( without potential for screening effect ) and after ( with potential for screening effect ) the first invitation for screening . We took competing causes of death into account by censoring women from further follow-up who died from other causes . Based on the observed mortality reduction combined with the all cause and breast cancer specific mortality in Norway in 2009 , we used the CISNET ( Cancer Intervention and Surveillance Modeling Network ) Stanford simulation model to estimate how many women would need to be invited to biennial mammography screening in the age group 50 - 69 years to prevent one breast cancer death during their lifetime . Results During 15 193 034 person years of observation ( 1986 - 2009 ) , deaths from breast cancer occurred in 1175 women with a diagnosis after being invited to screening and 8996 women who had not been invited before diagnosis . After adjustment for age , birth cohort , county of residence , and national trends in deaths from breast cancer , the mortality rate ratio associated with being invited to mammography screening was 0.72 ( 95 % confidence interval 0.64 to 0.79 ) . To prevent one death from breast cancer , 368 ( 95 % confidence interval 266 to 508 ) women would need to be invited to screening . Conclusion Invitation to modern mammography screening may reduce deaths from breast cancer by about 28 % Background . Few prospect i ve studies have examined associations between breast cancer worry and screening behaviours in women with elevated breast cancer risks based on family history . Methods . This study included 901 high familial risk women , aged 23–71 years , from the Ontario site of the Breast Cancer Family Registry . Self-reported breast screening behaviours at year-one followup were compared between women at low ( N = 305 ) , medium ( N = 433 ) , and high ( N = 163 ) levels of baseline breast cancer worry using logistic regression . Nonlinear relationships were assessed using likelihood ratio tests . Results . A significant non-linear inverted “ U ” relationship was observed between breast cancer worry and mammography screening ( P = 0.034 ) for all women , where women at either low or high worry levels were less likely than those at medium to have a screening mammogram . A similar significant non-linear inverted “ U ” relationship was also found among all women and women at low familial risk for worry and screening clinical breast examinations ( CBEs ) . Conclusions . Medium levels of cancer worries predicted higher rates of screening mammography and CBE among high-risk women Breast cancer is the most common cancer among women globally . This study was conducted to compare the awareness of breast cancer and the practice of breast self-examination ( BSE ) , clinical breast examination ( CBE ) and mammography screening among rural females in Pahang and Perak . A cross-sectional study was carried out in five selected rural districts of Pahang and Perak . Two hundred and fifty households were r and omly selected and interviewed face to face using a semi-structured question naire . The majority of residents from both states were Malay , aged between 50 and 60 years and had a secondary level of education . Malay women aged 40 - 49 years and women with a higher level of education were significantly more aware of breast cancer ( p<0.05 ) . About half of these women practice d BSE ( 60.7 % ) and CBE ( 56.1 % ) , and 7 % had underwent mammography screening . The results of this study suggest that women in Pahang and Perak have good awareness of breast cancer and that more than half practice BSE and CBE . The women 's level of education appears to contribute to their level of knowledge and health behaviour . However , more effort is needed to encourage all women in rural areas to acquire further knowledge on breast cancer Background Breast cancer screening can reduce morbidity and mortality and improve the survival rate for this malignancy . Low participation in screening programs has been attributable to many factors including lack of knowledge . The aim of this study was to assess breast cancer screening knowledge , attitudes and practice s among women of screening age ( ≥40 years old ) in the city of Al Ain , United Arab Emirates ( UAE ) . Methods A cross-sectional survey was conducted in 2013 using the Breast Cancer Awareness Measure ( CAM ) . Four out of twelve cultural and religious community centers in Al Ain city were r and omly selected . Two hundred and forty seven women were interviewed . Chi Square test and regression analysis were used to analyze the data . Results Despite the increase in the uptake of screening modalities in our study group , a lack of knowledge about breast cancer screening is still evident . Almost half ( 44.8 % ) of women who never had a Clinical Breast Exam ( CBE ) and 44.1 % of women who never had a mammography expressed a lack of knowledge about the existence of these screening techniques . Nearly one third of the participants interpreted the presence of a breast lump incorrectly and , moreover , expressed fewer worries about the nature of the lump than would normally be expected . Conclusions The National screening program needs to be improved and directed towards more efficient and targeted utilization of re sources . Healthcare professionals play a major role in alerting women to the importance of periodic screening BACKGROUND Breast cancer is the most common type of cancer in Jordan . Current efforts are focused on annual campaigns aim ed at increasing awareness about breast cancer and encouraging women to conduct mammogram screening . In the absence of regular systematic screening for breast cancer in Jordan , there is a need to evaluate current mammography screening uptake and its predictors , assess women 's knowledge and attitudes towards breast cancer and screening mammograms and to identify barriers to this preventive service . MATERIAL S AND METHODS This cross-sectional study was conducted in six governorates in Jordan through face- to-face interviews on a r and om sample of women aged 40 to 69 years . RESULTS A total of 507 participants with mean age of 46.8±7.8 years were interviewed . There was low participation rate in early detection of breast cancer practice s. Breast self-examination , doctor examination and periodic mammography screening were reported by 34.9 % , 16.8 % and 8.6 % of study participants , respectively . Additionally 3.8 % underwent breast cancer screening at least once but not periodically , while 87.6 % had never undergone mammography screening . Reported reasons for conducting the screening were : perceived benefit ( 50 % ) ; family history of breast cancer ( 23.1 % ) ; perceived severity ( 21.2 % ) ; and advice from friend or family member ( 5.8 % ) . City residents have shown higher probability of undergoing mammogram than those who live in towns or villages . Results revealed negative perceptions and limited knowledge of study participants on breast cancer and breast cancer screening . The most commonly reported barriers for women who never underwent screening were : fear of results ( 63.8 % ) ; no support from surrounding environment ( 59.7 ) ; cost of the test ( 53.4 % ) ; and religious belief , i.e. Qadaa Wa Qadar ( 51.1 % ) . CONCLUSIONS In the absence of regular systematic screening for breast cancer in Jordan , the uptake of this preventive service is very low . It is essential for the country of Jordan to work on applying regular systematic mammography screening for breast cancer . Additionally , there is a need for improvement in the current health promotion programmes targeting breast cancer screening . Other areas that could be targeted in future initiatives in this field include access to screening in rural areas and removal of current barriers INTRODUCTION Breast cancer is the leading cancer in women today and the major challenge is late presentation then later contributes to poor outcome and high fatality rate . Mammography is effective in early detection of breast cancer and consequently significantly improves the breast cancer survival . MATERIAL S AND METHODS This cross-sectional study was used to study the knowledge and awareness towards mammogram amongst women aged 15 years old and above . A systemic r and om sampling was applied and information gathered through guided interview by using a structured question naire . RESULTS Eighty-six respondents were recruited . The mean age of respondents was 40.5 years ( SD : 15.51 ) and more than 80 % had secondary and tertiary level of education . The percentage of respondents ever performed mammogram was 10.5 % ( 95 % CI : 4.0%-17.0 % ) . The rate of correct answers was between 8.1 % and 48.8 % . Most of the respondents do not sure the answer ( 45.3%-61.6 % ) rather than wrongly answer ( 4.7%-43.0 % ) . Only about 8 % truly answer that mammogram should be done once in a life . There are 10.5 % of women cl aim ed that mammogram had no serious side effect and not a painful procedure . Nearly half of respondents ( 48.8 % ) correctly mentioned that Mammogram can detect breast cancer in early stage . CONCLUSION Only a small percentage of women ever performed mammogram and there are seriously unaware and poor knowledge pertaining to mammography screening for breast cancer among women in sub urban area . A massive health education campaign through multiple methods and agencies are needed to enhance the knowledge and awareness on mammogram |
12,050 | 20,687,094 | There is insufficient evidence from r and omised trials to determine which interventions are best for osteochondral defects of the talus in adults . | BACKGROUND Osteochondral defects of the talus are usually a consequence of trauma .
They can cause chronic pain and serious disability .
Various interventions , non-surgical and surgical , have been used for treating these defects .
OBJECTIVES The objective of this review is to determine the benefits and harms of the interventions used for treating osteochondral defects of the talus in adults . | Background Osteochondral talar defects usually affect athletic patients . The primary surgical treatment consists of arthroscopic debridement and microfracturing . Although this is mostly successful , early sport resumption is difficult to achieve , and it can take up to one year to obtain clinical improvement . Pulsed electromagnetic fields ( PEMFs ) may be effective for talar defects after arthroscopic treatment by promoting tissue healing , suppressing inflammation , and relieving pain . We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports , and aim at 25 % increase in patients that resume sports . Methods / Design A prospect i ve , double-blind , r and omized , placebo-controlled trial ( RCT ) will be conducted in five centers throughout the Netherl and s and Belgium . 68 patients will be r and omized to either active PEMF-treatment or sham-treatment for 60 days , four hours daily . They will be followed-up for one year . The combined primary outcome measures are ( a ) the percentage of patients that resume and maintain sports , and ( b ) the time to resumption of sports , defined by the Ankle Activity Score . Secondary outcome measures include resumption of work , subjective and objective scoring systems ( American Orthopaedic Foot and Ankle Society – Ankle-Hindfoot Scale , Foot Ankle Outcome Score , Numeric Rating Scales of pain and satisfaction , EuroQol-5D ) , and computed tomography . Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests . Discussion This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy . Trial registration Netherl and s Trial Register ( NTR1636 Background R and omized trials are essential in assessing the effects of healthcare interventions and are a key component in systematic review s of effectiveness . Search ing for reports of r and omized trials in data bases is problematic due to the absence of appropriate indexing terms until the 1990s and inconsistent application of these indexing terms thereafter . Objectives The objectives of this study are to devise a search strategy for identifying reports of r and omized trials in EMBASE which are not already indexed as trials in MEDLINE and to make these reports easily accessible by including them in the Cochrane Central Register of Controlled Trials ( CENTRAL ) in The Cochrane Library , with the permission of Elsevier , the publishers of EMBASE . Methods A highly sensitive search strategy was design ed for EMBASE based on free-text and thesaurus terms which occurred frequently in the titles , abstract s , EMTREE terms ( or some combination of these ) of reports of trials indexed in EMBASE . This search strategy was run against EMBASE from 1980 to 2005 ( 1974 to 2005 for four of the terms ) and records retrieved by the search , which were not already indexed as r and omized trials in MEDLINE , were downloaded from EMBASE , printed and read . An analysis of the language of publication was conducted for the reports of trials published in 2005 ( the most recent year completed at the time of this study ) . Results Twenty-two search terms were used ( including nine which were later rejected due to poor cumulative precision ) . More than a third of a million records were downloaded and scanned and approximately 80,000 reports of trials were identified which were not already indexed as r and omized trials in MEDLINE . These are now easily identifiable in CENTRAL , in The Cochrane Library . Cumulative sensitivity ranged from 0.1 % to 60 % and cumulative precision ranged from 8 % to 61 % . The truncated term ' r and om$ ' identified 60 % of the total number of reports of trials but only 35 % of the more than 130,000 records retrieved by this term were reports of trials . The language analysis for the sample year 2005 indicated that of the 18,427 reports indexed as r and omized trials in MEDLINE , 959 ( 5 % ) were in language s other than English . The EMBASE search identified an additional 658 reports in language s other than English , of which the highest number were in Chinese ( 320 ) . Conclusion The results of the search to date have greatly increased access to reports of trials in EMBASE , especially in some language s other than English . The search strategy used was subjectively derived from a small ' gold st and ard ' set of test records and was not vali date d in an independent test set . We intend to design an objective ly-derived vali date d search strategy using logistic regression based on the frequency of occurrence of terms in the approximately 80,000 reports of r and omized trials identified compared with the frequency of these terms across the entire EMBASE data base A linear analogue for rating pain with 10 , 15 and 20 cm lines is significantly less variable than a 5 cm line ( mean error of 15 cm line is 0 - 19 % , 95 % confidence limits for the group + /- 2 % and an inood correlation between repeated ratins of a recalled pain distant in time . The variance of the rating is significantly less than the repeated rating of a r and om mark . The linear analogue rating of a constant pain stimulus is reproducible and changes in rating are likely to be real changes of opinion . Pethidine 150 mg intramuscularly had no significant effect , tested 30 minutes after the administration , on the accuracy or reproducibility of the analogue rating . A linear analogue seems a suitable method of recording the patient 's opion of a severe pain such as that of labour Background Arthroscopic examination has shown that the regenerative cartilage that appears after arthroscopic drilling for thetreatment of osteochondral lesions of the talar dome does not always cover the cartilage defect sufficiently . Hypothesis The remaining degenerative cartilage at the lesions may obstruct the healing of the articular cartilage . Study Design Prospect i ve cohort study . Methods Thirty-nine patients underwent arthroscopic drilling that kept the remaining cartilage at the lesion ( group A ) , and 30 patients underwent arthroscopic drilling that removed the remaining cartilage at the lesion ( group B ) . At 1 year after theoperation , we performed ankle arthroscopy to evaluate the cartilage condition . Results The arthroscopic findings revealed that in group A , 11 cases ( 28.2 % ) were improved , 12 cases ( 30.8 % ) wereunchanged , and 16 cases ( 41.0 % ) had deteriorated ; in group B , 27 cases ( 93.1 % ) were improved and 2 cases were unchanged . There were significant differences between group A and group B in the rate of cases whose cartilage condition was seen toimprove under arthroscopic examination ( P < 0.0001 ) . Conclusions The study shows that in the treatment of osteochondral lesions of the talar dome , the removing of the remainingdegenerative cartilage may be of some benefit in the treatment of these lesions PURPOSE The purpose of this study was to compare outcomes of chondroplasty versus microfracture versus osteochondral autologous transplantation ( OAT ) in patients with osteochondral lesions of the talus ( OLT ) . METHODS After prospect i ve sample size analysis , patients with symptomatic , recalcitrant Ferkel class 2b , 3 , and 4 OLT were r and omized to chondroplasty , microfracture , or OAT treatment groups . Outcomes were measured with use of the American Orthopaedic Foot and Ankle Society ( AOFAS ) Ankle-Hindfoot Scale ( AHS ) , the Subjective Assessment Numeric Evaluation ( SANE ) rating , Numeric Pain Intensity ( NPI ) , and magnetic resonance imaging ( MRI ) . RESULTS Eleven patients had chondroplasty , 10 ankles ( 9 patients ) had microfracture , and 12 patients had OAT . Mean time to follow-up was 53 months ( range , 24 to 119 months ) . AHS scores showed no differences at 12 and 24 months , and SANE ratings showed no differences at final follow-up . NPI was significantly lower ( P < .001 ) in chondroplasty and microfracture cases as compared with OAT at 24 hours postoperatively . Pearson 's correlation analysis demonstrated an inverse relation between microfracture and OAT groups in that better outcome was associated with smaller lesions , compared with the chondroplasty group , which revealed mixed results with no particular trend . MRI revealed incomplete fill and edema after chondroplasty or microfracture and chondral gaps after OAT . CONCLUSION Our results demonstrate no difference between chondroplasty , microfracture , and OAT with regard to AHS and SANE ratings in patients with OLT . However , NPI at 24 hours postoperatively was significantly lower in patients who had chondroplasty and microfracture . LEVEL OF EVIDENCE Level I , Therapeutic study , high- quality r and omized controlled trial with no statistically significant differences but narrow confidence interval |
12,051 | 24,234,875 | It has been suggested that these agents will reduce operating time , improve the intrauterine operating environment and reduce absorption of fluid used for intraoperative uterine cavity distension .
For other intraoperative and postoperative outcomes , any differences were minimal , and no benefits of GnRHa pretreatment were noted in studies in which women underwent second-generation ablation techniques .
When reported , the long-term effects of endometrial thinning agents on benefits such as postoperative amenorrhoea were reduced with time .
The quality of reporting of adverse events was generally poor , but , when described in the studies , they included menopausal symptoms such as hot flushes , vaginal dryness , hirsutism , decreased libido and voice changes , as well as other side effects such as headache and weight gain .
AUTHORS ' CONCLUSIONS Low- quality evidence suggests that endometrial thinning with GnRHa and danazol before hysteroscopic surgery improves operating conditions and short-term postoperative outcomes .
GnRHa produced slightly more consistent endometrial thinning than was produced by danazol , although both achieved satisfactory results .
The effect of these agents on longer-term postoperative outcomes was reduced with time .
No benefits of GnRHa pretreatment were apparent with second-generation ablation techniques .
Also , side effects were more common when these agents were used | BACKGROUND Heavy menstrual bleeding is one of the most common reasons for referral of premenopausal women to a gynaecologist .
Although medical therapy is generally first line , many women eventually will require further treatment .
Endometrial ablation by hysteroscopic and more recent " second-generation " devices such as balloon , radiofrequency or microwave ablation offers a day-case surgical alternative to hysterectomy .
Complete endometrial destruction is one of the main determinants of treatment success .
Surgery is most effective if undertaken when endometrial thickness is less than four millimeters .
One option is to perform the surgery in the immediate postmenstrual phase , which is not always practical .
The other option is to use hormonal agents that induce endometrial thinning pre-operatively .
The most commonly evaluated agents are goserelin ( a gonadotrophin-releasing hormone analogue , or GnRHa ) and danazol .
Other GnRH analogues and progestogens have also been studied , although fewer data are available .
They may also improve long-term outcomes , including menstrual loss and dysmenorrhoea .
OBJECTIVES To investigate the effectiveness and safety of pre-operative endometrial thinning agents ( GnRH agonists , danazol , estrogen-progestins and progestogens ) versus another agent or placebo when given before endometrial destruction in premenopausal women with heavy menstrual bleeding . | Please cite this paper as : Sambrook A , Jack S , Cooper K. Outpatient microwave endometrial ablation : 5‐year follow‐up of a r and omised controlled trial without endometrial preparation versus st and ard day surgery with endometrial preparation . BJOG 2010;117:493–496 STUDY OBJECTIVES To determine the safety and efficacy of endometrial resection , and to provide an indicator of the operative problems and treatment outcomes . DESIGN Prospect i ve study . SETTING Academic practice tertiary care setting . PATIENTS One hundred twenty-six consecutive women undergoing endometrial resection because of menorrhagia , who wished to retain their uterus . INTERVENTION Hysteroscopic endometrial resection performed as a day procedure . MEASUREMENTS AND MAIN RESULTS In 126 women , 2 cases of uterine perforation were readily identified on the operating monitor screen ; they had no serious sequelae . Three patients had heavy uterine bleeding , which was controlled by intrauterine tamponade . No women had other serious complications . CONCLUSION Hysteroscopic endometrial resection is a safe , successful , and cost-effective treatment of menorrhagia OBJECTIVE To compare danazol and gestrinone treatment as preoperative endometrial preparation for operative hysteroscopy . DESIGN Prospect i ve , r and omized clinical study . SETTING University department of gynecological , obstetrical sciences and reproductive medicine . PATIENT(S ) One hundred thirty-five patients with endouterine pathologies ( endometrial polyps , submucous myoma , septate uterus ) . INTERVENTION(S ) Patients pretreated with gestrinone ( n = 68 ) and with danazol ( n = 67 ) underwent operative hysteroscopy . MAIN OUTCOME MEASURE(S ) Endometrial response to the medical pretreatment , side effects , procedure time , intraoperative bleeding , infusion volume , patient satisfaction . RESULT ( S ) Side effects were infrequent in both groups , though the patients ' personal satisfaction was in favor of gestrinone . The rate of endometrial response was higher for the gestrinone group ( 97.1 % vs. 83.6 % ) . Operative time ( mean + /- SD ) was 12 + /- 1.8 and 15.2 + /- 1.9 minutes for the gestrinone and danazol groups , respectively . The gestrinone group showed a lower incidence of moderate bleeding ( 3 % vs. 22.4 % ) and a lower infusion volume ( 2,100 + /- 200 mL vs. 2,400 + /- 250 mL ) . Regarding cervical dilatation time , no significant difference was found between the two groups ( 1.6 + /- 0.3 minutes vs. 1.5 + /- 0.4 minutes ) . CONCLUSION ( S ) Both treatments are good ways to prepare the endometrium for operative hysteroscopy . However , the data suggest that gestrinone pretreatment is preferable to danazol The aim of this study was to determine whether or not the use of medical pre-treatment of the endometrium improves the outcome of transcervical resection of the endometrium with regards to long-term operative outcome , histological findings and patient satisfaction . A prospect i ve r and omized trial comparing three endometrial pre-treatment agents ( danazol , medroxyprogesterone acetate or nafarelin ) with no pre-treatment was conducted . The main outcome measures were : ( i ) thickness of the endometrium and myometrium resected ; ( ii ) histological stage of the endometrium at the time of operation ; ( iii ) the presence or absence of menses and ( iv ) patient satisfaction 1 year post-operatively . Of the three pre-treatments studied , danazol produced a lower median endometrial thickness than the control , showed the greatest ability to induce atrophy of the endometrial gl and s and stroma ( not statistically significant ) and produced the highest rate of amenorrhoea ( not different to the control ) . Danazol and nafarelin produced significantly lower median endometrial thickness than no pre-treatment . There were , however , no significant differences in the rates of amenorrhoea in any of the pre-treatment groups compared with that in the control group . No improvement in clinical outcome or patient satisfaction is conferred by the use of medical pre-treatments if transcervical resection of the endometrium is performed in the proliferative phase of the menstrual cycle OBJECTIVE To investigate the management of menorrhagia in primary care and its impact on referral and hysterectomy rates . DESIGN Prospect i ve observational study . SETTING 11 general practice s from the Somerset Morbidity Project . SUBJECTS 885 women consulting their general practitioner with menorrhagia over four years . MAIN OUTCOME MEASURES Proportions of these women investigated and treated with drugs in primary care , referred to a gynaecologist and undergoing operative procedures . The relation between investigation and prescribing in primary care and referral to and surgery in secondary care . RESULTS Less than half of women had a vaginal examination ( 42 % , 95 % CI 39 % to 45 % ) , or a full blood count ( 39 % , 95 % CI 36 % to 43 % ) . Almost a quarter of women , 23 % ( 95 % CI 20 % to 26 % ) , received no drugs and 37 % ( 95 % CI 34 % to 40 % ) received norethisterone . Over a third , 38 % ( 95 % CI 34 % to 40 % ) , of women were referred , and once referred 43 % ( 95 % CI 38 % to 48 % ) of women were operated on . Women referred to a gynaecologist were significantly more likely to have received tranexamic acid and /or mefenamic acid in primary care ( chi(2)=16.4 , df=1 , p<0.001 ) . There were substantial between practice variations in management , for example in prescribing of tranexamic acid and /or mefenamic acid ( range 16 % to 72 % ) and referral to gynaecology ( range 24 % to 52 % ) . There was a significant association between high referral and high operative rates ( Spearman 's correlation coefficient=0.86 , p=0.001 ) . CONCLUSIONS Substantial differences in management exist between practice s when investigating and prescribing for menorrhagia in primary care . Rates of prescribing of effective medical treatment remain low . The decision to refer a woman impacts markedly on her chances of subsequently being operated on . Effective management in primary care may not reduce referral or hysterectomy rates In a prospect i ve study in 40 patients the pretreatment for endometrial ablation with a gestagen ( Orgametril 10 mg/die ) , danazol ( 600 mg/die ) and an injection of a GnRH-analogon ( Decapeptyl-Depot ) was compared with a control group without pretreatment . The subjective estimation of the surgeon ( endometrial thickness and depth of coagulation ) showed a sufficient pretreatment in 90 % of all cases following danazol- and GnRH-analogon-pretreatment . In 90 % of the danazol- and GnRH-analogon pretreated group the histological findings showed also an atrophic or little proliferative endometrium . In a follow up of 6 months after endometrial ablation the highest amenorrhoea-rates were reached following danazol- and GnRH-analogon pretreatment . These two regimes should be used for the pretreatment for endometrial ablation Objective To compare the effectiveness of goserelin and danazol prior to endometrial laser ablation and assess different dosage regimens This r and omized , double blind , placebo-controlled study compared the usefulness of danazol 400 mg vaginally versus 600 mg orally in women as a preoperative preparation for hysteroscopic surgery . Ninety-one fertile women were r and omly allocated to Group A ( 46 patients received 400 mg of danazol placed into the posterior vaginal fornix and three oral tablets of commercially available folic acid as a placebo ) , and Group B [ 45 women treated with 600 mg of danazol orally ( 200 mg three times daily ) and two vaginal tablets of Lactobacillus rhamnosus as a placebo ] . The patients underwent an operative hysteroscopy , transvaginal sonography , blood tests , and a histological assay . A visual analog scale ( VAS ) score to compute the degree of the surgeon 's satisfaction was used . The outcome measures were as follows : an evaluation of the changes in the endometrial thickness , the prevalence of endometrial atrophy , changes in the blood tests , any collateral effects , the degree of difficulty and view , the duration of the surgical procedure , any complications during the operative hysteroscopy and associated side effects , and the surgeon 's satisfaction with the endometrial preparation . The vaginal administration route was associated with a more pronounced effect on the endometrial thickness . Significantly more patients receiving vaginal danazol ( 45/46 ) had a hypotrophic endometrium than those receiving oral danazol ( 37/45 , P<0.01 ) . In addition , the patients receiving danazol vaginally had a shorter operating time , lower infusion volume , fewer side effects , and a higher surgeon satisfaction . Vaginal danazol adequately prepares the endometrium for an operative hysteroscopy by thinning the endometrium effectively with few side effects and little impact on the metabolic parameters OBJECTIVE To evaluate the efficacy of GnRH analogue treatment before hysteroscopic resection of submucous myomas in patients with abnormal uterine bleeding . DESIGN Multicenter , prospect i ve , r and omized , clinical study . SETTING Tertiary-care university hospitals . PATIENT(S ) Thirty-nine consecutive patients with submucous myomas grade d as G0 or G1 according to the European Society for Gynecological Endoscopy classification ( myoma size 10 - 35 mm ) . INTERVENTION(S ) Patients were r and omized to either direct surgery or 2 months of GnRH analogues before undergoing hysteroscopic resection of the submucous myoma . MAIN OUTCOME MEASURE(S ) Operating times , fluid absorption , difficulty of the operation , surgeon satisfaction with the procedure , intra- and postoperative complications , postoperative pain , and patient satisfaction were recorded . RESULT ( S ) Patients treated with GnRH analogue had significantly shorter operative times ( 15.9+/-3.1 minutes vs. 21.3+/-4.0 minutes ) and significantly reduced fluid absorption ( 378+/-137 mL vs. 566+/-199 mL ) compared with no preoperative medical treatment . Operative difficulty and overall surgeon satisfaction were significantly better in the GnRH analogue group . Patient satisfaction was similar in the two groups . CONCLUSION ( S ) GnRH analogue treatment before hysteroscopic resection of G0-G1 10 - 35 mm submucous myomas was effective in reducing operative times , fluid absorption , and difficulty of the procedure STUDY OBJECTIVE To compare the effectiveness and safety of thermal balloon ablation without pretreatment with endometrium-thinning agents compared with delayed ablation with pretreatment for women with perimenopausal menorrhagia . DESIGN Prospect i ve , r and omized , controlled trial ( Canadian Task Force classification I ) . SETTING Hospital-based ambulatory medical center . PATIENTS Thirty women age 46 to 51 years with severe enough perimenopausal menorrhagia to make them c and i date s for either hysterectomy or endometrial ablation . Two patients with submucosal myomas and six who had undergone cesarean section were included . INTERVENTIONS Thirteen patients were r and omly assigned to be treated within 30 days and received a single intramuscular administration of gonadotropin releasing hormone ( GnRH ) analog ; 17 women were allocated to be treated within 3 days of enrollment without uterine preparation . A thermal balloon was inserted transcervically under general anesthesia , and after inflation in the endometrial cavity with 5 % dextrose in water , was heated to 87 degrees C for 8 minutes . MEASUREMENTS AND MAIN RESULTS Immediate and long-term major and minor complications and success rates were analyzed . Bleeding patterns and mean duration of menstrual flow were compared between groups at 6-month follow-up . No major intraoperative or postoperative complications occurred in either group , including the women who had recently undergone hysteroscopic myomectomy or had a history of cesarean section . Minor side effects were similar in both groups , and did not exceed 5 % . Overall , at 6-month follow-up , 7 women were amenorrheic , 20 hypomenorrheic , and 3 eumenorrheic . No significant differences were noted between women treated with immediate or delayed ablation in either the distribution of bleeding patterns or days of flow per cycle ( mean + /- SEM 1.8 + /- 0.42 vs 2.1 + /- 0.75 days , respectively ) . CONCLUSION This pilot study suggests that prompt treatment of perimenopausal menorrhagia with thermal balloon endometrial ablation is as effective and safe as deferred therapy combined with GnRH analog as an endometrium-thinning agent . In light of our results , the theory that previous cesarean section and presence of small submucosal myomas constitute relative contraindications for the procedure merits further consideration . ( J Am Assoc Gynecol Laparosc 6(2):145 - 150 , 1999 Objective : To evaluate the efficacy of depot medroxy progesterone acetate ( DMPA ) as a preparatory agent for endometrial resection . Study Design : Endometrial resection was performed on 50 women for excessive uterine bleeding . The patients were r and omly divided into 2 equal groups , with the first group receiving DMPA and the second group not receiving any hormonal pre-medication . The resected tissue was sent for histopathology and all the patients were followed up regularly for a maximum period of 4 years . Results : DMPA was found to increase the thickness of the endometrium , making it more fluffy and oedematous . The procedure in these patients was associated with a significantly greater fluid consumption and deficit . A power analysis showed the overall power of the study to be > 90 % . Forty-four percent of group 1 and 64 % of group 2 patients achieved amenorrhoea or spotting . Three patients in all underwent a repeat procedure , and 1 a hysterectomy , following a dissatisfactory result . However , no statistically significant difference was found in the outcomes of the 2 groups . Conclusion : As a preparatory agent , DMPA , seems to have no added benefit . Larger studies are required to bring out differences in outcomes , if any OBJECTIVES To evaluate the clinical outcomes following the use of goserelin and suction curettage prior to ThermaChoice II balloon endometrial ablation to treat menorrhagia . METHODS Qualified patients ( n = 105 ) were r and omized to receive either goserelin 3.6 mg one month before or suction curettage immediately before undergoing thermal balloon endometrial ablation . All patients had negative Papanicolaou smears , normal endometrial histology , and normal findings on transvaginal sonography . Uterine bleeding was documented by menstrual diary scores at baseline ( Higham score > 150 ) , and at three , six , and 12 months after the procedure . Five patients withdrew prior to surgery and 50 patients were anaesthetized in each group . Two patients in the suction curettage group had their management converted to hysteroscopic ablation , one because of a large uterine cavity ( > 12 mL ) and one because of a submucous myoma . The ThermaChoice II system circulated the liquid within the silicone balloon for eight minutes at approximately 180 mmHg pressure and 87 ° C . RESULTS Participants ' mean age , weight , and duration of menorrhagia were not significantly different between the groups . No safety issues related to the device were noted . At one year after ablation , the median reduction in Higham score was from 286 to 10 ( 96.5 % ) in the goserelin group ( n = 47 ) , and from 272 to 14 ( 94.9 % ) in the curettage group ( n = 45 ) . The combined amenorrhea/hypomenorrhea rates ( higham score 0 to 35 ) , eumenorrhea rate ( higham score 36 to 75 ) and menorrhagia rate ( higham score > 75 ) were 85 % , 9 % , and 6 % ( goserelin ) , and 76 % , 16 % , 9 % ( curettage ) , respectively . Patients ' reported self- assessment of dysmenorrhea was none ( 51 % ) , mild ( 30 % ) , moderate ( 10 % ) , and severe ( 9 % ) in both groups . Patient satisfaction was 89 % in the goserelin group and 95 % in the curettage group . In the goserelin group , one patient had a hysterectomy for bleeding and two had repeat resectoscopic endometrial ablations , one for pain ( hematometra ) and one for pain and bleeding . In the curettage group , one patient had repeat resectoscopic ablation , one patient withdrew , and one requested hormone therapy . The overall success rates were 88 % in the goserelin group and 89 % in the curettage group . CONCLUSION At one year after ThermaChoice II treatment , 88.5 % of women had normal menstrual bleeding or less . There was a non-significant trend ( a lower Higham score ) towards superiority of goserelin therapy before ablation compared with curettage OBJECTIVES To assess the effect of danazol pretreatment in women undergoing endometrial resection for dysfunctional uterine bleeding . STUDY DESIGN A total of 132 patients were r and omly divided into danazol pretreated and untreated groups . Endometrial resection was carried out using a 24Fr cutting wire loop electrode and 1.5 % glycine as the distension media . Patients were followed-up for 6 years . The t-test and Chi-square tests were used to test differences between the two groups . RESULTS The mean endometrial thickness , fluid used , fluid deficit , weight of resected tissue and duration of surgery were significantly greater in the unprepared group . Over 70 % of patients in both the groups achieved amenorrhoea or spotting . Two ( 1.5 % ) patients underwent a repeat procedure and two ( 1.5 % ) others a hysterectomy , while the rest had hypomenorrhoea . The perimenstrual symptoms also showed significant improvement . No statistically significant difference was found in the outcomes of the two groups . CONCLUSION Endometrial resection is an effective alternative to hysterectomy and pretreatment of the endometrium is not necessary for good outcomes Objective To compare the safety and efficacy of a GnRH agonist , deport goserelin , and danazol as preoperative treatments before rollerball endometrial ablation . Methods We performed an open , r and omized study of women with clinical ly convincing histories of menorrhagia . Two treatment groups of equal size ( goserelin acetate , 3.6 mg subcutaneous implant given monthly , n = 30 ; and danazol , 200 mg two times per day , n = 30 ) were treated for 2 months before undergoing endometrial ablation , which entailed using the rollerball with 80–100 watts of coagulating current . Results Measured menstrual blood loss decreased dramatically after ablation , with 74 % of goserelin users and 62 % of danazol users achieving complete amenorrhea by the end of the 6-month follow-up period . Among women who did not achieve complete amenorrhea , those in the danazol group were more likely to experience occasional episodes of moderate or heavy bleeding . Mean measured blood loss decreased from 94.8 to 1.1 mL at 3 months and 1.0 mL at 6 months after goserelin , and 97.9 to 15.0 mL and 7.4 mL after danazol . Menstrual pain also improved markedly . The median duration of surgery was 20 minutes ( range 5–55 ) in both groups , median irrigation fluid deficit was 100 mL ( range 0–800 ) , and median operative blood loss was 20 mL ( range 1–50 ) . Endometrium was less than 2 mm thick in all goserelin and most danazol users . Side effects of goserelin and danazol therapy were all within the expected pattern for these drugs . Conclusion Depot goserelin and danazol both provide adequate endometrial preparation before rollerball endometrial ablation for treatment of menorrhagia due to ovulatory dysfunctional uterine bleeding OBJECTIVE To evaluate the effects after 10 days of an original treatment combining oral progestins with vaginal raloxifene to maximize the antiproliferative effect on the endometrium . DESIGN Prospect i ve , r and omized , clinical pilot study . SETTING Academic research environment . PATIENT(S ) Ninety women with endometrial polyps . INTERVENTION(S ) On day 1 of the subsequent menstrual cycle , patients were r and omized to receive oral desogestrel ( n = 30 ) for 10 days combined with a tablet of raloxifene ( 60 mg ) per vaginam ( group A ) ; oral desogestrel at 60 mg/day ( n = 30 ; group B ) ; or oral danazol at 200 mg , three times a day ( n = 30 ; group C ) . MAIN OUTCOME MEASURE(S ) Ultrasound measurement of endometrial thickness on day 11 of both the pretreatment and treatment cycles , surgeon satisfaction ( 0 to 10 , visual analogue scale ) , and side effects . RESULT ( S ) At the second evaluation , the mean percentage reduction in endometrial thickness in group A was statistically significantly greater than in the other groups . Surgeon satisfaction in terms of endometrial thinning was also greater with group A. CONCLUSION ( S ) Oral desogestrel plus vaginal raloxifene provides a fast , low-cost , and satisfactory preparation of the endometrium for operative hysteroscopy Objective To ascertain whether treatment with a gonadotrophin releasing hormone agonist before endometrial resection reduces absorption of distension fluid and operating time and facilitates the procedure Background . To assess the value of endometrial preparation , with preoperative and pre‐ and postoperative GnRH agonist therapy in transcervical endometrial resection OBJECTIVE To evaluate the effectiveness of endometrial resection as a surgical treatment for menorrhagia . DESIGN R and omised controlled trial . SETTING Gynaecology department at a teaching hospital . SUBJECTS Two hundred women needing surgical treatment for menorrhagia between January 1990 and May 1991 . After withdrawal of four women 97 underwent hysterectomy and 99 underwent endometrial resection . MAIN OUTCOME MEASURES Patient satisfaction 4 months after surgery ; post-operative complications ; length of hospital stay ; duration of time before return to work , normal daily activities and sexual intercourse ; change in premenstrual symptoms . RESULTS The difference in patient satisfaction between endometrial resection ( 84 out of 99 ) and abdominal hysterectomy ( 89 out of 95 ) just reached statistical significance in favour of abdominal hysterectomy at 4 months after surgery ( difference = 9 % , 95 % confidence intervals ( CI ) 1.1%-17.5 % ) . Post-operative morbidity , length of hospital stay and time taken to return to work , normal daily activities and sexual intercourse were significantly less in the endometrial resection group . However , the premenstrual symptoms of dysmenorrhoea , bloating and breast tenderness were less frequent after hysterectomy . CONCLUSION In the short term , endometrial resection was almost as satisfactory as abdominal hysterectomy for the surgical treatment of menorrhagia , and was associated with less morbidity . However , even at 4 months after surgery , there was a failure rate of at least 10 % in those in whom endometrial resection appeared complete . Longer term comparative studies are necessary before the widespread introduction of endometrial resection as an alternative to abdominal hysterectomy for the surgical treatment of menorrhagia Abstract Objective : To evaluate the effectiveness and safety of endometrial laser ablation and transcervical resection of the endometrium compared with hysterectomy in the surgical treatment of women with dysfunctional uterine bleeding . Design : Prospect i ve r and omised controlled trial . Setting : Gynaecology department of a large teaching hospital . Subjects : 204 women who would otherwise have been undergoing hysterectomy for menorrhagia were recruited between August 1990 and March 1992 and r and omly allocated to hysterectomy ( n=99 ) or conservative ( hysteroscopic ) surgery ( transcervical resection ( n=52 ) and laser ablation ( n=53 ) ) . Main outcome measures : Operative complications , postoperative recovery , relief of menstrual and other symptoms , patient satisfaction with treatment after six and 12 months . Results - Women treated by hysteroscopic surgery had less early morbidity and a significantly shorter recovery period than those treated by hysterectomy ( median time to full recovery 2 - 4 weeks v 2 - 3 months , P<0.001 ) . Twelve months later 17 women in the hysteroscopy group had had a hysterectomy , 11 for continuing symptoms ; 11 women had had a repeat hysteroscopic procedure ; 45 were amenorrhoeic or had only a brown discharge ; and 35 had light periods . Dysmenorrhoea and premenstrual symptoms improved in most women in both groups . After 12 months 89 % ( 79/89 ) in the hysterectomy group and 78 % ( 75/96 ) in the hysteroscopy group were very satisfied with the effect of surgery ( P<0.05 ) ; 95 % ( 85/89 ) and 90 % ( 86/96 ) thought that there had been an acceptable improvement in symptoms , and 72 % ( 64/89 ) and 71 % ( 68/96 ) would recommend the same operation to others . Conclusions : Hysteroscopic endometrial ablation was superior to hysterectomy in terms of operative complications and postoperative recovery . Satisfaction after hysterectomy was significantly higher , but between 70 % and 90 % of the women were satisfied with the outcome of hysteroscopic surgery . Hysteroscopic surgery can be recommended as an alternative to hysterectomy for dysfunctional uterine bleeding STUDY OBJECTIVE To verify if more favorable long-term results of endometrial resection can be obtained with preoperative gonadotropin-releasing hormone ( GnRH ) agonist treatment . DESIGN Multicenter , r and omized , controlled trial ( Canadian Task Force classification I ) . SETTING Tertiary care academic department . PATIENTS Sixty-three premenopausal women with established menorrhagia . INTERVENTION Eight weeks of goserelin depot treatment before endometrial resection or immediate surgery in the early proliferative phase of the cycle . MEASUREMENTS AND MAIN RESULTS Variations in menstrual patterns and bleeding scores as well as overall degree of satisfaction with treatment were determined 1 year after endometrial resection . Mean + /- SD monthly pictorial blood loss- assessment chart scores in the second 6-month follow-up period were 26.9 + /- 31.6 in the goserelin group and 44.0 + /- 45.7 in the immediate surgery group ( mean difference 17.1 points , 95 % CI -3.0 to + 37.2 , p = 0.09 , unpaired t test ) . Respective amenorrhea rates were 34 % ( 11/32 ) and 20 % ( 6/20 , p = 0.26 , Fisher 's exact test , 95 % CI of difference -8 % to + 37 % ) . Overall satisfaction with treatment was 91 % and 87 % , respectively . CONCLUSION Administration of a GnRH agonist before endometrial resection is advantageous for surgery , but has a limited effect in terms of postoperative bleeding pattern and appears not to offer clear-cut long-term clinical benefit OBJECTIVES To evaluate the effects of treatment with the gonadotropin releasing hormone ( GnRH ) agonist goserelin before endometrial resection on absorption of distension medium fluid and technical feasibility of the surgical procedure . METHODS Fifty-five patients reporting menorrhagia underwent endometrial resection after 2 months of goserelin depot therapy ( 33 cases ) or during the proliferative phase of the cycle ( 22 controls ) . RESULTS In the cases , the mean distension medium deficit + /- S.D. was 511 + /- 196 ml versus 647 + /- 245 ml in controls ( P = 0.03 ) , and the operating times were , respectively , 14 + /- 4 versus 18 + /- 5 min ( P = 0.002 ) . The intrauterine operating conditions were considered excellent or good in 64 % of the cases versus 27 % of the controls ( chi 2 = 5.60 , P = 0.02 ) . CONCLUSIONS GnRH agonists induce endometrial thinning , so that when administered before intrauterine interventions , mucus cellular debris and bleeding should be reduced during surgery and hysteroscopic visibility increased ; the operating time may thus be shorter and fluid absorption decreased . However , more data are needed before considering GnRH agonists a proven effective means of facilitating endometrial resection STUDY OBJECTIVE To investigate the effects of gonadotropin-releasing hormone ( GnRH ) analog pretreatment on endometrial Na+ , K+-adenosine triphosphatase ( ATPase ) pump function and peripheral blood vasopressin levels , and their role in fluid absorption and mechanisms of hyponatremia in patients undergoing hysteroscopic endometrial ablation . DESIGN Prospect i ve , r and omized , placebo-controlled study ( Canadian Task Force classification I ) . SETTING University-affiliated hospital . PATIENTS Seventeen women with dysfunctional uterine bleeding . INTERVENTION Nine women received a GnRH analog and eight received saline approximately 6 to 8 weeks before hysteroscopic ablation by electrosurgery . MEASUREMENTS AND MAIN RESULTS Both before r and omization and immediately before surgery , endometrial biopsy sample s were obtained and numbered consecutively without patient identification . Operative hysteroscopy was performed with glycine 1.5 % mixed with 2 % alcohol . The amount of irrigant and irrigant deficit ; blood levels of albumin and ethanol ; hematocrit and hemoglobin ; changes in sodium levels ; and central venous pressure were compared . The Na+ , K+-ATPase pump activity was significantly increased in the GnRH analog group compared with the saline group and correlated with decreased estradiol levels ( 0.4 + /- 0.08 vs 0.26 + /- 0.06 micro mol/min/ml ) . Vasopressin levels were significantly lower in the GnRH group ( 3.2 + /- 0.9 vs 7.6 + /- 1.7 micro mol/L ) . Mean volume of irrigant used and operating time were similar in both groups . Volume deficit , decrease in protein , and hematocrit were less in GnRH than in the saline group . Blood ethanol levels , decrease in sodium , and irrigant deficit were significantly lower in GnRH group . CONCLUSION Pretreatment with GnRH analogs may prevent the adverse effects of estradiol on endometrial Na+ , K+-ATPase and creates a protective mechanism against iatrogenic hyponatremia , which is more critical in women than men in case of absorption of irrigating fluid . Moreover , created hypoestrogenism may enhance Na+ , K+-ATPase activity in brain as well as endometrium , thus decreasing women 's susceptibility to hyponatremic complications and brain damage . Suppressed vasopressin levels may be protective against fluid absorption in GnRH analog-treated patients AIM To compare postoperative outcomes and effects on quality of life following thermal balloon ablation ( TBA ) or laparoscopic supracervical hysterectomy ( LSH ) in women with heavy menstrual bleeding ( HMB ) . MATERIAL AND METHODS Sixty-eight women requiring surgical treatment for HMB were r and omly allocated into two treatment arms : TBA ( n = 34 ) and LSH ( n = 34 ) . The r and omization procedure was based on a computer-generated list . The primary outcome was a comparison of the effects on menstrual bleeding ( Pictorial Blood Loss Assessment Chart [ PBAC ] ) between the two procedures . The secondary outcome measures were quality of life , improvement of bleeding patterns , intensity of postoperative pain , and early postoperative complications . Continuous outcome variables were analyzed using Student 's t-test . Discrete variables were analyzed with the χ2 test or Fisher 's exact test . P < 0.05 was considered statistically significant . RESULTS The PBAC score was significantly reduced in both treatment groups . After LSH all women had amenorrhea . After TBA there was a significant improvement of bleeding frequency and length . The postoperative pain intensity at 24 h was significantly minor in women treated with TBA rather than with LSH . The Medical Outcomes Survey Short Form 36 ( SF-36 ) score improved in both groups . However , LSH showed a negative impact on the emotional state . No intraoperative complications occurred , and no case was returned to the theatre in either group . CONCLUSION The effectiveness of TBA as a possible treatment of HMB is confirmed . However , LSH showed a definitive improvement of the symptoms , and a better life quality profile . Further controlled prospect i ve studies are required for identifying the best surgical approach in women with HMB A r and omized controlled trial of 160 patients undergoing endometrial laser ablation ( ELA ) was performed . Patients selected for ELA were r and omized to receive either danazol or the GnRH analog Zoladex . Eighty patients were allocated to each group . Each group was also r and omized to receive either 1 or 2 months of treatment prior to surgery The major end points for the study were patient compliance and drug-related side-effects , operative time and complications , effectiveness of endometrial thinning as judged by ultrasound , histologic measurements , and clinical response at 6 months assessment . Significant differences in the effectiveness of the two preparations were noted BACKGROUND Submucous fibroids are common benign tumours responsible for menorrhagia , subfertility and miscarriage . They can be readily removed by hysteroscopic transcervical resection of myoma ( TCRM ) . To facilitate resection , pre-operative GnRH analogues have been suggested , but the value of this treatment is uncertain . Our aim was to assess the value of pre-operative GnRH analogues for the resection of submucous fibroids . METHODS This was a prospect i ve , double-blind , placebo-controlled , r and omized trial . Women found to have submucous fibroids on three-dimensional saline infusion sonohysterography ( 3D SIS ) were r and omized to receive GnRH or placebo . Following treatment patients underwent TCRM by a single operator blinded to the group allocation . Women were followed up 6 weeks after their operation to ascertain resolution of symptoms . The primary outcome measure of the study was completeness of fibroid resection . Secondary outcome measures included the duration of the TCRM , the fluid deficit recorded at TCRM , the resolution of symptoms post-operatively and the number of subsequent fibroid related operations . RESULTS Forty-seven women were r and omized to GnRH or placebo . On the basis of intention-to-treat analysis , there was no significant difference in the number of complete fibroid resections between women who received GnRH analogues [ 14/24 , 58.3 % ( 95 % CI 38.6 - 78.1 ) ] and those who received placebo [ 16/23 , 69.6 % ( 50.8 - 88.4 ) ] ( RR 0.84 , 95 % CI 0.54 - 1.29 ; P = 0.43 ) . Similarly there was no significant difference between the groups in any of the secondary outcome measures . CONCLUSIONS Our study does not support routine administration of GnRH analogues before transcervical resection of fibroid as we did not identify any benefit in such treatment A prospect i ve 5‐year multicentre study , involving three UK gynaecology centres with a special interest in endoscopic laser surgery , was set up to determine the safety , acceptability , clinical effectiveness and complications of neodymium yttrium‐aluminium‐garnet laser ablation of the endometrium in the treatment of menorrhagia . A total of 2342 women with disabling menorrhagia that was unresponsive to medical therapy were involved . The main outcome measures were : preoperative endometrial preparation , duration of laser ablation , intra‐ and postoperative complications , amenorrhoea rate , oligomenorrhoea rate , and the women 's subjective assessment of treatment . No major complications occurred in the 2342 treatments . Nine ( 0.4 % ) cases of transient fluid overload , 11 ( 0.5 % ) of infection and five ( 0.2 % ) of uterine perforation occurred . None of the women required a laparotomy . The mean duration of the laser ablation was 24 min . The post‐surgery amenorrhoea rate was higher in women pretreated with danazol . Of the 1866 women followed up for at least 1 year after treatment , 1043 ( 56 % ) developed complete amenorrhoea , 701 ( 38 % ) reported continuing but satisfactorily reduced menstruation , and 122 ( 7 % ) patients failed to improve with the first treatment ( 57 of these 122 women responded to a second laser ablation ) . Overall , 1744 ( 93 % ) had a satisfactory response to laser ablation and only 33 ( 1.8 % ) required subsequent hysterectomy . In conclusion , this study showed that hysteroscopic endometrial laser ablation is an acceptable alternative to hysterectomy for the treatment of menorrhagia References 1 Melin P. Oxytocin antagonists in preterm labour and delivery . Baillieres Clin Obstet Gynaecol 1993 ; 7 : 577 - 600 . 2 Thornton S , Davison JM , Baylis PH . Plasma oxytocin during the first and second stages of spontaneous human labour . Acra Endocrinologica ( Copenhagen ) 1992 ; 126 : 425 - 429 . 3 Thornton S , Charlton L , Murray BJ , Davison JM , Baylis PH . The effect of early labour , maternal analgesia and fetal acidosis on fetal plasma oxytocin concentrations . Br J Obstet Gynaecol1993 Menstrual problems account for one-third of gynaecological outpatient clinic consultations in the UK , with 60 % of these women undergoing hysterectomy within 5 years of presentation ' . In 50 % of the women who have a hysterectomy , no pathology is p re ~ en t ' , ~ . Endometrial resection and ablation with laser or rollerball electrocoagulation have been introduced in an attempt to avoid major surgery in such women . The aim of surgery is the complete removal or ablation of the endometrium to resolve the patient 's menorrhagia . Endometrial gl and ular elements are present deep in the myometrium , and ablation or resection should therefore include endometrium and 2.5 - 3.0 mm of myometrium ' . The depth of cut of the resection loop is 2 - 3 mm and , therefore , a satisfactory depth of destruction can only be achieved with a single pass of the loop if the endometrium has been prethinned ' . Similarly , for neodymium yttriumaluminium-garnet laser endometrial ablation , the depth of penetration and tissue destruction is 4 - 5 mm , which means that surgery is best carried out after endometrial suppressionfi . Endometrial ablation by rollerball electrocoagulation is an increasingly popular technique , as it may be safer than transcervical resection and less expensive than laser techniques . The in vivo studies of uterine electrosurgery undertaken by Duffy and colleagues ' demonstrate that rollerball coagulation at 75 or 100 W applied for 1 - 5 s results in thermal necrosis of 3.3G3.77 mm depth ( mean 3.59 mm for all delivered energies ) . Clearly , using this technique of endometrial ablation . prethinning of the endometrium is required to attain a satisfactory depth of tissue destruction to include deep endometrial gl and ular elements and achieve the best clinical results STUDY OBJECTIVE To assess the effects of pretreatment with the gonadotropin-releasing hormone analog goserelin on fluid absorption in patients undergoing hysteroscopic endometrial ablation . DESIGN Prospect i ve , r and omized , placebo-controlled study . SETTING A university-based clinic . PATIENTS Thirteen women with dysfunctional uterine bleeding who were scheduled for electrosurgical hysteroscopic ablation . INTERVENTIONS Seven women were r and omized to receive luteal phase goserelin 3.75 mg and six saline in the menstrual cycle approximately 10 weeks before surgery . Operative hysteroscopy was carried out with glycine 1.5 % mixed with 2 % alcohol medium under constant pressure as an irrigant . The amount of irrigant used , irrigant deficit , blood levels of albumin and ethanol , hematocrit , hemoglobin , changes in sodium levels , and central venous pressure were compared between the groups . MEASUREMENTS AND MAIN RESULTS All of the patients had an unsuccessful course of medical therapy for at least 3 months and a normal endometrial biopsy . The age , weight , and uterine size were similar between the groups . The mean volume of irrigant used and operating time were similar in both groups ( 4.18 + /- 0.2 vs 4.5 + /- 0.5 L , and 33.7 + /- 1.5 vs 37 + /- 2.1 min ) . Although operating time , volume deficit , decrease in protein level , and hematocrit were less in the goserelin than in the saline group , the differences were not statistically significant ( p > 0.05 ) . The ethanol levels in blood , decrease in Na+ , and irrigant deficit were significantly lower in the goserelin than in the saline group ( 17.4 + /- 3.8 vs 25.3 + /- 4.2 mg/ml , 6.7 + /- 1.2 vs 9.1 + /- 0.9 mEq/L , and 0.49 + /- 0.08 vs 0.66 + /- 0.05 L , respectively ; p < 0.05 ) . CONCLUSION Based on these results we conclude that in women undergoing hysteroscopic endometrial ablation , pretreatment with goserelin may decrease the absorption of hysteroscopic medium , prevent fluid overload , and improve the outcome possibly by causing hypovascularity and decreased endometrial growth Objective : To compare the outcome and cost-effectiveness of various forms of preoperative endometrial preparation prior to hysteroscopic endometrial destruction for abnormal uterine bleeding . Methods : This was a multicenter , prospect i ve , comparative , r and omized study conducted in a tertiary care hospital in Cairo , Egypt and 2 academic tertiary care teaching hospitals in the United States . One hundred thirty-one premenopausal women , who had completed child-bearing , mean age of 45.7 years , with abnormal uterine bleeding refractory to medical management without histologic evidence of endometrial neoplasia were studied . The 131 patients were r and omized for preoperative preparation for hysteroscopic endometrial destruction into 1 of 5 groups as follows : Group I , dilation and curettage ( D & C ) ( 39 ) ; Group II , gonadotropin-releasing hormone analogue ( GnRHa ) for 1 month ( 23 ) ; Group III , GnRHa for 3 months ( 26 ) ; Group IV , danazol for 3 months ( 26 ) ; and Group V , medroxyprogesterone acetate ( MPA ) 15 mg for 3 months ( 27 ) . The choice of endometrial ablation or endometrial resection was left to the surgeon . Results : Improvement in bleeding patterns , amenorrhea , operative times , complications , and relative cost were the measured outcomes . The mean follow-up time was 1 year from the time of the procedure . Overall , in Group I , 39/39 ( 100 % ) improved and 7/39 ( 18.0 % ) experienced amenorrhea ; in Group II , 21/23 ( 91.3 % ) improved and 9/23 ( 39.1 % ) experienced amenorrhea ; in Group III , 24/26 ( 92.3 % ) improved and 10/26 ( 38.5 % ) experienced amenorrhea ; in Group IV , 24/26 ( 92.3 % ) improved and 9/26 ( 34.6 % ) experienced amenorrhea ; and in Group V , 23/27 ( 85.1 % ) improved and 7/27 ( 25.9 % ) experienced amenorrhea . Conclusion : Endometrial destruction whether by the ablation or resection technique , regardless of the type of surgical pretreatment is a safe and effective surgical approach for treating abnormal uterine bleeding . D & C or MPA appear to be the most cost-effective pretreatment regimens . MPA pretreatment may confer the added advantage of decreasing blood flow and allowing better hysteroscopic visualization than D & C pretreatment OBJECTIVE To confirm the advantages of goserelin prior to endometrial ablation for the treatment of dysfunctional uterine bleeding . DESIGN Multicenter , prospect i ve , r and omized , double-blind study . PATIENT(S ) Cycling premenopausal women with dysfunctional uterine bleeding . TREATMENT Patients were r and omized to goserelin or placebo ( sham depot ) once monthly for 2 months prior to endometrial ablation . Treatment was timed to allow surgery 6 weeks later on day 7 of the menstrual cycle . MAIN OUTCOME MEASURE(S ) Amenorrhea rates , endometrial histology and thickness , pain and blood loss scores , and surgical parameters . RESULT ( S ) At 24 weeks after surgery , significantly more goserelin than placebo patients experienced amenorrhea ( 40 % versus 26 % ) . Blood loss was reduced from baseline , but not different between the groups . At surgery , mean endometrial thickness was 1.6 mm and 3.4 mm for the goserelin and placebo groups , respectively , with significantly more atrophic gl and s and stroma in the goserelin group . Surgery was significantly shorter ( by 22 % ) and easier in the goserelin than in the placebo group , with a significantly lower median fluid absorption in the goserelin groups . In both groups , pain scores were reduced patient satisfaction was high ( > 92 % ) , and re-intervention rate was low ( 2.8 % ) . CONCLUSION ( S ) Goserelin in combination with endometrial ablation was superior to endometrial ablation alone for the treatment of dysfunctional uterine bleeding OBJECTIVE To determine the best pretreatment of the endometrium prior to roller ball endometrial ablation . STUDY DESIGN Forty patients with recurrent hypermenorrhea underwent diagnostic hysteroscopy and dilation and curettage . They were then assigned to receive either no pretreatment or pretreatment with danazol , a GnRH-analogue , or a gestagen prior to roller ball endometrial ablation . Endometrial suppression was estimated by the surgeon at the time of the procedure , and endometrial biopsies were obtained . Patients were followed for 24 months . RESULTS The subjective estimation of the surgeon showed a sufficient pretreatment after danazol or a GnRH-analogue in 90 % of the cases . Histological findings correlated with these findings . The highest level of amenorrhoea at 2 years of follow-up was also reached after danazol or GnRH-analogue pretreatment . CONCLUSIONS Danazol- or GnRH-analogue should be used for pretreatment prior to endometrial ablation using the roller ball technique OBJECTIVE To evaluate the benefits of systematic preoperative treatment with LH-RH agonists prior to endometrial resection ( ER ) . STUDY DESIGN The study population was made up of 98 premenopausal women who underwent resectoscopic treatment for abnormal uterine bleeding ( AUB ) between January 1996 and December 1997 . Only patients with endometrial polyps or dysfunctional bleeding were included . The population was divided into two groups : patients who had ( group B ) and those who had not ( group A ) received LH-RH before the surgical intervention . RESULTS ER was carried out as a single procedure in 66 ( 67.5 % ) of the patients . ER plus polypectomy was necessary in 32 ( 32.5 % ) patients . There were no differences between the two groups as far as the operating time and total volume of distension medium were concerned . No intraoperative complications were seen in either group . A higher negative balance of distension medium was achieved in group A ( 320 + /- 23 mL versus 187 + /- 16 mL ; P < 0.001 ) , and this difference was not modified when cases with polyps were excluded . The failure rate was similar in both groups both at 12 months [ group A 6 ( 14.8 % ) versus group B 7 ( 14.9 % ) patients ] and at 60 months [ group A , 11 ( 21.6 % ) versus group B 10 ( 21.2 % ) patients ] . Likewise , the amenorrhea and hypomenorrhea rates at 12 months and at 60 months were also shown to be the same in both groups . When two doses of LH-RH are used and the failure rate is taken into account the cost of an acceptable outcome increases from 843.37 Euro to 1373.49 Euro per patient , while the total cost of a hysterectomy is 1355.42 Euro . CONCLUSIONS Endometrial suppression with LH-RH agonists did not guarantee better results of ER , but they are strongly recommended during the learning curve to achieve a safer procedure OBJECTIVE To report the results of a 3-year follow-up evaluation of a trial comparing goserelin acetate depot injections with sham injections before endometrial ablation for the treatment of dysfunctional uterine bleeding ( DUB ) . DESIGN Prospect i ve , r and omized , double-blind , parallel-group study . SETTING Thirty-seven centers in 12 countries . PATIENT(S ) Three-hundred and fifty-eight premenopausal women aged over 30 years with DUB . INTERVENTION(S ) Goserelin acetate ( 3.6 mg depot ) every 28 days for 8 weeks , or sham depot every 28 days for 8 weeks , with endometrial ablation 6 weeks + /- 3 days after the first depot injection ( i.e. , when the endometrium is at its thinnest ) . The follow-up continued for 3 years . MAIN OUTCOME MEASURE(S ) At the 3-year follow-up , bleeding in the previous 3 months and need for surgical intervention were recorded . RESULT ( S ) At 3 years , amenorrhea rates were 21 % in the goserelin acetate group and 14 % in the control group ( estimated odds ratio , 1.8 ; 95 % CI , 0.98 - 3.25 ; P=.0571 ) . The surgical intervention rate ( since the original procedure ) was low and did not differ significantly between groups . For hysterectomy , it was 21 % for the goserelin acetate group and 15 % for the control group . For repeat ablations , it was 5.6 % for the goserelin acetate group and 2.1 % for the control group . CONCLUSION ( S ) Prethinning with goserelin acetate before endometrial ablation result ed in higher long-term amenorrhea rates than ablation without prethinning |
12,052 | 32,276,950 | After completion of therapy , among trials recruiting only patients with refractory symptoms , group CBT and gut-directed hypnotherapy were more efficacious than either education and /or support or routine care , and CBT via the telephone , contingency management , CBT via the internet and dynamic psychotherapy were all superior to routine care .
Several psychological therapies are efficacious for IBS , although none were superior to another .
CBT-based interventions and gut-directed hypnotherapy had the largest evidence base and were the most efficacious long term . | OBJECTIVES National guidelines for the management of irritable bowel syndrome ( IBS ) recommend that psychological therapies should be considered , but their relative efficacy is unknown , because there have been few head-to-head trials .
We performed a systematic review and network meta- analysis to try to resolve this uncertainty . | The aim of this study was to investigate if cognitive behavior therapy ( CBT ) based on exposure and mindfulness exercises delivered via the Internet would be effective in treating participants with irritable bowel syndrome ( IBS ) . Participants were recruited through self-referral . Eighty-six participants were included in the study and r and omized to treatment or control condition ( an online discussion forum ) . One participant was excluded after r and omization . The main outcome measure was IBS-symptom severity and secondary measures included IBS-related quality of life , GI-specific anxiety , depression and general functioning . Participants were assessed at pre-treatment , post-treatment and 3 month follow-up ( treatment condition only ) . Four participants ( 5 % of total sample ) in the treatment condition did not participate in post-treatment assessment . Participants in the treatment condition reported a 42 % decrease and participants in the control group reported a 12 % increase in primary IBS-symptoms . Compared to the control condition , participants in the treatment group improved on all secondary outcome measures with a large between group effect size on quality of life ( Cohen 's d = 1.21 ) . We conclude that CBT-based on exposure and mindfulness delivered via the Internet can be effective in treating IBS- patients , alleviating the total burden of symptoms and increasing quality of life OBJECTIVES : Psychological and behavioral therapies are being increasingly used for symptom management in patients with irritable bowel syndrome ( IBS ) . The aims of this study were to compare two delivery modes for a comprehensive self-management ( CSM ) intervention , primarily by telephone vs. entirely in person , and to compare each with usual care ( UC ) . METHODS : Adults with IBS were recruited through community advertisement . Subjects ( N=188 ) were r and omly assigned to three groups : one in which all nine weekly CSM sessions were delivered in person , one in which six of the nine sessions were conducted over telephone , and one in which subjects received UC . Primary outcome measures were a gastrointestinal ( GI ) symptom score based on six symptoms from a daily diary and disease-specific quality of life ( QOL ) . These and other outcomes were assessed at baseline and at 3 , 6 , and 12 months after r and omization . Mixed model analyses tested for differences between the three groups in each outcome variable at the three follow-up occasions , controlling for the baseline level of each outcome . RESULTS : Both GI symptom score and QOL showed significantly greater improvement in the two CSM groups than in the UC group ( P<0.001 ) , with the magnitude of this difference being quite similar for the three follow-up time points . The two CSM groups experienced a very similar degree of improvement , and there were no statistically significant differences between the two . CONCLUSIONS : A CSM program is efficacious whether delivered primarily by telephone or totally in person , and there is no evidence that replacing six of the in-person sessions by telephone sessions reduces the efficacy of the intervention Objectives : Tenapanor is a first-in-class , small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger NHE3 . This study assessed the efficacy and safety of tenapanor in patients with constipation-predominant irritable bowel syndrome ( IBS-C ) . Methods : In this phase 2 , double-blind study , patients with IBS-C ( Rome III criteria ) were r and omized ( 1:1:1:1 ) to receive tenapanor 5 mg , 20 mg , or 50 mg b.i.d . , or placebo b.i.d . for 12 weeks . The primary end point was the complete spontaneous bowel movement ( CSBM ) responder rate , defined as the proportion of patients reporting an increase from baseline of ≥1 CSBM/week for ≥6/12 treatment weeks . Secondary end points included abdominal symptom responder rates ( ≥30 % score improvement from baseline for ≥6/12 weeks ) and a composite responder rate ( CSBM and abdominal pain response in the same week for ≥6/12 weeks ) . Results : Overall , 356 patients were r and omized ( mean age : 45.7 years ; 86.8 % women ) and 304 completed the study . The CSBM responder rate was significantly higher in the tenapanor 50 mg b.i.d . group than in the placebo group ( 60.7 vs. 33.7 % ; P<0.001 ) , as was the composite responder rate ( 50.0 vs. 23.6 % ; P<0.001 ) . Responder rates for abdominal symptoms ( pain , discomfort , bloating , cramping , and fullness ) were significantly higher in the tenapanor 50 mg b.i.d . group than in the placebo group ( all P<0.05 ) . Diarrhea was the most frequent adverse event ( tenapanor b.i.d . : 20 mg , 12.4 % ; 50 mg , 11.2 % ) . Conclusions : Tenapanor 50 mg b.i.d . significantly increased stool frequency and reduced abdominal symptoms in patients with IBS-C. Further research into tenapanor as a potential treatment for these patients is justified Twenty patients with irritable bowel syndrome ( IBS ) were r and omly assigned either to intensive , individualized cognitive therapy ( 10 sessions over 8 weeks ) or to 8 weeks of daily gastrointestinal ( GI ) symptom monitoring . Pre- to posttreatment evaluations showed significantly ( p = .005 ) greater GI symptom reduction for those receiving cognitive therapy than for those in symptom monitoring . At posttreatment , 80 % of the cognitive therapy group showed clinical ly significant improvement , whereas only 10 % of the monitoring group showed this . Results held up well at a 3-month follow-up . Within the cognitive therapy group , GI symptom reductions correlated significantly with increases in positive and reductions in negative automatic thoughts Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose OBJECTIVES : Two identical , phase 3 , r and omized , double‐blind , placebo‐controlled trials evaluated the efficacy and safety of plecanatide in patients with irritable bowel syndrome with constipation ( IBS‐C ) . METHODS : Adults meeting Rome III criteria for IBS‐C were r and omized ( 1:1:1 ) to placebo or plecanatide ( 3 or 6 mg ) for 12 weeks . The primary efficacy end point was the percentage of overall responders ( patients reporting ≥30 % reduction from baseline in worst abdominal pain plus an increase of ≥1 complete spontaneous bowel movement (CSBM)/week from baseline in the same week for ≥6 of 12 treatment weeks ) . Safety was assessed by adverse events ( AEs ) . RESULTS : Overall , 2189 individuals were r and omized across the two studies and 1879 completed the studies . Demographic and baseline characteristics were similar across treatment groups and between studies . The percentage of overall responders in Study 1 was 30.2 % and 29.5 % for plecanatide 3 and 6 mg , respectively , vs. 17.8 % placebo ( P < 0.001 for each dose vs. placebo ) , and in Study 2 was 21.5 % ( P = 0.009 ) and 24.0 % ( P < 0.001 ) for plecanatide 3 and 6 mg , respectively , compared to 14.2 % for placebo . The percentage of sustained efficacy responders ( overall responders plus weekly responders for ≥2 of last 4 weeks of the 12‐week treatment period ) was significantly greater for both doses of plecanatide vs. placebo across both studies . All secondary end points ( stool frequency/consistency , straining , abdominal symptoms ) showed statistically significant improvements compared with placebo . The most common AE was diarrhea ( 3 mg , 4.3 % ; 6 mg , 4.0 % ; placebo , 1.0 % ) . Discontinuation due to diarrhea was infrequent ( 3 mg , 1.2 % ; 6 mg , 1.4 % ; placebo , 0 ) . CONCLUSIONS : Plecanatide significantly improved both abdominal pain and constipation symptoms of IBS‐C with minimal associated side effects and high levels of tolerability Background and objectives : We have previously shown that hypnosis can be used to study the effect of different emotions on the motility of the gastrointestinal tract . These studies demonstrated that both anger and excitement increased colonic motility while happiness led to a reduction . The purpose of this study was to investigate the effect of hypnotically induced emotion on the visceral sensitivity of the gut . Methods : Sensory responses to balloon distension of the rectum and compliance were assessed in 20 patients with irritable bowel syndrome ( IBS ) ( aged 17–64 years ; 17 female ) diagnosed by the Rome I criteria . Patients were studied on four separate occasions in r and om order either awake ( control ) or in hypnosis , during which anger , happiness , or relaxation ( neutral emotion ) were induced . Results : Hypnotic relaxation increased the distension volume required to induce discomfort ( p=0.05 ) while anger reduced this threshold compared with relaxation ( p<0.05 ) , happiness ( p<0.01 ) , and awake conditions ( p<0.001 ) . Happiness did not further alter sensitivity from that observed during relaxation . There were no associated changes in rectal compliance or wall tension . Conclusions : Further to our previous observations on motility , this study shows that emotion can also affect an IBS patient ’s perception of rectal distension and demonstrates the critical role of the mind in modulating gastrointestinal physiology . These results emphasise how awareness of the emotional state of the patient is important when either measuring visceral sensitivity or treating IBS OBJECTIVES : Psychological treatments are considered to be useful in the irritable bowel syndrome ( IBS ) , although the evidence is based on small , often flawed trials . Although cognitive behavior therapy ( CBT ) and relaxation therapy have both been promising , we hypothesized that CBT would be superior to relaxation and st and ard care alone in IBS patients . The objective of this study was to test this assumption by comparing the effects of cognitive behavior therapy with relaxation therapy and routine clinical care alone in individuals with IBS . METHODS : Patients ( n = 105 ) with Rome I criteria for IBS were recruited from advertisement ( n = 51 ) and outpatient clinics ( n = 54 ) ; those patients with resistant IBS were not included . A r and omized controlled trial with three arms ( st and ard care for all groups plus either CBT or relaxation ) for 8 wk was conducted , which applied blinded outcome assessment s using vali date d measures with 1 yr of follow-up . The primary outcome for this study was bowel symptom severity . RESULTS : Of 105 patients at the commencement of treatment , the mean bowel symptom frequency score for the whole sample was 21.1 and at the end of treatment had fallen to 18.1 ; this persisted at the 52-wk follow-up , with a significant linear trend for scores to change over time ( F= 39.57 p < 0.001 ) . However , there were no significant differences among the three treatment conditions . Significant changes over time were found for physical functioning ( F= 4.37 , p < 0.001 ) , pain ( F= 3.12 , p < 0.05 ) , general health ( F= 2.71 , p < 0.05 ) , vitality ( F= 2.94 , p < 0.05 ) , and the social functioning scales on the Medical Outcomes Study Short Form 36 ( F= 4.08 , p < 0.05 ) ; however , all three arms showed similar improvement . There were significant reductions in anxiety , depression , and locus of control scales , but no significant differences among the treatment groups were detected . CONCLUSION : Cognitive behavior and relaxation therapy seem not to be superior to st and ard care alone in IBS CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult to manage in primary practice . Behavioral and pharmacological therapies each appear modestly effective , but data are lacking on their separate and combined effects . OBJECTIVE To evaluate the clinical efficacy of behavioral and pharmacological therapies , singly and combined , for chronic tension-type headaches . DESIGN AND SETTING R and omized placebo-controlled trial conducted from August 1995 to January 1998 at 2 outpatient sites in Ohio . PARTICIPANTS Two hundred three adults ( mean age , 37 years ; 76 % women ) with diagnosis of chronic tension-type headaches ( mean , 26 headache d/mo ) . INTERVENTIONS Participants were r and omly assigned to receive tricyclic antidepressant ( amitriptyline hydrochloride , up to 100 mg/d , or nortriptyline hydrochloride , up to 75 mg/d ) medication ( n = 53 ) , placebo ( n = 48 ) , stress management ( eg , relaxation , cognitive coping ) therapy ( 3 sessions and 2 telephone contacts ) plus placebo ( n = 49 ) , or stress management therapy plus antidepressant medication ( n = 53 ) . MAIN OUTCOME MEASURES Monthly headache index scores calculated as the mean of pain ratings ( 0 - 10 scale ) recorded by participants in a daily diary 4 times per day ; number of days per month with at least moderate pain ( pain rating > /=5 ) , analgesic medication use , and Headache Disability Inventory scores , compared by intervention group . RESULTS Tricyclic antidepressant medication and stress management therapy each produced larger reductions in headache activity , analgesic medication use , and headache-related disability than placebo , but antidepressant medication yielded more rapid improvements in headache activity . Combined therapy was more likely to produce clinical ly significant ( > /=50 % ) reductions in headache index scores ( 64 % of participants ) than antidepressant medication ( 38 % of participants ; P = .006 ) , stress management therapy ( 35 % ; P = .003 ) , or placebo ( 29 % ; P = .001 ) . On other measures the combined therapy and its 2 component therapies produced similar outcomes . CONCLUSIONS Our results indicate that antidepressant medication and stress management therapy are each modestly effective in treating chronic tension-type headaches . Combined therapy may improve outcome relative to monotherapy BACKGROUND Recent guidelines for the treatment of irritable bowel syndrome ( IBS ) emphasize the need for research to facilitate home-based self-management for these patients in primary care . The aim of the current study was to test the efficacy of a manualized cognitive behavioural therapy (CBT)-based self-management programme for IBS in a pilot r and omized controlled trial ( RCT ) . METHOD Sixty-four primary -care patients meeting Rome criteria for IBS were r and omized into either self-management plus treatment as usual ( TAU ) ( n=31 ) or a TAU control condition ( n=33 ) . The self-management condition included a structured 7-week manualized programme that was self-administered in conjunction with a 1-hour face-to-face therapy session and two 1-hour telephone sessions . The primary outcome measures were the Subject 's Global Assessment ( SGA ) of Relief and the Irritable Bowel Syndrome Severity Scoring System ( IBS-SSS ) assessed at baseline , end of treatment ( 2 months ) , and 3 and 6 months post-treatment . RESULTS Analysis was by intention-to-treat . Twenty-three ( 76.7 % ) of the self-management group rated themselves as experiencing symptom relief across all three time periods compared to seven ( 21.2 % ) of the TAU controls [ odds ratio ( OR ) 12.2 , 95 % confidence interval ( CI ) 3.72 - 40.1 ] . At 8 months , 25 ( 83 % ) of the self-management group showed a clinical ly significant change on the IBS-SSS compared to 16 ( 49 % ) of the control group ( OR 5.3 , 95 % CI 1.64 - 17.26 ) . CONCLUSIONS This study provides preliminary evidence that CBT-based self-management in the form of a structured manual and minimal therapist contact is an effective and acceptable form of treatment for primary -care IBS patients BACKGROUND Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome ( IBS ) . We evaluated rifaximin , a minimally absorbed antibiotic , as treatment for IBS . METHODS In two identically design ed , phase 3 , double-blind , placebo-controlled trials ( TARGET 1 and TARGET 2 ) , patients who had IBS without constipation were r and omly assigned to either rifaximin at a dose of 550 mg or placebo , three times daily for 2 weeks , and were followed for an additional 10 weeks . The primary end point , the proportion of patients who had adequate relief of global IBS symptoms , and the key secondary end point , the proportion of patients who had adequate relief of IBS-related bloating , were assessed weekly . Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment . Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating , abdominal pain , and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study . RESULTS Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment ( 40.8 % vs. 31.2 % , P=0.01 , in TARGET 1 ; 40.6 % vs. 32.2 % , P=0.03 , in TARGET 2 ; 40.7 % vs. 31.7 % , P<0.001 , in the two studies combined ) . Similarly , more patients in the rifaximin group than in the placebo group had adequate relief of bloating ( 39.5 % vs. 28.7 % , P=0.005 , in TARGET 1 ; 41.0 % vs. 31.9 % , P=0.02 , in TARGET 2 ; 40.2 % vs. 30.3 % , P<0.001 , in the two studies combined ) . In addition , significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms , bloating , abdominal pain , and stool consistency . The incidence of adverse events was similar in the two groups . CONCLUSIONS Among patients who had IBS without constipation , treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms , bloating , abdominal pain , and loose or watery stools . ( Funded by Salix Pharmaceuticals ; Clinical Trials.gov numbers , NCT00731679 and NCT00724126 . ) OBJECTIVES : Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome ( IBS ) . However , r and omized , controlled studies are rare and few have been performed outside highly specialized research centers . The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical setting s outside the traditional research units . METHODS : The study population included IBS patients refractory to st and ard management . In study 1 , patients were r and omized to receive gut-directed hypnotherapy ( 12 sessions , 1 h/week ) in psychology private practice s or supportive therapy , whereas patients were r and omized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2 . Gastrointestinal symptom severity and quality of life were evaluated at baseline , at 3 months follow-up and after 1 year . RESULTS : We r and omized 138 IBS patients refractory to st and ard management , 90 in study 1 and 48 in study 2 . In both the studies , IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups ( P<0.05 ) , but not in the control groups ( ns ) . In study 1 , a significantly greater improvement of IBS-related symptom severity could be detected in the gut-directed hypnotherapy group than in the control group ( P<0.05 ) , and a trend in the same direction was seen in study 2 ( P=0.17 ) . The results seen at 3 months were sustained up to 1 year . CONCLUSIONS : Gut-directed hypnotherapy is an effective treatment alternative for patients with refractory IBS , but the effectiveness is lower when the therapy is given outside the highly specialized research centers 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 OBJECTIVES : Our research group has developed an internet-delivered cognitive behavioral treatment ( ICBT ) for irritable bowel syndrome ( IBS ) . We compared ICBT with internet-delivered stress management ( ISM ) for IBS to assess whether the effects of ICBT are specific . METHODS : This was a r and omized controlled trial , including 195 self-referred participants diagnosed with IBS . The treatment interventions lasted for 10 weeks and included an online therapist contact . The ICBT emphasized acceptance of symptoms through exposure to IBS symptoms and related negative feelings . The ICBT also included mindfulness training . The ISM emphasized symptom control through relaxation techniques , dietary adjustments , and problem-solving skills . Severity of IBS symptoms was measured with the gastrointestinal symptom rating scale — IBS version ( GSRS-IBS ) . Credibility of the treatments and expectancy of improvement were assessed with the treatment credibility scale . The participants ’ perceived therapeutic alliance with their online therapist was measured with the working alliance inventory . RESULTS : At post-treatment and 6-month follow-up , 192 ( 99 % ) and 169 ( 87 % ) participants returned data , respectively . At post-treatment and 6-month follow-up , we found significant differences on the GSRS-IBS , favoring ICBT . The difference on GSRS-IBS scores was 4.8 ( 95 % confidence interval ( CI ) : 1.2–8.4 ) at post-treatment and 5.9 ( 95 % CI : 1.9–9.9 ) at 6-month follow-up . There were no significant differences on the treatment credibility scale or the working alliance inventory between the groups . CONCLUSIONS : Internet-delivered CBT has specific effects that can not be attributed only to treatment credibility , expectancy of improvement , therapeutic alliance , or attention . Furthermore , a treatment based on exposure exercises specifically tailored for IBS may be a better treatment option than general stress and symptom management for IBS patients . ICBT is a promising treatment modality for IBS as it can be offered to IBS patients in much larger scale than conventional psychological treatments One hundred two patients with irritable bowel syndrome were studied in a controlled trial of psychological treatment involving psychotherapy , relaxation , and st and ard medical treatment compared with st and ard medical treatment alone . Patients were only selected if their symptoms had not improved with st and ard medical treatment over the previous 6 months . At 3 months , the treatment group showed significantly greater improvement than the controls on both gastroenterologists ' and patients ' ratings of diarrhea and abdominal pain , but constipation changed little . Good prognostic factors included overt psychiatric symptoms and intermittent pain exacerbated by stress , whereas those with constant abdominal pain were helped little by this treatment . This study has demonstrated that psychological treatment is feasible and effective in two thirds of those patients with irritable bowel syndrome who do not respond to st and ard medical treatment BACKGROUND Irritable bowel syndrome ( IBS ) is a chronic and debilitating medical condition with few efficacious pharmacological or psychosocial treatment options available . Evidence suggests that visceral anxiety may be implicated in IBS onset and severity . Thus , cognitive-behavioral treatment ( CBT ) that targets visceral anxiety may alleviate IBS symptoms . METHODS The current study examined the efficacy of a CBT protocol for the treatment of IBS which directly targeted visceral sensations . Participants ( N = 110 ) were r and omized to receive 10 sessions of either : ( a ) CBT with interoceptive exposure ( IE ) to visceral sensations ; ( b ) stress management ( SM ) ; or ( c ) an attention control ( AC ) , and were assessed at baseline , mid-treatment , post-treatment , and follow-up sessions . RESULTS Consistent with hypotheses , the IE group outperformed AC on several indices of outcome , and outperformed SM in some domains . No differences were observed between SM and AC . The results suggest that IE may be a particularly efficacious treatment for IBS . CONCLUSIONS Implication s for research and clinical practice are discussed Objective Postpr and ial symptoms in irritable bowel syndrome are common and relate to an exaggerated motor and sensory component of the gastrocolonic response . We investigated whether this response can be affected by hypnotherapy . Methods We included 28 patients with irritable bowel syndrome refractory to other treatments . They were r and omized to receive gut-directed hypnotherapy 1 hour per week for 12 weeks ( N = 14 ) or were provided with supportive therapy ( control group ; N = 14 ) . Before r and omization and after 3 months , all patients underwent a colonic distension trial before and after a 1-hour duodenal lipid infusion . Colonic sensory thresholds and tonic and phasic motor activity were assessed . Results Before r and omization , reduced thresholds after vs. before lipid infusion were seen in both groups for all studied sensations . At 3 months , the colonic sensitivity before duodenal lipids did not differ between groups . Controls reduced their thresholds after duodenal lipids for gas ( 22 ± 1.7 mm Hg vs. 16 ± 1.6 mm Hg , p < .01 ) , discomfort ( 29 ± 2.9 mm Hg vs. 22 ± 2.6 mm Hg , p < .01 ) , and pain ( 33 ± 2.7 mm Hg vs. 26 ± 3.3 mm Hg , p < .01 ) , whereas the hypnotherapy group reduced their thresholds after lipids only for pain ( 35 ± 4.0 mm Hg vs. 29 ± 4.7 mm Hg , p < .01 ) . The colonic balloon volumes and tone response at r and omization were similar in both groups . At 3 months , baseline balloon volumes were lower in the hypnotherapy group than in controls ( 83 ± 14 ml vs. 141 ± 15 ml , p < .01 ) . In the control group , reduced balloon volumes during lipid infusion were seen ( 141 ± 15 ml vs. 111 ± 19 ml , p < .05 ) , but not after hypnotherapy ( 83 ± 14 ml vs. 80 ± 16 ml , p > .20 ) . Conclusion Hypnotherapy reduces the sensory and motor component of the gastrocolonic response in patients with irritable bowel syndrome . These effects may be involved in the clinical efficacy of hypnotherapy in IBS BACKGROUND Abdominal pain/discomfort , bloating , and constipation are gastrointestinal dysmotility and sensory symptoms associated with irritable bowel syndrome ( IBS ) . No studies have followed patients with IBS symptoms for 1 year under conditions of routine clinical practice to assess prospect ively the impact of treatments on health outcomes . OBJECTIVE The objective of this ongoing , naturalistic study is to assess the long-term impact of IBS treatments on quality of life ( QOL ) , work productivity , and re source utilization . This report describes the baseline characteristics and patterns of care of the patients enrolled in this study . METHODS Patients with physician-diagnosed IBS symptoms were enrolled from 147 physician sites across Canada between May 4 , 2004 , and March 31 , 2005 . Clinical data were collected at baseline and at the end of the 12-month follow-up ( patients were followed for 1 year between May 4 , 2005 , and March 31 , 2006 ) . Patient-reported outcomes were collected at baseline and at months 1 , 2 , 6 , 9 , and 12 . Health-related QOL , health status , and work productivity were assessed with the IBS-QOL , a 5-item EuroQol descriptive system , and Work Productivity and Activity Impairment question naires , respectively . A re source utilization question naire elicited information on physician ; visits , treatments , and procedures . Baseline data are reported here . RESULTS Data were obtained from 1555 patients ; 85.1 % ( 1320/1552 ) were women . Patients had a mean ( SD ) age of 45.8 ( 15.0 ) years and mean ( SD ) duration of IBS symptoms of 11.4 ( 11.5 ) years . Self-reported bowel patterns were predominantly constipation ( 41.0 % , 587/1433 ) and constipation alternating with diarrhea ( 39.4 % , 564/1433 ) ; 60.3 % ( 938/1555 ) of subjects used > or =3 IBS treatments in the previous 4 weeks . Approximately 50 % of all patients reported distress " quite a bit or " extremely " for abdominal pain , gas , bloating , and constipation . The mean overall IBS-QOL score ( 0 - 100 scale , with 0 indicating poor QOL ) was 66.3 ; food avoidance ( 51.8 ) and health worry ( 59.3 ) were the most serious concerns . Patients reported 5.6 % work absenteeism , 31.4 % presenteeism , and 34.6 % overall work productivity loss , equivalent to 13.8 hours lost productivity per 40-hour workweek . CONCLUSIONS The baseline data from this ongoing , prospect i ve , naturalistic study are consistent with previous findings that suggested significant use of health care re sources with concomitant low QOL and decreased work productivity in patients with IBS symptoms BACKGROUND & AIMS There is an urgent need for safe treatments for irritable bowel syndrome ( IBS ) that relieve treatment-refractory symptoms and their societal and economic burden . Cognitive behavior therapy ( CBT ) is an effective treatment that has not been broadly adopted into routine clinical practice . We performed a r and omized controlled trial to assess clinical responses to home-based CBT compared with clinic-based CBT and patient education . METHODS We performed a prospect i ve study of 436 patients with IBS , based on Rome III criteria , at 2 tertiary centers from August 23 , 2010 , through October 21 , 2016 . Subjects ( 41.4 ± 14.8 years old ; 80 % women ) were r and omly assigned to groups that received the following : st and ard-CBT ( S-CBT , n = 146 , comprising 10 weekly , 60-minute sessions that emphasized the provision of information about brain-gut interactions ; self-monitoring of symptoms , their triggers , and consequences ; muscle relaxation ; worry control ; flexible problem solving ; and relapse prevention training ) , or 4 sessions of primarily home-based CBT requiring minimal therapist contact ( MC-CBT , n = 145 ) , in which patients received home- study material s covering the same procedures as S-CBT ) , or 4 sessions of IBS education ( EDU , n = 145 ) that provided support and information about IBS and the role of lifestyle factors such as stress , diet , and exercise . The primary outcome was global improvement of IBS symptoms , based on the IBS-version of the Clinical Global Impressions-Improvement Scale . Ratings were performed by patients and board-certified gastroenterologists blinded to treatment allocation . Efficacy data were collected 2 weeks , 3 months , and 6 months after treatment completion . RESULTS A higher proportion of patients receiving MC-CBT reported moderate to substantial improvement in gastrointestinal symptoms 2 weeks after treatment ( 61.0 % based on ratings by patients and 55.7 % based on ratings by gastroenterologists ) than those receiving EDU ( 43.5 % based on ratings patients and 40.4 % based on ratings by gastroenterologists ) ( P < .05 ) . Gastrointestinal symptom improvement , rated by gastroenterologists , 6 months after the end of treatment also differed significantly between the MC-CBT ( 58.4 % ) and EDU groups ( 44.8 % ) ( P = .05 ) . Formal equivalence testing applied across multiple contrasts indicated that MC-CBT is at least as effective as S-CBT in improving IBS symptoms . Patients tended to be more satisfied with CBT vs EDU ( P < .05 ) based on immediate posttreatment responses to the Client Satisfaction Question naire . Symptom improvement was not significantly related to concomitant use of medications . CONCLUSIONS In a r and omized controlled trial , we found that a primarily home-based version of CBT produced significant and sustained gastrointestinal symptom improvement for patients with IBS compared with education . Clinical trials.gov no. : NCT00738920 OBJECTIVES : This prospect i ve , r and omized controlled trial explored the feasibility and efficacy of a group program of mindfulness training , a cognitive-behavioral technique , for women with irritable bowel syndrome ( IBS ) . The technique involves training in intentionally attending to present-moment experience and non-judgmental awareness of body sensations and emotions . METHODS : Seventy-five female IBS patients were r and omly assigned to eight weekly and one half-day intensive sessions of either mindfulness group ( MG ) training or a support group ( SG ) . Participants completed the IBS severity scale ( primary outcome ) , IBS- quality of life , brief symptom inventory-18 , visceral sensitivity index , treatment credibility scale , and five-facet mindfulness question naire before and after treatment and at 3-month follow-up . RESULTS : Women in the MG showed greater reductions in IBS symptom severity immediately after training ( 26.4 % vs. 6.2 % reduction ; P=0.006 ) and at 3-month follow-up ( 38.2 % vs. 11.8 % ; P=0.001 ) relative to SG . Changes in quality of life , psychological distress , and visceral anxiety were not significantly different between groups immediately after treatment , but evidence d significantly greater improvements in the MG than in the SG at the 3-month follow-up . Mindfulness scores increased significantly more in the MG after treatment , confirming effective learning of mindfulness skills . Participants ’ ratings of the credibility of their assigned interventions , measured after the first group session , were not different between groups . CONCLUSIONS : This r and omized controlled trial demonstrated that mindfulness training has a substantial therapeutic effect on bowel symptom severity , improves health-related quality of life , and reduces distress . The beneficial effects persist for at least 3 months after group training Background The efficacy of antidepressants in irritable bowel syndrome ( IBS ) is controversial . No trials have directly compared a tricyclic with a selective serotonin reuptake inhibitor . Our aim was to determine whether imipramine and citalopram are efficacious in IBS . Methods This was a r and omized , double-blind , placebo-controlled , parallel group pilot trial with imipramine ( 50 mg ) and citalopram ( 40 mg ) . Results Of 51 IBS patients r and omized , baseline characteristics were comparable among the treatment arms ; the majority was diarrhea-predominant . Adequate relief of IBS symptoms ( primary endpoint ) was similar for each treatment arm . Improvements in bowel symptom severity rating for interference ( P = 0.05 ) and distress ( P = 0.02 ) were greater with imipramine versus placebo , but improvements in abdominal pain were not . There was a greater improvement in depression score ( P = 0.08 ) and in the SF-36 Mental Component Score ( P = 0.07 ) , with imipramine . Citalopram was not superior to placebo . Approximately 20 % of the variance in scores was explained by treatment differences for abdominal pain , bowel symptom severity disability , depression and the mental component of the SF-36 . Conclusion Neither imipramine nor citalopram significantly improved global IBS endpoints over placebo BACKGROUND & AIMS Given the limitations of conventional therapies and restrictions imposed on newer pharmacologic agents , there is an urgent need to develop efficacious and efficient treatments that teach patients behavioral self-management skills for relieving irritable bowel syndrome ( IBS ) symptoms and associated problems . METHODS Seventy-five Rome II diagnosed IBS patients ( 86 % female ) without comorbid gastrointestinal disease were recruited from local physicians and the community and r and omized to either 2 versions of cognitive behavior therapy ( CBT ) ( 10-session , therapist-administered CBT vs 4-session , patient-administered CBT ) or a wait list control ( WLC ) that controlled for threats to internal validity . Final assessment occurred 2 weeks after the 10-week treatment phase ended . Outcome measures included adequate relief from pain and bowel symptoms , global improvement of IBS symptoms ( CGI-Improvement Scale ) , IBS symptom severity scale ( IBS SSS ) , quality of life ( IBSQOL ) , psychological distress ( Brief Symptom Inventory ) , and patient satisfaction ( Client Satisfaction Scale ) . RESULTS At week 12 , both CBT versions were significantly ( P < .05 ) superior to WLC in the percentage of participants reporting adequate relief ( eg , minimal contact CBT , 72 % ; st and ard CBT , 60.9 % ; WLC , 7.4 % ) and improvement of symptoms . CBT-treated patients reported significantly improved quality of life and IBS symptom severity but not psychological distress relative to WLC patients ( P < .0001 ) . CONCLUSIONS Data from this pilot study lend preliminary empirical support to a brief patient-administered CBT regimen capable of providing short-term relief from IBS symptoms largely unresponsive to conventional therapies Previous research from the United Kingdom has shown hypnotherapy to be effective in the treatment of irritable bowel syndrome ( IBS ) . The current study provides a systematic replication of this work in the United States . Six matched pairs of IBS patients were r and omly assigned to either a gut-directed hypnotherapy ( n=6 ) or to a symptom monitoring wait-list control condition ( n=6 ) in a multiple baseline across subjects design . Those assigned to the control condition were later crossed over to the treatment condition . Subjects were matched on concurrent psychiatric diagnoses , susceptibility to hypnosis , and various demographic features . On a composite measure of primary IBS symptoms , treatment was superior ( p=.016 ) to symptom monitoring . Results from the entire treated sample ( n=11 ; one subject was removed from analysis ) indicate that the individual symptoms of abdominal pain , constipation , and flatulence improved significantly . State and trait anxiety scores were also seen to decrease significantly . Results at the 2-month follow-up point indicated good maintenance of treatment gains . No significant correlation was found between initial susceptibility to hypnosis and treatment gain . A positive relationship was found between the incidence of psychiatric diagnosis and overall level of improvement Despite the accumulation of efficacy data for cognitive-behavioral treatment of Irritable Bowel Syndrome ( IBS ) , efforts to investigate methods for increasing access to psychological treatments are in their infancy . The current study examined the efficacy of self-administered treatment in comparison to a wait list control . Twenty-eight participants monitored gastrointestinal ( GI ) symptoms and completed measures of quality of life ( QOL ) and psychological distress prior to r and omized assignment to self-help treatment or wait list . Wait listed participants later received treatment . A 3 month post-treatment follow-up was included . Seven participants completed immediate treatment ; nine the wait list . The self-help treatment significantly decreased composite GI symptom scores in comparison to the wait list , but did not lead to significant improvements in QOL or distress . In the entire treated sample , including wait list crossovers , analyses showed significant improvement in abdominal pain , average GI symptoms , and perceived health and well-being . Interpretation of these results should be considered in the context of several limitations , including small sample size , brief baseline symptom monitoring , and high drop out rate . Despite these limitations , this study is an important first step in empirically validating low-cost , self-administered treatments as a first line psychological intervention for IBS To investigate the efficacy and safety of tegaserod , a novel 5‐HT4 receptor partial agonist , in a r and omized , double‐blind , placebo‐controlled , 12‐week treatment , multicentre study Thirty-four patients with irritable bowel syndrome were r and omly assigned to 1 of 3 treatment conditions : individualized cognitive treatment ( CT ) , self-help support group ( SG ) , or symptom-monitoring waiting-list control ( WL ) . Each of the 3 conditions lasted approximately 8 weeks . Pre- to posttreatment analyses revealed significantly greater reductions in both individual gastrointestinal ( GI ) symptoms and in a composite index for GI symptom change for the CT condition than for the SG or WL conditions . When compared with the SG and WL conditions , the CT condition also showed significant improvement on psychological measures of depression and anxiety . At 3-month follow-up , the results for the CT condition were maintained and revealed further numerical improvements Background Irritable bowel syndrome ( IBS ) is a functional disorder of the lower gastrointestinal ( GI ) tract affected by stress , which may benefit from a biopsychosocial treatment approach such as mindfulness-based stress reduction ( MBSR ) . Purpose A treatment as usual ( TAU ) wait-list controlled trial was conducted in Calgary , Canada to investigate the impact of MBSR on IBS symptoms . It was hypothesized that MBSR patients would experience greater reduction in overall IBS symptom severity and self-reported symptoms of stress relative to control patients . Method Ninety patients diagnosed with IBS using the Rome III criteria were r and omized to either an immediate MBSR program ( n = 43 ) or to wait for the next available program ( n = 47 ) . Patients completed IBS symptom severity , stress , mood , quality of life ( QOL ) , and spirituality scales pre- and post-intervention or waiting period and at 6-month follow-up . Intent-to-treat linear mixed model analyses for repeated measures were conducted , followed by completers analyses . Results While both groups exhibited a decrease in IBS symptom severity scores over time , the improvement in the MBSR group was greater than the controls and was clinical ly meaningful , with symptom severity decreasing from constantly to occasionally present . Pre- to post-intervention dropout rates of 44 and 23 % for the MBSR and control groups , respectively , were observed . At 6-month follow-up , the MBSR group maintained a clinical ly meaningful improvement in overall IBS symptoms compared to the wait-list group , who also improved marginally , result ing in no statistically significant differences between groups at follow-up . Improvements in overall mood , QOL , and spirituality were observed for both groups over time . Conclusions The results of this trial provide preliminary evidence for the feasibility and efficacy of a mindfulness intervention for the reduction of IBS symptom severity and symptoms of stress and the maintenance of these improvements at 6 months post-intervention . Attention and self-monitoring and /or anticipation of MBSR participation may account for smaller improvements observed in TAU patients BACKGROUND & AIMS Pinaverium bromide ( pinaverium ) is an antispasmodic commonly used to treat irritable bowel syndrome ( IBS ) , but there has been no convincing evidence for its effectiveness and safety . We evaluated these in a prospect i ve , double-blind , placebo-controlled trial . METHODS Patients with IBS , based on Rome III criteria , were assigned r and omly to groups given pinaverium ( 50 mg , 3 times/day ; n = 218 ) or placebo ( 3 times/day ; n = 209 ) at 4 hospitals in China , from August 2012 through December 2013 . The primary end points were reductions in abdominal pain and Bristol stool score . Secondary end points were reductions in pain and stool frequencies and abdominal discomfort and its frequency . We also evaluated changes in IBS global symptom scores and the number of adverse effects . RESULTS Based on an intention-to-treat analysis , a significantly larger proportion of patients receiving pinaverium met either of the primary end points ( 50.0 % met an end point at week 2 , and 77.5 % met an end point at week 4 ) , compared with placebo ( P < .001 ) . Pinaverium reduced at least 1 secondary end point in significantly more patients receiving pinaverium ( 76.1 % had a reduction at week 2 , and 91.7 % had a reduction at week 4 ) than placebo ( P < .001 ) . Based on symptom scores , significantly higher percentages of patients receiving pinaverium believed that their IBS symptoms improved ( 60 % ) than in the placebo group ( 34 % ; P < .001 ) ; 29 % of patients in the pinaverium group believed that their IBS symptoms stayed the same ( 29 % ) and 11 % said they worsened . Pinaverium was not associated with severe adverse effects ; common side effects included nausea ( 3.7 % ) , dizziness ( 3.2 % ) , increased blood pressure ( 2.3 % ) , and abdominal discomfort ( 2.3 % ) . CONCLUSIONS Based on a controlled trial , pinaverium reduces symptoms of IBS . It can be considered a first-line treatment for IBS . TRIAL REGISTRATION NCT01641224 ( www . Clinical Trials.gov ) We report two controlled comparisons of a previously vali date d multicomponent ( relaxation , thermal biofeedback , and cognitive therapy ) treatment for irritable bowel syndrome ( IBS ) to an ostensible attention-placebo control ( pseudo-meditation and EEG alpha suppression biofeedback ) and to a symptom-monitoring control . In Study 1 ( n = 10 per condition ) there were nonsignificant trends for the multicomponent treatment to be superior to the attention-placebo condition . In Study 2 ( n = 30 per condition ) , we found no advantage for the multicomponent treatment over the attention-placebo condition . Subjects in both treatment conditions showed significant reductions in GI symptoms , as measured by daily symptom diaries , and significant reductions in trait anxiety and depression . The GI symptom reductions held up over a 6 month follow-up . Possible explanations for the results are explored OBJECTIVES : Gut-directed hypnotherapy ( GHT ) in individual sessions is highly effective in the treatment of irritable bowel syndrome ( IBS ) . This study aim ed to assess the long-term effect of GHT in group sessions for refractory IBS . METHODS : A total of 164 patients with IBS ( Rome-III- criteria ) were screened , and 100 refractory to usual treatment were r and omized 1:1 either to supportive talks with medical treatment ( SMT ) or to SMT with GHT ( 10 weekly sessions within 12 weeks ) . The primary end point was a clinical ly important improvement on several dimensions of daily life ( assessed by IBS impact scale ) after treatment and 12-month follow-up . The secondary end point was improvement in general quality of life ( QOL ; Medical Outcome Study Short-Form-36 ) , psychological status ( Hospital Anxiety Depression Scale ) and reduction of single IBS symptoms . Analysis was by intention to treat . RESULTS : A total of 90 patients received allocated intervention . After treatment , 28 ( 60.8 % ) out of 46 GHT patients and 18 ( 40.9 % ) out of 44 SMTs improved ( absolute difference 20.0 % ; 95 % confidence interval ( CI ) : 0–40.2 % ; P=0.046 ) ; over 15 months , 54.3 % of GHT patients and 25.0 % of controls improved ( absolute difference 29.4 % ; 95 % CI 10.1–48.6 % ; P=0.004 ) . GHT with SMT improved physical and psychological well being significantly more than SMT alone ( P<0.001 ) . Gender , age , disease duration and IBS type did not have an influence on the long-term success of GHT . CONCLUSIONS : GHT improves IBS-related QOL , is superior to SMT alone , and shows a long-term effect even in refractory IBS BACKGROUND & AIMS Studies of antidepressants and psychological treatments in functional bowel disorders ( FBD ) are method ologically limited . The aim of this study was to assess the clinical efficacy and safety of cognitive-behavioral therapy ( CBT ) against education ( EDU ) and desipramine ( DES ) against placebo ( PLA ) in female patients with moderate to severe FBD ( irritable bowel syndrome , functional abdominal pain , painful constipation , and unspecified FBD ) . We also evaluated the amenability of clinical ly meaningful subgroups to these treatments . METHODS This r and omized , comparator-controlled , multicenter trial enrolled 431 adults from the University of North Carolina and the University of Toronto with moderate to severe symptoms of FBD . Participants received psychological ( CBT vs. EDU ) or antidepressant ( DES vs. PLA ) treatment for 12 weeks . Clinical , physiologic , and psychosocial assessment s were performed before and at the end of treatment . RESULTS The intention-to-treat analysis showed CBT as significantly more effective than EDU ( P = 0.0001 ; responder rate , 70 % CBT vs. 37 % EDU ; number needed to treat [ NNT ] , 3.1 ) . DES did not show significant benefit over PLA in the intention-to-treat analysis ( P = 0.16 ; responder rate , 60 % DES vs. 47 % PLA ; NNT , 8.1 ) but did show a statistically significant benefit in the per- protocol analysis ( P = 0.01 ; responder rate , 73 % DES vs. 49 % PLA ; NNT , 5.2 ) , especially when participants with nondetectable blood levels of DES were excluded ( P = 0.002 ) . Improvement was best gauged by satisfaction with treatment . Subgroup analyses showed that DES was beneficial over PLA for moderate more than severe symptoms , abuse history , no depression , and diarrhea-predominant symptoms ; CBT was beneficial over EDU for all subgroups except for depression . CONCLUSIONS For female patients with moderate to severe FBD , CBT is effective and DES may be effective when taken adequately . Certain clinical subgroups are more or less amenable to these treatments While cognitive-behavioral therapy for IBS is quite effective , the limited availability of competent therapists and lack of access to treatment remain problematic . This paper reports on a small , r and omized , controlled trial of a five week internet based cognitive-behavioral intervention for IBS with limited therapist feedback via e-mail . Fifty-four IBS patients were recruited via the internet and r and omly assigned to either immediate treatment or a wait-list control group . Thirty-one subjects completed the post-treatment assessment . 77 % of treatment completers also completed a 3-month follow-up assessment . Treatment completers experienced statistically and clinical ly significant declines in IBS symptoms and improvements in quality of life . Those gains were substantially maintained at follow-up . Treatment efficacy was partially mediated by reductions in the tendency to catastrophize the social and occupational implication s of symptoms , suggesting that catastrophizing may be an important target for treatment BACKGROUND & AIMS A r and omized clinical trial was used to test the effectiveness of an 8-session multicomponent program ( Comprehensive ) compared to a Brief ( single session ) version and Usual Care for women with irritable bowel syndrome . METHODS Menstruating women , ages 18 - 48 years , were recruited from a health maintenance organization as well as community advertisements . Psychiatric nurse practitioners delivered both programs . The primary outcomes were improved symptoms , psychological distress , health-related quality of life , and indicators of stress-related hormones . Outcome indicators were measured at 3 points : ( 1 ) immediately after the Comprehensive program or 9 weeks after entry into the Usual Care and Brief Self-Management groups , ( 2 ) at 6 months , and ( 3 ) at 12 months . RESULTS Compared to Usual Care , women in the Comprehensive program had reduced gastrointestinal symptoms , psychological distress indicators , interruptions in activities because of symptoms , and enhanced quality of life that persisted at the 12-month follow-up evaluation . Women in the Brief group also demonstrated statistically significant improvements in quality of life and smaller nonsignificant improvements in other outcome variables than observed in the Comprehensive group . There were no group differences in urine catecholamines and cortisol levels . CONCLUSIONS A comprehensive self-management program is an important therapy approach for women with irritable bowel syndrome . The Brief 1-session version is also moderately helpful for some women with IBS Objective Psychological factors are known to be associated with functional gastrointestinal disorders ( FGIDs ) including irritable bowel syndrome ( IBS ) and functional dyspepsia ( FD ) . No prospect i ve studies have evaluated whether it is the brain ( eg , via anxiety ) that drives gut symptoms , or whether gut dysfunction precipitates the central nervous system features such as anxiety . In a 12-year longitudinal , prospect i ve , population -based study , we aim ed to determine the directionality of the brain – gut mechanism in FGIDs . Design Participants ( n=1775 ) were a r and om population sample from Australia who responded to a survey on FGIDs in 1997 and agreed to be contacted for future research ; 1002 completed the 12-year follow-up survey ( response rate = 60 % ) , with 217 , 82 and 45 people meeting Rome II for new onset FGIDs , IBS and FD , respectively . Anxiety and depression were measured using the Delusions Symptom States Inventory at baseline and follow-up . Results Among people free of a FGID at baseline , higher levels of anxiety ( OR 1.11 ; 95 % CI 1.03 to 1.19 , p=0.006 ) but not depression at baseline was a significant independent predictor of developing new onset FGIDs 12 years later . Among people who did not have elevated levels of anxiety and depression at baseline , those with a FGID at baseline had significantly higher levels of anxiety and depression at follow-up ( mean difference coefficient 0.76 , p<0.001 and 0.30 , p=0.01 for anxiety and depression , respectively ) . In IBS higher levels of anxiety and depression at baseline were predictive of IBS at follow-up , while only depression was predictive of FD at follow-up . Conclusions The central nervous system and gut interact bidirectionally in FGIDs BACKGROUND & AIMS Psychotherapy and antidepressants are effective in patients with severe irritable bowel syndrome ( IBS ) , but the cost-effectiveness of either treatment in routine practice has not been established . METHODS Patients with severe IBS were r and omly allocated to receive 8 sessions of individual psychotherapy , 20 mg daily of the specific serotonin reuptake inhibitor ( SSRI ) antidepressant , paroxetine , or routine care by a gastroenterologist and general practitioner . Primary outcome measures of abdominal pain , health-related quality of life , and health care costs were determined after 3 months of treatment and 1 year later . RESULTS A total of 257 subjects ( 81 % response rate ) from 7 hospitals were recruited ; 59 of 85 patients ( 69 % ) r and omized to psychotherapy and 43 of 86 ( 50 % ) of the paroxetine group completed the full course of treatment . Both psychotherapy and paroxetine were superior to treatment as usual in improving the physical aspects of health-related quality of life ( SF-36 physical component score improvement , 5.2 [ SEM , 1.26 ] , 5.8 [ SEM , 1.0 ] , and -0.3 [ SEM , 1.17 ] ; P < 0.001 ) , but there was no difference in the psychological component . During the follow-up year , psychotherapy but not paroxetine was associated with a significant reduction in health care costs compared with treatment as usual ( psychotherapy , $ 976 [ SD , $ 984 ] ; paroxetine , $ 1252 [ SD , $ 1616 ] ; and treatment as usual , $ 1663 [ SD , $ 3177 ] ) . CONCLUSIONS For patients with severe IBS , both psychotherapy and paroxetine improve health-related quality of life at no additional cost Assessment of the physiological effects of physical and emotional stress has been hampered by a lack of suitable laboratory techniques . Since hypnosis can be used safely to induce specific emotional states of considerable intensity , we studied the effect on distal colonic motility of three hypnotically induced emotions ( excitement , anger , and happiness ) in 18 patients aged 20 - 48 years with irritable bowel syndrome . Colonic motility index was reduced by hypnosis on its own ( mean change 19.1 ; 95 % CI 0.8 , 37.3 ; p less than 0.05 ) and this change was accompanied by decreases in both pulse ( 12 ; 8 , 15 ) and respiration ( 6 ; 4 , 8) rates ( p less than 0.001 for both ) . Anger and excitement increased the colonic motility index ( 50.8 ; 29.4 , 72.2 ; and 30.4 ; 8.9 , 51.9 , respectively ; p less than 0.01 for both ) , pulse rate ( 26 ; 22 , 30 ; and 28 ; 24 , 32 ; p less than 0.001 for both ) , and respiration rate ( 14 ; 12 , 16 ; and 12 ; 10 , 14 ; p less than 0.001 for both ) . Happiness further reduced colonic motility although not significantly from that observed during hypnosis alone . Changes in motility were mainly due to alterations in rate than in amplitude of contractions . Our results indicate that hypnosis may help in the investigation of the effects of emotion on physiological functions ; this approach could be useful outside the gastrointestinal system . Our observation that hypnosis strikingly reduces fasting colonic motility may partly explain the beneficial effects of this form of therapy in functional bowel disorders BACKGROUND Irritable bowel syndrome ( IBS ) is a common gastrointestinal disorder with symptoms of abdominal pain , discomfort , and altered bowel function . Antagonists of the type 3 serotonin receptor ( 5-HT3 ) have shown promising results in the relief of IBS-associated symptoms . We aim ed to confirm these findings by doing a r and omised , placebo-controlled trial . METHODS We studied 647 female IBS patients with diarrhoea-predominant or alternating bowel patterns ( diarrhoea and constipation ) . 324 patients were assigned 1 mg alosetron and 323 placebo orally twice daily for 12 weeks , followed by a 4-week post-treatment period . Adequate relief of abdominal pain and discomfort was the primary endpoint ; secondary endpoints included improvements in urgency , stool frequency , and stool consistency . Analysis was by intention to treat . FINDINGS 79 ( 24 % ) of patients in the alosetron group and 53 ( 16 % ) in the placebo group dropped out . The difference in the drop-out rate between groups was mainly due to a greater occurrence of constipation in the alosetron group . A greater proportion of alosetron-treated patients than placebo-treated patients ( 133 [ 41 % ] vs 94 [ 29 % ] , respectively ) reported adequate relief for all 3 months of treatment ( difference 12 % [ 4.7 - 19.2 ] ) . Alosetron also significantly decreased urgency and stool frequency , and increased stool firmness . Constipation occurred in 30 % and 3 % of patients in the alosetron and placebo groups , respectively . INTERPRETATION Alosetron was well tolerated and clinical ly effective in alleviating pain and bowel-related symptoms in this population of women with IBS Autogenic training ( AT ) is a useful and comprehensive relaxation technique . However , no studies have investigated the effects of AT on irritable bowel syndrome ( IBS ) . In this study we tested the hypothesis that AT improves symptoms of IBS . Twenty-one patients with IBS were r and omly assigned to AT ( n = 11 , 5 male , 6 female ) or control therapy ( n = 10 , 5 male , 5 female ) . AT patients were trained intensively , while the control therapy consisted of discussion s about patients ’ meal habits and life styles . All patients answered a question related to adequate relief ( AR ) of IBS symptoms and four question naires : Self-induced IBS Question naire ( SIBSQ ) , Self-reported Depression Scale ( SDS ) , State-Trait Anxiety Inventory ( STAI ) , and Medical Outcome Short Form 36 Health Survey ( SF-36 ) . The proportion of AR in the last AT session in the AT group ( 9/11 , 81.8 % ) was significantly higher than that in the controls ( 3/10 , 30.0 % , Chi-square test , p = 0.048 ) . Two subscales of the SF-36 , i.e. , social functioning and bodily pain , were significantly improved in the AT group ( p < 0.05 ) as compared to the control group . Role emotional ( p = 0.051 ) and general health ( p = 0.068 ) showed a tendency for improvement in the AT group . AT may be useful in the treatment of IBS by enhancing self-control OBJECTIVE Different forms of psychotherapeutic treatments have been proven effective in irritable bowel syndrome ( IBS ) , but disorder-oriented and integrative concepts are still rare . Therefore , we implemented and evaluated an integrative group therapeutic concept within an interdisciplinary tertiary care clinic for functional gastrointestinal disorders ( FGIDs ) . AIMS present our integrative group concept , assess feasibility issues , and evaluate efficacy . METHODS A pilot- RCT with a r and omized controlled wait-listed group design was conducted . The treatment concept was a disorder-oriented multicomponent group therapy ( 12 90-min weekly sessions ) integrating interactive psychoeducation , gut-directed hypnotherapy , and open group phases . All patients received enhanced medical care and completed a short online diary as an active wait-listed control condition . INCLUSION CRITERIA refractory IBS diagnosed as somatoform autonomic dysfunction of the lower gastrointestinal tract ( SAD ) . PRIMARY OUTCOME IBS symptom severity ( IBS-SSS ) . RESULTS Of 294 patients , 220 had IBS ( ROME III ) , 144 were diagnosed as SAD ( ICD-10 ) , 51 were eligible regarding inclusion /exclusion criteria , and 30 consented to participate ( group intervention : n=16 , wait-listed control condition : n=14 ) . Only 1 patient dropped out . Intention-to-treat- analysis with repeated- measures mixed ANOVA showed that the group intervention was not significantly superior to the wait-listed control condition . Nevertheless , the calculated effect size for the between-group difference in IBS-SSS at the end of treatment ( post ) was moderate ( d=0.539 ) . CONCLUSION Our disorder-oriented integrative group intervention for IBS proved to be acceptable and feasible in an interdisciplinary tertiary care setting . There is promise in this intervention , but a larger RCT may be needed to investigate efficacy Abstract Background . Gut-directed hypnotherapy is an effective treatment in irritable bowel syndrome ( IBS ) but little is known about the mechanisms of action . In this study we aim ed to investigate the effects on gastrointestinal motility when treating IBS with gut-directed hypnotherapy . Methods . We r and omized 90 patients with IBS , refractory to st and ard management to receive gut-directed hypnotherapy 1 h/week for 12 weeks or supportive treatment for the same time period . Eighty-one subjects ( 40 hypnotherapy , 41 controls ) could be evaluated by one or more of the following investigations , both before and after the intervention : gastric emptying time , small bowel transit time , colonic transit time , and antroduodenojejunal manometry . Results . No significant differences in gastric emptying time , small bowel transit time , or colonic transit time was found when comparing the baseline and post-intervention measurements in the hypnotherapy group or in the control group . The same was true concerning the results of the antroduodenojejunal manometry . However , there was a numerical trend toward a higher number of migrating motor complexes at manometry and an accelerated gastric emptying time after hypnotherapy that did not reach statistical significance . Conclusions . In this study , we were not able to find evidence for long-st and ing effects on gastrointestinal motility as a mediator of the effects on IBS when treating the condition with gut-directed hypnotherapy . Further research to underst and the mechanism of action is needed Gut‐directed hypnotherapy can reduce IBS symptoms , but the mechanisms underlying this therapeutic effect remain unknown Objectives Irritable bowel syndrome is often treated in primary -care setting s , and it has a relatively large economic impact . Cognitive behaviour therapy ( CBT ) in addition to mebeverine has been shown to be effective in the short term , compared with treatment with mebeverine alone . This study assesses the impact that CBT in addition to mebeverine has on re source use , and its cost-effectiveness . Methods Participants were recruited from general practice s : those with ongoing symptoms were r and omly allocated either to remain just on mebeverine or to receive CBT in addition to mebeverine . Service use and lost employment were measured at baseline and at the 3-month , 6-month and 12-month follow-ups . The net-benefit approach was used for combining the data on therapy costs and symptoms . Results The mean additional cost of CBT was £ 308 . No significant impact of CBT on the use of other services or on lost employment was noted . The cost per clinical ly important reduction in symptoms was £ 220 by the end of treatment , £ 171 at the 3-month follow-up , £ 1027 at the 6-month follow-up and £ 3080 at the 12-month follow-up , for CBT in addition to mebeverine compared with mebeverine alone . Conclusions CBT in addition to mebeverine seems to have reasonable cost-effectiveness in the short-term treatment of irritable bowel syndrome , but not beyond 3 months BACKGROUND Irritable bowel syndrome ( IBS ) is commonly thought to be associated with psychologic distress . However , in some studies only persons who had sought medical care for IBS ( IBS patients ) showed an increased frequency of psychiatric symptoms , and non patients did not differ significantly from normal subjects . Our aims were 1 ) to estimate the prevalence of IBS in the population aged 18 - 45 years , 2 ) to find the proportion seeking medical care for IBS , and 3 ) to compare IBS subjects with normals , and IBS patients with IBS non patients with regard to mental health . METHODS Question naires on IBS symptoms and the General Health Question naire ( GHQ ) were mailed to 5000 r and omly sample d persons aged 18 - 45 years . The response rate was 58 % . RESULTS IBS was found in 7.4 % of the men and 13.3 % of the women . Those who had sought medical attention had more severe symptoms . The Likert mean score on the GHQ was 4.7 ( 95 % confidence interval , 4.4 - 5.0 ) points higher for the IBS group than for normals ( P < 0.001 ) . There was no difference in GHQ scores between IBS patients and non patients . CONCLUSIONS The results indicate that IBS per se is associated with more psychiatric distress , regardless of medical care-seeking . Seeking medical care is associated with more severe IBS symptoms In this study , Herbert Benson 's ( 1975 ) Relaxation Response Meditation program was tested as a possible treatment for Irritable Bowel Syndrome ( IBS ) . Participants were 16 adults who were matched into pairs based on presence of Axis I disorder , primary IBS symptoms and demographic features and r and omized to either a six week meditation condition or a six week wait list symptom monitoring condition . Thirteen participants completed treatment and follow-up . All subjects assigned to the Wait List were subsequently treated . Patients in the treatment condition were taught the meditation technique and asked to practice it twice a day for 15 minutes . Composite Primary IBS Symptom Reduction ( CPSR ) scores were calculated for each patient from end of baseline to two weeks post-treatment ( or to post wait list ) . One tailed independent sample t-tests revealed that Meditation was superior to the control ( P=0.04 ) . Significant within-subject improvements were noted for flatulence ( P=0.03 ) and belching ( P=0.02 ) by post-treatment . By three month follow-up , significant improvements in flatulence ( P<0.01 ) , belching ( P=0.02 ) , bloating ( P=0.05 ) , and diarrhea ( P=0.03 ) were shown by symptom diary . Constipation approached significance ( P=0.07 ) . Benson 's Relaxation Response Meditation appears to be a viable treatment for IBS Abstract Objective To assess the efficacy of cognitive behaviour therapy delivered in primary care for treating irritable bowel syndrome . Design R and omised controlled trial . Setting 10 general practice s in London . Participants 149 patients with moderate or severe irritable bowel syndrome resistant to the antispasmodic mebeverine . Interventions Cognitive behaviour therapy delivered by trained primary care nurses plus 270 mg mebeverine taken thrice daily compared with mebeverine treatment alone . Main outcome measures Primary measures were patients ' scores on the irritable bowel syndrome symptom severity scale . Secondary measures were scores on the work and social adjustment scale and the hospital anxiety and depression scale . Results Of 334 referred patients , 72 were r and omised to mebeverine plus cognitive behaviour therapy and 77 to mebeverine alone . Cognitive behaviour therapy had considerable initial benefit on symptom severity compared with mebeverine alone , with a mean reduction in score of 68 points ( 95 % confidence interval 103 to 33 ) , with the benefit persisting at three months and six months after therapy ( mean reductions 71 points ( 109 to 32 ) and 11 points ( 20 to 3 ) ) but not later . Cognitive behaviour therapy also showed significant benefit on the work and social adjustment scale that was still present 12 months after therapy ( mean reduction 2.8 points ( 5.2 to 0.4 ) ) , but had an inconsistent effect on the hospital anxiety and depression scale . Conclusion Cognitive behaviour therapy delivered by primary care nurses offered additional benefit over mebeverine alone up to six months , although the effect had waned by 12 months . Such therapy may be useful for certain patients with irritable bowel syndrome in primary care Thirty-five patients with irritable bowel syndrome were r and omized to receive treatment in a stress management programme or conventional therapy which included the antispasmodic Colpermin . The stress management programme involved a median of six 40-min sessions with a physiotherapist during which patients were helped to underst and the nature of their symptoms , their relationship to stress and were taught relaxation exercises . Two thirds of those in the stress management programme found the programme effective in relieving symptoms and experienced fewer attacks of less severity . This benefit was maintained for at least 12 months . Few of those given conventional management had any benefit . A stress management programme would appear to be of value for patients with irritable bowel syndrome BACKGROUND Hypnotherapy for irritable bowel syndrome ( IBS ) has been used primarily in patients with refractory symptoms in specialised departments and delivered on an individual basis . We aim ed to test the hypothesis that hypnotherapy would be more effective than educational supportive therapy , and that group hypnotherapy would be non-inferior to individual hypnotherapy for patients with IBS referred from primary and secondary care . METHODS We did a multicentre r and omised controlled trial ( IMAGINE ) in 11 hospitals in the Netherl and s. Patients with IBS , aged 18 - 65 years , who were referred from primary or secondary care were r and omly allocated ( 3:3:1 ) in blocks of six using a computer-based r and om number table procedure by staff not involved in the treatment to receive six sessions of individual or group hypnotherapy or group educational supportive therapy ( control group ) . The primary outcome was adequate relief of IBS symptoms , with responders defined as patients who reported adequate relief when asked once weekly on three or four occasions in 4 consecutive weeks . We compared hypnotherapy ( both groups ) with control in the intention-to-treat population ( excluding individuals subsequently found to be ineligible for enrolment ) , and assessed non-inferiority of group hypnotherapy versus individual hypnotherapy in the per- protocol population ( with a non-inferiority margin of 15 % ) at 3 months and 12 months . This trial is registered with IS RCT N , number IS RCT N22888906 , and is completed . FINDINGS Between May 31 , 2011 , and April 6 , 2016 , 494 patients referred for psychological treatment for IBS were assessed for eligibility , of whom 354 were r and omly allocated to the three groups : 150 to individual hypnotherapy , 150 to group hypnotherapy , and 54 to educational supportive therapy . After exclusion of individuals subsequently found to be ineligible for enrolment , 142 patients in the individual hypnotherapy group , 146 in the group hypnotherapy group , and 54 in the control group were included in the intention-to-treat population . Of these , 22 ( 15 % ) patients in the individual hypnotherapy group , 22 ( 15 % ) in the group hypnotherapy group , and 11 ( 20 % ) in the control group dropped out before or during therapy . In the intention-to-treat analysis , the adequate response rate was 40·8 % ( 95 % CI 31·7 - 50·5 ) in the individual hypnotherapy group , 33·2 % ( 24·3 - 43·5 ) in the group hypnotherapy group , and 16·7 % ( 7·6 - 32·6 ) in the control group at 3 months . At 12 months , 40·8 % ( 31·3 - 51·1 ) of patients in the individual hypnotherapy group , 49·5 % ( 38·8 - 60·0 ) of patients in the group hypnotherapy group , and 22.6 % ( 11·5 - 39·5 ) of patients in the control group reported adequate relief . Hypnotherapy was more effective than control at 3 months ( odds ratio 2·9 , 95 % CI 1·2 - 7·4 , p=0·0240 ) and 12 months ( 2·8 , 1·2 - 6·7 , p=0·0185 ) . In the per- protocol analysis , 49·9 % ( 39·2 - 60·6 ) in the individual hypnotherapy group and 42·7 % ( 32·3 - 53·8 ) in the group hypnotherapy group had adequate relief at 3 months , and 55·5 % ( 43·4 - 67·1 ) of individual and 51·7 % ( 40·2 - 63·0 ) of group hypnotherapy patients reported adequate relief at 12 months . Group hypnotherapy was therefore non-inferior to individual hypnotherapy . Eight unexpected serious adverse reactions ( six in the individual hypnotherapy group and two in the group hypnotherapy group ) were reported , most of which were cancer or inflammatory bowel disease , and were judged by the medical ethics committee as not being related to the therapy . INTERPRETATION Hypnotherapy should be considered as a possible treatment for patients with IBS in primary and secondary care . Furthermore , group therapy could allow many more patients to be treated for the same cost . FUNDING None Objective To evaluate the clinical effectiveness of two modes of cognitive – behavioural therapy ( CBT ) for IBS compared with treatment as usual ( TAU ) in refractory IBS . Design A three-arm r and omised controlled trial assessing telephone-delivered CBT ( TCBT ) , web-based CBT ( WCBT ) with minimal therapist support , and TAU . Blinding participants and therapists was not possible . Chief investigator , assessors and statisticians were blinded . Participants were adults with refractory IBS ( clinical ly significant symptoms for ≥12 months despite first-line therapies ) , recruited by letter and opportunistically from 74 general practice s and three gastroenterology centres in London and South of Engl and between May 2014 to March 2016 . Co- primary outcomes were IBS Symptom Severity Score ( IBS-SSS ) and Work and Social Adjustment Scale ( WSAS ) at 12 months . Results 558/1452 ( 38.4 % ) patients screened for eligibility were r and omised : 76 % female : 91 % white : mean age 43 years . ( 391/558 ) 70.1 % completed 12 months of follow-up . Primary outcomes : Compared with TAU ( IBS-SSS 205.6 at 12 months ) , IBS-SSS was 61.6 ( 95 % CI 33.8 to 89.5 ) points lower ( p<0.001 ) in TCBT and 35.2 ( 95 % CI 12.6 to 57.8 ) points lower ( p=0.002 ) in WCBT at 12 months . Compared with TAU ( WSAS score 10.8 at 12 months ) WSAS was 3.5 ( 95 % CI 1.9 to 5.1 ) points lower ( p<0.001 ) in TCBT and 3.0 ( 95 % CI 1.3 to 4.6 ) points lower ( p=0.001 ) in WCBT . All secondary outcomes showed significantly greater improvement ( p≤0.002 ) in CBT arms compared with TAU . There were no serious adverse reactions to treatment . Conclusion Both CBT interventions were superior to TAU up to 12 months of follow-up . Trial registration number IS RCT N44427879 Background Effective and safe treatments are needed for patients who have irritable bowel syndrome ( IBS ) with diarrhea . We conducted two phase 3 trials to assess the efficacy and safety of eluxadoline , a new oral agent with mixed opioid effects ( μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist ) , in patients with IBS with diarrhea . Methods We r and omly assigned 2427 adults who had IBS with diarrhea to eluxadoline ( at a dose of 75 mg or 100 mg ) or placebo twice daily for 26 weeks ( IBS-3002 trial ) or 52 weeks ( IBS-3001 trial ) . The primary end point was the proportion of patients who had a composite response of decrease in abdominal pain and improvement in stool consistency on the same day for at least 50 % of the days from weeks 1 through 12 and from weeks 1 through 26 . Results For weeks 1 through 12 , more patients in the eluxadoline groups ( 75 mg and 100 mg ) than in the placebo group reached the primary end point ( IBS-3001 trial , 23.9 % with the 75-mg dose and 25.1 % with the 100-mg dose vs. 17.1 % with placebo ; P=0.01 and P=0.004 , respectively ; IBS-3002 trial , 28.9 % and 29.6 % , respectively , vs. 16.2 % ; P<0.001 for both comparisons ) . For weeks 1 through 26 , the corresponding rates in IBS-3001 were 23.4 % and 29.3 % versus 19.0 % ( P=0.11 and P<0.001 , respectively ) , and the corresponding rates in IBS-3002 were 30.4 % and 32.7 % versus 20.2 % ( P=0.001 and P<0.001 , respectively ) . The most common adverse events associated with 75 mg of eluxadoline and 100 mg of eluxadoline , as compared with placebo , were nausea ( 8.1 % and 7.5 % vs. 5.1 % ) , constipation ( 7.4 % and 8.6 % vs. 2.5 % ) , and abdominal pain ( 5.8 % and 7.2 % vs. 4.1 % ) . Pancreatitis developed in 5 ( 2 in the 75-mg group and 3 in the 100-mg group ) of the 1666 patients in the safety population ( 0.3 % ) . Conclusions Eluxadoline is a new therapeutic agent that reduced symptoms of IBS with diarrhea in men and women , with sustained efficacy over 6 months in patients who received the 100-mg dose twice daily . ( Funded by Furiex Pharmaceuticals , an affiliate of Allergan ; IBS-3001 and IBS-3002 Clinical Trials.gov numbers , NCT01553591 and NCT01553747 , respectively . ) BACKGROUND & AIMS Inflammatory bowel diseases ( IBD ) are associated with high psychosocial burden and economic cost . Integrating psychological care into routine management might lead to savings . We performed a 2-year investigation of the effects of integrated psychological care in reducing healthcare use and costs . METHODS We performed a prospect i ve study of 335 adult patients treated at a hospital-based IBD service in Australia . Participants were recruited between September 2015 and August 2016 and completed screening instruments to evaluate mental health and quality of life . Data on healthcare use and costs for the previous 12 months were also collected . Patients found to be at risk for mental health issues were offered psychological intervention . Patients were followed up 12 months after screening ( between September 2016 and August 2017 ) . RESULTS A significantly higher proportion of subjects at risk for mental health issues had presented to an emergency department in the 12 months before screening ( 51/182 , 28 % ) compared to psychologically healthy subjects ( 28/152 , 18 % ; X2(1)=4.23 ; P=.040 ) . Higher levels of depression and general distress ( but not anxiety ) were related to increased odds of hospital admission ( adjusted odds ratios , 1.07 and 1.05 , respectively ) . Among the patients who accepted psychological intervention , the number who presented to emergency departments was reduced significantly in the 12 months after screening ( follow-up ) compared to the 12 months before screening ( P=.047 ) , result ing in a cost saving of AU$30,140 ( $ 20,816 USD ) . A cost-benefit analysis of the integrated psychological care model revealed a net saving of AU$84,905 ( $ 58,647 USD ) over a 2-year period . CONCLUSIONS Risk for mental health issues is associated with higher healthcare costs in people with IBD . Providing integrated psychological care to individuals at risk for mental health issues can reduce costs , particularly by decreasing visits to emergency departments . Further studies are required to determine the best care to provide to reduce costs OBJECTIVES : Linaclotide is a minimally absorbed guanylate cyclase-C agonist . The objective of this trial was to determine the efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation ( IBS-C ) . METHODS : This phase 3 , double-blind , parallel-group , placebo-controlled trial r and omized IBS-C patients to placebo or 290 μg oral linaclotide once daily in a 12-week treatment period , followed by a 4-week r and omized withdrawal ( RW ) period . There were four primary end points , the Food and Drug Administration 's ( FDA 's ) primary end point for IBS-C ( responder : improvement of ≥30 % in average daily worst abdominal pain score and increase by ≥1 complete spontaneous bowel movement ( CSBM ) from baseline ( same week ) for at least 50 % of weeks assessed ) and three other primary end points , based on improvements in abdominal pain and CSBMs for 9/12 weeks . Adverse events ( AEs ) were monitored . RESULTS : The trial evaluated 800 patients ( mean age=43.5 years , female=90.5 % , white=76.9 % ) . The FDA end point was met by 136/405 linaclotide-treated patients ( 33.6 % ) , compared with 83/395 placebo-treated patients ( 21.0 % ) ( P<0.0001 ) ( number needed to treat : 8.0 , 95 % confidence interval : 5.4 , 15.5 ) . A greater percentage of linaclotide patients , compared with placebo patients , reported for at least 6/12 treatment period weeks , a reduction of ≥30 % in abdominal pain ( 50.1 vs. 37.5 % , P=0.0003 ) and an increase of ≥1 CSBM from baseline ( 48.6 vs. 29.6 % , P<0.0001 ) . A greater percentage of linaclotide patients vs. placebo patients were also responders for the other three primary end points ( P<0.05 ) . Significantly greater improvements were seen in linaclotide vs. placebo patients for all secondary end points ( P<0.001 ) . During the RW period , patients remaining on linaclotide showed sustained improvement ; patients re-r and omized from linaclotide to placebo showed return of symptoms , but without worsening of symptoms relative to baseline . Diarrhea , the most common AE , result ed in discontinuation of 5.7 % of linaclotide and 0.3 % of placebo patients . CONCLUSIONS : Linaclotide significantly improved abdominal pain and bowel symptoms associated with IBS-C for at least 12 weeks ; there was no worsening of symptoms compared with baseline following cessation of linaclotide during the RW period |
12,053 | 17,054,246 | There is evidence that LTME results in less blood loss , quicker return to normal diet , less pain , less narcotic use and less immune response .
It seems likely that LTME is associated with longer operative time and higher costs .
Based on evidence mainly from non-r and omized studies , LTME appears to have clinical ly measurable short-term advantages in patients with primary resectable rectal cancer . | BACKGROUND Because definitive long-term results are not yet available , the oncological safety of laparoscopic surgery for treatment of rectal cancer remains controversial .
However , laparoscopic total mesorectal excision ( LTME ) for rectal cancer has been proposed to have several short-term advantages in comparison with open total mesorectal excision ( OTME ) .
OBJECTIVES To evaluate whether there are any relevant differences in safety and efficacy after elective LTME , for the resection of rectal cancer , compared with OTME . | Bladder and sexual dysfunction are recognized complications of mesorectal resection . Their incidence following laparoscopic surgery is unknown OBJECTIVE The aims of this study were to evaluate the safety and efficacy of laparoscopic abdominoperineal resection compared to conventional approach for surgical treatment of patients with distal rectal cancer presenting with incomplete response after chemoradiation . METHOD Twenty eight patients with distal rectal adenocarcinoma were r and omized to undergo surgical treatment by laparoscopic abdominoperineal resection or conventional approach and evaluated prospect ively . Thirteen underwent laparoscopic abdominoperineal resection and 15 conventional approach . RESULTS There was no significant difference ( p<0,05 ) between the two studied groups regarding : gender , age , body mass index , patients with previous abdominal surgeries , intra and post operative complications , need for blood transfusion , hospital stay after surgery , length of resected segment and pathological staging . Mean operation time was 228 minutes for the laparoscopic abdominoperineal resection versus 284 minutes for the conventional approach ( p=0.04 ) . Mean anesthesia duration was shorter ( p=0.03 ) for laparoscopic abdominoperineal resection when compared to conventional approach : 304 and 362 minutes , respectively . There was no need for conversion to open approach in this series . After a mean follow-up of 47.2 months and with the exclusion of two patients in the conventional abdominoperineal resection who presented with unsuspected synchronic metastasis during surgery , local recurrence was observed in two patients in the conventional group and in none in the laparoscopic group . CONCLUSIONS We conclude that laparoscopic abdominoperineal resection is feasible , similar to conventional approach concerning surgery duration , intra operative morbidity , blood requirements and post operative morbidity . Larger number of cases and an extended follow-up are required to adequate evaluation of oncological results for patients undergoing laparoscopic abdominoperineal resection after chemoradiation for radical treatment of distal rectal cancer PURPOSE : Traumatic manipulation of cancer specimens during laparoscopic colectomy may increase exfoliation of malignant cells into the peritoneal cavity , causing an early occurrence of peritoneal carcinomatosis or port-sites recurrence . Because of this concern , the routine use of intraperitoneal chemotherapy after laparoscopic colectomy for cancer was suggested recently . We assessed if laparoscopicvs . conventional surgery increases exfoliated malignant cells in the peritoneal cavity during resection of colorectal cancer . METHODS : In a prospect i ve , r and omized fashion , 38 colorectal cancer patients undergoing an elective , curative operation were assigned to either a conventional or laparoscopic procedure between June 1996 and May 1997 . In either group ( n=19 ) , after the abdominal cavity was entered , saline was instilled into the peritoneal cavity , and the fluid was collected ( Specimen 1 ) . During surgery , all irrigating fluids were collected ( Specimen 2 ) . Both specimens were assessed for malignancy using four techniques : filtration process ( ThinPrep ® ) , smear , cell block , and immunochemistry using Ber-EP4 . The change in the amount of tumor cells in both specimens was compared between surgical groups . A pilot study was performed to vali date the proposed cytologic method . RESULTS : In the pilot study of 20 consecutive patients with colorectal cancer , postresectional peritoneal cytology was positive in six patients , including two Stage II ( T3,N0,M0 ) patients . The pilot study also vali date d that our semiquantitative scoring system can be reliably used to assess the amount of free peritoneal cancer cells . In the main study , 16 right colectomies , 3 extended right colectomies , 17 proctosigmoidectomies , and 1 left colectomy were performed . The T and N stages were T1 ( n=13 ) , T2 ( n=5 ) , T3 ( n=8 ) , T4 ( n=11 ) ; N0 ( n=22 ) , N1 ( n=8 ) , N2 ( n=7 ) . Malignant cells were not detected in any Specimens 1 or , more importantly , in Specimens 2 in either surgical group . CONCLUSION : When performed according to strict oncologic surgical principles , laparoscopic techniques in curative colorectal cancer surgery did not have an increased risk of intraperitoneal cancer cell spillage , compared with conventional techniques . We hope that these results can decrease some of the concerns about tumors cell spillage and seeding during laparoscopy Background and aims Evidence demonstrating improved short-term outcomes with laparoscopic surgery compared with open surgery for colorectal cancer is accumulating . In addition , programmes optimising peri-operative care for major abdominal surgery are becoming widespread . Evaluating laparoscopic surgery and enhanced recovery programmes usually focuses on short-term recovery . The aim of this study was to compare recovery after laparoscopic and open surgery for colorectal cancer up to 1 year post-operatively , using a combination of self-report and observer data . Patients / Methods From January 2002 to March 2004 , 62 patients were r and omised ( 2:1 ) to receive laparoscopic ( n = 43 ) or open surgery ( n = 19 ) within an enhanced recovery programme . Functional outcomes up to 1 year were assessed using interview-administered question naires . Results / Findings Question naire and health-related quality of life data were obtained in over 85 % of patients . Patients undergoing laparoscopic surgery felt fully recovered and resumed driving more quickly than those having open surgery ( p = 0.016 and p = 0.048 respectively ) . Fifty-eight percent of patients having open surgery felt fully recovered by 12 months versus 88 % of laparoscopic patients .Interpretation/ Conclusion Within an enhanced recovery programme , patients undergoing laparoscopic surgery recovered more quickly than after open resection . Both approaches however , were associated with slow recovery despite a relatively short hospital stay Purpose This study was design ed to evaluate the impact of laparoscopic rectal resection on short-term postoperative morbidity and costs . Methods A total of 168 patients with rectal cancer were r and omly assigned to laparoscopic ( n = 83 ) or open ( n = 85 ) resection . Outcome parameters were : postoperative morbidity , length of hospital stay , quality of life , long-term survival , and local recurrences . The mean follow-up period was 53.6 months . Cost-benefit analysis was based on hospital costs . Results Operative time was 53 minutes longer in the laparoscopic group ( P < 0.0001 ) . Postoperative morbidity rate was 28.9 percent in the laparoscopic vs. 40 percent in the open group ( P = 0.18 ) . The mean length of hospital stay was 10 ( 4.9 ) days in the laparoscopic group and 13.6 ( 10 ) days in the open group ( P = 0.004 ) . Local recurrence rate and five-year survival were similar in both groups ; however , the limited number of patients does not allow firm conclusions . Quality of life was better in the laparoscopic group only in the first year after surgery ( P < 0.0001 ) . The additional charge in the laparoscopic group was $ 1,748 per patient r and omized ( $ 1,194 the result of surgical instruments and $ 554 the result of longer operative time ) . The saving in the laparoscopic group was $ 1,396 per patient r and omized ( $ 647 the result of shorter length of hospital stay and $ 749 the result of the lower cost of postoperative complications ) . The net balance result ed in $ 351 extra cost per patient r and omly allocated to the laparoscopic group . Conclusions Short-term postoperative morbidity was similar in the two groups . Laparoscopic resection reduced length of hospital stay , improved first-year quality of life , and slightly increased hospital costs A r and omized controlled trial was started in Japan to evaluate whether laparoscopic surgery is the optimal treatment for colorectal cancer . Patients with T3 or deeper carcinoma in the colorectum without transverse and descending colons are pre-operatively r and omized to either open or laparoscopic colorectal resection . Surgeons in 24 specialized institutions will recruit 818 patients . The primary end-point is overall survival . Secondary end-points are relapse-free survival , short-term clinical outcome , adverse events , the proportion of conversion from laparoscopic surgery to open surgery , and the proportion of completion of laparoscopic surgery Laparoscopic surgery is believed to produce an attenuated metabolic stress response and to have a less dampening effect on the immune response than open surgery . To date , the effect has not been studied in a r and omized clinical trial of colorectal cancer PURPOSE : The aim of this study was to compare the safety and efficacy of laparoscopic abdominoperineal resection and open abdominoperineal resection for cancer . METHODS : Records of 194 patients who underwent laparoscopic abdominoperineal resection ( 42 patients ) or open abdominoperineal resection ( 152 patients ) at three institutions between 1991 and 1997 were review ed . Follow-up was through office charts , American College of Surgeons cancer registry , or telephone contact . Tumors included ( laparoscopic abdominoperineal resection and open abdominoperineal resection , respectively ) adenocarcinoma ( 86 and 92 percent ) , squamous ( 12 and 7 percent ) , and gastrointestinal stromal ( 2 and 1.4 percent ) types ; Stages I ( 17 and 26 percent ) , II ( 24 and 33 percent ) , III ( 43 and 32 percent ) , and IV ( 14 and 9 percent ) ; and those with invasion of pelvic structures ( 14 and 16 percent ) . RESULTS : Laparoscopic abdominoperineal resection was converted to open abdominoperineal resection in 21 percent because of vessel injury ( 33 percent ) , poor exposure ( 22 percent ) , adhesions ( 22 percent ) , inguinal hernia ( 11 percent ) , or radiation fibrosis ( 11 percent ) . Perineal infections occurred more often in the laparoscopic abdominoperineal resection group ( 24vs . 8 percent;P=0.02 ) . Late stoma complications were similar . Mean hospital stay was shorter after laparoscopic abdominoperineal resection ( 7vs . 12 days ) . Radial margins were positive in 12 percent of laparoscopic abdominoperineal resection and 12.5 percent of open abdominoperineal resection specimens . Tumor recurrence was similar for both local ( 19 and 14 percent ) and distant ( 38 and 26 percent ) recurrence . Survival rates were similar by Kaplan-Meier curves , with median follow-up of 19 and 24 months , respectively ( P=0.22 ; log rank ) . CONCLUSION : Laparoscopic abdominoperineal resection can be performed safely and results in a shorter hospital stay . A r and omized , prospect i ve trial is needed to determine the long-term outcome of cancer treatment The short-term clinical results of the CLASICC trial indicated that clinical outcomes were similar between laparoscopic and open approaches . This study presents the short-term ( 3 month ) cost analysis undertaken on a subset of patients entered into the CLASICC trial ( 682 of 794 patients ) . As expected the costs associated with the operation were higher in the 452 patients r and omised to laparoscopic surgery ( lap ) compared with the 230 r and omised to open procedure ( open ) , £ 1703 vs £ 1386 . This was partially offset by the other hospital ( nontheatre ) costs , which were lower in the lap group ( £ 2930 vs £ 3176 ) . The average cost to individuals for reoperations was higher in the lap group ( £ 762 vs £ 553 ) . Overall costs were slightly higher in the lap group ( £ 6899 vs £ 6631 ) , with mean difference of £ 268 ( 95%CI −689 to 1457 ) . Sensitivity analysis made little difference to these results . The cost of rectal surgery was higher than for colon , for lap ( £ 8259 vs £ 5586 ) and open procedures ( £ 7820 vs £ 5503 ) . The short-term cost analysis for the CLASICC trial indicates that the costs of either laparoscopic or open procedure were similar , lap surgery costing marginally more on average than open surgery Background : Laparoscopic resection of the rectum is still under scrutiny for its adequacy of oncological clearance . Aim : To assess lymph node yield after laparoscopic total mesorectal excision ( TME ) for rectal cancer as compared to the open approach . Methods : 74 patients with middle and low rectal cancer were prospect ively r and omized in two groups . Group A included 39 patients who had an open TME ( 35 with low anterior resection of the rectum ( LARR ) and 4 with abdominoperineal resection of the rectum ( APR ) ) . In group B , there were 34 patients who had a laparoscopic TME ( 27 with LARR and 7 with APR ) . 10 of the LARR patients in group A and 14 of the LARR patients in group B had a defunctioning ileostomy . All operations were performed by one surgeon or under his supervision . Results : Gender and age distribution were similar for both groups ( group A : 23 males ; mean age 69 ( 41–85 ) ; group B : 20 males ; mean age 72 ( 31–84 ) ) . The mean distance of the tumor from the dentate line was 7.6 cm ( 1–12 cm ) for group A and 6.1 cm ( 1–12 cm ) for group B. Anastomosis was formed at a mean distance of 5.5 cm ( 1.5–8.5 cm ) from the dentate line in group A and 3.5 cm ( 1–4.5 cm ) in group B. At histology , in group A there were 5 T4 tumors , 9 T3 , 10 T3 + ( < 1 mm distance from the circumferential resection margin ) , 13 T2 and 2 T1 . In group B , there were 3 T4 tumors , 14 T3 , 8 T3 + , 7 T2 and 2 T1 . Differences between groups were not significant . The mean number of lymph nodes retrieved in group A specimens was 19.2 ( 5–45 ) and in group B 19.2 ( 8–41 ) ( p = 0.2 ) . In group A , 3.9 ( 1–9 ) regional , 13.9 ( 3–34 ) intermediate and 1.5 ( 1–3 ) apical lymph nodes were retrieved . The respective values in group B were 3.7 ( 3–7 ) , 14.4 ( 4–33 ) and 1.3 ( 1–3 ) . Differences between groups were not significant . Also , the incidence of lymph node involvement by the tumor was not significantly different between groups ( group A : 23 ; group B : 19 ) . Conclusions : Laparoscopic resection of the rectum can achieve similar lymph node clearance to the open approach . Also , distribution of the lymph nodes along the resected specimens is similar between the two approaches Background The Laparoscopic approach has been applied to colorectal surgery for many years ; however , there are only a few reports on laparoscopic low and ultralow anterior resection with construction of coloanal anastomosis . This study compares open versus laparoscopic low and ultralow anterior resections , assesses the feasibility and efficacy of the laparoscopic approach of total mesorectal excision ( TME ) with anal sphincter preservation ( ASP ) , and analyzes the short-term results of patients with low rectal cancer . Methods We analyzed our experience via a prospect i ve , r and omized control trail . From June 2001 to September 2002 , 171 patients with low rectal cancer underwent TME with ASP , 82 by the laparoscopic procedure and 89 by the open technique . The lowest margin of tumors was below peritoneal reflection and 1.5–8 cm above the dentate line ( 1.5–4.9 cm in 104 cases and 5–8 cm in 67 cases ) . The grouping was r and omized . Results Results of operation , postoperative recovery , and short-term oncological follow-up were compared between 82 laparoscopic procedures and 89 controls who underwent open surgery during the same period . In the laparoscopic group , 30 patients in whom low anterior resection was performed had the anastomosis below peritoneal reflection and more than 2 cm above the dentate line , 27 patients in whom ultralow anterior resection was performed had anastomotic height within 2 cm of the dentate line , and 25 patients in whom coloanal anastomosis was performed had the anastomosis at or below the dentate line . In the open group , the numbers were 35 , 27 , and 27 , respectively . There was no statistical difference in operation time , administration of parenteral analgesics , start of food intake , and mortality rate between the two groups . However , blood loss was less , bowel function recovered earlier , and hospitalization time was shorter in the laparoscopic group . Conclusion Totally laparoscopic TME with ASP is feasible , and it is a minimally invasive technique with the benefits of much less blood loss during operation , earlier return of bowel function , and shorter hospitalization Background This study aim ed to compare quality of life ( QOL ) , functional outcome , body image , and cosmesis after h and -assisted laparoscopic ( LRP ) versus open restorative proctocolectomy ( ORP ) . The potential long-term advantages of LRP over ORP remain to be determined . The most likely advantage of LRP is the superior cosmetic result . It is , however , unclear whether the size and location of incisions affect body image and QOL . Methods In a previously conducted r and omized trial comparing LRP with ORP , 60 patients were prospect ively evaluated . The primary end points were body image and cosmesis . The secondary end points were morbidity , QOL , and functional outcome . A body image question naire was used to evaluate body image and cosmesis . The Short Form-36 Health Survey and the Gastrointestinal Quality of Life Inventory were used to assess QOL . Body image and QOL also were assessed preoperatively . Results A total of 53 patients completed the QOL and functional outcome question naires . There were no differences in functional outcome , morbidity , or QOL between LRP and ORP . At a median of 2.7 years after surgery , 46 patients returned the question naires regarding body image , cosmesis , and morbidity . The body image and cosmesis scores of female patients were significantly higher in the LRP group than in the ORP group ( body image , 17.4 vs 14.9 ; cosmesis , 19.1 vs 13.0 , respectively ) . The female patients in the ORP group had significantly lower body image scores than the male patients ( 14.9 vs 18.3 ) . Conclusions This study is the first to show that ORP has a negative impact on body image and cosmesis as compared with LRP . Functional outcome , QOL , and morbidity are similar for the two approaches . The advantages of a long-lasting improved body image and cosmesis for this relatively young patient population may compensate for the longer operating times and higher costs , particularly for women BACKGROUND Although laparoscopic resection of colorectal carcinoma improves post-operative recovery , long-term survival and disease control are the determining factors for its application . We aim ed to test the null hypothesis that there was no difference in survival after laparoscopic and open resection for rectosigmoid cancer . METHODS From Sept 21 , 1993 , to Oct 21 , 2002 , 403 patients with rectosigmoid carcinoma were r and omised to receive either laparoscopic assisted ( n=203 ) or conventional open ( n=200 ) resection of the tumour . Survival and disease-free interval were the main endpoints . Patients were last followed-up in March , 2003 . Perioperative data were recorded and direct cost of operation estimated . Data were analysed by intention to treat . FINDINGS The demographic data of the two groups were similar . After curative resection , the probabilities of survival at 5 years of the laparoscopic and open resection groups were 76.1 % ( SE 3.7 % ) and 72.9 % ( 4.0 % ) respectively . The probabilities of being disease free at 5 years were 75.3 % ( 3.7 % ) and 78.3 % ( 3.7 % ) , respectively . The operative time of the laparoscopic group was significantly longer , whereas postoperative recovery was significantly better than for the open resection group , but these benefits were at the expense of higher direct cost . The distal margin , the number of lymph nodes found in the resected specimen , overall morbidity and operative mortality did not differ between groups . INTERPRETATION Laparoscopic resection of rectosigmoid carcinoma does not jeopardise survival and disease control of patients . The justification for adoption of laparoscopic technique would depend on the perceived value of its effectiveness in improving short-term post-operative outcomes Bladder and sexual dysfunction , secondary to pelvic nerve injury , are recognized complications of rectal resection . This study investigated the frequency of these complications following laparoscopically assisted and conventional open mesorectal resection for cancer BACKGROUND Uncontrolled studies using laparoscopic techniques in colorectal surgery have not demonstrated clear advantages to these procedures compared with conventional ones , and surgeons are concerned about unusual early recurrences reported after laparoscopic colorectal cancer surgery . STUDY DESIGN We conducted a prospect i ve , r and omized trial in one surgical department comparing laparoscopic ( LAP ) and conventional ( CON ) techniques in 109 patients undergoing bowel resection for colorectal cancers or polyps . Postoperatively , all patients underwent measurement of pulmonary function tests every 12 hours , and were treated identically on a highly controlled protocol with regard to analgesic administration , feeding , and postoperative care . RESULTS Of the 55 patients assigned to LAP and 54 to the CON group , there were 42 and 38 with cancer , respectively ( the other patients had large adenomas ) . Overall recovery of 80 % of forced expiratory volume in 1 second and forced vital capacity was a median of 3 days for LAP and 6.0 days for CON ( p = 0.01 ) . LAP patients used significantly less morphine than CON patients up to the second day after surgery ( 0.78 + /- 0.32 versus 0.92 + /- 0.34 mg/kg per day , p = 0.02 ) . Flatus returned a median of 3.0 days after LAP versus 4.0 days after CON surgery ( p = 0.006 ) . Tumor margins were clear in all patients . After a median followup of 1.5 years ( LAP ) and 1.7 years ( CON ) , there were no port site recurrences in the LAP group . Seven cancer-related deaths have occurred ( three in the LAP group , four in the CON group ) . CONCLUSIONS Within this prospect i ve , r and omized trial , laparoscopic techniques were as safe as conventional surgical techniques and offered a faster recovery of pulmonary and gastrointestinal function compared with conventional surgery for selected patients undergoing large bowel resection for cancer or polyps . There were no apparent shortterm oncologic disadvantages . Longer followup is needed to fully assess oncologic outcomes Background : Laparoscopically assisted resection of colorectal carcinoma is technically feasible and minimally invasive . Postoperative immunosuppression also may be reduced . This study compared the lymphocyte subsets and natural killer ( NK ) cell cytotoxicity in patients after laparoscopically assisted resection with those after open resection of rectosigmoid carcinoma . Methods : In this study , 40 patients with rectosigmoid carcinoma , but no evidence of metastasis , were r and omized to receive either laparoscopically assisted or conventional open resection of the tumor . Blood was collected before the operation , then 24 h , 72 h , and 8 days after the operation for studies of lymphocyte subsets and NK cell cytotoxicity . Results : The lymphocyte subsets and NK cell cytotoxicity of both groups showed typical suppression after surgery . The suppression of T cell activation and NK-like T cells was significantly less after laparoscopically assisted resection than in after open resection , whereas the difference in other lymphocyte subsets and NK cell cytotoxicity was not significant . Conclusion : This study showed that some cellular components of the immune system are less suppressed after laparoscopically assisted than after conventional open resection of rectosigmoid carcinoma . This may have implication s for tumor recurrence and long-term patient survival Abstract Background : Conventional colorectal resections are associated with severe postoperative pain and prolonged fatigue . The laparoscopic approach to colorectal tumors may result in less pain as well as less fatigue , and may improve postoperative recovery after colorectal resections . Methods : Sixty patients were included into a prospect i ve r and omized trial to determine the influence of laparoscopic ( n= 30 ) or conventional ( n= 30 ) resection of colorectal tumors on postoperative pain and fatigue . Major endpoints of the study were dose of morphine sulfate during patient-controlled analgesia ( PCA ) , visual analog scale for pain while coughing ( VASC ) , and visual analogue scale for fatigue ( VASF ) . Efficacy of pain medication was assessed by visual analogue score at rest ( VASR ) . Results : Preoperative age , sex , stage , and localization of tumors were comparable in both groups . The PCA dose of morphine given immediately after surgery until postoperative day 4 was higher in the conventional group ( median , 1.37 mg/kg ; 5–95 percentile 0.71–2.46 mg/kg ) than the laparoscopic group ( 0.78 mg/kg ; 0.24–2.38 mg/kg , p < 0.01 ) . Postoperative VASR was comparable between both groups , but VASC was higher from the first to the seventh postoperative day ( p < 0.01 ) . Postoperative fatigue was higher after conventional than after laparoscopic surgery from the second to the seventh day ( p < 0.05 ) . Conclusions : This study confirms that analgetic requirements are lower and pain is less intense after laparoscopic than after conventional colorectal resection . Patients also experience less fatigue after minimal invasive surgery . Because of these differences , the duration of recovery is shortened , and the postoperative quality of life is improved after laparoscopic colorectal resections PURPOSE The aim of the current study is to report the long-term outcomes after laparoscopic-assisted surgery compared with conventional open surgery within the context of the UK MRC CLASICC trial . Results from r and omized trials have indicated that laparoscopic surgery for colon cancer is as effective as open surgery in the short term . Few data are available on rectal cancer , and long-term data on survival and recurrence are now required . METHODS The United Kingdom Medical Research Council Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer ( UK MRC CLASICC ; clinical trials number IS RCT N 74883561 ) trial study comparing conventional versus laparoscopic-assisted surgery in patients with cancer of the colon and rectum . The r and omization ratio was 2:1 in favor of laparoscopic surgery . Long-term outcomes ( 3-year overall survival [ OS ] , disease-free survival [ DFS ] , local recurrence , and quality of life [ QoL ] ) have now been determined on an intention-to-treat basis . RESULTS Seven hundred ninety-four patients were recruited ( 526 laparoscopic and 268 open ) . Overall , there were no differences in the long-term outcomes . The differences in survival rates were OS of 1.8 % ( 95 % CI , -5.2 % to 8.8 % ; P = .55 ) , DFS of -1.4 % ( 95 % CI , -9.5 % to 6.7 % ; P = .70 ) , local recurrence of -0.8 % ( 95 % CI , -5.7 % to 4.2 % ; P = .76 ) , and QoL ( P > .01 for all scales ) . Higher positivity of the circumferential resection margin was reported after laparoscopic anterior resection ( AR ) , but it did not translate into an increased incidence of local recurrence . CONCLUSION Successful laparoscopic-assisted surgery for colon cancer is as effective as open surgery in terms of oncological outcomes and preservation of QoL. Long-term outcomes for patients with rectal cancer were similar in those undergoing abdominoperineal resection and AR , and support the continued use of laparoscopic surgery in these patients OBJECTIVE To compare the systemic cytokine response in patients after laparoscopic-assisted resection with those after open resection of rectosigmoid carcinoma . SUMMARY BACKGROUND DATA Laparoscopic resection of colorectal carcinoma is technically feasible , but objective evidence of its benefit is scarce . Systemic cytokines are accepted as markers of postoperative tissue trauma and mediators of the host immune response . METHODS Thirty-four patients with rectosigmoid carcinoma , without evidence of metastatic disease and suitable for laparoscopic resection , were r and omized to undergo either laparoscopic ( n = 17 ) or conventional open ( n = 17 ) resection of the tumor . Clinical parameters were recorded . Sera were collected before surgery and at appropriate time points afterward and assayed for interleukin-1beta , tumor necrosis factor-alpha , interleukin-6 , and C-reactive protein . The primary end points were the cytokine and C-reactive protein levels . Data were analyzed by intention to treat . RESULTS The demographic data of the two groups were comparable . The clinical outcome of both groups was satisfactory , with no surgical deaths and a reasonable complication rate . Both interleukin-1beta and interleukin-6 levels peaked 2 hours after surgery , with the responses in the laparoscopic group significantly less than those in the open group . C-reactive protein levels peaked at 48 hours , and the difference was also statistically significant . Levels of tumor necrosis factor-alpha were not elevated after surgery , and there was no difference between the groups . CONCLUSIONS Tissue trauma , as reflected by systemic cytokine response , was less after laparoscopic resection than after open resection of rectosigmoid carcinoma . The difference in the systemic cytokine response may have implication s on the long-term survival PURPOSE This study was design ed to evaluate long-term complications , quality of life , and survival rate in a series of colorectal cancer patients r and omized to laparoscopic or open surgery . METHODS A total of 391 patients with colorectal cancer were r and omly assigned to laparoscopic ( n = 190 ) or open ( n = 201 ) resection . Long-term follow-up was performed every six months by office visits . Quality of life was assessed at 12 , 24 , and 48 months after surgery by a modified version of Short Form 36 Health Survey question naire . All patients were analyzed on an intention-to-treat basis . RESULTS Eight ( 4.2 percent ) laparoscopic group patients needed conversion to open surgery . Overall long-term morbidity rate was 6.8 percent ( 13/190 ) in the laparoscopic vs. 14.9 percent ( 30/201 ) in the open group ( P = 0.018 ) . Overall quality of life was significantly better in the laparoscopic group in the first 12 months after surgery , whereas at 24 months , patients of the laparoscopic group reported a significant advantage only in social functioning . No difference was found in both overall and disease-free survival rates by comparing laparoscopic vs. open group . CONCLUSIONS Laparoscopic colorectal resection was associated with a lower incidence of long-term complications and a better quality of life in the first 12 months after surgery compared with open surgery . No difference between groups was found in overall and disease-free survival rates Objective The primary endpoint was to compare the impact of laparoscopic and open colorectal surgery on 30-day postoperative morbidity . Lymphocyte proliferation to mitogens and gut oxygen tension were surrogate endpoints . Summary Background Data Evidence -based proof of the effect of laparoscopic colorectal surgery on immunometabolic response and clinical ly relevant outcome variables is scanty . Further r and omized trials are desirable before proposing laparoscopy as a superior technique . Methods Two hundred sixty-nine patients with colorectal disease were r and omly assigned to laparoscopic ( n = 136 ) or open ( n = 133 ) colorectal resection . Four trained members of the surgical staff who were not involved in the study registered postoperative complications . Lymphocyte proliferation to C and ida albicans and phytohemagglutinin was evaluated before and 3 and 15 days after surgery . Operative gut oxygen tension was monitored continuously by a polarographic microprobe . Results In the laparoscopic group the conversion rate was 5.1 % . The overall morbidity rate was 20.6 % in the laparoscopic group and 38.3 % in the open group . Postoperative infections occurred in 15 of the 136 patients in the laparoscopic group and 31 of the 133 patients in the open group . The mean length of hospital stay was 10.4 ± 2.9 days in the laparoscopic group and 12.5 ± 4.1 days in the open group . On postoperative day 3 , lymphocyte proliferation was impaired in both groups . Fifteen days after surgery , the proliferation index returned to baseline values only in the laparoscopic group . Intraoperative gut oxygen tension was higher in the laparoscopic than in the open group . Conclusions Laparoscopic colorectal surgery result ed in a significant reduction of 30-day postoperative morbidity . Lymphocyte proliferation and gut oxygen tension were better preserved in the laparoscopic group than in the open group Purpose : Oncologic concerns from high wound recurrence rates prompted a multi-institutional r and omized trial to test the hypothesis that disease-free and overall survival are equivalent , regardless of whether patients receive laparoscopic-assisted or open colectomy . Methods : Eight hundred seventy-two patients with curable colon cancer were r and omly assigned to undergo laparoscopic-assisted or open colectomy at 1 of 48 institutions by 1 of 66 credentialed surgeons . Patients were followed for 8 years , with 5-year data on 90 % of patients . The primary end point was time to recurrence , tested using a noninferiority trial design . Secondary endpoints included overall survival and disease-free survival . ( Kaplan – Meier ) Results : As of March 1 , 2007 , 170 patients have recurred and 252 have died . Patients have been followed a median of 7 years ( range 5–10 years ) . Disease-free 5-year survival ( Open 68.4 % , Laparoscopic 69.2 % , P = 0.94 ) and overall 5-year survival ( Open 74.6 % , Laparoscopic 76.4 % , P = 0.93 ) are similar for the 2 groups . Overall recurrence rates were similar for the 2 groups ( Open 21.8 % , Laparoscopic 19.4 % , P = 0.25 ) . These recurrences were distributed similarly between the 2 treatment groups . Sites of first recurrence were distributed similarly between the treatment arms ( Open : wound 0.5 % , liver 5.8 % , lung 4.6 % , other 8.4 % ; Laparoscopic : wound 0.9 % , liver 5.5 % , lung 4.6 % , other 6.1 % ) . Conclusion : Laparoscopic colectomy for curable colon cancer is not inferior to open surgery based on long-term oncologic endpoints from a prospect i ve r and omized trial Background Laparoscopic resection of colonic cancer has been shown to improve postoperative recovery without jeopardizing tumor clearance and survival , but information on low rectal cancer is scarce . The aim of this r and omized trial was to compare postoperative recovery between laparoscopic-assisted versus open abdominoperineal resection ( APR ) in patients with low rectal cancer . Recurrence and survival data were also recorded and compared between the two groups . Methods Between September 1994 and February 2005 , 99 patients with low rectal cancer were r and omized to receive either laparoscopic-assisted ( 51 patients ) or conventional open ( 48 patients ) APR . The median follow-up time of living patients was about 90 months for both groups . The primary and secondary endpoints of the study were postoperative recovery and survival , respectively . Data were analyzed by intention-to-treat principle . Results The demographic data of the two groups were comparable . Postoperative recovery was better after laparoscopic surgery , with earlier return of bowel function ( P < .001 ) and mobilization ( P = .005 ) , and less analgesic requirement ( P = .007 ) . This was at the expense of longer operative time and higher direct cost . There were no differences in morbidity and operative mortality rates between the two groups . After curative resection , the probabilities of survival at 5 years of the laparoscopic-assisted and open groups were 75.2 % and 76.5 % respectively ( P = .20 ) . The respective probabilities of being disease-free were 78.1 % and 73.6 % ( P = .55 ) . Conclusions Laparoscopic-assisted APR improves postoperative recovery and seemingly does not jeopardize survival when compared with open surgery for low rectal cancer . A larger sample size is needed to fully assess oncological outcomes Recently reported r and omized controlled trials demonstrated that laparoscopic surgery ( LS ) was comparable or superior to open surgery with regard to the long-term outcome for colon and rectosigmoidal carcinoma ; however , controversy persists with regard to the appropriateness of LS for patients with rectal carcinoma . To examine the technical and oncological feasibility of LS for rectal carcinoma , a phase II trial was started in patients with a preoperative diagnosis of Stage 0/I rectal carcinoma , under the direction of the Japan Society of Laparoscopic Colorectal Surgery . Surgeons in 39 specialized institutions will recruit 350 patients . The primary end-point in the first stage is the anastomotic leakage rate by double-stapling technique and that in the second stage is overall survival . Secondary end-points are relapse-free survival , short-term clinical outcome , adverse events , the rate of histologically curative operation , the proportion of completion of LS and the conversion rate BACKGROUND Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale r and omised trials to support its use . We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes . METHODS Between July , 1996 , and July , 2002 , we undertook a multicentre , r and omised clinical trial in 794 patients with colorectal cancer from 27 UK centres . Patients were allocated to receive laparoscopic-assisted ( n=526 ) or open surgery ( n=268 ) . Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins , proportion of Dukes ' C2 tumours , and in-hospital mortality . Analysis was by intention to treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N74883561 . FINDINGS Six patients ( two [ open ] , four [ laparoscopic ] ) had no surgery , and 23 had missing surgical data ( nine , 14 ) . 253 and 484 patients actually received open and laparoscopic-assisted treatment , respectively . 143 ( 29 % ) patients underwent conversion from laparoscopic to open surgery . Proportion of Dukes ' C2 tumours did not differ between treatments ( 18 [ 7 % ] patients , open vs 34 [ 6 % ] , laparoscopic ; difference -0.3 % , 95 % CI -3.9 to 3.4 % , p=0.89 ) , and neither did in-hospital mortality ( 13 [ 5 % ] vs 21 [ 4 % ] ; -0.9 % , -3.9 to 2.2 % , p=0.57 ) . Apart from patients undergoing laparoscopic anterior resection for rectal cancer , rates of positive resection margins were similar between treatment groups . Patients with converted treatment had raised complication rates . INTERPRETATION Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes . However , impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use Background Recent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs . Both focus on a faster recovery and shorter hospital stay . The r and omized controlled multicenter LAFA-trial ( LAparoscopy and /or FAst track multimodal management versus st and ard care ) was conceived to determine whether laparoscopic surgery , fast track perioperative care or a combination of both is to be preferred over open surgery with st and ard care in patients having segmental colectomy for malignant disease . Methods / design The LAFA-trial is a double blinded , multicenter trial with a 2 × 2 balanced factorial design . Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be r and omized to either open or laparoscopic colectomy , and to either st and ard care or the fast track program . This factorial design produces four treatment groups ; open colectomy with st and ard care ( a ) , open colectomy with fast track program ( b ) , laparoscopic colectomy with st and ard care ( c ) , and laparoscopic surgery with fast track program ( d ) . Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days . Secondary outcome parameters are quality of life two and four weeks after surgery , overall hospital costs , morbidity , patient satisfaction and readmission rate . Based on a mean postoperative hospital stay of 9 + /- 2.5 days a group size of 400 patients ( 100 each arm ) can reliably detect a minimum difference of 1 day between the four arms ( alfa = 0.95 , beta = 0.8 ) . With 100 patients in each arm a difference of 10 % in subscales of the Short Form 36 ( SF-36 ) question naire and social functioning can be detected . Discussion The LAFA-trial is a r and omized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease |
12,054 | 26,984,189 | The results of this review will provide new information regarding the question whether eHealth interventions are an effective intervention vehicle for PA promotion in this population . | Background It is known that regular physical activity ( PA ) is associated with improvements in physical , psychological , cognitive , and functional health outcomes .
The World Health Organization recommends 150 min of moderate exercise per week for older adults to achieve these health benefits .
However , only 20–60 % of adults aged 60 years and above currently meet these recommendations for exercise .
The widespread use of the internet and mobile phones among older adults may open new opportunities to promote PA in this population .
Findings of previous review s suggest that eHealth interventions are effective in promoting PA in adults of various ages .
However , to date , none of these review s have provided a differentiated picture of engagement in such interventions and effects on PA among older adults .
Also , we are unaware of any studies comparing effects of participation in eHealth vs. traditional paper- and -pencil interventions on PA in this population .
The aim of this systematic review and meta- analysis is to compare the effectiveness of eHealth interventions promoting PA in older adults aged 55 years and above with either a non-eHealth PA intervention or a group that is not exposed to any intervention .
Discussion The proposed systematic review will be the first review that compares the effectiveness of eHealth interventions promoting PA in older adults aged 55 years and above with control groups exposed to a non-eHealth intervention or to no intervention . | Mobile devices are a promising channel for delivering just-in-time guidance and support for improving key daily health behaviors . Despite an explosion of mobile phone applications aim ed at physical activity and other health behaviors , few have been based on theoretically derived constructs and empirical evidence . Eighty adults ages 45 years and older who were insufficiently physically active , engaged in prolonged daily sitting , and were new to smartphone technology , participated in iterative design development and feasibility testing of three daily activity smartphone applications based on motivational frames drawn from behavioral science theory and evidence . An “ analytically ” framed custom application focused on personalized goal setting , self-monitoring , and active problem solving around barriers to behavior change . A “ socially ” framed custom application focused on social comparisons , norms , and support . An “ affectively ” framed custom application focused on operant conditioning principles of reinforcement scheduling and emotional transference to an avatar , whose movements and behaviors reflected the physical activity and sedentary levels of the user . To explore the applications ' initial efficacy in changing regular physical activity and leisure-time sitting , behavioral changes were assessed across eight weeks in 68 participants using the CHAMPS physical activity question naire and the Australian sedentary behavior question naire . User acceptability of and satisfaction with the applications was explored via a post-intervention user survey . The results indicated that the three applications were sufficiently robust to significantly improve regular moderate-to-vigorous intensity physical activity and decrease leisure-time sitting during the 8-week behavioral adoption period . Acceptability of the applications was confirmed in the post-intervention surveys for this sample of midlife and older adults new to smartphone technology . Preliminary data exploring sustained use of the applications across a longer time period yielded promising results . The results support further systematic investigation of the efficacy of the applications for changing these key health-promoting behaviors Background Reaction time , coordination , and cognition performance typically diminish in older adults , which may lead to gait impairments , falls , and injuries . Regular strength – balance exercises are highly recommended to reduce this problem and to improve health , well-being , and independence in old age . However , many older people face a lack of motivation in addition to other strong barriers to exercise . We developed ActiveLifestyle , an information technology (IT)-based system for active and healthy aging aim ing at improving balance and strength . ActiveLifestyle is a training app that runs on a tablet and assists , monitors , and motivates older people to follow personalized training plans autonomously at home . Objective The objectives were to ( 1 ) investigate which IT-mediated motivation strategies increase adherence to physical exercise training plans in older people , ( 2 ) assess the impact of ActiveLifestyle on physical activity behavior change , and ( 3 ) demonstrate the effectiveness of the ActiveLifestyle training to improve gait speed . Methods A total of 44 older adults followed personalized , 12-week strength and balance training plans . All participants performed the exercises autonomously at home . Question naires were used to assess the technological familiarity and stage of behavior change , as well as the effectiveness of the motivation instruments adopted by ActiveLifestyle . Adherence to the exercise plan was evaluated using performance data collected by the app and through information given by the participants during the study . Pretests and posttests were performed to evaluate gait speed of the participants before and after the study . Results Participants were 75 years ( SD 6 ) , predominantly female ( 64 % ) , held a trade or professional diploma ( 54 % ) , and their past profession was in a sitting position ( 43 % ) . Of the 44 participants who enrolled , 33 ( 75 % ) completed the study . The app proved to assist and motivate independently living and healthy older adults to autonomously perform strength – balance exercises ( median 6 on a 7-point Likert scale ) . Social motivation strategies proved more effective than individual strategies to stimulate the participants to comply with the training plan , as well as to change their behavior permanently toward a more physically active lifestyle . The exercises were effective to improve preferred and fast gait speed . Conclusions ActiveLifestyle assisted and motivated independently living and healthy older people to autonomously perform strength – balance exercises over 12 weeks and had low dropout rates . The social motivation strategies were more effective to stimulate the participants to comply with the training plan and remain on the intervention . The adoption of assistive technology devices for physical intervention tends to motivate and retain older people exercising for longer periods of time Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background This study provides insight into the long-term efficacy ( i.e. 12 month results ) of the Web-based or print-delivered tailored Active Plus intervention ( with and without environmental approach ) to promote physical activity ( PA ) among the over-fifties . Differences in effect among subgroups are studied as well . Methods Intervention groups ( i.e. print-delivered basic ( PB ; N = 439 ) , print-delivered environmental ( PE ; N = 435 ) , Web-based basic ( WB ; N = 423 ) , Web-based environmental ( WE ; N = 432 ) ) and a waiting list control group ( N = 411 ) were studied in a clustered r and omized controlled trial . Intervention participants received tailored advice three times within 4 months . Long-term effects ( 12 months after the intervention has started , i.e. 8 months after the intervention was completed ) on PA ( i.e. self-reported weekly minutes and days of sufficient PA ) were tested using multilevel linear regression analyses . Participants ’ age , gender , BMI , educational level , PA intention and the presence of a chronic physical limitation were considered to be potential moderators of the effect . Results Overall , the Active Plus intervention was effective in increasing weekly days of sufficient PA ( B=0.49 ; p=.005 ) , but ineffective in increasing weekly minutes of PA ( B=84.59 ; p=.071 ) . Per intervention condition analysis showed that the PB-intervention ( Bdays=0.64 ; p=.002 ; Bmi n=111.36 ; p=.017 ) and the PE-intervention ( Bdays=0.70 ; p=.001 ; Bmi n=157.41 ; p=.001 ) were effective in increasing days and minutes of PA . Neither Web-based conditions significantly increased PA , while the control group decreased their PA . In contrast to the intervention effect on minutes of PA , the effect on weekly days of PA was significantly moderated by the participants ’ baseline intention to be sufficiently physically active . Conclusions In general , after 12 months the print-delivered interventions result ed in stronger effects than the Web-based interventions . The participants ’ baseline intention was the only significant moderator of the intervention effect . All other assessed user characteristics did not significantly moderate the effect of the intervention , which might indicate that the intervention is sufficiently tailored to the different participant characteristics . Additional efforts should be taken to increase the sustainability of Web-based interventions .Trial registration Dutch Trial Register : NTR2297 With more social support and environment-centered interventions being recommended in web-based interventions , this study examined the efficacy of three intervention conditions aim ed at promoting physical activity ( PA ) in older adults . The efficacy analyses included the self-reported PA level , stage of change for PA and awareness about PA among participants . Eligible participants ( N = 149 ; M = 65 years old , SD = 6 ) , recruited in a unique Belgian French-speaking municipality , were r and omized in four research arms for a 3-month intervention : ( i ) web-based ; ( ii ) center-based ; ( iii ) mixed ( combination of web- and center-based ) ; and ( iv ) control ( no intervention ) . Web-based condition included a PA website and monthly tailored emails whereas center-based condition comprised 12 sessions ( 1 per week ) of group exercising . With a significant increase in PA , the PA stage of change and the PA awareness at 12 months , the mixed intervention condition seemed to include the key social and motivating elements for sustainable behavior change . Center-based intervention was more likely to produce significant improvements of the PA level and the stage of change for PA change whereas web-based intervention was more likely to extend the awareness about PA BACKGROUND Remote and web 2.0 interventions for promoting physical activity ( PA ) are becoming increasingly popular but their ability to achieve long term changes are unknown . OBJECTIVES To compare the effectiveness of remote and web 2.0 interventions for PA promotion in community dwelling adults ( aged 16 years and above ) with a control group exposed to placebo or no or minimal intervention . SEARCH METHODS We search ed CENTRAL , MEDLINE , EMBASE , CINAHL , and some other data bases ( from earliest date s available to October 2012 ) . Reference lists of relevant articles were checked . No language restrictions were applied . SELECTION CRITERIA R and omised controlled trials ( RCTs ) that compared remote and web 2.0 PA interventions for community dwelling adults with a placebo or no or minimal intervention control group . We included studies if the principal component of the intervention was delivered using remote or web 2.0 technologies ( for example the internet , smart phones ) or more traditional methods ( for example telephone , mail-outs ) , or both . To assess behavioural change over time , the included studies had a minimum of 12 months follow-up from the start of the intervention to the final results . We excluded studies that had more than a 20 % loss to follow-up if they did not apply an intention-to-treat analysis . DATA COLLECTION AND ANALYSIS At least two authors independently assessed the quality of each study and extracted the data . Non-English language papers were review ed with the assistance of an interpreter who was an epidemiologist . Study authors were contacted for additional information where necessary . St and ardised mean differences ( SMDs ) and 95 % confidence intervals ( CIs ) were calculated for the continuous measures of self-reported PA and cardio-respiratory fitness . For studies with dichotomous outcomes , odds ratios and 95 % CIs were calculated . MAIN RESULTS A total of 11 studies recruiting 5862 apparently healthy adults met the inclusion criteria . All of the studies took place in high-income countries . The effect of the interventions on cardiovascular fitness at one year ( two studies ; 444 participants ) was positive and moderate with significant heterogeneity of the observed effects ( SMD 0.40 ; 95 % CI 0.04 to 0.76 ; high quality evidence ) . The effect of the interventions on self-reported PA at one year ( nine studies ; 4547 participants ) was positive and moderate ( SMD 0.20 ; 95 % CI 0.11 to 0.28 ; moderate quality evidence ) with heterogeneity ( I2 = 37 % ) in the observed effects . One study reported positive results at two years ( SMD 0.20 ; 95 % CI 0.08 to 0.32 ; moderate quality evidence ) . When studies were stratified by risk of bias , the studies at low risk of bias ( eight studies ; 3403 participants ) had an increased effect ( SMD 0.28 ; 95 % CI 0.16 to 0.40 ; moderate quality evidence ) . The most effective interventions applied a tailored approach to the type of PA and used telephone contact to provide feedback and to support changes in PA levels . There was no evidence of an increased risk of adverse events ( seven studies ; 2892 participants ) . Risk of bias was assessed as low ( eight studies ; 3060 participants ) or moderate ( three studies ; 2677 participants ) . There were no differences in effectiveness between studies using different types of professionals delivering the intervention ( for example health professional , exercise specialist ) . There was no difference in pooled estimates between studies that generated the prescribed PA using an automated computer programme versus a human , nor between studies that used pedometers as part of their intervention compared to studies that did not . AUTHORS ' CONCLUSIONS We found consistent evidence to support the effectiveness of remote and web 2.0 interventions for promoting PA . These interventions have positive , moderate sized effects on increasing self-reported PA and measured cardio-respiratory fitness , at least at 12 months . The effectiveness of these interventions was supported by moderate and high quality studies . However , there continues to be a paucity of cost effectiveness data and studies that include participants from varying socioeconomic or ethnic groups . To better underst and the independent effect of individual programme components , longer term studies , with at least one year follow-up , are required |
12,055 | 26,381,233 | Effects of multi-level interventions on ine quality were inconsistent .
Conclusions Universal school-based interventions may narrow , widen or have no effect on ine quality . | Background Socioeconomic inequalities in health behaviour emerge in early life before tracking into adulthood .
Many interventions to improve childhood health behaviours are delivered via schools , often targeting poorer areas .
However , targeted approaches may fail to address inequalities within more affluent schools .
Little is known about types of universal school-based interventions which make inequalities better or worse . | Background Obesity has become a global public health problem , which also affects children . It has been proposed that the educational interventions during childhood could be a key strategy in the prevention of obesity . Objective To evaluate the efficacy of an intervention on food habits and physical activity in school children . Methods A 2-year cluster-r and omised prospect i ve study with two parallel arms was used to evaluate an intervention programme in children in their first year of primary schooling ( 5–6 years of age ) in schools in the city of Granollers . The intervention consisted of the promotion of healthy eating habits and physical activity by means of the educational methodology Investigation , Vision , Action and Change ( IVAC ) . At the beginning and at the end of the study ( 2006 and 2008 ) the weight and height of each child was measured in situ , while the families were given a self-report physical activity question naire and the Krece Plus quick test . Results Two years after the beginning of the study , the body mass index of the children in the control group was 0.89 kg/m2 higher than that of the intervention schools . The intervention reduced by 62 % the prevalence of overweight children . Similarly , the proportion of children that ate a second piece of fruit and took part in an after-school physical activity increased in the intervention group . In the control group , the weekly consumption of fish was reduced . Conclusions The educational intervention in healthy eating habits and physical activity in the school could contribute to lessen the current increase in child obesity Objective To compare the effectiveness of classroom based cognitive behavioural therapy with attention control and usual school provision for adolescents at high risk of depression . Design Three arm parallel cluster r and omised controlled trial . Setting Eight UK secondary schools . Participants Adolescents ( n=5030 ) aged 12 - 16 years in school year groups 8 - 11 . Year groups were r and omly assigned on a 1:1:1 ratio to cognitive behavioural therapy , attention control , or usual school provision . Allocation was balanced by school , year , number of students and classes , frequency of lessons , and timetabling . Participants were not blinded to treatment allocation . Interventions Cognitive behavioural therapy , attention control , and usual school provision provided in classes to all eligible participants . Main outcome measures Outcomes were collected by self completed question naire administered by research ers . The primary outcome was symptoms of depression assessed at 12 months by the short mood and feelings question naire among those identified at baseline as being at high risk of depression . Secondary outcomes included negative thinking , self worth , and anxiety . Analyses were undertaken on an intention to treat basis and accounted for the clustered nature of the design . Results 1064 ( 21.2 % ) adolescents were identified at high risk of depression : 392 in the classroom based cognitive behavioural therapy arm , 374 in the attention control arm , and 298 in the usual school provision arm . At 12 months adjusted mean scores on the short mood and feelings question naire did not differ for cognitive behavioural therapy versus attention control ( −0.63 , 95 % confidence interval −1.85 to 0.58 , P=0.41 ) or for cognitive behavioural therapy versus usual school provision ( 0.97 , −0.20 to 2.15 , P=0.12 ) . Conclusion In adolescents with depressive symptoms , outcomes were similar for attention control , usual school provision , and cognitive behavioural therapy . Classroom based cognitive behavioural therapy programmes may result in increased self awareness and reporting of depressive symptoms but should not be undertaken without further evaluation and research . Trial registration Current Controlled Trials IS RCT N19083628 OBJECTIVE The present study evaluated the impact of a national school programme of universal free healthy breakfast provision in Wales , UK . DESIGN A cluster r and omised controlled trial with repeated cross-sectional design and a 12-month follow-up . Primary outcomes were breakfast skipping , breakfast diet and episodic memory . Secondary outcomes were frequency of eating breakfast at home and at school , breakfast attitudes , rest-of-day diet and class behaviour . SETTING Primary schools in nine local education authority areas . SUBJECTS A total of 4350 students ( aged 9 - 11 years ) at baseline and 4472 at follow-up in 111 schools . RESULTS Students in intervention schools reported significantly higher numbers of healthy food items consumed at breakfast and more positive attitudes towards breakfast eating at 12 months . Parents in intervention schools reported significantly higher rates of consumption of breakfast at school and correspondingly lower rates of breakfast consumption at home . No other significant differences were found . CONCLUSIONS The intervention did not reduce breakfast skipping ; rather , pupils substituted breakfast at home for breakfast at school . However , there were improvements in children 's nutritional intake at breakfast time , if not the rest of the day , and more positive attitudes to breakfast , which may have implication s for life-course dietary behaviours . There was no impact on episodic memory or classroom behaviour , which may require targeting breakfast skippers OBJECTIVE To explore whether the effects on dietary behaviours of a computer-tailored intervention aim ed to prevent excessive weight gain among adolescents , FATaintPHAT , were moderated by sociodemographic , cognitive and home environmental factors . DESIGN A two-group cluster r and omized trial . Potential moderation of the outcome measures ( consumption of sugar-sweetened beverages , snacks , fruits and vegetables ) was studied by gender , education level , ethnicity , awareness of risk behaviour , intention and home availability . SETTING Twenty schools in the Netherl and s. SUBJECTS Students ( n 883 ) aged 12 - 13 years . RESULTS Of the twenty-four interactions tested , only three were significant . The intervention effect on sugar-sweetened beverages was moderated by level of education ( P = 0·009 ) ; intervention effects were found only among academic preparatory students . The intervention effects on fruit and vegetable intake were moderated by awareness of fruit intake ( P < 0·001 ) and home availability of vegetables ( P = 0·007 ) ; an effect on fruit intake was found only among students who were aware of their low fruit intake at baseline and an effect on vegetable consumption was found only among students who reported that vegetables were always available at their home . CONCLUSIONS The effects of the intervention generally did not differ between sociodemographic subgroups . The moderation by home availability illustrates that the environment may influence the effects of educational interventions Background To promote well-being and health behaviors among adolescents , 2 interventions were implemented at 12 secondary schools . Adolescents in the E-health4Uth group received Web-based tailored messages focused on their health behaviors and well-being . Adolescents in the E-health4Uth and consultation group received the same tailored messages , but were subsequently referred to a school nurse for a consultation if they were at risk of mental health problems . Objective This study evaluated the effect of E-health4Uth and E-health4Uth and consultation on well-being ( ie , mental health status and health-related quality of life ) and health behaviors ( ie , alcohol and drug use , smoking , safe sex ) . Methods A cluster r and omized controlled trial was conducted among third- and fourth-year secondary school students ( mean age 15.9 , SD 0.69 ) . School classes ( clusters ) were r and omly assigned to ( 1 ) E-health4Uth group , ( 2 ) E-health4Uth and consultation group , or ( 3 ) control group ( ie , care as usual ) . Adolescents completed a question naire at baseline and at 4-month follow-up assessing alcohol consumption , smoking , drug use , condom use , mental health via the Strengths and Difficulties Question naire ( SDQ ) and the Youth Self Report ( YSR ; only measured at follow-up ) , and health-related quality of life . Multilevel logistic , ordinal , and linear regression analyses were used to reveal differences in health behavior and well-being between the intervention groups and the control group at follow-up . Subsequently , it was explored whether demographics moderated the effects . Results Data from 1256 adolescents were analyzed . Compared to the control intervention , the E-health4Uth intervention , as a st and alone intervention , showed minor positive results in health-related quality of life ( B=2.79 , 95 % CI 0.72 - 4.87 ) and condom use during intercourse among adolescents of Dutch ethnicity ( OR 3.59 , 95 % CI 1.71 - 7.55 ) not replicated in the E-health4Uth and consultation group . The E-health4Uth and consultation intervention showed minor positive results in the mental health status of adolescents ( SDQ : B=−0.60 , 95 % CI −1.17 to −0.04 ) , but a negative effect on drug use among boys ( OR 0.36 , 95 % CI 0.13 - 0.96 ) . In the subgroup of adolescents who were at risk of mental health problems at baseline ( and referred for a consultation with the nurse ) , the E-health4Uth and consultation group showed minor to moderate positive results in mental health status ( SDQ : B=−1.79 , 95 % CI −3.35 to −0.22 ; YSR : B=−9.11 , 95 % CI −17.52 to −0.71 ) and health-related quality of life ( B=7.81 , 95 % CI 2.41 - 13.21 ) at follow-up compared to adolescents in the control group who were at risk of mental health problems at baseline . Conclusions Findings from this study support the use of the E-health4Uth and consultation intervention in promoting the well-being of adolescents at risk of mental health problems . Future research is needed to further evaluate the effects of the consultation as a st and alone intervention , and the dual approach of further tailored eHealth messages and a consultation . Trial Registration Nederl and s Trial Register : NTR 3596 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=3596 ( Archived by WebCite at http://www.webcitation.org/6PmgrPOuv ) Background School-based interventions that target prevention of overweight and obesity in children have been tested with mixed results . Thus , successful interventions are still called for . The aim of the present study was to investigate effects of a multicomponent school-based intervention programme targeting physical activity , sedentary and dietary behaviours on anthropometric outcomes . Methods A 20-month intervention was evaluated in a cluster r and omised , controlled study of 1324 11-year-olds . Outcome variables were body mass index ( BMI ) , BMI -for-age z-score ( BMI z ) , waist circumference ( WC ) , waist-to-height ratio ( WTHR ) and weight status ( International Obesity Task Force 's cut-offs ) . Weight , height and WC were measured objective ly ; pubertal status was self-reported and parental education was self-reported by the parents . Intervention effects were determined by one-way analysis of covariance and logistic regression , after checking for clustering effects of school , and moderating effects of gender , pubertal status and parental education . Results Beneficial effects were found for BMI ( p=0.02 ) and BMI z ( p=0.003 ) in girls , but not in boys . While a beneficial effect was found for BMI ( p=0.03 ) in participants of parents reporting a high level of education , a negative effect was found for WTHR in participants with parents reporting a low level of education ( p=0.003 ) . There were no intervention effects for WC and weight status . Conclusions A multicomponent 20-month school-based intervention had a beneficial effect on BMI and BMI z in adolescent girls , but not in boys . Furthermore , children of higher educated parents seemed to benefit more from the intervention , and this needs attention in future interventions to avoid further increase in social inequalities in overweight and obesity Objective : To assess the efficacy of a school-based intervention programme to reduce the prevalence of overweight in 6 to 10-year-old children . Design : Cluster-r and omized , controlled study .Subjects : A total of 3135 boys and girls in grade s 1–4 were included in the study . Methods : Ten schools were selected in Stockholm county area and r and omized to intervention ( n=5 ) and control ( n=5 ) schools . Low-fat dairy products and whole-grain bread were promoted and all sweets and sweetened drinks were eliminated in intervention schools . Physical activity ( PA ) was aim ed to increase by 30 min day−1 during school time and sedentary behaviour restricted during after school care time . PA was measured by accelerometry . Eating habits at home were assessed by parental report . Eating disorders were evaluated by self-report . Results : The prevalence of overweight and obesity decreased by 3.2 % ( from 20.3 to 17.1 ) in intervention schools compared with an increase of 2.8 % ( from 16.1 to 18.9 ) in control schools ( P<0.05 ) . The results showed no difference between intervention and controls , after cluster adjustment , in the longitudinal analysis of BMI sds changes . However , a larger proportion of the children who were initially overweight reached normal weight in the intervention group ( 14 % ) compared with the control group ( 7.5 % ) , P=0.017 . PA did not differ between intervention and control schools after cluster adjustment . Eating habits at home were found to be healthier among families with children in intervention schools at the end of the intervention . There was no difference between children in intervention and control schools in self-reported eating disorders . Conclusions : A school-based intervention can reduce the prevalence of overweight and obesity in 6 to 10-year-old children and may affect eating habits at home . The effect of the intervention was possibly due to its effect on healthy eating habits at school and at home rather than on increased levels of PA Objective To investigate the effectiveness of a school based intervention to increase physical activity , reduce sedentary behaviour , and increase fruit and vegetable consumption in children . Design Cluster r and omised controlled trial . Setting 60 primary schools in the south west of Engl and . Participants Primary school children who were in school year 4 ( age 8 - 9 years ) at recruitment and baseline assessment , in year 5 during the intervention , and at the end of year 5 ( age 9 - 10 ) at follow-up assessment . Intervention The Active for Life Year 5 ( AFLY5 ) intervention consisted of teacher training , provision of lesson and child-parent interactive homework plans , all material s required for lessons and homework , and written material s for school newsletters and parents . The intervention was delivered when children were in school year 5 ( age 9 - 10 years ) . Schools allocated to control received st and ard teaching . Main outcome measures The pre-specified primary outcomes were accelerometer assessed minutes of moderate to vigorous physical activity per day , accelerometer assessed minutes of sedentary behaviour per day , and reported daily consumption of servings of fruit and vegetables . Results 60 schools with more than 2221 children were recruited ; valid data were available for fruit and vegetable consumption for 2121 children , for accelerometer assessed physical activity and sedentary behaviour for 1252 children , and for secondary outcomes for between 1825 and 2212 children for the main analyses . None of the three primary outcomes differed between children in schools allocated to the AFLY5 intervention and those allocated to the control group . The difference in means comparing the intervention group with the control group was –1.35 ( 95 % confidence interval –5.29 to 2.59 ) minutes per day for moderate to vigorous physical activity , –0.11 ( –9.71 to 9.49 ) minutes per day for sedentary behaviour , and 0.08 ( –0.12 to 0.28 ) servings per day for fruit and vegetable consumption . The intervention was effective for three out of nine of the secondary outcomes after multiple testing was taken into account : self reported time spent in screen viewing at the weekend ( –21 ( –37 to –4 ) minutes per day ) , self reported servings of snacks per day ( –0.22 ( –0.38 to –0.05 ) ) , and servings of high energy drinks per day ( –0.26 ( –0.43 to –0.10 ) ) were all reduced . Results from a series of sensitivity analyses testing different assumptions about missing data and from per protocol analyses produced similar results . Conclusion The findings suggest that the AFLY5 school based intervention is not effective at increasing levels of physical activity , decreasing sedentary behaviour , and increasing fruit and vegetable consumption in primary school children . Change in these activities may require more intensive behavioural interventions with children or upstream interventions at the family and societal level , as well as at the school environment level . These findings have relevance for research ers , policy makers , public health practitioners , and doctors who are involved in health promotion , policy making , and commissioning services . Trial registration Current Controlled Trials IS RCT N50133740 Background Although school-based interventions to promote physical activity in adolescents have been suggested in several recent review s , questions have been raised regarding the effects of the strategies and the methodology applied and for whom the interventions are effective . The aim of the present study was to investigate effects of a school-based intervention program : the HEalth in Adolescents ( HEIA ) study , on change in physical activity , and furthermore , to explore whether potential effects varied by gender , weight status , initial physical activity level and parental education level . Methods This was a cluster r and omized controlled 20 month intervention study which included 700 11-year-olds . Main outcome -variable was mean count per minute ( cpm ) derived from ActiGraph accelerometers ( Model 7164/GT1 M ) . Weight and height were measured objective ly . Adolescents reported their pubertal status in a question naire and parents reported their education level on the consent form . Linear mixed models were used to test intervention effects and to account for the clustering effect of sampling by school . Results The present study showed an intervention effect on overall physical activity at the level of p = 0.05 with a net effect of 50 cpm increase from baseline to post intervention in favour of the intervention group ( 95 % CI −0.4 , 100 ) . Subgroup analyses showed that the effect appeared to be more profound among girls ( Est 65 cpm , CI 5 , 124 , p = 0.03 ) and among participants in the low-activity group ( Est 92 cpm , CI 41 , 142 , p < 0.001 ) , as compared to boys and participants in the high-activity group , respectively . Furthermore , the intervention affected physical activity among the normal weight group more positively than among the overweight , and participants with parents having 13–16 years of education more positively than participants with parents having either a lower or higher number of years of education . The intervention seemed to succeed in reducing time spent sedentary among girls but not among boys . Conclusions A comprehensive but feasible , multi-component school-based intervention can affect physical activity patterns in adolescents by increasing overall physical activity . This intervention effect seemed to be more profound in girls than boys , low-active adolescents compared to high-active adolescents , participants with normal weight compared to the overweight , and for participants with parents of middle education level as opposed to those with high and low education levels , respectively . An implementation of the HEIA intervention components in the school system may have a beneficial effect on public health by increasing overall physical activity among adolescents and possibly among girls and low-active adolescents in particular Background Improving nutrition knowledge among children may help them to make healthier food choices . The aim of this study was to assess the effectiveness and acceptability of a novel educational intervention to increase nutrition knowledge among primary school children . Methods We developed a card game ' Top Grub ' and a ' healthy eating ' curriculum for use in primary schools . Thirty-eight state primary schools comprising 2519 children in years 5 and 6 ( aged 9 - 11 years ) were recruited in a pragmatic cluster r and omised controlled trial . The main outcome measures were change in nutrition knowledge scores , attitudes to healthy eating and acceptability of the intervention by children and teachers . Results Twelve intervention and 13 control schools ( comprising 1133 children ) completed the trial . The main reason for non-completion was time pressure of the school curriculum . Mean total nutrition knowledge score increased by 1.1 in intervention ( baseline to follow-up : 28.3 to 29.2 ) and 0.3 in control schools ( 27.3 to 27.6 ) . Total nutrition knowledge score at follow-up , adjusted for baseline score , deprivation , and school size , was higher in intervention than in control schools ( mean difference = 1.1 ; 95 % CI : 0.05 to 2.16 ; p = 0.042 ) . At follow-up , more children in the intervention schools said they ' are currently eating a healthy diet ' ( 39.6 % ) or ' would try to eat a healthy diet ' ( 35.7 % ) than in control schools ( 34.4 % and 31.7 % respectively ; chi-square test p < 0.001 ) . Most children ( 75.5 % ) enjoyed playing the game and teachers considered it a useful re source . Conclusions The ' Top Grub ' card game facilitated the enjoyable delivery of nutrition education in a sample of UK primary school age children . Further studies should determine whether improvements in nutrition knowledge are sustained and lead to changes in dietary behaviour Background The aim of the Boost study was to produce a persistent increase in fruit and vegetable consumption among 13-year-olds . This paper describes the development , implementation and evaluation of a school- and community-based , multi-component intervention guided by theory , evidence , and best practice . Methods / design We used the Intervention Mapping protocol to guide the development of the intervention . Programme activities combined environmental and educational strategies and focused on increasing access to fruit and vegetables in three setting s : School : Daily provision of free fruit and vegetables ; a pleasant eating environment ; classroom curricular activities ; individually computer tailored messages ; one-day-workshop for teachers . Families : school meeting ; guided child-parent activities ; newsletters . Local community : guided visits in grocery stores and local area as part of classroom curriculum ; information sheets to sports- and youth clubs . The Boost study employed a cluster-r and omised controlled study design and applied simple two-stage cluster sampling : A r and om sample of 10 municipalities followed by a r and om sample of 4 schools within each municipality ( N = 40 schools ) . Schools were r and omised into a total of 20 intervention- and 20 control schools . We included all year 7 pupils except those from school classes with special needs . Timeline : Baseline survey : August 2010 . Delivery of intervention : September 2010-May 2011 . First follow-up survey : May/June 2011 . Second follow-up survey : May/June 2012 . Primary outcome measures : Daily mean intake of fruit and vegetables and habitual fruit and vegetable intake measured by vali date d 24-hour recall- and food frequency question naires . Secondary outcome measures : determinants of fruit and vegetable intake , positive side-effects and unintended adverse effects . Implementation was monitored by thorough process evaluation . Discussion The baseline data file included 2,156 adolescents ( 95 % ) . There was baseline equivalence between intervention- and control groups for sociodemographics , primary outcomes , and availability at home , school and sports- and youth clubs . Significantly larger proportions of pupils in the control group had parents born in Denmark . The study will provide insights into effective strategies to increase fruit and vegetable intake among teenagers . The study will gain knowledge on implementation processes , intervention effects in population subgroups with low intake , and opportunities for including local communities in interventions .Trial registration Current Controlled Trials IS RCT N11666034 Background The aim of the School site , Play Spot , Active transport , Club fitness and Environment ( SPACE ) Study was to develop , document , and assess a comprehensive intervention in local school districts that promote everyday physical activity ( PA ) among 11 - 15-year-old adolescents . The study is based on a social ecological framework , and is design ed to implement organizational and structural changes in the physical environment . Methods / design The SPACE Study used a cluster r and omized controlled study design . Twenty-one eligible schools in the Region of Southern Denmark were matched and r and omized in seven pairs according to eight matching variables summarized in an audit tool ( crow-fly distance from residence to school for 5 - 6th grade rs ; area household income ; area education level ; area ethnicity distribution ; school district urbanity ; condition and characteristics of school outdoor areas ; school health policy ; and active transport in the local area ) . Baseline measurements with accelerometers , question naires , diaries , and physical fitness tests were obtained in Spring 2010 in 5 - 6th grade in 7 intervention and 7 control schools , with follow-up measurements to be taken in Spring 2012 in 7 - 8th grade . The primary outcome measure is objective average daily physical activity and will be supported by analyses of time spent in moderate to vigorous activity and time spent sedentary . Other secondary outcome measures will be obtained , such as , overweight , physical fitness , active commuting to/from school and physical activity in recess periods . Discussion A total of 1348 adolescents in 5 - 6th grade in the Region of Southern Denmark participated at baseline ( n = 14 schools ) . The response rate was high in all type of measurements ( 72.6 - 97.4 % ) . There were no significant differences between intervention and control groups at baseline according to selected background variables and outcome measures : gender ( p = .54 ) , age ( p = .17 ) , BMI ( p = .59 ) , waist circumference ( p = .17 ) , physical fitness ( p = .93 ) , and physical activity ( accelerometer ) ( p = .09).The r and omization and matched pair design produced equivalent groups according to central outcome measures and background variables . The SPACE for physical activity Study will provide new insights on the effectiveness of multicomponent interventions to improve adolescents ' physical activity level . Trial registration Current Controlled Trials IS RCT Summary Background Schools in many countries undertake programmes for smoking prevention , but systematic review s have shown mixed evidence of their effectiveness . Most peer-led approaches have been classroom-based , and rigorous assessment s are scarce . We assessed the effectiveness of a peer-led intervention that aim ed to prevent smoking uptake in secondary schools . Methods We undertook a cluster r and omised controlled trial of 10 730 students aged 12–13 years in 59 schools in Engl and and Wales . 29 schools ( 5372 students ) were r and omly assigned by stratified block r and omisation to the control group to continue their usual smoking education and 30 ( 5358 students ) to the intervention group . The intervention ( ASSIST [ A Stop Smoking In Schools Trial ] programme ) consisted of training influential students to act as peer supporters during informal interactions outside the classroom to encourage their peers not to smoke . Follow-up was immediately after the intervention and at 1 and 2 years . Primary outcomes were smoking in the past week in both the school year group and in a group at high risk of regular smoking uptake , which was identified at baseline as occasional , experimental , or ex-smokers . Analysis was by intention to treat . This study is registered , number IS RCT N55572965 . Findings The odds ratio of being a smoker in intervention compared with control schools was 0·75 ( 95 % CI 0·55–1·01 ) immediately after the intervention ( n=9349 students ) , 0·77 ( 0·59–0·99 ) at 1-year follow-up ( n=9147 ) , and 0·85 ( 0·72–1·01 ) at 2-year follow-up ( n=8756 ) . The corresponding odds ratios for the high-risk group were 0·79 ( 0·55–1·13 [ n=3561 ] ) , 0·75 ( 0·56–0·99 [ n=3483 ] ) , and 0·85 ( 0·70–1·02 [ n=3294 ] ) , respectively . In a three-tier multilevel model with data from all three follow-ups , the odds of being a smoker in intervention compared with control schools was 0·78 ( 0·64–0·96 ) . Interpretation The results suggest that , if implemented on a population basis , the ASSIST intervention could lead to a reduction in adolescent smoking prevalence of public-health importance . Funding MRC ( UK ) Background Over the last three decades there has been a substantial increase in the proportion of children who are overweight or obese . The Healthy Lifestyles Programme ( HeLP ) is a novel school-based intervention , using highly interactive and creative delivery methods to prevent obesity in children . Methods / Design We describe a cluster r and omised controlled trial to evaluate the effectiveness and cost effectiveness of HeLP . The intervention has been developed using intervention mapping ( involving extensive stakeholder involvement ) and has been guided by the Information , Motivation , Behavioural Skills model . HeLP includes creating a receptive environment , drama activities , goal setting and reinforcement activities and runs over three school terms . Piloting showed that 9 to 10 year olds were the most receptive and participative . This study aims to recruit 1,300 children from 32 schools ( over half of which will have ≥19 % of pupils eligible for free school meals ) from the southwest of Engl and . Participating schools will be r and omised to intervention or control groups with baseline measures taken prior to r and omisation . The primary outcome is change in body mass index st and ard deviation score ( BMI SDS ) at 24 months post baseline . Secondary outcomes include , waist circumference and percent body fat SDS and proportion of children classified as overweight or obese at 18 and 24 months and objective ly measured physical activity and food intake at 18 months . Between-group comparisons will be made using r and om effects regression analysis taking into account the hierarchical nature of the study design . An economic evaluation will estimate the incremental cost-effectiveness of HeLP , compared to control , from the perspective of the National Health Service (NHS)/third party payer . An in-depth process evaluation will provide insight into how HeLP works , and whether there is any differential uptake or engagement with the programme . Discussion The results of the trial will provide evidence on the effectiveness and cost effectiveness of the Healthy Lifestyles Programme in affecting the weight status of children . Trial registration IS RCT R and omized trials of complex public health interventions generally aim to identify what works , accrediting specific intervention ' products ' as effective . This approach often fails to give sufficient consideration to how intervention components interact with each other and with local context . ' Realists ' argue that trials misunderst and the scientific method , offer only a ' successionist ' approach to causation , which brackets out the complexity of social causation , and fail to ask which interventions work , for whom and under what circumstances . We counter-argue that trials are useful in evaluating social interventions because r and omized control groups actually take proper account of rather than bracket out the complexity of social causation . Nonetheless , realists are right to stress underst and ing of ' what works , for whom and under what circumstances ' and to argue for the importance of theorizing and empirically examining underlying mechanisms . We propose that these aims can be ( and sometimes already are ) examined within r and omized trials . Such ' realist ' trials should aim to : examine the effects of intervention components separately and in combination , for example using multi-arm studies and factorial trials ; explore mechanisms of change , for example analysing how pathway variables mediate intervention effects ; use multiple trials across context s to test how intervention effects vary with context ; draw on complementary qualitative and quantitative data ; and be oriented towards building and validating ' mid-level ' program theories which would set out how interventions interact with context to produce outcomes . This last suggestion resonates with recent suggestions that , in delivering truly ' complex ' interventions , fidelity is important not so much in terms of precise activities but , rather , key intervention ' processes ' and ' functions ' . Realist trials would additionally determine the validity of program theory rather than only examining ' what works ' to better inform policy and practice in the long-term Objectives Universal interventions may widen or narrow inequalities if disproportionately effective among higher or lower socio-economic groups . The present paper examines impacts of the Primary School Free Breakfast Initiative in Wales on inequalities in children 's dietary behaviours and cognitive functioning . Design Cluster-r and omised controlled trial . Responses were linked to free school meal ( FSM ) entitlement via the Secure Anonymised Information Linkage data bank . Impacts on inequalities were evaluated using weighted school-level regression models with interaction terms for intervention × whole-school percentage FSM entitlement and intervention × aggregated individual FSM entitlement . Individual-level regression models included interaction terms for intervention × individual FSM entitlement . Setting Fifty-five intervention and fifty-six wait-list control primary schools . Subjects Approximately 4500 children completed measures of dietary behaviours and cognitive tests at baseline and 12-month follow-up . Results School-level models indicated that children in intervention schools ate a greater number of healthy items for breakfast than children in control schools ( b = 0·25 ; 95 % CI 0·07 , 0·44 ) , with larger increases observed in more deprived schools ( interaction term b = 1·76 ; 95 % CI 0·36 , 3·16 ) . An interaction between intervention and household-level deprivation was not significant . Despite no main effects on breakfast skipping , a significant interaction was observed , indicating declines in breakfast skipping in more deprived schools ( interaction term b = −0·07 ; 95 % CI −0·15 , −0·00 ) and households ( OR = 0·67 ; 95 % CI 0·46 , 0·98 ) . No significant influence on ine quality was observed for the remaining outcomes . Conclusions Universal breakfast provision may reduce socio-economic inequalities in consumption of healthy breakfast items and breakfast skipping . There was no evidence of intervention-generated inequalities in any outcomes BACKGROUND A number of different socio-economic classifications have been used in relation to health in the United Kingdom . The aim of this study was to compare the predictive power of different socio-economic classifications in relation to a range of health measures . METHODS A postal question naire was sent to a r and om sample of adults in the West of Scotl and ( sampling from 1997 electoral roll , response rate 50 percent achieved sample 2,867 ) . RESULTS Associations between social position and health vary by socio-economic classification , health measure and gender . Limiting long-st and ing illness is more socially patterned than recent illness ; income , Registrar General Social Class , housing tenure and car access are more predictive of health than the new National Statistics Socio Economic Classification ; and men show steeper socio-economic gradients than women . CONCLUSION Although there is a consistent picture of poorer health among more disadvantaged groups , however measured , in seeking to explain and reduce social inequalities in health we need to take a more differentiated approach that does not assume equivalence among social classifications and health measures INTRODUCTION A smoking prevention program was developed to prepare children in elementary school for secondary school . This study assessed the effects on smoking in secondary school . METHODS In 2002 , 121 schools in The Netherl and s were r and omly assigned to the intervention or control group . The intervention group received 3 lessons in 5th grade of elementary school and a second 3 lessons in 6th grade . The control group received " usual care " . Students completed 5 question naires : before and after the lessons in 5th and 6th grade and in the first class of secondary school . At baseline , 3173 students completed the question naire ; 57 % completed all question naires . RESULTS The program had limited effect at the end of elementary school . One year later in secondary school significant effects on behavioral determinants and smoking were found . The intervention group had a higher intention not to smoke ( β=0.13 , 95 % confidence interval=0.01 - 0.24 ) and started to smoke less often than the control group ( odds ratio=0.59 , 95 % confidence interval=0.35 - 0.99 ) : smoking increased from 2.5 % to 3.6 % in the intervention group and from 3.2 % to 6.5 % in the control group . Girls showed the largest differences in smoking between intervention and control condition . CONCLUSIONS A prevention program in elementary school seems to be effective in preventing smoking OBJECTIVES We assessed the effectiveness of a 2-year multicomponent , school-based intervention design ed to reduce tobacco use rates among adolescents in an urban area of India . METHODS Students from 32 schools in Delhi and Chennai , India , were recruited and r and omly assigned to an intervention or control group . Baseline , intermediate , and outcome data were collected from 2 cohorts of 6th- and 8th- grade students in 2004 ; 14,063 students took part in the study and completed a survey in 2004 , 2005 , or 2006 . The intervention consisted of behavioral classroom curricula , school posters , a parental involvement component , and peer-led activism . The main outcome measures were self-reported use of cigarettes , bidis ( small h and -rolled , often flavored , cigarettes ) , and chewing tobacco and future intentions to smoke or use chewing tobacco . RESULTS Findings showed that students in the intervention group were significantly less likely than were students in the control group to exhibit increases in cigarette smoking or bidi smoking over the 2-year study period . They were also less likely to intend to smoke or chew tobacco in the future . CONCLUSIONS School-based programs similar to the intervention examined here should be considered as part of a multi strategy approach to reducing tobacco use among young people in India Through-school nutrition and physical activity interventions are design ed to help reduce excess weight gain and risk of chronic disease . From 2004 to 2006 , Project Energize was delivered in the Waikato Region of New Zeal and as a longitudinal r and omised controlled study of 124 schools ( year 1 - 6 ) , stratified by rurality and social deprivation , and r and omly assigned to intervention or control . Children ( 686 boys and 662 girls ) aged 5 ( 1926 ) and 10 ( 1426 ) years ( 692 interventions and 660 controls ) had height , weight , body fat ( by bioimpedance ) and resting blood pressure ( BP ) measured at baseline and 2 years later . Each intervention school was assigned an ' Energizer ' ; a trained physical activity and nutrition change agent , who worked with the school to achieve goals based on healthier eating and quality physical activity . After adjustment for baseline measures , rurality and social deprivation , the intervention was associated with a reduced accumulation of body fat in younger children and a reduced rate of rise in systolic BP in older children . There was some evidence that the pattern of change within an age group varied with rurality , ethnicity and sex . We conclude that the introduction of an ' Energizer led ' through-school programme may be associated with health benefits over 2 years , but the trajectory of this change needs to be measured over a longer period . Attention should also be paid to the differing response by ethnicity , sex , age group and the effect of rurality and social deprivation Objective : The aim of this study was to evaluate the 8-year outcome of school-based intervention on weight status , lifestyle and blood pressure ( BP ) as part of the Kiel Obesity Prevention Study ( KOPS ) . Methods : Within a quasi-r and omized controlled trial , 240 intervention ( I ) and 952 non-intervention ( NI ) students at age 6 and 14 years were assessed in schools . Six nutrition units followed by 20-min running games were performed within the first year at school . Primary outcome was the 8-year change in body mass index st and ard deviation score ( BMI -SDS ) according to German references . Effective intervention was tested using multilevel linear regression analysis . Results : Eight-year changes in BMI SDS were + 0.18 and + 0.22 with increases in prevalence of overweight from 8.3 to 10.4 % and 7.0 to 11.2 % in I and NI students , respectively . Cumulative 8-year incidence of overweight was 5.9 % and 7.1 % in I and NI students , respectively . There was no overall effect of intervention , but a significant interaction was shown between the intervention and the socio-economic status ( SES ) , which demonstrated that in high SES , the 8-year change in BMI -SDS was in favour of I ( –0.17 in I and + 0.17 in NI ; p < 0.01 ) . Intervention had no measurable effects on lifestyle and BP . Conclusions : School-based health promotion has some favourable and sustained effects on 8-year changes in BMI -SDS , which are most pronounced in students of high SES families . The data argue in favour of further preventive measures The aim of this study was to evaluate the effect of an intervention targeting the physical and organizational school environment for noncurricular physical activity ( SPACE ) on adiposity , aerobic fitness , and musculo-skeletal strength in Danish adolescents . The study used a cluster r and omized controlled design . Fourteen schools and 1348 adolescents aged 11 - 14 years were included at baseline . Seven schools were r and omized to the intervention , which was design ed to change the organizational and physical environment of the school . The analysis revealed no significant differences between the adolescents in the intervention group compared to the comparison group after a 2-year follow-up . Adjusted for baseline , sex , age , and clustering within schools , the difference between the intervention schools compared to the comparison schools was 6 m in the shuttle run test [ 95 % confidence interval ( CI ) : -21 ; 33 ] , 0.2 cm in waist circumference ( 95 % CI : -2.6 ; 3.1 ) , and -1.1 kg in h and grip strength ( 95 % CI : -2.2 ; -0.1 ) . The results did not provide evidence for the effect of the intervention on adiposity , aerobic fitness , or musculo-skeletal strength in adolescents . Reasons for not finding an effect could be related to both the design and the implementation of the intervention OBJECTIVE To evaluate the effectiveness of the school-based drug abuse prevention program developed in the EU-Dap study ( EUropean Drug Abuse Prevention trial ) in preventing the use of tobacco , alcohol and drugs at the post-test . METHODS Cluster R and omised Controlled Trial . Seven European countries participated in the study ; 170 schools ( 7079 pupils 12 - 14 years of age ) were r and omly assigned to one of three experimental conditions or to a control condition during the school year 2004/2005 . A pre-test survey assessing past and current substance use was conducted before the implementation of the program . The program consisted in 12-hour class-based curriculum based on a comprehensive social-influence approach . A post-test survey was carried out in all participating schools , 3 months after the end of the program . The association between program condition and change in substance use at post-test was expressed as adjusted Prevalence Odds Ratio ( POR ) , estimated by multilevel regression model . RESULTS Program effects were found for daily cigarette smoking ( POR=0.70 ; 0.52 - 0.94 ) and episodes of drunkenness in the past 30 days ( POR=0.72 ; 0.58 - 0.90 for at least one episode , POR=0.69 ; 0.48 - 0.99 for three or more episodes ) , while effects on Cannabis use in the past 30 days were of marginal statistical significance ( POR=0.77 ; 0.60 - 1.00 ) . The curriculum was successful in preventing baseline non-smokers or sporadic smokers from moving onto daily smoking , but it was not effective in helping baseline daily smokers to reduce or stop smoking . CONCLUSION School curricula based on a comprehensive social-influence model may delay progression to daily smoking and episodes of drunkenness STUDY OBJECTIVE To measure the health , educational and social impacts of breakfast club provision in schools serving deprived areas across Engl and . DESIGN A cluster r and omized controlled trial and an observational analysis . SETTING Engl and , the UK . INTERVENTION funding to establish a school-based breakfast club vs. control ( no funding ) . MAIN RESULTS Intention to treat analysis showed improved concentration ( Trail Making Test Part A ) amongst the intervention group at 3 months . Fewer pupils within the intervention group reported having skipped classes within the last month and fewer pupils within the intervention group reported having skipped 1 or more days of school within the last month at 1 year . Observational analysis at 1 year showed a higher proportion of primary -aged breakfast club attendees reported eating fruit for breakfast in comparison to non-attendees . A higher proportion of breakfast club attendees had borderline or abnormal conduct and total difficulties scores ( primary -aged pupils ) and prosocial score ( secondary -aged pupils ) . CONCLUSIONS Analyses revealed a mixed picture of benefit and apparent disbenefit . This study illustrated the challenges of evaluating a complex intervention in which the evaluators had less control than is usual in r and omized trials over recruitment , eligibility checking and implementation . If the impact of new policy initiatives is to be assessed using the most robust forms of evaluation , social policy needs to be organized so that evaluations can be constructed as experiments . This is likely to prove most difficult where the perceived value of implementing an intervention rapidly is high The objective of the present study was to evaluate the effects of the Pro Children intervention on schoolchildren 's fruit and vegetable ( FV ) intake after 1 and 2 years of follow-up . The intervention combined a FV curriculum with efforts to improve FV availability at schools and at home . Effects were examined in a group-r and omised trial among 1,472 10 - 11-year-old children from sixty-two schools in Norway , the Netherl and s and Spain . FV intake was assessed by means of vali date d self-administered question naires completed before the intervention ( September 2003 ) , immediately after the first year of the intervention ( May 2004 ) and 1 year later ( May 2005 ) . Data were analysed using multilevel linear regression analyses with age and sex as covariates . Significant intervention effects for FV intake were found at first follow-up in the total sample . The adjusted FV intake reported by the children from intervention schools was 20 % higher than FV intake reported by children from control schools . At 1 year later , a significant impact was only observed in Norway . Positive intervention effects on FV intake occurred both at school and outside school . We conclude that the Pro Children intervention is a promising means to promote European schoolchildren 's FV intakes , but mainly fruit intake , in the short term . As shown in Norway , where the intervention was best implemented , the intervention might also result in longer-term effects . Further strategies need to be developed that can improve implementation , have an impact on vegetable intake and can secure sustained effects AIMS To evaluate the effectiveness of two preventive interventions to reduce heavy drinking in first- and second-year high school students . DESIGN AND SETTING Cluster r and omized controlled trial using four conditions for comparing two active interventions with a control group from 152 classes of 19 high schools in the Netherl and s. PARTICIPANTS A total of 3490 first-year high school students ( mean 12.68 years , SD=0.51 ) and their parents . Intervention conditions ( i ) Parent intervention ( modelled on the Swedish Örebro Prevention Program ) aim ed at encouraging parental rule- setting concerning their children 's alcohol consumption ; ( ii ) student intervention consisting of four digital lessons based on the principles of the theory of planned behaviour and social cognitive theory ; ( iii ) interventions 1 and 2 combined ; and ( iv ) the regular curriculum as control condition . Main outcome measures Incidence of ( heavy ) weekly alcohol use and frequency of monthly drinking at 10 and 22 months after baseline measurement . FINDINGS A total of 2937 students were eligible for analyses in this study . At first follow-up , only the combined student-parent intervention showed substantial and statistically significant effects on heavy weekly drinking , weekly drinking and frequency of drinking . At second follow-up these results were replicated , except for the effects of the combined intervention on heavy weekly drinking . These findings were consistent across intention-to-treat and completers-only analyses . CONCLUSIONS Results suggest that adolescents as well as their parents should be targeted in order to delay the onset of drinking , preferably prior to onset of weekly drinking Background Multicomponent school-based interventions have the potential to reduce the age-related decline in adolescents ' physical activity ( PA ) , yet there is not consistent evidence to guide non-curricular and school environment interventions . The aim of this study was to assess the effectiveness of a multicomponent environmental school-based intervention , design ed to reduce the age-related decline in PA among adolescents . Methods A cluster r and omized controlled trial was conducted with 7 intervention and 7 control schools . Baseline measurements were carried out in spring 2010 with 2 years of follow-up . A total of 1,348 students ( 11–13 years , in grade 5 and 6 ) enrolled in the study at baseline . The 14 schools included in the study were located in the Region of Southern Denmark . The intervention consisted of organizational and physical changes in the school environment with a total of 11 intervention components . The primary outcome measure was overall PA ( cpm , counts per minute ) and was supported by analyses of time spent in MVPA , and time spent sedentary . Furthermore , a secondary outcome measure was PA in school time and during recess . PA was measured using accelerometer ( Actigraph GT3X ) . Results A total of 797 students completed the trial and had valid accelerometer data . No significant difference was found for overall PA with an adjusted difference of −19.1 cpm ( 95 % CI : −93 , 53 ) or for school time activity with an adjusted difference of 6 cpm ( 95 % CI : −73 , 85 ) . A sensitivity analysis revealed a positive significant intervention effect of PA in recess with an adjusted difference of 95 cpm . Conclusions No evidence was found of the overall effect of a non-curricular multicomponent school-based intervention on PA among Danish adolescents . The intervention was positively associated with PA during school time and recess , however , with small estimates . Lack of effect on overall PA could be due to both program theory and different degrees of implementation . Trial Registration www.Controlled-Trials.com IS RCT |
12,056 | 20,877,299 | However , there was limited evidence of the role of CYP2D6 polymorphisms in antipsychotic efficacy , although there was an association between CYP2D6 genotype and extrapyramidal adverse effects . | There is wide variability in the response of individuals to st and ard doses of antipsychotic drugs .
It has been suggested that this may be partly explained by differences in the cytochrome P450 ( CYP450 ) enzyme system responsible for metabolizing the drugs .
We conducted a systematic review and meta-analyses to consider whether testing for CYP450 single nucleotide polymorphisms in adults starting antipsychotic treatment for schizophrenia predicts and leads to improvements in clinical outcomes . | STUDY OBJECTIVE To investigate the relationships between cytochrome P450 ( CYP ) 2D6 genotype , antipsychotic drug exposure , abnormal movements and tardive dyskinesia , and cigarette smoking . DESIGN Prospect i ve , longitudinal study . SETTING University mental health research center . PATIENTS Thirty-seven patients with schizophrenia . INTERVENTION Patients were genotyped for CYP2D6 * 1 , * 3 , and * 4 alleles , and data were collected on their psychiatric symptoms , cigarette smoking status , and antipsychotic drug exposure . Abnormal movements were measured using the Abnormal Involuntary Movement Scale ( AIMS ) . Presence of tardive dyskinesia was also evaluated . MEASUREMENTS AND MAIN RESULTS A linear regression model used the AIMS scores as the dependent variable , and genotype , sex , smoking status , and antipsychotic drug exposure as independent variables . Antipsychotic drug exposure , genotype , and cigarette smoking interaction was significant ( p<0.0212 ) for patients with the CYP2D6 * 1/*3 , * 4 genotype . Seventy-eight percent of smokers with the CYP2D6 * 1/*3 , * 4 genotype had tardive dyskinesia compared with 20 - 33 % of patients in other groups . CONCLUSION Patients with a CYP2D6 * 3 or * 4 allele may shunt antipsychotic metabolism through other pathways that are induced by cigarette smoke . This induction may result in formation of neurotoxic metabolites , leading to increased AIMS scores and a higher frequency of tardive dyskinesia compared with patients without these alleles Cytochrome P450 ( CYP ) genotyping can be used to prospect ively identify individuals at risk for adverse drug reactions or therapeutic failure due to altered drug metabolism . Based on the specific CYP(s ) affected , individuals may require less or more of a particular drug than people with unaffected CYP-mediated metabolism , or may be best managed by avoiding certain drugs entirely . Here we evaluated the Tag-It ™ CYP mutation detection reagents ( Tm Bioscience Corp. ) . As these reagents , based on a universal bead array , detect more than 20 clinical ly significant variants common to different ancestries , it was important to consider DNA from genetically diverse population s. Thus , we also report CYP2D6 , CYP2C9 and CYP2C19 genotypes for DNA available through the Coriell Institute for Medical Research ( NJ , USA ) . These sample s represent individuals from Caucasian , Japanese , Chinese , Southeast Asian , African – American and Middle Eastern ancestry , and provide an excellent re source for evaluating and validating CYP genotyping methods . Using these sample s , the Tag-It mutation detections assays reliably provided genotypes for CYP2D6 , CYP2C9 and CYP2C19 . The CYP2C9 and CYP2C19 assays were particularly robust and were easily implemented in our clinical laboratory . The CYP2D6 assay was somewhat less robust and could be improved by associating the 2850C > T variant with a specific allele , as well as by discriminating the allele affected when gene duplication is detected Abstract . Objective : In order to evaluate whether poor metabolizers ( PM ) of debrisoquine are overrepresented among patients with acute dystonic reactions and chronic movement disorders associated with the administration of antipsychotic drugs , the CYP2D6 genotype was determined in schizophrenic patients . Methods : Allele status for CYP2D6 * 3 , CYP2D6 * 4 , CYP2D6 * 5 , and CYP2D6 * 6 as well as gene duplication was determined by allele-specific PCR , long-PCR and restriction fragment length polymorphism analysis ( RFLP ) in 119 schizophrenic patients ( 99 males and 20 females ) . All subjects were treated with antipsychotics metabolized , at least partially , by this isozyme . Sixty-three of the patients ( 52.9 % ) had a history of extrapyramidal side effects ( EPS ) , while 56 ( 47.1 % ) had not experienced such problems ( controls ) . Results : Sixty-five patients ( 54.6 % ) were homozygous for a functional CYP2D6 * 1 allele , 44 ( 37.0 % ) were heterozygous for detrimental alleles , and 4 ( 3.4 % ) , who carried two detrimental alleles , were classified as PM . In six patients ( 5.0 % ) duplication of a functional CYP2D6 gene was found , and they were consequently classified as ultrarapid metabolizers ( UM ) . Homo- and heterozygous extensive metabolizers ( EM ) as well as UM were equally distributed between patients with and without EPS , whereas all the PM had a history of EPS . No significant differences in allele frequencies between the two groups were found . Conclusion : Although the results can not be considered conclusive due to the small number of PM patients in our study , the PM genotype may be a predisposing factor for antipsychotic-induced EPS . Knowledge of the CYP2D6 genotype , before starting antipsychotic therapy , might be useful in identifying subjects at risk of developing EPS Abstract Introduction Assessment of the relation between oral risperidone dose , serum drug levels and clinical response may provide important information for rational treatment decisions . Inter – individual differences in the liver cytochrome P450 system , especially in the CYP2D6 subsystem , which account for a significant portion of risperidone metabolism , may also influence plasma drug levels and alter clinical response parameters . We thus prospect ively investigated risperidone serum concentrations in relation to clinical efficacy and side – effects and genotyped major CYP2D6 polymorphisms to determine their effect upon these parameters . Methods Neuroleptic monotherapy with risperidone was administered to schizophrenia patients in a 6–week open dose clinical trial . Weekly assessment s including CGI and PANSS ratings to assess psychopathology ; SAS to assess medication side effects ; and blood draws to quantify steady state plasma levels of risperidone and 9–OH – risperidone were carried out . In addition , major CYP2D6 polymorphisms including alleles * 4 , * 6 and * 14 were genotyped . Results Eighty – two patients were recruited . Mean oral dose of risperidone was 4.3 ± 0.9 mg . Mean plasma level of both risperidone and 9–OH – risperidone together ( “ active moiety ” ) was 41.6 ± 26.6 ng/ml . Significant improvements in PANSS scales and the various subscales ensued . There was a positive linear correlation between active moiety plasma levels and dose ( r = 0.291 , p = 0.015 ) and between risperidone and 9–OH – risperidone levels ( r = 0.262 ; p = 0.016 ) . Nonresponders to pharmacotherapy ( PANSS – Improvement < 30 % ) showed significantly higher active moiety plasma levels ( 49.9 ± 30.7 ng/ml ) than responders ( 38.2 ± 17.0 ng/ml ; p = 0.045 ) without significantly higher oral doses ( p = 0.601 ) . Patients with longer illness duration ( ≥ 3 years ) had significantly higher plasma drug levels than those with a shorter course ( < 3 years ; p = 0.039 ) . Extrapyramidal side effects ( EPS ) and plasma levels were not correlated ( r = 0.028 ; p = 0.843 ) , but higher plasma levels at week 2 predicted an incidence for EPS ( p < 0.050 ) . Accordingly , patients initially receiving higher oral doses of risperidone were significantly more likely to respond with EPS in the trial course . Eight patients ( 9.8 % ) were heterozygous carriers of the CYP2D6 allele * 4 . CYP2D6 polymorphisms did not predict clinical response , but predicted a tendential increase in the plasma risperidone to 9–OH – risperidone ratio ( 0.5 ± 0.6 vs. 1.9 ± 1.8 ; p = 0.120 ) . Discussion The major finding was that responders to risperidone treatment had significantly lower blood levels of risperidone and 9–OH risperidone than patients who did not respond to the treatment despite administration of similar oral doses . The observed CYP2D6 polymorphisms did not contribute to altered clinical efficacy , but affected risperidone to 9–OH – risperidone ratios . Increased plasma levels of the active moiety in patients with longer illness may represent general aging effects . Conversely , the observed higher plasma levels in nonresponders may derive from unaccounted genetic metabolism abnormalities or Phase II metabolism disturbances . Patients initially receiving higher oral risperidone doses were more likely to respond with extrapyramidal side effects which reaffirms the need for careful titration . The high inter – individual variability in risperidone and 9–OH – risperidone metabolization and the relationship between clinical outcome and plasma levels warrants regular plasma level monitoring of both compounds to assess for the clinical ly relevant active moiety AIM Cytochrome P450 2C9 ( CYP2C9 ) is a polymorphic enzyme responsible for the metabolism of a large number of clinical ly important drugs . Individuals with mutant enzymes may risk serious side effects under routine therapy with certain drugs metabolized by CYP2C9 . In order to facilitate the detection of the known SNPs of CYP2C9 , an allele-specific oligonucleotide ( ASO ) based microarray was made . METHODS An oligonucleotide microarray was made to facilitate the SNP ( single nucleotide polymorphism ) screening and was applied for the detection of CYP2C9 polymorphism in 62 high blood pressure ( HBP ) patients who received Irbesartan for treatment . Part of the genotyping results was confirmed by direct sequencing . And the relation between CYP2C9 polymorphism and therapeutic outcome of Irbesartan was statistically analyzed . RESULTS Heterozygous alleles of CYP2C9 * 1/*3 were found in 7 out of 62 subjects . No mutant alleles of CYP2C9 * 2 , * 4 and * 5 and no homozygous mutant alleles were detected . The 7 heterozygous CYP2C9 * 1/*3 and 13 r and om wild type DNA sample s were subjected to direct sequencing with purified PCR products and same genotyping results were obtained with the 20 DNA sample s. There was no significant difference in the odds of effectiveness of Irbesartan between the wild type ( normal ) group and CYP2C9 * 1/*3 ( mutant ) group ( P>0.05 ) . CONCLUSION The oligonucleotide microarray made in this study is a reliable assay for detecting the CYP2C9 known alleles and the heterozygous CYP2C9 * 1/*3 has no significant effects on the therapeutic outcome of Irbesartan Tardive dyskinesia ( TD ) is a movement disorder characterized by involuntary oro‐facial , limb , and truncal movements . As a genetic basis for inter‐individual variation is assumed , there have been a sizeable number of c and i date gene studies . All subjects met diagnostic criteria for schizophrenia and were r and omized to receive antipsychotic medications as participants in the Clinical Antipsychotic Trials of Intervention Effectiveness project ( CATIE ) . TD was assessed via the Abnormal Involuntary Movement Scale at regular intervals . Probable TD was defined as meeting Schooler – Kane criteria at any scheduled CATIE visit ( 207/710 subjects , 29.2 % ) . A total of 128 c and i date genes were studied in 710 subjects—2,580 SNPs in 118 c and i date genes selected from the literature ( e.g. , dopamine , serotonin , glutamate , and GABA pathways ) and composite genotypes for 10 drug‐metabolizing enzymes . No single marker or haplotype association reached statistical significance after adjustment for multiple comparisons . Thus , we found no support for either novel or prior associations from the literature . © 2009 Wiley‐Liss , BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism STUDY OBJECTIVE To investigate whether a relationship exists between the most common known cytochrome P450 ( CYP ) isozyme 2D6 mutations and schizophrenia . Because most antipsychotic and antidepressant agents interact with CYP2D6 , we also investigated clinical outcomes in schizophrenic poor metabolizers ( PMs ) and extensive metabolizers ( EMs ) . DESIGN Prospect i ve , observational study . SETTING Two psychiatric hospitals and a university-affiliated nonpsychiatric hospital . SUBJECTS Thirty-nine consecutive schizophrenic patients ( POP 1 ) , 89 schizophrenics of French Canadian origin ( POP 2 ) , and 384 healthy French Canadians ( POP 3 ) . INTERVENTION All study subjects were genotyped for CYP2D6 mutant alleles . POP 1 patients were evaluated before and after 21 or more days of treatment with antipsychotic drugs metabolized at least in part by CYP2D6 . MEASUREMENTS AND MAIN RESULTS Whole blood was collected to determine CYP2D6 alleles * 1 , * 3 , * 4 , * 5 , * 6 , and * 7 using st and ard restriction fragment length polymorphisms and polymerase chain reaction techniques . In comparison , CYP2D6 genotypes were determined in POP 2 and POP 3 . Twenty-three ( 59.0 % ) of 39 patients in POP 1 were genotypically EM homozygotes , 15 ( 38.4 % ) were EM heterozygotes , and 1 ( 2.6 % ) was a PM . Similar genotype distributions were determined in POP 2 and in POP 3 . Genotype distributions for all three population s were in Hardy-Weinberg equilibrium ( p>0.05 ) , and there was no significant difference among them ( p=0.857 ) . In POP 1 , no differences were seen among genotypes in disease symptom severity , number and severity of adverse drug effects , or attitudes toward drug treatment at baseline and at the end of the study . In fact , all patients improved significantly during their hospital stay ( all p<0.05 ) , although independent of the CYP2D6 genotype . CONCLUSION Common CYP2D6 mutant alleles were not associated with schizophrenia or with disease symptoms , antipsychotic-related adverse effects , or attitudes toward treatment Objective : A serious side effect of atypical antipsychotics is increased body weight , which leads to further morbidity and nonadherence to medication . It has been suggested that both genetic and nongenetic variables may influence antipsychotics-related weight gain . This study aim ed to simultaneously explore the effects of multiple c and i date genes and environment factors on body weight of schizophrenia patients who received risperidone , a commonly used atypical antipsychotic agent . Methods : One hundred twenty-three ethnically Han Chinese in patients with acutely exacerbated schizophrenia were given risperidone monotherapy for up to 42 days . Body weight and clinical manifestations were assessed biweekly . Drug efficacy was measured by the Positive and Negative Syndrome Scale ( PANSS ) , and safety was evaluated by the Extrapyramidal Symptom Rating Scale ( ESRS ) and the UKU Side Effect Rating Scale . We collected body weight as the response value . Potential prognostic factors were baseline body weight , age , sex , diagnosis subtypes , risperidone dosage , PANSS total scores , treatment duration ( weeks 0 - 6 ) , and 15 genetic variants [ across 10 c and i date genes : 5-HT1A , 5-HT2A , 5-HT2C , 5-HT6 , D1 , D2 , D3 , and & agr;1-adrenergic receptors , brain-derived neurotrophic factor ( BDNF ) , and cytochrome P450 2D6 ( CYP2D6 ) ] . Because there were repeated assessment s , multiple linear regression with the generalized estimating equation ( GEE ) method was used to adjust the within-subject dependence . Results : Of 15 genetic polymorphisms examined , 5-HT2A 102-T/C , 5-HT2C −759-C/T , 5-HT6 267-C/T , BDNF 66-Val/Met , and CYP2D6 188-C/T significantly influenced body weight , and so did baseline body weight , age , gender , schizophrenia subtype , and treatment duration and efficacy . Conclusions : These results suggest that numerous genetic and nongenetic factors affect antipsychotics-related weight gain The genetically polymorphic enzyme cytochrome P450 ( CYP ) 2D6 contributes to the biotransformation of the antipsychotic drug haloperidol . The impact of the polymorphism on haloperidol pharmacokinetics , adverse events , and efficacy was prospect ively evaluated under naturalistic conditions in 172 unselected psychiatric in patients with acute psychotic symptoms Abstract : In normal subjects after a single oral dose , haloperidol half-life has been reported to range 14.5 - 36.7 hours ( or up to 1.5 days ) . After chronic administration , half-lives of up to 21 days have been reported . The objective of this study was to evaluate specific factors that might account for differences in haloperidol half-life in patients taking haloperidol chronically , including gender , age , weight , race , CYP2D6 and CYP3A5 genotypes , comedication , and smoking . Thirty-one patients were administered haloperidol for 4 weeks followed by a 1-week washout before administration of clozapine . Haloperidol plasma levels were measured weekly for at least 2 months after discontinuation . The geometric mean for haloperidol half-life and detectable levels duration were 3.9 and 13.8 days , respectively . Within 31 subjects , 58 % ( 18/31 ) had half-lives <3 days ( 1.2 - 2.3 days ) and 42 % ( 13/31 ) had half-lives ≥3 days . Two of 3 patients with half-lives longer than 30 days ( 720 hours ) and levels detectable > 2 months had received haloperidol decanoate . Five patients who received haloperidol decanoate in the prior year were excluded from a comparison between patients with long haloperidol half-lives ( ≥3 days , n = 10 ) and patients with short half-lives ( <3 days , n = 16 ) . The only significant difference between the two groups was that African-Americans ( n = 4 ) were all found to have a long haloperidol half-life ( P = 0.014 ) . CYP3A5 genotype did not appear to influence haloperidol half-life but the two CYP2D6 poor metabolizer had half-lives ≥3 days . This study suggests that haloperidol half-life following repeated drug administration is substantially more prolonged than what has been observed after acute haloperidol administration |
12,057 | 22,943,270 | RESULTS Acetazolamide prophylaxis was associated with a 48 % relative-risk reduction compared to placebo .
There was no evidence of an association between efficacy and dose of acetazolamide .
Adverse effects were often not systematic ally reported but appeared to be common but generally mild .
Acetazolamide is effective prophylaxis for the prevention of symptoms of AMS in those going to high altitude .
A dose of 250 mg/day has similar efficacy to higher doses and may have a favorable side-effect profile | BACKGROUND Acetazolamide has been reported to be effective in the prevention of acute mountain sickness ( AMS ) .
Our aim was to conduct a systematic review of r and omized , placebo-controlled trials of acetazolamide in the prevention of AMS . | This study evaluated the relevance of the Lake Louise acute mountain sickness ( AMS ) scoring system in comparison with other AMS scoring systems . To achieve this objective nine subjects were su bmi tted to a 9-hr exposure to hypoxia in a hypobaric chamber ( altitude 4500 - 5500 m ) that led to the development of AMS . AMS was scored at the end of this exposure period both by question naires ( Hackett AMS question naire , Lake Louise AMS self-report question naire , Environmental Symptoms Question naire ESQ II and ESQ IV ) and by a clinical investigation following the Lake Louise AMS clinical and functional AMS assessment . The AMS scores were between 0 and 9 for the Hackett AMS score , 0 and 38 for the ESQ II AMS score , 0 and 13.7 for the ESQ IV AMS score , 0 and 10 for the Lake Louise AMS self-report , 0 and 2 for the Lake Louise AMS clinical assessment score , and between 0 and 2 for the Lake Louise functional score . All the AMS question naire scores were related to the clinical AMS assessment score ( p < 0.05 ) without significant differences between them . The Lake Louise AMS self-report score appeared highly correlated to other AMS scoring systems ( Hackett , ESQ II and ESQ IV ) ( p < 0.05 ) . Suggestions were proposed to improve the sensitivity and the specificity of the Lake Louise AMS scoring question naire but also the Lake Louise AMS clinical assessment . In conclusion , this study suggests the relevance of the Lake Louise AMS self-report question naire to assess and score AMS with simplicity and rapidity Abstract : A study was carried out to determine the effectiveness of low doses of acetazolamide in ameliorating the symptoms of altitude sickness . Subjects were placed in a low pressure chamber at either 14,000 ft . or 3,000 ft . for 24 hours . Before entering the chamber each subject took a total of 750 mg . of acetazolamide or a placebo . During their 24-hour stay , the subjects filled out a question naire design ed to evaluate their state of well-being . End-tidal PCO2 was measured , and electrodes were applied for monitoring respiratory pattern and EEG . Subjects were given a ranking of 1 ( worst ) to 4 ( best ) comparing individual clinical states . Sample s of arterial blood and cerebrospinal fluid were obtained and analyzed for pH , PO2 , PCO2 , CO2 , HCO3(- ) , and lactate . Twenty-four-hour urine volumes were analyzed for Na , K , and 17-hydroxycorticosteroids . Acetazolamide significantly lowered arterial and CSF HCO3(- ) , arterial and end-tidal PCO2 , and arterial pH. The mean arterial PO2 was higher in those receiving acetazolamide , but the increase was not significant ( P < .10 ) . Pretreatment with acetazolamide was of sufficient clinical benefit to allow its recommendation prior to altitude exposure . ( Author In this r and omized , double-blind placebo controlled trial our objectives were to determine if acetazolamide is capable of preventing high altitude pulmonary edema ( HAPE ) in trekkers traveling between 4250 m (Pheriche)\4350 m ( Dingboche ) and 5000 m ( Lobuje ) in Nepal ; to determine if acetazolamide decreases pulmonary artery systolic pressures ( PASP ) at high altitude ; and to determine if there is an association with PASP and signs and symptoms of HAPE . Participants received either acetazolamide 250 mg PO BID or placebo at Pheriche\Dingboche and were reassessed in Lobuje . The Lake Louise Consensus Criteria were used for the diagnosis of HAPE , and cardiac ultrasonography was used to measure the velocity of tricuspid regurgitation and estimate PASP . Complete measurements were performed on 339 of the 364 subjects ( 164 in the placebo group , 175 in the acetazolamide group ) . No cases of HAPE were observed in either study group nor were differences in the signs and symptoms of HAPE found between the two groups . Mean PASP values did not differ significantly between the acetazolamide and placebo groups ( 31.3 and 32.6 mmHg , respectively ) . An increasing number of signs and symptoms of HAPE was associated with elevated PASP ( p < 0.01 ) . The efficacy of acetazolamide against acute mountain sickness , however , was significant with a 21.9 % incidence in the placebo group compared to 10.2 % in the acetazolamide group ( p < 0.01 ) . Given the lack of cases of HAPE in either group , we can draw no conclusions about the efficacy of acetazolamide in preventing HAPE , but the absence of effect on PASP suggests that any effect may be minor possibly owing to partial acclimatization during the trek up to 4200 Self-rated moods were determined twice daily with the Clyde Mood Scale on 35 human subjects at 200 m ( baseline ) during a study concerned with evaluating the efficacy of staging plus acetazolamide ( treatment ) for the prevention of acute mountain sickness ( AMS ) . Mood states also were determined on all subjects at 4300 m ( Pikes Peak , Co ) and on 18 of these subjects at 1600 m ( staging site ) . Mood state changes were not observed at 1600 m , but four of the six mood factors were sensitive to the 4300 m altitude . At 4300 m , all subjects , treatment and control , rated themselves as less friendly and clear thinking and more sleepy and dizzy . At 4300 m , the treatment strategy result ed in an improved mood on the friendly , sleepy , and dizzy factors . Altitude-induced changes in clear thinking were not altered by the treatment strategy Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Acute mountain sickness ( A.M.S. ) and its severe complications , high-altitude pulmonary oedema ( H.A.P.O. ) and cerebral oedema ( C.O. ) , were studied in 278 unacclimatised hikers at 4243 m altitude at Pheriche in the Himalayas of Nepal . The overall incidence of A.M.S. was 53 % , the incidence being increased in the young and in those who flew to 2800 m , climbed fast , and spent fewer nights acclimatising en route . It was unrelated to sex , to previous altitude experience , to the load carried , and to recent respiratory infections . The severity of A.M.S. was inversely related to age ( independent of rate of ascent ) and the highest altitude attained , and was highly ocrrelated with speed of ascent . There were 7 cases of H.A.P.O. and 5 with the more intractable C.O. and , of these 12 , 11 had flown in , 9 had spent only one night at Pheriche , and none were on acetazolamide . 11 required evacuation . Acetazolamide , compared in a double-blind study with a placebo and also compared with no tablets at all , reduced both the incidence and the severity of A.M.S. in those who flew to 2800 m but not in those who hiked up to that altitude . Prevention consists in slow ascent , rapid recognition of warning signs , and prompt descent to avoid progression BACKGROUND Acute mountain sickness ( AMS ) commonly occurs when unacclimatized individuals ascend to altitudes above 2000 m. Acetazolamide and Ginkgo biloba have both been recommended for AMS prophylaxis ; however , there is conflicting evidence regarding the efficacy of Ginkgo biloba use . We performed a r and omized , placebo-controlled trial of acetazolamide vs Ginkgo biloba for AMS prophylaxis . METHODS We r and omized unacclimatized adults to receive acetazolamide , Ginkgo biloba , or placebo in double-blind fashion and took them to an elevation of 3800 m for 24 hours . We grade d AMS symptoms using the Lake Louise Acute Mountain Sickness Scoring System ( LLS ) and compared the incidence of AMS ( defined as LLS score > or =3 and headache ) . RESULTS Fifty-seven subjects completed the trial ( 20 received acetazolamide ; 17 , Ginkgo biloba , and 20 , placebo ) . The LLS scores were significantly different between groups ; the median score of the acetazolamide group was significantly lower than that of the placebo group ( P=.01 ; effect size , 2 ; and 95 % confidence interval [ CI ] , 0 to 3 ) , unlike that of the Ginkgo biloba group ( P=.89 ; effect size , 0 ; and 95 % CI , -2 to 2 ) . Acute mountain sickness occurred less frequently in the acetazolamide group than in the placebo group ( effect size , 30 % ; 95 % CI , 61 % to -15 % ) , and the frequency of occurrence was similar between the Ginkgo biloba group and the placebo group ( effect size , -5 % ; 95 % CI , -37 % to 28 % ) . CONCLUSIONS In this study , prophylactic acetazolamide therapy decreased the symptoms of AMS and trended toward reducing its incidence . We found no evidence of similar efficacy for Ginkgo biloba Previous attempts to detect global cerebral hemodynamic differences between those who develop headache , nausea , and fatigue following rapid exposure to hypoxia [ acute mountain sickness ( AMS ) ] and those who remain healthy have been inconclusive . In this study , we investigated the effects of two drugs known to reduce symptoms of AMS to determine if a common cerebral hemodynamic mechanism could explain the prophylactic effect within individuals . With the use of r and omized , placebo-controlled , double-blind , crossover design , 20 healthy volunteers were given oral acetazolamide ( 250 mg ) , dexamethasone ( 4 mg ) , or placebo every 8 h for 24 h prior to and during a 10-h exposure to a simulated altitude of 4,875 m in a hypobaric chamber , which included 2 h of exercise at 50 % of altitude-specific VO(2max ) . Cerebral hemodynamic parameters derived from ultrasound assessment s of dynamic cerebral autoregulation and vasomotor reactivity were recorded 15 h prior to and after 9 h of hypoxia . AMS symptoms were scored using the Lake Louise Question naire ( LLQ ) . It was found that both drugs prevented AMS in those who became ill on placebo ( ~70 % decrease in LLQ ) , yet a common cerebral hemodynamic mechanism was not identified . Compared with placebo , acetazolamide reduced middle cerebral artery blood flow velocity ( 11 % ) and improved dynamic cerebral autoregulation after 9 h of hypoxia , but these effects appeared independent of AMS . Dexamethasone had no measureable cerebral hemodynamic effects in hypoxia . In conclusion , global cerebral hemodynamic changes result ing from hypoxia may not explain the development of AMS During an expedition to the Himalayas , we studied the sleep and respiration of six climbers . Three ingested acetazolamide ( 500 mg ) daily throughout the climb and the other three ingested placebo . At high altitude ( 4,150 - 4,846 m ) , each subject ingested temazepam ( 10 mg ) for one night and placebo for another . Acetazolamide improved sleep above 2,750 m , but it is uncertain whether this was due to sedation or to improvements in arterial oxygen saturation . Sleep was markedly disturbed in all subjects above 4,000 m. Temazepam improved sleep , and in subjects taking acetazolamide , it reduced sleep-onset latencies and increased sleep efficiency close to that of sea level values . These observations suggest that the prophylactic use of acetazolamide is likely to improve sleep in climbers and that a low dose of a benzodiazepine such as temazepam ( 10 mg ) may be beneficial at high altitude . Studies are now needed to exclude any possibility of respiratory impairment at altitude before a firm recommendation can be made regarding the routine use of this hypnotic Abstract Objective To evaluate the efficacy of ginkgo biloba , acetazolamide , and their combination as prophylaxis against acute mountain sickness . Design Prospect i ve , double blind , r and omised , placebo controlled trial . Setting Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002 . Participants 614 healthy western trekkers ( 487 completed the trial ) assigned to receive ginkgo , acetazolamide , combined acetazolamide and ginkgo , or placebo , initially taking at least three or four doses before continued ascent . Main outcome measures Incidence measured by Lake Louise acute mountain sickness score ≥ 3 with headache and one other symptom . Secondary outcome measures included blood oxygen content , severity of syndrome ( Lake Louise scores ≥ 5 ) , incidence of headache , and severity of headache . Results Ginkgo was not significantly different from placebo for any outcome ; however participants in the acetazolamide group showed significant levels of protection . The incidence of acute mountain sickness was 34 % for placebo , 12 % for acetazolamide ( odds ratio 3.76 , 95 % confidence interval 1.91 to 7.39 , number needed to treat 4 ) , 35 % for ginkgo ( 0.95 , 0.56 to 1.62 ) , and 14 % for combined ginkgo and acetazolamide ( 3.04 , 1.62 to 5.69 ) . The proportion of patients with increased severity of acute mountain sickness was 18 % for placebo , 3 % for acetazoalmide ( 6.46 , 2.15 to 19.40 , number needed to treat 7 ) , 18 % for ginkgo ( 1 , 0.52 to 1.90 ) , and 7 % for combined ginkgo and acetazolamide ( 2.95 , 1.30 to 6.70 ) . Conclusions When compared with placebo , ginkgo is not effective at preventing acute mountain sickness . Acetazolamide 250 mg twice daily afforded robust protection against symptoms of acute mountain sickness The objective of this study was to determine the efficacy of low-dose acetazolamide ( 125 mg twice daily ) for the prevention of acute mountain sickness ( AMS ) . The design was a prospect i ve , double-blind , r and omized , placebo-controlled trial in the Mt. Everest region of Nepal between Pheriche ( 4243 m ) , the study enrollment site , and Lobuje ( 4937 m ) , the study endpoint . The participants were 197 healthy male and female trekkers of diverse background , and they were evaluated with the Lake Louise Acute Mountain Sickness Scoring System and pulse oximetry . The main outcome measures were incidence and severity of AMS as judged by the Lake Louise Question naire score at Lobuje . Of the 197 participants enrolled , 155 returned their data sheets at Lobuje . In the treatment group there was a statistically significant reduction in incidence of AMS ( placebo group , 24.7 % , 20 out of 81 subjects ; acetazolamide group , 12.2 % , 9 out of 74 subjects ) . Prophylaxis with acetazolamide conferred a 50.6 % relative risk reduction , and the number needed to treat in order to prevent one instance of AMS was 8 . Of those with AMS , 30 % in the placebo group ( 6 of 20 ) versus 0 % in the acetazolamide group ( 0 of 9 ) experienced a more severe degree of AMS as defined by a Lake Louise Question naire score of 5 or greater ( p = 0.14 ) . Secondary outcome measures associated with statistically significant findings favoring the treatment group included decrease in headache and a greater increase in final oxygen saturation at Lobuje . We concluded that acetazolamide 125 mg twice daily was effective in decreasing the incidence of AMS in this Himalayan trekking population The study objective was to determine whether acetazolamide is effective in prophylaxis of acute mountain sickness ( AMS ) at moderate altitude in ambulatory travelers not undergoing vigorous exercise . Volunteers vacationing in La Paz , Bolivia ( 3630 m ) , immediately after arrival from sea level were studied . The design was a double-blind , r and omized trial of two doses of acetazolamide ( 125 mg twice daily , 250 mg twice daily ) versus placebo twice daily over a 24-h period . The main outcome measure was AMS score and score trend , using the Lake Louise consensus question naire . Nine of 32 subjects ( 28 % ) had symptom scoring diagnostic of AMS at 0 h. At 0 and 24 h ( respectively ) , the mean Lake Louise scores were 1.73 and 1.09 for the 11 subjects receiving placebo , 1.45 and 1.36 for the 11 subjects receiving the 125-mg dose , and 2.7 and 0.6 for the 11 subjects receiving the 250-mg dose . The absolute change in these mean scores was not significant for placebo ( p = 0.21 ) or the 125-mg dose ( p = 0.88 ) , but was significant for the 250-mg dose ( p = 0.008 ) . A comparison of a difference in decline in average AMS score over time showed a statistically significant decline for the 250-mg dosing group versus placebo ( p = 0.002 ) . The 250-mg dose of acetazolamide twice daily ( but not 125 mg twice daily ) was effective in inducing a significant decline in AMS symptoms over the 24-h period after arrival to 3630 m. These results suggest that the dosing of acetazolamide for AMS prevention in nonmountaineering tourists at altitudes below 3700 m should not be lowered below 250 mg twice daily OBJECTIVE To study the effect of medroxyprogesterone on blood gases and cerebral regional oxygenation at high altitude , alone and in conjunction with acetazolamide , and to assess the effect on acute mountain sickness ( AMS ) . DESIGN Two placebo-controlled trials during rapid ascent to high altitude . PARTICIPANTS In the first trial , 20 participants , and in the second trial , 24 participants . SETTING During rapid ascent to 4680 m and on rapid ascent to 5200 m. INTERVENTION In the first trial , participants were r and omized to receive medroxyprogesterone 30 mg or a placebo twice a day . In the second trial , participants were r and omly assigned to one of 4 groups : a placebo twice daily , medroxyprogesterone 30 mg twice daily , acetazolamide 250 mg plus a placebo twice daily , or acetazolamide 250 mg plus medroxyprogesterone 30 mg twice daily . MAIN OUTCOME MEASURES Blood gas changes and symptom scores of AMS in both trials and cerebral regional oxygen saturations in the first trial only . RESULTS Medroxyprogesterone improved peripheral oxygen saturations in both trials and improved PaO2 in combination with acetazolamide . Cerebral regional oxygen saturation was not altered by medroxyprogesterone . The reduction in symptom scores and in the extent of AMS was not significant in this limited study . CONCLUSIONS Medroxyprogesterone acts as a respiratory stimulant , but the clinical benefit regarding the development of AMS was unproven at high altitude . Combined medroxyprogesterone and acetazolamide gave the best PaO2 Previous studies have shown low-dose acetazolamide to be effective in preventing AMS in persons already at high altitude and then moving higher , a relatively low risk situation . We wished to evaluate prophylactic administration of low-dose acetazolamide for reducing the incidence and severity of AMS in a high-risk setting : rapid ascent from 1600 to 4300 m. We performed a double-blind , r and omized , placebo-controlled study with human subjects ( n=44 ) exposed to 4300 m for 24 h. Subjects were treated for 3 days prior to ascent to 4300 m and during day 1 at altitude with placebo ( n=22 ) or acetazolamide 250 mg/day ( 125 mg bid , n=22 ) . AMS diagnosis required both an AMS-C score from the Environmental Symptom Question naire-III > or=0.7 and a Lake Louise Symptom ( LLS ) question naire score > or=3 plus headache . Acetazolamide reduced the incidence of AMS compared to placebo-treated subjects ( 14 % vs. 45 % , respectively , p=0.02 ) , and the number needed to treat was 3 . The AMS-C and LLS scores were lower in acetazolamide-treated subjects , indicating less severe AMS . Low-dose acetazolamide administered prior to ascent and on day 1 at 4300 m effectively reduced the incidence and severity of AMS in a high-risk setting Abstract Objective .—This study aim ed to determine the efficacy , tolerability , and practicality of acetazolamide for the prevention of acute mountain sickness ( AMS ) in Nepali trekking porters early in the trekking season . Methods .—This study was a r and omized , double-blind controlled trial with 400 male Nepali porters in the Mount Everest region of Nepal , trekking from Namche Bazaar ( 3440 m ) to Lobuche ( 4930 m ) , the study endpoint . Participants were r and omized to receive 250 mg acetazolamide daily or placebo , and AMS symptom scores ( Lake Louise ) were compared in highl and ers vs lowl and ers . Results .—Only 109 ( 27.2 % ) of the 400 porters completed the trial ( 28 highl and ers , 81 lowl and ers ) . The rest either dropped out ( 275/400 porters , 68.8 % ) or were excluded ( 16/400 porters , 4 % ) . Acute mountain sickness occurred in 13 ( 11.9 % ) of 109 porters ; all were lowl and ers ; 7 were taking acetazolamide , 6 taking placebo . Birthplace , acclimatization in the week before the trial , ascent rate , and rest days were the most important variables affecting the incidence of AMS . No highl and ers , but 13 ( 16.1 % ) of 81 lowl and ers had AMS ( P = .016 ) . Acclimatization in the pretrial week reduced AMS incidence ( P = .013 ) , as did a slower ascent rate ( P = .0126 ) , but rest days were the most potent prophylactic variable ( P = .0001 ) . Side effects were more frequent in porters taking acetazolamide than in the placebo group ( P = .0001 ) , but there were no serious side effects . Conclusions .—Acetazolamide was tolerable , but impractical for the routine prevention of AMS in Nepali porters . A good trekking schedule and adequate acclimatization remain the most effective preventive measures . This study identified lowl and porters as a high-risk group for developing AMS Abstract The influence of acetazolamide on acute mountain sickness was tested in a double-blind study of forty-three volunteers given acetazolamide or placebo , 250 mg every eight hours , for 32 hours before and 40 hours after abrupt transportation from sea level to 12,800 feet . In response to hypoxia , control subjects hyperventilated and developed mild respiratory alkalosis with increased blood pH and reduced carbon dioxide tension and bicarbonate within eight hours after arrival at altitude . These changes persisted over the five days of the study . Alkalosis was prevented in the acetazolamide-treated group , with a greater increase in ventilation and alveolar oxygen tension and a greater decrease in carbon dioxide tension and bicarbonate than in controls . Significant reductions in frequency and severity of the most prominent symptoms of acute mountain sickness — headache , insomnia and gastrointestinal symptoms — were observed in treated subjects . In control subjects , occurrence and severity of symptoms corr We r and omly assigned 32 healthy backpackers to receive placebo , acetazolamide ( 250 mg twice a day ) , dexamethasone acetate ( 4 mg four times a day ) , or both drugs in combination to determine the drug efficacy in preventing acute mountain sickness ( AMS ) at altitudes of 3,650 to 4,050 m ( 12,000 to 13,300 ft ) . The incidence of AMS was high but symptoms were generally mild . Combined drug therapy was superior to both placebo and single drug therapy in risk reduction . Using acetazolamide alone was moderately beneficial in preventing the occurrence of AMS , although minor side effects were frequent . The use of dexamethasone alone did not significantly reduce the AMS incidence , and discontinuing its use result ed in symptoms suggestive of adrenal insufficiency . For recreational backpackers , routine drug prophylaxis is not recommended , in view of the mild nature of this illness and the adverse effects of medications . The efficacy of combined acetazolamide-dexamethasone therapy warrants further investigation at higher altitudes , where AMS is more severe , and the dexamethasone should be withdrawn gradually to avoid a possible adrenal crisis Forty-seven climbers participated in a double-blind , r and omized trial comparing acetazolamide 250 mg , dexamethasone 4 mg , and placebo every eight hours as prophylaxis for acute mountain sickness during rapid , active ascent of Mount Rainier ( elevation 4,392 m ) . Forty-two subjects ( 89.4 percent ) achieved the summit in an average of 34.5 hours after leaving sea level . At the summit or high point attained above base camp , the group taking dexamethasone reported less headache , tiredness , dizziness , nausea , clumsiness , and a greater sense of feeling refreshed ( p less than or equal to 0.05 ) . In addition , they reported fewer problems of runny nose and feeling cold , symptoms unrelated to acute mountain sickness . The acetazolamide group differed significantly ( p less than or equal to 0.05 ) from other groups at low elevations ( 1,300 to 1,600 m ) , in that they experienced more feelings of nausea and tiredness , and they were less refreshed . These drug side effects probably obscured the previously established prophylactic effects of acetazolamide for acute mountain sickness . Separate analysis of an acetazolamide subgroup that did not experience side effects at low elevations revealed a prophylactic effect of acetazolamide similar in magnitude to the dexamethasone effect but lacking the euphoric effects of dexamethasone . This study demonstrates that prophylaxis with dexamethasone can reduce the symptoms associated with acute mountain sickness during active ascent and that acetazolamide can cause side effects that may limit its effectiveness as prophylaxis against the disease BACKGROUND Hypoxemia is the immediate consequence of hyobaric hypoxia , which is the crucial starting mechanism of acute mountain sickness ( AMS ) . The AMS is generally a benign and self-limiting condition which can be prevented by gradual ascent . However , ascent rates recommended for prophylaxis of AMS are far slower than those attempted during military operations and by climbers . OBJECTIVE The current study was carried out to quantify the relationship between AMS and hypoxemia alongwith evaluating the benefits of acetazolamide-dexamethasone chemoprophylaxis during acute ascent . SUBJECTS AND METHODS Twenty-four low l and er male adults ( age mean + /- SE 27.8 + /- 1.24 years ) were selected . They were grouped in a double-blind fashion into four groups and each group ( n = 6 ) received placebo ( multivitamin ) or acetazolamide ( 250 mg ) or dexamethasone ( 4 mg ) or a combined regimen of the two drugs twice daily for 5 days , commencing 24 hours before ascent . The volunteers reached the altitude of 4578 meters within a span of one day . Their AMS symptoms were recorded on modified environmental symptoms question naire ( ESQ ) , after 24 and 72 hours of ascent . Arterial PO2 , SO2 and PCO2 were measured by GEMSTAT blood-gas analyzer ( Mallincrodt-USA ) . RESULTS The ESQ , AMS-C ( cerebral ) and AMS-R ( respiratory ) scores of combined therapy group were significantly lower as compared to the other groups on the symptom rating scale . The significant finding amongst the volunteers taking acetazolamide was mild to moderate diuresis whereas severity of headache was markedly less in dexamethasone group . The commonest feature of combined therapy was that none of the volunteers complained of headache , dysponea , irritability and more than mild disturbance of sleep . The ESQ scores of volunteers were inversely correlated to PaO2 and SaO2 after 24 hours of ascent to 4578 meters . CONCLUSION The study concludes that severity of AMS is closely related to hypoxemia and combination therapy of acetazolamide-dexamethasone may be effective in preventing AMS 750 mg per day of acetazolamide in the prevention of acute mountain sickness ( AMS ) , as recommended in the meta- analysis published in 2000 in the British Medical Journal , may be excessive and is controversial . To determine if the efficacy of low-dose acetazolamide 125 mg bd ( 250 mg ) , as currently used in the Himalayas , is significantly different from 375 mg bd ( 750 mg ) of acetazolamide in the prevention of AMS , we design ed a prospect i ve , double-blind , r and omized , placebo-controlled trial . The participants were sample d from a diverse population of ( non-Nepali ) trekkers at Namche Bazaar ( 3440 m ) in Nepal on the Everest trekking route as they ascended to study midpoints ( 4280 m/4358 m ) and the endpoint , Lobuje ( 4928 m ) , where data were collected . Participants were r and omly assigned to receive 375 mg bd of acetazolamide ( 82 participants ) , 125 mg bd of acetazolamide ( 74 participants ) , or a placebo ( 66 participants ) , beginning at 3440 m for up to 6 days as they ascended to 4928 m. The results revealed that composite AMS incidence for 125 mg bd was similar to the incidence for 375 mg bd ( 24 % vs. 21 % , 95 % confidence interval , -12.6 % , 19.8 % ) , in contrast to significantly greater AMS ( 51 % ) observed in the placebo group ( 95 % confidence interval for differences : 8 % , 46 % ; 12 % , 49 % for low and high comparisons , respectively ) . Both doses of acetazolamide improved oxygenation equally ( 82.9 % for 250 mg daily and 82.8 % for 750 mg daily ) , while placebo endpoint oxygen saturation was significantly less at 80.7 % ( 95 % confidence interval for differences : 0.5 % , 3.9 % and 0.4 % , 3.7 % for low and high comparisons , respectively ) . There was also more paresthesia in the 375-mg bd group ( p < 0.02 ) . We conclude that 125 mg bd of acetazolamide is not significantly different from 375 mg bd in the prevention of AMS ; 125 mg bd should be considered the preferred dosage when indicated for persons ascending to altitudes above 2500 Sixty-four climbers participated in a r and omized clinical trial of acetazolamide prophylaxis for acute mountain sickness ( AMS ) during rapid , active ascent of MT Rainier . Twenty-nine ( 93.6 % ) of 31 climbers receiving acetazolamide and 25 ( 75.8 % ) of 33 receiving placebo attained the summit . Time spent ascending from sea level to the summit ( 4,394 m ) averaged 33.5 hours ( range , 23 to 48 hours ) . On the summit AMS was less common in climbers receiving acetazolamide , and they experienced less headache , nausea , drowsiness , shortness of breath , and dizziness and a greater sense of satisfaction and psychological well-being . Minute ventilation on the summit was significantly greater in subjects taking acetazolamide ( 24.9 + /- 2.0 L/min compared with 16.9 + /- 3.8 L/min ) . Expired vital capacity was also greater on the summit in the acetazolamide group ( 6.9 + /- 0.4 L compared with 5.8 + /- 0.4 L ) . We conclude that acetazolamide is effective in the prophylaxis of AMS for climbers attempting rapid , active ascent . Increased ventilation at altitude , producing an increased alveolar oxygen tension , may be related to the observed amelioration of symptoms The aim of the study was to assess effects of acetazolamide in prevention of acute mountain sickness ( AMS ) and on overnight oxygenation , in patients with asthma treated at the altitude of 3,200 m. Sixteen patients with asthma , 6 males and 10 females , mean age 32 yrs , were first investigated at low altitude ( 760 m ) . They presented with mild airways obstruction , normal arterial blood gases , and normal oxygenation at night studied by pulse oximetry . After initial investigations , patients were divided by r and om number into the treated ( T ) and control ( C ) groups of eight patients each . T group patients received acetazolamide , 750 mg daily for 2 days , before the ascent and on the first day at altitude ( 3,200 m ) . Symptoms of AMS developed in seven patients from group C and in three from group T. The overnight pulse oximetry , performed on the first night at altitude , revealed that group T patients had statistically higher ( p < 0.05 ) initial , 91 vs 87 % , mean , 90 vs 86 % , and minimum , 84 vs 75 % , arterial oxygen saturation than group C patients . Overnight pulse oximetry was repeated on the 5th , 10th and 17th day at altitude , and showed that in group C patients , from the 5th day onwards , oxygenation improved to the level observed in group T patients on the first night . We conclude that pretreatment with acetazolamide before the ascent prevented patients with asthma from developing symptoms of AMS , and alleviated acute changes in arterial oxygen saturation brought about by the high altitude hypoxia Twenty-four amateur climbers took part in a double-blind controlled cross-over trial of acetazolamide versus placebo for the prevention of acute mountain sickness . They climbed Kilimanjaro ( 5895 m ) and Mt Kenya ( 5186 m ) in three weeks with five rest days between ascents . The severity of acute mountain sickness was gauged by a score derived from symptoms recorded daily by each subject . On kilimanjaro those taking acetazolamide reached a higher altitude ( 11 v 4 reached the summit ) and had a lower symptom score than those taking placebo ( mean 4.8 v 14.3 ) . Those who had taken acetazolamide on Kilimanjaro maintained their low symptom scores while taking placebo on Mt Kenya ( mean score 1.9 ) , whereas those who had taken placebo on Kilimanjaro experienced a pronounced improvement when they took acetazolamide on Mt Kenya ( mean score 2.5 ) . Acute mountain sickness prevented one subject for completing either ascent . Acetazolamide was acceptable to 23 of the 24 subjects . Acetazolamide is recommended as an acceptable and effective prophylactic for acute mountain sickness Eighteen climbers actively ascended Mount Rainier ( elevation 4,392 m ) twice during a r and omized , double-blind , concurrent , placebo-controlled , crossover trial comparing the use of acetazolamide , 250 mg , dexamethasone , 4 mg , and placebo every 8 hours as prophylaxis for acute mountain sickness . Each subject was r and omly assigned to receive placebo during one ascent and one of the active medications during the other ascent . Assessment of acute mountain sickness was performed using the Environmental Symptoms Question naire and a clinical interview . At the summit or high point attained above base camp , the use of dexamethasone significantly reduced the incidence of acute mountain sickness and the severity of symptoms . Cerebral and respiratory symptom severity scores for subjects receiving dexamethasone ( 0.26 + /- 0.16 and 0.20 + /- 0.19 , respectively ) were significantly lower than similar scores for both acetazolamide ( 0.80 + /- 0.80 and 1.20 + /- 1.05 ; P = 0.25 ) and placebo ( 1.11 + /- 1.02 and 1.45 + /- 1.27 ; P = .025 ) . Neither the use of dexamethasone nor that of acetazolamide measurably affected other physical or mental aspects . Compared with placebo , dexamethasone appears to be effective for prophylaxis of symptoms associated with acute mountain sickness accompanying rapid ascent . The precise role of dexamethasone for the prophylaxis of acute mountain sickness is not known , but it can be considered for persons without contraindications who are intolerant of acetazolamide , for whom acetazolamide is ineffective , or who must make forced , rapid ascent to high altitude for a short period of time with a guaranteed retreat route Vuyk , Jaap , Jan Van Den Bos , Kees Terhell , Rene De Bos , Ad Vletter , Pierre Valk , Martie Van Beuzekom , Jack Van Kleef , and Albert Dahan . Acetazolamide improves cerebral oxygenation during exercise at high altitude . High Alt . Med . Biol . 7:290 - 301 , 2006.--Acute mountain sickness is thought to be triggered by cerebral hypoxemia and be prevented by acetazolamide ( Actz ) . The effect of Actz on cerebral oxygenation at altitude remains unknown . In 16 members of the 2005 Dutch Cho Oyu ( 8201 m , Tibet ) expedition , the influence of Actz and exercise ( 750 mg PO daily ) on heart rate , peripheral and regional cerebral oxygen saturation ( Sa(O(2 ) ) and rS(O(2 ) ) ) , the Lake Louise score ( LLS ) , and psychomotor function were studied at 0 m 14 days prior to the expedition , after arrival at 3700 m on day 3 , after arrival at 5700 m on day 29 , and again at 5700 m before the end of the expedition on day 51 . After arrival at 3700 m , the LLS of the climbers taking Actz ( n = 8) was significantly lower compared to those who did not take Actz ( n = 8) : 0.75 + /- 1.0 versus 2.9 + /- 2.0 , p < 0.05 ( ANOVA ) . High LLSs were associated with low rS(O(2 ) ) values in rest and exercise ( p < 0.01 and p < 0.001 ) . With altitude , resting Sa(O(2 ) ) and resting rS(O(2 ) ) decreased significantly ( p < 0.001 ) , irrespective of Actz use . Exercise at 3700 m and 5700 m reduced Sa(O(2 ) ) and rS(O(2 ) ) even further compared to rest ( p < 0.001 ) , although at 3700 m the rS(O(2 ) ) was preserved better in those who took Actz ( 55.3 + /- 4.3 % versus 47.9 + /- 5.7 % , p < 0.05 ) . Irrespective of Actz use , with altitude , the percentage of omissions in the vigilance and tracking test increased while the climbers ' scores on vigor decreased ( p < 0.05 ) . In conclusion , at altitude , exercise-induced reduction in cerebral oxygenation is less in climbers on Actz compared to climbers not taking Actz . This effect is nullified after several weeks at altitude due to acclimatization in climbers not taking Actz OBJECTIVE High altitude headache ( HAH ) is the most common neurological complaint at altitude and the defining component of acute mountain sickness ( AMS ) . However , there is a paucity of literature concerning its prevention . Toward this end , we initiated a prospect i ve , double-blind , r and omized , placebo-controlled trial in the Nepal Himalaya design ed to compare the effectiveness of ibuprofen and acetazolamide for the prevention of HAH . METHODS Three hundred forty-three healthy western trekkers were recruited at altitudes of 4280 m and 4358 m and assigned to receive ibuprofen 600 mg , acetazolamide 85 mg , or placebo 3 times daily before continued ascent to 4928 m. Outcome measures included headache incidence and severity , AMS incidence and severity on the Lake Louise AMS Question naire ( LLQ ) , and visual analog scale ( VAS ) . RESULTS Two hundred sixty-five of 343 subjects completed the trial . HAH incidence was similar when treated with acetazolamide ( 27.1 % ) or ibuprofen ( 27.5 % ; P = .95 ) , and both agents were significantly more effective than placebo ( 45.3 % ; P = .01 ) . AMS incidence was similar when treated with acetazolamide ( 18.8 % ) or ibuprofen ( 13.7 % ; P = .34 ) , and both agents were significantly more effective than placebo ( 28.6 % ; P = .03 ) . In fully compliant participants , moderate or severe headache incidence was similar when treated with acetazolamide ( 3.8 % ) or ibuprofen ( 4.7 % ; P = .79 ) , and both agents were significantly more effective than placebo ( 13.5 % ; P = .03 ) . CONCLUSIONS Ibuprofen and acetazolamide were similarly effective in preventing HAH . Ibuprofen was similar to acetazolamide in preventing symptoms of AMS , an interesting finding that implies a potentially new approach to prevention of cerebral forms of acute altitude illness OBJECTIVES Over the last 20 years a number of small trials have reported that spironolactone effectively prevents acute mountain sickness ( AMS ) , but to date there have been no large r and omized trials investigating the efficacy of spironolactone in prevention of AMS . Hence , a prospect i ve , double-blind , r and omized , placebo-controlled trial was conducted to evaluate the efficacy of spironolactone in the prevention of AMS . METHODS Participants were sample d from a diverse population of western trekkers recruited at 4300 m on the Mount Everest base camp approach ( Nepal side ) en route to the study endpoint at 5000 m. Three hundred and eleven healthy trekkers were enrolled , and 251 completed the trial from October to November 2007 . Participants were r and omly assigned to receive at least 3 doses of spironolactone 50 mg BID , acetazolamide 250 mg BID , or visually matched placebo . A Lake Louise AMS Score of 3 or more , together with the presence of headache and 1 other symptom , was used to evaluate the incidence and severity of AMS . Secondary outcome measures were blood oxygen content and the incidence and severity of high altitude headache ( HAH ) . RESULTS Acetazolamide was more effective than spironolactone in preventing AMS ( OR = 0.28 , 95 % CI 0.12 - 0.60 , p < 0.01 ) . Spironolactone was not significantly different from placebo in the prevention of AMS . AMS incidence for placebo was 20.3 % , acetazolamide 10.5 % , and spironolactone 29.4 % . Oxygen saturation was also significantly increased in the acetazolamide group ( 83 % ± 0.04 ) vs spironolactone group ( 80 % ± 0.05 , p < 0.01 ) . CONCLUSIONS Spironolactone ( 50 mg BID ) was ineffective in comparison to acetazolamide ( 250 mg BID ) in the prevention of AMS in partially acclimatized western trekkers ascending to 5000 m in the Nepali Himalaya |
12,058 | 25,597,034 | Compared to placebo , antibiotic treatment relieves symptoms in a significantly higher proportion of patients within the first days of treatment .
Reporting an overall average treatment efficacy may underestimate treatment benefits in patients with a self-limiting illness | The aim of this systematic review was to synthesize the results of original studies assessing antibiotic efficacy at different time points after initiating treatment in patients with a moderate probability of acute bacterial rhinosinusitis . | In this double-blind , parallel-group , multicenter study , 169 patients with symptoms of maxillary sinusitis but without radiographically confirmed empyema ( pus ) were r and omly assigned to receive either 500 mg azithromycin once daily for 3 days ( 87 patients ) or placebo daily for 3 days ( 82 patients ) . Nasal secretion , maxillary tenderness and pain , nasal obstruction , general malaise , and hyposmia were assessed at the start of the study and on days 4 , 11 , and 25 of treatment . After 11 days 58 % of the patients in the azithromycin group were cured versus 31 % in the placebo group ; after 25 days the cure rate was 79 % versus 67 % , respectively . When both cure and improvement were considered , the corresponding figures after day 25 were 90 % and 88 % , respectively . Adverse events , predominantly gastrointestinal , occurred in 24 ( 27 % ) of the azithromycin-treated patients and in 15 ( 18 % ) of those treated with placebo , but the difference was not statistically significant . There was a difference in efficacy in favor of azithromycin in the treatment of rhinitis with symptoms of maxillary sinusitis but without radiological signs of empyema ( pus ) . Antibiotics should only be used to alleviate symptoms in patients with moderate to severe symptoms , as the results after 25 days for both improvement and cure are equal . In the treatment of acute rhinitis with symptoms and signs of maxillary sinusitis but without empyema , treatment with azithromycin seems to result in a better cure rate after 10–12 days when compared with placebo OBJECTIVE To compare the efficacy of amoxicillin vs placebo in patients with an acute upper respiratory tract infection and purulent rhinorrhea . STUDY DESIGN Double-blind r and omized placebo-controlled trial . POPULATION The 416 patients included from 69 family practice s were 12 years or older , presenting with acute upper respiratory complaints , and having a history of purulent rhinorrhea and no signs of complications of sinusitis . OUTCOMES MEASURED Therapy success ( disappearance of symptoms that most greatly affected the patient 's health ) at day 10 and duration of general illness , pain , and purulent rhinorrhea . RESULTS Therapy was successful in 35 % of patients with amoxicillin and in 29 % of patients with placebo ( relative risk [ RR ] 1.14 , 95 % confidence interval [ CI ] , 0.92 - 1.42 ) . There was no effect on duration of general illness or pain . Duration of purulent rhinorrhea was shortened by amoxicillin ( 9 days vs 14 for clearing of purulent rhinorrhea in 75 % of patients ; P = .007 ) . Diarrhea was more frequent with amoxicillin ( 29 % vs 19 % , RR 1.28 , 95 % CI , 1.05 - 1.57 ) . No complications were reported . One patient ( 0.5 % ) receiving amoxicillin and 7 ( 3.4 % ) receiving placebo discontinued trial therapy because of exacerbation of symptoms ( RR 0.25 , 95 % CI 0.04 - 1.56 , P = .07 ) . All 8 patients recovered with antibiotic therapy . CONCLUSIONS Amoxicillin has a beneficial effect on purulent rhinorrhea caused by an acute infection of the nose or sinuses but not on general recovery . The practical implication is that all such patients , whatever the suspected diagnosis , can be safely treated with symptomatic therapy and instructed to return if symptoms worsen BACKGROUND Sinusitis is the fifth most common reason for patients to visit primary care physicians , yet clinical outcomes relevant to patients are seldom studied . OBJECTIVE To determine whether patients with purulent rhinitis , " sinusitis-type symptoms , " improved with antibiotics . Second , to examine a clinical prediction rule to provide preliminary validation data . METHODS Prospect i ve clinical trial , with double-blinded placebo controlled r and omization . The setting was a suburb of Washington , DC , from Oct 1 , 2001 , to March 31 , 2003 . All participants were 18 years or older , presenting to a family practice clinic with a complaint of sinusitis and with pus in the nasal cavity , facial pressure , or nasal discharge lasting longer than 7 days . The main outcome measures were resolution of symptoms within a 14-day follow-up period and the time to improvement ( days ) . RESULTS After exclusion criteria , 135 patients were r and omized to either placebo ( n=68 ) or amoxicillin ( n=67 ) for 10 days . Intention-to-treat analyses showed that 32 ( 48 % ) of the amoxicillin group vs 25 ( 37 % ) of the placebo group ( P=.26 ) showed complete improvement by the end of the 2-week follow-up period ( relative risk=1.3 ; 95 % confidence interval [ CI ] , 0.87 - 1.94 ] ) . Although the rates of improvement were not statistically significantly different at the end of 2 weeks , the amoxicillin group improved significantly earlier , in the course of treatment , a median of 8 vs 12 days , than did the placebo group ( P=.039 ) . CONCLUSION For most patients with sinusitis-type complaints , no improvement was seen with anti-biotics over placebo . For those who did improve , data suggested there is a subgroup of patients who may benefit from antibiotics Summary In 50 adults with bacterial sinusitis , cyclacillin ( 1500 mg . per day for 7 days ) proved significantly more effective than placebo in eliminating the signs and symptoms and in eradicating the causative microorganisms , ( Staphylococcus aureus , Proteus mirabilis , and Staph , epidermidis were most frequently isolated in this series ) . Sixty percent of the cultures in the cyclacillin series were sterilized , compared with only 10 % in the placebo series . Globally , 93 % of the cyclacillin-treated patients and only 55 % of the placebo-treated patients were considered improved . Of the P. mirabilis strains encountered , 72 % were eradicated by cyclacillin ( only 40 % by placebo ) despite the relatively high cyclacillin M.I.C.s for this microorganism ( 50 to 100 μg/ml . ) . Cyclacillin was much more effective in treating human sinusitis than would have been anticipated from the M.I.C.s alone Sc and J Prim Health Care 2003;21:00 - 00 . ISSN 0281 - 34323 Objectives r - r To compare antibiotics and placebo in patients with clinical ly diagnosed acute maxillary sinusitis ( AMS ) . To study whether sinus ultrasound examination would help to detect those patients who benefit from antibiotic therapy . Design r - r A double-blind , r and omised , placebo-controlled multicentre trial . Setting r - r Nine primary care sites in Finl and . Subjects r - r 150 adult patients ( mean age 39.7 years ) with a clinical diagnosis of sinusitis . Intervention r - r Antibiotics ( amoxicillin 750 mg 2 2 , doxycycline 100 mg 2 2 or penicillin V 1500 mg 2 2 ) or placebo twice daily for 7 days ; all patients were examined with sinus ultrasound after r and omisation . Main outcome measure r - r Clinical success ( patients ' report of recovery ) in telephone interview at 2 weeks . Results r - r A total of 146 patients completed the 2-week follow-up . Patients receiving antibiotics achieved a slightly higher rate of clinical success than patients receiving placebo ( 80 % vs 66 % ; p=0.068 ) . Conclusions r - r Antibiotics hasten symptom relief in AMS . Yet many patients recover in 2 weeks without antimicrobial treatment . Only half of patients with a clinical diagnosis of AMS have sinusitis in ultrasound examination Abstract Objective : To compare the effectiveness of penicillin V and amoxycillin with placebo in treatment of adult patients with acute sinusitis . Design : R and omised , double blind , placebo controlled trial . Setting : Norwegian general practice . Subjects : 130 adult patients with a clinical diagnosis of acute sinusitis confirmed by computed tomography . Main outcome measures : Subjective status after three and 10 days of treatment , difference in clinical severity score between day 0 and day 10 as evaluated by the general practitioner , difference in score from computed tomography on day 0 and day 10 , and duration of sinusitis . Results : Amoxycillin and penicillin V led to significantly faster and better recovery than placebo . By day 10 , 71 patients receiving antibiotic treatment ( 86 % ) considered themselves to be recovered or much better compared with 25 ( 57 % ) receiving placebo . The mean ( 95 % confidence interval ) reductions in clinical severity scores by day 10 were 5.4 ( 5.0 to 5.8 ) for penicillin V , 5.5 ( 4.9 to 6.0 ) for amoxycillin , and 3.4 ( 2.8 to 4.0 ) for placebo . For the antibiotic groups combined the number of patients with the greatest degree of improvement on computed tomography ( scale 0 - 16)—that is , score 5 - 16 on day 10—was 31/83 ( 37 % ) compared with 10/44 ( 23 % ) receiving placebo . The median duration of the sinusitis was nine days in the amoxycillin group , 11 days in the penicillin V group , and 17 days in the placebo group . Conclusion : Penicillin V and amoxycillin are significantly more effective than placebo in the treatment of acute sinusitis . Key messages The median duration of sinusitis with different treatment was nine days for amoxycillin , 11 days for penicillin V , and 17 days for placebo More than half of the patients receiving antibiotic treatment reported side effects but few gave severe discomfort Half of the patients receiving placebo tablets felt restored or much better after 10 BACKGROUND Acute rhinosinusitis is one of the most common reasons for prescribing antibiotics in primary care . However , it is not clear whether antibiotics improve the outcome for patients with clinical ly diagnosed acute rhinosinusitis . We evaluated the effect of a combination product of amoxicillin-potassium clavulanate on adults with acute rhinosinusitis that was clinical ly diagnosed in a general practice setting . METHODS We conducted a r and omized , placebo-controlled , double-blind trial with 252 adults recruited at 24 general practice s and 2 outpatient clinics . Each patient had a history of purulent nasal discharge and maxillary or frontal pain for at least 48 hours . Patients were given amoxicillin , 875 mg , and clavulanic acid , 125 mg , or placebo twice daily for 6 days . Main outcome measures were time to cure ( primary outcome ) , number of days during which rhinosinusitis restricted activities at home or work , and frequency of adverse effects ( secondary outcomes ) . RESULTS The adjusted hazard ratio for the effect of amoxicillin-clavulanate was 0.99 ( 95 % confidence interval [ CI ] , 0.68 - 1.45 ) on time to cure and 1.28 ( 95 % CI , 0.80 - 2.05 ) in the prespecified subgroup of patients with a positive rhinoscopy result . At 7 days the mean difference between amoxicillin-clavulanate and placebo was -0.29 ( 95 % CI , -0.93 to 0.34 ) in the number of days with restrictions due to rhinosinusitis and -0.60 ( 95 % CI , -1.41 to 0.21 ) in patients with a positive rhinoscopy result . At 7 days patients who took amoxicillin-clavulanate were more likely to have diarrhea ( odds ratio , 3.89 ; 95 % CI , 2.09 - 7.25 ) . CONCLUSIONS Adult patients in general practice with clinical ly diagnosed acute rhinosinusitis experience no advantage with antibiotic treatment with amoxicillin-clavulanate and are more likely to experience adverse effects We compared the efficacy of penicillin V and amoxycillin treatment with placebo in 70 adult patients from Norwegian family practice with a clinical diagnosis of acute sinusitis and mucosal thickening on CT , but without fluid level or total opacification . The study was r and omized and double-blind . Three different outcomes were evaluated ; subjective status after 10 days of treatment , difference in clinical score between day 0 and day 10 , and duration of the illness episode . Amoxycillin and penicillin V gave no better response to treatment than placebo , evaluated by all three outcome measures . The median duration of the sinusitis episode was 10 days in the amoxycillin- and placebo groups and 13 days in the penicillin-V group . In patients with a clinical diagnosis of acute sinusitis , fluid level and total opacification on CT are good criteria to differentiate between groups of patients that need or do not need antibiotic treatment Abstract The aim of the present study was to assess the hypothesis that , when present in nasopharyngeal secretions , Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis play a pathogenic role early in the course of an upper respiratory tract infection . Adults with a clinical diagnosis of acute sinusitis or common cold were enrolled . Participants were r and omly assigned in a double-blind manner to receive azithromycin 500 mg daily or placebo for 3 days . The effect of treatment on symptom evolution in the predefined subset of patients with Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis in their nasopharyngeal secretions was assessed . Of 265 patients enrolled , 132 received placebo and 133 azithromycin . Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis was identified in nasopharyngeal secretions of 77 patients ( 29 % ) . In this predefined subgroup of patients with Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis , resolution of symptoms by day 7 occurred in 73 % of those treated with azithromycin compared with 47 % of those who received placebo ( P=0.007 ) . The median time before resolution of symptoms was 5 days in the azithromycin group compared to 7 days in the placebo group . Respiratory complications requiring antibiotic treatment occurred in 19 % of patients in the placebo group and in 3 % of the azithromycin group ( P=0.025 ) . In the remaining 188 patients without Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis , resolution of symptoms by day 7 was similar in both groups ( 69 % in the placebo group vs. 64 % in the azithromycin group [ P=0.75 ] ) . Antibiotic treatment is of clinical benefit for patients with acute sinusitis or common cold when Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis is present in nasopharyngeal secretions . This observation provides new insights into the pathogenic role of these bacteria in the early stage of the common cold BACKGROUND Acute sinusitis-like complaints are very common and are usually treated with antibiotics in spite of the lack of evidence for the effectiveness of antibiotic therapy and the increasing number of resistant strains . AIM To assess the effectiveness of doxycycline in adults with acute sinusitis-like complaints in general practice . METHOD The effects of doxycycline in a placebo-controlled , double-blind , r and omized trial were assessed in adults consulting their general practitioner ( GP ) with complaints after a common cold or influenza , pain in the head when bending forward , purulent nasal discharge , predominantly unilateral maxillary pain , toothache , or pain when chewing . Primary outcome events were the resolution of facial pain and the resumption of daily activities . Treatment differences were assessed by means of Kaplan-Meier curves and hazard ratios . The follow-up period was 42 days . RESULTS No significant difference was found in time to recover between the doxycycline-treated group and the placebo-treated group . However , the adjusted hazard ratio for the group receiving doxycycline was 1.17 ( 95 % CI = 0.87 - 1.57 ) for the resolution of pain and 1.31 ( 95 % CI = 0.96 - 1.78 ) for the resumption of daily activities . After 10 days , 85 % of all patients reported improvement and 60 % were completely cured . Side effects were reported by 17 % of the doxycycline-treated group , with two patients withdrawing because of side effects . CONCLUSIONS Data from this study indicate that doxycycline does not add to the effectiveness of decongestive nose drops and steam inhalation in treating acute sinusitis-like complaints in general practice adults OBJECTIVES To evaluate the efficacy and safety of moxifloxacin in the treatment of acute bacterial rhinosinusitis ( ABRS ) . STUDY DESIGN Prospect i ve , multicenter , r and omized , double-blind , phase III trial . METHODS Patients with ABRS defined by clinical , radiologic , and bacteriologic criteria were recruited to the study . Study treatments were 400 mg of oral moxifloxacin or a matching placebo daily for 5 days . The primary end point was clinical response at test-of-cure , 1 to 3 days after the end of therapy in the modified intent-to-treat ( mITT ) population ( patients with positive culture for one of five prespecified pathogens ) . Secondary efficacy variables included patient-reported symptom improvement measured using the Sino-Nasal Outcome Test-16 ( SNOT-16 ) , and concomitant medication use . RESULTS The mITT population consisted of 118 patients ( moxifloxacin , n = 73 ; placebo , n = 45 ) . Clinical success rates were numerically higher for moxifloxacin ( 78.1 % , 57/73 ) versus placebo ( 66.7 % , 30/45 ) ; ( P = .189 ) . Significantly greater mean reductions in SNOT-16 scores occurred in moxifloxacin- versus placebo-treated patients ( -17.54 vs. -12.83 ; P = .032 ) . Overall concomitant medication use was lower in moxifloxacin versus placebo patients ( 38.4 % , 28/73 vs. 55.6 % , 25/45 respectively ) . Premature discontinuation due to insufficient therapeutic effect was significantly lower in moxifloxacin- versus placebo-treated patients ( 8.2 % , 6/73 vs. 22.2 % , 10/45 ; P = .031 ) . The rate of treatment-emergent adverse events in the ITT population was similar between arms ( moxifloxacin 38.2 % , 96/251 ; placebo 40.7 % , 50/123 ) . CONCLUSIONS Although moxifloxacin 5-day therapy for ABRS was not statistically superior to placebo for the primary end point , patients who received moxifloxacin had significantly greater improvements in health outcomes and used fewer concomitant medicines than patients treated with placebo , while experiencing no increase in adverse events This study compared the relative effectiveness of two antimicrobial preparations , amoxicillin and amoxicillin-clavulanate potassium ( Augmentin ) , in the treatment of acute maxillary sinusitis in children 2 to 16 years of age . Of 171 children with persistent ( ten to 30 days ' duration ) nasal discharge or daytime cough or both , 136 ( 80 % ) had abnormal maxillary sinus radiographs . These children were stratified by age and severity of symptoms and r and omly assigned to receive either amoxicillin , amoxicillin-clavulanate potassium , or placebo . After the exclusion of 28 children with throat cultures positive for group A Streptococcus and 15 who did not complete their medication , the remaining 93 children were evaluated : 30 received amoxicillin , 28 received amoxicillin-clavulanate potassium , and 35 received placebo . Clinical assessment was performed at three and ten days . On each occasion , children treated with an antibiotic were more likely to be cured than children receiving placebo ( P less than .01 at three days , P less than .05 at ten days ) . The overall cure rate was 67 % for amoxicillin , 64 % for amoxicillin-clavulanate potassium , and 43 % for placebo BACKGROUND The value of antibiotics in acute rhinosinusitis is uncertain . Although maxillary sinusitis is commonly diagnosed and treated in general practice , no effectiveness studies have been done on unselected primary -care patients . We used a r and omised , placebo-controlled design to test the hypothesis that there would be an improvement associated with amoxycillin treatment for acute maxillary sinusitis patients presenting to general practice . METHODS Adult patients with suspected acute maxillary sinusitis were referred by general practitioners for radiographs of the maxillary sinus . Those with radiographic abnormalities ( n = 214 ) were r and omly assigned treatment with amoxycillin ( 750 mg three times daily for 7 days ; n = 108 ) or placebo ( n = 106 ) . Clinical course was assessed after 1 week and 2 weeks , and reported relapses and complications were recorded during the following year . FINDINGS After 2 weeks , symptoms had improved substantially or disappeared in 83 % of patients in the study group and 77 % of patients taking placebo . Amoxycillin did not influence the clinical course of maxillary sinusitis nor the frequency of relapses during the 1-year follow-up . Radiographs had no prognostic value , nor were they an effect modifier . Side-effects were recorded in 28 % of patients given amoxycillin and in 9 % of those taking placebo ( p < 0.01 ) . The occurrence of relapses was similar in both groups ( 21 vs 17 % ) during the follow-up year . INTERPRETATION Antibiotic treatment did not improve the clinical course of acute maxillary sinusitis presenting to general practice . For these patients , an initial radiographic examination is not necessary and initial management can be limited to symptomatic treatment . Whether antibiotics are necessary in more severe cases warrants further study Very few investigations comparing the results of different therapeutic measures in acute sinusitis have been reported . The present investigation is an attempt to evaluate objective ly the clinical course in treated acute maxillary sinusitis by the aid of radiological registration of the sinus state . Difficulties were encountered in establishing a radiological gradation corresponding to the clinical state in the diseased sinus . A radiological gradation is suggested . A group treated with nasal decongestant only , may be regarded as a control group . The results of the treatment by nasal decongestant combined with irrigation or penicillin V or lincomycin respectively were similar and significantly better than in the control group . The patient 's evaluation of the treatment after 5 days did not correlate with the radiological state but did so after 10 days OBJECTIVE To compare the effectiveness of penicillin V with placebo in the treatment of adult patients with acute maxillary sinusitis in general practice . DESIGN R and omised , double blind , placebo controlled trial . SETTING 26 Danish general practice s. PATIENTS 133 adult patients with a clinical diagnosis of acute maxillary sinusitis based on maxillary pain and raised values of either C-reactive protein ( CRP ) or erythrocyte sedimentation rate ( ESR ) . MAIN OUTCOME MEASURES Pain score and illness score as well as measurement of CRP and ESR values after initiation of treatment . RESULTS Penicillin V led to a better recovery than did placebo . The difference was statistically significant 3 days after the initiation of treatment with regard to pain reduction , whereas no significant difference was found with regard to the reduction in the sense of illness . At the end of the study , significantly more patients in the penicillin group were completely free of pain compared to the placebo group . This difference was only found in patients with an initial pain score of more than three . The cure rate was 71 % in the penicillin group and 37 % in the placebo group . Significantly more patients achieved normal CRP values when treated with penicillin ( 88 % ) as opposed to placebo ( 75 % ) . CONCLUSION Penicillin V is more effective than placebo in the treatment of acute maxillary sinusitis in adults in general practice , but only in patients with pronounced pain |
12,059 | 29,052,865 | Two variables significantly moderated this effect .
Specifically , the association increased in strength with increasing age and when the content of ambiguous scenarios matched the anxiety subtype under investigation .
Results extend findings from adult literature by demonstrating an association in children and adolescents with evidence for content specificity in the association .
Age effects imply a role for development . | BACKGROUND The tendency to interpret ambiguity as threat ( negative interpretation ) has been implicated in cognitive models of anxiety .
A significant body of research has examined the association between anxiety and negative interpretation , and review s suggest there is a robust positive association in adults .
However , evidence with children and adolescents has been inconsistent .
This study aim ed to provide a systematic quantitative assessment of the association between anxiety and negative interpretation in children and adolescents . | Publication bias , sometimes known as the " file-drawer problem " or " funnel-plot asymmetry , " is common in empirical research . The authors review the implication s of publication bias for quantitative research synthesis ( meta- analysis ) and describe existing techniques for detecting and correcting it . A new approach is proposed that is suitable for application to meta-analytic data sets that are too small for the application of existing methods . The model estimates parameters relevant to fixed-effects , mixed-effects or r and om-effects meta- analysis contingent on a hypothetical pattern of bias that is fixed independently of the data . The authors illustrate this approach for sensitivity analysis using 3 data sets adapted from a commonly cited reference work on research synthesis ( H. M. Cooper & L. V. Hedges , 1994 ) Theoretical frameworks highlight the importance of threat-related information-processing biases for underst and ing the emergence of anxiety in childhood . The psychometric properties of several tasks measuring these biases and their associations with anxiety were examined in an unselected sample of 9-year-old children ( N=155 ) . In each task , threat bias was assessed using bias scores reflecting task performance on threat versus non-threat conditions . Reliability was assessed using split-half and test-retest correlations of mean reaction times ( RTs ) , accuracy and bias indices . Convergence between measures was also examined . Mean RTs showed substantial split-half and test-retest correlations . Bias score reliability coefficients were near zero and non-significant , suggesting poor reliability in children of this age . Additionally , associations between bias scores and anxiety were weak and inconsistent and performance between tasks showed little convergence . Bias scores from RT based paradigms in the current study lacked adequate psychometric properties for measuring individual differences in anxiety-related information-processing in children Social fears and worries in children are common and impairing . Yet , questions have been raised over the efficacy , suitability and accessibility of current frontline treatments . Here , we present data on the effectiveness of a novel parent-administered Cognitive Bias Modification of Interpretations ( CBM-I ) training tool . CBM-I capitalises on findings demonstrating an association between anxiety symptoms and biased interpretations , the tendency to interpret ambiguous situations negatively . Through CBM-I training , participants are exposed to benign resolutions , and reinforced for selecting these . In adults and adolescents , CBM-I training is effective at reducing symptoms and mood reactivity . In the present study , we developed a novel , child-appropriate form of CBM-I training , by presenting training material s within bedtime stories , read by a parent to the child across three consecutive evenings . Compared to a test-retest control group ( n = 17 ) , children receiving CBM-I ( n = 19 ) reported greater endorsement of benign interpretations of ambiguous situations post-training ( compared to pre-training ) . These participants ( but not the test-retest control group ) also showed a significant reduction in social anxiety symptoms . Pending replication and extensions to a clinical sample , these data may implicate a cost-effective , mechanism-driven and developmentally-appropriate re source for targeting social anxiety problems in children According to cognitive theories of anxiety , anxious adults interpret ambiguous situations in a negative way : They overestimate danger and underestimate their abilities to cope with danger . The present study investigated whether children with social phobia , separation anxiety disorder , and generalized anxiety disorder have such a bias , compared to a clinical and a normal control group . Children were exposed to stories in which ambiguous situations were described , and asked to give their interpretations , using open and closed responses . Results showed that anxious children reported more negative cognitions than control children . However , anxious children did not overestimate danger on the free responses , but they did judge the situations as more dangerous on the closed responses . Anxious children had lower estimations of their own competency to cope with danger than the control groups on both open and closed responses . The results indicate that children with anxiety disorders have dysfunctional cognitions about ambiguous situations OBJECTIVE This study evaluated follow-up outcomes associated with cognitive behavioral therapy ( CBT ) for childhood anxiety by comparing successfully and unsuccessfully treated participants 6.72 to 19.17 years after treatment . METHOD Participants were a sample of 66 youths ( ages 7 - 14 years at time of treatment , ages 18 - 32 years at present follow-up ) who had been diagnosed with an anxiety disorder and r and omized to treatment in a r and omized clinical trial on average 16.24 ( SD = 3.56 , range = 6.72 - 19.17 ) years prior . The present follow-up included self-report measures and a diagnostic interview to assess anxiety , depression , and substance misuse . RESULTS Compared with those who responded successfully to CBT for an anxiety disorder in childhood , those who were less responsive had higher rates of panic disorder , alcohol dependence , and drug abuse in adulthood . Relative to a normative comparison group , those who were less responsive to CBT in childhood had higher rates of several anxiety disorders and substance misuse problems in adulthood . Participants remained at particularly increased risk , relative to the normative group , for generalized anxiety disorder and nicotine dependence regardless of initial treatment outcome . CONCLUSIONS The present study is the first to assess the long-term follow-up effects of CBT treatment for an anxiety disorder in youth on anxiety , depression , and substance abuse through the period of young adulthood when these disorders are often seen . Results support the presence of important long-term benefits of successful early CBT for anxiety Many anxiety disorders begin in adolescence . Early interventions that target adolescent anxiety may prevent later disabling consequences . Previous studies show that cognitive bias modification training can generate positive interpretative styles of ambiguous information in adolescents but effects on anxious mood reduction are less clear . Adult studies suggest more consistent training effects on mood when assessed in response to a psychological challenge . Here , we assess whether positive training reduces adolescent anxious responses to a laboratory stressor . A total of 40 adolescents were r and omly assigned to positive or negative computerised training . During training , ambiguous scenarios were resolved positively or negatively . After training , adolescents completed a test of interpretation bias and a difficult mental arithmetic task while believing that they were being videotaped for teaching purpose s. First , positively-trained adolescents endorsed more positive and fewer negative interpretations of new ambiguous situations than negatively-trained adolescents . Second , positively-trained adolescents also showed attenuated anxiety levels after but not before the challenge . Induced positive interpretations via computerised cognitive training may modify anxious responsivity . Although there are some caveats to these data , in general they justify extensions of computerised training to adolescents with clinical anxiety , to reduce anxious responsivity Social functioning was assessed using the Child Behavior Checklist and Teacher Report Form for children with anxiety disorders who participated in a r and omized clinical trial ( N = 161 , aged 7–14 ) . Significant relationships were found between severity of children ’s principal anxiety disorder and most measures of social functioning , such that poorer social functioning was associated with more severe anxiety . Among youth who received cognitive-behavioral therapy ( n = 111 ) , significant associations were found between parent-reported social competence and both absence of principal anxiety disorder and lower anxiety severity at posttreatment and 1-year follow-up , controlling for the severity of the child ’s principal anxiety disorder at pretreatment . Findings support a relationship between anxiety severity and social difficulties , and suggest the importance of social competence for a favorable treatment response |
12,060 | 23,549,792 | Conclusion On the basis of the available ( albeit limited ) evidence , while fDNA is cost-effective when compared with no screening , it is currently dominated by most of the other available screening options .
Cost and test performance appear to be the main influences on cost-effectiveness | Background Fecal DNA ( fDNA ) testing is a noninvasive potential alternative to current colorectal cancer screening tests .
Objective We conducted a systematic review and quality assessment of studies of cost-effectiveness of fDNA as a colorectal cancer screening tool ( compared with no screening and other screening modalities ) , and identified key variables that impinged on cost-effectiveness . | All 68,308 inhabitants of Göteborg born between 1918 and 1931 were r and omly divided into a test and a control group . The subjects in the test group were invited to perform Hemoccult II fecal occult blood testing on 3 days and to repeat the test after 16 to 24 months . In the prevalence screening 21,347 ( 63 % ) performed the test , and in the rescreening 19,991 ( 60 % ) . Investigation of the 942 ( 4.4 % ) with positive tests in the prevalence screening showed 47 cancers and 129 subjects with adenomas > or = 1.0 cm . In the rescreening 5.1 % had a positive test , and 34 cancers and 122 subjects with adenomas ( > or = 1.0 cm ) were found among those . Cancer had also been diagnosed in 19 subjects in the interval between the two screening occasions and in 15 subjects among the non-responders . Forty-four cancers had been diagnosed in the control group during the same period . Cancers detected by screening were at a less advanced stage than in the control group . It is too early to show any effect of screening on mortality from colorectal cancer Purpose Fecal immunochemical tests ( FITs ) have been developed to address analytical problems inherent in the older guaiac-based fecal occult blood tests ( g-FOBTs ) . Our aim was to compare the performance characteristics of one g-FOBT ( Hemoccult II ) and two FITs ( the Hemoccult ICT and MagStream HemSp ) relative to colonoscopy for the detection of colorectal cancer and significant precursor lesions . We also examined whether a 1-day collection strategy would negatively impact test diagnostic performance . Methods We used a prospect i ve observational cohort design in a Canadian population eligible for screening . All participants received colonoscopy after performing the occult blood tests . Results One thous and seventy-five individuals were enrolled ( mean age 56.3 years , 53.8 % females ) . Using colonoscopy as the gold st and ard , the sensitivity for screen-relevant neoplasm was determined for Hemoccult II ( 7.2 , 95 % CI : 1.1–13.4 ) , Hemoccult ICT ( 23.2 % : 13.2–33.1 ) , and MagStream HemSp using 67 μg/gram stool as the cut-off ( 23.2 % : 13.2–33.1 ) . The Magstream HemSp , using a cut-off threshold of 30 μg/gram stool , had the lowest specificity at 87.6 % ( 85.4–89.6 ) , while the Hemoccult II had the highest at 98.8 % ( 98.1–99.5 ) . Single-day stool testing reduced the false-positive rates of all tests without significantly reducing the sensitivity . Conclusion We found that FITs have a significantly increased sensitivity but reduced specificity for screen-relevant neoplasm compared to g-FOBT using colonoscopy as the gold st and ard . Optimal threshold levels for hemoglobin detection depend on the desired trade off between sensitivity and false-positive rate . Single-day testing with an FIT may be an option to enhance population compliance with screening BACKGROUND & AIMS Fecal DNA testing has shown greater sensitivity than guaiac-based occult blood tests for noninvasive colorectal cancer ( CRC ) screening . The prototype assay ( version 1 ) , which analyzed 22 gene mutations and DNA integrity assay ( DIA ) , showed a sensitivity of 52 % for CRC detection and a specificity of 94 % in average-risk individuals . The present study was conducted to determine the sensitivity and specificity of a second-generation assay ( version 2 ) that uses improved DNA stabilization/isolation techniques and a new promoter methylation marker . METHODS Forty patients with CRC and 122 subjects with normal colonoscopy provided stool sample s to which DNA preservation buffer was added immediately . DNA was purified using gel-based capture , and analyzed for the original panel of 22 mutations , DIA , and 2 new promoter methylation markers . RESULTS By using DNA that was optimally preserved and purified from stool , the sensitivity of the prototype version 1 assay increased to 72.5 % because of enhanced performance of DIA . Vimentin gene methylation alone provided sensitivity and specificity of 72.5 % and 86.9 % , respectively . The optimal combination of vimentin methylation plus DIA result ed in 87.5 % sensitivity and 82 % specificity ; cancers were detected regardless of stage or location . False-positive vimentin methylation was associated with older age . CONCLUSIONS An improved fecal DNA test that incorporates only 2 markers shows much higher sensitivity for CRC . The new assay is easier to perform and should be less costly , thereby facilitating its use for noninvasive CRC screening OBJECTIVES To determine if participation in colorectal cancer screening using faecal occult blood testing ( FOBT ) is affected by a restrictive diet and if it is associated with certain demographic variables . PARTICIPANTS AND SETTING 1,203 residents of South Australia aged 50 - 69 years , with no " currently active bowel disease " , r and omly selected from a data base of people willing to be contacted about unspecified health issues . DESIGN R and omised controlled trial : participants were offered screening by immunochemical FOBT by mail in 1998 . Half were r and omly allocated to a group instructed to follow a low-peroxidase diet , as required for guaiac FOBT , while the other group was not so restricted . MAIN OUTCOME MEASURES Effect of diet restriction on participation ( return of correctly completed FOBT sample cards within 15 weeks ) ; time taken to return cards ; relationships between participation and demographic variables . RESULTS Participation rates were 65.9 % ( no-diet group ) and 53.3 % ( diet group ) ( difference , 12.6 % ; 95 % CI , 7.1%-18.1 % ) . In the first week , rates of return as a proportion of all tests returned were 13.1 % ( no-diet ) and 1.6 % ( diet ) ( difference , 11.5 % ; 95 % CI , 8.6%-14.4 % ) , increasing to 54.3 % and 44.5 % , respectively , after five weeks ( difference , 9.8 % ; 95 % CI , 4.2%-15.4 % ) . Participation was significantly associated with older age ( odds ratio , 1.40 ; 95 % CI , 1.10 - 1.78 ) , but not sex , Index of Social Disadvantage or rural versus urban address . CONCLUSIONS Dietary restrictions create a barrier to FOBT-based screening for colorectal cancer . The use of immunochemical rather than guaiac FOBT removes this barrier Colorectal cancer is the second-leading cause of cancer death . New noninvasive options for screening capable of diagnosing cancer at an early stage are needed to improve compliance and reduce mortality . This study was design ed to provide an estimate of the sensitivity and specificity of a multitarget assay panel ( MTAP ) of stool DNA changes . Eighty patients with advanced colorectal neoplasia and 212 control subjects provided stool sample s before colonoscopy . Patients with hereditary colorectal cancer syndromes were excluded . The MTAP included 21 specific mutations in the adenomatous polyposis coli ( APC ) , p53 , and K-ras genes , a microsatellite instability marker ( BAT-26 ) , and a marker of abnormal apoptosis ( DNA Integrity Assay ) . All sample s were analyzed in the clinical laboratory at EXACT Sciences . Multitarget assay panel detected 33 of 52 patients ( 63.5 % , 95 % confidence interval [ CI ] , 49.0%-76.4 % ) with invasive colorectal cancer , including 26 of 36 ( 72.2 % ) with node-negative disease ( American Joint Committee on Cancer [ AJCC ] stage I/II ) and 7 of 16 ( 43.7 % ) with advanced disease ( AJCC stage III/IV ) . Sixteen of 28 patients ( 57.1 % ; 95 % CI , 37.2%-75.5 % ) with advanced adenomas ( lesions containing high- grade dysplasia , villous adenomas , or tubular adenomas > 1 cm in size ) were detected , including 6 of 7 ( 85.7 % ) with high- grade dysplasia and 10 of 21 ( 47.6 % ) with other advanced adenomas . Specificity was 96.2 % ( 95 % CI , 92.7%-98.4 % ) in patients with either no colorectal lesions or diminutive polyps . Multitarget assay panel has better sensitivity than that reported with use of Hemoccult(R ) II in fecal occult blood testing , with similar specificity . Sensitivity appeared to be equally high for patients with node-negative and advanced disease , as well as for advanced adenomas . This study contained a disproportionately high number of distal cancers and , as such , may not be representative of results in proximal lesions . Although a prospect i ve study in an average-risk population is needed to vali date these findings , MTAP may offer an important noninvasive option for population -based screening BACKGROUND Although fecal occult-blood testing is the only available noninvasive screening method that reduces the risk of death from colorectal cancer , it has limited sensitivity . We compared an approach that identifies abnormal DNA in stool sample s with the Hemoccult II fecal occult-blood test in average-risk , asymptomatic persons 50 years of age or older . METHODS Eligible subjects su bmi tted one stool specimen for DNA analysis , underwent st and ard Hemoccult II testing , and then underwent colonoscopy . Of 5486 subjects enrolled , 4404 completed all aspects of the study . A subgroup of 2507 subjects was analyzed , including all those with a diagnosis of invasive adenocarcinoma or advanced adenoma plus r and omly chosen subjects with no polyps or minor polyps . The fecal DNA panel consisted of 21 mutations . RESULTS The fecal DNA panel detected 16 of 31 invasive cancers , whereas Hemoccult II identified 4 of 31 ( 51.6 percent vs. 12.9 percent , P=0.003 ) . The DNA panel detected 29 of 71 invasive cancers plus adenomas with high- grade dysplasia , whereas Hemoccult II identified 10 of 71 ( 40.8 percent vs. 14.1 percent , P<0.001 ) . Among 418 subjects with advanced neoplasia ( defined as a tubular adenoma at least 1 cm in diameter , a polyp with a villous histologic appearance , a polyp with high- grade dysplasia , or cancer ) , the DNA panel was positive in 76 ( 18.2 percent ) , whereas Hemoccult II was positive in 45 ( 10.8 percent ) . Specificity in subjects with negative findings on colonoscopy was 94.4 percent for the fecal DNA panel and 95.2 percent for Hemoccult II . CONCLUSIONS Although the majority of neoplastic lesions identified by colonoscopy were not detected by either noninvasive test , the multitarget analysis of fecal DNA detected a greater proportion of important colorectal neoplasia than did Hemoccult II without compromising specificity BACKGROUND One type of fecal occult blood test ( FOBT ) , the unrehydrated guaiac fecal occult blood test ( GT ) , is recommended by the United States Preventive Services Task Force and the Institute of Medicine for use in screening programs , but it has relatively low sensitivity as a single test for detecting advanced colonic neoplasms ( cancer and adenomatous polyps > or = 1 cm in diameter ) . Thus , improving the sensitivity of FOBT should make colon cancer screening programs that use these tests more effective . METHODS We assessed prospect ively the performance characteristics of two newer FOBTs in 5841 subjects at average risk for colorectal cancer in a large group-model managed care organization . The tests evaluated included a sensitive GT , a fecal immunochemical test ( FIT ) , and the combination of both tests . Patients with positive and negative test results were advised to have colonoscopy and sigmoidoscopy , respectively . Sensitivity and specificity for detecting advanced neoplasms in the left colon within 2 years after the FOBT screening were evaluated for the two tests administered separately and in combination . RESULTS A total of 139 patients were diagnosed with advanced colorectal neoplasms ( n = 14 cancers , n = 128 adenomas ) within the 2 years following their initial FOBT screening . Sensitivity for detecting cancer was 81.8 % ( 95 % confidence interval [ CI ] = 47.8 % to 96.8 % ) for the FIT alone and 64.3 % ( 95 % CI = 35.6 % to 86.0 % ) for the sensitive GT and the combination test . Sensitivity for detecting advanced colorectal adenomas was 41.3 % ( 95 % CI = 32.7 % to 50.4 % ) for the sensitive GT , 29.5 % ( 95 % CI = 21.4 % to 38.9 % ) for the FIT , and 22.8 % ( 95 % CI = 16.1 % to 31.3 % ) for the combination test . Specificity for detecting cancer and adenomas was 98.1 % ( 95 % CI = 97.7 % to 98.4 % ) and 98.4 % ( 95 % CI = 98.0 % to 98.7 % ) , respectively , for the combination test ; 96.9 % ( 95 % CI = 96.4 % to 97.4 % ) and 97.3 % ( 95 % CI = 96.8 % to 97.7 % ) , respectively , for the FIT ; and 90.1 % ( 95 % CI = 89.3 % to 90.8 % ) and 90.6 % ( 95 % CI = 89.8 % to 91.4 % ) , respectively , for the sensitive GT . CONCLUSIONS The FIT has high sensitivity and specificity for detecting left-sided colorectal cancer , and it may be a useful replacement for the GT BACKGROUND Case-control studies and a voluntary-based follow-up study have suggested that repeated screening with faecal-occult-blood ( FOB ) tests can lead to a reduction in mortality from colorectal cancer ( CRC ) . The aim of this r and omised study was to compare mortality rates after FOB tests every 2 years during a 10-year period with those of unscreened similar controls . METHODS 140,000 people aged 45 - 75 years lived in Funen , Denmark , in August , 1985 , and were considered for inclusion in our study . Before r and omisation we excluded individuals who had CRC or precursor adenomas and those who had taken part in a previous pilot study . R and omisation of 137,485 people in blocks of 14 allocated three per 14 to the screening group ( 30,967 ) , three per 14 to the control group ( 30,966 ) , and eight not to be enrolled in the study ( 75,552 ) . Controls were not told about the study and continued to use health-care facilities as normal . Hemoccult-II blood tests ( with dietary restrictions but without rehydration ) were sent to screening-group participants . Only those participants who completed the first screening round were invited for further screening -- five rounds of screening during a 10-year period . Participants with positive tests were asked to attend to full examination and were offered colonoscopy whenever possible . The primary endpoint was death from CRC . FINDINGS Of the 30,967 screening-group participants , 20,672 ( 67 % ) completed the first screening round and were invited for further screening ; more than 90 % accepted repeated screenings . During the 10-year study , 481 people in the screening group had a diagnosis of CRC , compared with 483 unscreened controls . There were 205 deaths attributable to CRC in the screening group , compared with 249 deaths in controls . CRC mortality , including deaths attributable to complications from CRC treatment , was significantly lower in the screening group than in controls ( mortality ratio 0.82 [ 95 % CI 0.68 - 0.99 ] ) p = 0.03 ) . INTERPRETATION Our findings indicate that biennial screening by FOB tests can reduce CRC mortality . This study is being continued to improve its statistical power and to assess the effect of the removal of more precursor adenomas in the screening-group participants than in controls on CRC incidence Background : Screening for colorectal cancer ( CRC ) is widely accepted , but there is no consensus on the preferred strategy . We conducted a r and omised trial comparing participation and detection rates ( DR ) per screenee of guaiac-based faecal occult blood test ( gFOBT ) , immunochemical FOBT ( FIT ) , and flexible sigmoidoscopy ( FS ) for CRC screening . Methods : A representative sample of the Dutch population ( n = 15 011 ) , aged 50–74 years , was 1:1:1 r and omised prior to invitation to one of the three screening strategies . Colonoscopy was indicated for screenees with a positive gFOBT or FIT , and for those in whom FS revealed a polyp with a diameter ⩾10 mm ; adenoma with ⩾25 % villous component or high grade dysplasia ; serrated adenoma ; ⩾3 adenomas ; ⩾20 hyperplastic polyps ; or CRC . Results : The participation rate was 49.5 % ( 95 % confidence interval ( CI ) 48.1 to 50.9 % ) for gFOBT , 61.5 % ( CI , 60.1 to 62.9 % ) for FIT and 32.4 % ( CI , 31.1 to 33.7 % ) for FS screening . gFOBT was positive in 2.8 % , FIT in 4.8 % and FS in 10.2 % . The DR of advanced neoplasia was significantly higher in the FIT ( 2.4 % ; OR , 2.0 ; CI , 1.3 to 3.1 ) and the FS arm ( 8.0 % ; OR , 7.0 ; CI , 4.6 to 10.7 ) than the gFOBT arm ( 1.1 % ) . FS demonstrated a higher diagnostic yield of advanced neoplasia per 100 invitees ( 2.4 ; CI , 2.0 to 2.8 ) than gFOBT ( 0.6 ; CI , 0.4 to 0.8 ) or FIT ( 1.5 ; CI , 1.2 to 1.9 ) screening . Conclusion : This r and omised population -based CRC-screening trial demonstrated superior participation and detection rates for FIT compared to gFOBT screening . FIT screening should therefore be strongly preferred over gFOBT screening . FS screening demonstrated a higher diagnostic yield per 100 invitees than both FOBTs |
12,061 | 31,420,668 | Currently recommended fluconazole doses may be inadequate for cryptococcosis . | BACKGROUND Fluconazole is lifesaving for treatment and prevention of cryptococcosis ; however , optimal dosing is unknown .
Initial fluconazole doses of 100 mg to 2000mg/day have been used .
Prevalence of fluconazole non-susceptible Cryptococcus is increasing over time , risking the efficacy of long-established st and ard dosing .
Based on current minimum inhibitory concentration ( MIC ) distribution , we modeled fluconazole concentration and area under the curve ( AUC ) relative to MIC to propose a rational fluconazole dosing strategy . | BACKGROUND Treatment with low-dose amphotericin B ( 0.4 mg per kilogram of body weight per day ) or oral azole therapy in patients with the acquired immunodeficiency syndrome ( AIDS ) and cryptococcal meningitis has been associated with high mortality and low rates of cerebrospinal fluid sterilization . METHODS In a double-blind multicenter trial we r and omly assigned patients with a first episode of AIDS-associated cryptococcal meningitis to treatment with higher-dose amphotericin B ( 0.7 mg per kilogram per day ) with or without flucytosine ( 100 mg per kilogram per day ) for two weeks ( step one ) , followed by eight weeks of treatment with itraconazole ( 400 mg per day ) or fluconazole ( 400 mg per day ) ( step two ) . Treatment was considered successful if cerebrospinal fluid cultures were negative at 2 and 10 weeks or if the patient was clinical ly stable at 2 weeks and asymptomatic at 10 weeks . RESULTS At two weeks , the cerebrospinal fluid cultures were negative in 60 percent of the 202 patients receiving amphotericin B plus flucytosine and in 51 percent of the 179 receiving amphotericin B alone ( P=0.06 ) . Elevated intracranial pressure was associated with death in 13 of 14 patients during step one . The clinical outcome did not differ significantly between the two groups . Seventy-two percent of the 151 fluconazole recipients and 60 percent of the 155 itraconazole recipients had negative cultures at 10 weeks ( 95 percent confidence interval for the difference in percentages , -100 to 21 ) . The proportion of patients who had clinical responses was similar with fluconazole ( 68 percent ) and itraconazole ( 70 percent ) . Overall mortality was 5.5 percent in the first two weeks and 3.9 percent in the next eight weeks , with no significant difference between the groups . In a multivariate analysis , the addition of flucytosine during the initial two weeks and treatment with fluconazole for the next eight weeks were independently associated with cerebrospinal fluid sterilization . CONCLUSIONS For the initial treatment of AIDS-associated cryptococcal meningitis , the use of higher-dose amphotericin B plus flucytosine is associated with an increased rate of cerebrospinal fluid sterilization and decreased mortality at two weeks , as compared with regimens used in previous studies . Although consolidation therapy with fluconazole is associated with a higher rate of cerebrospinal fluid sterilization , itraconazole may be a suitable alternative for patients unable to take fluconazole Background Cryptococcus is the most common cause of adult meningitis in Africa . We evaluated the activity of adjunctive sertraline , previously demonstrated to have in vitro and in vivo activity against Cryptococcus . Methods We enrolled 172 HIV-infected Ug and ans with cryptococcal meningitis from August 2013 through August 2014 into an open-label dose-finding study to assess safety and microbiologic efficacy . Sertraline 100–400mg/day was added to st and ard therapy of amphotericin + fluconazole 800mg/day . We evaluated early fungicidal activity via Cryptococcus cerebrospinal fluid ( CSF ) clearance rate , sertraline pharmacokinetics , and in vitro susceptibility . Findings Participants receiving any sertraline dose averaged a CSF clearance rate of −0·37 ( 95%CI : −0·41 , −0·33 ) colony forming units (CFU)/mL/day . Incidence of paradoxical immune reconstitution inflammatory syndrome ( IRIS ) was 5 % ( 2/43 ) and relapse was 0 % through 12-weeks . Sertraline reached steady state concentrations in plasma by day 7 , with median steady-state concentrations of 201 ng/mL ( IQR , 90–300 ; n=49 ) with 200mg/day and 399 ng/mL ( IQR , 279–560 ; n=30 ) with 400mg/day . Plasma concentrations reached 83 % of steady state levels by day 3 . The median projected steady state brain tissue concentration at 200mg/day was 3·7 ( IQR , 2·0–5·7 ) mcg/mL and 6·8 ( IQR , 4·6–9·7 ) mcg/mL at 400mg/day . Minimum inhibitory concentrations were ≤2 mcg/mL for 27 % ( 35/128 ) , ≤4 mcg/mL for 84 % ( 108/128 ) , ≤6 mcg/mL for 91 % ( 117/128 ) , and ≤8 mcg/mL for 100 % of 128 Cryptococcus isolates . Interpretation Sertraline had faster cryptococcal CSF clearance , decreased IRIS , and decreased relapse compared with historical experiences . Sertraline reaches therapeutic levels in a clinical setting . This inexpensive and off-patent oral medication is a promising adjunctive antifungal therapy . Funding National Institutes of Health , Gr and Challenges Canada BACKGROUND Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)–related deaths per year . We tested two treatment strategies that could be more sustainable in Africa than the st and ard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy . METHODS We r and omly assigned HIV‐infected adults with cryptococcal meningitis to receive an oral regimen ( fluconazole [ 1200 mg per day ] plus flucytosine [ 100 mg per kilogram of body weight per day ] for 2 weeks ) , 1 week of amphotericin B ( 1 mg per kilogram per day ) , or 2 weeks of amphotericin B ( 1 mg per kilogram per day ) . Each patient assigned to receive amphotericin B was also r and omly assigned to receive fluconazole or flucytosine as a partner drug . After induction treatment , all the patients received fluconazole consolidation therapy and were followed to 10 weeks . RESULTS A total of 721 patients underwent r and omization . Mortality in the oral‐regimen , 1‐week amphotericin B , and 2‐week amphotericin B groups was 18.2 % ( 41 of 225 ) , 21.9 % ( 49 of 224 ) , and 21.4 % ( 49 of 229 ) , respectively , at 2 weeks and was 35.1 % ( 79 of 225 ) , 36.2 % ( 81 of 224 ) , and 39.7 % ( 91 of 229 ) , respectively , at 10 weeks . The upper limit of the one‐sided 97.5 % confidence interval for the difference in 2‐week mortality was 4.2 percentage points for the oral‐regimen group versus the 2‐week amphotericin B groups and 8.1 percentage points for the 1‐week amphotericin B groups versus the 2‐week amphotericin B groups , both of which were below the predefined 10‐percentage‐point noninferiority margin . As a partner drug with amphotericin B , flucytosine was superior to fluconazole ( 71 deaths [ 31.1 % ] vs. 101 deaths [ 45.0 % ] ; hazard ratio for death at 10 weeks , 0.62 ; 95 % confidence interval [ CI ] , 0.45 to 0.84 ; P=0.002 ) . One week of amphotericin B plus flucytosine was associated with the lowest 10‐week mortality ( 24.2 % ; 95 % CI , 16.2 to 32.1 ) . Side effects , such as severe anemia , were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen . CONCLUSIONS One week of amphotericin B plus flucytosine and 2 weeks of fluconazole plus flucytosine were effective as induction therapy for cryptococcal meningitis in re source ‐limited setting s. ( ACTA Current Controlled Trials number , IS RCT N45035509 . Objective : HIV-infected patients with treated cryptococcal meningitis are at risk for further neurological deterioration after commencing combination antiretroviral therapy ( cART ) , mostly because of cryptococcosis-associated immune reconstitution inflammatory syndrome ( C-IRIS ) . Identifying predictors of C-IRIS could enable risk stratification . Design : Prospect i ve , longitudinal cohort study for 24 weeks . Setting : Durban , South Africa . Participants : One hundred and thirty HIV-infected patients with first cryptococcal meningitis episode Intervention : Antifungal therapy ( amphotericin 1 mg/kg median 14 days , followed by consolidation and maintenance fluconazole ) and cART ( commenced median of 18 days from cryptococcal meningitis diagnosis ) . Main outcome measure : Clinical , blood , and cerebrospinal fluid ( CSF ) markers associated with C-IRIS before and during cART and clinical significance of CSF cryptococcal culture negativity pre-cART commencement . Results : Of 106 patients commencing cART , 27 ( 25.5 % ) developed C-IRIS , 16 ( 15.1 % ) neurological deterioration-not C-IRIS , and 63 ( 59.4 % ) no neurological deterioration . On multivariable analysis , C-IRIS was associated with persistent CSF cryptococcal growth [ hazard ratio ( HR ) 0.27 , P = 0.026 ] and lower CSF protein ( HR 0.53 , P = 0.059 ) prior to cART and lower CD4 + T-cell increases ( HR 0.99 , P = 0.026 ) but not change in HIV viral load during cART . Using survival analysis , patients with a negative cryptococcal culture pre-cART commencement ( n = 51 ; 48.1 % ) experienced fewer episodes of neurological deterioration , C-IRIS , and cryptococcal relapse/persistence than patients with culture positivity ( n = 55 ; 51.9 % , HR 0.33 , 0.33 , and 0.12 and P = 0.0003 , 0.0042 , and 0.0004 , respectively ) . Conclusion : Persistent CSF cryptococcal growth at cART initiation and poor CD4 + T-cell increases on cART are strong predictors of C-IRIS . Approaches aim ed at achieving CSF culture negativity prior to cART should be evaluated as a strategy to reduce rates of C-IRIS David Boulware and colleagues investigate clinical features in a prospect i ve cohort with AIDS and recent cryptococcal meningitis after initiation of antiretroviral therapy to identify biomarkers for prediction and diagnosis of CM-IRIS ( cryptococcal meninigitis-related immune reconstitution inflammatory syndrome ) Background . Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis . However , 40%–50 % of individuals have positive cerebrospinal fluid ( CSF ) fungal cultures at completion of 2 weeks of amphotericin induction therapy . Residual CSF culture positivity has historically been associated with poor clinical outcomes . We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort . Methods . Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Ug and a and South Africa received amphotericin ( 0.7–1.0 mg/kg per day ) plus fluconazole ( 800 mg/day ) for 2 weeks , followed by “ enhanced consolidation ” therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile , and then 400 mg/day for 8 weeks . Participants were r and omized to receive antiretroviral therapy ( ART ) either 1–2 or 5 weeks after diagnosis and observed for 6 months . Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures . Mortality , immune reconstitution inflammatory syndrome ( IRIS ) , and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression . Results . Of 132 participants surviving 2 weeks , 57 % had sterile CSF at 2 weeks , 23 died within 5 weeks , and 40 died within 6 months . Culture positivity was not significantly associated with mortality ( adjusted 6-month hazard ratio , 1.2 ; 95 % confidence interval , 0.6–2.3 ; P = .28 ) . Incidence of IRIS or relapse was also not significantly related to culture positivity . Conclusions . Among patients , all treated with enhanced consolidation antifungal therapy and ART , residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes An all oral treatment for cryptococcal meningitis is attractive , particularly where amphotericin B use is impractical . Both fluconazole and flucytosine are available in oral formulations and have activity against Cryptococcus neoformans . We conducted a prospect i ve phase II dose escalation study employing doses of fluconazole ranging from 800 to 2000 mg daily for 10 weeks used alone or combined with flucytosine at 100 mg/kg per day for the first 4 weeks . We found that increasing doses of fluconazole were associated with an increase in survival and a decrease in the time to conversion of the cerebrospinal fluid from culture positive to culture negative . Addition of flucytosine to fluconazole improved outcomes in each dosing cohort . High doses of fluconazole alone or combined with flucytosine were well tolerated Objectives The aim of the present study was to assess fluconazole pharmacokinetic measures in serum and cerebrospinal fluid ( CSF ) ; and the correlation of these measures with clinical outcomes of invasive fungal infections A trial of the antifungal triazole fluconazole was conducted in cancer patients with presumed or proven mold infection . Groups of patients received fluconazole at four dosages ( 800 , 1200 , 1600 , or 2000 mg/day ) . Adverse events , plasma levels , and clinical response were examined . Thirty-nine patients were enrolled . The 28 evaluable patients had presumed ( 13 patients ) or proven ( 15 ) mold infection with Aspergillus ( 4 ) and Fusarium ( 3 ) species , Zygomycetes organisms ( 1 ) , or nonspeciated mold ( 7 ) . Adverse effects included elevated liver function test results ( 8 patients ) , nausea and vomiting ( 2 ) , and erythema multiforme ( 1 ) . Neurologic toxicity occurred in 3 patients receiving 2000 mg/day . Average steady-state peak plasma concentrations were 51.8 , 74.4 , and 91.8 mg/L for dosages 1200 , 1600 , and 2000 mg/day , respectively . Seven of 28 evaluable patients responded . Response did not appear to be related to dose . Fluconazole is well tolerated at total daily doses up to 1600 mg . The data suggest a linear plasma concentration-dose relationship . The activity of fluconazole in refractory mold infections seems to be limited ABSTRACT Cryptococcal antigen screening is recommended among people living with AIDS when entering HIV care with a CD4 count of < 100 cells/μl , and preemptive fluconazole monotherapy treatment is recommended for those with sub clinical cryptococcal antigenemia . Yet , knowledge is limited of current antimicrobial resistance in Africa . We examined antifungal drug susceptibility in 198 clinical isolates collected from Kampala , Ug and a , between 2010 and 2014 using the CLSI broth microdilution assay . In comparison with two previous studies from 1998 to 1999 that reported an MIC50 of 4 μg/ml and an MIC90 of 8 μg/ml prior to widespread human fluconazole and agricultural azole fungicide usage , we report an upward shift in the fluconazole MIC50 to 8 μg/ml and an MIC90 value of 32 μg/ml , with 31 % of isolates with a fluconazole MIC of ≥16 μg/ml . We observed an amphotericin B MIC50 of 0.5 μg/ml and an MIC90 of 1 μg/ml , of which 99.5 % of isolates ( 197 of 198 isolates ) were still susceptible . No correlation between MIC and clinical outcome was observed in the context of amphotericin B and fluconazole combination induction therapy . We also analyzed Cryptococcus susceptibility to sertraline , with an MIC50 of 4 μg/ml , suggesting that sertraline is a promising oral , low-cost , available , novel medication and a possible alternative to fluconazole . Although the CLSI broth microdilution assay is ideal to st and ardize results , limit human bias , and increase assay capacity , such assays are often inaccessible in low-income countries . Thus , we also developed and vali date d an assay that could easily be implemented in a re source -limited setting , with similar susceptibility results ( P = 0.52 ) This study was design ed to compare the effectiveness of fluconazole vs. itraconazole as maintenance therapy for AIDS-associated cryptococcal meningitis . HIV-infected patients who had been successfully treated ( achieved negative culture of CSF ) for a first episode of cryptococcal meningitis were r and omized to receive fluconazole or itraconazole , both at 200 mg/d , for 12 months . The study was stopped prematurely on the recommendation of an independent Data Safety and Monitoring Board . At the time , 13 ( 23 % ) of 57 itraconazole recipients had experienced culture-positive relapse , compared with 2 relapses ( 4 % ) noted among 51 fluconazole recipients ( P = .006 ) . The factor best associated with relapse was the patient having not received flucytosine during the initial 2 weeks of primary treatment for cryptococcal disease ( relative risk = 5.88 ; 95 % confidence interval , 1.27 - 27.14 ; P = .04 ) . Fluconazole remains the treatment of choice for maintenance therapy for AIDS-associated cryptococcal disease . Flucytosine may contribute to the prevention of relapse if used during the first 2 weeks of primary therapy BACKGROUND Identifying new antifungals for cryptococcal meningitis is a priority given the inadequacy of current therapy . Sertraline has previously shown in vitro and in vivo activity against cryptococcus . We aim ed to assess the efficacy and cost-effectiveness of adjunctive sertraline in adults with HIV-associated cryptococcal meningitis compared with placebo . METHODS In this double-blind , r and omised , placebo-controlled trial , we recruited HIV-positive adults with cryptococcal meningitis from two hospitals in Ug and a. Participants were r and omly assigned ( 1:1 ) to receive st and ard therapy with 7 - 14 days of intravenous amphotericin B ( 0·7 - 1·0 mg/kg per day ) and oral fluconazole ( starting at 800 mg/day ) with either adjunctive sertraline or placebo . Sertraline was administered orally or via nasogastric tube at a dose of 400 mg/day for 2 weeks , followed by 200 mg/day for 12 weeks , then tapered off over 3 weeks . The primary endpoint was 18-week survival , analysed by intention-to-treat . This study is registered with Clinical Trials.gov , number NCT01802385 . FINDINGS Between March 9 , 2015 , and May 29 , 2017 , we screened 842 patients with suspected meningitis and enrolled 460 of a planned 550 participants , at which point the trial was stopped for futility . Three patients in the sertraline group and three patients in the placebo group were lost to follow-up and therefore discontinued before study end . At 18 weeks , 120 ( 52 % ) of 229 patients in the sertraline group and 106 ( 46 % ) of 231 patients in the placebo group had died ( hazard ratio 1·21 , 95 % CI 0·93 - 1·57 ; p=0·15 ) . The fungal clearance rate from cerebrospinal fluid was similar between groups ( 0·43 -log10 CFU/mL per day [ 95 % CI 0·37 - 0·50 ] in the sertraline group vs 0·47 -log10 CFU/mL per day [ 0·40 - 0·54 ] in the placebo group ; p=0·59 ) , as was occurrence of grade 4 or 5 adverse events ( 72 [ 31 % ] of 229 vs 75 [ 32 % ] of 231 ; p=0·98 ) , most of which were associated with amphotericin B toxicity . INTERPRETATION Sertraline did not reduce mortality and should not be used to treat patients with HIV-associated cryptococcal meningitis . The reasons for sertraline inactivity appear to be multifactorial and might be associated with insufficient duration of therapeutic sertraline concentrations . FUNDING National Institutes of Health and Medical Research Council , Wellcome Trust BACKGROUND Cryptococcal meningitis accounts for 20 to 25 % of acquired immunodeficiency syndrome-related deaths in Africa . Antiretroviral therapy ( ART ) is essential for survival ; however , the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered . METHODS We assessed survival at 26 weeks among 177 human immunodeficiency virus-infected adults in Ug and a and South Africa who had cryptococcal meningitis and had not previously received ART . We r and omly assigned study participants to undergo either earlier ART initiation ( 1 to 2 weeks after diagnosis ) or deferred ART initiation ( 5 weeks after diagnosis ) . Participants received amphotericin B ( 0.7 to 1.0 mg per kilogram of body weight per day ) and fluconazole ( 800 mg per day ) for 14 days , followed by consolidation therapy with fluconazole . RESULTS The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation ( 45 % [ 40 of 88 patients ] vs. 30 % [ 27 of 89 patients ] ; hazard ratio for death , 1.73 ; 95 % confidence interval [ CI ] , 1.06 to 2.82 ; P=0.03 ) . The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis ( P=0.007 for the comparison between groups ) ; mortality was similar in the two groups thereafter . Among patients with few white cells in their cerebrospinal fluid ( < 5 per cubic millimeter ) at r and omization , mortality was particularly elevated with earlier ART as compared with deferred ART ( hazard ratio , 3.87 ; 95 % CI , 1.41 to 10.58 ; P=0.008 ) . The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group ( 20 % and 13 % , respectively ; P=0.32 ) . All other clinical , immunologic , virologic , and microbiologic outcomes , as well as adverse events , were similar between the groups . CONCLUSIONS Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival , as compared with initiating ART at 1 to 2 weeks , especially among patients with a paucity of white cells in cerebrospinal fluid . ( Funded by the National Institute of Allergy and Infectious Diseases and others ; COAT Clinical Trials.gov number , NCT01075152 . ) |
12,062 | 31,648,271 | Economic evaluation of interventions for management of CAP to date supports cost-effectiveness of studied interventions .
However , evidence relates largely to antimicrobials choice in older population s in developed countries . | BACKGROUND Community-acquired pneumonia ( CAP ) is a major cause of mortality and morbidity worldwide .
Efficient use of re sources is fundamental for best use of money among the available and novel treatment options for the management of pneumonia .
The objective of this study was to systematic ally review the economic analysis of management strategies of pneumonia . | OBJECTIVE This study presents a cost-minimisation analysis of moxifloxacin compared to combination treatment with levofloxacin and ceftriaxone in patients hospitalised with community-acquired pneumonia ( CAP ) in Germany . RESEARCH DESIGN AND METHODS In the MOTIV study , 738 adult patients with CAP requiring hospitalisation and initial parenteral antibiotic therapy were r and omised to sequential IV/oral therapy with either moxifloxacin ( n = 368 ) , or levofloxacin and ceftriaxone ( n = 365 ) . The primary effectiveness endpoint was the proportion of patients demonstrating clinical improvement 5 - 7 days after the completion of study treatment . Subgroup analysis considered patients with severe CAP according to pneumonia severity index ( PSI ) risk class IV and V , microbiologically proven infection , a history of chronic obstructive pulmonary disease , and a history of cardiovascular disease . The analysis included the cost of study medication , hospital stay , readmission and inpatient procedures and diagnostics . Event frequency in the study was multiplied by German unit costs to estimate per-patient expenditure . The analysis was conducted from a hospital perspective . Sensitivity analysis investigated the effect of costing from an insurer perspective . RESULTS No significant difference was found in the percentage of successfully treated patients . Average per patient cost was euro 2190 for the moxifloxacin group , and euro 2619 for the levofloxacin + ceftriaxone group ( difference -euro 430 , 95 % CI : -euro 138 , -euro 740 ; p < 0.05 ) . Variability in total costs was wide , with some patients accruing up to euro 18,000 . Medication cost was significantly lower with moxifloxacin than levofloxacin + ceftriaxone ( -euro 470 , 95 % CI : -euro 522 , -euro 421 ) , and accounted for between 15 and 30 % of total costs . CONCLUSIONS In this analysis of patients hospitalised with CAP in Germany , treatment with moxifloxacin was significantly less costly than treatment with levofloxacin and ceftriaxone Current World Health Organization ( WHO ) guidelines for severe pneumonia treatment of under-5 children recommend hospital referral . However , high treatment cost is a major barrier for communities . We compared household costs for referred cases with management by lady health workers ( LHWs ) using oral antibiotics . This study was nested within a cluster r and omized trial in Haripur , Pakistan . Data on direct and indirect costs were collected through interviews and record review s in the 14 intervention and 14 control clusters . The average household cost/case for a LHW managed case was $ 1.46 compared with $ 7.60 for referred cases . When the cost of antibiotics provided by the LHW program was excluded from the estimates , the cost/case came to $ 0.25 and $ 7.51 for the community managed and referred cases , respectively , a 30-fold difference . Exp and ing severe pneumonia treatment with oral amoxicillin to community level could significantly reduce household costs and improve access to the underprivileged population , preventing many child deaths Background Knowledge of treatment cost is essential in assessing cost effectiveness in healthcare . Evidence of the potential impact of implementing available interventions against childhood illnesses in developing countries challenges us to define the costs of treating these diseases . The purpose of this study is to describe the total costs associated with treatment of pneumonia , malaria and meningitis in children less than five years in seven Kenyan hospitals . Methods Patient re source use data were obtained from largely prospect i ve evaluation of medical records and household expenditure during illness was collected from interviews with caretakers . The estimates for costs per bed day were based on published data . A sensitivity analysis was conducted using WHO-CHOICE values for costs per bed day . Results Treatment costs for 572 children ( pneumonia = 205 , malaria = 211 , meningitis = 102 and mixed diagnoses = 54 ) and household expenditure for 390 households were analysed . From the provider perspective the mean cost per admission at the national hospital was US $ 95.58 for malaria , US $ 177.14 for pneumonia and US $ 284.64 for meningitis . In the public regional or district hospitals the mean cost per child treated ranged from US $ 47.19 to US $ 81.84 for malaria and US $ 54.06 to US $ 99.26 for pneumonia . The corresponding treatment costs in the mission hospitals were between US $ 43.23 to US $ 88.18 for malaria and US $ 43.36 to US $ 142.22 for pneumonia . Meningitis was treated for US $ 189.41 at the regional hospital and US $ 201.59 at one mission hospital . The total treatment cost estimates were sensitive to changes in the source of bed day costs . The median treatment related household payments within quintiles defined by total household expenditure differed by type of facility visited . Public hospitals recovered up to 40 % of provider costs through user charges while mission facilities recovered 44 % to 100 % of costs . Conclusion Treatments cost for inpatient malaria , pneumonia and meningitis vary by facility type , with mission and tertiary referral facilities being more expensive compared to primary referral . Households of sick children contribute significantly towards provider cost through payment of user fees . These findings could be used in cost effectiveness analysis of health interventions Background : Practice guidelines suggest that all patients hospitalised with community-acquired pneumonia ( CAP ) should receive antibiotics within 4 h of admission . An audit at our hospital during 1999–2000 showed that this target was achieved in less than two thirds of patients with severe CAP . Methods : An experienced multidisciplinary steering group design ed a management pathway to improve the early delivery of appropriate antibiotics to patients with CAP . This was implemented using a multifaceted strategy . The effect of implementation was evaluated using a controlled before- and -after study design over two winter seasons ( November – April 2001–2 and 2002–3 ) . Cost-effectiveness analyses were performed from the hospital ’s perspective . Results : The proportion of patients receiving appropriate antibiotics within 4 h of admission to hospital increased from 33 % to 56 % at the intervention site , and from 32 % to 36 % at the control site ( absolute change adjusted for differences in severity of illness 17 % , p = 0.035 ) . The cost per additional patient receiving appropriate antibiotics within 4 h was £ 132 with no post-implementation evaluation , and £ 456 for a limited post-implementation evaluation . Simple modelling from the results of a large observational study suggests that the cost per death prevented could be £ 3003 with no post-implementation evaluation , or £ 16 632 with a limited post-implementation evaluation . Conclusions : The intervention markedly improved door-to-antibiotic time , albeit at considerable cost . It might still be a cost-effective strategy , however , to reduce mortality in CAP . Uncertainty about the cost effectiveness of such interventions is likely to be resolved only by a well- design ed , cluster r and omised trial Background Clinical efficacy of antibiotics may be affected by changes in the susceptibility of microorganisms to antimicrobial agents . The purpose of this study is to assess how these changes could affect the initial efficacy of ertapenem and ceftriaxone in the treatment of community-acquired pneumonia ( CAP ) in elderly patients and the potential consequences this may have in health care costs . Methods Initial efficacy in elderly was obtained from a combined analysis of two multicenter , r and omized studies . An alternative scenario was carried out using initial efficacy data according to the pneumonia severity index ( PSI ) . Country-specific pathogens distribution was obtained from a national epidemiological study , and microbiological susceptibilities to first- and second-line therapies were obtained from Spanish or European surveillance studies . A decision analytic model was used to compare ertapenem versus ceftriaxone for CAP inpatient treatment . Inputs of the model were the expected effectiveness previously estimated and re source use considering a Spanish national health system perspective . Outcomes include difference in proportion of successfully treated patients and difference in total costs between ertapenem and ceftriaxone . The model performed one-way and probabilistic sensitivity analyses . Results First-line treatment of CAP with ertapenem led to a higher proportion of successfully treated patients compared with ceftriaxone in Spain . One-way sensitivity analysis showed that length of stay was the key parameter of the model . Probabilistic sensitivity analysis showed that ertapenem can be a cost-saving strategy compared with ceftriaxone , with a 59 % probability of being dominant ( lower costs with additional health benefits ) for both , elderly patients ( > 65 years ) and patients with PSI > 3 . Conclusion The incorporation of the current antimicrobial susceptibility into the initial clinical efficacy has a significant impact in outcomes and costs in CAP treatment . The treatment with ertapenem compared with ceftriaxone result ed in better clinical outcomes and lower treatment costs for two segments of the Spanish population : elderly patients and patients with severe pneumonia ( PSI > 3 ) Background : Pneumonia is one of the leading causes of morbidity and mortality among children in many developing countries . It is reported that 12.9 million children under 5 years of age died world-wide in 1990 and one-third of these deaths or 4.3 million annually were attributed to acute respiratory infection with pneumonia . Objectives : On this basis , a study was conducted in a district hospital to study the therapy outcomes of antibiotic regimens used in pediatric community-acquired pneumonia ( CAP ) management and to conduct a cost-effectiveness analysis ( CE ) between IV ampicillin versus combination therapy of IV ampicillin and IV gentamicin . Method : A prospect i ve , r and omized , controlled , single blind study was conducted in a pediatric ward in a 80-bed district hospital . Pediatric patients diagnosed with CAP aged 2 months to 5 years old were r and omly and equally divided into two treatment arms : ampicillin versus ampicillin plus gentamicin . The dose of IV ampicillin used in this study was 100 mg/kg/day divided every 6 h and 5 mg/kg of IV gentamicin as a single daily dose . Both clinical and economic evaluations were carried out to compare both treatment arms . Results : With the inclusion and exclusion criteria , only 40 patients diagnosed with CAP were included in the study . The results showed that the two treatment arms were significantly different ( P < 0.05 ) in terms of duration of patients on ampicillin , number of days of hospitalization and time to switch to oral therapy . A significant difference was noted between the two treatment modalities in terms of effectiveness and cost ( P < 0.05 ) . Conclusion : Overall , the endpoint of this study showed that the total cost per patient of ampicillin-treated group is cheaper than the total cost with the combination therapy ( ampicillin plus gentamicin ) and reduced unnecessary exposure to adverse effects or toxicities . Besides that , addition of gentamicin in the treatment modalities will only increase the cost of treatment without introducing any changes in the treatment outcome Background To determine the cost-effectiveness of strategies of preferred antibiotic treatment with beta-lactam/macrolide combination or fluoroquinolone monotherapy compared to beta-lactam monotherapy . Methods Costs and effects were estimated using data from a cluster-r and omized cross-over trial of antibiotic treatment strategies , primarily from the reduced third payer perspective ( i.e. hospital admission costs ) . Cost-minimization analysis ( CMA ) and cost-effectiveness analysis ( CEA ) were performed using linear mixed models . CMA results were expressed as difference in costs per patient . CEA results were expressed as incremental cost-effectiveness ratios ( ICER ) showing additional costs per prevented death . Results A total of 2,283 patients were included . Crude average costs within 90 days from the reduced third payer perspective were € 4,294 , € 4,392 , and € 4,002 per patient for the beta-lactam monotherapy , beta-lactam/macrolide combination , and fluoroquinolone monotherapy strategy , respectively . CMA results were € 106 ( 95 % CI € -697 to € 754 ) for the beta-lactam/macrolide combination strategy and € -278 ( 95%CI € -991 to € 396 ) for the fluoroquinolone monotherapy strategy , both compared to the beta-lactam monotherapy strategy . The ICER was not statistically significantly different between the strategies . Other perspectives yielded similar results . Conclusions There were no significant differences in cost-effectiveness of strategies of preferred antibiotic treatment of CAP on non-ICU wards with either beta-lactam monotherapy , beta-lactam/macrolide combination therapy , or fluoroquinolone monotherapy . Trial registration The trial was registered with Clinical Trials.gov , number NCT01660204 , on May 2nd , 2012 OBJECTIVE To examine treatment costs of community-acquired pneumonia ( CAP ) in adult out patients given oral ( p.o . ) levofloxacin or cefuroxime axetil as initial therapy . STUDY DESIGN Patients with a primary diagnosis of CAP were enrolled in a multicenter , prospect i ve , r and omized , open-label , active-controlled Phase III clinical trial . Both in patients and out patients were assigned to 1 of 2 treatment groups : ( 1 ) intravenous ( i.v . ) or p.o . levofloxacin ; or ( 2 ) i.v . ceftriaxone and /or p.o . cefuroxime axetil . METHODS To make legitimate and meaningful cost comparisons between similar types of patients receiving drugs via the same route of administration ( i.e. , orally ) , this outpatient economic study examined the re source utilization of the 211 patients enrolled as out patients who received oral formulations as initial treatment ( levofloxacin , 103 patients ; cefuroxime axetil , 108 patients ) . Re source utilization data and clinical trial data were collected concurrently . To generate cost estimates , Medicare cost estimates for re sources were multiplied by the re source units used by patients in each treatment arm . RESULTS Cost estimates indicated a total cost difference that favored the levofloxacin group ( base case : $ 169 ; sensitivity analysis : $ 223 [ P = .008 ] ) . The results for the base case were not significant ( P = .094 ) . In addition , within the cost categories , there was a statistically significant study drug cost differential favoring levofloxacin ( $ 86 ; P = .0001 for both the base case and sensitivity analysis ) . CONCLUSION Oral levofloxacin is less costly than oral cefuroxime axetil in the outpatient treatment of adults with CAP STUDY OBJECTIVE To evaluate costs , clinical consequences , and cost-effectiveness from a German and French health-care system perspective of sequential i.v./po moxifloxacin monotherapy compared to co-amoxiclav with or without clarithromycin ( AMC + /- CLA ) in patients with community-acquired pneumonia ( CAP ) who required parenteral treatment . METHODS Costs and consequences over 21 days were evaluated based on clinical cure rates 5 to 7 days after treatment and health re source use reported for the TARGET multinational , prospect i ve , r and omized , open-label trial . This trial compared sequential i.v./po monotherapy with moxifloxacin ( 400 mg qd ) to i.v./po co-amoxiclav ( 1.2 g i.v./625 mg po tid ) with or without clarithromycin ( 500 mg bid ) for 7 to 14 days in hospitalized patients with CAP . Since no country-by-treatment interaction was found in spite of some country differences for length of hospital stays , re source data ( antimicrobial treatment , hospitalization , and out-of-hospital care ) from all centers were pooled and valued using German and French unit prices to estimate CAP-related cost to the German Sickness Funds and French public health-care sector , respectively . RESULTS Compared to AMC + /- CLA , treatment with moxifloxacin result ed in 5.3 % more patients achieving clinical cure 5 to 7 days after therapy ( 95 % confidence interval [ CI ] , 1.2 to 11.8 % ) , increased speed of response ( 1 day sooner for median time to first return to apyrexia , p = 0.008 ) , and a reduction in hospital stay by 0.81 days ( 95 % CI , - 0.01 to 1.63 ) within the 21-day time frame . Treatment with moxifloxacin result ed in savings of 266 euro and 381 euro for Germany and France respectively , primarily due to the shorter length of hospital stay . Cost-effectiveness acceptability curves show moxifloxacin has a > or = 95 % chance of being cost saving from French and German health-care perspectives , and higher probability of being cost-effective at acceptability thresholds up to 2,000 euro per additional patient cured . CONCLUSION i.v./po monotherapy with moxifloxacin shows clinical benefits including increased speed of response and is cost-effective compared to i.v./po AMC + /- CLA in the treatment of CAP BACKGROUND A r and omized trial was performed comparing azithromycin and levofloxacin for treating moderately to severely ill patients hospitalized with community-acquired pneumonia . This is a cost-minimization analysis comparing those regimens . METHODS The cost-minimization analysis compares 81 patients receiving sequential therapy with IV azithromycin plus IV ceftriaxone followed by oral azithromycin with 82 patients receiving IV levofloxacin followed by oral levofloxacin , all with complete economic data over approximately 30 days , including information about hospitalization , study medications , home care , postdischarge utilization , and lost productivity . Units of utilization were multiplied by unit prices in order to estimate cost per patient . These total costs were compared using a two- sample t test . RESULTS Direct medical costs of the azithromycin group were 2,481 US dollars less than the corresponding costs in the levofloxacin group ( p = 0.03 ; 95 % confidence interval , 238 US dollars to 4,724 US dollars ) . Most of the cost difference ( 2,300 US dollars ) is attributable to hospital days , with the majority of these days being spent on the general medicine wards . The precise magnitude of the cost advantage attributable to azithromycin , if any , depends on both the reduction in length of hospital stay and its associated daily cost . CONCLUSIONS Azithromycin was no more costly than levofloxacin , and perhaps less so . Cost is but one of many factors that should be considered by clinicians in decisions involving any individual patient STUDY OBJECTIVE To conduct a cost-effectiveness analysis of IV-to-oral regimens of azithromycin vs cefuroxime with or without erythromycin in the treatment of patients hospitalized with community-acquired pneumonia ( CAP ) . PATIENTS Of the 268 evaluable patients enrolled into a r and omized , multicenter clinical trial of adults , 266 patients had sufficient data to be included in this cost-effectiveness analysis . One hundred thirty-six patients received azithromycin , and 130 patients received cefuroxime with or without erythromycin . METHODS A pharmacoeconomic analysis from the hospital provider perspective was conducted . Health-care re source utilization was extracted from the clinical data base and converted to national reference costs . Decision analysis was used to structure and characterize outcomes . Sensitivity analyses were performed , and statistics were applied to the cost-effectiveness ratios . RESULTS The clinical success and adverse event rates and antibiotic-related length of stay were 78 % , 11.8 % , and 5.8 days for the azithromycin group and 75 % , 20.7 % , and 6.4 days for the group receiving cefuroxime with or without erythromycin , respectively . Geometric mean treatment costs were 4,104 US dollars ( 95 % confidence interval [ CI ] , 3,874 to 4,334 US dollars ) for the azithromycin group , and 4,578 US dollars ( 95 % CI , 4,319 to 4,837 US dollars ) for the group receiving cefuroxime with or without erythromycin ( p = 0.06 ) . The cost-effectiveness ratios were 5,265 US dollars per expected cure for the azithromycin group , and 6,145 US dollars per expected cure for group receiving cefuroxime with or without erythromycin ( p = 0.05 ) . CONCLUSIONS Despite a higher per-dose purchase price , overall costs with azithromycin tended to be lower due to decreased duration of therapy , lower preparation and administration costs , and reduced hospital length of stay . As empiric therapy , azithromycin monotherapy was cost-effective compared to cefuroxime with or without erythromycin for patients hospitalized with CAP who have no underlying cardiopulmonary disease , and no risk factors for either drug-resistant pneumococci or enteric Gram-negative pathogens A recent multicentre clinical study evaluated the safety and efficacy of i.v . ciprofloxacin therapy compared with imipenem-cilastatin in hospitalized patients with severe pneumonia . Monotherapy with i.v . ciprofloxacin was at least equivalent to imipenem in terms of bacteriological eradication and clinical response . In a single-centre , retrospective , post-therapy evaluation of persistent and subsequent infection , the incidence of gram-negative infections and associated costs were compared . The main elements of the economic analysis included costs of additional antimicrobial therapy and hospitalization . Thirty-two patients were r and omized into the study , of whom 27 were efficacy-valid . The 13 patients r and omized into the ciprofloxacin group were not significantly different from the 14 patients in the imipenem group in terms of clinical parameters . Clinical cure occurred in ten of 13 patients ( 77 % ) in the ciprofloxacin group and in seven of 14 ( 50 % ) in the imipenem group . Bacteriological eradication was achieved in 11 of 13 ( 85 % ) ciprofloxacin-treated and eight of 14 ( 57 % ) imipenem-treated patients . Five of 13 ( 38 % ) patients in the ciprofloxacin group and nine of 14 ( 64 % ) in the imipenem group experienced persistent or subsequent infection requiring post-treatment antimicrobials . In these five ciprofloxacin patients , three had cultures with gram-positive organisms only and two had cultures with both gram-positive and gram-negative organisms . In the nine imipenem-treated patients requiring post- study antimicrobials , all had gram-negative bacteria and three also had gram-positive organisms . The incidence of subsequent gram-negative infection in the two groups ( 15 % vs 64 % ) was significantly different ( P < 0.05 ) . Pseudomonas aeruginosa was isolated from seven patients in the imipenem group but only one in the ciprofloxacin group ( P < 0.05 ) . Subsequent costs for post-therapy antimicrobials and hospital stay while receiving study and post- study drug therapy were evaluated ; the cost per patient cure was US$ 29,000 for ciprofloxacin and US$ 76,000 for imipenem . Initial treatment of severe pneumonia with ciprofloxacin result ed in significantly less subsequent gram-negative infection and was associated with substantially lower curative costs STUDY OBJECTIVE To determine the cost-effectiveness of sequential IV to oral gatifloxacin therapy vs IV ceftriaxone with or without IV erythromycin to oral clarithromycin therapy to treat community-acquired pneumonia ( CAP ) patients requiring hospitalization . PATIENTS Two hundred eighty-three patients enrolled in a r and omized , double-blind , clinical trial were eligible for inclusion in the cost-effectiveness analysis . METHODS Data collected included patient demographics , clinical and microbiological outcomes , length of stay ( LOS ) , and antibiotic-related LOS ( LOSAR ) . Costs evaluated include drug acquisition ( level 1 ) ; plus costs of preparation , dispensing , and administration , treating adverse events , and clinical failures ( level 2 ) ; plus hospital per diem costs ( level 3 ) . Robustness of economic findings was tested using sensitivity analyses . RESULTS Two hundred three patients were clinical ly and economically evaluable ( 98 receiving gatifloxacin and 105 receiving ceftriaxone ) . IV erythromycin was administered to 35 patients in the ceftriaxone-treated group . Oral conversion was achieved in 98 % of patients in each group . Clinical cure and microbiological eradication rates did not differ statistically ( 98 % and 97 % with gatifloxacin vs 92 % and 92 % with ceftriaxone , respectively ) . Overall , neither geometric mean LOS nor LOSAR differed significantly ( 4.2 days and 4.1 days with gatifloxacin vs 4.9 days and 4.9 days with ceftriaxone , respectively ) . Treatment failures in the ceftriaxone group contributed to a mean incremental increase in LOSAR of 1.09 days and increased mean cost per patient . The geometric mean costs per patient ( level 3 ) were $ 5,109 for gatifloxacin and $ 6,164 for ceftriaxone ( p = 0.011 ) . The cost-effectiveness ratios ( mean cost per expected success ) were $ 5,236:1 and $ 7,047:1 for gatifloxacin and ceftriaxone , respectively . CONCLUSIONS Gatifloxacin monotherapy for CAP patients requiring hospitalization is clinical ly effective and provides an economic advantage compared to the regimen of ceftriaxone with or without erythromycin IV with a switch to oral clarithromycin OBJECTIVES To determine the population -based incidence of community-acquired pneumonia ( CAP ) in adults and to assess the relative importance of age and gender on the incidence of infections caused by different microbial pathogens . METHODS A two-year prospect i ve study in a well-defined geographic area of the Spanish Mediterranean coast . RESULTS The overall incidence rate of CAP was 12 cases ( 95 % CI 11.25 - 13.45 ) per 10,000 person-years . Incidence rates increased by age ( p<0.0001 ) and they were higher in males ( 16 versus 9 cases per 10,000 person-years ; p<0.0001 ) . The rate was especially high among males aged > or = 75 years ( 87 cases per 10,000 person-years ) . The incidence of pneumococcal pneumonia increased significantly with ageing and it was particularly high among people aged > or = 75 years ( 10 cases per 10,000 person-years ) . Very elderly people had also a 15-fold higher incidence of CAP associated with influenza virus and a 5-fold higher incidence of infections by Chlamydophila spp . , than young adults . The incidence of infections with Legionella pneumophila also increased with age and it was 10 times higher in males . In contrast , the incidence of pneumonia caused by Mycoplasma pneumoniae was unrelated to age and gender . CONCLUSIONS Age and gender have a strong influence on the overall incidence of CAP and on the incidence of pneumonia caused by the main microbial pathogens , including not only Streptococcus pneumoniae , but also influenza virus , Chlamydophila spp . and L. pneumophila . Ageing is associated with a higher risk of acquiring pneumonia by S. pneumoniae , influenza virus and Chlamydophila spp . , whereas male gender increases greatly the incidence of L. pneumophila and Chlamydophila spp We studied the cost-effectiveness of oral gemifloxacin with intravenous ceftriaxone followed by oral cefuroxime with or without a macrolide to treat patients hospitalized with community-acquired pneumonia . Data were prospect ively collected as part of a r and omized multicenter study . The costs evaluated included antimicrobial acquisition ( 1st level ) ; plus preparation , dispensing , and administration costs , and treatment of antimicrobial-related adverse events and clinical failures ( 2nd level ) ; plus per diem costs for hospital stay related to study drug administration ( 3rd level ) . At follow-up , clinical success was similar between gemifloxacin (76.9%)- and ceftriaxone (79.1%)-treated patients . The median 1st-level costs for gemifloxacin and ceftriaxone were $ 136 and $ 470 ( P<0.001 ) , respectively . For the 2nd level , these costs were $ 158 and $ 542 ( P<0.001 ) , and for the 3rd level , these were $ 5052 and $ 5789 ( P=0.025 ) , respectively . The median cost per expected success was $ 6568 for gemifloxacin and $ 7321 for ceftriaxone ( P=0.29 ) . Oral gemifloxacin is clinical ly effective and has an economic advantage over ceftriaxone , followed by oral cefuroxime with or without a macrolide Summary The cost-effectiveness of ceftriaxone 1 g in the treatment of pneumonia in general medical wards was compared with that of second-generation cephalosporins . A total of 1,706 patients were treated with either a second-generation cephalosporin ( cefotiam , cefuroxime ) or ceftriaxone ( single daily dose of 1 g ) , and 604 in each group were included in a matched-pair analysis . Cure or improvement in response to monotherapy was observed in 81.4 % of patients on cefuroxime/cefotiam vs 91 % of those on ceftriaxone ( P<0.0001 ) . Adverse events occurred with equal frequency in both groups ( 1.9 % ) . In terms of mean hospital costs for antimicrobial medication , the staff required to administer it as well as laboratory and X-ray examinations , effective treatment with ceftriaxone is DM 193/$ 105 ( 25 % ) less expensive than effective treatment with a second-generation cephalosporin ( P < 0.001 ) . From the perspective of the health insurance , the costs for a patient treated with ceftriaxone are DM 3,910/$ 2,140 vs DM 4,392/$ 2,400 for a patient treated with a second-generation cephalosporin ( March 1998 : USD 1=DM 1.83 ) |
12,063 | 31,978,280 | Statistically significant or positive trends were found in mortality , hospitalization rates , self-care ability , quality of life , anxiety , depression , and sleep , but findings were not robust or consistent . | AIMS Heart failure with preserved ejection fraction ( HFpEF ) poses a substantial challenge for clinicians , but there is little guidance for effective management .
The aim of this systematic review was to determine if there was evidence that disease management programmes ( DMPs ) improved outcomes for patients with HFpEF . | Background The efficacy of disease management programs in improving the outcome of heart failure patients remains uncertain and may vary across health systems . This study explores whether a countrywide disease management program is superior to usual care in reducing adverse health outcomes and improving well-being among community-dwelling adult patients with moderate-to-severe chronic heart failure who have universal access to advanced health-care services and technologies . Methods In this multicenter open-label trial , 1,360 patients recruited after hospitalization for heart failure exacerbation ( 38 % ) or from the community ( 62 % ) were r and omly assigned to either disease management or usual care . Disease management , delivered by multi-disciplinary teams , included coordination of care , patient education , monitoring disease symptoms and patient adherence to medication regimen , titration of drug therapy , and home tele-monitoring of body weight , blood pressure and heart rate . Patients assigned to usual care were treated by primary care practitioners and consultant cardiologists . The primary composite endpoint was the time elapsed till first hospital admission for heart failure exacerbation or death from any cause . Secondary endpoints included the number of all hospital admissions , health-related quality of life and depression during follow-up . Intention-to-treat comparisons between treatments were adjusted for baseline patient data and study center . Results During the follow-up , 388 ( 56.9 % ) patients assigned to disease management and 387 ( 57.1 % ) assigned to usual care had a primary endpoint event . The median ( range ) time elapsed until the primary endpoint event or end of study was 2.0 ( 0–5.0 ) years among patients assigned to disease management , and 1.8 ( 0–5.0 ) years among patients assigned to usual care ( adjusted hazard ratio , 0.908 ; 95 % confidence interval , 0.788 to 1.047 ) . Hospital admissions were mostly ( 70 % ) unrelated to heart failure . Patients assigned to disease management had a better health-related quality of life and a lower depression score during follow-up . Conclusions This comprehensive disease management intervention was not superior to usual care with respect to the primary composite endpoint , but it improved health-related quality of life and depression . A disease-centered approach may not suffice to make a significant impact on hospital admissions and mortality in patients with chronic heart failure who have universal access to health care . Clinical trial registration Clinical trials.gov identifier : NCT00533013 . Trial registration date : 9 August 2007 . Initial protocol release date : 20 September 2007 Abstract Background : Disease management programmes ( DMPs ) improve quality of care for patients with heart failure ( HF ) . However , only a limited number of trials have studied the efficacy of such programmes for patients with heart failure with preserved ejection fraction ( HFPEF ) . Objective : To estimate the impact of a structured , nurse-led patient education programme and care plan in general practice on outcome parameters and events in patients with HFPEF . Methods : Single blinded r and omized clinical trial with an intervention over six months and a follow-up during 12 additional months . In the control group , the patients ( n = 41 ) were managed according to Russian national guidelines . Patients in the intervention group ( n = 44 ) received education on individual lifestyle changes and modifications of cardiovascular disease ( CVD ) risk factors , home-based exercise training and weekly nurse consultations in addition to usual care . Results : Six months after their inclusion , patients in the intervention group significantly improved body mass index , waist circumference , six-min walk test distance , total cholesterol , low-density lipoprotein , left ventricular end-diastolic volume index , quality of life and level of anxiety . After 18 months , there were 11 deaths ( 25 % ) or hospitalizations in the intervention group and 12 ( 29 % ) in the control group ( P = 0.134 ) . Cardiovascular mortality and readmission rate were not reduced significantly after six months of follow-up : the hazard ratio was 0.47 ( 95 % CI : 0.17–1.28 ; P = 0.197 ) . After 18 months , this was 0.85 ( 0.42–1.73 ; P = 0.658 ) . Conclusion : This primary care based DMP for patients with HFPEF improved the patients ’ emotional status and quality of life , positively influenced body weight , functional capacity and lipid profile , and attenuated heart remodelling Importance Many patients with chronic heart failure experience reduced health status despite receiving conventional therapy . Objective To determine whether a symptom and psychosocial collaborative care intervention improves heart failure – specific health status , depression , and symptom burden in patients with heart failure . Design , Setting , and Participants A single-blind , 2-arm , multisite r and omized clinical trial was conducted at Veterans Affairs , academic , and safety-net health systems in Colorado among out patients with symptomatic heart failure and reduced health status recruited between August 2012 and April 2015 . Data from all participants were included regardless of level of participation , using an intent-to-treat approach . Interventions Patients were r and omized 1:1 to receive the Collaborative Care to Alleviate Symptoms and Adjust to Illness ( CASA ) intervention or usual care . The CASA intervention included collaborative symptom care provided by a nurse and psychosocial care provided by a social worker , both of whom worked with the patients ’ primary care clinicians and were supervised by a study primary care clinician , cardiologist , and palliative care physician . Main Outcomes and Measures The primary outcome was patient-reported heart failure – specific health status , measured by difference in change scores on the Kansas City Cardiomyopathy Question naire ( range , 0 - 100 ) at 6 months . Secondary outcomes included depression ( measured by the 9-item Patient Health Question naire ) , anxiety ( measured by the 7-item Generalized Anxiety Disorder Question naire ) , overall symptom distress ( measured by the General Symptom Distress Scale ) , specific symptoms ( pain , fatigue , and shortness of breath ) , number of hospitalizations , and mortality . Results Of 314 patients r and omized ( 157 to intervention arm and 157 to control arm ) , there were 67 women and 247 men , mean ( SD ) age was 65.5 ( 11.4 ) years , and 178 ( 56.7 % ) had reduced ejection fraction . At 6 months , the mean Kansas City Cardiomyopathy Question naire score improved 5.5 points in the intervention arm and 2.9 points in the control arm ( difference , 2.6 ; 95 % CI , –1.3 to 6.6 ; P = .19 ) . Among secondary outcomes , depressive symptoms and fatigue improved at 6 months with CASA ( effect size of –0.29 [ 95 % CI , –0.53 to –0.04 ] for depressive symptoms and –0.30 [ 95 % CI , –0.55 to –0.06 ] for fatigue ; P = .02 for both ) . There were no significant changes in overall symptom distress , pain , shortness of breath , or number of hospitalizations . Mortality at 12 months was similar in both arms ( 10 patients died receiving CASA , and 13 patients died receiving usual care ; P = .52 ) . Conclusions and Relevance This multisite r and omized clinical trial of the CASA intervention did not demonstrate improved heart failure – specific health status . Secondary outcomes of depression and fatigue , both difficult symptoms to treat in heart failure , improved . Trial Registration clinical trials.gov Identifier : Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more To determine the reliability and validity of a patient outcome question naire for chronic heart failure , a r and omized , double-blind , placebo-controlled , 3-month trial of pimobendan , an investigational medication with inotropic and vasodilator activities , was performed . Evaluated were 198 ambulatory patients with primarily New York Heart Association ( NYHA ) class III heart failure from 20 referral centers . Baseline therapy included digoxin , diuretics and , in 80 % , a converting enzyme inhibitor . Oral pimobendan at 2.5 ( n = 49 ) , 5.0 ( n = 51 ) , or 10 ( n = 49 ) mg daily or matching placebo ( n = 49 ) was administered . The Minnesota Living with Heart Failure ( LIhFE ) question naire was a primary outcome measure , along with an exercise test . Interitem correlations identified subgroups of questions representing physical and emotional dimensions . Repeated baseline scores were highly correlated ( r = 0.93 ) , as were the physical ( r = 0.89 ) and emotional ( r = 0.88 ) dimension scores . Placebo did not have a significant effect with median ( 25th , 75th percentile ) changes from baseline scores of 1 ( -3 , 5 ) , 1 ( -2 , 3 ) , and 0 ( -1 , 2 ) , respectively ( all p values greater than 0.10 ) . The 5 mg dose significantly improved the total score , 7.5 ( 0 , 18 ; p = 0.01 ) and the physical dimension , 4 ( 0 , 8 ; p = 0.01 ) , compared with placebo . Changes in the total ( r = 0.33 ; p less than 0.01 ) and physical ( r = 0.35 ; p less than 0.01 ) scores were weakly related to changes in exercise times , but corresponded well with changes in patients ' ratings of dyspnea and fatigue . ( ABSTRACT TRUNCATED AT 250 WORDS IMPORTANCE Heart failure ( HF ) has a major effect on patients ' health status , including their symptom burden , functional status , and health-related quality of life . OBJECTIVE To determine the effectiveness of a collaborative care patient-centered disease management ( PCDM ) intervention to improve the health status of patients with HF . DESIGN , SETTING , AND PARTICIPANTS The Patient-Centered Disease Management ( PCDM ) trial was a multisite r and omized clinical trial comparing a collaborative care PCDM intervention with usual care in patients with HF . A population -based sample of 392 patients with an HF diagnosis from 4 Veterans Affairs centers who had a Kansas City Cardiomyopathy Question naire ( KCCQ ) overall summary score of less than 60 ( heavy symptom burden and impaired functional status and quality of life ) were enrolled between May 2009 and June 2011 . INTERVENTIONS The PCDM intervention included collaborative care by a multidisciplinary care team consisting of a nurse coordinator , cardiologist , psychiatrist , and primary care physician ; home telemonitoring and patient self-management support ; and screening and treatment for comorbid depression . MAIN OUTCOMES AND MEASURES The primary outcome was change in the KCCQ overall summary score at 1 year ( a 5-point change is clinical ly significant ) . Mortality , hospitalization , and depressive symptoms ( Patient Health Question naire 9 ) were secondary outcomes . RESULTS There were no significant differences in baseline characteristics between patients r and omized to the PCDM intervention ( n=187 ) vs usual care ( n=197 ) ; baseline mean KCCQ overall summary scores were 37.9 vs 36.9 ( P=.48 ) . There was significant improvement in the KCCQ overall summary scores in both groups after 1 year ( mean change , 13.5 points in each group ) , with no significant difference between groups ( P=.97 ) . The intervention was not associated with greater improvement in the KCCQ overall summary scores when the effect over time was estimated using 3-month , 6-month , and 12-month data ( P=.74 ) . Among secondary outcomes , there were significantly fewer deaths at 1 year in the intervention arm ( 8 of 187 [ 4.3 % ] ) than in the usual care arm ( 19 of 197 [ 9.6 % ] ) ( P = .04 ) . Among those who screened positive for depression , there was a greater improvement in the Patient Health Question naire 9 scores after 1 year in the intervention arm than in the usual care arm ( 2.1 points lower , P=.01 ) . There was no significant difference in 1-year hospitalization rates between the intervention arm and the usual care arm ( 29.4 % vs 29.9 % , P=.87 ) . CONCLUSIONS AND RELEVANCE This multisite r and omized trial of a multifaceted HF PCDM intervention did not demonstrate improved patient health status compared with usual care . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00461513 Background Heart failure ( HF ) patients discharged from rural hospitals have higher 30-day readmission rates . Self-management ( SM ) reduces readmissions , but adherence to SM guidelines is low in the rural HF population . We tested a home-based intervention to enhance patient activation and lead to improved SM adherence . Methods In this two-group , repeated measures r and omized control trial , the main outcomes were patient reported and clinical outcomes associated with SM adherence , and all-cause readmission at 30 , 90 and 180 days . Results The study included 100 HF patients discharged from a rural critical access hospital . The intervention group received a 12-week SM training and coaching program delivered by telephone and tailored on subjects ’ activation levels . At α = .10 , the PATCH intervention showed significantly greater improvement compared to usual care in patient-reported SM adherence : weighing themselves , following a low-sodium diet , taking prescribed medication , and exercising daily ( all p < .0005 ) at 3 and 6 months after discharge . In contrast , groups did not differ in physical activity assessed by actigraphy or in clinical biomarkers . Contrary to expectation , the 30-day readmission rate was significantly higher ( p = .088 ) in the intervention group ( 19.6 % ) than in the control group ( 6.1 % ) , with no differences at 90 or 180 days . Conclusion It is feasible to conduct a r and omized controlled trial in HF patients discharged from rural critical access hospitals . Significantly higher patient-reported SM adherence was not accompanied by lower clinical biomarkers or readmission rates . Further research is needed to underst and mechanisms that influence outcomes and healthcare utilization in this population .Trial registration Clinical Trial Registration Information : Clinical Trials.gov ; NCT01964053 INTRODUCTION AND OBJECTIVES The objective of this study was to determine whether a home-based intervention can reduce mortality and hospital readmissions and improve quality of life in patients with heart failure . METHODS A r and omized clinical trial was carried out between January 2004 and October 2006 . In total , 283 patients admitted to hospital with a diagnosis of heart failure were r and omly allocated to a home-based intervention ( intervention group ) or usual care ( control group ) . The primary end-point was the combination of all-cause mortality and hospital readmission for worsening heart failure at 1-year follow-up . RESULTS The primary end-point was observed in 41.7 % of patients in the intervention group and in 54.3 % in the control group . The hazard ratio was 0.70 ( 95 % confidence interval [ CI ] 0.55 - 0.99 ) . Taking significant clinical variables into account slightly reduced the hazard ratio to 0.62 ( 95 % CI 0.50 - 0.87 ) . At the end of the study , the quality of life of patients in the intervention group was better than in the control group ( 18.57 vs. 31.11 ; P < .001 ) . CONCLUSIONS A home-based intervention for patients with heart failure reduced the aggregate of mortality and hospital readmissions and improved quality of life BACKGROUND A disease management program can reduce mortality and rehospitalization of patients with heart failure ( HF ) , but little is known about whether it can improve psychological status . The purpose of this study was to determine the effects of home-based disease management on the psychological status of patients with HF . METHODS AND RESULTS We r and omly assigned patients hospitalized for HF to undergo either home-based disease management ( n=79 ) or usual care ( n=82 ) . The mean age of the study patients was 76 years , 30 % were female , and 93 % were in NYHA class I or II . Home-based disease management was delivered by nurses via home visit and telephone follow-up to monitor symptoms and body weight and to educate patients . The primary endpoint was psychological status , including depression and anxiety assessed by the Hospital Anxiety and Depression Scale during follow-up of 1 year . Secondary endpoints included quality of life , all-cause death and hospitalization for HF . The intervention group had significantly lower depression ( P=0.043 ) and anxiety ( P=0.029 ) scores than the usual-care group . There were no significant differences in all-cause death [ hazard ratio ( HR ) 1.02 , 95 % confidence interval ( CI ) 0.37 - 2.61 , P=0.967 ] . However , hospitalization for HF was significantly lower in the intervention group than in the usual-care group ( HR 0.52 , 95 % CI 0.27 - 0.96 , P=0.037 ) . CONCLUSIONS Home-based disease management improved psychological status and also reduced rehospitalization for HF in patients with HF AIMS This paper is a report on the effectiveness of a self-management programme based on the self-efficacy construct , in older people with heart failure . BACKGROUND Heart failure is a major health problem worldwide , with high mortality and morbidity , making it a leading cause of hospitalization . Heart failure is associated with a complex set of symptoms that arise from problems in fluid and sodium retention . Hence , managing salt and fluid intake is important and can be enhanced by improving patients ' self-efficacy in changing their behaviour . DESIGN R and omized controlled trial . METHODS Heart failure patients attending cardiac clinics in northern Taiwan from October 2006-May 2007 were r and omly assigned to two groups : control ( n = 46 ) and intervention ( n = 47 ) . The intervention group received a 12-week self-management programme that emphasized self-monitoring of salt/fluid intake and heart failure-related symptoms . Data were collected at baseline as well as 4 and 12 weeks later . Data analysis to test the hypotheses used repeated- measures anova models . RESULTS Participants who received the intervention programme had significantly better self-efficacy for salt and fluid control , self-management behaviour and their heart failure-related symptoms were significantly lower than participants in the control group . However , the two groups did not differ significantly in health service use . CONCLUSION The self-management programme improved self-efficacy for salt and fluid control , self-management behaviours , and decreased heart failure-related symptoms in older Taiwanese out patients with heart failure . Nursing interventions to improve health-related outcomes for patients with heart failure should emphasize self-efficacy in the self-management of their disease OBJECTIVE The purpose of this study was to test the efficacy of a tailored motivational interviewing ( MI ) intervention versus usual care for improving HF self-care behaviors , physical HF symptoms and quality of life . METHODS This is a single-center , r and omized controlled trial . Participants were enrolled in the hospital . Immediately after discharge , those in the intervention group received a single home visit and 3 - 4 follow-up phone calls by a nurse over 90 days . RESULTS A total of 67 participants completed the study ( mean age 62±12.8 years ) , of which 54 % were African American , 30 % were female , 84 % had class III/IV symptoms , and 63 % were educated at a high school level or less . There were no differences between the groups in self-care maintenance , self-care confidence , physical HF symptoms , or quality of life at 90 days . CONCLUSION Patients who received the MI intervention had significant and clinical ly meaningful improvements in HF self-care maintenance over 90 days that exceeded that of usual care . PRACTICE IMPLICATION S These data support the use of a nurse-led MI intervention for improving HF self-care . Identifying methods to improve HF self-care may lead to improved clinical outcomes AIM The aim of this study was to evaluate a heart failure education programme developed for patients and carers in Thail and . BACKGROUND Heart failure is major health problem . This is the first trial of a family-based education programme for heart failure patients and carers residing in rural Thail and . DESIGN R and omized controlled trial . METHODS One hundred patient-carer dyads attending cardiac clinics in southern Thail and from April 2014 - March 2015 were r and omized to usual care ( n = 50 ) or a family-based education programme ( n = 50 ) comprising face-to-face counselling , a heart failure manual and DVD and telephone support . Assessment s of heart failure knowledge , health-related quality of life , self-care behaviours and perceived control were conducted at baseline , three and six months . RESULTS Linear mixed-effects model revealed that patients and carers who received the education programme had higher knowledge scores at three and six months than those who received usual care . Among those who received the education programme , when compared with those who received usual care , patients had better self-care maintenance and confidence , and health-related quality of life scores at three and six months , and better self-care management scores at six months , whereas carers had higher perceived control scores at three months . CONCLUSION Addressing a significant service gap in rural Thail and , this family-based heart failure programme improved patient knowledge , self-care behaviours and health-related quality of life and carer knowledge and perceived control PRINCIPLES International guidelines for heart failure ( HF ) care recommend the implementation of inter-professional disease management programmes . To date , no such programme has been tested in Switzerl and . The aim of this r and omised controlled trial ( RCT ) was to test the effect on hospitalisation , mortality and quality of life of an adult ambulatory disease management programme for patients with HF in Switzerl and . METHODS Consecutive patients admitted to internal medicine in a Swiss university hospital were screened for decompensated HF . A total of 42 eligible patients were r and omised to an intervention ( n = 22 ) or usual care group ( n = 20 ) . Medical treatment was optimised and lifestyle recommendations were given to all patients . Intervention patients additionally received a home visit by a HF-nurse , followed by 17 telephone calls of decreasing frequency over 12 months , focusing on self-care . Calls from the HF nurse to primary care physicians communicated health concerns and identified goals of care . Data were collected at baseline , 3 , 6 , 9 and 12 months . Mixed regression analysis ( quality of life ) was used . Outcome assessment was conducted by research ers blinded to group assignment . RESULTS After 12 months , 22 ( 52 % ) patients had an all-cause re-admission or died . Only 3 patients were hospitalised with HF decompensation . No significant effect of the intervention was found on HF related to quality of life . CONCLUSIONS An inter-professional disease management programme is possible in the Swiss healthcare setting but effects on outcomes need to be confirmed in larger studies BACKGROUND Heart failure ( HF ) disease management programs are widely implemented , but data about their effect on outcome have been inconsistent . METHODS The Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure ( COACH ) was a multicenter , r and omized , controlled trial in which 1023 patients were enrolled after hospitalization because of HF . Patients were assigned to 1 of 3 groups : a control group ( follow-up by a cardiologist ) and 2 intervention groups with additional basic or intensive support by a nurse specializing in management of patients with HF . Patients were studied for 18 months . Primary end points were time to death or rehospitalization because of HF and the number of days lost to death or hospitalization . RESULTS Mean patient age was 71 years ; 38 % were women ; and 50 % of patients had mild HF and 50 % had moderate to severe HF . During the study , 411 patients ( 40 % ) were readmitted because of HF or died from any cause : 42 % in the control group , and 41 % and 38 % in the basic and intensive support groups , respectively ( hazard ratio , 0.96 and 0.93 , respectively ; P = .73 and P = .52 , respectively ) . The number of days lost to death or hospitalization was 39 960 in the control group , 33 731 days for the basic intervention group ( P = .81 ) , and 34 268 for the intensive support group ( P = .49 ) . All-cause mortality occurred in 29 % of patients in the control group , and there was a trend toward lower mortality in the intervention groups combined ( hazard ratio , 0.85 ; 95 % confidence interval , 0.66 - 1.08 ; P = .18 ) . There were slightly more hospitalizations in the 2 intervention groups ( basic intervention group , P = .89 ; and intensive support group , P = .60 ) . CONCLUSIONS Neither moderate nor intensive disease management by a nurse specializing in management of patients with HF reduced the combined end points of death and hospitalization because of HF compared with st and ard follow-up . There was a nonsignificant , potentially relevant reduction in mortality , accompanied by a slight increase in the number of short hospitalizations in both intervention groups . Clinical Trial Registry http://trialregister.nl Identifier : NCT 98675639 BACKGROUND Up to 74 % of patients with heart failure report poor sleep in Taiwan . Poor symptom management or sleep hygiene may affect patients ' sleep quality . An effective educational programme was important to improve patients ' sleep quality and psychological distress . However , research related to sleep disturbance in patients with heart failure is limited in Taiwan . OBJECTIVES To examine the effects of a tailored educational supportive care programme on sleep disturbance and psychological distress in patients with heart failure . DESIGN r and omised controlled trial . PARTICIPANTS AND SETTING Eighty-four patients with heart failure were recruited from an outpatient department of a medical centre in Taipei , Taiwan . Patients were r and omly assigned to the intervention group ( n=43 ) or the control group ( n=41 ) . METHODS Patients in the intervention group received a 12-week tailored educational supportive care programme including individualised education on sleep hygiene , self-care , emotional support through a monthly nursing visit at home , and telephone follow-up counselling every 2 weeks . The control group received routine nursing care . Data were collected at baseline , the 4th , 8th , and 12th weeks after patients ' enrollment . Outcome measures included sleep quality , daytime sleepiness , anxiety , and depression . RESULTS The intervention group exhibited significant improvement in the level of sleep quality and daytime sleepiness after 12 weeks of the supportive nursing care programme , whereas the control group exhibited no significant differences . Anxiety and depression scores were increased significantly in the control group at the 12th week ( p<.001 ) . However , anxiety and depression scores in the intervention group remained unchanged after 12 weeks of the supportive nursing care programme ( p>.05 ) . Compared with the control group , the intervention group had significantly greater improvement in sleep quality ( β=-2.22 , p<.001 ) , daytime sleepiness ( β=-4.23 , p<.001 ) , anxiety ( β=-1.94 , p<.001 ) , and depression ( β=-3.05 , p<.001 ) after 12 weeks of the intervention . CONCLUSION This study confirmed that a supportive nursing care programme could effectively improve sleep quality and psychological distress in patients with heart failure . We suggested that this supportive nursing care programme should be applied to clinical practice in cardiovascular nursing HEART FAILURE ( HF ) IS A MAJOR PUBLIC HEALTH PROBlem , with a prevalence of more than 5 million cases and an incidence of 660 000 new cases per year in the United States alone . Among patients older than 65 years , HF has become the most common discharge diagnosis and the primary cause of readmission within 60 days of discharge , result ing in estimated costs of $ 34.8 billion per year . Nearly half of all patients with HF have a preserved ejection fraction ( HFPEF ) . Patients with HFPEF have a high all-cause mortality after hospitalization for HF : 2.9 % , in-hospital mortality ; 9.5 % , 60to 90-day mortality ; 22 % to 29 % , 1-year mortality ; and 65 % , 5-year mortality . These data underscore the urgent need to find ways to improve outcomes for these patients . Unlike patients with HF and reduced ejection fraction , few large r and omized controlled trials have been specifically design ed for patients with HFPEF . These trials have shown minimal benefit , result ing in persons concluding that there is little evidence on which treatments to use for patients with HFPEF . Underlying the belief that there are few evidence -based therapies for patients with HFPEF is the implication that adverse outcomes in these patients are driven by worsening HF , which may not necessarily be accurate . Although recent large observational studies have shown high rates of morbidity and mortality in patients with HFPEF , these studies have not documented causes of rehospitalization or death . However , data from prior observational studies and clinical trials suggest that these outcomes are driven by important comorbidities that are common in patients with HFPEF . Patients diagnosed with HFPEF are typically elderly ( mean age , 74 - 76 years ) , more often women ( 62%-66 % ) , and frequently have multiple comorbidities , including hypertension ( 55%-77 % ) , coronary artery disease ( CAD ) ( 36%-53 % ) , atrial fibrillation ( 32%-41 % ) , diabetes mellitus ( 32%-45 % ) , chronic kidney disease ( 23%-26 % ) , cerebrovascular disease ( 15 % ) , as well as obesity and anemia . In the Acute Decompensated Heart Failure National Registry ( ADHERE ) study , 91 % of patients with HFPEF had a diagnosis of hypertension , CAD , or diabetes . Secular trends demonstrate that the prevalence of comorbidities in patients with HFPEF is continuing to increase . CAD may be especially important in patients with HFPEF . Although CAD appears to be less common in patients with HFPEF than in patients with HF and reduced ejection fraction , the prevalence and severity of angiographically documented CAD in patients with HFPEF has not been well studied . In the Coronary Artery Surgery Study ( CASS ) , in which CAD was documented by coronary angiography , the presence and extent of CAD was a major determinant of prognosis in patients with HFPEF . Similarly , in the Duke Cardiovascular Data bank of patients with angiographically documented CAD , the presence of severe multivessel coronary disease has been associated with increased mortality in patients with HFPEF . Unlike recent large outcome studies of patients with HFPEF that have primarily examined all-cause rehospitalization and all-cause mortality , prior studies have ascertained the specific causes of adverse events , which help inform the cause of morbidity and mortality in patients with HFPEF . Two large r and omized clinical trials of patients with HFPEF and mortality data have been completed to date : the C and esartan in Heart Failure — Preserved ( CHARMPreserved ) and the Ancillary Digitalis Investigation Group ( Ancillary DIG ) trial , which showed that an angiotensinreceptor blocker and digoxin , respectively , did not improve survival . Although susceptible to selection bias , the CHARM-Preserved trial and Ancillary DIG trial provide important insight into the causes of morbidity and mortality in patients with HFPEF . In each trial , during AIMS AND OBJECTIVES To evaluate the effectiveness and cost-effectiveness of a community nurse-supported hospital discharge programme in preventing hospital re-admissions , improving functional status and h and icap of older patients with chronic heart failure . DESIGN R and omized controlled trial ; 105 hospitalized patients aged 60 years or over with chronic heart failure and history of hospital admission(s ) in previous year were r and omly assigned into intervention group ( n = 49 ) and control group ( n = 56 ) for six months . Intervention group subjects received community nurse visits before discharge , within seven days of discharge , weekly for four weeks , then monthly . Community nurse liaised closely with a design ated specialist in hospital and were accessible to subjects during normal working hours . Control and intervention group subjects were followed up in the same specialist medical clinics . Primary outcome was the rate of unplanned re-admission at six months . Secondary outcomes were number of unplanned re-admissions , six-minute walking distance , London H and icap Scale and public health care and personal care costs . RESULTS At sixth months , the re-admission rates were not significantly different ( 46 vs. 57 % in control subjects , p = 0.233 , Chi-square test ) . But the median number of re-admissions tended to lower in the intervention group ( 0 vs. 1 in control group , p = 0.057 , Mann Whitney test ) . Intervention group subjects had less h and icap in independence ( median change 0 vs. 0.5 in control subjects , p = 0.002 , Mann Whitney test ) , but there was no difference in six-minute walking distance . There was no significant group difference in median total public health care and personal care costs . CONCLUSION Community nurse-supported post-discharge programme was effective in preserving independence and was probably effective in reducing the number of unplanned re-admissions . The cost benefits to public health care were not significant . RELEVANCE TO CLINICAL PRACTICE Older chronic heart failure patients are likely to benefit from post-discharge community nurse intervention programmes . More comprehensive health economic evaluation needs to be undertaken BACKGROUND Remote patient management in patients with heart failure might help to detect early signs and symptoms of cardiac decompensation , thus enabling a prompt initiation of the appropriate treatment and care before a full manifestation of a heart failure decompensation . We aim ed to investigate the efficacy of our remote patient management intervention on mortality and morbidity in a well defined heart failure population . METHODS The Telemedical Interventional Management in Heart Failure II ( TIM-HF2 ) trial was a prospect i ve , r and omised , controlled , parallel-group , unmasked ( with r and omisation concealment ) , multicentre trial with pragmatic elements introduced for data collection . The trial was done in Germany , and patients were recruited from hospitals and cardiology practice s. Eligible patients had heart failure , were in New York Heart Association class II or III , had been admitted to hospital for heart failure within 12 months before r and omisation , and had a left ventricular ejection fraction ( LVEF ) of 45 % or lower ( or if higher than 45 % , oral diuretics were being prescribed ) . Patients with major depression were excluded . Patients were r and omly assigned ( 1:1 ) using a secure web-based system to either remote patient management plus usual care or to usual care only and were followed up for a maximum of 393 days . The primary outcome was percentage of days lost due to unplanned cardiovascular hospital admissions or all-cause death , analysed in the full analysis set . Key secondary outcomes were all-cause and cardiovascular mortality . This study is registered with Clinical Trials.gov , number NCT01878630 , and has now been completed . FINDINGS Between Aug 13 , 2013 , and May 12 , 2017 , 1571 patients were r and omly assigned to remote patient management ( n=796 ) or usual care ( n=775 ) . Of these 1571 patients , 765 in the remote patient management group and 773 in the usual care group started their assigned care , and were included in the full analysis set . The percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause death was 4·88 % ( 95 % CI 4·55 - 5·23 ) in the remote patient management group and 6·64 % ( 6·19 - 7·13 ) in the usual care group ( ratio 0·80 , 95 % CI 0·65 - 1·00 ; p=0·0460 ) . Patients assigned to remote patient management lost a mean of 17·8 days ( 95 % CI 16·6 - 19·1 ) per year compared with 24·2 days ( 22·6 - 26·0 ) per year for patients assigned to usual care . The all-cause death rate was 7·86 ( 95 % CI 6·14 - 10·10 ) per 100 person-years of follow-up in the remote patient management group compared with 11·34 ( 9·21 - 13·95 ) per 100 person-years of follow-up in the usual care group ( hazard ratio [ HR ] 0·70 , 95 % CI 0·50 - 0·96 ; p=0·0280 ) . Cardiovascular mortality was not significantly different between the two groups ( HR 0·671 , 95 % CI 0·45 - 1·01 ; p=0·0560 ) . INTERPRETATION The TIM-HF2 trial suggests that a structured remote patient management intervention , when used in a well defined heart failure population , could reduce the percentage of days lost due to unplanned cardiovascular hospital admissions and all-cause mortality . FUNDING German Federal Ministry of Education and Research IMPORTANCE More than 80 % of patients with heart failure with preserved ejection fraction ( HFPEF ) , the most common form of heart failure among older persons , are overweight or obese . Exercise intolerance is the primary symptom of chronic HFPEF and a major determinant of reduced quality of life ( QOL ) . OBJECTIVE To determine whether caloric restriction ( diet ) or aerobic exercise training ( exercise ) improves exercise capacity and QOL in obese older patients with HFPEF . DESIGN , SETTING , AND PARTICIPANTS R and omized , attention-controlled , 2 × 2 factorial trial conducted from February 2009 through November 2014 in an urban academic medical center . Of 577 initially screened participants , 100 older obese participants ( mean [ SD ] : age , 67 years [ 5 ] ; body mass index , 39.3 [ 5.6 ] ) with chronic , stable HFPEF were enrolled ( 366 excluded by inclusion and exclusion criteria , 31 for other reasons , and 80 declined participation ) . INTERVENTIONS Twenty weeks of diet , exercise , or both ; attention control consisted of telephone calls every 2 weeks . MAIN OUTCOMES AND MEASURES Exercise capacity measured as peak oxygen consumption ( V̇O2 , mL/kg/min ; co- primary outcome ) and QOL measured by the Minnesota Living with Heart Failure ( MLHF ) Question naire ( score range : 0 - 105 , higher scores indicate worse heart failure-related QOL ; co- primary outcome ) . RESULTS Of the 100 enrolled participants , 26 participants were r and omized to exercise ; 24 to diet ; 25 to exercise + diet ; 25 to control . Of these , 92 participants completed the trial . Exercise attendance was 84 % ( SD , 14 % ) and diet adherence was 99 % ( SD , 1 % ) . By main effects analysis , peak V̇O2 was increased significantly by both interventions : exercise , 1.2 mL/kg body mass/min ( 95 % CI , 0.7 to 1.7 ) , P < .001 ; diet , 1.3 mL/kg body mass/min ( 95 % CI , 0.8 to 1.8 ) , P < .001 . The combination of exercise + diet was additive ( complementary ) for peak V̇O2 ( joint effect , 2.5 mL/kg/min ) . There was no statistically significant change in MLHF total score with exercise and with diet ( main effect : exercise , -1 unit [ 95 % CI , -8 to 5 ] , P = .70 ; diet , -6 units [ 95 % CI , -12 to 1 ] , P = .08 ) . The change in peak V̇O2 was positively correlated with the change in percent lean body mass ( r = 0.32 ; P = .003 ) and the change in thigh muscle : intermuscular fat ratio ( r = 0.27 ; P = .02 ) . There were no study -related serious adverse events . Body weight decreased by 7 % ( 7 kg [ SD , 1 ] ) in the diet group , 3 % ( 4 kg [ SD , 1 ] ) in the exercise group , 10 % ( 11 kg [ SD , 1 ] in the exercise + diet group , and 1 % ( 1 kg [ SD , 1 ] ) in the control group . CONCLUSIONS AND RELEVANCE Among obese older patients with clinical ly stable HFPEF , caloric restriction or aerobic exercise training increased peak V̇O2 , and the effects may be additive . Neither intervention had a significant effect on quality of life as measured by the MLHF Question naire . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00959660 OBJECTIVES We compared the longer-term impact of the two most commonly applied forms of post-discharge management design ed to minimize recurrent hospitalization and prolong survival in typically older patients with chronic heart failure ( CHF ) . METHODS We followed a multi-center r and omized controlled trial cohort of Australian patients hospitalized with CHF and initially allocated to home-based or specialized CHF clinic-based intervention for 1368 ± 216 days . Blinded endpoints included event-free survival from all-cause emergency hospitalization or death , all-cause mortality and rate of all-cause hospitalization and stay . RESULTS 280 patients ( 73 % male , aged 71 ± 14 years and 73 % left ventricular systolic dysfunction ) were initially r and omized to home-based ( n=143 ) or clinic-based ( n=137 ) intervention . During extended follow-up ( complete for 274 patients ) , 1139 all-cause hospitalizations ( 7477 days of hospital stay ) and 121 ( 43.2 % ) deaths occurred . There was no difference in the primary endpoint ; 20 ( 14.0 % ) home-based versus 13 ( 7.4 % ) clinic-based patients remained event-free ( adjusted HR 0.89 , 95 % CI 0.70 to 1.15 ; p=0.378 ) . Significantly fewer home-based ( 51/143 , 35.7 % ) than clinic-based intervention ( 71/137 , 51.8 % ) patients died ( adjusted HR 0.62 , 95 % CI 0.42 to 0.90 : p=0.012 ) . Home-based versus clinic-based intervention patients accumulated 592 and 547 all-cause hospitalizations ( p=0.087 ) associated with 3067 ( median 4.0 , IQR 2.0 to 6.8 ) versus 4410 ( 6.0 , IQR 3.0 to 12.0 ) days of hospital stay ( p<0.01 for rate and duration of hospital stay ) . CONCLUSIONS Relative to clinic-based intervention , home-based intervention was not associated with prolonged event-free survival . Home-based intervention was , however , associated with significantly fewer all-cause deaths and significantly fewer days of hospital stay in the longer-term . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry number 12607000069459 ( http://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=81803 ) Background — Patients with heart failure ( HF ) who live in rural areas have less access to cardiac services than patients in urban areas . We conducted a r and omized , clinical trial to determine the impact of an educational intervention on the composite end point of HF rehospitalization and cardiac death in this population . Methods and Results — Patients ( n=602 ; age , 66±13 years ; 41 % female ; 51 % with systolic HF ) were r and omized to 1 of 3 groups : control ( usual care ) , Fluid Watchers LITE , or Fluid Watchers PLUS . Both intervention groups included a face-to-face education session delivered by a nurse focusing on self-care . The LITE group received 2 follow-up phone calls , whereas the PLUS group received biweekly calls ( mean , 5.3±3.6 ; range , 1–19 ) until the nurse judged the patient to be adequately trained . Over 2 years of follow-up , 35 % of patients ( n=211 ) experienced cardiac death or hospitalization for HF , with no difference among the 3 groups in the proportion who experienced the combined clinical outcome ( P=0.06 ) . Although patients in the LITE group had reduced cardiac mortality compared with patients in the control group over the 2 years of follow-up ( 7.5 % and 17.7 % , respectively ; P=0.003 ) , there was no significant difference in cardiac mortality between patients in the PLUS group and the control group . Conclusions — A face-to-face education intervention did not significantly decrease the combined end point of cardiac death or hospitalization for HF . Increasing the number of contacts between the patient and nurse did not significantly improve outcome . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00415545 |
12,064 | 28,780,622 | They also allow us to evaluate infrequent situations for which r and omized control trials are not feasible and add specific information that can complement the quality of surgical knowledge | Purpose The rapid development of technological tools to record data allows storage of enormous data sets , often termed “ big data ” .
In the USA , three large data bases have been developed to store data regarding surgical outcomes : the American College of Surgeons National Surgical Quality Improvement Program ( ACS-NSQIP ) , the Healthcare Cost and Utilization Project ( HCUP ) National Inpatient Sample ( NIS ) and the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program ( MBSAQIP ) .
We aim ed to evaluate the clinical impact of studies found in these data bases concerning outcomes of bariatric surgery . | BACKGROUND There is limited outcome data for super-super-obese ( SSO ) patients , those with Body Mass Index ( BMI ) ≥ 60 kg/m(2 ) , who seek surgical treatment with Laparoscopic Roux-en-Y Gastric Bypass ( LRYGB ) . A large single center LRYGB experience was review ed to compare the safety and efficacy of LRYGB in SSO patients to the st and ard obese population undergoing this procedure . METHODS The American College of Surgeons National Surgical Quality Improvement Program ( ACS NSQIP ) data base and an Institutional Review Board approved prospect i ve data base was used to identify all patients undergoing LRYGB by multiple surgeons at a single institution between 1/1/1994 and 11/15/2013 . Preoperative co-morbidities , postoperative complications , 30-day outcomes , and weight loss at yearly intervals were analyzed to determine difference between SSO patients and NonSSO patients ( BMI < 60 kg/m(2 ) ) . RESULTS Of the 2009 patients undergoing LRYGB over the past 20 years ; 328 had BMI ≥ 60 kg/m(2 ) . Preoperative co-morbidities , conversion to open , and length of stay were significantly increased among SSO patients ; however there was no significant difference in postoperative outcomes or complications . Percent reduction of excess BMI beyond 12 months was significantly improved among NonSSO patients with less than 30 % follow-up beyond 2 years . CONCLUSIONS LRYGB appears well tolerated for super-super-obese patients with BMI ≥ 60 kg/m(2 ) in experienced centers . These patients still have significant reduction in excess BMI despite being less than NonSSO patients undergoing RYGB . The ACS NSQIP data base provides excellent tracking of institutional progress with bariatric surgical outcomes to facilitate the improvement of best practice techniques BACKGROUND Studies have demonstrated that laparoscopic Roux-en-Y gastric bypass ( RYGB ) is associated with the greatest readmission rate among bariatric surgeries . Some readmissions might be avoidable . We sought to evaluate the risk factors for readmission in a high-volume bariatric surgery program at a university hospital in the United States . METHODS We performed a retrospective review of prospect ively maintained data . Patients readmitted within 30 days of laparoscopic RYGB were r and omly matched to control patients who had undergone RYGB in the same year but were not readmitted . The readmissions were categorized as technical complications ( leak ) , wound infections , or malaise ( nausea , dehydration , or benign abdominal pain ) . Patients with a wound infection treated in an outpatient setting were also evaluated and compared with the patients admitted with a wound infection . RESULTS From July 2002 to July 2008 , 450 patients underwent RYGB . Readmission occurred in 42 patients ( 9 % ) . Of these 42 patients , 6 were admitted with wound infections ( 14 % ) , 18 ( 43 % ) with malaise , and 18 ( 43 % ) with technical complications . The patients admitted with wound infections were similar to their controls , except that they were more likely to have publicly funded insurance ( Medicare or Medicaid ) and more likely to present for medical attention to the emergency department after clinic hours . The patients admitted with malaise reported a greater pain score at discharge and were also more likely to have public health insurance than controls . The patients with technical complications did not differ from the control patients in any examined variable . CONCLUSIONS Patients with publicly funded insurance are at increased risk of readmission after RYGB . Outpatient mechanisms for managing wound infections and malaise might result in decreased readmissions Objective : To compare laparoscopic versus open gastric bypass procedures with respect to 30-day morbidity and mortality rates , using multi-institutional , prospect i ve , risk-adjusted data . Summary Background Data : Laparoscopic Roux-en-Y gastric bypass for weight loss is being performed with increasing frequency , partly driven by consumer dem and . However , there are no multi-institutional , risk-adjusted , prospect i ve studies comparing laparoscopic and open gastric bypass outcomes . Methods : A multi-institutional , prospect i ve , risk-adjusted cohort study of patients undergoing laparoscopic and open gastric bypass procedures was performed from hospitals ( n = 15 ) involved in the Private Sector Study of the National Surgical Quality Improvement Program ( NSQIP ) . Data points have been extensively vali date d , are based on st and ardized definitions , and were collected by nurse review ers who are audited for accuracy . Results : From 2000 to 2003 , data from 1356 gastric bypass procedures was collected . The 30-day mortality rate was zero in the laparoscopic group ( n = 401 ) , and 0.6 % in the open group ( n = 955 ) ( P = not significant ) . The 30-day complication rate was significantly lower in the laparoscopic group as compared with the open group : 7 % versus 14.5 % ( P < 0.0001 ) . Multivariate logistic regression analysis was performed to control for potential confounding variables and showed that patients undergoing an open procedure were more likely to develop a complication , as compared with patients undergoing an laparoscopic procedure ( odds ratio = 2.08 ; 95 % confidence interval , 1.33–3.25 ) . Propensity score modeling revealed similar results . A prediction model was derived , and variables that significantly predict higher complication rates after gastric bypass included an open procedure , a high ASA class ( III , IV , V ) , functionally dependent patient , and hypertension as a comorbid illness . Conclusions : Multicenter , prospect i ve , risk-adjusted data show that laparoscopic gastric bypass is safer than open gastric bypass , with respect to 30-day complication rate Objective To compare outcomes , quality of life ( QOL ) , and costs of laparoscopic and open gastric bypass ( GBP ) . Summary Background Data Laparoscopic GBP has been reported to be a safe and effective approach for the treatment of morbid obesity . The authors performed a prospect i ve r and omized trial to compare outcomes , QOL , and costs of laparoscopic GBP with those of open GBP . Methods From May 1999 to March 2001 , 155 patients with a body mass index ( BMI ) of 40 to 60 kg/m2 were r and omly assigned to undergo laparoscopic ( n = 79 ) or open ( n = 76 ) GBP . The two groups were similar in age , sex ratio , mean BMI , and comorbidities . Main outcome measures included operative time , estimated blood loss , length of hospital stay , operative complications , percentage of excess body weight loss , and time to return to activities of daily living and work . Changes in QOL were assessed using the SF-36 Health Survey and the bariatric analysis of reporting outcome system ( BAROS ) . Operative and hospital costs of the two operations were also compared . Results There were no deaths in either group . Mean operative time was longer for laparoscopic GBP than for open GBP , but operative blood loss was less . Two ( 2.5 % ) of the 79 patients in the laparoscopic group required conversion to laparotomy . Median length of hospital stay was shorter for laparoscopic GBP patients ( 3 vs 4 days ) . The rate of postoperative anastomotic leak was similar between groups . Wound-related complications such as infection ( 10.5 vs 1.3 % ) and incisional hernia ( 7.9 vs 0 % ) were more common after open GBP ; late anastomotic stricture was less frequent after open GBP ( 2.6 vs 11.4 % ) . Time to return to activities of daily living and work were shorter after laparoscopic GBP than after open GBP . Weight loss at 1 year was similar between groups . Preoperative SF-36 scores were similar between groups ; however , at 1 month after surgery , laparoscopic patients had better physical conditioning , social functioning , general health , and less body pain than open GBP patients . At 6 months , the BAROS outcome was classified as good or better in 97 % of laparoscopic GBP patients compared with 82 % of open GBP patients . Operative costs were higher for laparoscopic GBP patients , but hospital costs were lower . Conclusions Laparoscopic GBP is a safe and cost-effective alternative to open GBP . Despite a longer operative time , patients undergoing laparoscopic GBP benefited from less blood loss , a shorter hospital stay , and faster convalescence . Laparoscopic GBP patients had comparable weight loss at 1 year but a more rapid improvement in QOL than open GBP patients . The higher initial operative costs for laparoscopic GBP were adequately offset by the lower hospital costs BACKGROUND Our objective was to ascertain procedure-related morbidity among laparoscopic Roux-en-Y gastric bypass ( LRYGB ) , laparoscopic sleeve gastrectomy ( LSG ) , and laparoscopic adjustable gastric b and ing ( LAGB ) patients . These are the 3 most common bariatric procedures performed worldwide . We review ed our experience since the introduction of LSG and compared the procedure-related morbidity among all 3 procedures . STUDY DESIGN We conducted a retrospective review of a prospect ively collected data base of all morbidly obese patients who underwent bariatric surgery between the years 2005 and 2011 . We identified and compared complications , mortality , readmissions , and reoperations in patients who underwent LRYGB , LAGB , and LSG . RESULTS A total of 2,199 bariatric procedures were performed during this period of time . Of those procedures , 1,327 were LRYGB , 619 were LSG , and 253 were LAGB . Perioperative mortality was not applicable for all 3 procedures . The leak rate was 0.5 % for LRYGB and 0.3 % for LSG , and was not applicable for LAGB . The average number of readmissions postoperatively was less than 2 times for all 3 procedures : LRYGB 1.96 times , LSG 1.49 times , and LAGB 1.54 times . The percentages of procedures requiring reoperations due to complications or failures were 14.6 % in the LAGB group , 6.6 % in the LRYGB group , and 1.8 % in the LSG group . CONCLUSIONS In short- and mid-term follow-up , LSG appears to have the lowest procedure-related morbidity when compared with LRYGB and LAGB |
12,065 | 27,289,303 | The anti-suicidal effects of clozapine and lithium have been substantiated , but might be less specific than previously thought .
Insufficient evidence exists to assess the possible benefits for suicide prevention of screening in primary care , in general public education and media guidelines . | BACKGROUND Many countries are developing suicide prevention strategies for which up-to- date , high- quality evidence is required .
We present up date d evidence for the effectiveness of suicide prevention interventions since 2005 . | This experimental study examined the effect of communication about type of screening follow-up ( in-person follow-up vs. no in-person follow-up ) on adolescents ' responses to a self-report suicide risk screen . Participants were 245 adolescents ( 131 girls , 114 boys ; ages 13–17 ; 80 % White , 21.6 % Black , 9.8 % American Indian , 2.9 % Asian ) seeking medical emergency services . They were r and omized to a screening follow-up condition . Screening measures assessed primary risk factors for suicidal behavior , including suicidal thoughts , depressive symptoms , alcohol use , and aggressive/delinquent behavior . There was no main effect of follow-up condition on adolescents ' screening scores ; however , significant interactions between follow-up condition and public assistance status were evident . Adolescents whose families received public assistance were less likely to report aggressive-delinquent behavior if assigned to in-person follow-up . Adolescents whose families did not receive public assistance reported significantly higher levels of suicidal ideation if assigned to in-person follow-up . Findings suggest that response biases impact some adolescents ' responses to suicide risk screenings . Because national policy strongly recommends suicide risk screening in emergency setting s , and because screening scores are used to make critical decisions regarding risk management and treatment recommendations , findings indicate the importance of improving the reliability and validity of suicide risk screening for adolescents Objective To assess whether an assertive outreach intervention after suicide attempt could reduce the frequency of subsequent suicidal acts , compared with st and ard treatment . Design R and omised , parallel group , superiority trial with blinded outcome assessment . Setting Outpatient intervention at one location at Copenhagen University Hospital , Denmark . Participants Patients older than 12 years admitted to regional hospitals in Copenhagen with a suicide attempt within the past 14 days . We excluded patients diagnosed with schizophrenia spectrum disorders and patients living in institutions . Intervention Case management through assertive outreach that provided crisis intervention and flexible problem solving . This approach incorporated motivational support and actively assisted patients to scheduled appointments to improve adherence with after-treatment as an add on to st and ard treatment . Main outcome Repeated suicide attempt and death by suicide , recorded in medical records and death register at 1-year follow-up . Results 243 patients were included . During 12 months of follow-up , 20/123 ( 16 % ) patients in the intervention group had been registered in hospital records with subsequent suicide attempt , compared with 13/120 ( 11 % ) in the control group ( odds ratio 1.60 , 95 % confidence interval 0.76 to 3.38 ; P=0.22 ) . By contrast , self reported data on new events showed 11/95 ( 12 % ) in the intervention group versus 13/74 ( 18 % ) in the control group ( 0.61 , 0.26 to 1.46 ; P=0.27 ) . By imputing missing data on the selfreported outcomes , we estimated 15/123 ( 12 % ) events in the intervention group and 23/120 ( 19 % ) in the control group ( 0.69 , 0.34 to 1.43 ; P=0.32 ) . Conclusion Assertive outreach showed no significant effect on subsequent suicide attempt . The difference in rates of events between register data and self reported data could indicate detection bias . Trial registration Clinical Trials.gov NCT00700089 A central component of Dialectical Behavior Therapy ( DBT ) is the teaching of specific behavioral skills with the aim of helping individuals with Borderline Personality Disorder ( BPD ) replace maladaptive behaviors with skillful behavior . Although existing evidence indirectly supports this proposed mechanism of action , no study to date has directly tested it . Therefore , we examined the skills use of 108 women with BPD participating in one of three r and omized control trials throughout one year of treatment and four months of follow-up . Using a hierarchical linear modeling approach we found that although all participants reported using some DBT skills before treatment started , participants treated with DBT reported using three times more skills at the end of treatment than participants treated with a control treatment . Significant mediation effects also indicated that DBT skills use fully mediated the decrease in suicide attempts and depression and the increase in control of anger over time . DBT skills use also partially mediated the decrease of nonsuicidal self-injury over time . Anger suppression and expression were not mediated . This study is the first to clearly support the skills deficit model for BPD by indicating that increasing skills use is a mechanism of change for suicidal behavior , depression , and anger control In a prospect ive-longitudinal study of a representative birth cohort , we tested why stressful experiences lead to depression in some people but not in others . A functional polymorphism in the promoter region of the serotonin transporter ( 5-HT T ) gene was found to moderate the influence of stressful life events on depression . Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms , diagnosable depression , and suicidality in relation to stressful life events than individuals homozygous for the long allele . This epidemiological study thus provides evidence of a gene-by-environment interaction , in which an individual 's response to environmental insults is moderated by his or her genetic makeup Background There have been only a few reports illustrating the moderate effectiveness of suicide-preventive interventions in reducing suicidal behavior , and , in most of those studies , the target population s were primarily adults , whereas few focused on adolescents . Essentially , there have been no r and omized controlled studies comparing the efficacy , cost-effectiveness and cultural adaptability of suicide-prevention strategies in schools . There is also a lack of information on whether suicide-preventive interventions can , in addition to preventing suicide , reduce risk behaviors and promote healthier ones as well as improve young people 's mental health . The aim of the SEYLE project , which is funded by the European Union under the Seventh Framework Health Program , is to address these issues by collecting baseline and follow-up data on health and well-being among European adolescents and compiling an epidemiological data base ; testing , in a r and omized controlled trial , three different suicide-preventive interventions ; evaluating the outcome of each intervention in comparison with a control group from a multidisciplinary perspective ; as well as recommending culturally adjusted models for promoting mental health and preventing suicidal behaviors . Methods and design The study comprises 11,000 adolescents emitted from r and omized schools in 11 European countries : Austria , Estonia , France , Germany , Hungary , Irel and , Israel , Italy , Romania , Slovenia and Spain , with Sweden serving as the scientific coordinating center . Each country performs three active interventions and one minimal intervention as a control group . The active interventions include gatekeeper training ( QPR ) , awareness training on mental health promotion for adolescents , and screening for at-risk adolescents by health professionals . Structured question naires are utilized at baseline , 3- and 12-month follow-ups in order to assess changes . Discussion Although it has been reported that suicide-preventive interventions can be effective in decreasing suicidal behavior , well-documented and r and omized studies are lacking . The effects of such interventions in terms of combating unhealthy lifestyles in young people , which often characterize suicidal individuals , have never been reported . We know that unhealthy and risk-taking behaviors are detrimental to individuals ' current and future health . It is , therefore , crucial to test well- design ed , longitudinal mental health-promoting and suicide-preventive interventions by evaluating the implication s of such activities for reducing unhealthy and risk behaviors while concurrently promoting healthy ones . Trial registration The German Clinical Trials Register , DRKS00000214 OBJECTIVE To determine whether brief intervention and contact is effective in reducing subsequent suicide mortality among suicide attempters in low and middle-income countries . METHODS Suicide attempters ( n = 1867 ) identified by medical staff in the emergency units of eight collaborating hospitals in five culturally different sites ( Campinas , Brazil ; Chennai , India ; Colombo , Sri Lanka ; Karaj , Islamic Republic of Iran ; and Yuncheng , China ) participated , from January 2002 to October 2005 , in a r and omized controlled trial to receive either treatment as usual , or treatment as usual plus brief intervention and contact ( BIC ) , which included patient education and follow-up . Overall , 91 % completed the study . The primary study outcome measurement was death from suicide at 18-month follow-up . FINDINGS Significantly fewer deaths from suicide occurred in the BIC than in the treatment-as-usual group ( 0.2 % versus 2.2 % , respectively ; chi2 = 13.83 , P < 0.001 ) . CONCLUSION This low-cost brief intervention may be an important part of suicide prevention programmes for underre source d low- and middle-income countries CONTEXT Universal screening for mental health problems and suicide risk is at the forefront of the national agenda for youth suicide prevention , yet no study has directly addressed the potential harm of suicide screening . OBJECTIVE To examine whether asking about suicidal ideation or behavior during a screening program creates distress or increases suicidal ideation among high school students generally or among high-risk students reporting depressive symptoms , substance use problems , or suicide attempts . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled study conducted within the context of a 2-day screening strategy . Participants were 2342 students in 6 high schools in New York State in 2002 - 2004 . Classes were r and omized to an experimental group ( n = 1172 ) , which received the first survey with suicide questions , or to a control group ( n = 1170 ) , which did not receive suicide questions . MAIN OUTCOME MEASURES Distress measured at the end of the first survey and at the beginning of the second survey 2 days after the first measured on the Profile of Mood States adolescent version ( POMS-A ) instrument . Suicidal ideation assessed in the second survey . RESULTS Experimental and control groups did not differ on distress levels immediately after the first survey ( mean [ SD ] POMS-A score , 5.5 [ 9.7 ] in the experimental group and 5.1 [ 10.0 ] in the control group ; P = .66 ) or 2 days later ( mean [ SD ] POMS-A score , 4.3 [ 9.0 ] in the experimental group and 3.9 [ 9.4 ] in the control group ; P = .41 ) , nor did rates of depressive feelings differ ( 13.3 % and 11.0 % , respectively ; P = .19 ) . Students exposed to suicide questions were no more likely to report suicidal ideation after the survey than unexposed students ( 4.7 % and 3.9 % , respectively ; P = .49 ) . High-risk students ( defined as those with depression symptoms , substance use problems , or any previous suicide attempt ) in the experimental group were neither more suicidal nor distressed than high-risk youth in the control group ; on the contrary , depressed students and previous suicide attempters in the experimental group appeared less distressed ( P = .01 ) and suicidal ( P = .02 ) , respectively , than high-risk control students . CONCLUSIONS No evidence of iatrogenic effects of suicide screening emerged . Screening in high schools is a safe component of youth suicide prevention efforts The purpose of this study was to examine the efficacy of the Youth-Nominated Support Team-Version II ( YST-II ) for suicidal adolescents , an intervention based on social support and health behavior models , which was design ed to supplement st and ard treatments . Psychiatrically hospitalized and suicidal adolescents , 13 - 17 years of age , were r and omly assigned to treatment-as-usual ( TAU ) + YST-II ( n = 223 ) or TAU only ( n = 225 ) . YST-II provided tailored psychoeducation to youth-nominated adults in addition to weekly check-ins for 3 months following hospitalization . In turn , these adults had regular supportive contact with adolescents . Adolescents assigned to TAU + YST-II had an average of 3.43 ( SD = 0.83 ) nominated adults . Measures included the Suicidal Ideation Question naire-Junior ( SIQ-JR ; W. M. Reynolds , 1988 ) , Children 's Depression Rating Scale-Revised ( E. O. Poznanski & H. B. Mokros , 1996 ) , Beck Hopelessness Scale ( A. T. Beck & R. A. Steer , 1993 ) , and Child and Adolescent Functional Assessment Scale ( CAFAS ; K. Hodges , 1996 ) . YST-II had very limited positive effects , which were moderated by history of multiple suicide attempts , and no negative effects . It result ed in more rapid decreases in suicidal ideation ( SIQ-JR ) for multiple suicide attempters during the initial 6 weeks after hospitalization ( small-to-moderate effect size ) . For nonmultiple attempters , it was associated with greater declines in functional impairment ( CAFAS ) at 3 and 12 months ( small effect sizes ) . YST-II had no effects on suicide attempts and no enduring effects on SIQ-JR scores AIM Suicide attempt , ideation and deliberate self-harm are common among adolescents . Limited evidence exists regarding interventions that can reduce risk ; however , research indicates that maintaining contact with at-risk adults following discharge from services via letter or postcard can reduce risk . The aim of the study was to test a postcard intervention among people aged 15 - 24 who presented to mental health services but were not accepted , yet were at risk of suicide . METHODS A r and omized controlled trial of 3 years in duration was used . The intervention consisted of 12 postcards sent once a month for 12 months following presentation to the service . Key outcomes of interest were reduced rates of suicide attempt , suicidal ideation and deliberate self-harm , assessed at 12 and 18 months . RESULTS Participants reported that they liked receiving the postcard and that they used the strategies recommended . However , no significant effect of the postcard intervention was found on suicide risk , although participants in both groups improved on measures of mental health over the course of the study . CONCLUSIONS There remains a need for further research into youth-friendly interventions for young people at risk of suicide Gatekeeper-training programs , design ed to increase identification and referral of suicidal individuals , are widespread but largely untested . A group-based r and omized trial with 32 schools examined impact of Question , Persuade , Refer ( QPR ) training on a stratified r and om sample of 249 staff with 1-year average follow-up . To test QPR impact , the authors introduced and contrasted 2 models of gatekeeper-training effects in a population : gatekeeper surveillance and gatekeeper communication . Intent-to-treat analyses showed that training increased self-reported knowledge ( effect size [ ES ] = 0.41 ) , appraisal s of efficacy ( ES = 1.22 ) , and service access ( ES = 1.07 ) . Training effects varied dramatically . Appraisal s increased most for staff with lowest baseline appraisal s , and suicide identification behaviors increased most for staff already communicating with students about suicide and distress . Consistent with the communication model , increased knowledge and appraisal s were not sufficient to increase suicide identification behaviors . Also consistent with the communication model were results from 2,059 8th and 10th grade rs surveyed showing that fewer students with prior suicide attempts endorsed talking to adults about distress . Skill training for staff serving as " natural gatekeepers " plus interventions that modify students ' help-seeking behaviors are recommended to supplement universal gatekeeper training Mr. B , age 20 , has taken a semester leave from college because of gradually worsening depressed mood . Over the past 2 months he has lost interest in jogging and playing piano -- which he usually enjoys . He reports reduced libido , middle insomnia , loss of appetite , feeling as if his head is " full of cotton , " trouble concentrating , and waking in the morning with a sense of dread . His anxiety dissipates during the day , but he continues to feel sad and sometimes weepy , which is unusual for him . [ ILLUSTRATION OMITTED ] Mr. B reports feeling hopeless at times and has had vague thoughts about life being " not worth it if I continue to feel like this " but denies specific suicide plans . Your initial impression is that Mr. B is in the midst of a major depressive episode and that a selective serotonin reuptake inhibitor ( SSRI ) is indicated . As you finish taking his history , you run through your mind the pros and cons of the recommendation you will make to him . Do SSRIs raise or lower the risk for suicidal behavior in young adults such as Mr. B ? The answer is complicated and goes beyond an " either/or " question , as the FDA acknowledged in May 2007 when it : * extended the black-box warning of increased suicidality risk with antidepressants to cover adults age 18 to 24 as well as children and adolescents * included language in the warning about the benefits of treating depression and the suicide risk associated with untreated depression , given concerns about declining antidepressant prescriptions and rising suicides among youth . ( 1 ) To help you make informed decisions when treating depression in adults , this article review s the studies leading up to and following the FDA 's meta- analysis of antidepressant trial data in patients age 18 and older . Our goal is to provide a framework for clinical treatment of adults age 18 to 24 and those age [ greater than or equal to]25 . First hints of suicidality SSRIs revolutionized depression treatment . From 1985 to 1999 , annual U.S. antidepressant prescriptions quadrupled , with SSRIs accounting for 70 % of the increase ( see " Antidepressants and suicide risk , 1985 to 2007 , " pages 36 - 37 ) . At the same time , the age-adjusted suicide rate : * dropped 22.5 % for women ( who account for twice as many antidepressant prescriptions as men ) * dropped 12.8 % for men ( without change in the rank order of suicide methods ) . ( 2 ) For many patients , increased antidepressant use improved treatment of major depressive and other antidepressant-responsive disorders . In 1990 , however , case reports suggested SSRIs might cause suicidal thoughts or behavior . ( 3 ) Hypothesized mechanisms included increased aggression ( 4 ) and akathisia . ( 5 ) An FDA review found no proof , and a meta- analysis of data from 17 double-blind , r and omized , controlled trials found no association between fluoxetine and suicidal thoughts or behavior . ( 6 ) The debate rekindled in June 2003 when the British Committee on Safety of Medicines warned against using paroxetine or venlafaxine in children . After conducting its own meta- analysis , the FDA in 2004 ordered a black-box warning about suicidality and the use of antidepressants in children and adolescents ( Box ) . ( 7 ) After the pediatric ' black box . ' Antidepressant prescriptions for children and adolescents declined in the years 2003 to 2004 , as did diagnosis of pediatric depression . ( 8 - 10 ) Antidepressant prescribing also showed signs of shifting from general practitioners to psychiatrists . ( 8) At the same time , the suicide rate among youth age 60 , SSRI prescriptions continued to rise and suicide rates fell , ( 9 ) a pattern of change consistent with antidepressants protecting against suicide . An independent meta- analysis by Bridge et al ( 12 ) examined the pediatric trial data used in the FDA meta- analysis plus 7 additional studies . OBJECTIVE To determine effects of sertraline on suicidal thinking and behavior in patients with late-life major depression . METHODS This was a secondary analysis of an eight-week , placebo-controlled , double-blind r and omized trial of a multicenter trial at 66 clinical sites . Out patients > /=60 years of age with major depression and a Hamilton Depression Rating ( HAMD ) score > /=18 were included . Intervention was sertraline 50 - 100 mg/day or placebo for eight weeks . Measurements were 17-item HAMD administered at baseline and two-week intervals . HAMD Item 3 used to assess suicidal ideation ( SI ) and behavior . Reports of serious adverse events ( SAEs ) , adverse events ( AEs ) leading to discontinuation , and spontaneously reported adverse events review ed . RESULTS A total of 747 patients received at least one dose of medication , and 728 had at least one posttreatment assessment . Mean age ( + /-SD ) was 69.8 + /- 6.7 years ( range : 59 - 97 years ) and 56 % were female . There were no completed suicides or suicide attempts during the double-blind trial . One SAE , hospitalization , was associated with SI in a patient on sertraline . No other AEs were associated with SI or behavior . HAMD Item 3 ratings progressively declined during the trial with significantly lower values for sertraline than placebo ( Z = 2.41 , p < 0.02 ) . In 248 patients with HAMD Item 3 of zero at baseline , the percentage of patients whose Item 3 ratings increased during treatment did not differ in the two groups ( 22.4 % versus 25.8 % for sertraline and placebo , respectively . ) CONCLUSION Sertraline was associated with significantly lower HAMD Item 3 scores than placebo during treatment . There was no evidence of greater emergent suicidal thinking or behavior with sertraline than placebo BACKGROUND Suicidal behaviours in adolescents are a major public health problem and evidence -based prevention programmes are greatly needed . We aim ed to investigate the efficacy of school-based preventive interventions of suicidal behaviours . METHODS The Saving and Empowering Young Lives in Europe ( SEYLE ) study is a multicentre , cluster-r and omised controlled trial . The SEYLE sample consisted of 11,110 adolescent pupils , median age 15 years ( IQR 14 - 15 ) , recruited from 168 schools in ten European Union countries . We r and omly assigned the schools to one of three interventions or a control group . The interventions were : ( 1 ) Question , Persuade , and Refer ( QPR ) , a gatekeeper training module targeting teachers and other school personnel , ( 2 ) the Youth Aware of Mental Health Programme ( YAM ) targeting pupils , and ( 3 ) screening by professionals ( ProfScreen ) with referral of at-risk pupils . Each school was r and omly assigned by r and om number generator to participate in one intervention ( or control ) group only and was unaware of the interventions undertaken in the other three trial groups . The primary outcome measure was the number of suicide attempt(s ) made by 3 month and 12 month follow-up . Analysis included all pupils with data available at each timepoint , excluding those who had ever attempted suicide or who had shown severe suicidal ideation during the 2 weeks before baseline . This study is registered with the German Clinical Trials Registry , number DRKS00000214 . FINDINGS Between Nov 1 , 2009 , and Dec 14 , 2010 , 168 schools ( 11,110 pupils ) were r and omly assigned to interventions ( 40 schools [ 2692 pupils ] to QPR , 45 [ 2721 ] YAM , 43 [ 2764 ] ProfScreen , and 40 [ 2933 ] control ) . No significant differences between intervention groups and the control group were recorded at the 3 month follow-up . At the 12 month follow-up , YAM was associated with a significant reduction of incident suicide attempts ( odds ratios [ OR ] 0·45 , 95 % CI 0·24 - 0·85 ; p=0·014 ) and severe suicidal ideation ( 0·50 , 0·27 - 0·92 ; p=0·025 ) , compared with the control group . 14 pupils ( 0·70 % ) reported incident suicide attempts at the 12 month follow-up in the YAM versus 34 ( 1·51 % ) in the control group , and 15 pupils ( 0·75 % ) reported incident severe suicidal ideation in the YAM group versus 31 ( 1·37 % ) in the control group . No participants completed suicide during the study period . INTERPRETATION YAM was effective in reducing the number of suicide attempts and severe suicidal ideation in school-based adolescents . These findings underline the benefit of this universal suicide preventive intervention in schools . FUNDING Coordination Theme 1 ( Health ) of the European Union Seventh Framework Programme Treatment with selective serotonin reuptake inhibitors ( SSRIs ) may increase the risk of impulsive acts including suicide , while data from epidemiological studies suggest that the effect of SSRIs in the elderly may be beneficial . We aim ed to evaluate the association between exposure to antidepressants and suicidality in a cohort of elderly patients suffering from major depressive disorder ( MDD ) . This was a retrospective matched case-controlled evaluation over a 10-year period . All records of admissions of patients with MDD ( ICD-10 ) were assessed . The index group comprised all patients who had attempted suicide in the month prior to admission . The case-controlled group was the next admission of a patient suffering from MDD , matched for sex and age who had not attempted suicide in the month prior to admission . The index group during the 10-year period ( 1995–2004 ) consisted of 101 patients suffering from MDD who were hospitalized following a suicide attempt . Mean age for the group was 76.5±6.6 years ; there were 42 men and 59 women . The control group patients ( N=101 ) were matched for age ( mean 76.6±6.9 years ) and sex . The proportion of patients exposed to an antidepressant was significantly greater in the control group , than in the group of patients who had attempted suicide ( 58 vs 42 % , odds ratio 1.94 ( 95 % CI : 1.1–3.4 ) , p=0.019 ) . SSRIs were prescribed in 29 % of patients in the control group vs 21 % of patients in the index group ( p=0.03 ) . It is of interest to note that concomitant prescription of benzodiazepines also conferred a protective effect . In conclusion , elderly depressed patients treated with antidepressants may be at reduced risk of attempting suicide . These findings need support from prospect i ve r and omized trials BACKGROUND Hospital-treated self-poisoning is common , with limited effective interventions for reducing subsequent suicidal behaviour . AIMS To test the efficacy of a postcard intervention to reduce suicidal behaviour . METHOD R and omised controlled trial of individuals who self-poisoned ( n = 2300 ) , the intervention consisted of nine postcards sent over 12 months versus usual treatment . Outcomes assessed at 12 months ( n = 2113 ) were suicidal ideation , suicide attempts and self-cutting ( proportion and event rates ) . RESULTS There was a significant reduction in any suicidal ideation ( relative risk reduction ( RRR ) = 0.31 , 95 % CI 0.22 - 0.38 ) , any suicide attempt ( RRR = 0.42 , 95 % CI 0.11 - 0.63 ) and number of attempts ( incidence rate ratios ( IRR ) = 0.64 , 95 % CI 0.42 - 0.97 ) . There was no significant reduction in any self-cutting ( RRR = 0.14 , 95 % CI -0.29 to 0.42 ) or self-cutting events ( IRR = 1.03 95 % CI 0.76 - 1.39 ) . CONCLUSIONS A postcard intervention reduced suicidal ideation and suicide attempts in a non-Western population . Sustained , brief contact by mail may reduce suicidal ideation and suicide attempts in individuals who self-poison Background Pesticide ingestion is a common method of self-harm in the rural developing world . In an attempt to reduce the high case fatality seen with the herbicide paraquat , a novel formulation ( INTEON ) has been developed containing an increased emetic concentration , a purgative , and an alginate that forms a gel under the acid conditions of the stomach , potentially slowing the absorption of paraquat and giving the emetic more time to be effective . We compared the outcome of paraquat self-poisoning with the st and ard formulation against the new INTEON formulation following its introduction into Sri Lanka . Methods and Findings Clinical data were prospect ively collected on 586 patients with paraquat ingestion presenting to nine large hospitals across Sri Lanka with survival to 3 mo as the primary outcome . The identity of the formulation ingested after October 2004 was confirmed by assay of blood or urine sample s for a marker compound present in INTEON . The proportion of known survivors increased from 76/297 with the st and ard formulation to 103/289 with INTEON ingestion , and estimated 3-mo survival improved from 27.1 % to 36.7 % ( difference 9.5 % ; 95 % confidence interval [ CI ] 2.0%–17.1 % ; p = 0.002 , log rank test ) . Cox proportional hazards regression analyses showed an approximately 2-fold reduction in toxicity for INTEON compared to st and ard formulation . A higher proportion of patients ingesting INTEON vomited within 15 min ( 38 % with the original formulation to 55 % with INTEON , p < 0.001 ) . Median survival time increased from 2.3 d ( 95 % CI 1.2–3.4 d ) with the st and ard formulation to 6.9 d ( 95 % CI 3.3–10.7 d ) with INTEON ingestion ( p = 0.002 , log rank test ) ; however , in patients who did not survive there was a comparatively smaller increase in median time to death from 0.9 d ( interquartile range [ IQR ] 0.5–3.4 ) to 1.5 d ( IQR 0.5–5.5 ) ; p = 0.02 . Conclusions The survey has shown that INTEON technology significantly reduces the mortality of patients following paraquat ingestion and increases survival time , most likely by reducing absorption OBJECTIVE To evaluate whether Attachment-Based Family Therapy ( ABFT ) is more effective than Enhanced Usual Care ( EUC ) for reducing suicidal ideation and depressive symptoms in adolescents . METHOD This was a r and omized controlled trial of suicidal adolescents between the ages of 12 and 17 , identified in primary care and emergency departments . Of 341 adolescents screened , 66 ( 70 % African American ) entered the study for 3 months of treatment . Assessment occurred at baseline , 6 weeks , 12 weeks , and 24 weeks . ABFT consisted of individual and family meetings , and EUC consisted of a facilitated referral to other providers . All participants received weekly monitoring and access to a 24-hour crisis phone . Trajectory of change and clinical recovery were measured for suicidal ideation and depressive symptoms . RESULTS Using intent to treat , patients in ABFT demonstrated significantly greater rates of change on self-reported suicidal ideation at post-treatment evaluation , and benefits were maintained at follow-up , with a strong overall effect size ( ES = 0.97 ) . Between-group differences were similar on clinician ratings . Significantly more patients in ABFT met criteria for clinical recovery on suicidal ideation post-treatment ( 87 % ; 95 % confidence interval [ CI ] = 74.6 - 99.6 ) than patients in EUC ( 51.7 % ; 95 % CI = 32.4 - 54.32 ) . Benefits were maintained at follow-up ( ABFT , 70 % ; 95 % CI = 52.6 - 87.4 ; EUC 34.6 % ; 95 % CI = 15.6 - 54.2 ; odds ratio = 4.41 ) . Patterns of depressive symptoms over time were similar , as were results for a sub sample of adolescents with diagnosed depression . Retention in ABFT was higher than in EUC ( mean = 9.7 versus 2.9 ) . CONCLUSIONS ABFT is more efficacious than EUC in reducing suicidal ideation and depressive symptoms in adolescents . Additional research is warranted to confirm treatment efficacy and to test the proposed mechanism of change ( the Family Safety Net Study ) . Clinical Trial Registry Information : Preventing Youth Suicide in Primary Care : A Family Model , URL : http://www . clinical trials.gov , unique identifier : NCT00604097 OBJECTIVE This paper reports the impact of two first- and second- grade classroom based universal preventive interventions on the risk of Suicide Ideation ( SI ) and Suicide Attempts ( SA ) by young adulthood . The Good Behavior Game ( GBG ) was directed at socializing children for the student role and reducing aggressive , disruptive behavior . Mastery Learning ( ML ) was aim ed at improving academic achievement . Both were implemented by the teacher . METHODS The design was epidemiologically based , with r and omization at the school and classroom levels and balancing of children across classrooms . The trial involved a cohort of first- grade children in 19 schools and 41 classrooms with intervention at first and second grade s. A replication was implemented with the next cohort of first grade children with the same teachers but with little mentoring or monitoring . RESULTS In the first cohort , there was consistent and robust GBG-associated reduction of risk for suicide ideation by age 19 - 21 years compared to youths in st and ard setting ( control ) classrooms regardless of any type of covariate adjustment . A GBG-associated reduced risk for suicide attempt was found , though in some covariate-adjusted models the effect was not statistically robust . No statistically significant impact on these outcomes was found for ML . The impact of the GBG on suicide ideation and attempts was greatly reduced in the replication trial involving the second cohort . CONCLUSIONS A universal preventive intervention directed at socializing children and classroom behavior management to reduce aggressive , disruptive behavior may delay or prevent onset of suicide ideation and attempts . The GBG must be implemented with precision and continuing support of teachers Background Suicide is a leading cause of death for children and youth in the United States . Although school based programs have been the principal vehicle for youth suicide prevention efforts for over two decades , few have been systematic ally evaluated . This study examined the effectiveness of the Signs of Suicide ( SOS ) prevention program in reducing suicidal behavior . Methods 4133 students in 9 high schools in Columbus , Georgia , western Massachusetts , and Hartford , Connecticut were r and omly assigned to intervention and control groups during the 2001–02 and 2002–03 school years . Self-administered question naires were completed by students in both groups approximately 3 months after program implementation . Results Significantly lower rates of suicide attempts and greater knowledge and more adaptive attitudes about depression and suicide were observed among students in the intervention group . Students ' race/ethnicity , grade , and gender did not alter the impact of the intervention on any of the outcomes assessed in this analysis . Conclusion This study has confirmed preliminary analysis of Year 1 data with a larger and more racially and socio-economically diverse sample . SOS continues to be the only universal school-based suicide prevention program to demonstrate significant effects of self-reported suicide attempts in a study utilizing a r and omized experimental design . Moreover , the beneficial effects of SOS were observed among high school-aged youth from diverse racial/ethnic background s , highlighting the program 's utility as a universal prevention program . Trial registration clinical trials.gov NCT000387855 Background Pesticide suicides are considered the single most important means of suicide worldwide . Central ized pesticide storage facilities have the possible advantage of delaying access to pesticides thereby reducing suicides . We undertook this study to examine the feasibility and acceptability of a central ized pesticide storage facility as a preventive intervention strategy in reducing pesticide suicides . Methods A community r and omized controlled feasibility study using a mixed methods approach involving a household survey ; focus group discussion s ( FGDs ) and surveillance were undertaken . The study was carried out in a district in southern India . Eight villages that engaged in floriculture were identified . Using the lottery method two were r and omized to be the intervention sites and two villages constituted the control site . Two central ized storage facilities were constructed with local involvement and lockable storage boxes were constructed . The household survey conducted at baseline and one and a half years later documented information on sociodemographic data , pesticide usage , storage and suicides . Results At baseline 4446 individuals ( 1097 households ) in the intervention and 3307 individuals ( 782 households ) in the control sites were recruited while at follow up there were 4308 individuals ( 1063 households ) in the intervention and 2673 individuals ( 632 households ) in the control sites . There were differences in baseline characteristics and imbalances in the prevalence of suicides between intervention and control sites as this was a small feasibility study .The results from the FGDs revealed that most participants found the storage facility to be both useful and acceptable . In addition to protecting against wastage , they felt that it had also helped prevent pesticide suicides as the pesticides stored here were not as easily and readily accessible . The primary analyses were done on an Intention to Treat basis . Following the intervention , the differences between sites in changes in combined , completed and attempted suicide rates per 100,000 person-years were 295 ( 95 % CI : 154.7 , 434.8 ; p < 0.001 ) for pesticide suicide and 339 ( 95 % CI : 165.3 , 513.2 , p < 0.001 ) for suicide of all methods . Conclusions Suicide by pesticides poisoning is a major public health problem and needs innovative interventions to address it . This study , the first of its kind in the world , examined the feasibility of a central storage facility as a means of limiting access to pesticides and , has provided preliminary results on its usefulness . These results need to be interpreted with caution in view of the imbalances between sites . The facility was found to be acceptable , thereby underscoring the need for larger studies for a longer duration .Trial registration IS RCT N : IS RCT Objective To examine the effectiveness and cost-effectiveness of group therapy for self harm in young people . Design Two arm , single ( assessor ) blinded parallel r and omised allocation trial of a group therapy intervention in addition to routine care , compared with routine care alone . R and omisation was by minimisation controlling for baseline frequency of self harm , presence of conduct disorder , depressive disorder , and severity of psychosocial stress . Participants Adolescents aged 12 - 17 years with at least two past episodes of self harm within the previous 12 months . Exclusion criteria were : not speaking English , low weight anorexia nervosa , acute psychosis , substantial learning difficulties ( defined by need for specialist school ) , current containment in secure care . Setting Eight child and adolescent mental health services in the northwest UK . Interventions Manual based developmental group therapy programme specifically design ed for adolescents who harm themselves , with an acute phase over six weekly sessions followed by a booster phase of weekly groups as long as needed . Details of routine care were gathered from participating centres . Main outcome measures Primary outcome was frequency of subsequent repeated episodes of self harm . Secondary outcomes were severity of subsequent self harm , mood disorder , suicidal ideation , and global functioning . Total costs of health , social care , education , and criminal justice sector services , plus family related costs and productivity losses , were recorded . Results 183 adolescents were allocated to each arm ( total n=366 ) . Loss to follow-up was low ( < 4 % ) . On all outcomes the trial cohort as a whole showed significant improvement from baseline to follow-up . On the primary outcome of frequency of self harm , proportional odds ratio of group therapy versus routine care adjusting for relevant baseline variables was 0.99 ( 95 % confidence interval 0.68 to 1.44 , P=0.95 ) at 6 months and 0.88 ( 0.59 to 1.33 , P=0.52 ) at 1 year . For severity of subsequent self harm the equivalent odds ratios were 0.81 ( 0.54 to1.20 , P=0.29 ) at 6 months and 0.94 ( 0.63 to 1.40 , P=0.75 ) at 1 year . Total 1 year costs were higher in the group therapy arm ( £ 21 781 ) than for routine care ( £ 15 372 ) but the difference was not significant ( 95 % CI −1416 to 10782 , P=0.132 ) . Conclusions The addition of this targeted group therapy programme did not improve self harm outcomes for adolescents who repeatedly self harmed , nor was there evidence of cost effectiveness . The outcomes to end point for the cohort as a whole were better than current clinical expectations . Trial registration IS RCT N The objectives of this study are to assess the magnitude and course of suicidal ideation during outpatient treatment and aftercare for adolescents with alcohol use disorders ( AUD ) . One hundred seventy-seven adolescents meeting eligibility criteria , including no past 30-day suicidal behavior , participated in 9 weeks of outpatient cognitive-behavioral group therapy . Treatment completers were r and omized into : ( 1 ) No-Active , ( 2 ) In-Person , or ( 3 ) Telephone aftercare conditions for a period of 12 weeks . No specific intervention for suicidal behavior was provided during the study . The Suicide Ideation Question naire ( SIQ-JR , Reynolds , 1988 ) was administered at baseline , end of treatment , and end of aftercare . The results are as follows , a higher baseline suicidal ideation was associated with higher retention at the end of treatment and through aftercare . The In-Person Aftercare condition showed a significant decrease in suicidal ideation , relative to the No-Active Aftercare condition . There was a trend for similarly reduced severity of suicidal ideation in the Telephone Aftercare condition . In conclusion , the type of aftercare and result ing decrease in AUD may play a role in the reduction in suicidal ideation . The mechanism of change by which suicidal ideation is reduced in adolescents in treatment for AUD needs to be further explored The Collaborative Assessment and Management of Suicidality ( CAMS ) is a novel clinical approach used to identify , assess , and manage suicidal out patients ( Jobes & Drozd , 2004 ) . The results of a retrospective study evaluating the impact of CAMS versus treatment as usual ( TAU ) on suicidal out patients are presented . Patients in the CAMS treatment group ( n = 25 ) resolved their suicidality significantly more quickly than TAU patients ( n = 30 ) . CAMS was also significantly associated with decreased medical health care utilization in the 6 months after the start of suicide-related mental health treatment . These results provide promising preliminary support for the effectiveness of CAMS and a foundation for prospect i ve research BACKGROUND Attempted suicide is a strong risk factor for subsequent suicidal behaviors . Innovative strategies to deal with people who have attempted suicide are needed , particularly in re source -poor setting s. AIMS To evaluate a brief educational intervention and periodic follow-up contacts ( BIC ) for suicide attempters in five culturally different sites ( Campinas , Brazil ; Chennai , India ; Colombo , Sri Lanka ; Karaj , Islamic Republic of Iran ; and Yuncheng , People 's Republic of China ) as part of the WHO Multisite Intervention Study on Suicidal Behaviors ( SUPRE-MISS ) . METHODS Among the 1,867 suicide attempters enrolled in the emergency departments of the participating sites , 922 ( 49.4 % ) were r and omly assigned to a brief intervention and contact ( BIC ) group and 945 ( 50.6 % ) to a treatment as usual ( TAU ) group . Repeated suicide attempts over the 18 months following the index attempt - the secondary outcome measure presented in this paper - were identified by follow-up calls or visits . Subsequent completed suicide - the primary outcome measure - has been reported in a previous paper . RESULTS Overall , the proportion of subjects with repeated suicide attempts was similar in the BIC and TAU groups ( 7.6 % vs. 7.5 % , chi(2 ) = 0.013 ; p = .909 ) , but there were differences in rates across the five sites . CONCLUSIONS This study from five low- and middle-income countries does not confirm the effectiveness of brief educational intervention and follow-up contacts for suicide attempters in reducing subsequent repetition of suicide attempts up to 18 months after discharge from emergency departments BACKGROUND Psychiatric in- patients are at high risk of suicide . Recent reductions in bed numbers in many countries may have affected this risk but few studies have specifically investigated temporal trends . We aim ed to explore trends in psychiatric in-patient suicide over time . METHOD A prospect i ve study of all patients admitted to National Health Service ( NHS ) in-patient psychiatric care in Engl and ( 1997 - 2008 ) . Suicide rates were determined using National Confidential Inquiry and Hospital Episode Statistics ( HES ) data . RESULTS Over the study period there were 1942 psychiatric in-patient suicides . Between the first 2 years of the study ( 1997 , 1998 ) and the last 2 years ( 2007 , 2008 ) the rate of in-patient suicide fell by nearly one-third from 2.45 to 1.68 per 100,000 bed days . This fall in rate was observed for males and females , across ethnicities and diagnoses . It was most marked for patients aged 15 - 44 years . Rates also fell for the most common suicide methods , particularly suicide by hanging on the ward ( a 59 % reduction ) . Although the number of post-discharge suicides fell , the rate of post-discharge suicide may have increased by 19 % . The number of suicide deaths in those under the care of crisis resolution/home treatment teams has increased in recent years to approximately 160 annually . CONCLUSIONS The rate of suicide among psychiatric in- patients in Engl and has fallen considerably . Possible explanations include falling general population rates , changes in the at-risk population or improved in-patient safety . However , a transfer of risk to the period after discharge or other clinical setting s such as crisis resolution teams can not be ruled out We conducted a r and omized controlled trial to test whether a Brief Mobile Treatment ( BMT ) intervention could improve outcomes relative to usual care among suicide attempters . The intervention included training in problem solving therapy , meditation , a brief intervention to increase social support as well as advice on alcohol and other drugs , and mobile phone follow-up . The effect of the intervention was measured in terms of a reduction in suicidal ideation , depression and self-harm at Baseline , six and 12 months . A wait-list control group received usual care . A total of 68 participants was recruited from a Sri Lankan hospital following a suicide attempt . Participants who received the intervention were found to achieve significant improvements in reducing suicidal ideation and depression than those receiving usual care . The BMT group also experienced a significant improvement of social support when compared to the control group . However , the BMT group did not demonstrate a significant effect in reducing actual self-harm and most substance use , and differential effects on alcohol use were restricted to men . Although the present study was limited in revealing which component of the intervention was more effective in preventing suicide , it showed its efficacy in reducing suicide as a whole Background : Despite the ubiquity of suicidality in behavioral health setting s , empirically supported interventions for suicidality are surprisingly rare . Given the importance of resolving suicidality and therapists ' anxieties about treating suicidal patients , there is a clear need for innovative services and clinical approaches . The purpose of the current study was an attempt to address some of these needs by examining the feasibility and use of a new intervention called the “ Collaborative Assessment and Management of Suicidality ” ( CAMS ) within a “ Next‐Day Appointment ” ( NDA ) outpatient treatment setting . Methods : As part of a larger feasibility study , n = 32 suicidal patients were r and omly assigned to CAMS care versus Enhanced Care as Usual ( E‐CAU ) in an outpatient crisis intervention setting attached to a safety net hospital . Intent to treat suicidal patients were seen and assessed before , during , and after treatment ( with follow‐up assessment s conducted at 2 , 4 , 6 , and 12 months ) . Results : The feasibility of using CAMS in the NDA setting was clear ; both groups appeared to initially benefit from their respective treatments in terms of decreased suicidal ideation and overall symptom distress . Although patients rated both treatments favorably , the CAMS group had significantly higher satisfaction and better treatment retention than E‐CAU . At 12 months post‐treatment , CAMS patients showed significantly better and sustained reductions in suicidal ideation , overall symptom distress , and increased hope in comparison to E‐CAU patients . Conclusions : CAMS was both feasible in this NDA setting and effective in treating suicidal ideation , distress , and hopelessness ( particularly at 12 months followup ) . Depression and Anxiety , 2011 . © 2011 Wiley Periodicals , This study explored intervention outcomes and mechanisms that could help explain why low-income , African American women with a history of intimate partner abuse and suicide attempt improve in response to a culturally-informed intervention , the Grady Nia Project . Specifically , the investigation examined whether or not the intervention had effects on the women and whether or not spiritual well-being and coping mediated the effects of the intervention on suicidal ideation and depressive symptoms . In this r and omized controlled clinical trial , data from 89 women who completed both pre- and post-intervention assessment s were analyzed . During the post-intervention follow-up , women in the active intervention group reported lower levels of suicidal ideation and depressive symptoms and higher levels of existential well-being and adaptive coping skills than those women r and omized to the treatment as usual group . However , only existential well-being was found to mediate treatment effects on suicidal ideation and depressive symptoms . Religious well-being , as well as adaptive and maladaptive coping , did not serve a mediational function . These findings highlight the importance of design ing and implementing culturally-sensitive and evidence -based strategies that enhance existential well-being in this population OBJECTIVES To determine the effect of a primary care-based collaborative care program for depression on suicidal ideation in older adults . DESIGN R and omized , controlled trial . SETTING Eighteen diverse primary care clinics . PARTICIPANTS One thous and eight hundred one adults aged 60 and older with major depression or dysthymia . INTERVENTION Participants r and omized to collaborative care had access to a depression care manager who supported antidepressant medication management prescribed by their primary care physician and offered a course of Problem Solving Treatment in Primary Care for 12 months . Participants in the control arm received care as usual . MEASUREMENTS Participants had independent assessment s of depression and suicidal ideation at baseline and 3 , 6 , 12 , 18 , and 24 months . Depression was assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders , 4th Edition ( SCID ) . Suicidal ideation was determined using the SCID and the Hopkins Symptoms Checklist . RESULTS At baseline , 139 ( 15.3 % ) intervention subjects and 119 ( 13.3 % ) controls reported thoughts of suicide . Intervention subjects had significantly lower rates of suicidal ideation than controls at 6 months ( 7.5 % vs 12.1 % ) and 12 months ( 9.8 % vs 15.5 % ) and even after intervention re sources were no longer available at 18 months ( 8.0 % vs 13.3 % ) and 24 months ( 10.1 % vs 13.9 % ) . There were no completed suicides in either group . Information on suicide attempts or hospitalization for suicidal ideation was not available . CONCLUSION Primary care-based collaborative care programs for depression represent one strategy to reduce suicidal ideation and potentially the risk of suicide in older primary care patients BACKGROUND In addition to implementing a depression screening program , conducting a survey beforeh and might contribute to suicide risk reduction for the elderly . AIMS This study evaluates outcomes of a community-based program to prevent suicide among individuals aged 60 and over , using a quasiexperimental design with an intervention region ( 41,337 residents , 35.1 % aged 60 and over ) and a neighboring reference region . METHODS Our 2-year intervention program included an anonymous survey by r and om sample in the entire intervention region and , in the second year , a depression screening with follow-up by a psychiatrist in the higher-risk districts . Changes in the risk of completed suicide were estimated by the incidence-rate ratio ( IRR ) . RESULTS The risk for men in the intervention region was reduced by 61 % ( age-adjusted IRR = 0.39 ; 90 % CI = 0.18 - 0.87 ) , whereas there was a ( statistically insignificant ) 51 % risk reduction for women in the intervention region , and no risk reduction for either men or women in the reference region . The ratio of the crude IRR for elderly men in the intervention region to that for all elderly men in Japan was estimated at 0.42 ( 90 % CI = 0.18 - 0.92 ) , showing that the risk reduction was greater than the national change . CONCLUSIONS The management of depression through a combination of an initial survey and subsequent screening holds clear promise for prompt effectiveness in the prevention of suicide for elderly men , and potentially for women This study examines the efficacy of a short-term individual therapy , Manual Assisted Cognitive Treatment ( MACT ) , which was developed to treat parasuicidal ( suicidal or self-harming ) patients . In this trial , MACT was modified to focus on deliberate self-harm ( DSH ) in patients with borderline personality disorder ( BPD ) . Thirty BPD patients who were engaged in DSH while in ongoing treatments , i.e. , treatment-as-usual ( TAU ) , were r and omly assigned to receive MACT ( N = 15 ) or not . DSH and level of suicide ideation were assessed at the baseline , at completion of the MACT intervention , and six months later . Results indicated that MACT was associated with significantly less frequent DSH upon completion of the intervention and with significantly decreased DSH frequency and severity at the six months follow-up . Moreover , MACT 's contribution to reducing DSH frequency and severity was greater than the contribution by the amount of concurrent treatments . In contrast , MACT did not affect the level of suicide ideation and time-to-repeat of DSH . In conclusion , MACT seems to be a promising intervention for DSH in patients with BPD . More definitive studies are needed OBJECTIVE The Prevention of Suicide in Primary Care Elderly : Collaborative Trial ( PROSPECT ) evaluated the impact of a care management intervention on suicidal ideation and depression in older primary care patients . This is the first report of outcomes over a 2-year period . METHOD Study participants were patients 60 years of age or older ( N=599 ) with major or minor depression selected after screening 9,072 r and omly identified patients of 20 primary care practice s r and omly assigned to provide either the PROSPECT intervention or usual care . The intervention consisted of services of 15 trained care managers , who offered algorithm-based recommendations to physicians and helped patients with treatment adherence over 24 months . RESULTS Compared with patients receiving usual care , those receiving the intervention had a higher likelihood of receiving antidepressants and /or psychotherapy ( 84.9%-89 % versus 49%-62 % ) and had a 2.2 times greater decline in suicidal ideation over 24 months . Treatment response occurred earlier on average in the intervention group and increased from months 18 to 24 , while no appreciable increase in treatment response occurred in the usual care group during the same period . Among patients with major depression , a greater number achieved remission in the intervention group than in the usual-care group at 4 months ( 26.6 % versus 15.2 % ) , 8 months ( 36 % versus 22.5 % ) , and 24 months ( 45.4 % versus 31.5 % ) . Patients with minor depression had favorable outcomes regardless of treatment assignment . CONCLUSIONS Sustained collaborative care maintains high utilization of depression treatment , reduces suicidal ideation , and improves the outcomes of major depression over 2 years 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 CONTEXT Dialectical behavior therapy ( DBT ) is a treatment for suicidal behavior and borderline personality disorder with well-documented efficacy . OBJECTIVE To evaluate the hypothesis that unique aspects of DBT are more efficacious compared with treatment offered by non-behavioral psychotherapy experts . DESIGN One-year r and omized controlled trial , plus 1 year of posttreatment follow-up . SETTING University outpatient clinic and community practice . PARTICIPANTS One hundred one clinical ly referred women with recent suicidal and self-injurious behaviors meeting DSM-IV criteria , matched to condition on age , suicide attempt history , negative prognostic indication , and number of lifetime intentional self-injuries and psychiatric hospitalizations . INTERVENTION One year of DBT or 1 year of community treatment by experts ( developed to maximize internal validity by controlling for therapist sex , availability , expertise , allegiance , training and experience , consultation availability , and institutional prestige ) . MAIN OUTCOME MEASURES Trimester assessment s of suicidal behaviors , emergency services use , and general psychological functioning . Measures were selected based on previous outcome studies of DBT . Outcome variables were evaluated by blinded assessors . RESULTS Dialectical behavior therapy was associated with better outcomes in the intent-to-treat analysis than community treatment by experts in most target areas during the 2-year treatment and follow-up period . Subjects receiving DBT were half as likely to make a suicide attempt ( hazard ratio , 2.66 ; P = .005 ) , required less hospitalization for suicide ideation ( F(1,92 ) = 7.3 ; P = .004 ) , and had lower medical risk ( F(1,50 ) = 3.2 ; P = .04 ) across all suicide attempts and self-injurious acts combined . Subjects receiving DBT were less likely to drop out of treatment ( hazard ratio , 3.2 ; P < .001 ) and had fewer psychiatric hospitalizations ( F(1,92 ) = 6.0 ; P = .007 ) and psychiatric emergency department visits ( F(1,92 ) = 2.9 ; P = .04 ) . CONCLUSIONS Our findings replicate those of previous studies of DBT and suggest that the effectiveness of DBT can not reasonably be attributed to general factors associated with expert psychotherapy . Dialectical behavior therapy appears to be uniquely effective in reducing suicide attempts The efficacy of two types of theapy conducted exclusively over the telephone was studied . Clients ( N=55 ) were recruited from a pool of callers to a suicide hotline and were r and omly assigned to a waiting list control ( WC ) or Solution Focused Brief Therapy ( SFBT ) or Common Factors Therapy ( CFT ) . It was hypothesized that improvements would be significantly higher in the two therapy conditions compared to the waitlist control and SFBT would be significantly more efficacious than CFT . Results confirmed that improvement was significantly higher in the two treatment conditions compared to the waitlist control , but no difference in improvement was found between SFBT and CFT . The implication s of these findings for suicide hotlines are discussed Repetition after attempted suicide is high but only few effect studies have been carried out . The Baerum Model from Norway offers practical and affordable intervention for those not being offered psychiatric treatment . During a period from 2005–2007 , all attempted suicide patients except those with major psychiatric diagnoses ( schizophrenia , bipolar disorder , severe/psychotic depression ) , were offered participation . The intervention group received the OPAC programme ( outreach , problem solving , adherence , continuity ) and the control group received treatment as usual ( TAU ) . The intervention period was 6 months . After this intervention period , all patients were followed passively for an extra 6 months . The design was an intent-to-treat one . The outcomes were : 1 ) repetition of attempted suicide or suicide , and 2 ) total number of suicidal acts . A total of 200 patients were offered participation , 67 refused . Of the 133 participants , 69 were r and omized to the OPAC programme and 64 to the ( non-intervention ) control group . Four in each group dropped out after initial participation . There was a significant lower proportion who repeated a suicide attempt the intervention group ( proportion 8.7 % ) than in the control group ( proportion 21.9 % ) and the number of repetitive acts was also significant lower ( eight repetitions in the intervention group vs. 22 in the control group ) . In conclusion , our findings suggest a protective effect of the OPAC programme on the proportion who repeated a suicide attempt and on the total number of repetitions during the follow-up In this study , the authors investigated the efficacy of the Youth-Nominated Support Team-Version 1 ( YST-1 ) , a psychoeducational social network intervention , with 289 suicidal , psychiatrically hospitalized adolescents ( 197 girls , 92 boys ) . Adolescents were r and omly assigned to treatment-as-usual plus YST-1 or treatment-as-usual only . Assessment s were completed pre- and postintervention ( 6 months ) . There were no main effects for YST-1 on suicide ideation or attempts , internalizing symptoms , or related functional impairment . Relative to other girls , however , those who received YST-1 reported greater decreases in self-reported suicidal ideation ( actually treated analytic strategy ) and significantly greater decreases in mood-related functional impairment reported by their parents ( intent to treat and actually treated analytic strategies ) . This is the first r and omized controlled clinical trial to investigate the efficacy of a social network intervention with suicidal youths Patients with schizophrenia are at high risk of suicide . Cognitive behavior therapy ( CBT ) has been shown to reduce symptoms in schizophrenia . This study examines whether CBT also changes the level of suicidal ideation in patients with schizophrenia compared to a control group . Ninety ambulatory patients with symptoms of schizophrenia resistant to conventional antipsychotic medication were r and omized to CBT or befriending . They were assessed using the Comprehensive Psychopathological Rating Scale , including a rating of suicidal ideation at baseline , post intervention , and after 9 months . Post-hoc analysis revealed that CBT provided significant reductions in suicidal ideation at the end of therapy , and sustained at the follow-up . Further research is required to substantiate these findings and determine the process and mechanisms through which this reduction is achieved This study aims to evaluate outcomes of a community-based program to prevent suicide among the elderly ( > or=65 years old ) using a quasi-experimental design with two neighboring references . During 1999 - 2004 , the program including depression screening and group activity was conducted by the public health nurses in the Minami district ( population 1685 ) of Nagawa town , rural Japan . Pre-post changes in the risk of completing suicide were estimated by the incidence rate ratios ( IRR ) . The risk for Minami 's elderly females was reduced by 74 % ( age-adjusted IRR , 0.26 ; 90 % CI , 0.07 - 0.98 ) more than the historical trend , while there was no change in the risk of Minami 's males and nor in the male or female references . The local intervention using public health nursing would be effective against suicide for elderly females without diffusing to the surroundings BACKGROUND Self-harm and suicidal behaviour are common reasons for emergency department presentation . Those who present with self-harm have an elevated risk of further suicidal behaviour and death . AIMS To examine whether a postcard intervention reduces self-harm re-presentations in individuals presenting to the emergency department . METHOD R and omised controlled trial conducted in Christchurch , New Zeal and . The intervention consisted of six postcards mailed during the 12 months following an index emergency department attendance for self-harm . Outcome measures were the proportion of participants re-presenting with self-harm and the number of re-presentations for self-harm in the 12 months following the initial presentation . RESULTS After adjustment for prior self-harm , there were no significant differences between the control and intervention groups in the proportion of participants re-presenting with self-harm or in the total number of re-presentations for self-harm . CONCLUSIONS The postcard intervention did not reduce further self-harm . Together with previous results this finding suggests that the postcard intervention may be effective only for selected subgroups Sturm J , Plöderl M , Fartacek C , Kralovec K , Neunhäuserer D , Niederseer D , Hitzl W , Niebauer J , Schiepek G , Fartacek R. Physical exercise through mountain hiking in high‐risk suicide patients . A r and omized crossover trial To test feasibility of a routine screening tool and to examine factors associated with suicide and suicidal behaviors . Subjects included out patients with serious mental disorders . One hundred and sixteen clinicians routinely screened r and omly selected adult clients for suicide risk during a 6-month period . Forty-three ( 9 % ) clients reported thoughts to hurt/kill self ( screened positive ) , which spurred enhanced clinical intervention . There was no increase in frequency of suicide attempts . A history of multiple suicide attempts , recent stressful events , and present hopelessness were associated with a positive risk screen , clinician rating of risk , or altered treatment plan . It is feasible to safely implement a brief routine screening process in psychiatric outpatient setting s. Future research is needed to determine overall utility for routine screening Objective To investigate whether an intervention to improve treatment of depression in older adults in primary care modified the increased risk of death associated with depression . Design Long term follow-up of multi-site practice r and omized controlled trial ( PROSPECT —Prevention of Suicide in Primary Care Elderly : Collaborative Trial ) . Setting 20 primary care practice s in New York City , Philadelphia , and Pittsburgh , USA , r and omized to intervention or usual care . Participants 1226 participants identified between May 1999 and August 2001 through a two stage , age stratified ( 60 - 74 ; ≥75 years ) depression screening of r and omly sample d patients ; enrollment included patients who screened positive and a r and om sample of patients who screened negative . Intervention For two years , a depression care manager worked with primary care physicians in intervention practice s to provide algorithm based care for depression , offering psychotherapy , increasing antidepressant dose if indicated , and monitoring symptoms , adverse effects of drugs , and adherence to treatment . This paper reports the long term follow-up . Main outcome measure Mortality risk based on a median follow-up of 98 ( range 0.8 - 116.4 ) months through 2008 . Results In baseline clinical interviews , 396 people were classified as having major depression , 203 had clinical ly significant minor depression , and 627 did not meet criteria for depression . At follow-up , 405 patients had died . Patients with major depression in usual care were more likely to die than were those without depression ( hazard ratio 1.90 , 95 % confidence interval 1.57 to 2.31 ) . In contrast , patients with major depression in intervention practice s were at no greater risk than were people without depression ( hazard ratio 1.09 , 0.83 to 1.44 ) . Patients with major depression in intervention practice s , relative to usual care , were 24 % less likely to have died ( hazard ratio 0.76 , 0.57 to 1.00 ; P=0.05 ) . Preliminary data on cause of death are provided . No significant effect on mortality was found for minor depression . Conclusions Older adults with major depression in practice s provided with additional re sources to intensively manage depression had a mortality risk lower than that observed in usual care and similar to older adults without depression . Trial registration Clinical trials NCT00000367 This study examined the efficacy of Manual Assisted Cognitive Therapy ( MACT ) as a st and -alone treatment for Borderline Personality Disorder ( BPD ) with suicidal ideation , and piloted a Therapeutic Assessment ( TA ) intervention among 16 patients r and omly assigned to MACT or MACT+TA . Although MACT was associated with significant reductions in BPD features and suicidal ideation , less than half of the sample completed the treatment . The TA augmentation did not improve treatment retention but it was associated with somewhat greater clinical improvement . Although findings associate MACT with symptom reduction among persisting patients , attrition rate was problematically high in the overall sample OBJECTIVE Bipolar disorder is associated with high risk for suicidal acts . Observational studies suggest a protective effect of lithium against suicidal behavior . However , testing this effect in r and omized clinical trials is logistically and ethically challenging . The authors tested the hypothesis that lithium offers bipolar patients with a history of suicide attempt greater protection against suicidal behavior compared to valproate . METHOD Patients with bipolar disorder and past suicide attempts ( N=98 ) were r and omly assigned to treatment with lithium or valproate , plus adjunctive medications as indicated , in a double-blind 2.5-year trial . An intent-to-treat analysis was performed using the log-rank test for survival data . Two models were fitted : time to suicide attempt and time to suicide event ( attempt or hospitalization or change in medication in response to suicide plans ) . RESULTS There were 45 suicide events in 35 participants , including 18 suicide attempts made by 14 participants , six from the lithium group and eight from the valproate group . There were no suicides . Intent-to-treat analysis using the log-rank test showed no differences between treatment groups in time to suicide attempt or to suicide event . Post hoc power calculations revealed that the modest sample size , reflective of challenges in recruitment , only permits detection of a relative risk of 5 or greater . CONCLUSIONS Despite the high frequency of suicide events during the study , this r and omized controlled trial detected no difference between lithium and valproate in time to suicide attempt or suicide event in a sample of suicide attempters with bipolar disorder . However , smaller clinical ly significant differences between the two drugs were not ruled out |
12,066 | 22,578,048 | Findings of the review were : SRTs result in an improvement in knowledge and skills in those who attend them , deterioration in skills and , to a lesser extent , knowledge is highly likely as early as three months following SRTs , booster or refresher sessions may improve an individual 's ability to retain resuscitation skills after initial training and the instigation of resuscitation training in a healthcare institution significantly improves clinical management of resuscitations and patient outcome ( including survival ) after resuscitation attempts | A large number of resuscitation training courses ( structured resuscitation training programmes ( SRT ) ) take place in many countries in the world on a regular basis .
This review aim ed to determine whether after attending SRT programmes , the participants have a sustained retention of resuscitation knowledge and skills after their initial acquisition and whether there is an improvement in outcome for patients and /or their healthcare organisation after the institution of an SRT programme . | & NA ; To increase cardiopulmonary arrest survival , the American Heart Association developed basic and advanced cardiac life support ( ACLS ) courses that expose participants to realistic learning situations . This experimental study compared results of two ACLS classes on measures of knowledge ( content exam ) and resuscitation skills ( performance exam ) . Both the control and experimental groups consisted of physicians , nurses , emergency medical technicians , respiratory therapists , and advanced health care providers . The control group used low‐fidelity simulation ( LFS ) ; the experimental group was exposed to enhanced realism via high‐fidelity simulation ( HFS ) . The findings showed a positive correlation between enhanced practice and learning but no significant correlation between posttest and skills test scores for the LFS and HFS groups . The HFS group did score higher on both cognitive and behavioral tests , but the difference was not statistically significant . Participants from both groups indicated satisfaction with their forms of simulation experience and course design . In addition , participants ' self‐confidence to care for a victim of cardiopulmonary arrest was increased after completing their course ; profession and work experience had no effect on responses . The largest difference noted was in verbal responses to course satisfaction . The experimental group stated that learning using HFS was enjoyable and adamantly recommended that ACLS should only be taught using HFS . Further study is required to assess if practicing beyond the course enhances short‐ and long‐term retention of ACLS techniques Objectives : To assess the effect of high-fidelity simulation ( SIM ) on cognitive performance after a training session involving several mock resuscitations design ed to teach and reinforce Pediatric Advanced Life Support ( PALS ) algorithms . Methods : Pediatric residents were r and omized to high-fidelity simulation ( SIM ) or st and ard mannequin ( MAN ) groups . Each subject completed 3 study phases : ( 1 ) mock code exercises ( asystole , tachydysrhythmia , respiratory arrest , and shock ) to assess baseline performance ( PRE phase ) , ( 2 ) a didactic session review ing PALS algorithms , and ( 3 ) repeated mock code exercises requiring identical cognitive skills in a different clinical context to assess change in performance ( POST phase ) . SIM subjects completed all 3 phases using a high-fidelity simulator ( SimBaby , Laerdal Medical , Stavanger , Norway ) , and MAN subjects used SimBaby without simulated physical findings ( ie , as a st and ard mannequin ) . Performance in PRE and POST was measured by a scoring instrument design ed to measure cognitive performance ; scores were scaled to a range of 0 to 100 points . Improvement in performance from PRE to POST phases was evaluated by mixed modeling using a r and om intercept to account for within-subject variability . Results : Fifty-one subjects ( SIM , 25 ; MAN , 26 ) completed all phases . The PRE performance was similar between groups . Both groups demonstrated improvement in POST performance . The improvement in scores between PRE and POST phases was significantly better in the SIM group ( mean [ SD ] , 11.1 [ 4.8 ] vs. 4.8 [ 1.7 ] , P = 0.007 ) . Conclusions : The use of high-fidelity simulation in a PALS training session result ed in improved cognitive performance by pediatric house staff . Future studies should address skill and knowledge decays and team dynamics , and clearly defined and reproducible outcome measures should be sought OBJECTIVE To assess the educational efficacy of a Web-based pediatric advanced life support course ( Web-PALS ) . DESIGN Nonr and omized , prospect i ve , cohort study . SETTING University medical center . PARTICIPANTS Health care providers ( includes physicians , nurses , paramedics , and respiratory therapists ) taking either the Web-PALS or a traditional PALS course ( Trad-PALS ) . MAIN EXPOSURE Web-PALS . MAIN OUTCOME MEASURES Postcourse written examination scores and scored videotapes of students performing 5 PALS procedures were compared between study groups . Students completed precourse and postcourse question naires , rating on a 5-point Likert scale their self-confidence to perform PALS assessment s and procedures . A structured , course satisfaction survey was given after students had taken the Web-PALS course . RESULTS Eighty-six students completed the study ( 44 Web-PALS and 42 Trad-PALS ) . All students achieved a passing score on the written examination on their first attempt . Compared with students in the Trad-PALS group , students in the Web-PALS group scored slightly lower ( 97.1 % vs 95.4 % ; difference , 1.7 % ; 95 % confidence interval , 0.1 - 3.2 ) . Mean overall videotape scores were similar among the Web-PALS and Trad-PALS groups ( 75.0 % vs 73.0 % ; difference , 2.0 % ; 95 % confidence interval , -2.0 to 6.0 ) . After completing the Web-PALS course , the mean level of confidence improved from 3.77 to 4.28 ( difference , 0.51 ; 95 % confidence interval , 0.33 - 0.69 ) . Ninety-six percent of respondents indicated that Web-PALS met all of the stated objectives of the PALS course . All respondents indicated that they would recommend Web-PALS to a colleague . CONCLUSIONS Students perceive Web-PALS as a positive educational experience . Though not identical to students taking the Trad-PALS course , they performed well on postcourse cognitive and psychomotor testing . These findings support Web-PALS as an acceptable format for administering the PALS course Objective This feasibility study aim ed to describe and evaluate the effectiveness of a novel chest re-opening paediatric resuscitation scenario training scheme . Methods A novel scheme offering training on specialist skills required for post-operative cardiac patients such as chest re-opening and cardiac pacing via simulation was described . A prospect i ve audit of the first 23 consecutive training sessions was conducted to assess the scheme ’s effectiveness . Parameters assessed included timing of chest re-opening or cardiac pacing orders , and any delays in carrying out these orders . Results The median time required for the medical team leader to order chest re-opening was 4 min . New medical leaders took significantly longer to order chest re-opening than experienced medical team leaders ( P = 0.02 , Mann – Whitney U test ) . The performance of the team-in-training deteriorated with the introduction of new members but was correctable with serial training . Conclusions Effective simulation training integrating chest re-opening and cardiac pacing into st and ard paediatric resuscitation guidelines may be achieved without high fidelity simulation equipment One hundred thirty-two physicians who successfully completed advanced cardiac life support ( ACLS ) training were r and omly placed in a control group or one of two groups receiving interventions design ed to provide reinforcement of previously mastered knowledge and skills . These interventions included mailed periodic reprints ( group 1 ) or quarterly patient management problems ( group 2 ) . All physicians were retested for knowledge and skills related to ACLS one year later . Fifty-two ( 39.4 % ) could successfully ventilate the mannequin , and 62 ( 47.0 % ) could perform cardiac compression adequately . No differences were noted among groups . Significant differences in knowledge were found . The control group initiated appropriate therapy in a mock-arrest situation 52 % of the time , while group 1 averaged 75 % and group 2 averaged 82 % . These results indicate that reinforcement after continuing medical education may enhance knowledge retention , but does not maintain motor skills . Yearly recertification in ACLS skills should be considered , and frequent practice sessions should be encouraged for those physicians who are not active participants in ACLS activities INTRODUCTION The CAREvent Public Access Resuscitator ( PAR , O-Two Medical Technologies , Ontario , Canada ) is a new oxygen-driven device alternating two ventilations with 15 prompts for chest compressions . The PAR is design ed for use with a st and ard resuscitation face mask and is equipped with mask leakage and obstruction alarms . The purpose of this study was to assess the quality of basic life support ( BLS ) by hospital nurses and to evaluate if BLS with the PAR is better than BLS using the mouth-to-mask technique . METHODS The study group consisted of 352 nurses from Ghent University Hospital working outside the critical care and emergency departments . BLS skills were measured using a Laerdal Skillreporter manikin ( Laerdal , Norway ) connected to a Laerdal PC Skillreporting system . To assess base line skills , 200 nurses were tested without previous notice in single rescuer BLS using a pocket mask ( PM , Laerdal , Norway ) or a bag-valve mask device ( Laerdal , Norway ) over a period of 2 min . A separate consecutive sample of 152 nurses was r and omised to the PM or PAR groups after a st and ard BLS refresher course . The PAR group received a short period of training in PAR use . Immediately after training , both groups performed the 2 min single rescuer BLS test . RESULTS Unprepared nurses achieved only 26 compressions and 3 ventilations/min . Immediately after training , nurses using the PAR delivered 54 compressions/min as opposed to 35 for the PM group ( p<0.0001 ) . PAR users ventilated six times/min compared to five times for PM users ( p<0.0001 ) . CONCLUSION Immediately after training , the use of the PAR improved BLS performance by ward nurses significantly , bringing the number of ventilations and compressions per minute close to the theoretical maximum achievable within the current guidelines . Retention tests after 6 and 12 months will show if the effect is sustained Problem : Advance cardiac life support ( ACLS ) training does not address coordination of team re sources to improve the ability of teams to deliver needed treatments reliably and rapidly . Our objective was to use a human simulation training educational environment to develop multidisciplinary team skills and improve medical emergency team ( MET ) performance . We report findings of a crisis team training course that is focused on organization . Setting : Large center for human simulation training at a university affiliated tertiary care hospital . Participants : Ten courses were delivered and 138 clinical ly experienced individuals were trained ( 69 critical care nurses , 48 physicians , and 21 respiratory therapists ) . All participants were ACLS trained and experienced in responding to cardiac arrest situations . Course design : Each course had four components : ( 1 ) a web based presentation and pretest before the course ; ( 2 ) a brief reinforcing didactic session on the day of the course ; ( 3 ) three of five different simulated scenarios ; each followed by ( 4 ) debriefing and analysis with the team . Three of five simulator scenarios were used ; scenario selection and order was r and om . Trainees did not repeat any scenario or role during the training . Participants were video recorded to assist debriefing . Debriefing focused on reinforcing organizational aspects of team performance : assuming design ated roles independently , completing goals ( tasks ) assigned to each role , and directed communication . Measures for improvement : Participants grade d their performance of specific organizational and treatment tasks within specified time intervals by consensus . Simulator “ survival ” depended on supporting oxygenation , ventilation , circulation within 60 seconds , and delivering the definitive treatment within 3 minutes . Effects of change : Simulated survival ( following predetermined criteria for death ) increased from 0 % to 89 % . The initial team task completion rate was 10–45 % and rose to 80–95 % during the third session . Lessons learnt : Training multidisciplinary teams to organize using simulation technology is feasible . This preliminary report warrants more detailed inquiry BACKGROUND Critical pediatric illness or injury occurs infrequently in out-of-hospital setting s , making it difficult for paramedics to maintain physical assessment , treatment , and procedure skills . OBJECTIVES To document the ability of paramedics to retain clinical knowledge over a one-year interval after completing a pediatric resuscitation course and to determine whether clinical experience or retesting improves retention . METHODS This was a r and omized controlled study assessing retention of knowledge in pediatric resuscitation soon after , six months after , and 12 months following completion of a pediatric advanced life support course . Forty-three paramedics participated in pre- and post-pediatric resuscitation course testing and were r and omly assigned to one of four groups . Group 1 received a knowledge examination ( KE ) and mock resuscitation scenarios ( MR ) at six months . Group 2 received only the KE at six months . Group 3 received the MR only at six months . Group 4 received no intermediate testing . All groups were reassessed at 12 months . RESULTS Pediatric clinical knowledge ( as measured by KE ) rose sharply immediately after the course but returned to baseline levels within six months . There was no difference between the groups in knowledge scores at 12 months , despite the interventions at six months . CONCLUSIONS Although intensive out-of-hospital pediatric education enhances knowledge , that knowledge rapidly decays . Emergency medical services programs need to find novel ways to increase retention and ensure paramedic readiness OBJECTIVE To evaluate the effectiveness of an educational intervention on pediatric residents ' resuscitation fund of knowledge , technical skills , confidence , and overall performance . DESIGN Prospect i ve , nonconcurrent , controlled interventional trial . SETTING Urban pediatric tertiary care hospital . PARTICIPANTS An intervention group ( IG ) of 28 pediatric residents graduating in 1997 , and a control group ( CG ) of 30 pediatric residents graduating in 1996 . INTERVENTIONS Resuscitation course with didactic lectures and skills practice stations , as well as a minimum of 3 practice mock resuscitations with immediate feedback throughout postgraduate year 3 . MAIN OUTCOME MEASURES Fund of knowledge , using the Pediatric Advanced Life Support test and short answer test ; technical skills , using the Airway and Vascular Access Skills Assessment ; experience and confidence , using an anonymous survey ; and overall performance , evaluated using a videotaped mock resuscitation test . RESULTS The IG scored better on the short answer test ( P<.001 ) . A larger number of IG residents were successful in the completion of ancillary airway maneuvers and femoral vascular access ( P = .02 ) , as well as endotracheal intubation ( P = .004 ) and intraosseous access ( P = .002 ) . The IG was more confident in their leadership role ( P = .0001 ) and technical skills ( P = .05 ) . Trends toward improved overall performance were noted for the IG mock resuscitations . Residents in the IG were more likely to assess the airway in fewer than 2 minutes ( P = .02 ) , recognize the threat to life in fewer than 5 minutes ( P = .02 ) , and complete the primary survey in a timely fashion ( P = .05 ) . They required fewer prompts ( P = .04 ) and made fewer mistakes ( P = .07 ) . CONCLUSIONS A structured , formal curriculum can improve the necessary fund of knowledge , skills , confidence , and leadership required for resuscitation The purpose of the present study was to evaluate the cardiopulmonary resuscitation ( CPR ) skills of medical students after a 2-h basic life support class ( n = 129 ) and 6 months later ( n = 113 ) . Mean + /- SD written test score decreased from 6.4 + /- 0.7 to 6.2 + /- 0.8 ( P = 0.03 ) . Mean + /- SD breaths delivered before CPR decreased from 2.9 + /- 0.6 to 2.2 + /- 1.2 ( P = 0.0001 ) , ventilation rate increased from 12.2 + /- 1.9 to 14.3 + /- 5.0 breaths/min ( P = 0.0001 ) , tidal volume increased from 0.75 + /- 0.2 to 0.8 + /- 0.31 ( P = 0.11 ) , minute ventilation from 9.1 + /- 2.6 to 10.8 + /- 3.61 ( P = 0.0001 ) , and stomach inflation from 13 + /- 22 to 18 + /- 27 % of CPR breaths ( P = 0.11 ) . Mean + /- SD chest compression/min decreased from 56 + /- 9 to 54 + /- 12 ( P = 0.34 ) , depth of chest compression increased from 41 + /- 6 to 46 + /- 7 mm ( P = 0.0001 ) , h and s held incorrectly on the thorax increased from 22 + /- 27 to 23 + /- 32 % ( P = 0.59 ) , and leaning on the chest from 4 + /- 12 to 18 + /- 28 % of compressions ( P < 0.0001 ) . In summary , ventilation skills were unpredictable ; there was only a 5 % chance that a given student would achieve the same mouth-to-mouth ventilation performance in both the BLS class and 6 months later . Despite the respiratory mechanics of the CPR manikin which prevented stomach inflation much better than an unconscious patient with an unprotected airway , stomach inflation occurred repeatedly . Teachers of basic life support classes need to consider the respiratory mechanics of the CPR manikin being used to assure clinical ly realistic and appropriate mouth-to-mouth ventilation skills AIM OF THE STUDY There is consent that the use of automated external defibrillators ( AED ) by laypersons improves survival rates in case of cardiac arrest , but no evident consensus exists on the content and duration of training for this purpose . Acceptance of the implementation of Public Access Defibrillation programmes will depend on practical and target-oriented training concepts . The aim of this prospect i ve r and omised interventional study was to evaluate long-term effects of a specific , minimal training programme on using semiautomatic and fully automatic AEDs in simulated cardiac arrest . MATERIAL S AND METHODS In a mock cardiac arrest scenario 59 medical students with no specific previous medical education were tested during their first semester at medical school . Students who passed any medical emergency training were excluded . The subjects were evaluated before and after attending specified instructions of 15 min duration and after a period of 6 months . Main end points were time to first shock , electrode-positioning and safety throughout the procedure . RESULTS Mean time to first shock without prior instructions was 77.7+/-17.05 s. After instruction there was a significant improvement to 56.5+/-9.5 s ( p < or=0.01 ) and after 6 months this time had only slightly elongated ( 59.9+/-8.9 s ; p < or=0.01 ) . Initially , correct electrode placement was observed in 84.4 % . No difference was found immediately and 6 months after instructions ( 93.2 % and 98.3 % ) . All individuals performed safely . CONCLUSION First year medical students with minimal instruction are able to use semiautomatic as well as fully automatic AED sufficiently fast and safe without prior training . A significant improvement in time to first shock can be detected up to 6 months after receiving non-specific instructions of 15 min duration The need to train perinatal staff in neonatal resuscitation is widely accepted ; however , st and ardized educational programs have not been available . This study used a r and omized control trial to evaluate a one-day neonatal resuscitation education program with 190 nurses . Experimental subjects receiving the program had significantly improved knowledge and skill performance . Knowledge , but not skill performance , was maintained at six months for the experimental group . There was a significant relationship between subjects ' self-rating of knowledge and performance , suggesting that this method could be used to prioritize staff for basic or refresher training . An effective format and evaluation instruments for neonatal resuscitation training have been developed . Strategies to maintain skills should be addressed in future research Background Internal medicine residents must be competent in Advanced Cardiac Life Support ( ACLS ) for board certification . Traditional ACLS courses have limited ability to enable residents to achieve and maintain skills . Educational programs featuring reliable measurements and improved retention of skills would be useful for residency education . Method We developed a training program using a medical simulator , small-group teaching and deliberate practice . Residents received traditional ACLS education and subsequently participated in four two-hour educational sessions using the simulator . Resident performance in six simulated ACLS scenarios was assessed using a st and ardized checklist . Results After the program , resident ACLS skill improved significantly . The cohort was followed prospect ively for 14 months and the skills did not decay . Conclusions Use of a simulation-based educational program enabled us to achieve and maintain high levels of resident performance in simulated ACLS events . Given the limitations of traditional methods to train , assess and maintain competence , simulation technology can be a useful adjunct in high- quality ACLS education BACKGROUND Studies show that acquisition and retention of BLS skills is poor , and this may contribute to low survival from cardiac arrest . Feedback from instructors during BLS training is often lacking . This study investigates the effects of continuous feedback from a manikin on chest compression and ventilation techniques during training compared to instructor feedback alone . MATERIAL S AND METHODS A prospect i ve r and omised controlled trial . First-year healthcare students at the University of Birmingham were r and omised to receive training in st and ard or feedback groups . The st and ard group were taught by an instructor using a conventional manikin . The feedback group used a ' Skillreporter ' manikin , which provides continuous feedback on ventilation volume and chest compression depth and rate in addition to instructor feedback . Skill acquisition was tested immediately after training and 6 weeks later . RESULTS Ninety-eight participants were recruited ( conventional n=49 ; Skillreporter n=49 ) and were tested after training . Sixty-six students returned ( Skillreporter n=34 ; conventional n=32 ) for testing 6 weeks later . The Skillreporter group achieved better compression depth ( 39.96 mm versus 36.71 mm , P<0.05 ) , and more correct compressions ( 58.0 % versus 40.4 % , P<0.05 ) at initial testing . The Skillreporter group also achieved more correct compressions at week 6 ( 43.1 % versus 26.5 % , P<0.05 ) . CONCLUSIONS This study demonstrated that objective feedback during training improves the performance of BLS skills significantly when tested immediately after training and at re-testing 6 weeks later . However , CPR performance declined substantially over time in both groups The American Association of Critical-Care Nurses ' Position Statement on cardiopulmonary resuscitation ( CPR ) certification states that " nurses who care for the critically ill must have annual BCLS or CLS certification .... " Review of literature , however , did not reveal any studies among nurses that examined the question of whether Basic Cardiac Life Support ( BCLS ) was superior to other forms of CPR education , such as Basic Life Support-A ( BLS-A ) ( Heartsaver ) . The purpose of this 2 by 3 factorial design study was to examine the relationship between the method of instruction and the quality of retention of one-person CPR skills at 4 and 8 months after the initial class . The two methods of instruction under consideration were a BLS-course A ( hospital-wide Heartsaver course ) and a BLS-course C ( Basic Cardiac Life Support course ) . In addition , the variable of potential use of CPR skills was studied . The three levels of potential use ( high , medium , low ) were identified according to the area of work , such as critical care , general medical-surgical , and obstetrics-psychiatric , respectively . Other variables that were described in the literature were education , practice of skills , current position , years in profession , previous CPR training , motivation , and felt level of competence . These variables also were included in the study to find out the total variable impact on CPR retention . At least 30 registered nurses were selected from each of the high , medium , and low use areas and r and omly assigned to one of the instruction groups . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To determine the retention of Advanced Cardiac Life Support training of internal medicine residents as a function of the time since successfully completing ACLS training . DESIGN Prospect i ve , consecutive sample of patients who underwent a cardiopulmonary resuscitation effort directed by physicians who successfully completed ACLS . SETTING Eastern community teaching hospital . PATIENTS 180 consecutive patients over the age of 18 years who sustained a cardiopulmonary arrest and whose resuscitation efforts were directed by physicians who successfully completed ACLS . Forty-five additional resuscitative efforts hospital wide were led by non-ACLS-trained physicians during the study period . OUTCOME MEASURES Correctness of the diagnosis of rhythms and treatment of the rhythms diagnosed were assessed , as per ACLS protocol s in effect at the time of the study , in 1991 . INTERVENTION None . RESULTS Chi-squares were used for analysis . Seventy-six of the resuscitative efforts were run by medical residents with a 13.2 % error rate . The error rate in the first 6 months after ACLS completion among residents was 5.1 % , as compared with 21.6 % in the next 6 months ( p = 0.033 ) , with no impact on actual survival rate . During the study period , error rates among other groups were 8.8 % in Emergency Department physicians and 17.8 % among non-ACLS-trained physicians . CONCLUSIONS The error rate found was lower than in previous studies evaluating retention of ACLS education . It is important to have regular up date s in ACLS to ensure proper protocol use CONTEXT Advanced cardiac life support ( ACLS ) training was introduced to bring order and a systematic approach to the treatment of cardiac arrest by professional responders . In spite of the wide dissemination of ACLS training , it has been difficult to demonstrate improved outcome following such training . OBJECTIVE To determine the value of formal ACLS training in improving survival from in-hospital cardiac arrest . DESIGN , SETTING , AND PARTICIPANTS A multi-center , prospect i ve cohort study examined patient outcomes after resuscitation efforts by in-hospital rescue teams with and without ACLS-trained personnel . A total of 156 patients , experiencing 172 in-hospital cardiopulmonary arrest events over a 38-month period ( January 1998 to March 2001 ) were studied . MAIN OUTCOME MEASURES Primary endpoints included return of spontaneous circulation ( ROSC ) , survival to hospital discharge , 30-day survival , and 1-year survival . RESULTS The immediate success of resuscitation efforts for all patients was 39.7 % ( 62/156 ) . There was a significant increase in ROSC with ACLS-trained personnel ( 49/113 ; 43.4 % ) versus no ALCS-trained personnel ( 16/59 ; 27.1 % ; p=0.04 ) . Likewise , patients treated by ACLS-trained personnel had increased survival to hospital discharge ( 26/82 ; 31.7 % versus 7/34 ; 20.6 % ; p=0.23 ) , significantly better 30-day survival ( 22/82 ; 26.8 % versus 2/34 ; 5.9 % ; p<0.02 ) , and significantly improved 1-year survival ( 18/82 ; 21.9 % versus 0/34 ; 0 % ; p<0.002 ) . CONCLUSION The presence of at least one ACLS-trained team member at in-hospital resuscitation efforts increases both short and long-term survival following cardiac arrest Background : Neonatal resuscitation knowledge and skills deteriorate after initial training . Purpose : To evaluate the effectiveness of a computerized simulator system ( ANAKIN ) as a means for boosting neonatal resuscitation knowledge , skills , and self-reported confidence beliefs . Method : A r and omized pretest-posttest control group study design involving 60 3rd-year medical students . At a 4-month , post-training interval , experimental group was exposed to ANAKIN and control group to a training video . Both groups assessed at an 8-month , post-neonatal resuscitation training interval . Results : Knowledge level for both groups decreased significantly at 4- and 8-month , post-training intervals despite booster exposure . Confidence level for both study groups increased significantly following booster exposure . However , no significant difference between study group skill levels at 8 months and no significant relation between neonatal resuscitation knowledge , confidence , or skills . Conclusion : Computerized simulator system was as effective as video for maintaining resuscitation skills of medical students , and students were very satisfied with experience of remote computer simulation training OBJECTIVE To assess the cognitive knowledge decline among graduates of the Advanced Trauma Life Support ( ATLS ) program in Israel , to compare the rate of decline between surgeons and nonsurgeons , and to recommend appropriate timing for refresher courses . METHODS A prospect i ve study based on multiple-choice question test results of 220 ATLS course graduates was conducted 3 to 60 months after course completion . These results were then compared with the examination results immediately after the course . A statistical model based on survival analysis was used to evaluate the decline pattern and extent and to compare the study groups . RESULTS A significant decline of cognitive knowledge over time among ATLS graduates was demonstrated . This decline was significantly greater in the nonsurgical group . A critical point of 20 % cognitive knowledge loss among 50 % of the examined physicians was observed around the 180th week after completion of the course . CONCLUSION Physicians taking the ATLS course lose a significant part of their acquired cognitive knowledge after 3.5 years . Surgeons retain their cognitive knowledge for longer periods of time . Based on the study results , the optimal timing for a refresher course is between 3 and 4 years after the initial ATLS course Background : Internal medicine residents must be competent in Advanced Cardiac Life Support ( ACLS ) for board certification . Purpose : The purpose was to use a medical simulator to assess baseline proficiency in ACLS and determine the impact of an intervention on skill development . Method : This was a r and omized trial with wait-list controls . After baseline evaluation in all residents , the intervention group received 4 education sessions using a medical simulator . All residents were then retested . After crossover , the wait-list group received the intervention , and residents were tested again . Performance was assessed by comparison to American Heart Association guidelines for treatment of ACLS conditions with interrater and internal consistency reliability estimates . Results : Performance improved significantly after simulator training . No improvement was detected as a function of clinical experience alone . The educational program was rated highly Purpose : This study evaluated the introduction of the Neonatal Resuscitation Program ( NRP ) of the American Academy of Pediatrics and the American Heart Association into the delivery room of an Irish maternity hospital . Design : Prospect i ve , controlled observational study of 51 deliveries before and 51 deliveries following the training of delivery room personnel in the NRP . Sample : Participants were 33 nurse-midwives and 11 pediatric resident physicians . Main outcome variable : Evaluation of postdelivery , newborn resuscitation practice s. Results : The introduction of the NRP was associated with significant improvements in delivery room preparation , in the evaluation and management of the newborn infant , and in thermal protection at birth . Although there was a trend to use more free-flow oxygen following the introduction of the NRP , this was not statistically significant . Bag and mask ventilation was also used more frequently following NRP training . However , there were no significant differences in the use of endotracheal intubation , chest compressions , and medications . Fifteen of the 51 infants became hypothermic prior to the introduction of the NRP ; none of the infants developed hypothermia in the post-NRP part of the study CONTEXT The impact of clinical experience on learning outcome from a resuscitation course has not been systematic ally investigated . AIM To determine whether half a year of clinical experience before participation in an Advanced Life Support ( ALS ) course increases the immediate learning outcome and retention of learning . MATERIAL S AND METHODS This was a prospect i ve single blinded r and omised controlled study of the learning outcome from a st and ard ALS course on a volunteer sample of the entire cohort of newly graduated doctors from Copenhagen University . The outcome measurement was ALS-competence assessed using a vali date d composite test including assessment of skills and knowledge . INTERVENTION The intervention was half a year of clinical work before an ALS course . The intervention group received the course after a half-year of clinical experience . The control group participated in an ALS course immediately following graduation . RESULTS Invitation to participate was accepted by 154/240 ( 64 % ) graduates and 117/154 ( 76 % ) completed the study . There was no difference between the intervention and control groups with regard to the immediate learning outcome . The intervention group had significantly higher retention of learning compared to the control group , intervention group mean 82 % ( CI 80 - 83 ) , control group mean 78 % ( CI 76 - 80 ) , P=0.002 . The magnitude of this difference was medium ( effect size=0.57 ) . CONCLUSIONS Half a year of clinical experience , before participation in an ALS course had a small but statistically significant impact on the retention of learning , but not on the immediate learning outcome OBJECTIVES / PURPOSE To test registered nurses ' abilities to retain basic or advanced life support psychomotor skills and theoretical knowledge . DESIGN A repeated- measures , quasi-experimental design was used . METHODS Written and performance tests ( initial , post-training , and final testing ) used scenarios requiring performance of advanced cardiac life support ( ACLS ) or basic life support ( BLS ) skills . Final testing was by r and om assignment to 3 , 6 , 9 , or 12 months . SAMPLE A convenience sample ( n=133 ) was used . INSTRUMENTATION American Heart Association 2000 ACLS and BLS evaluation tools were used in a simulated testing environment . FINDINGS Findings show nurses retain theoretical knowledge but performance skills de grade quickly . ACLS skills de grade faster than BLS skills with 63 % passing BLS at 3 months and 58 % at 12 months . Only 30 % of participants passed ACLS skills at 3 months and 14 % at 12 months . These findings are similar to the results of other investigators in over a decade of research . CONCLUSIONS Study results showed a decline in skills retention with nurses unable to perform ACLS and BLS skills to st and ard for the entire certification period . The need for more frequent refresher training is needed . No formal research at this institution indicates skill degradation adversely affected patient outcomes . Further research on ACLS and BLS course content , design , management , and execution is needed INTRODUCTION The neonatal resuscitation programme ( NRP ) published by the American Academy of Paediatrics and American Heart Association was launched in Malaysia in 1996 . This study aim ed to review the outcome of NRP in Malaysia during the first eight years . METHODS Information on basic demographical data and training activities of NRP providers were collected prospect ively from NRP instructors from all over Malaysia during the eight years following the inception of the NRP . The national perinatal and neonatal mortality data during the five-year period before and eight years following implementation of the NRP were compared . RESULTS During the eight years following the launch , 14,575 personnel were trained . 40 percent of NRP-certified personnel worked in areas where delivery services were provided , viz . labour room , operation theatre , obstetric ward , emergency department and maternal and child health clinic . There were very few NRP-certified providers working in emergency departments and most of them were medical assistants . Most of the providers working in neonatal intensive care units ( NICUs ) and labour rooms were nurses while those in paediatric wards were doctors . All NRP-certified doctors working in NICUs and labour rooms obtained full certificates . Only 80 percent of NRP-certified nurses in these two areas obtained full certificates . There was further serial decrease in perinatal mortality and neonatal mortality rates in Malaysia during the years following the launch of the NRP programme . CONCLUSION The launch of the Malaysian NRP was associated with further improvement in perinatal and neonatal mortality rates STUDY OBJECTIVE To describe the effectiveness of an emergency medical education program in a postwar developing country . METHODS A prospect i ve , nonr and omized interrupted time-series study was conducted in an emergency department at a national referral hospital in Rw and a immediately after the 1994 civil war . Participants included 11 medical personnel staffing the ED comprising physicians , nurses , and medical assistants . International medical relief workers in the ED identified deficiencies by directly observing routine clinical practice s. On the basis of this assessment , formal training programs in trauma resuscitation , airway management , wound care , and blood/fluid pre caution s were conducted . Subjects were then observed 1 week and 2 months after the educational programs and scored on a st and ardized data - collection form . Scores before and after intervention were compared with the use of Fisher 's exact test to determine program effectiveness . RESULTS Educational interventions with statistically significantly longer term effects included wound management principles and blood/fluid pre caution s ( before versus after intervention , P < .05 ) . Interventions with the least sustained effect included advanced airway interventions and procedures related to trauma resuscitation . CONCLUSION Educational seminars proved to have the greatest sustained effect on those behaviors requiring minimal equipment and noncomplex medical decisionmaking Successful resuscitation depends upon several factors including the underlying cause for the cardiac arrest and the availability of advanced life support . Another key factor is the ability of those first on the scene to administer basic life support . Knowledge and skills in basic life support were tested in six registered children 's nurses , who were r and omly chosen to take part in a small exploratory study . Knowledge was tested by means of a question naire and skill was tested with a practical test using an infant manikin . The Resuscitation Council ( RC ) ( 1997 ) guidelines were used as a guide . The results demonstrated that the knowledge and skills of those assessed were unsatisfactory , so a resuscitation up date was arranged . The sample group was re-tested using the same question naire and practical test immediately following the resuscitation up date and again six weeks later . Knowledge and skills improved in five of the six participants , although the order in which they were performing aspects of basic infant life support was beginning to alter by the six-week retest Abstract . Although the Advanced Trauma Life Support ( ATLS ) course is now taught internationally , its teaching effectiveness still requires confirmation . The Objective Structured Clinical Examination ( OSCE ) reliably assesses clinical performance by utilizing st and ardized patients . An OSCE of eight 15 minute trauma patient stations and two 40 item MCQ tests were used to test the teaching effectiveness of the ATLS program in 32 practicing physicians who applied for an ATLS program in Trinidad and Tobago . The physicians were r and omly assigned to an ATLS group ( n = 16 ) that completed the ATLS course and a non-ATLS group ( n = 16 ) . Before and after the ATLS course , all physicians completed MCQ tests and trauma OSCE . Mean ( ± SD ) OSCE scores ( st and ardized to 20 ) ranged from 9.8 ± 1.7 to 10.0 ± 1.7 and 9.5 ± 1.8 to 10.8 ± 1.3 in the ATLS and non-ATLS groups , respectively , prior to the ATLS course ( NS ) . Post-ATLS OSCE scores ranged from 15.9 ± 1.7 to 17.6 ± 1.7 in the ATLS group ( p < 0.05 compared to pre-ATLS ) and 9.5 ± 1.4 to 10.1 ± 1.3 in the non-ATLS group , which did not improve their OSCE scores . Adherence to priorities was grade d 1 to 7 with the pre-ATLS grade s of 1.7 ± 0.6 ( ATLS ) and 1.8 ± 0.7 ( non-ATLS ) and post-ATLS grade s of 6.4 ± 1.1 ( ATLS ) and 2.1 ± 0.6 ( non-ATLS ) . Organized approach to trauma was grade d 1 to 5 with pre-ATLS grade s of 1.6 ± 0.5 ( ATLS ) and 1.7 ± 0.6 ( non-ATLS ) and post-ATLS grade s of 4.5 ± 0.6 ( ATLS ) and 1.9 ± 0.6 ( non-ATLS ) . Pre-ATLS MCQ scores ( % ) were similar : 53.1 ± 8.4 ( ATLS ) and 57.3 ± 5.4 ( non-ATLS ) , but post-ATLS scores were greater in the ATLS group : 85.8 ± 7.1 ( ATLS ) and 64.2 ± 3.6 ( non-ATLS ) . Our data support the teaching effectiveness of the ATLS program among practicing physicians as measured by improvement in OSCE scores , adherence to trauma priorities , maintenance of an organized approach to trauma care , and cognitive performance in MCQ examinations The Advanced Trauma Life Support ( ATLS ) course sponsored by the American College of Surgeons Committee On Trauma ( ACSCOT ) presents a st and ardized method of initial trauma care . This study attempted to measure any changes in morbidity and mortality in trauma patients after the introduction of ATLS training . Over a 3-year period ( May 1996 to September 1997-pre-ATLS period ; December 1997 to April 1999-post-ATLS period ) , 63 trauma patients with an Injury Severity Scale ( ISS ) > or = 16 ( n = 31 , pre-ATLS and n = 32 , post-ATLS ) were prospect ively studied in two community teaching hospitals . There was no significant difference in mortality rate between groups ( 48 % [ 15 of 31 ] pre-ATLS vs. 30 % [ 10 of 32 ] post-ATLS ; P = .203 , Fisher exact test ) . Mortality rates within the ISS range of 16 to 25 were 64 % ( nine of 14 pre-ATLS ) versus 29 % ( five of 17 post-ATLS ) , and for the ISS 26 to 35 subgroup , 40 % ( four of 10 pre-ATLS ) versus 25 % ( two of eight post-ATLS ) , and within the ISS 36 to 75 subgroup , 29 % ( two of seven pre-ATLS ) versus 43 % ( three of seven post-ATLS ) . There was a significant difference in mortality during the first 60 minutes after admission : 0.0 % post-ATLS versus 24.2 % pre-ATLS ( P = .002 , Fisher exact test ( 95 % confidence interval ranged from 12 - 45 % in the pre-ATLS group and 0 - 11 % in the post-ATLS group ) . According to the TRISS methodology ( a worldwide-accepted mathematical method to calculate chances of survival through logistical regression),ATLS improved outcome from sub-"Major Trauma Outcome Study " ( MTOS ) st and ard results ( z = -2.9 to a MTOS st and ard result z = -0.49 ) . Our data demonstrate that introduction of the ATLS program significantly improved trauma patient outcome in the first hour after admission , as well as improvement from sub-MTOS st and ard to MTOS st and ard levels Objectives : Patient simulation is emerging as a training technique in the field of medicine . It has particular application in training responses to high-risk , low-frequency clinical events , of which a typical example is in-hospital cardiac arrest . A critical element of response by the cardiac arrest team is initial airway management . In teaching hospitals , medical interns are first responders to in-hospital cardiac arrests . Our objective was to design and test a program using a computer-controlled patient simulator to train medical interns and demonstrate their competence in initial airway management . Design : Prospect i ve , r and omized , controlled , unblinded trial . Setting : Internal medicine residency training program in an urban teaching hospital . Participants : All 50 starting internal medicine interns in July 2002 , all Advanced Cardiac Life Support certified in June 2002 . Interventions : All interns were tested in initial airway management skills and then were r and omly assigned to receive either immediate or delayed individualized training using a computer-controlled patient simulator . The computer-simulated training process consisted of a scenario of respiratory arrest . The interns were challenged with the scenario twice following testing . The interns were debriefed extensively and given h and s-on training by the attending using the simulator until they achieved perfect performance . Measurements and Main Results : Initial airway management was divided into specific scorable steps . Individual step scores and total scores were recorded for each intern on initial and repeat testing . For 10 months following simulator training , intern airway management skills were scored in actual patient airway events . Despite recent Advanced Cardiac Life Support training and certification , all starting medical interns demonstrated poor airway management skills . The immediate training group showed significant improvement in initial airway management when tested before and 4 wks after training . In contrast , the delayed training group showed no significant improvement . Direct observation of interns in actual initial airway events revealed excellent clinical performance . Conclusions : Individualized training of medical interns using a computer-controlled patient simulator is an effective means of achieving and measuring competence in initial airway management skills . The improvement appears to be transferable to the bedside of real patients STUDY OBJECTIVE This study was conducted to determine the natural history of airway management skill decay and examine the effect of independent practice and periodic feedback on airway management skill maintenance . METHODS This prospect i ve , r and omized controlled study conducted at Dalhousie University in Halifax , Nova Scotia , Canada , between November 1997 and September 1998 . A convenience sample of 84 health sciences students with no prior airway management experience was used . Participants were trained using an advanced airway manikin and then were r and omly assigned to control ( n=24 ) , periodic feedback only ( n=30 ) , and independent practice plus periodic feedback ( n=30 ) groups . Performance was measured by a 52-point weighted checklist at 0 , 16 , 25 , and 40 weeks after the initial program . RESULTS Group scores were analyzed using a mixed-model repeated- measures analysis of variance and Bonferroni-adjusted P values . Overall group ( P = .0002 ) and time ( P = .0001 ) effects were significant . At time 0 , there was no statistical difference in mean scores between groups ( range 45.0 to 45.2 ) . Control group performance fell over the first time interval ( 0 to 16 weeks ) ( mean score=34.0 , P = .002 ) and remained lower at all intervals without further significant change . Scores in the independent practice plus feedback group revealed no significant changes over time and were significantly higher than the control group throughout . Performance in the periodic feedback only group showed a nonsignificant trend to improved performance over the control group . CONCLUSION Airway management skill performance declines early after initial training . Independent practice combined with periodic feedback was effective in maintaining performance scores in an advanced airway management simulation . Periodic evaluation with feedback alone showed a nonsignificant trend toward improvement over control BACKGROUND The Resuscitation Council ( UK ) Immediate Life Support ( ILS ) course provides training in the prevention and management of cardiac arrest . This course was introduced at our institution and we subsequently undertook an analysis to determine its impact on the incidence and outcome of in-hospital cardiac arrest . METHODS A 6-year prospect i ve audit of 3126 in-hospital emergency alert calls within a multi-site 1200 bedded London teaching hospital following the organisation-wide adoption of the ILS course . Key measures used to detect improvement were the incidence of emergency alert calls , in particular the proportion of calls which were pre-arrest versus cardiac arrest calls , episodes of resuscitations without return of spontaneous circulation , survival to hospital discharge ; the proportion of clinical staff who were ILS trained was an important organisational measure . RESULTS The total number of emergency alert calls showed no significant change . We observed a reduction in the proportion of calls for cardiac arrests ( p<0.0001 ; from 85 % in 2002 to 45 % in 2007 ) , a corresponding increase in the proportion of ' pre-arrest ' calls ( p<0.0001 ; from 15 % in 2002 to 55 % in 2007 ) , a reduction in deaths at cardiac arrest ( p=0.0002 ) and an increased survival to hospital discharge following an emergency call from 28 % in 2004 to 39 % in 2007 . There was a temporal relationship between the proportion of staff who were ILS trained and outcome . CONCLUSION The introduction of a simple and widespread educational programme was associated with a reduction in both the number of in-hospital cardiac arrests and unsuccessful cardiopulmonary resuscitation attempts Neonatal resuscitation is a common and important intervention . It is also a stressful and sometimes chaotic experience . Re collection s of events may be inaccurate and teaching and learning in such circumstances are difficult . Video can accurately document events during delivery room ( DR ) resuscitation ; it can therefore be used to assess compliance with guidelines and the effect of interventions . In many hospitals photographs or video recordings of infants can only be made with written parental permission . It is difficult and may be inappropriate to prospect ively obtain parental permission to video all DR resuscitations . When a high-risk delivery is imminent , parents are invariably anxious and mothers may be in pain or unwell . They may thus be unable to give permission appropriately . If previous permission is needed , it is only possible to record resuscitations where there is considerable advance warning . This seriously limits the applicability of the findings because infants born after an unanticipated emergency , likely to be the most ill and thus of most interest , are excluded . We wished to audit the care given to newborns in the DRs of our hospital . Here , we describe the ethical and legal issues we encountered before we commenced recording DR resuscitations at our hospital . Audit is the testing of current practice against previously established guidelines or benchmarks ; this contrasts with research , which is aim ed at the discovery of new knowledge that is intended ultimately to help establish guidelines . In general , previous informed consent of participants is a prerequisite for research , but not for audit . Quality assurance activities are an integral part of healthcare delivery.1 Healthcare providers recognise the need to ensure that their service is of a high quality and consistent with available re sources ; and that not to do so is unethical.2 First reported in the 1960s,3 videotaping emergency medical procedures has long BACKGROUND AND OBJECTIVES This study compared the effectiveness of two booster strategies design ed to improve retention of skills and knowledge in neonatal resuscitation by family practice residents . METHODS Residents were r and omly allocated to one of three groups : video , h and s on , or control . Residents in the two experimental groups received a " booster " 3 - 5 months after the Neonatal Resuscitation Program ( NRP ) course . All participants completed the follow-up test 6 - 8 months after taking the course . The main outcome measures consisted of the NRP written examination and the performance checklists . RESULTS A total of 44 residents completed the study ( video , n = 13 ; h and s-on , n = 14 ; control , n = 17 ) . Overall , participants had significantly lower scores at follow-up than at baseline , indicating deterioration in both neonatal skills and knowledge . Residents in the h and s-on booster group made significantly fewer errors across all five checklists in life-supporting but not in lifesaving scores than those allocated to the control and video groups . CONCLUSIONS The beneficial effect of mannequin practice or video boosters on skills and knowledge retention was less than what had been anticipated , and no benefit could be demonstrated in comparison to the control group . Deteriorating knowledge and skills remain a major concern , since boostering by h and s-on or video at 3 - 5 months do not seem to have an impact on the retention of knowledge or lifesaving skills This study was undertaken to determine whether using a model-telephone to simulate the emergency medical services activation component ( EMSAC ) during adult cardiopulmonary resuscitation ( CPR ) training practice would lead to better retention of this component during end-of-class assessment . In a prospect i ve r and omized manner , 233 medical professionals and lay-persons taking American Heart Association ( AHA ) CPR classes were evaluated for EMSAC retention during CPR skills performance at the end of class . During the assessment correct versus incorrect activation of EMS was noted . Subject response by age , exposure to previous CPR training , and medical professional or lay-person status was examined . Differences in results among instructors also were examined . Overall , those in the group using the model-telephone remembered to activate EMS correctly more frequently than those in the group not using the phone ( 69 vs 52 % , P = 0.009 ) . The < 30 age group was unaffected by the use of the phone ( P = 0.85 ) . The group between 30 and 50 years of age did significantly better with the use of the phone ( P = 0.007 ) , as did those 50 years of age and older ( P = 0.03 ) . Previous CPR training did not affect the response ( P = 0.18 ) . We conclude that use of the model-telephone improved EMSAC retention significantly overall except in the < 30 year-old age group . We recommend using the model-telephone in future adult CPR classes Many studies have investigated the ability of health care professionals to provide competent Basic Life Support ( BLS ) and all results indicate that the majority of staff fail to demonstrate competence . However , it has not yet been shown whether this poor performance is due to deterioration of skill or the nonacquisition of the skill during BLS training . This study seeks to identify aspects of BLS acquisition and retention by student nurses during their three years of training . The two issues under consideration are the effect of teacher-student ratio and the effect of regular practice on BLS performance . This paper provides a review of the methodology and the initial findings In this study , the authors compare knowledge scores , pass/fail rate , time spent , satisfaction , and skill retention between two teaching methods used in cardiopulmonary resuscitation ( CPR ) recertification . Seventy subjects were assigned r and omly to either traditional or computer method of instruction . Knowledge was evaluated by written examination . Psychomotor skills were evaluated either by a Basic Cardiac Life Support certified instructor ( control group ) or the computer ( experimental group ) and reevaluated by an instructor at a 6-month interval . There was no significant difference between the groups in knowledge or performance scores . However , significant differences in time spent , learner satisfaction , and pass/fail rate all favored the traditional method of instruction . These findings conflict with the results of prior studies on the use of the computer interactive learning system STUDY OBJECTIVES To evaluate a teaching protocol comparing a critical care attending to a housestaff team in training medical interns in initial airway management skills using a computer-controlled patient simulator ( CPS ) and scenario-based simulation training ( SST ) . DESIGN Prospect i ve , r and omized , controlled , unblinded trial . SETTING Internal medicine residency training program in an urban teaching hospital . PARTICIPANTS Forty-nine starting internal medicine interns in July 2003 , all of whom had been certified in advanced cardiac life support in June 2003 . INTERVENTIONS All interns were tested and scored with a CPS while responding to a st and ardized respiratory arrest scenario . R and om allocation to either training by a single experienced teaching attending or by a housestaff team occurred immediately following testing . All interns were retested using the same scenario 6 weeks following the initial training , and their clinical performance of airway management was scored during actual patient events throughout the year . MEASUREMENTS Initial airway management was divided into specific scorable steps . For each intern , individual step scores and total scores were recorded before and after training . For 10 consecutive months following training , intern airway management scores were recorded for actual patient airway events . RESULTS All starting medical interns demonstrated poor initial airway management skills . SST was effective in improving these skills , both on retesting with the patient simulator and in actual patient situations . Interns trained by a housestaff team performed as well as interns trained by the attending . CONCLUSIONS SST is effective in training medical interns , and the results are equivalent whether the training is provided by an experienced teaching attending or by a housestaff training team This article describes a study of two methods of teaching CPR where immediate and long-term retention of CPR skills and knowledge were compared . Forty-nine subjects were r and omly assigned to either a control group ( didactic instruction ) or an experimental group ( modular instruction ) . Knowledge retention was evaluated by means of a written examination . Skills retention was evaluated by the M and el observation instrument . The knowledge and skills performance of both groups , immediately following the class and at 3 months follow up , were not significantly different . Based on these results , modular instruction appears to be an effective alternative to the conventional time-consuming and expensive method commonly used for CPR instruction |
12,067 | 22,615,534 | Conclusion Using treatment-completion rates as a proxy measure of medication effectiveness , olanzapine long-acting injection did not differ significantly from risperidone long-acting injection when including all eligible studies . | Background Little is known about the comparative effectiveness of atypical antipsychotics in long-acting injection formulation .
Due to the absence of head-to-head studies comparing olanzapine long-acting injection and risperidone long-acting injection , this study was intended to make exploratory , indirect , cross- study comparisons between the long-acting formulations of these two atypical antipsychotics in their effectiveness in treating patients with schizophrenia .
Methods Indirect , cross- study comparisons between olanzapine long-acting injection and risperidone long-acting injection used 12-month treatment-completion rates , because discontinuation of an antipsychotic for any cause is a recognized proxy measure of the medication ’s effectiveness in treating schizophrenia . | BACKGROUND The Intercontinental Schizophrenia Outpatient Health Outcomes ( IC-SOHO ) study was design ed to provide information regarding use and outcome of antipsychotic treatments in a large , diverse population in real practice setting s. METHOD Out patients with schizophrenia ( ICD-10 or DSM-IV ) who initiated or changed to a new antipsychotic entered this 3-year , naturalistic , prospect i ve observational study . Four monotherapy treatment groups were defined according to the antipsychotic prescribed at baseline , namely olanzapine , risperidone , quetiapine , and haloperidol . Efficacy was assessed using the Clinical Global Impressions-Severity of Illness rating scale ( CGI-S ) , inclusive of subscales for positive , negative , depressive , and cognitive symptoms . Tolerability was assessed by adverse event question naires and weight measurements . Six-month findings are described . RESULTS At baseline , 5833 participants were prescribed monotherapy and the mean severity of illness was moderate to marked ( CGI-S ) . At 6 months , olanzapine result ed in significantly greater improvements in overall , positive , negative , depressive , and cognitive symptoms compared with quetiapine , risperidone or haloperidol ( p < .001 ) . Improvements in overall , negative , and cognitive symptoms were significantly higher for risperidone compared with haloperidol ( p < .001 ) , whereas improvements across all symptoms were comparable for quetiapine and haloperidol . Extra-pyramidal symptoms and tardive dyskinesia decreased compared with baseline in the olanzapine , quetiapine , and risperidone groups but increased in the haloperidol group ( p < .001 , likelihood of extrapyramidal symptoms with haloperidol compared with olanzapine , quetiapine , or risperidone ) . Sexual function adverse events were most prominent in the haloperidol and risperidone treatment groups . Weight change was significantly greater for olanzapine compared with the other antipsychotics ( p < .001 ) . CONCLUSION Our results support the previously reported positive impact of atypical antipsychotics , particularly olanzapine , in patients with schizophrenia To evaluate the maintenance of efficacy of risperidone long‐acting injectable ( RLAI ) in stable patients with schizophrenia or schizoaffective disorders . The prevalence of patients who met st and ardized remission criteria will be also evaluated as well as the predictors factors of remission according to psychopathological , psychosocial and subjective correlates OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate Background Because wide variations in mental health care utilization exist throughout the world , determining long-term effectiveness of psychotropic medications in a real-world setting would be beneficial to physicians and patients . The purpose of this analysis was to describe the effectiveness of injectable risperidone long-acting therapy ( RLAT ) for schizophrenia across countries . Methods This was a pragmatic analysis of data from two prospect i ve observational studies conducted in the US ( Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation [ SOURCE ] ; Clinical Trials.gov registration number for the SOURCE study : NCT00246194 ) and Spain , Australia , and Belgium ( electronic Schizophrenia Treatment Adherence Registry [ eSTAR ] ) . Two separate analyses were performed to assess clinical improvement during the study and estimate psychiatric hospitalization rates before and after RLAT initiation . Clinical improvement was evaluated using the Clinical Global Impressions-Severity ( CGI-S ) and Global Assessment of Functioning ( GAF ) scales , and change from baseline was evaluated using paired t tests . Psychiatric hospitalization rates were analyzed using incidence densities , and the bootstrap resampling method was used to examine differences between the pre-baseline and post-baseline periods . Results The initial sample comprised 3,069 patients ( US , n = 532 ; Spain , n = 1,345 ; Australia , n = 784 ; and Belgium , n = 408 ) . In all , 24 months of study participation , completed by 39.3 % ( n = 209 ) , 62.7 % ( n = 843 ) , 45.8 % ( n = 359 ) , and 64.2 % ( n = 262 ) of patients from the US , Spain , Australia , and Belgium , respectively , were included in the clinical analysis . Improvements compared with baseline were observed on both clinical assessment s across countries ( P < 0.001 at all post-baseline visits ) . The mean improvement was approximately 1 point on the CGI-S and 15 points on the GAF . A total of 435 ( 81.8 % ) , 1,339 ( 99.6 % ) , 734 ( 93.6 % ) , and 393 ( 96.3 % ) patients from the US , Spain , Australia , and Belgium , respectively , had ≥1 post-baseline visit and were included in the analysis of psychiatric hospitalization rates . Hospitalization rates decreased significantly in all countries regardless of hospitalization status at RLAT initiation ( P < 0.0001 ) and decreased significantly in the US and Spain ( P < 0.0001 ) when the analysis was limited to out patients only . Conclusions RLAT in patients with schizophrenia was associated with improvements in clinical and functional outcomes and decreased hospitalization rates in the US , Spain , Australia , and Belgium , despite differences in health care delivery systems OBJECTIVE Adding another antipsychotic to a treatment regimen was previously used in evaluating the medication 's efficacy . Supplementation of depot antipsychotics with oral antipsychotics is particularly meaningful because depot formulations are typically chosen for patients struggling with adherence to oral antipsychotics . This post-hoc analysis assessed supplementation of olanzapine long-acting injection ( olanzapine-LAI ) with oral olanzapine . SUBJECTS AND METHODS We used 12 months of data from an open-label , single-arm extension study of patients with schizophrenia or schizoaffective disorder ( N=931 ) treated with olanzapine-LAI . The prevalence , duration , time to first supplementation , and best predictors of oral supplementation were assessed . RESULTS Oral supplementation occurred in 21 % of patients for a median of 31 days with mean modal dose of 10.8 mg/day . Mean time to first supplementation was shorter for patients who were at least moderately ill at baseline compared to less ill patients ( 47 vs. 97 days , p<0.001 ) . Best predictors of oral supplementation included a more severe illness profile at baseline , lower olanzapine-LAI dose prior to oral supplementation , supervised living arrangements , and being African-American . CONCLUSION Supplementation of olanzapine-LAI appears to be infrequent , of relatively short duration , and reserved for more severely ill patients who may require a targeted rescue medication due to signs of impending relapse This study assessed the efficacy and the safety of a dosing regimen that was revised from earlier studies for the investigational injectable atypical antipsychotic paliperidone palmitate ( approved in the USA , August 2009 ) for adult patients with acutely exacerbated schizophrenia . The patients ( N = 652 ) were r and omly assigned ( 1:1:1:1 ) to paliperidone palmitate at 25 , 100 , or 150 mg eq. or placebo in this 13-week double-blind study . The patients received an injection of paliperidone palmitate at 150 mg eq. or placebo in the deltoid muscle on day 1 and the assigned fixed dose or placebo in the deltoid or muscle on day 8 and then once monthly ( days 36 and 64 ) . No oral supplementation was used . Target plasma levels were achieved by day 8 in all paliperidone palmitate groups . The mean change in Positive and Negative Syndrome Scale total score from baseline to end point improved significantly ( P ≤ 0.034 ) in all the paliperidone palmitate dose-groups versus placebo . Paliperidone palmitate treatment with this revised dosing regimen led to the achievement of rapid and consistent therapeutically effective plasma levels that were maintained by once-monthly dosing in either the deltoid or gluteal muscle . Common treatment-emergent adverse events ( ≥2 % of patients in any of the treatment groups ) that occurred more frequently in the total paliperidone palmitate group versus the placebo group ( with ≥1 % difference ) were injection-site pain ( 7.6 % vs 3.7 % ) , dizziness ( 2.5 % vs 1.2 % ) , sedation ( 2.3 % vs 0.6 % ) , pain in the extremity ( 1.6 % vs 0.0 % ) , and myalgia ( 1.0 % vs 0.0 % ) . The paliperidone palmitate treatment was efficacious and generally tolerated across the dose range ( 25 , 100 , or 150 mg eq. ) in adult patients with acutely exacerbated schizophrenia . Abbreviations : BMI - body mass index , CGI-S - Clinical Global Impression-Severity , EPS - extrapyramidal symptoms , ER - extended release , ITT - intent-to-treat , LAI - long-acting injectable , PANSS - Positive and Negative Syndrome Scale , PK - pharmacokinetic , PSP - Personal and Social Performance Scale , TEAE - treatment-emergent adverse events , VAS - Visual Analogue OBJECTIVE The authors assessed the efficacy and safety of the first long-acting atypical antipsychotic ( long-acting injectable risperidone ) in patients with schizophrenia . METHOD In a 12-week , multicenter , double-blind , r and omized study , patients received intramuscular injections every 2 weeks of placebo or long-acting risperidone ( 25 mg , 50 mg , or 75 mg ) . The primary measure of efficacy was the change in total score on the Positive and Negative Syndrome Scale . RESULTS Of the 554 patients who were enrolled , 400 entered the double-blind study , and 370 received at least one postbaseline assessment . Mean changes in score of -6.2 , -8.5 , and -7.4 on the Positive and Negative Syndrome Scale were seen at endpoint for the 25- , 50- , and 75-mg risperidone groups , respectively ; all three change scores were significantly different from that seen with placebo ( + 2.6 ) . Improvements in positive and negative symptoms were also significantly greater in patients receiving risperidone . Long-acting risperidone was well tolerated . Adverse events related to extrapyramidal symptoms were spontaneously reported by 13 % of patients receiving placebo and 10 % of patients in the 25-mg risperidone group , with higher rates in the 50-mg and 75-mg groups . Severity of extrapyramidal symptoms was mild at baseline and throughout the trial in each treatment group . Mean weight changes were small in the 25- , 50- , and 75-mg risperidone groups ( 0.5 kg , 1.2 kg , and 1.9 kg , respectively ) . Injection site pain was rated as low by the patients , consistent with the investigators ' pain ratings . CONCLUSIONS Long-acting injectable risperidone was efficacious and well tolerated and provides both clinicians and patients with a new mode of treatment that can improve the outcome of long-term therapy Abstract Objective To study the association between prescribed antipsychotic drugs and outcome in schizophrenia or schizoaffective disorder in the community . Design Prospect i ve cohort study using national central registers . Setting Community care in Finl and . Participants Nationwide cohort of 2230 consecutive adults hospitalised in Finl and for the first time because of schizophrenia or schizoaffective disorder , January 1995 to December 2001 . Main outcome measures Rates of discontinuation of drugs ( all causes ) , rates of rehospitalisation , and mortality associated with monotherapy with the 10 most commonly used antipsychotic drugs . Multivariate models and propensity score methods were used to adjust estimates of effectiveness . Results Initial use of clozapine ( adjusted relative risk 0.17 , 95 % confidence interval 0.10 to 0.29 ) , perphenazine depot ( 0.24 , 0.13 to 0.47 ) , and olanzapine ( 0.35 , 0.18 to 0.71 ) were associated with the lowest rates of discontinuation for any reason when compared with oral haloperidol . During an average follow-up of 3.6 years , 4640 cases of rehospitalisation were recorded . Current use of perphenazine depot ( 0.32 , 0.22 to 0.49 ) , olanzapine ( 0.54 , 0.41 to 0.71 ) , and clozapine ( 0.64 , 0.48 to 0.85 ) were associated with the lowest risk of rehospitalisation . Use of haloperidol was associated with a poor outcome among women . Mortality was markedly raised in patients not taking antipsychotics ( 12.3 , 6.0 to 24.1 ) and the risk of suicide was high ( 37.4 , 5.1 to 276 ) . Conclusions The effectiveness of first and second generation antipsychotics varies greatly in the community . Patients treated with perphenazine depot , clozapine , or olanzapine have a substantially lower risk of rehospitalisation or discontinuation ( for any reason ) of their initial treatment than do patients treated with haloperidol . Excess mortality is seen mostly in patients not using antipsychotic drugs BACKGROUND The efficacy and safety of long-acting injectable risperidone have not been compared with those of an oral atypical antipsychotic . AIMS To compare long-acting risperidone and oral olanzapine in 377 patients with DSM-IV schizophrenia or schizoaffective disorder . METHOD Patients were r and omised to receive long-acting risperidone ( 25 mg or 50 mg every 14 days ) or olanzapine ( 5 - 20 mg/day ) . RESULTS In the 13-week phase , long-acting risperidone was at least as effective as ( not inferior to ) oral olanzapine . In the 12-month phase , significant improvements in the Positive and Negative Syndrome Scale ( PANSS ) total and factor scores from baseline to month 12 and end-point were seen in both groups of patients . Few patients discontinued treatment because of an adverse event . CONCLUSIONS Both treatments were efficacious and well tolerated BACKGROUND Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia ; however , their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated . We aim ed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol , in first-episode schizophrenia . METHODS We did an open r and omised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites , in 14 countries . Eligible patients were aged 18 - 40 years , and met diagnostic criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder . 498 patients were r and omly assigned by a web-based online system to haloperidol ( 1 - 4 mg per day ; n=103 ) , amisulpride ( 200 - 800 mg per day ; n=104 ) , olanzapine ( 5 - 20 mg per day ; n=105 ) , quetiapine ( 200 - 750 mg per day ; n=104 ) , or ziprasidone ( 40 - 160 mg per day ; n=82 ) ; follow-up was at 1 year . The primary outcome measure was all-cause treatment discontinuation . Patients and their treating physicians were not blinded to the assigned treatment . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N68736636 . FINDINGS The number of patients who discontinued treatment for any cause within 12 months was 63 ( Kaplan-Meier estimate 72 % ) for haloperidol , 32 ( 40 % ) for amisulpride , 30 ( 33 % ) for olanzapine , 51 ( 53 % ) for quetiapine , and 31 ( 45 % ) for ziprasidone . Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride ( hazard ratio [ HR ] 0.37 , [ 95 % CI 0.24 - 0.57 ] ) , olanzapine ( HR 0.28 [ 0.18 - 0.43 ] ) , quetiapine ( HR 0.52 [ 0.35 - 0.76 ] ) , and ziprasidone ( HR 0.51 [ 0.32 - 0.81 ] ) . However , symptom reductions were virtually the same in all the groups , at around 60 % . INTERPRETATION This pragmatic trial suggests that clinical ly meaningful antipsychotic treatment of first-episode of schizophrenia is achievable , for at least 1 year . However , we can not conclude that second-generation drugs are more efficacious than is haloperidol , since discontinuation rates are not necessarily consistent with symptomatic improvement Objective To compare adherence and persistence to typical versus atypical antipsychotics and between specific atypical agents in the usual care of schizophrenia and to examine the association between adherence and persistence . Method Data were drawn from a 3-year prospect i ve , nonr and omized , noninterventional study of schizophrenia conducted during 1997–2003 . Initiators on haloperidol , risperidone , olanzapine , quetiapine , and clozapine with at least 1 year of follow-up were included ( n = 878 ) . Adherence ( Medication Possession Ratio , MPR ) and persistence ( time to all-cause medication discontinuation ) were assessed using medical record prescription information . Analyses employed multivariate statistics adjusted for group differences . Results Overall , 58 % of the patients were deemed adherent ( MPR > 80 % ) . Adherence rates were higher : for atypical ( 59.4 % ) than typical antipsychotics ( 34.5 % , p < 0.001 ) , for clozapine ( 77 % ) than each comparator excluding olanzapine ( p < 0.01 ) , and for olanzapine ( 64 % ) than risperidone ( 57 % , p = 0.027 ) and quetiapine ( 52 % , p = 0.019 ) . Differences between risperidone and quetiapine were not statistically significant . Adherence and persistence were highly correlated ( r = 0.957 , p < 0.001 ) . Conclusion In the usual care of schizophrenia , medication adherence and persistence appear to be highly correlated and to significantly differ between typical and atypical antipsychotics and among atypical agents . The choice of antipsychotic may play a meaningful role in patients ’ adherence to and persistence with antipsychotic medications BACKGROUND Long-acting injectable risperidone , a second-generation antipsychotic agent , may improve adherence to treatment and outcomes in schizophrenia , but it has not been tested in a long-term r and omized trial involving patients with unstable disease . METHODS We r and omly assigned patients in the Veterans Affairs ( VA ) system who had schizophrenia or schizoaffective disorder and who had been hospitalized within the previous 2 years or were at imminent risk for hospitalization to 25 to 50 mg of long-acting injectable risperidone every two weeks or to a psychiatrist 's choice of an oral antipsychotic . All patients were followed for up to 2 years . The primary end point was hospitalization in a VA or non-VA psychiatric hospital . Symptoms , quality of life , and functioning were assessed in blinded videoconference interviews . RESULTS Of 369 participants , 40 % were hospitalized at r and omization , 55 % were hospitalized within the previous 2 years , and 5 % were at risk for hospitalization . The rate of hospitalization after r and omization was not significantly lower among patients who received long-acting injectable risperidone than among those who received oral antipsychotics ( 39 % after 10.8 months vs. 45 % after 11.3 months ; hazard ratio , 0.87 ; 95 % confidence interval , 0.63 to 1.20 ) . Psychiatric symptoms , quality of life , scores on the Personal and Social Performance scale of global functioning , and neurologic side effects were not significantly improved with long-acting injectable risperidone as compared with control treatments . Patients who received long-acting injectable risperidone reported more adverse events at the injection site and more extrapyramidal symptoms . CONCLUSIONS Long-acting injectable risperidone was not superior to a psychiatrist 's choice of oral treatment in patients with schizophrenia and schizoaffective disorder who were hospitalized or at high risk for hospitalization , and it was associated with more local injection-site and extrapyramidal adverse effects . ( Supported by the VA Cooperative Studies Program and Ortho-McNeil Janssen Scientific Affairs ; Clinical Trials.gov number , NCT00132314 . ) OBJECTIVE The purpose of the present study was to evaluate the efficacy and tolerability of olanzapine long-acting injection for maintenance treatment of schizophrenia . METHOD Out patients with schizophrenia who had maintained stability on an oral regimen of olanzapine ( 10 , 15 , or 20 mg/day ) for 4 to 8 weeks were r and omly assigned to 24 weeks of double-blind treatment with " low " ( 150 mg every 2 weeks ; N=140 ) , " medium " ( 405 mg every 4 weeks ; N=318 ) , or " high " ( 300 mg every 2 weeks ; N=141 ) doses of olanzapine long-acting injection ; a very low reference dose of olanzapine long-acting injection ( 45 mg every 4 weeks ; N=144 ) ; or their stabilized dose of oral olanzapine ( N=322 ) . Rates of and time to psychotic exacerbation were estimated using Kaplan-Meier methodology . RESULTS At 24 weeks , the majority of oral olanzapine-treated patients ( 93 % ) , as well as most olanzapine long-acting injection-treated patients receiving high ( 95 % ) , medium ( 90 % ) , low ( 84 % ) , and very low doses ( 69 % ) , remained exacerbation free , with the therapeutic 4-week regimen ( medium dose ) and pooled 2-week regimen ( low and high doses ) demonstrating efficacy similar to that of oral olanzapine as well as to each other . The three st and ard long-acting doses were superior to the very low reference dose based on time to exacerbation . Incidence of weight gain > or = 7 % of baseline was 21 % for oral olanza-pine compared with 21 % , 15 % , 16 % , and 8 % for the high , medium , low , and very low olanzapine long-acting treatment groups , respectively . No clinical ly significant differences were observed between the long-acting injection and oral olanzapine groups in general safety parameters . Few injection-site reactions occurred ( 3 % ) . Two patients experienced sedation and delirium consistent with olanzapine overdose following possible accidental intravascular injection . CONCLUSIONS Olanzapine long-acting injection was efficacious in maintenance treatment of schizophrenia for up to 24 weeks , with a safety profile similar to oral olanzapine except for injection-related adverse events BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism This report presents data from the extension phase of a 6-month trial that evaluated the efficacy of risperidone long-acting injectable ( RLAI ) in stable psychotic patients requiring a treatment change . Patients continued to receive RLAI every 2 weeks for a maximum of 12 months from study entry . Symptoms were assessed using the PANSS after 1 , 3 , 6 , 9 and 12 months of treatment ( or treatment endpoint ) . Remission of severity criteria were defined as ≤3 points in all PANSS items suggested by the Remission in Schizophrenia Working Group . 715 patients ( 63 % male ) entered the extension phase and 508 completed the 12-month study . The mean PANSS total score at Day 0 was 74.9±22.7 . This was significantly reduced after 1 month ( 67.7 ±22.3 , p≤0.001 ) , with continued improvements over the 12 months of the study until treatment endpoint ( 59.7±21.9 ) . Significant improvements from Day 0 to endpoint were also seen in the scores for all PANSS subscales and symptom factors . The proportion of patients who met the PANSS severity criteria for remission increased from 29 % at Day 0 to 60 % at endpoint , and the proportion of patients who met these criteria for ≤ 6 months increased from 24 % at Month 6 to 45 % at endpoint . Treatment with RLAI for up to 12 months provided significant and sustained improvements in symptom control in patients with schizophrenia . These improvements may help patients to achieve and remain in remission OBJECTIVES This r and omized , open-label trial was design ed to help inform antipsychotic treatment policies . It compared the 1-year cost-effectiveness of initial treatment with olanzapine ( OLZ ) ( n = 229 ) versus a " fail-first " algorithm on conventional antipsychotics ( then olanzapine if indicated ) ( CON ) ( n = 214 ) ; and versus initial treatment with risperidone ( RIS ) ( n = 221 ) . METHODS Individuals with schizophrenia or schizoaffective disorder were recruited from May 1998 to September 2001 . Clinical , functioning , and re source utilization data were collected at baseline and five postbaseline visits . Brief Psychiatric Rating Scale scores defined " clinical effectiveness ; " Lehman Quality of Life Scale social relations scores defined " social effectiveness . " RESULTS Requiring failure on less expensive antipsychotics before use of olanzapine did not result in total cost savings , despite significantly higher antipsychotic costs with OLZ . Total 1-year mean costs were 21,283 dollars for CON ; 20,891 dollars for OLZ ; and 21,347 dollars for RIS ( pair-wise comparisons nonsignificant ) . Intent-to-treat effectiveness comparisons ( nonsignificant ) were augmented by analyses that adjusted for duration on initial antipsychotic treatment , and by comparisons of patients remaining on initial antipsychotic treatment versus those who required switching . When accounting for differential switching rates ( OLZ 0.14 vs. CON 0.53 , P < 0.0001 ; vs. RIS 0.31 , P < 0.0001 ) , OLZ was significantly more effective than CON on clinical ( P = 0.025 ) and social ( P = 0.043 ) measures , and significantly more effective than RIS on the social ( P = 0.002 ) measure . Further , patients initiated on an antipsychotic from which they needed to switch required additional re sources for hospitalization ( P = 0.036 ) and crisis services ( P = 0.029 ) . CONCLUSIONS Approaches that integrate costs , effectiveness , and treatment patterns are important for providing optimal information regarding the value of first-line antipsychotic options for schizophrenia Data from the 3-year , prospect i ve , observational SOHO study were used to compare the effectiveness ( in terms of treatment discontinuation ) and the tolerability of olanzapine , risperidone , other atypicals and typical antipsychotics in 1009 previously untreated out patients with schizophrenia who started monotherapy at baseline . Kaplan-Meier survival analysis estimated the time to treatment discontinuation by the treatment group , Cox proportional hazards regression models identified the variables associated with treatment discontinuation ( adjusted for baseline differences between treatment groups ) , and logistic regression models compared the tolerability profiles of the different treatment groups . Of the 931 patients analyzed , 31.9 % discontinued the medication initiated at baseline during the 3-year follow-up . Olanzapine had the lowest rate of discontinuation ( 28.9 % ) , followed by other atypical ( 34.0 % ) , risperidone ( 36.2 % ) and typical antipsychotics ( 44.5 % ) . Compared to olanzapine , risk of treatment discontinuation was higher with typical antipsychotics ( hazard ratio [ HR ] 1.75 ; 95 % confidence interval [ CI ] 1.11 , 2.78 ) or risperidone ( HR 1.36 ; 95 % CI 1.02 , 1.82 ) . A higher baseline Clinical Global Impression ( CGI ) positive score was associated with a higher risk of treatment discontinuation ( HR 1.18 ; 95 % CI 1.06 , 1.30 ) . Olanzapine was associated with a lower frequency of extrapyramidal symptoms than other antipsychotics , fewer prolactin-related adverse events than risperidone and other atypical antipsychotics , but greater weight gain than typicals and risperidone . For all analyses , comparison with the other atypical group is limited due to its small sample size ( n=50 ) . In conclusion , treatment effectiveness and tolerability varied among antipsychotic medications in previously untreated patients with schizophrenia . The results should be interpreted conservatively given the observational study design BACKGROUND The safety and efficacy of the first long-acting injectable atypical antipsychotic , risperidone , were assessed in stable patients with schizophrenia switched from oral antipsychotic medications . METHOD Data were collected between July 1 , 2001 , and October 25 , 2002 . The study population included patients from clinics , hospitals , and physicians ' offices . After a 4-week run-in period , symptomatically stable patients with schizophrenia ( DSM-IV ) who had been taking haloperidol ( N = 46 ) , quetiapine ( N = 45 ) , or olanzapine ( N = 50 ) received 25 mg of long-acting risperidone . The oral antipsychotics were continued for 3 weeks after the first injection of long-acting risperidone . Injections were administered every 2 weeks at 25 mg up to a maximum dose of 50 mg for 12 weeks in this multicenter , open-label study . RESULTS Long-acting risperidone was well tolerated . Of the 141 patients who participated in the study , the most frequently reported adverse events were insomnia ( 16 % ) , headache ( 15 % ) , psychosis ( 11 % ) , and agitation ( 11 % ) . The mean increase in body weight was 0.4 kg . No other clinical ly relevant laboratory abnormalities or significant electrocardiogram changes were observed during the 12-week treatment . Extrapyramidal Symptom Rating Scale total scores were reduced during treatment with long-acting risperidone . Improvements in symptoms of schizophrenia were observed with long-acting risperidone at week 4 and continued through the 12-week treatment with significant reductions in total Positive and Negative Syndrome Scale ( PANSS ) scores at week 8 ( -2.5 , p < .01 ) and week 12 ( -3.9 , p < .001 ) . At endpoint , 37 % ( 50/135 ) of these stable patients were rated as clinical ly improved ( > or = 20 % decrease in PANSS total scores ) . CONCLUSIONS Switching treatment from oral antipsychotics to long-acting risperidone without an intervening period of oral risperidone was safe and well tolerated . Long-acting risperidone also significantly reduced the severity of symptoms in these stable patients with schizophrenia A double-blind study of long-acting injectable risperidone and oral risperidone tablets was conducted in 640 patients with schizophrenia . All patients received flexible doses of 1 - 6 mg of oral risperidone for 8 weeks . Doses were stable during weeks 5 - 8 . At the end of week 8 , symptomatically stable patients were r and omly assigned to receive long-acting risperidone ( active injections , dummy oral ) or continued oral risperidone ( dummy injections , active oral ) for 12 weeks . Significant improvements were demonstrated from baseline to endpoint in Positive and Negative Syndrome Scale ( PANSS ) total ( P<0.001 ) and factor scores ( P<0.05 ) in both groups . According to a noninferiority analysis , the two treatments showed comparable efficacy in total PANSS scores over the short-term . No unexpected adverse events were recorded . The findings indicate that symptomatically stable patients can be safely switched from oral risperidone to long-acting injectable risperidone without compromising efficacy PURPOSE Although olanzapine may have advantages over other second-generation antipsychotics ( SGAs ) regarding longer time to treatment discontinuation among chronically ill patients , little evidence has been provided for the comparative effectiveness of SGAs in the acute phase . We aim ed to determine if any of four SGAs were more effective in treating newly admitted acute schizophrenic patients . We performed a rater-blinded , r and omized controlled trial of four SGAs in 15 psychiatric emergency sites . Eligible patients were 18 - 64 years old and met diagnostic criteria for schizophrenia , acute schizophrenia-like psychotic disorder , or schizoaffective disorder . A final total of 78 patients were r and omly assigned by means of sealed envelopes to receive risperidone ( 3 - 12 mg/day ; n=20 ) , olanzapine ( 10 - 20 mg/day ; n=17 ) , quetiapine ( 300 - 750 mg/day ; n=20 ) , or aripiprazole ( 12 - 30 mg/day ; n=21 ) , with follow-up at 8 weeks . The primary outcome measure was all-cause treatment discontinuation . RESULTS Overall , 37 % ( 29/78 ) of patients discontinued the study medication before 8 weeks : 25 % for risperidone ; 12 % for olanzapine ; 55 % for quetiapine ; and 52 % for aripiprazole . Time to treatment discontinuation for any cause was significantly longer in the olanzapine group than in the quetiapine ( p=0.006 ) or aripiprazole ( p=0.008 ) groups , but not compared to the risperidone group ( p=0.32 ) . Time to treatment discontinuation was significantly longer in the risperidone group than in the quetiapine group ( p=0.048 ) , but not compared to the aripiprazole group ( p=0.062 ) . However , the rate of p.r.n . intramuscular haloperidol use was significantly higher in the aripiprazole group than in other groups ( p=0.029 ) . CONCLUSION Olanzapine and risperidone are superior to quetiapine and aripiprazole for the acute treatment of psychosis in hospitalized patients OBJECTIVES We evaluated the efficacy and safety of long-acting risperidone for 48-week period in Korean patients . METHODS This was a non-r and omized , open-label , single-centered , 48-week study . Each of the participants visited the hospital every 2 weeks , and injections were given at each visit . Complete evaluations were done on five occasions ( baseline , 12 , 24 , 36 , 48 weeks ) . We used Clinical Global Impression , Positive and Negative Syndrome Scale , Global Assessment of Functioning , Subjective Well-being under Neuroleptic treatment scale and Short-form-36 health survey . Drug attitude inventory and Drug Induced Extra-Pyramidal Symptoms Scale were also used . RESULTS Forty patients were enrolled , and twenty-five patients completed this study . The therapeutic response rate was 36.1 % in LOCF and 48 % in completer 's analysis . Scores on CGI , PANSS subscales and total were significantly decreased over 48-week period . Scores on other assessment s did not show any significant changes over the period . At weeks 48 , there was no significant difference in the changes of scores from baseline on self-rated assessment s between the clinical improvement and non-improvement groups . CONCLUSIONS Our study showed significant improvement of investigator-rated psychiatric symptoms in long-term follow-up using long-acting risperidone . Further research es would be required to find out the effects of the psychiatric symptom improvements on overall changes in perceived functioning and well-being BACKGROUND The long-term safety and efficacy of long-acting injectable risperidone , the first long-acting second-generation antipsychotic , were evaluated in stable patients with schizophrenia . METHOD After a 2-week run-in period during which patients with DSM-IV schizophrenia received flexible doses of 1 to 6 mg of oral risperidone , patients received injections of 25 mg , 50 mg , or 75 mg of long-acting risperidone every 2 weeks for 12 months . Severity of extrapyramidal symptoms was assessed with the Extrapyramidal Symptom Rating Scale ( ESRS ) , and efficacy was assessed with the Positive and Negative Syndrome Scale ( PANSS ) . This study was conducted from March 29 , 1999 to July 19 , 2000 . RESULTS The subjects were 615 patients with schizophrenia who received at least 1 injection of long-acting risperidone . The 12-month trial was completed by 65 % of patients . Treatment was discontinued because of adverse events in 5 % of patients . Extrapyramidal symptoms as adverse events were reported by 25 % of the patients . Severity of extrapyramidal symptoms ( according to ESRS scores ) was low at baseline and decreased in each of the groups during the 12 months . The other most common adverse events were anxiety in 24 % , insomnia in 21 % , psychosis in 17 % , and depression in 14 % of the patients . Little pain was associated with the injections . Severity of symptoms of schizophrenia was improved in each group , with significant reductions in PANSS total scores ( p < .01 ) and positive ( p < .01 ) and negative ( p < .001 ) factor scores . CONCLUSION In terms of both safety and efficacy , symptomatically stable patients with schizophrenia benefit from being switched to long-acting injectable risperidone BACKGROUND Few studies have compared long-acting injectable second-generation antipsychotics with oral antipsychotics . Long-acting injectable antipsychotics-developed specifically to address the problem of adherence-might have an important role to play in treating early psychosis . OBJECTIVE The effects of oral antipsychotics versus risperidone long-acting injection ( RLAI ) were compared between 2 similar studies lasting 2 years each that were conducted at our site in South Africa . METHODS Results of an open-label study in which patients were treated with flexible doses of RLAI were compared with the results of a r and omized controlled trial of flexible doses of oral risperidone or haloperidol . Inclusion criteria for both studies were age 16 to 45 years ; confirmed diagnosis of schizophrenia , schizophreniform disorder , or schizoaffective disorder ; < or=2 hospitalizations for psychosis ; and lifetime exposure to < or=12 weeks of antipsychotic medication . The dose of RLAI was 25 mg every 2 weeks , which could be increased to 50 mg . Doses of oral risperidone or haloperidol began at 1 mg/d and were increased if necessary up to a maximum dose of 4 mg/d ( 8 mg/d in exceptional cases ) . Study assessment s included the Positive and Negative Syndrome Scale ( PANSS ) , the Extrapyramidal Symptom Rating Scale ( ESRS ) , and body mass index ( BMI ) . RESULTS The RLAI group included 50 patients ( 32 men and 18 women ; mean [ SD ] age , 25.4 [ 7.4 ] years ; BMI , 20.6 [ 4.6 ] kg/m(2 ) ) . The oral risperidone or haloperidol group included 47 patients ( 27 men and 20 women ; mean [ SD ] age , 25.9 [ 5.8 ] years ; BMI , 20.1 [ 3.4 ] kg/m(2 ) ) . Compared with patients treated with oral risperidone or haloperidol , RLAI-treated patients had significantly fewer all-cause discontinuations ( 26.0 % [ 13/50 ] vs 70.2 % [ 33/47 ] at 24 months ; P < 0.005 ) , greater reduction on the PANSS total score ( -39.7 vs -25.7 ; P = 0.009 ) , higher remission rate ( 64.0 % [ 32/50 ] vs 40.4 % [ 19/47 ] ; P = 0.028 ) , and lower relapse rate ( 9.3 % [ 4/43 ] vs 42.1 % [ 16/38 ] ; P = 0.001 ) among the responders . Extrapyramidal symptoms were significantly lower in the RLAI group than in patients treated with oral risperidone or haloperidol , as measured by the maximum change in the mean [ SD ] ESRS total score ( 1.40 [ 2.60 ] vs 5.61 [ 5.21 ] vs 9.04 [ 6.21 ] , respectively ; P < or= 0.001 ) . The increase in BMI after 6 months was significantly greater in the RLAI group than in oral haloperidol-treated patients ( mean [ SD ] , 3.9 [ 1.9 ] vs 2.2 [ 1.3 ] kg/m(2 ) ; P = 0.001 ) but not significantly different from oral risperidone ( 3.4 [ 2.0 ] kg/m(2 ) ; P = NS ) . Four patients in the RLAI group had adverse events that were possibly related to prolactin , compared with 1 each in the oral risperidone and haloperidol groups . CONCLUSIONS The findings of this post hoc analysis suggest that there were advantages in terms of efficacy , fewer extrapyramidal symptoms , and more weight gain with long-acting injectable second-generation antipsychotics as compared with oral antipsychotic treatment in early-episode psychosis We found no difference for the outcome of unchanged or worse in the short term ( n = 548 , 2 r and omized control trial ( RCTs ) , RR = 1.00 , 95 % CI = 0.88 to 1.15 ) . One study favored olanzapine for the outcome of relapse/rehospitalization by 12 months ( n = 279 , 1 RCT , RR = 2.16 , 95 % CI = 1.31 to 3.54 , NNH = 7 , 95 % CI = 3 to 25 ) . Most mental state data showed the 2 drugs to be as effective as each other ( n = 552 , 2 RCTs , RR ‘ no < 20 % decrease Positive and Negative Syndrome Scale by 8 weeks ’ 1.00 , 95 % CI = 0.87 to 1.15 ) ( Figure 1 ) . Both drugs commonly cause adverse events : 75%given eitherdrug experiencedan adverse event ; 20 % experienced anticholinergic symptoms ; both groups experienced insomnia although it was more frequent with risperidone ( n = 1588 , 5 RCTs , RR = 1.41 , 95 % CI = 1.15 to 1.72 , NNH = 15 , 95 % CI = 9 to 41 ) ; and about 30 % experienced sleepiness ( n = 1713 , 6 RCTs , RR = 0.92 , 95 % CI = 0.79 to 1.07 ) . People given either drugoften experienced extrapyramidal symptoms ( n = 893 , 3 RCTs , RR = 1.18 , 95%CI = 0.75 to 1.88 ) ; 25 % of people using risperidone and 18 % of people using olanzapine required medication to alleviate these symptoms ( n = 419 , 2 RCTs , RR = 1.76 , 95 % CI = 1.25 to 2.48 , NNH = 8 , 95 % CI = 4 to 25 ) . People allocated to risperidone ( 13 % ) were less likely to gain more than 7 % of their baseline weight compared with those given olanzapine ( 28 % ) , and the weight gain was often considerable and of quick onset ( n = 984 , 2 RCTs , RR gain more than 7 % of their baseline weight in the short term 0.47 95 % CI = 0.36 to 0.61 , NNH = 7 , 95 % CI = 6 to 10 ) . Risperidone participants were less likely to leave the study due to metabolic side effects and weight gain compared with olanzapine participants ( n = 667 , 1 RCT , RR = 0.19 , 95 % CI = 0.08 to 0.45 ) . Patients on risperidone were more likely to experience abnormal ejaculation ( n = 370 , 2 RCTs , RR = 4.36 , 95 % CI = 1.38 to 13.76 , NNH = 20 , 95 % CI = 6 to 176 ) . Both drugs are associated with high attrition rates ; in the long term , 66 % of those allocated risperidone left the study early compared with 56 % given olanzapine ( n = 1440 , 5 To whom correspondence should be addressed ; tel : þ44 - 1133058302 , fax : þ44 - 113 - 277 - 2830 , e-mail : [email protected] . Schizophrenia Bulletin vol . 33 no. 6 pp . 1274–1276 , 2007 doi:10.1093/schbul/sbm101 Advance Access publication on October 5 , OBJECTIVE To examine the efficacy and tolerability of a new injectable formulation of olanzapine , olanzapine long-acting injection ( LAI ) , relative to placebo for treatment of acutely ill patients with schizophrenia . METHOD Patients with DSM-IV or DSM-IV-TR schizophrenia in this 8-week , double-blind study were r and omly assigned to receive 210 mg/2 weeks , 300 mg/2 weeks , or 405 mg/4 weeks of olanzapine LAI or placebo/2 weeks . No oral antipsychotic supplementation was permitted . The primary efficacy measure was mean baseline-to-end point change in Positive and Negative Syndrome Scale ( PANSS ) total score . The study was conducted from June 2004 to April 2005 . RESULTS Mean baseline-to-end point decreases in PANSS total scores were significantly greater for all olanzapine LAI regimens relative to placebo ( all p values < .001 ) . The 300 mg/2 weeks and 405 mg/4 weeks olanzapine LAI groups separated from placebo on the PANSS total at 3 days after starting treatment , and all olanzapine LAI groups separated from placebo by 7 days . Rates of clinical improvement ( end point Clinical Global Impressions-Improvement scale score < or= 3 ) were significantly higher for all olanzapine LAI groups relative to placebo ( p < .001 ) . Incidences of sedation and increased appetite were significantly higher for 300 mg/2 weeks olanzapine LAI relative to placebo ( p < .05 ) . Mean weight gain ( 3.2 - 4.8 vs. 0.3 kg , p < .001 ) and incidence of weight gain > or= 7 % of baseline ( 23.6 - 35.4 % vs. 12.4 % , p < or= .046 ) were significantly greater for olanzapine LAI relative to placebo . Significant differences between all olanzapine LAI groups and placebo were observed regarding mean baseline-to-end point changes in fasting total cholesterol ( 5.5 - 10.4 vs. -7.0 mg/dL ; p < or= .015 ) and between the 210 mg/2 weeks and 405 mg/4 weeks groups ( 26.3 - 30.3 vs. -9.4 mg/dL ; p < or= .016 ) , but not the 300 mg/2 weeks group ( 17.6 mg/dL ; p = .055 ) , and placebo for fasting triglycerides . CONCLUSIONS In this 8-week study , olanzapine LAI administered at 2- or 4-week injection intervals was significantly more efficacious than placebo for the treatment of acutely ill patients with schizophrenia despite no use of supplemental oral antipsychotics . Consistent with changes previously observed with oral olanzapine , clinical ly significant weight gain and changes in some lipid parameters were observed in patients treated with olanzapine LAI BACKGROUND The electronic Schizophrenia Treatment Adherence Registry ( e-STAR ) is a prospect i ve , observational study of patients with schizophrenia design ed to evaluate long-term treatment outcomes in routine clinical practice . METHODS Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection ( RLAI ) ( n=1345 ) or a new oral antipsychotic ( AP ) ( n=277 ; 35.7 % and 36.5 % on risperidone and olanzapine , respectively ) in Spain . Hospitalization prior to therapy was assessed by a retrospective chart review . RESULTS At 24 months , treatment retention ( 81.8 % for RLAI versus 63.4 % for oral APs , p<0.0001 ) and reduction in Clinical Global Impression Severity scores ( -1.14 for RLAI versus -0.94 for APs , p=0.0165 ) were significantly higher with RLAI . Compared to the pre-switch period , RLAI patients had greater reductions in the number ( reduction of 0.37 stays per patient versus 0.2 , p<0.05 ) and days ( 18.74 versus 13.02 , p<0.01 ) of hospitalizations at 24 months than oral AP patients . CONCLUSIONS This 2 year , prospect i ve , observational study showed that , compared to oral antipsychotics , RLAI was associated with better treatment retention , greater improvement in clinical symptoms and functioning , and greater reduction in hospital stays and days in hospital in patients with schizophrenia . Improved treatment adherence , increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia Antipsychotic discontinuation rates are a powerful indicator of medication effectiveness in schizophrenia . We examined antipsychotic discontinuation in the Schizophrenia Outpatient Health Outcomes ( SOHO ) study , a 3-year prospect i ve , observational study in out patients with schizophrenia in 10 European countries . Patients ( n=7728 ) who started antipsychotic monotherapy were analyzed . Medication discontinuation for any cause ranged from 34 % and 36 % for clozapine and olanzapine , respectively , to 66 % for quetiapine . Compared to olanzapine , the risk of treatment discontinuation before 36 months was significantly higher for quetiapine , risperidone , amisulpride , and typical antipsychotics ( oral and depot ) , but similar for clozapine . Longer medication maintenance was associated with being socially active and having a longer time since first treatment contact for schizophrenia , whereas higher symptom severity , treatment with mood stabilizers , substance abuse , having hostile behaviour were associated with lower medication maintenance . Antipsychotic maintenance in SOHO was higher than the results of previous r and omized studies |
12,068 | 25,466,470 | According to the evidence available now , mixing CH with CHX does not significantly increase the antimicrobial activity of CH against E. faecalis .
It appears that mixing CH with CHX does not improve its ex vivo antibacterial property as an intracanal medicament against E. faecalis . | OBJECTIVE Enterococcus faecalis ( E. faecalis ) is the most frequently isolated strain in failed endodontic therapy cases since it is resistant to calcium hydroxide ( CH ) .
Whether a combination of CH and chlorhexidine ( CHX ) is more effective than CH alone against E. faecalis is a matter of controversy .
Thus , the aim of this study was to conduct a systematic review and meta- analysis of the literature . | Aim : To evaluate and compare the pH and antibacterial property of Ca(OH)2 combined with iodine potassium iodide ( IKI ) or chlorhexidine ( CHX ) on E. faecalis and to assess and compare their effect on fracture resistance of root dentin . Material s and Methods : CHX ( 0.5 % ) The following test material s were used : Group I Calcium hydroxide + saline , Group II Calcium hydroxide + CHX ( 0.5 % ) and Group III Calcium hydroxide + IKI ( 2 % ) . For antibacterial activity , 60 root dentin blocks ( 20 in each group ) were infected by E. faecalis followed by placement of medicaments . At the end of 24 h and 7 days , 10 sample s from each group were r and omly chosen and assessed for antibacterial activity . For evaluation of root strength , 30 teeth were used and stored in sterile saline after placement of medicament . At the end of 30 days , sample s were subjected to fracture resistance testing on the Universal Strength Testing Machine . Hounsfield strength testing machine , UK pH of the various calcium hydroxide combinations was determined with a digital pH meter . Statistical analysis : Kruskal Wallis test , Mann Whitney U test , and one-way ANOVA test for intergroup comparison and Wilcoxon 's signed rank test and student 's paired t test for intragroup comparison . Results : Group III showed significantly greater antibacterial activity against E. faecalis , followed by group II and control group . There was no statistically significant change in the pH and root strength values among all the groups . Conclusion : The present study revealed that IKI or CHX in combination with Ca(OH)2 is an effective medicament against E. faecalis Contamination of the root canal system by persistent , enteric bacteria via leakage through interim restorations has been well documented . This in vitro study evaluated the ability of interappointment medications to prevent contamination of the root canal system by Enterococcus faecalis . Coronally unsealed , medicated tooth roots fixed in a closed system were contaminated daily with a st and ardized , aerobic , broth culture of E. faecalis . Four medications were evaluated ( n = 15 ) : group A , calcium hydroxide/methylcellulose paste ; group B , camphorated parachlorophenol/calcium hydroxide paste ; group C , 1 % chlorhexidine/methylcellulose gel ; and group D , calcium hydroxide points . The mean number of days to contamination as indicated by turbidity in the closed system was the following : group A , 37 ; group B , 46 ; group C , 16 ; group D , 5 ; and a positive control ( no medication ) , 3 . A one-way analysis of variance with a Scheffe post hoc test ( p = 0.05 ) detected significant differences in effectiveness with A and B superior to C and D , and C superior to OBJECTIVE The aim of this in vitro study was to assess the substantive antimicrobial activity of different medicaments in human root dentin . STUDY DESIGN Canals of 98 roots were enlarged to st and ard size and medicated for 7 days with the following : ( 1 ) 2 % chlorhexidine ( CHX ) gel , ( 2 ) 0.2 % CHX gel , ( 3 ) 2 % CHX solution , ( 4 ) Ca(OH)(2 ) , ( 5 ) Ca(OH)(2)+ 0.2 % CHX gel , ( 6 ) 2 % CHX solution + a 25 % CHX-containing controlled-release device , ( 7 ) saline , and ( 8) gel vehicle . After medication , canals were inoculated with Enterococcus faecalis for 21 days . Dentin sample s were collected with Gates-Glidden burs into brain heart infusion broth , and bacterial growth was assessed with spectrophotometric analysis of optical density after 72 hours of incubation . RESULTS Mean optical densities were significantly lower for groups with 2 % CHX ( 1 , 3 , and 6 ) when compared with those of the controls ( P < .05 , analysis of variance with the Tukey test ) . Other groups did not differ significantly from the controls . CONCLUSIONS Canal dressing for 1 week with 2 % CHX may provide residual antimicrobial activity against E faecalis Previous studies have demonstrated antimicrobial substantivity in root canal dentin up to 7 days after treatment with chlorhexidine . This in vitro study assessed the antimicrobial substantivity of chlorhexidine-treated bovine root dentin over a period of 21 days . Sixty st and ardized bovine root sections were r and omly divided into three equal groups , and their canals immersed in one of the following solutions : ( i ) sterile saline ; ( ii ) 2.5 % NaOCl ; or ( iii ) 0.2 % chlorhexidine ( CHX ) . Half the specimens in each group were treated with the solution for 5 min and the other half for 7 days . After solutions were removed , the specimens were incubated at 37 degrees C in Brain Heart Infusion broth containing Enterococcus faecalis ( ATCC 29212 ) . A fresh inoculum was added to the broth every other day over a 21-day period . The canals were then enlarged with sterile burs , and the dentin shavings collected and cultured for the presence of cultivable bacteria in the dentinal tubules . Specimens treated with CHX for 7 days demonstrated significantly less dentin colonization by E. faecalis than the other specimens . CHX has potential as an intracanal medicament , if it can be applied for a period of at least 7 days AIM To determine the viability of Enterococcus faecalis in infected human root dentine in vitro after exposure to root canal medicaments based on chlorhexidine and octenidine . METHODOLOGY Human root segments ( n = 40 ) were infected with E. faecalis for 8 weeks . Root dentine sample s ( rd ) collected at week 4 served as individual baseline values . At week 8 , the root segments were r and omly divided into four test groups ( n = 10 each ) for the placement of one of the following medicaments in the root canals : calcium hydroxide paste ( CH ) , chlorhexidine gel ( CHX-gel ) ( 5.0 % ) , chlorhexidine/gutta-percha points ( CHX-GP ) ( active points ( ® ) ; Roeko , Langenau , Germany ) and octenidine gel ( OCT-gel ) ( 5.0 % ) followed by incubation for 4 weeks . The effect on E. faecalis viability was assessed by two fluorescent dyes ( syto 9/propidium iodide ) to determine the ' proportion of viable bacteria ' ( PVB% ) and number of ' colony-forming units ' ( CFU ) . Mean values and 95 % confidence intervals ( CI ) were calculated for PVB% and log CFU , and the difference between groups was established . RESULTS Viable and dead bacterial cells were detected in all ' rd ' sample s at weeks 4 and 8 . The treatment with CHX-gel , CHX-GP and OCT-gel result ed in significantly lower PVB% values with 15.4 % , 3.5 % and 0 % , respectively . No growth ( CFU ) was recorded for these sample s at week 12 . When medicated by CH , the PVB% was increased without a corresponding change in CFUs . CONCLUSIONS In contrast to calcium hydroxide , both CHX - and octenidine-based intracanal medicaments were effective in decreasing the viability of E. faecalis . OCT showed the most favourable results and may have potential as an endodontic medicament |
12,069 | 25,682,377 | These findings can aid clinicians in differentiating the two forms of MDD in youth | INTRODUCTION While pediatric mania and depression can be distinguished from each other , differentiating between unipolar major depressive disorder ( unipolar MDD ) and bipolar major depression ( bipolar MDD ) poses unique clinical and therapeutic challenges .
Our aim was to examine the current body of knowledge on whether unipolar MDD and bipolar MDD in youth could be distinguished from one another in terms of clinical features and correlates . | Using a structured interview with 150 r and omly selected 14 - 16-year-olds and their parents , we found 20 who endorsed four or more manic symptoms of at least 2 days duration . Compared to the rest of the sample , these teenagers had significantly higher rates of attention deficit , conduct , and anxiety disorders and psychotic symptoms , and were seen as needing treatment by the interviewers . However , most of the pathology was endorsed by teenagers rather than parents . Other assessment s confirmed this group as dysphoric , impulsive and emotionally labile . We discuss the normative and diagnostic implication s of these findings though long-term follow-up is necessary to draw more certain conclusions Twenty percent of a cohort of 206 outpatient depressives with no past bipolar history switched during prospect i ve observation . These 41 prob and s developed manic periods on the average of 6.4 years ( median 4 , range 1 - 25 ) after their first depressive episode . The change in polarity occurred throughout the life span , but was most common in adolescence and early adulthood . The following variables were found useful in predicting this outcome : onset less than or equal to 25 years , bipolar family history , loaded pedigrees , precipitation by childbirth , hypersomnic-retarded phenomenology , and pharmacologically-mobilized hypomania . Although the respective sensitivities of these findings were relatively low ( 32 - 71 % ) , their specificities ranged from 69 % to 100 % for bipolar outcome ; the diagnostic specificity of any 3 of these variables when combined was 98 % . When compared with nonbipolar depression , bipolar disorder was seldom chronologically secondary to nonaffective psychiatric disorders . These findings suggest that many young depressives with lethargy and oversleeping are not manifesting a " neurotic " disorder , but rather a precursor of primary bipolar affective disorder . Finally , a psychotically depressed adolescent or young adult with positive bipolar family history should be observed for eventual bipolar outcome , especially when the clinical presentation is that of stupor CONTEXT There is growing evidence that major depressive disorder ( MDD ) might be overdiagnosed at the expense of bipolar disorder ( BPD ) . OBJECTIVES To identify a subgroup of subthreshold BPD among DSM-IV MDD , which is distinct from pure MDD regarding a range of validators of bipolarity , and to examine the pattern of these validators among different groups with affective disorders . DESIGN Ten-year prospect i ve longitudinal and family study including 3 follow-up waves . Data were assessed with the DSM-IV Munich Composite International Diagnostic Interview . SETTING Community sample in Munich , Germany . PARTICIPANTS A total of 2210 subjects ( aged 14 - 24 years at baseline ) who completed the third follow-up . MAIN OUTCOME MEASURES Cumulative incidence of pure MDD , BPD , and subthreshold BPD ( defined as fulfilling criteria for MDD plus having manic symptoms but never having met criteria for [hypo]mania ) . RESULTS Among 488 respondents with MDD , 286 ( 58.6 % ) had pure MDD and 202 ( 41.4 % ) had subthreshold BPD ( cumulative incidence , 9.3 % ) . Compared with respondents who had pure MDD , respondents with subthreshold BPD were found to have a significantly increased family history of mania , considerably higher rates of nicotine dependence and alcohol use disorders , rates of panic disorder that were twice as high , and a tendency toward higher rates of criminal acts . Prospect i ve analyses showed that subthreshold BPD converted more often into BPD during follow-up , with DSM-IV criterion D ( symptoms observable by others ) being of critical predictive relevance . With increasing severity of the manic component , rates for diverse validators accordingly increased ( eg , alcohol use disorders , parental mania ) or decreased ( harm avoidance ) . CONCLUSIONS Data suggest that MDD is a heterogeneous concept including a large group with subthreshold BPD , which is clinical ly significant and shares similarities with BPD . Findings might support the need for a broader concept and a more comprehensive screening of bipolarity , which could be substantial for future research and adequate treatment of patients with bipolarity OBJECTIVES Significant questions remain regarding both the incidence patterns of mood episodes in adolescents and young adults from the community and the conversion rate from unipolar to bipolar disorders . We addressed these issues by examining data from a prospect i ve longitudinal community study to ( i ) determine the cumulative incidence of mood episodes and disorders in the first three decades of life ; ( ii ) determine the risk for first onset of depression among individuals with a previous history of hypomanic/manic episodes and vice versa ; and ( iii ) determine the clinical and treatment characteristics of these subjects . METHODS Using the Munich-Composite International Diagnostic Interview , clinical ly trained interviewers assessed mood episodes and mental disorders in 3,021 community subjects ( aged 14 - 24 at baseline and 21 - 34 at third follow-up ) . RESULTS The estimated cumulative incidence at age 33 was 2.9 % for manic , 4.0 % for hypomanic , 29.4 % for major depressive , and 19.0 % for minor depressive episodes ; overall , 26.0 % had unipolar major depression , 4.0 % bipolar depression , 1.5 % unipolar mania , and 3.6 % unipolar hypomania ( no major depression ) . Overall , 0.6 % and 1.8 % had unipolar mania or hypomania , respectively , without indication for even minor depression . A total of 3.6 % of the initial unipolar major depression cases subsequently developed (hypo)mania , with particularly high rates in adolescent onset depression ( < 17 years : 9 % ) . A total of 49.6 % of the initial unipolar mania cases subsequently developed major depression and 75.6 % major or minor depression . While bipolar cases had more adverse clinical and course depression characteristics and higher treatment rates than unipolar depressed cases , bipolar cases did not significantly differ in mania characteristics from unipolar mania cases . CONCLUSIONS Unipolar and bipolar mood disorders are more frequent than previously thought in adolescence and young adulthood , a time period when both the recognition and the intervention rates by the healthcare system are rather low . ' Conversion ' to bipolar disorder is limited in initial unipolar depression , but common in initial unipolar mania . The remaining unipolar mania cases appear to be significant in terms of clinical and course characteristics and thus require more research attention to replicate these findings OBJECTIVES To analyse the time course and some risk factors for a diagnostic change from major depression to bipolar disorders ( BP ) over an average of 20 years from the onset of the disorders . METHODS Patients ( 406 ) with major mood disorders hospitalised at some time between 1959 and 1963 were followed-up until 1985 . The analysis also included the course prior to hospitalisation . Survival analyses and Cox regression models were applied . RESULTS A diagnostic change from depression to bipolar I occurred in about 1 % of the patients per year and to bipolar II disorders in about 0.5 % per year . Risk factors for a change from depression to BP-I disorder were male sex and an early onset of the disorder ; risk factors for a change from depression to BP-II disorder were female sex , a later onset of the disorder and a positive family history of mania . CONCLUSIONS Across the entire lifetime , every new episode of depression brings a new risk for mania ; more than half of our severe mood disorder cases became bipolars . The risk of depression developing into bipolar disorder remains constant lifelong . LIMITATIONS The diagnostic classification of ICD-9 met RDC criteria for bipolar disorder in only 90 % of cases . Part of the data collected in retrospect may be less reliable ; the prospect i ve data were only collected every 5 years from 1965 to 1985 using multiple sources ; mild manifestations between the follow-ups may have been partially missed . The sample of subsequent hospital admissions for major depression and mania represents a severe group of patients and generalisations to ambulatory cases may not be possible . Not all risk factors for diagnostic conversion described in the literature could be assessed in this study INTRODUCTION We have developed ultra-high risk criteria for bipolar affective disorder ( bipolar at-risk - BAR ) which include general criteria such as being in the peak age range of the onset of the disorder and a combination of specific criteria including sub-threshold mania , depressive symptoms , cyclothymic features and genetic risk . In the current study , the predictive validity of these criteria were tested in help-seeking adolescents and young adults . METHOD This medical file-audit study was conducted at ORYGEN Youth Health ( OYH ) , a public mental health program for young people aged between 15 and 24years and living in metropolitan Melbourne , Australia . BAR criteria were applied to the intake assessment s of all non-psychotic patients who were being treated in OYH on 31 January , 2008 . All entries were then checked for conversion criteria . Hypomania/mania related additions or alterations to existing treatments or initiation of new treatment by the treating psychiatrist served as conversion criteria to mania . RESULTS The BAR criteria were applied to 173 intake assessment s. Of these , 22 patients ( 12.7 % ) met BAR criteria . The follow-up period of the sample was 265.5days on average ( SD 214.7 ) . There were significantly more cases in the BAR group ( 22.7 % , n=5 ) than in the non-BAR group ( 0.7 % , n=1 ) who met conversion criteria ( p<.001 ) . CONCLUSIONS These findings support the notion that people who develop a first episode of mania can be identified during the prodromal phase . The proposed criteria need further evaluation in prospect i ve clinical trials OBJECTIVE To investigate the rate and predictors of onset of DSM-III bipolar I and bipolar II disorders among 6- to 12-year-old prepubertal subjects with DSM-III major depressive disorder ( MDD ) who were followed for a 2- to 5-year period . METHODS This was a prospect i ve , blindly rated study of 79 children with MDD and 31 normal control children matched for age , gender , and socioeconomic status . Subjects and a second informant were assessed at 4-month intervals using the Kiddie Schedule for Affective Disorders and Schizophrenia-Present Episode Version-1986 modified to include 4-month interval ratings and to include DSM-III diagnoses . Family history ( FH ) was assessed using the FH- Research Diagnostic Criteria obtained from the mother about the subject 's first- and second-degree relatives . RESULTS Bipolarity developed in 31.7 % ( N = 25 ) of the children with MDD at a mean age of 11.2 + /- 2.0 years and 80 % were prepubertal . Loaded FH and multigenerational FH were significantly associated with bipolar I. Neither prior nor current use of tricyclic antidepressants nor atypical depressive features were predictive . CONCLUSIONS These findings strongly support the need to educate families of children with prepubertal-onset MDD about the possibility of the emergence of manic and hypomanic symptoms to encourage early recognition and appropriate treatment BACKGROUND To investigate whether ADHD is a risk factor for switches from unipolar to bipolar disorder over time . METHODS Data from two large controlled longitudinal family studies of boys and girls with and without ADHD and their siblings were used . Subjects ( n=168 ) were followed prospect ively and blindly over an average follow-up period of 7 years . Comparisons were made between youth with unipolar major depression who did and did not switch to full or subthreshold BP-I disorder at the follow-up assessment . Subjects were assessed at baseline and follow-up on multiple domains of functioning . Positive family history of parental psychiatric disorders was also compared between groups . RESULTS ADHD was associated with a significantly higher risk for switches from unipolar to bipolar disorder ( 28 % versus 6 % ; z=2.80 , p=0.005 ) . In subjects with ADHD , switches from unipolar to bipolar disorder were predicted by baseline comorbid conduct disorder , school behavior problems , and a positive family history of parental mood disorder . LIMITATIONS Psychosis was an exclusionary criterion in the original ascertainment of the studies of ADHD prob and s , so we were unable to test this as a predictor of switching to BPD . CONCLUSIONS ADHD is a risk factor for switches from unipolar to bipolar disorder , and switches could be predicted by the presence of baseline conduct disorder , school behavior problems , and a positive family history of a mood disorder in a parent . These characteristics can aid clinicians in their treatment of youth with MDD |
12,070 | 29,036,173 | Conclusion Administration of GnRHa prior to laparotomic myomectomy reduces blood loss and might decrease uterine adhesion formation . | Background Myomectomy has potential risks of complications .
To reduce these risks , medical pre-treatment can be applied to reduce fibroid size and thereby potentially decrease intra-operative blood loss , the need for blood transfusion and emergency hysterectomy .
The aim of this systematic review and meta- analysis is to study the effectiveness of medical pre-treatment with Gonadotropin-releasing hormone agonists ( GnRHa ) or ulipristal acetate prior to laparoscopic or laparotomic myomectomy on intra-operative and post-operative outcomes . | BACKGROUND The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear . METHODS In this double-blind noninferiority trial , we r and omly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate ( at a dose of either 5 mg or 10 mg ) or once-monthly intramuscular injections of leuprolide acetate ( at a dose of 3.75 mg ) . The primary outcome was the proportion of patients with controlled bleeding at week 13 , with a prespecified noninferiority margin of -20 % . RESULTS Uterine bleeding was controlled in 90 % of patients receiving 5 mg of ulipristal acetate , in 98 % of those receiving 10 mg of ulipristal acetate , and in 89 % of those receiving leuprolide acetate , for differences ( as compared with leuprolide acetate ) of 1.2 percentage points ( 95 % confidence interval [ CI ] , -9.3 to 11.8 ) for 5 mg of ulipristal acetate and 8.8 percentage points ( 95 % CI , 0.4 to 18.3 ) for 10 mg of ulipristal acetate . Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate , 5 days for those receiving 10 mg of ulipristal acetate , and 21 days for those receiving leuprolide acetate . Moderate-to-severe hot flashes were reported for 11 % of patients receiving 5 mg of ulipristal acetate , for 10 % of those receiving 10 mg of ulipristal acetate , and for 40 % of those receiving leuprolide acetate ( P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate ) . CONCLUSIONS Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes . ( Funded by PregLem ; Clinical Trials.gov number , NCT00740831 . ) OBJECTIVE To investigate the effect of 2 medications ; Diphereline and Cabergoline , on uterine leiomyoma growth , and its histologic , sonographic , and intra-operative changes . METHODS In an effort to treat large uterine leiomyoma in symptomatic patients in the Gynecology Clinics of the Alzahra Teaching Hospital of Tabriz University of Medical Sciences , Tabriz , Iran , from September 2007 to November 2008 , 60 c and i date s r and omized to receive Diphereline 3.75 mg , 4 times every 28 days ( group I ) , and Cabergoline 0.5 mg , once a week for 6 weeks ( group II ) , were included in this study . Clinical symptoms , feasibility of intra-operative dissection , intraoperative complications , sonographic , and pathologic characteristics of the tumor were evaluated . RESULTS Thirteen patients from group I , and 10 patients from group II underwent surgery . There was a significant difference between the groups in the rate of lymphocyte infiltration ( p=0.003 ) , but not in other pathologic features . In both groups , the mitotic index was between 0 - 10 . While there was no significant difference between the groups in the number ( p=0.30 ) , and volume of leiomyomas ( p=0.65 ) , however , changes in the uterine artery circulation was significant ( p=0.001 [ group I ] , p=0.026 [ group II ] ) . In addition , there was a significant difference between the groups for intra-operative hemorrhage and adhesion of leiomyomas to the uterine wall . CONCLUSION This study found that Cabergoline is as effective as Diphereline in the shrinkage of myomas , accompanied by improvement in the sonographic , clinical , and intra-operative outcomes without any adverse pathological changes , and could be a good medical regimen as an adjunct to surgical management A. J. M. AUDEBERT , P. MADENELAT * , D. Q U E R L E U ? , G. P O N T O N N I E R ~ , C . R A C I N E T ~ , R.R E N A U D ~ , J.-Y. GILLET * * , D. R A U D R A N T ? ~ , J. LANSAC:~ , J.-P. B R E T T E ~ Cnbitiet Medical . Bordeaus : * Hdpital Bichat , Paris ; ? Centre Hospitalier , Roubai.r ; 1 Hdpital de la Grave , Toulouse ; $ Centre Hospiialier Sud , Ecliirolles : Hfipital Central , Strasbourg ; * * Hi?pital Saint Roch , Nice ; ttH6pital de I'Hdtel Dieu , Lyon ; : $ Hdpital de Tours , Tours ; and # Hipito1 Monwti . Brest . OBJECTIVE To assess the reproductive outcomes after minilaparotomic and laparoscopic myomectomy in patients wishing to conceive . DESIGN R and omized controlled trial . SETTING Departments of obstetrics and gynecology of the universities of Catanzaro , Rome , and Florence , Italy . PATIENT(S ) One hundred thirty-six women with symptomatic uterine leiomyomas or unexplained infertility . INTERVENTION(S ) Laparoscopic and minilaparotomic myomectomy . MAIN OUTCOME MEASURE(S ) Pregnancy , abortion , and live-birth rates . RESULT ( S ) Between the laparoscopic and minilaparotomic groups no difference was observed in cumulative pregnancy , live-birth , and abortion rates , whereas pregnancy and live-birth rates per cycle , and time to first pregnancy and live-birth were significantly higher in the laparoscopic than in the minilaparotomic group . Categorizing the patients according to surgical indication for myomectomy , cumulative pregnancy rate , pregnancy , and live-birth rates per cycle , and time to first pregnancy and live-birth were significantly better after laparoscopic myomectomy in symptomatic patients , whereas all reproductive outcomes were similar between the two groups in patients with unexplained infertility . CONCLUSION ( S ) Minilaparotomic and laparoscopic myomectomy improves in a similar manner the reproductive outcomes in patients with unexplained infertility , whereas the laparoscopic approach provides the best benefits in fertile patients with symptomatic leiomyomas Summary . Twenty‐four women with symptomatic multiple uterine myomas were allocated r and omly to treatment with buserelin , 1200μg/day intranasally , for 3 months followed by myomectomy ( n = 8) or to immediate myomectomy ( n = 16 ) . Pre‐operative treatment with buserelin reduced the mean uterine volume from 432 ( SD 165 ) to 242 ( SD 82 ) ml ( P < 0.01 ) but intra‐operative blood loss and postoperative morbidity were not significantly less in this group . Six months after operation , pelvic examination was normal in all the patients . However , ultrasonography with transvaginal probe demonstrated the presence of myomas of < 1.5 cm in five women ( 63 % ) treated pre‐operatively with the analogue and in two women ( 13 % ) who underwent immediate surgery ( P < 0.05 ) . Induction of a period of hypo‐oestrogenism before myomectomy seems to favour short‐term recurrence of uterine myomas , limiting the efficacy of surgery OBJECTIVE To ascertain whether adjuvant gonadotropin-releasing hormone ( GnRH ) agonist therapy decreases blood loss during abdominal myomectomy . DESIGN R and omized controlled trial . SETTING Academic reproductive surgery center . PATIENT(S ) One hundred premenopausal women requiring first-line conservative surgery for symptomatic intramural or subserous fibroids . INTERVENTION(S ) Eight weeks of treatment with depot triptorelin before myomectomy or immediate surgery . MAIN OUTCOME MEASURES Intraoperative blood loss , operating time , degree of difficulty of the procedure , and short-term rate of fibroid recurrence . RESULT ( S ) Mean ( + /-SD ) intraoperative blood loss was 265 + /- 181 mL in triptorelin recipients and 296 + /- 204 in patients who had immediate surgery ( mean difference , -31 mL [ 95 % CI , -108 to 46 mL ] ) . No significant differences were observed in blood loss according to uterine volume , number of fibroids removed , or total length of myometrial incisions . Most procedures in either group were of routine difficulty . On ultrasonography 6 months after myomectomy , four women in the GnRH agonist group and one in the immediate surgery group had tumor recurrence . CONCLUSION ( S ) Treatment with a GnRH agonist before abdominal myomectomy has no significant effect on intraoperative blood loss . Thus , systematic use of medical therapy before abdominal myomectomy does not seem to be justified OBJECTIVE To assess the usefulness of 3-month treatment with ulipristal acetate ( UPA ) before laparoscopic myomectomy of large uterine myomas . STUDY DESIGN This retrospective analysis of a prospect ively collected data base included women of reproductive age requiring laparoscopic myomectomy with the following characteristics : FIGO type 3 , 4 or 5 myomas ; largest diameter of the main myoma ≥10 cm ; number of myomas ≤3 ; largest diameters of the other myomas ≤5 cm ( second myoma ) and ≤3 cm ( third myoma ) . Patients either underwent direct surgery ( group S ) or were treated before surgery with UPA for 3 months ( group UPA ) . RESULTS The mean ( ±SD ) intraoperative blood loss was lower in group UPA ( 507.1±214.9ml ) than in group S ( 684.2±316.8 ; p=0.012 ) . The total operative time was lower in group UPA ( 137.6±26.8min ) than in group S ( 159.7±26.8min ; p<0.001 ) ; there was no significant difference in the suturing time between the two study groups ( p=0.076 ) . Hemoglobin drop was lower in group UPA ( 1.1±0.5g/dl ) than in group S ( 1.3±0.7g/dl ; p=0.034 ) . Six patients in group S and no patient in group UPA required postoperative blood transfusions ( p=0.031 ) . Complications were not different between the two groups ( p=0.726 ) . Moreover , preoperative treatment with UPA caused a significant increase in hemoglobin levels ( 11.9±1.6g/dl ) compared with baseline ( 9.1±1.1g/dl ; p<0.001 ) . CONCLUSION A 3-month treatment with UPA before laparoscopy for large uterine myomas decreases intraoperative blood loss , hemoglobin drop , postoperative blood transfusion and length of surgery Abstract The aim of this r and omised prospect i ve study was to investigate the impact of preoperative gonadotrophin-releasing hormone agonist ( GnRHa ) compared with a control group with myomectomy . A total of 36 women ( n = 36 , group 1 ) with fibroids were r and omised to receive either two monthly doses ( n = 18/36 , group 1a ) or three monthly doses of goserelin ( n = 18/36 , group 1b ) prior to myomectomy . The 32 women who received no treatment ( group 2 ) comprised the controls . All patients had similar demographic features . There were no significant differences among the three groups with respect to : ( 1 ) mean intraoperative blood loss ; ( 2 ) preoperative and postoperative blood transfusion or ( 3 ) length of hospital stay . The only advantage of administering GnRHa prior to myomectomy for symptomatic fibroids in our population was a higher haemoglobin level prior to surgery among the women who received three doses of the drug Objectives To evaluate the efficacy and safety of 2.5 mg and 5 mg mifepristone during 3 months for the treatment of uterine fibroids before surgery . Design Multicenter r and omized clinical trial . Locations Eusebio Hernández Hospital , Havana , Cuba and the Alemán Hospital , Managua , Nicaragua . Subjects Included in the study were 146 women with symptomatic uterine fibroids . Treatment Group I : half a tablet of 5 mg ( 2.5 mg ) mifepristone taken orally every 24 hours , and Group II : one tablet of 5 mg mifepristone taken orally every 24 hours over a period of 3 months in both groups . Two endometrial biopsies were performed . Variables to evaluate efficacy Increase in average hemoglobin , changes in fibroid and uterine volume , and symptomatic improvement . Results The average hemoglobin at the end of treatment was 0.6 g/dL greater in the 5 mg mifepristone group ( P = 0.033 ) . In both groups there were similar reductions in fibroid volumes . Clinical improvement was more significant in the 5 mg group . Conclusion The dose to be used should be 5 mg The present study was undertaken in order to evaluate the usefulness or otherwise of preoperative gonadotrophin-releasing hormone ( GnRH ) analogue treatment prior to laparoscopic myomectomy . From June 1993 through December 1996 , 60 premenopausal women aged between 25 and 42 years and with a sonographic diagnosis of intramural or subserous myomas were selected for laparoscopic myomectomy at the Department of Obstetrics and Gynaecology of the Catholic University of The Sacred Heart , Rome . According to a computer-generated sequence , 30 patients were su bmi tted to three cycles of GnRH analogue treatment prior to surgery , whereas no preoperative treatment was prescribed to the other 30 patients . Laparoscopic myomectomy was successfully performed in all patients for a total of 174 myomas excised laparoscopically . The patients ' mean age , the number of myomas per patient , the mean diameter of the myomas , parity and estimated blood loss were similar in both groups . The operative time was significantly longer in the group of patients su bmi tted to GnRH analogue treatment than that of the group of patients not su bmi tted to any preoperative medical therapy ( 157.5 + /- 74.71 versus 112.33 + /- 54.71 min ; P = 0.01 ) . No intra-operative complications occurred . In no case was blood transfusion necessary . Two patients developed post-operative fever ( temperature > 38 degrees C. ) . The mean length of hospital stay was 2.39 days and was similar in both groups . Thirteen spontaneous pregnancies occurred among 24 infertile patients ( 54.1 % ) . The pregnancy rate for these patients was similar in both groups . The viable term delivery rate was 45.8 % . The authors conclude that laparoscopic myomectomy is a feasible and safe procedure . The post-operative pregnancy rate for infertile patients is similar to that following laparotomic myomectomy . The present study suggests that preoperative GnRH analogue treatment does not offer any significant advantages for laparoscopic myomectomy OBJECTIVE To determine if 3 months of preoperative gonadotropin-releasing hormone agonist ( GnRH-a ) treatment decreases postoperative uterine adhesions after open abdominal surgery for the removal of uterine fibroids . DESIGN Prospect i ve , r and omized , clinical study . SETTING A tertiary care medical center . PATIENT(S ) Women of reproductive age with symptomatic uterine fibroids not amenable to hysteroscopic removal . INTERVENTION(S ) Twenty patients underwent an initial abdominal myomectomy followed by a second-look laparoscopy for evaluating uterine adhesions after r and om allocation to groups receiving either GnRH analog or placebo for 3 months before the initial surgery . MAIN OUTCOME MEASURE(S ) Adhesion formation between treatment groups and by incision number and aggregate length . RESULT ( S ) Presurgical GnRH-a treatment did not decrease adhesion formation compared with placebo . For every additional centimeter of incision length , the total adhesion area over the uterine serosal surface increased by 0.55 cm(2 ) . The number of myomas removed and the number of incisions were positively correlated with total adhesion area . CONCLUSION ( S ) Preoperative treatment with GnRH-a for 3 months before open abdominal myomectomy did not decrease postoperative uterine adhesions . Following the st and ards of good surgical technique , adhesions are minimized with fewer and smaller incisions OBJECTIVE To evaluate the effects of two different doses ( 3.75 mg versus 7.5 mg ) of leuprolide acetate ( LA , Lupron ; Tap Pharmaceuticals , Deerfield , IL ) on myoma size , blood loss during myomectomy , on magnetic resonance imaging ( MRI ) signal quality , and histopathologic changes in women requiring myomectomy . DESIGN Prospect i ve , nonr and omized , sequential study . SETTING Urban center teaching hospital . PATIENTS Twenty-eight women with uterine leiomyomata requiring myomectomy . INTERVENTIONS Nine women were entered as controls ( group 1 ) , 10 women received 3.75 mg IM ( group 2 ) , and 9 women received 7.5 mg IM of LA ( group 3 ) each for 3 months before myomectomy . RESULTS The uterine size and hematocrit among the three groups of patients before treatment was not significantly different . A significant reduction of 34.5 % and 34.6 % in myomata size was seen in groups 2 and 3 . The estimated average blood loss at myomectomy was 745 + /- 101 mL , 615 + /- 177 mL , and 722 + /- 192 mL in groups 1 , 2 , and 3 , respectively . The postoperative hematocrit was not different among the three groups ( 29.8 % + /- 0.9 % , 30.4 % + /- 1.6 % , and 29.8 % + /- 1.2 % ) . There was no evidence of cytologic atypia , increased mitosis , or change in fibrosis in LA-treated women . There were no characteristic MRI or histologic changes seen after LA treatment as compared with controls . CONCLUSIONS The results of this study have demonstrated that both doses of LA ( 3.75 and 7.5 mg ) can induce a significant and similar degree of size reduction in myomas and that neither dose of LA aided in the reduction of blood loss at myomectomy and therefore should not be used routinely STUDY OBJECTIVE To evaluate the efficacy of gonadotropin-releasing hormone analogue ( GnRHa ) use before laparoscopic myomectomy ( LM ) in large myomas . DESIGN Prospect i ve study ( Canadian Task Force classification II-1 ) . SETTING University-affiliated hospital . PATIENTS Ninety-one women with large myomas ( ≥10 cm ) or more than 2 myomas ≥ 5 cm underwent LM between July 2011 and March 2014 . INTERVENTIONS Forty patients underwent LM after GnRHa use ( group A ) and 51 underwent LM only ( group B ) . GnRHa was used for 3 doses every 4 weeks before LM in group A. MEASUREMENTS AND MAIN RESULTS Group A had a significantly smaller maximum diameter of the largest myoma than group B ( 8.5 ± 2.1 vs 10.7 ± 2.4 , p < .001 ) and fewer patients with myomas larger than 10 cm after GnRHa administration ( 33 % vs 67 % , p = .001 ) . In group A , there was a decrease in 2 or more myomas ≥ 5 cm ( 20 % vs 50 % ) after GnRHa use . Group A also had significantly smaller mean myoma weight ( 448 vs 567 g , p = .045 ) and significantly shorter mean operative time ( 129 ± 30 vs 152 ± 34 minutes , p = .001 ) . Most patients in group A ( 40 % ) had an operative time < 119 minutes , whereas most patients in group B ( 37 % ) had an operative time between 150 and 179 minutes . Group A also had less intraoperative blood loss ( 84 ± 53 vs 137 ± 166 mL , p < .001 ) , drop in hemoglobin ( 1.5 ± 0.8 vs 3.0 ± 1.7 g/dl , p < .001 ) , excessive bleeding ( 5 % vs 33 % , p = .001 ) , postoperative hematoma ( 2.5 % vs 9.8 % , p = .168 ) , and blood transfusion ( 7.5 % vs 35 % , p = .001 ) . CONCLUSION GnRHa before LM in large myomas may be an effective adjuvant treatment for women with large and multiple myomas . This method is beneficial in decreasing operative time , intraoperative bleeding , postoperative hemorrhage , and need of blood transfusion Evaluation of clinical intra- and post-operative benefits of pre-myomectomy therapy with a Gonadotropin-Releasing Hormone Agonist ( GnRH-A ) ( Goserelin ) in anemic and non-anemic patients suffering from uterine leiomyomas . Evaluation of ultrasound , estradiol ( E2 ) and hematological measurements before and during treatment with a GnRH-a in thirty women with uterine leiomyomas , comparing pre-treated patients operative time , total intraoperative blood loss , blood counts and febrile morbidity with of thirty-five control women . GnRH-A pre-treatment cures , iron-deficiency anemia , significantly reduces myoma and uterine volume ( p < 0.01 ) , total intra-operative blood loss ( p < 0.001 ) , decreases post-operative febrile morbidity , though it does not reduce operative time . GnRH-A pre-treatment over a period no longer than two months should be suggested in anemic patients suffering from uterine leiomyomas who have to undergo myomectomy The recurrence of myomas and myoma-related symptoms was evaluated in women participating in a r and omized , double-blind , P-controlled study of the efficacy of LA depot before myomectomy . After 27 to 38 months of follow-up , the recurrence of myomas was found to be greater when at least four myomas were resected . Myoma recurrence was not associated with pretreatment or preoperative uterine volume , resected myoma mass , or preoperative medical therapy To determine whether pre-operative treatment with gonadotrophin-releasing hormone ( GnRH ) analogue may have a beneficial effect on surgery outcome , 53 patients with symptomatic fibroid uteri awaiting myomectomy or transabdominal hysterectomy ( TAH ) , were r and omly divided into a study group ( n = 29 ) and a control group ( n = 24 ) . The study group of patients were treated by an i.m . injection of D-Trp6 LHRH microcapsules at 2 months and 1 month prior to surgery . The control group had no pre-operative treatment . Haemoglobin concentration and oestradiol , follicle-stimulating hormone and luteinizing hormone concentrations were measured at 2 months and 1 month prior to surgery , and at surgery . The duration of surgery was shorter in the study group ( 49 versus 70 min in the hysterectomy group ) and intra-operative blood loss was less ( 208 versus 309 ml in the hysterectomies and 320 versus 476 ml in the myomectomies ) . Pre-operative treatment with GnRH-agonists which induces shrinkage of the uterus and fibroids is therefore efficient in shortening the duration of surgery , and diminishing the intra-operative blood loss in surgery for fibroid uteri . Such pre-operative treatment is therefore a useful addition to surgery in cases with symptomatic fibroid uteri The aim of this study was to evaluate uterine adhesions after myomectomy and peritoneal fibrinolytic capacity in women treated with gonadotrophin-releasing hormone agonist ( GnRHa ) before surgery . A prospect i ve observational study comprised 15 infertile women who underwent myomectomy . Before surgery , 10 were treated with buserelin acetate ( 900 μg/day ) for 10 – 12 weeks followed by additional postoperative treatment with GnRHa for 4 weeks ( GnRHa group ) and five received no treatment ( control group ) . Peritoneal fluid specimens were taken at the beginning of myomectomy and the adhesions were estimated by second-look surgery ( caesarean section or laparoscopy ) . Levels of plasminogen activator ( PA ) and PA inhibitor ( PAI ) were determined by enzyme-immunosorbent assays . Pre- and postoperative GnRHa therapy significantly reduced adhesion formation compared with control groups ( adhesion scores ; 0.2 ± 0.4 vs. 2 ± 1 , P < 0.0001 ) . GnRHa group showed a significant decrease in PAI level ( P < 0.0001 ) but no significant change in PA level , suggesting increased fibrinolytic capacity in peritoneal fluid from GnRHa-treated patients . These data suggest that GnRHa therapy is successful in preventing adhesion formation after myomectomy . GnRHa-induced shift to more fibrinolytic activity , mainly because of a decreased level of PAI , may play a critical role in the mechanism of the GnRHa 's action on postoperative adhesion development STUDY OBJECTIVE To compare the postoperative recovery of patients undergoing laparoscopic and minilaparotomic myomectomy . DESIGN R and omized study ( Canadian Task Force classification I ) . SETTING University hospital . PATIENTS One hundred forty-eight women requiring surgical myomectomy . INTERVENTIONS Myomectomy by minilaparotomy or laparoscopy . MEASUREMENTS AND MAIN RESULTS Operation time was significantly lower in the minilaparotomy group ( p < .001 ) . When compared with minilaparotomy , laparoscopy was associated with a lower decline of hemoglobin concentration ( p < .001 ) , a reduced length of postoperative ileus ( p < .001 ) , and a shorter time to discharge ( p < .001 ) . Pain intensity at 6 hours after surgery was significantly lower in the laparoscopy group ( p < .001 ) ; also , patients who underwent laparoscopy requested analgesics less frequently in the first 48 hours after the operation ( p < .001 ) . Patients included in the laparoscopy group were fully recuperated on postoperative day 15 more frequently than those included in the minilaparotomy group ( p = .012 ) . No complications were observed in the minilaparotomy group . There were two complications in the laparoscopy group ( one laparoconversion caused by difficulties of hemostasis and one acute diffuse peritonitis caused by ileal perforation ) . Laparoscopic and minilaparotomic myomectomy cost , respectively , 2250 euros and 1975 euros . CONCLUSION When compared with minilaparotomic myomectomy , laparoscopic myomectomy may offer the benefits of lower postoperative analgesic use and faster postoperative recovery OBJECTIVE To evaluate whether administration of tibolone changes the effectiveness of GnRH analogue administered before laparoscopic myomectomy . DESIGN Prospect i ve , r and omized , open , placebo-controlled clinical trial . SETTING Department of Gynecology and Obstetrics , University of Naples Federico II , Naples , Italy . PATIENT(S ) 66 women with symptomatic uterine leiomyomas . INTERVENTION(S ) Treatment for 2 months with leuprolide acetate and iron tablets , plus tibolone ( group A ) or placebo tablets ( group B ) ; or with leuprolide acetate and iron tablets ( group C ) . MAIN OUTCOME MEASURE(S ) Laparoscopic myomectomy at the end of treatment . Operative time and blood loss during surgery were recorded . Uterine volume , volume and number of uterine leiomyomas , volume and echogenicity of the largest uterine leiomyomas , hematologic data , and myoma-related symptoms were evaluated at baseline and 1 week before and after surgery . RESULT ( S ) Uterine and leiomyomata volume and myoma-related symptoms were significantly reduced and hematologic variables improved significantly in groups A and B , compared with baseline values and with group C. Operative time and blood loss were significantly less in groups A and B than in group C. After surgery , hematologic variables were significantly worse in group C compared with groups A and B. During the study no significant difference was detected between groups A and B. CONCLUSIONS Administration of tibolone administration in patients treated with GnRH analogue before laparoscopic myomectomy does not change the effectiveness of the analogue administered alone Object . To determine whether length of pre‐operative treatment with gonadotrophin‐releasing hormone agonists ( GnRHa ) may have different effects on uterine shrinkage and intra‐operative blood loss , 36 patients with symptomatic uterine fibroids awaiting myomectomy were r and omly divided into two groups OBJECTIVE To evaluate if pre-operative GnRH-a modify uterine leiomyoma pseudocapsule and the possible clinical effects of these changes . STUDY DESIGN The study was performed at the University Federico II of Naples on 33 premenopausal patients su bmi tted to laparotomic myomectomy after treatment with triptorelin depot . 29 untreated patients formed the control group . The operating time , the intraoperative bleeding and the prompt identification of the cleavage plan between myoma and myometrium were evaluated . The pseudocapsule features and the immunoexpression of PCNA and CD34 in this area were studied . RESULTS Treated patients showed lower blood loss and not clearly identifiable cleavage plan , but without any significant increase in the operating time . Treated lesions showed less evident border between myoma and myometrium and lower PCNA and CD34 pseudocapsule immunoexpression than untreated ones . CONCLUSION We propose the changes of leiomyoma pseudocapsule as partial explanations of the reported clinical and surgical findings after pre-operative GnRH-a The advantages of laparoscopic over open surgery have been documented in nonblinded setting s. Our prospect i ve , double-blind setting evaluated pain scores 72 h after surgery by comparing patients who underwent laparoscopic myomectomy or with laparotomy . Forty women referred for conservative myomectomy were included in the study . After stratification ( myoma size , number of myomas , and surgeon ) , patients were r and omized to either laparoscopy ( n = 19 ) or laparotomy ( n = 21 ) and received a st and ardized anesthesia and patient-controlled analgesia for 24 h after surgery . Identical wound dressings were applied to blind the patient and the observer to the surgical approach . The postoperative pain scores were documented on a visual analog scale ( VAS ; 0 = no and 10 = unbearable pain ) at 24 , 48 , and 72 h after surgery . As the primary outcome variable , we calculated the mean overall VAS-score at these time points . P < 0.05 ( t-test and analysis of covariance ) was considered statistically significant . There were no differences in patient characteristics among the groups . The mean overall VAS score at 24 , 48 , and 72 h was statistically significantly lower in the laparoscopic group compared with the laparotomy group ( 2.28 ± 1.38 versus 4.03 ± 1.63 ; P < 0.01 ) . Our data demonstrate , for the first time in a double-blind setting , that laparoscopic myomectomy reduces postoperative pain for 72 h after surgery compared with laparotomy OBJECTIVE To evaluate the role of three-monthly pre-treatment with gonadothropin releasing hormone ( GnRH ) analogues prior to myomectomy for women in comparison with control group of patients with no application . Analysis is focused on peroperative and postoperative results of surgery treatment for women with clinical ly symptomatic uterine fibroids in reproductive age with interest in getting pregnant . DESIGN Prospect i ve clinical study . SETTING Gynecological and Obstetric Clinic of Medical Faculty of Masaryk University and the University Hospital Brno . MAIN MEASURES The group of 212 patients with symptomatic uterine fibroids detected by ultrasound . 90 patients ( 42.5 % ) underwent laparoscopic myomectomy ( LM ) and 122 patients ( 57.5 % ) underwent open laparotomic myomectomy ( OM ) . In the selected group we were observing the common number of exstirpated uterine fibroids , their size , anatomical localisation , depth of invasion of dominant exstirpated uterine fibroid in relation to uterine wall . METHODS Both groups of patients were r and omised into two parts . The group LM with GnRH pretreatment contained 42 patients ( 19,8 % ) and control group with no pre-treatment 48 patients ( 22.7 % ) . Laparotomic part of study was divided into two groups with preoperative application of GnRH analogues 44 patients ( 36,7 % ) and control group OM with no application 44 patients ( 20.8 % ) . The main outcome measures were peroperative blood loss , duration of surgery , the length of hospital stay , evidence of per- and postoperative complications and the final results by second look laparoscopy ( SLL ) . RESULTS In the observed group LM with pre-treatment of GnRh analogues there was significantly higher volume of blood loss ( p = 0.0003 ) , significantly longer duration of surgery ( p = 0.0063 ) and significantly higher lenght of hospital stay ( p = 0.0025 ) compared with control group . We have not found a significant difference in the incidence of peroperational converse to laparotomy , final result of neoformation of uterus wall and occurrence of postoperative adhesions by SLL in observed LM group compared with control group . In the observed OM group with pre-treatment of GnRH analogues there was no significant difference in : peroperative blood loss ( p = 0.5324 ) , duration of surgery ( p = 0.3927 ) neither average length of hospital stay compared with control group . In the OM group , there was significantly lower incidence of recidives of uterine fibroids observed by SLL ( p = 0.0025 ) and no significant difference of occurrence of postoperative adhesions compared with control group . We have not found significant difference in the incidence of peroperative complications , early and late postoperative complications in group of LM and OM in comparison with control groups . CONCLUSION Application of GnRH analogues in observed group of patients before LM and OM have not lead to improvement of peroperative results in comparison with control group . Pre-treatment of GnRh analogues before OM have lead to significant drop in recidives of uterine fibroids observed by SLL ( p = 0.0025 ) compared with control group OBJECTIVES To compare the effect of the gonadotrophin-releasing hormone agonist leuprorelin and progestin lynestrenol , given prior to surgical treatment of symptomatic uterine myomas , on the pre-operative symptoms , tolerance , and operative blood loss . STUDY DESIGN Fifty-six women were r and omly selected to receive , during 16 weeks , either monthly subcutaneous injections of leuprorelin 3.75 mg sustained release ( n=33 ) or lynestrenol 5 mg two tabs per day ( 5th to the 25th menstrual cycle ) ( n=23 ) . RESULTS Intent-to-treat analysis of the main efficacy criterion , namely ultrasonographic reduction of myoma(s ) diameter , showed a significant difference in favour of leuprorelin ( P=0.02 ) with a mean decrease of 26.5+/-4.5 % ( n=29 ) as opposed to 7.3+/-5 % in the lynestrenol group ( n=17 ) . Clinical improvement was satisfactory in both groups . Hematocrit decrease between the preoperative value and the value measured 48 h postoperatively was significantly lower in the leuprorelin group than in the lynestrenol one ( P=0.02 ) ( for hemoglobin : P=0.07 ) . CONCLUSION Leuprorelin was more effective than lynestrenol because of its more intense antigonadotropic activity . The tolerance was good , reflecting each drug mechanism of action Laparoscopic myomectomy is still a debated procedure and there are conflicting opinions regarding the recurrence rate . Laparoscopic myomectomy may present a higher risk of recurrence compared with abdominal myomectomy . The aim of this investigation was to analyse the recurrence rate of myomas after surgery . From January 1991 to June 1998 , 165 myomectomies were performed for symptomatic myomas measuring at least 3 cm in diameter and numbering seven or less per patient . During the first 3 years of this survey , 81 patients were r and omized for abdominal or laparoscopic myomectomy . Transvaginal ultrasound examination was performed within 15 - 30 days of surgery and every 6 months for a post-operative period of 40 months . The two groups had similar pre-operative clinical features and the number and volume of myomas did not differ between the two groups . At the end of the study the group of abdominal myomectomies showed nine recurrences ( 23 % ) against 11 ( 27 % ) of the laparoscopic group . In order to evaluate the recurrence rate in relation to several risk factors , laparoscopic myomectomies were performed from 1991 in 84 patients who agreed to follow-up ( and were not in the r and omized group ) . Of these , 78 patients were evaluated with transvaginal ultrasound for a mean interval of 26 months and 17 ( 21.78 % ) recurrences were found . Most recurrences ( 75 % ) were seen at ultrasound between 10 and 30 months after surgery . The patient 's age , pre- and post-operative gravidity and parity had no influence on recurrence . Neither the number of myomas removed nor the depth of penetration or size were positively associated with the risk of recurrence . However , an associated risk factor was pre-operative gonadotrophin-releasing hormone agonist treatment ( P < 0.02 ) . None of the women with recurrence required additional surgery . We conclude that laparoscopic myomectomy is a reliable procedure . The recurrence rate is similar to that seen after abdominal myomectomy OBJECTIVE To compare the usefulness of preoperative treatment with triptorelin , letrozole or ulipristal acetate or no treatment before hysteroscopic removal of uterine submucosal myomas . STUDY DESIGN Single center prospect i ve non-r and omized comparative pilot study . The study included consecutive premenopausal patients undergoing hysteroscopic resection of myomas grade d as type 0 , type 1 or type 2 according to the FIGO classification with diameter between 20 and 35 mm . Exclusion criteria were : associated polyps , associated non-hysteroscopic surgical procedures , > 2 myomas requiring hysteroscopic resection . This study enrolled patients who underwent either direct surgery ( group S ; n=23 ) or 3-month preoperative treatment with triptorelin ( 3.75 mg every 28 days ; group T ; n=20 ) , letrozole ( 2.5 mg/day ; group L ; n=11 ) or ulipristal acetate ( 5 mg/day ; group U ; n=7 ) . Patients underwent hysteroscopic resection of the myomas . RESULTS All medical treatments caused a significant decrease in the volume of myomas ( group T , p<.001 ; group L , p<.001 ; group U , p=.006 ) ; however , the percentage decrease in myoma volume was lower in group U than in group T ( p=.001 ) and in group L ( p=.010 ) . The hysteroscopy time was higher in group S than in group T ( p<.001 ) and in group L ( p=.001 ) ; there was no significant difference in the hysteroscopy time between group S and group U ( p=.206 ) . Fluid absorption was lower in group T than in group S ( p=.002 ) and in group L than in group S ( p=.048 ) ; fluid absorption was similar in group S and group U ( p=.110 ) . Intra- and postoperative complications , postoperative pain , and patient satisfaction were similar in the four study groups . Surgeon 's evaluation of operative difficulty was better in group T than in group S ( p<.005 ) . CONCLUSIONS Preoperative treatment with triptorelin and letrozole decreases the hysteroscopy time and the volume of fluid absorbed during hysteroscopic resection of uterine submucosal myomas Eighteen premenopausal women with symptomatic leiomyomata uteri were enrolled in a stratified , r and omized , double-blind , placebo-controlled study evaluating the efficacy of leuprolide acetate ( LA ) depot treatment before myomectomy . Stratification was based on pretreatment uterine volume ( less than 600 cm3 versus greater than or equal to 600 cm3 ) . Nine women received intramuscular ( IM ) depot LA 3.75 mg every 4 weeks for 12 weeks ( group A ) ; nine women received IM placebo with the same injection schedule ( group B ) . All women underwent myomectomy within 4 weeks of their last injection . Mean total intraoperative blood loss was 213 + /- 44 mL ( mean + /- st and ard error of the mean [ SEM ] ) in group A and 302 + /- 43 mL in group B. When data from patients with large uteri ( pretreatment uterine volumes of 600 cm3 or greater ) were analyzed , mean total blood loss was 189 + /- 44 mL in group A and 390 + /- 20 mL in group B. These data suggest that leuprolide depot treatment before myomectomy may decrease intraoperative blood loss in women with large leiomyomata uteri |
12,071 | 15,480,086 | There is at present insufficient good- quality evidence to conclude whether or not TM has a cumulative positive effect on blood pressure | Objective To carry out an independent , systematic review of r and omized clinical trials of Transcendental Meditation ( TM ) for cumulative effects on blood pressure . | The objective of this study was to determine the impact of stress reduction on blood pressure ( BP ) in adolescents by the Transcendental Meditation ( TM ) program . African-American adolescents ( aged 16.2 + /- 1.3 years ) with high normal systolic BP were r and omly assigned to either 4-month TM ( n = 50 ) or health education control ( n = 50 ) groups . Ambulatory 24-h BP measures were recorded at pretest , 2- and 4-month post-tests , and 4-month follow-up . Greater decreases in daytime systolic BP ( P < .04 ) and diastolic BP ( P < .06 ) in the TM group compared with the control group across the visits demonstrate a beneficial impact of the TM program in youth at risk for the development of hypertension Background Slow , controlled breathing has been shown by cross-spectral techniques to potentiate arterial baroreflex control of heart rate . However , crucial aspects of the effects of slow breathing on the arterial baroreflex remain unsettled , namely whether the major function of the arterial baroreflex ( i.e. the control of blood pressure ) is also potentiated and whether baroreflex function is differentially modulated according to the age of the individual . Objective To examine the bradycardic and depressor responses to selective carotid baroreceptor stimulation by the neck chamber technique ( −15 and −30 mmHg neck suction ) and the cross-spectral R – R interval/systolic blood pressure relationship ( α index ) . Methods In 24 resting , supine healthy male volunteers ( aged 19–66 years , mean ±SEM 37.5 ± 3.19 years ) , blood pressure ( Finapres ) , R – R interval ( electrocardiogram ) and ventilation ( impedance ) were recorded continuously . Both assessment s were performed during spontaneous breathing and during 6 cycles/min controlled ventilation in r and om order . Results The depressor and bradycardic responses to neck suction were significantly larger during slow breathing than in spontaneous breathing ( + 32 and + 85 % , respectively ; both P < 0.01 ) . The α index was also significantly larger during slow breathing ( + 62 % ; P < 0.01 ) . Even after the volunteers were divided into older ( > 50 years , n = 9 ) and younger ( < 30 years , n = 9 ) groups , the baroreflex potentiation related to slow breathing was clearcut and significant for both the depressor ( + 46 and + 24 % older and younger volunteers ; both P < 0.01 ) and the bradycardic ( + 130 and + 73 % older and younger volunteers ; both P < 0.01 ) responses . When the assessment was made by computing the cross-spectral α index , a marked potentiation related to slow breathing was observed in younger volunteers ( + 99 % ; P < 0.01 ) , whereas in older volunteers only a trend to an enhancement ( by 32 % ; P < 0.055 ) was observed . Conclusions Slow controlled breathing is associated with potentiation of both the depressor and the cardio-inhibitory components of the arterial baroreflex , the potentiation being largely similar regardless of the age of the individual In man evaluation of neural cardiovascular regulation makes use of a variety of tests which address the excitatory and reflex inhibitory neural influences that control circulation . Because interpretation of these tests is largely based on the magnitude of the elicited haemodynamic responses , their reproducibility in any given subject is critical . In 39 subjects with continuous blood pressure ( intra-arterial catheter ) and heart rate monitoring we measured the blood pressure and heart rate rises during h and -grip and cold-pressor test , the heart rate changes occurring during baroreceptor stimulation and deactivation by injection of phenylephrine and trinitroglycerine , and the heart rate and blood pressure changes occurring with alteration in carotid baroreceptor activity by a neck chamber . Each test was carefully st and ardized and performed at 30 min intervals for a total of six times in each subject . The results showed that the responses to any test were clearly different from one another and that this occurred in all subjects studied . For the group as a whole the average response variability ( coefficient of variation ) ranged from 10.2 % for the blood pressure response to carotid baroreceptor stimulation to 44.2 % for the heart rate response to cold-pressor test . The variability of the responses was not related to basal blood pressure or heart rate , nor to the temporal sequence of the test performance . Thus tests employed for study ing neural cardiovascular control in man produce responses whose reproducibility is limited . This phenomenon may make it more difficult to define the response magnitude typical of each subject , as well as its comparison in different conditions and diseases OBJECTIVE --To establish whether stress management had a larger effect than a control treatment on resting blood pressure , ambulatory blood pressure , and left ventricular mass . DESIGN --A 12 week baseline period of habituation to measurement of blood pressure was followed by r and omisation to either stress management or mild exercise for six months and follow up six months later . SETTING --General practice , district general hospital , and medical school . PATIENTS --Of the 184 patients aged under 60 with mild primary hypertension who entered the baseline habituation period , 88 were excluded because they failed to meet the entry criteria or they withdrew from the study . The remaining 46 men and 50 women underwent treatment . INTERVENTIONS --10 clinical sessions and daily practice at home of either stress management based on relaxation or non-aerobic stretching exercises . Mildly stressful 15 minute interviews before and after treatment . MAIN OUTCOME MEASURES --Diastolic and systolic blood pressure in the clinic and during 12 hours of ambulatory recording , and left ventricular mass measured by echocardiography . RESULTS --The patients ' blood pressure fell during habituation ( systolic pressure from 152 mmHg to 140 mmHg , diastolic pressure from 98 to 93 mm Hg ) , but neither resting nor ambulatory blood pressure was changed by the treatments . Left ventricular mass was also unchanged . Blood pressure rose during the stressful interview , but this rise was reduced by stress management ( systolic pressure rose by 7.4 mmHg before treatment and by 3.7 mmHg after treatment ) . CONCLUSION --Stress management of a type advocated for treating mild primary hypertension is ineffective in lowering blood pressure in patients who are well habituated to measuring blood pressure 34 hypertensive patients were assigned at r and om either to six weeks ' treatment by yoga relaxation methods with bio-feedback or to placebo therapy ( general relaxation ) . Both groups showed a reduction in blood-pressure ( from 168/100 to 141/84 mm . Hg in the treated group and from 169/101 to 160/96 mm Hg in the control group ) . The difference was highly significant . The control group was then trained in yoga relaxation , and their blood-pressure fell to that of the other group ( now used as controls ) BACKGROUND In chronic heart failure ( CHF ) , impaired pulmonary function can independently contribute to oxygen desaturation and reduced physical activity . We investigated the effect of breathing rate on oxygen saturation and other respiratory indices . METHODS Arterial oxygen saturation ( SaO2 ) and respiratory indices were recorded during spontaneous breathing ( baseline ) and during controlled breathing at 15 , six , and three breaths per min in 50 patients with CHF and in 11 healthy volunteers ( controls ) . 15 patients with CHF were r and omly allocated 1 month of respiratory training to decrease their respiratory rate to six breaths per min . Respiratory indices were recorded before training , at the end of training , and 1 month after training . FINDINGS During spontaneous breathing , mean SaO2 was lower in CHF patients than in controls ( 91 - 4 % [ SD 0.4 ] vs 95.4 % [ 0.2 ] , p<0.001 ) . Controlled breathing increased SaO2 at all breathing rates in patients with CHF . Compared with baseline , minute ventilation increased at 15 breaths per min ( + 45.9 % [ 9.8 ] , p<0.01 ) , did not change at six breaths per min , and decreased at three breaths per min ( -40.3 % [ 4.8 ] , p<0.001 ) . In the nine CHF patients who had 1 month of respiratory training , resting SaO2 increased from 92.5 % ( 0.3 ) at baseline to 93.2 % ( 0.4 ) ( p<0.05 ) , their breathing rate per min decreased from 13.4 ( 1.5 ) to 7.6 ( 1.9 ) ( p<0.001 ) , peak oxygen consumption increased from 1157 ( 83 ) to 1368 ( 110 ) L/min ( p<0.05 ) , exercise time increased from 583 ( 29 ) to 615 ( 23 ) min/s ( p<0.05 ) , and perception of dyspnoea reduced from a score of 19.0 ( 0.4 ) to 17.3 ( 0.9 ) on the Borg scale ( p<0.05 ) . There were no changes in the respiratory indices in the patients who did not have respiratory training . INTERPRETATION Slowing respiratory rate reduces dyspnoea and improves both resting pulmonary gas exchange and exercise performance in patients with CHF 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 |
12,072 | 14,754,709 | The 3 placebo-controlled , r and omized trials did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight gain .
In addition , discontinuation of combination contraceptives because of weight gain did not differ between groups when this factor was studied .
: Available evidence is insufficient to determine the effect of combination contraceptives on weight , but no large effect is evident | OBJECTIVE : Many women and clinicians believe that combination estrogen – progestin contraceptive use can lead to weight gain .
This concern can deter women from starting hormonal contraception or lead to premature quitting .
This review evaluated the association between combination contraceptive use and change in body weight . | A comparison of cycle control , efficacy and tolerability of two oral contraceptive preparations containing 20 microg ethinylestradiol combined with either 100 microg levonorgestrel ( EE/LNG 20/100 ) or 500 microg norethisterone ( EE/NET 20/500 ) was conducted . These results were compared to a st and ard reference preparation , containing 30 microg ethinylestradiol combined with 150 microg levonorgestrel ( EE/LNG 30/150 ) . Efficacy data from 8,544 treatment cycles were obtained from 767 women . Good cycle control and effective contraception was achieved with the two LNG preparations , however , the cycle control results were less favorable with EE/NET 20/500 . The cumulative incidence of women with at least one episode of intermenstrual bleeding from cycles 2 to 7 ( primary target variable ) was 43.9 % for EE/LNG 20/100 , 72.7 % for EE/NET 20/500 , and 15.7 % for the st and ard EE/LNG 30/150 . The difference between the 2 20 microg of EE preparations , which favored EE/LNG 20/100 , was statistically significant ( p = 0.001 ) . The overall spotting rates ( cycles 1 - 13 ) were 9.3 % for EE/LNG 20/100 , 21.7 % for EE/NET 20/500 , and 3.3 % for the st and ard EE/LNG 30/150 . Amenorrhea was reported in 7.1 % ( EE/LNG 20/100 ) , 20.6 % ( EE/NET 20/500 ) , and 0.9 % ( st and ard EE/LNG 30/150 ) , respectively . Intermenstrual bleeding episodes were shorter with EE/LNG 20/100 and EE/LNG 30/150 of the 13 treatment cycles . The study Pearl indices were 0.9 for EE/LNG 20/100 , 1.9 for EE/NET 20/500 , and 0.0 for EE/LNG 30/150 . All three treatments were well tolerated . However , tolerability was somewhat less favorable with EE/NET 20/500 . A total of 160 women prematurely discontinued the study for various reasons ( EE/LNG 20/100 : 7 % ; EE/NET 20/500 : 18 % ; EE/LNG 30/150 : 4 % ) . The overall adverse event incidence rate during the trial was low in all groups . Blood pressure remained largely unaffected . Thirteen serious adverse events were recorded for all treatment groups , all but one were assessed as not related to the treatments . There were no remarkable treatment related differences in mean body weight throughout the study and the laboratory values were largely unaffected in all three treatments groups In a parallel , multicenter study in Norway and Finl and involving a total of 196 healthy women ( mean age 22.4 years , range 18–30 ) , the effects on serum lipids and lipoproteins of two multiphasic oral contraceptives containing ethinyl estradiol ( EE ) but different progestins were examined . One formulation contained EE 35 μg and norethisterone ( NET ) 0.5 mg on days 1–7 and days 17–21 and elevated NET 1.0 mg during the midphase ( days 8–16 ) . The other formulation contained EE 30 μg on days 1–6 and days 12–21 and 40 μg on days 7–11 and phased levonorgestrel ( LGN ) : 50 μg ( days 1–6 ) , 75 μg ( days 7–11 ) and 125 μg ( days 12–21 ) . Both formulations induced significant elevation of total cholesterol ( 6.7 and 4.1 % ) , Apo B ( 8.1 and 7.0 % ) as well as HDL ( 6.4 and 3.7 % ) for the EE/NET and EE/LGN formulation respectively . Mean serum levels of triglycerides were significantly elevated ( 58 and 47 % ) . However , all mean serum lipid and lipoprotein values remained within the normal range , and no change in the calculated cholesterol ratio ( HDL/total cholesterol ) nor lipoprotein ratio ( HDL/(HDL+LDL ) ) was observed . No significant difference between the formulations could be detected with respect to the effect on serum lipids and lipoproteins measured . The change in total cholesterol was smaller than reported in many studies of monophasic preparations . Taken together , these data suggest that only small alterations in lipid metabolism are elicited by these oral contraceptives In an open , r and omized study in an outpatient clinic of a large teaching hospital , thirty-one female volunteers with regular cycles and established ovulation by ultrasonography were given one of two triphasic oral contraceptives containing ethinylestradiol combined with levonorgestrel or desogestrel during six cycles of treatment . The main outcome measures were transvaginal ultrasonography and serum E2 and P measurements in pill cycles 1 , 3 and 6 . No ovarian activity was found in 10 subjects . Among the remaining 21 women who showed ovarian activity , most follicle-like structures developed in the pill-free week and decreased in size or disappeared in the first pill week . One women taking triphasic desogestrel had evidence of a luteinized unruptured follicle and one women taking triphasic levonorgestrel had a possible ovulation . The latter women also showed symptoms of lower abdominal pain . A statistically significant difference in ovarian activity between the two oral contraceptives could not be established . The two triphasic oral contraceptives suppressed ovarian activity to the same degree . A trend was seen towards increasing ovarian activity with duration of use in both treatment groups 398 new users of oral contraceptives at the Research Clinic of the Southwest Foundation Texas were asked if they experienced nausea vomiting headache or breast discomfort nervousness or depression and had weight and blood pressure recorded in the pretreatment cycle and at monthly visits . Each received placebo Oracon ( sequential ) Ovulen-21 ( combination ) Norinyl-1 or .5 mg chlormadinone acetate in a double-blind protocol incorporating a pretreatment placebo cycle crossover to an active pill for 4 cycles and 2 more crossovers for Cyles 5 and 6 . The only symptoms significantly higher than in the pretreatment ( placebo ) cycle were nausea and vomiting with Oracon ( p greater than .05 ) and headache with Ovulen ( p greater than .05 ) . Pointing out that the highest incidence of complaints occurred in the placebo cycle the authors conclude that controls are necessary in contraceptive trials but the first cycle is not valid for comparison A phase III clinical study was carried out among 5680 fertile Chinese women to evaluate efficacy and side effects of three monthly injectable contraceptives : Mesigyna , Cyclofem and Chinese Injectable No. 1 . When used in a once-a-month treatment schedule ( part 1 of study ) , the effectiveness of Chinese Injectable No. 1 was unacceptably low ; 36 pregnancies occurred during the first 1743 women-months of use , 16 before the second injection . The study was restarted with a revised injection schedule for Injectable No. 1 : two injections separated by 9 + /- 1 days during the first month and subsequent injections given 10 - 12 days after the onset of bleeding , or if no bleeding occurred , 28 days after previous injection . In part 2 of the study , 988 , 990 and 992 subjects were provided Mesigyna , Cyclofem and Injectable No. 1 , respectively . Life-table pregnancy rates at one year were 0.41 % , 0 % and 0.77 % ( p < 0.05 ) , respectively ; the overall discontinuation rates at one year were 13.9 % , 19.1 % and 20.4 % ( p < 0.001 ) . Discontinuation rates for bleeding problems were significantly different between the groups : discontinuation rates for amenorrhea were 0.58 % , 3.71 % and 0.68 % ( p < 0.001 ) for Mesigyna , Cyclofem and Injectable No. 1 ; for other bleeding problems , the rates were 4.88 % , 8.38 % and 12.64 % ( p < 0.001 ) . There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons . Mean weight changes after one year of use were small : 0.73 , 0.86 and 0.17 kg for the three groups , respectively . Both Mesigyna and Cyclofem were very effective for contraception , but Mesigyna appeared to be tolerated slightly better with regard to cycle control ; the modified dose regimen for Injectable No. 1 also gave a low pregnancy rate but was associated with higher rates of discontinuation The efficacy and acceptability of two third generation oral contraceptives in Thai women were evaluated in a prospect i ve , open , group-comparative , r and omized , multicenter trial of women asking for contraception . In six Family Planning Centers and Outpatient Gynaecological Clinics in urban areas in Thail and , 783 healthy women who were at risk for pregnancy and did not have contraindications to oral contraceptive use were r and omly allocated to one of the two study groups . An oral contraceptive containing 30 mcg ethinylestradiol and 150 mcg desogestrel was given to 394 women and an oral contraceptive with the same amount of ethinylestradiol and 75 mcg gestodene to 389 women during 6 cycles . Criteria of cycle control , side effects and the presence and severity of acne vulgaris were assessed and blood pressure and body weight measured at pretreatment and after cycles 1 , 3 and 6 . Furthermore , the efficacy was evaluated after the last cycle . No pregnancies occurred with either of the contraceptives . The incidences of irregular bleeding and minor side effects in both groups were very low and decreased after an initial increase in the first cycle . Acne improved in both groups . Blood pressure and body weight remained unchanged . The two oral contraceptives were found to be effective and acceptable in Thai women . Compared to Caucasian women , the incidences of irregular bleeding and side effects were apparently lower in these Asian women . Furthermore , the effects of both oral contraceptives were comparable Blinding embodies a rich history spanning over two centuries . Most research ers worldwide underst and blinding terminology , but confusion lurks beyond a general comprehension . Terms such as single blind , double blind , and triple blind mean different things to different people . Moreover , many medical research ers confuse blinding with allocation concealment . Such confusion indicates misunderst and ings of both . The term blinding refers to keeping trial participants , investigators ( usually health-care providers ) , or assessors ( those collecting outcome data ) unaware of the assigned intervention , so that they will not be influenced by that knowledge . Blinding usually reduces differential assessment of outcomes ( information bias ) , but can also improve compliance and retention of trial participants while reducing biased supplemental care or treatment ( sometimes called co-intervention ) . Many investigators and readers naïvely consider a r and omised trial as high quality simply because it is double blind , as if double-blinding is the sine qua non of a r and omised controlled trial . Although double blinding ( blinding investigators , participants , and outcome assessors ) indicates a strong design , trials that are not double blinded should not automatically be deemed inferior . Rather than solely relying on terminology like double blinding , research ers should explicitly state who was blinded , and how . We recommend placing greater credence in results when investigators at least blind outcome assessment s , except with objective outcomes , such as death , which leave little room for bias . If investigators properly report their blinding efforts , readers can judge them . Unfortunately , many articles do not contain proper reporting . If an article cl aims blinding without any accompanying clarification , readers should remain sceptical about its effect on bias reduction The aim of this study was to compare contraceptive reliability , cycle control , and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol ( EE2 ) and 75 micrograms gestodene ( GSD ) , with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol . A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive . For the 20 micrograms EE2 preparation , 47.4 % of all women reported spotting at least once over a period of 12 treatment cycles , whereas this figure was 35.5 % for the 30 micrograms EE2 pill ( p < 0.05 ) . However , the incidence was within a range that corresponds to that of other OCs . The cumulative breakthrough bleeding rates ( at least once during the one year of treatment ) of 14.5 % ( 20 micrograms EE2 ) and 11.8 % ( 30 micrograms EE2 ) of women were not significantly different . In relation to all cycles , the intermenstrual bleeding rates were remarkably lower , indicating that the majority of the volunteers experienced such events only in few cycles under treatment : the spotting rate was 11.5 % ( 20 micrograms EE2 ) and 7.2 % ( 30 micrograms EE2 ) of all cycles , and the breakthrough bleeding rate was 2.6 % and 1.6 % of all cycles , respectively . Three pregnancies were recorded during the study ( one in the 20 micrograms EE2 + 75 micrograms GSD group , two in the 30 micrograms EE2 + 75 micrograms GSD group ) . All three could be explained either by intake irregularities or by circumstances impairing the contraceptive effect . The influence of both treatments on the blood pressure and body weight proved to be extremely slight . Adverse events in both groups were rare and differences in the frequency of adverse events were not apparent . The discontinuation rate due to adverse events , including intermenstrual bleeding , was low ( 9.8 % for 20 micrograms EE2 + 75 micrograms GSD , and 7.2 % for 30 micrograms EE2 + 75 micrograms GSD ) and was in the lower range known for other oral contraceptives . Both preparations were well accepted by the volunteers . The data obtained demonstrate clinical ly acceptable cycle control , good tolerance , and a high st and ard of contraceptive reliability for both drugs . Prescription of the 20 micrograms EE2 preparation could be the first-line therapy in order to provide the lowest amount of EE2 possible . In case of persistent cycle control problems , a switch to the 30 micrograms EE2 drug should be considered A r and omized multicenter study was performed in order to investigate the acceptance of a low-dose OC ( 30 micrograms of ethinyloestradiol and 150 micrograms of desogestrel ) , using a 9 weeks on and 1 week off schedule ( prolonged regimen , n = 198 ) , compared to a traditional 3 weeks on , 1 week off schedule ( st and ard regimen , n = 96 ) . Haemoglobin and blood pressure remained the same in both groups during the study . No significant differences were found in body weight changes between the two groups . There was significantly more breakthrough bleeding and spotting in the group with prolonged regimen than in the group with st and ard regimen , but both breakthrough bleeding and spotting decreased during the trial . Irregular bleeding was significantly less in women who were already using OC , compared to " new starters . " No serious side effects occurred . Significantly more women stopped the trial because of bleeding problems in the group with prolonged regimen , while there were significantly more women who stopped the trial because of headache in the group with st and ard regimen . After completing 12 months , or after premature withdrawal from the study , each women completed a question naire . Sixty-three per cent of the women preferred the studied alternative and twenty-six per cent preferred the traditional OC OBJECTIVE To compare the cycle control and tolerability of two oral contraceptives containing 20 micrograms ethinylestradiol and either 150 micrograms desogestrel or 75 micrograms gestodene . METHODS A r and omized , multicenter study was conducted in which 1016 healthy adult women received the desogestrel ( n = 509 ) or the gestodene ( n = 507 ) preparation for six treatment cycles . RESULTS No significant differences in bleeding patterns were detected between the two treatments . The incidence and duration of irregular bleeding decreased markedly , and to a similar extent , during each treatment . The occurrence of irregular bleeding per cycle decreased from 24.6 to 9.4 % in the desogestrel group and from 19.7 to 8.6 % in the gestodene group . Its duration fell from 1.1 to 0.2 days and from 0.9 to 0.3 days , respectively . There was a consistently low incidence of amenorrhea ( 1.0 - 2.8 % ) . There were no significant differences between treatments for the incidence , intensity or emergence of dysmenorrhea . During both treatments , the incidence of premenstrual syndrome and complaints such as breast tenderness , nausea and headache dropped markedly . CONCLUSION Ultra low-dose oral contraceptives containing desogestrel or gestodene offer equivalent , good cycle control and improvements in dysmenorrhea and premenstrual syndrome and have similar , excellent tolerability profiles Although weight gain is among the most common complaints of women using oral contraceptives ( OC ) and a frequent reason for discontinuation , studies demonstrate little basis for this perception . We explored this issue by analyzing the daily weights of 128 women during four cycles of triphasic OC use . The mean weight at the end of the fourth cycle of use was the same as baseline weight ( average weight change , 0.0 pounds ) . The largest proportion of women , 52 % , remained within 2 pounds ( 0.9 kg ) of their starting weight , and 72 % of women had either no weight change or a loss . Over each menstrual cycle , regular but minor weight shifts were observed , with the mean weight rising by one-half pound ( 0.2 kg ) during the first weeks of each cycle and falling by the same amount during the last few days . These results emphasize the lack of association of OC use with weight gain but OC may be blamed at least in part , based on cyclic fluctuations . Counseling should emphasize weight gain as a misperception and stress the fact that a highly effective and safe form of contraception should not be ruled out or discontinued because of concern about weight The aim of the present study was to compare changes in the endogenous and rogen environment in healthy women while on low-dose oral contraceptives ( OCs ) . One-hundred healthy women were r and omized to receive one of four OCs during six months : 21 tablets of Cilest , Femodeen , Marvelon , or Mercilon . During the luteal phase of the pretreatment cycle , body weight and blood pressure were recorded and the following parameters were measured : sex hormone-binding globulin ( SHBG ) , corticosteroid-binding globulin ( CBG ) , testosterone ( T ) , free testosterone ( FT ) , 5 alpha-dihydrotestosterone ( DHT ) , and rostenedione ( A ) , dehydroepi and rosterone-sulphate ( DHEA-S ) and 17 alpha-hydroxyprogesterone ( 170HP ) while also the free and rogen index ( FAI ) was calculated . Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month . There were no differences on body mass and blood pressure with the use of the four OCs . The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon ( approximately 20 % vs 45 % ) . Mean serum SHBG and CBG increased significantly in all four groups approximately 250 % and 100 % , respectively . In each group CBG also increased significantly but less in women taking Mercilon ( -75 % ) as compared to the others ( -100 % ) . Current low-dose OCs were found to have similar impact on the endogenous and rogen metabolism with significant decreases of serum testosterone , DHT , A , and DHEA-S. They may be equally beneficial in women with and rogen related syndromes such as acne and hirsutism Thirty-five young women completed the Profile of Mood States and tests of automatization and perceptual restructuring ability before and after commencing one of three forms of oral contraception ( OC ) or one form of intrauterine contraception ( the loop ) . For each subject on each experimental variable the difference between the first and second tests was computed . These data were then analysed by covariance and discriminant function analyses . Two sets of functions were derived . The first distinguished the loop users from the OC users . The latter exhibited significantly greater increases in anger and significantly greater reductions in vigor than the former . The second set of discriminant functions distinguished users of Neogynon from the women in the other three groups . Neogynon users ' performances on the Color Words Test ( a measure of automatization ability ) worsened and their anger , vigor and tension scores had decreased to a greater extent than was the case for members of the other groups . It is suggested that the changes in affect demonstrated by the first discriminant function were related to personal and attitudinal variables associated with the Loop users . The second discriminant function was interpreted as an indication that the varying progestagen content of OC may have differential effects upon both affect and automatization ability OBJECTIVE To compare a traditional 28‐day cycle to an extended 49‐day cycle of the 30 μg ethinyl estradiol (E2)/300 μg norgestrel monophasic birth control pill regimen . METHODS Ninety subjects r and omized to either 28‐day cycles with 21 active pills or 49‐day cycles with 42 active pills for a prospect i ve open label trial over four 84‐day reference periods or trimesters . Bleeding , pill taking , and symptom diaries were completed . The sample size with 80 % power to detect a 40 % reduction in bleeding days required 24 subjects in each arm . RESULTS Of the 90 women , 24 subjects ( 54.5 % ) on the 28‐day cycle and 29 ( 63 % ) on the 49‐day cycle completed the entire study ( P = .41 ) . There were no statistically significant differences between the two groups in demographics or continuation rates . There was a significant reduction in bleeding days in the experimental arm beginning in the first trimester ( 28‐day = 10.9 , 49‐day = 6.4 mean days of bleeding , P < .001 ) and continuing to the fourth trimester ( 28‐day = 11.3 , 49‐day = 5.8 mean days , P = .005 ) . The number of spotting days was similar between both schedules in the first trimester ( 28‐day = 4.8 , 49‐day = 3.7 mean days , P = .24 ) and continued into the fourth trimester ( 28‐day = 3.4 , 49‐day = 2.9 mean days , P = .30 ) . Annual expenditure for hygiene products was significantly less for extended use subjects ( 28‐day = $ 41.45 , 49‐day = $ 17.54 spent , P < .001 ) . CONCLUSION Extension of the 28‐day oral contraceptive ( OC ) cycle to a 49‐day cycle result ed in fewer bleeding days and no increase in mean spotting days or bleeding episodes The contraceptive efficacy , cycle control , and safety of a new low-dose , triphasic desogestrel/ethinyl estradiol oral contraceptive ( CTR 77 , Cyclessa(TM ) ) was compared to that of a marketed , triphasic norethindrone/ethinyl estradiol oral contraceptive ( Ortho-Novum(R ) 7/7/7 ) . Two identical multicenter , open-label , r and omized , parallel group , comparative Phase III 6-cycle trials were design ed to each enroll 4200 healthy women . The combined comparative data for Cyclessa versus Ortho-Novum 7/7/7 for both studies are reported here . Cyclessa and Ortho-Novum 7/7/7 had comparable contraceptive efficacy . Despite a lower ethinyl estradiol dose ( 25 microg/day vs. 35 microg/day ) , the Cyclessa group had significantly improved cycle control in comparison to the Ortho-Novum 7/7/7 group for presence of a withdrawal bleed ( p = 0.001 ) , lack of early withdrawal bleed ( p = 0.01 ) , and breakthrough bleeding/spotting ( p = 0.001 ) . For each of the months of the study , the incidence of breakthrough bleeding/spotting was lower in the Cyclessa group than the Ortho-Novum 7/7/7 group ( breakthrough bleeding , p = 0.006 ; breakthrough spotting , p = 0.001 ) . The incidence of other adverse events was similar among treatment groups , an observation that supports the safety of both formulations . There was significantly less weight gain ( p = 0.0002 ) and less increase in the body mass index ( BMI ) ( p = 0.0002 ) in the Cyclessa group . The contraceptive efficacy and safety of Cyclessa is comparable to Ortho-Novum 7/7/7 . Cyclessa provides significantly improved cycle control with no weight gain OBJECTIVE To assess the contraceptive efficacy , cycle control and acceptability of two monophasic oral contraceptives containing either 30 micrograms ethinylestradiol plus 150 micrograms desogestrel or 30 micrograms ethinylestradiol plus 75 micrograms gestodene . METHODS In a r and omized , open-label , six-cycle , group-comparative , multicenter study performed in Brazil , pregnancies , cycle-control parameters , incidence of side-effects and the presence and severity of acne vulgaris were assessed , and blood pressure and body weight were measured at pretreatment and after one , three and six cycles of oral contraceptive use . RESULTS Of the 595 women enrolled , 274 ( 86.7 % ) in the desogestrel/ethinylestradiol group and 227 ( 81.4 % ) in the gestodene/ethinylestradiol group completed the six cycles , providing data for 1753 and 1487 treatment cycles , respectively . Two pregnancies occurred , one of which ( in the desogestrel/ethinylestradiol group ) was attributed to user failure , whilst the other ( in the gestodene/ethinylestradiol group ) was thought to result from method failure . Cycle control was observed to be excellent ; the incidences of irregular bleeding and minor side-effects were low in both groups and decreased after an initial increase in the first cycle . Pre-existing acne improved in both groups , whereas blood pressure and body weight remained essentially unchanged . CONCLUSIONS Both desogestrel/ethinylestradiol and gestodene/ethinylestradiol provide effective oral contraception with comparable cycle control and acceptability Drospirenone is a new synthetic progestogen with both progestational , antimineralocorticoid and anti and rogenic properties . In combination with ethinylestradiol , it is being developed as an oral contraceptive which will contain 30 μg ethinylestradiol and 3 mg drospirenone ( Yasmin ® , Schering AG , Germany ) . The effects of drospirenone alone , and in combination with ethinylestradiol , upon the renin – angiotensin – aldosterone system ( RAAS ) have been evaluated in healthy female volunteers . RAAS activity was assessed by measurement of plasma renin substrate ( PRS ) concentration ( otherwise known as angiotensinogen ) , plasma renin activity ( PRA ) , and plasma aldosterone ( P-Aldo ) concentration . An antimineralocorticoid effect was observed when volunteers received drospirenone alone at doses in the range 0.5–3.0 mg/day for one cycle . The effect was dose-dependent for P-Aldo but was not dose-dependent for PRA . When ethinylestradiol ( 30 μg ) was combined with either 2 mg or 3 mg drospirenone and given to volunteers for three cycles , an increase in PRS was observed with both preparations , which was indicative of estrogenic stimulation , and increases in PRA and P-Aldo were shown which were indicative of an antimineralocorticoid effect of drospirenone . Increases in PRA and P-Aldo were significantly higher with the preparation containing 3 mg drospirenone in cycle 1 but not in cycle 3 . The effect of the preparation containing 30 μg ethinylestradiol/3 mg drospirenone upon RAS activity was also compared with that of a commercially available preparation also containing 30 μg ethinylestradiol but combined with 150 μg desogestrel ( Marvelon ® ) . Over a period of 13 cycles , increases in PRS were seen with both treatments , the effect being slightly more pronounced with 30 μg ethinylestradiol/150 μg desogestrel . A markedly greater increase in PRA was seen following treatment with 30 μg ethinylestradiol/3 mg drospirenone , and , in cycle 3 , this difference was statistically significant . In contrast , P-Aldo was increased markedly with 30 μg ethinylestradiol/3 mg drospirenone in all measured cycles , whereas , in the 30 μg ethinylestradiol/150 μg desogestrel group , changes were minimal . The increases in PRA and P-Aldo are interpreted as endogenous counter-regulation against the antimineralocorticoid activity of drospirenone . PRS increases under all combinations are an expression of estrogenic stimulation . Measurement of body weight and blood pressure in the studies with combined ethinyl-estradiol and drospirenone revealed that drospirenone was associated with either stable body weight or with a slight loss in body weight , while blood pressure remained largely unchanged . Overall , the results indicate that 30 μg ethinylestradiol/3 mg drospirenone has a distinct antimineralocorticoid effect Objective To investigate ovulation inhibition with drospirenone , a novel progestogen that has a profile similar to natural progesterone , when given alone or in combination with ethinylestradiol . Method Hormonal parameters ( LH , FSH , 17ß-estradiol and progesterone ) and peripheral parameters ( cervical score , spinnbarkeit and crystallization ) , as well as follicle size assessed by ultrasonography , were measured in two groups of healthy women . Forty-eight women aged 19–35 years were r and omly assigned to receive 0.5 mg , 1.0 mg , 2.0 mg or 3.0 mg of drospirenone over a single treatment cycle , and 52 women aged 20–35 years were r and omized to receive either 2 mg drospirenone/30 μg ethinylestradiol or 3 mg drospirenone/30 μg ethinylestradiol over three treatment cycles . Baseline measurements were taken during a control pretreatment cycle . Results Adequate ovarian suppression with drospirenone alone was evident at dose levels of 2 and 3 mg , and at 3 mg all subjects had anovulatory cycles . Although both combined preparations ( 2 mg and 3 mg drospirenone/30 μg ethinylestradiol ) inhibited the hypothalamic – pituitary – ovarian axis , follicular maturation leading to escape ovulation was observed in three subjects in the 2 mg drospirenone/30 μg ethinylestradiol group . Only one of these ovulations was considered to be definitely the result of treatment failure . All cycles in the 3 mg drospirenone/30 μg ethinylestradiol group were anovulatory . No statistically significant difference was found between treatment groups . Conclusion The combination of 3 mg drospirenone/30 μg ethinylestradiol ( Yasmin ® , Schering AG ) reliably inhibits ovulation , with a low frequency of follicular maturation , and provides a reasonable safety margin This study was design ed to determine the effects of two low-dose oral contraceptives , most frequently given in our area , monophasic desogestrel/ethinylestradiol ( DG/EE ) and triphasic levonorgestrel/ethinylestradiol ( LNG/EE ) , on lipoprotein parameters , especially LDL particle size and HDL subclass distribution ( determined by lipid-stained 2%-20 % polyacrylamide gradient gel electrophoresis ) in 37 healthy normolipidemic women aged 19 to 27 years . Lipid and lipoprotein parameters were measured before the start of treatment and in the third month of oral contraceptive use . Results reflected the estrogen-progestin balance . As compared with baseline values , with both formulations , plasma total cholesterol , phospholipids , and HDL3 cholesterol increased , and LDL-predominant peak size decreased , with a translation of LDL pattern A towards pattern I. With DG/EE , plasma triglycerides , apolipoproteins AI and B increased . With LNG/EE , LDL cholesterol increased , and HDL2 cholesterol decreased . All these modifications were moderate , within threshold limits . Estrogen-dominant monophasic DG/EE appears to be more favorable than progestin-dominant triphasic LNG/EE , since the reduction in LDL-predominant peak size is not associated with an increase in LDL cholesterol or with a decrease in HDL2 cholesterol Changes in body weight and the incidence of estrogen-related side effects with low-dose oral contraceptives ( OCs ) containing 20 microg ethinyl estradiol ( EE ) have not been demonstrated in placebo-controlled trials . Two placebo-controlled , r and omized trials demonstrated the efficacy of a low-dose OC for the treatment of acne in healthy females ( n = 704 ; > or=14 years old ) with regular menstrual cycles and moderate facial acne . Patients were r and omized to receive 20 microg EE/100 microg levonorgestrel ( LNG ) or placebo for six cycles . Body weight was measured at baseline and during Cycles 1 , 3 , and 6 . The occurrence of adverse events was recorded at each visit . Mean changes in weight from baseline were similar with 20 microg EE/100 microg LNG [ 0.72 kg + /- 2.64 ( SD ; n = 349 ) ] and placebo [ 0.56 kg + /- 2.64 ( SD ; n = 355 ; p > 0.05 ) ] for the last measured weight of each patient . Rates of headache , nausea , weight gain , and breast pain , side effects commonly attributed to OCs , were also similar between groups ( p > 0.05 ) . No serious , unexpected , drug-related adverse events occurred during the study . The low-dose OC containing 20 microg EE/100 microg LNG is safe , well tolerated , and does not cause weight gain OBJECTIVE To determine in a prospect i ve study if the use of two low-dose estrogen oral contraceptives is associated with changes in weight or body composition . DESIGN 80 out patients referring to the family planning service , aged 18 - 43 years were r and omly assigned to a treatment with the EE/desogestrel or EE/gestodene association , 20 patients with IUD , aged 26 - 40 years , were selected as a control group . Anthropometric data and body composition were taken at enrollment and after 6 and 12 months . MAIN OUTCOME MEASURES Anthropometric measurements included body mass index ( BMI ) , body composition estimated by mean of Bioelectrical Impendance Analysis ( BIA ) . RESULTS In the three groups weight , BMI , and total body water ( TBW ) , and body cellular mass ( BCM ) remained unchanged during the study period . CONCLUSIONS The use of EE/desogestrel and EE/gestodene is not associated with significant variations of body weight and body composition during one year treatment The objective of the study was to determine the suppressive effect on ovarian activity of 20 micrograms ethinylestradiol plus 75 micrograms gestodene administered for 21 or 23 days . The study was design ed as a double-blind , r and omized , multicenter trial in 60 women . A pre-treatment cycle , three treatment cycles and a post-treatment period were monitored by ovarian ultrasound and by LH , FSH , 17 beta-estradiol and progesterone measurements every other day . No ovulation and no luteinized , unruptured follicle were observed . Suppression of ovarian activity was more pronounced by the 23-day regimen . 17 beta-Estradiol serum levels during the last six days of a cycle and during the first six days of the next cycle were significantly less ( p < 0.05 ) in the 23-day regimen . The superiority of the 23-day regimen in comparison to the 21-day regimen with regard to the suppression of ovarian activity was shown in this study . The observed differences in the 17 beta-estradiol levels and follicular development between a 21-day and 23-day preparation combine to suggest that shortening the pill-free interval in combined oral contraceptives may increase the contraceptive safety margin in women on low-dose formulations Metabolic parameters were studied in 30 patients over 12 treatment cycles in a double-blind r and omized comparative trial of the new progestogen gestoden in a triphasic formulation against a fixed dose combination pill containing desogrestrel , in B and ung , Indonesia . The results of this laboratory experience affirm findings in similar previous metabolic studies that : ( 1 ) the changes induced by modern low-dose pills are clinical ly and statistically insignificant ; ( 2 ) throughout the treatment cycles , the values of the various laboratory tests remain well within the normal range ; and ( 3 ) the favorable balance between coagulation and fibrinolysis is maintained . Results of lipoprotein , coagulation , fibrinolytic and liver function tests in 27 patients are presented . Gestoden 's pharmacologic profile , and the worldwide clinical experience with the triphasic gestoden formulation in 4285 women are discussed . ResuméA B and ung en Indonésie , on a procédé à une étude des paramètres métaboliques chez trente patientes pendant 12 cycles de traitement dans le cadre d'un essai r and omisé en double-aveugle . Cette étude comparait un nouveau protestogène , le gestoden , de formule triphasique , à une pillule comportant un mélange fixe contenant du désogestrel . Les résultats de cette expérience en laboratoire confirment les constatations faites précédemment lors d'études métaboliques similaires , à savoir que : ( 1 ) les changements apportés par les pillules modernes minidoses ne sont pas significatifs des points de vue clinique et statistique : ( 2 ) pendant les cycles de traitement , les valeurs des divers tests en laboratoire restent bien dans les limites normales ; et ( 3 ) l'équilibre entre coagulation et fibrinolyse est maintenu de façon favorable . Cette étude présente les résultats des tests , chez 27 patientes , de lipoprotéine , de coagulation , de fibrinolyse et de la fonction hépatique . Elle examine également le profil pharmacologique du gestoden ainsi que l'expérience clinique sur le plan mondial de la formule triphasique du gestoden sur 4285 femmes . ResumenEn B and ung , Indonesia , se realizó un estudio de los parámetros metabólicos de treinta pacientes durante 12 ciclos de tratamiento , en un ensayo al azar doble ciego . Este estudio comparaba un nuevo progestógeno , gestoden , de fórmula trifásica , con una píddora combinada de dosis fija que contenía desogestrel . Los result ados de esta experiencia de laboratorio confirman las constataciones hechas anteriormente en estudios metabólicos similares , a saber , que : 1 ) los cambios aportados por las píldoras modernas de dosis baja no son significativos desde el punto de vista clínico y estadístico ; 2 ) durante los ciclos de tratamiento , los valores de las diversas pruebas de laboratorio permanecen esencialmente dentro de los límites normales ; 3 ) el equilibro entre la coagulación y la fibrinólisis se mantiene de modo favorable . Este estudio presenta los result ados de las pruebas , entre 27 pacientes , de lipoprotreína , coagulación , fibrinólisis y función hepática . Examina asimismo el perfil farmacológico del gestoden así como la experiencia clínica mundial de la fórmula trifásica del gestoden en 4.285 mujeres This prospect i ve , open , r and omized study was conducted to compare the contraceptive reliability , cycle control , and tolerability of a 23-day regimen with 20 microg ethinyl estradiol ( EE ) and 75 microg gestodene ( GSD ) and a 21-day regimen with 20 microg EE and 150 microg desogestrel ( DSG ) . Participants took either 23 tablets with active substances plus 5 placebo tablets ( 23-day EE/GSD ) or 21 tablets with active substances followed by 7 days without pill-taking ( 21-day EE/DSG ) . Contraceptive efficacy , cycle control , and tolerability were evaluated over a period of seven cycles . Efficacy data gathered from 5967 treatment cycles ( 23-day EE/GSD : 2975 cycles ; 21-day EE/DSG : 2992 cycles ) were obtained from 890 participants ( 445 in each group ) . Both preparations proved to be effective contraceptives and provided good cycle control . No pregnancy during treatment was recorded . This result ed in a study Pearl Index of 0.0 for both treatments . For 23-day EE/GSD , 32.4 % of participants reported at least one intracyclic bleeding episode during Cycles 2 - 4 ( primary target ) compared to 31.5 % for 21-day EE/DSG . In the 23-day EE/GSD group , intracyclic bleeding episodes were reported by 48.8 % of the participants in Cycle 1 but in only 15.1 % in Cycle 7 , and in the 21-day regimen group by 43.4 % in Cycle 1 and only 14.2 % in Cycle 7 . Overall , intracyclic bleeding was reported in 20.9 % of cycles for both treatments . A greater number of 23-day EE/GSD participants had shorter withdrawal bleeding periods than with 21-day EE/DSG . In significantly ( p < 0.0001 ) more cycles in the 23-day EE/GSD group participants reported withdrawal bleeding periods that lasted only 1 - 4 days compared to the 21-day EE/DSG group . For the majority of the treatment cycles , the median number of bleeding days in the 23-day EE/GSD group was 4 days and in the 21-day EE/DSG group 5 days . Both preparations were well tolerated and showed a similar adverse events pattern . The discontinuation rate because of adverse events was low ( 23-day EE/GSD : 6.1 % ; 21-day EE/DSG : 5.6 % ) . No serious vascular adverse events were reported . More than 82 % in the 23-day EE/GSD group and 79 % in the 21-day EE/DSG group either lost more than 2 kg of weight or did not gain weight during the study . The treatment effect on blood pressure was negligible . There were no appreciable changes in mean laboratory values over the course of the study compared to baseline 150 women participated in a double-blind clinical trial comparing 2 dosages of an oral contraceptive agent : 250 mcg d-norgestrel + 50 mcg ethinyl estradiol and 150 mcg d-norgestrel + 30 mcg ethinyl estradiol . The 150/30 combination result ed in shorter cycles , longer menses ( p.001 ) , shorter latent period ( p.001 ) , and a higher instance of breakthrough bleeding and spotting ( p.05 and p.001 ) . The 250/50 dose caused a significantly higher incidence of breast discomfort ( p.001 ) , leg cramps ( .02 ) , and nausea ( .001 ) . More 250/50 dose women dropped out for more than 1 reason than in the lower dose group This study compares the contraceptive reliability , cycle control , and tolerability of two oral contraceptive preparations containing 20 micrograms of ethinyl estradiol combined with either 75 micrograms of gestodene ( EE/GSD ) or 150 micrograms of desogestrel ( EE/DSG ) . Women received the trial preparations daily for 21 days , followed by a 7-day pill-free interval . Contraceptive efficacy , cycle control , and tolerability were evaluated over a period of 12 cycles . Efficacy data of 14,700 treatment cycles ( EE/GSD : 7299 ; EE/DSG : 7401 ) were obtained from 1476 women ( EE/GSD , n = 740 ; EE/DSG , n = 736 ) . Both preparations provided effective contraception and good cycle control with a similarly low incidence of both spotting and breakthrough bleeding . The spotting rates in both treatment groups decreased from 35.1 % ( EE/GSD ) and 37.5 % ( EE/DSG ) in the first treatment cycle to approximately 10 % in the fourth treatment cycle . The spotting incidence as percent of the total number of cycles was 12.7 % for EE/GSD and 14.3 % for EE/DSG . The breakthrough bleeding incidence was 5.2 % of all cycles for EE/GSD and 6.0 % of all cycles for EE/DSG . For 84.7 % of the cycles in the gestodene group and for 82.5 % of the cycles in the desogestrel group , neither spotting nor breakthrough bleeding were recorded . Overall , the spotting and breakthrough bleeding incidence tended to be lower with EE/GSD than with EE/DSG . However , the difference was not statistically significant . Amenorrhea was recorded in 2.7 % of the cycles with EE/GSD and in 2.9 % with EE/DSG . Both preparations were well tolerated and showed a similar pattern of adverse events . More than 83 % of the women in both groups either did not gain weight or lost more than 2 kg . Both preparations had a beneficial effect on dysmenorrhea . Both regimens provided reliable contraception and good cycle control . The incidence of adverse events was relatively low and both preparations were well tolerated Body weight , systolic and diastolic blood pressure and plasma renin activity ( PRA ) were longitudinally followed in two groups of women during 2 years ' oral contraception . One group ( n = 10 ) received a combination of 0.150 mg levonorgestrel plus 0.030 mg ethinyloestradiol and the other ( n = 10 ) a combination of 0.150 mg desogestrel plus 0.030 mg ethinyloestradiol . Three subjects discontinued the study due to relocation . No statistically significant changes occurred in any of the measured parameters Blood pressure was prospect ively studied in 57 women during pregnancy labor the late postpartum period and after 6 cycles of oral contraceptive ( OC ) use . The women were r and omly given either a combination type ( COC ) or sequential type ( SOC ) OC . There were no significant differences between the groups in age parity weight weight gain while using OCs or development of hypertension during pregnancy . 8 women using the COD ( 33 % ) developed hypertension ( diastolic blood pressure 90 + mm Hg ) as opposed to 1 ( 3 % ) using the SOC ( p less than .05 ) . When the absolute blood pressures for the 2 groups were compared the mean diastolic pressure for the COC group of 77.3 mm Hg is significantly higher than that of the SOC group of 72.0 . Of the 9 women who developed hypertension during OC use 7 also had hypertension during pregnancy . The different progestins in the OCs may have different direct effects on the cardiovascular system Desogestrel ( DSG ) is a less- and rogenic progestogen than levonorgestrel ( LNG ) . This difference in and rogenicity may be responsible for observed differences in metabolic effects between oral contraceptive ( OC ) formulations containing almost equivalent estrogen doses but with either DSG or LNG as a progestogen . To test the hypothesis , a prospect i ve 9-month r and omized comparison of plasma lipids , glucose , insulin , hemostasis , and sex hormone binding globulin ( SHBG ) was conducted in 66 healthy women using phasic formulations of OCs containing either DSG ( DSG-OC ) or LNG ( LNG-OC ) . The study results showed that SHBG increased 3-fold with DSG-OC and 2-fold with LNG-OC . DSG-OC increased HDL-C , HDL(2)-C and HDL(3)-C ; LDL-C decreased transiently . LNG-OC decreased HDL(2)-C and increased HDL(3)-C ; HDL-C was unchanged and LDL-C decreased transiently . Both formulations increased VLDL-C and triglycerides , more with DSG-OC , but apolipoprotein B levels increased equally . Apo A-I and A-II increased more with DSG-OC than with LNG-OC . Neither formulation altered Lp(a ) or fasting glucose and insulin levels . Postpr and ially , both formulations decreased glucose and increased insulin responses , but to an equivalent degree . Both OCs slightly enhanced procoagulant and profibrinolytic parameters to the same extent except for internally compensating decreases in Factor V and protein S with DSG-OC . In summary , at almost equivalent estrogen doses , a phasic OC containing DSG compared with LNG has a less and rogenic effect on lipoproteins and SHBG , similar effects on hemostatic parameters with lower protein S and factor V activity and equivalent effects on carbohydrate metabolism . The lipoprotein , SHBG , and protein S and factor V differences are likely due to the lesser and rogenicity of DSG allowing for a greater expression of the dose of estrogen This prospect i ve , r and omized comparative clinical study involving 416 women investigated follicle development over a period of 12 oral contraceptive treatment cycles . Women were allocated to two groups , one group ( n = 207 ) received a preparation containing 30 micrograms ethinylestradiol and 75 micrograms gestodene daily , and the other group ( n = 209 ) received 20 micrograms ethinylestradiol and 150 micrograms desogestrel , daily . Follicular development was monitored by transvaginal ultrasonography of the ovaries , during days 18 - 21 in the pretreatment cycle and in treatment cycles 1 , 3 , 6 , 9 and 12 . Follicular development was found to be twice as frequent in the group receiving 20 micrograms ethinylestradiol/desogestrel as in the group receiving 30 micrograms ethinylestradiol/gestodene . For all cycles , follicles of 10 - 30 mm were found in 18 % of women in the desogestrel group , compared with 9.7 % in the gestodene group , whilst follicles with a diameter of > 30 mm were present in 5 % of the desogestrel group compared with 1.9 % of the gestodene group . The difference between the treatment groups with respect to follicle diameters of 10 - 30 mm and > 30 mm was statistically significant ( p < 0.05 and p < 0.001 , respectively ) . No ruptured follicles were observed in either group throughout the study , suggesting that there was no escape ovulation , however , there was one pregnancy in the desogestrel group that could not be explained either by drug interactions or missed pills . It can be concluded that the ethinylestradiol dose in an oral contraceptive has a significant effect on follicular ovarian activity , and that reducing the dose to 20 micrograms is associated with a significant increase in follicle size Two combined contraceptive vaginal rings ( CVR ) each releasing approximately 1 mg norethindrone acetate ( NET-Ac ) and either 20 micrograms or 15 micrograms ethinyl estradiol over 24 h were tested at three clinic sites in Los Angeles , San Francisco , and Sydney . A total of 61 women were enrolled to use the ring on a schedule of 3 weeks in/1 week out for four treatment cycles . Serum estradiol , progesterone , norethindrone ( NET ) , and ethinyl estradiol ( EE ) levels were assayed twice weekly in all four treatment cycles . Both CVR performed well , with no pregnancies occurring and only one cycle of luteal activity suggestive of ovulation ( serum progesterone > 32 nmol/L ) occurring with each ring ( 0.9 % of cycles with the 1/15 ring and 1.2 % of cycles with the 1/20 ring ) . Although there was significantly more luteal activity in women using the 1/15 CVR ( 5.9 % compared with 1.2 % of cycles ) , only three cycles with a marked degree of luteal activity ( progesterone > 10 nmol/L ) occurred among compliant women . Serum levels of NET and EE were consistently elevated during use of both rings . There was no significant difference between serum levels with the two rings because of wide interindividual variations , although both NET and EE levels tended to be higher with the 1/20 ring . However , there was a significant difference in EE levels between the women in Los Angeles and Sydney using the same dose rings . Total cholesterol , HDL , and LDL cholesterol values were not significantly changed during treatment . Triglycerides increased but remained within the normal range . Overall cycle control was good with both formulations , but there was slightly more cycle disturbance with the lower dose ring . There was no change in mean body weight during the study , and individual weight changes appeared to be idiosyncratic . Side effects were infrequent and similar to those reported with other steroidal contraceptive methods . Three women complained of vaginal discharge , one with accompanying itch and one with a vaginal C and ida infection in cycle 1 . Overall , both of these EE/NET-Ac rings performed well , with only minor and mainly nonsignificant differences in effect on serum EE , NET , E2 , and progesterone levels and lipids , and on vaginal bleeding patterns The effect of two triphasic oral contraceptives ( Triquilar [ TRQ ] and Trisiston [ TRS ] ) containing ethinyl estradiol ( EE ) and levonorgestrel ( LNG ) on various hormonal parameters was investigated in 26 women during a cross-over study . TRS consisted of 0.03 mg EE + 0.05 mg LNG ( six tablets ) , 0.04 mg EE + 0.075 mg LNG ( six tablets ) , and 0.03 mg EE + 0.15 mg LNG ( nine tablets ) , whereas TRQ was different in the second phase ( five tablets ) and third phase ( 10 tablets ) . Blood sample s were taken on days 6 , 11 , 21 , and 28 of the control and washout cycles and the third treatment cycle . Both formulations inhibited ovulation reliably and decreased the serum levels of gonadotropins , free testosterone , and dehydroepi and osterone sulfate in a time-dependent manner , whereas estradiol and testosterone were already suppressed on day 6 , indicating a direct suppressive effect on ovarian steroid synthesis . Prolactin , which rose sporadically in some women , was not significantly changed . In contrast , the levels of sex hormone binding globulin , corticosteroid binding globulin , and cortisol were significantly elevated by 100 % . During the hormone-free interval of 7 days , all parameters returned at least partly to baseline . There was no significant difference between the effects of both formulations . The results suggest the possibility of a direct inhibitory effect of contraceptive steroids on ovarian steroid synthesis The effect of a triphasic oral contraceptive containing ethinylestradiol and gestodene ( EE/GSD ) on various serum hormonal parameters was compared with that of a monophasic formulation containing 35 micrograms ethinylestradiol and 250 micrograms norgestimate ( EE/NGM ) . Blood sample s were collected from 46 women on days 2 , 11 , and 21 of the preceding control cycle and of the third , sixth and twelfth treatment cycle . There was no significant difference in the influence on any hormonal parameter between both formulations . Both EE/GSD and EE/NGM caused a time-dependent suppression of serum dehydroepi and rosterone sulphate ( DHEA-S ) by 20 - 30 % ( p < 0.01 ) and a reduction of 5 alpha- and rostane-3 alpha , 17 beta-diol glucuronide by 50 - 60 % ( p < 0.01 ) during each treatment cycle , while and rostenedione levels were reduced by 25 % ( p < 0.01 ) . There was also a significant decrease in the levels of total testosterone by 30 - 35 % ( p < 0.01 ) and free testosterone by 60 % ( p < 0.01 ) , while sex hormone-binding globulin ( SHBG ) was increased by 200 - 240 % on days 11 and 21 ( p < 0.01 ) . During the pill-free interval the SHBG levels were reduced to a certain degree but remained elevated by 100 % as compared to the pretreatment values . The serum levels of corticosteroid-binding globulin ( CBG ) which is known to be influenced only by the estrogenic component of combination pills , increased significantly by 170 % ( p < 0.01 ) during each treatment cycle . During the pill-free interval of 7 days , the CBG levels decreased but were still elevated by 90 - 100 % as compared to the control cycle . Similarly , the serum levels of cortisol were significantly elevated by 110 - 140 % ( p < 0.01 ) during treatment with both preparations . The results demonstrate a profound suppression of and rogen levels and peripheral and rogen metabolism The effects of two oral contraceptives , containing gestodene and either 20 micrograms or 30 micrograms ethinylestradiol , on hemostatic parameters was investigated in a six-month r and omized study involving a total of 40 healthy women between the ages of 18 and 30 years . A large number of hemostatic parameters were measured , which were categorized as either pro-coagulatory , anti-coagulatory , profibrinolytic , anti-fibrinolytic or indicative of fibrin turnover . Additionally , tissue plasminogen activator ( t-PA ) and plasminogen activator inhibitor ( PAI-1 ) were measured before and after venous occlusion and delta and ratio values calculated . Pro-coagulatory factors as well as reaction products reflecting in vivo coagulatory activity ( thrombin-antithrombin III complex , prothrombin fragment 1 + 2 ) were found to increase . Among the anti-coagulatory parameters , only protein S concentration and protein S activity decreased , most notably in the 30 micrograms EE group . There was a corresponding increase in fibrinolytic activity reflected by reaction products of in vivo fibrinolysis ( plasmin-antiplasmin 2-complex , fibrin-degradation products ) . Measurement of t-PA and PAI-1 , before and after venous occlusion , revealed that the fibrinolytic response was more pronounced in the 20 micrograms EE group . There was also an increase in the threshold of fibrinolytic inhibition ( ratio PAI-1 ) in both groups , which was less pronounced in the 20 micrograms EE group . Apart from isolated measurements , all parameters remained within their normal ranges and values returned to baseline in the follow-up cycle . It is concluded that both preparations had a balanced effect on the hemostatic system stimulating both pro-coagulant and fibrinolytic activity . No statistically significant differences were observed between the two groups ; however , there was a trend towards greater fibrinolytic capacity in the 20 micrograms EE group A comparative study of two low-dose oral contraceptives , gestodene ( GES ) 75 mcg/ethinyl oestradiol ( EE ) 30 mcg and desogestrel ( DES ) 150 mcg/EE 20 mcg , was conducted in women over 30 years of age . This r and omised , open-label study was organised in Denmark , Italy , New Zeal and and United Kingdom . A total of 505 women received GES/EE and 501 received DES/EE for 6 consecutive menstrual cycles . The two groups were comparable in terms of demographic and gynaecologic characteristics at baseline . However , the menstrual flow length was slightly longer in the GES/EE group before the start of the treatment . The mean age ( + /- SD ) was 35 + /- 4 years in the GES/EE group and 35 + /- 5 years in the DES/EE group . The subjects in the GES/EE group contributed data for a total of 2800 cycles and those in the DES/EE group , data for 2796 cycles . There were no pregnancies on medication with either preparation . The results showed that there were significantly more normal cycles in the GES/EE group for cycles 1 to 6 . Irregular bleeding between withdrawal bleeds occurred in 10 % of GES/EE and 18.5 % of DES/EE cycles . Absence of all bleeding was reported in 29 ( 1 % ) and 63 ( 2 % ) cycles , respectively . The incidence of missed pills was low in both groups ( 11 % of cycles ) . No significant differences were observed in cycle length or withdrawal bleeding episode length . Withdrawal bleeding mean intensity was statistically significantly greater with GES/EE . However , for both preparations , the mean intensity was close to light bleeding . No clinical ly significant differences were noted in weight , blood pressure , Papanicolaou smears or laboratory data . Sixty-eight ( 13.5 % ) subjects in the GES/EE group and 64 ( 12.8 % ) in the DES/EE group discontinued before the end of the study . Among them , 37 ( 7 % ) and 40 ( 8 % ) in the respective groups withdrew because of adverse reactions . There was no difference between groups in terms of primary reasons for withdrawal . The most frequently reported complaints that led to discontinuation in both groups were headache , nausea and metrorrhagia . Breast tenderness led to the discontinuation of 1 subject in the GES/EE group and 3 in the DES/EE group . These results show excellent cycle control , efficacy and very low rate of side effects with both GES/EE and DES/EE . These low-dose oral contraceptives could be well suited to healthy nonsmoking women requiring contraception up to the age of menopause |
12,073 | 30,134,867 | Conclusions Sarcopenia is a significant predictor of hospitalization among older individuals , and the association may not be significantly affected by the characteristics of the population or the definition of sarcopenia | Background Previous cohort studies investigating the association between sarcopenia and the risk of hospitalization have been inconsistent .
We performed a meta- analysis to determine if sarcopenia is a predictor of hospitalization . | BACKGROUND Several studies in older people have shown that grip strength predicts all-cause mortality . The mechanisms are unclear . Muscle strength declines with age , accompanied by a loss of muscle mass and an increase in fat , but the role that body composition plays in the association between grip strength and mortality has been little explored . We investigated the relation between grip strength , body composition , and cause-specific and total mortality in 800 men and women aged 65 and over . METHODS During 197374 the UK Department of Health and Social Security surveyed r and om sample s of men and women aged 65 and over living in eight areas of Britain to assess the nutritional state of the elderly population . The survey included a clinical examination by a geriatrician who assessed grip strength and anthropometry . We used Cox proportional hazards models to examine mortality over 24 years of follow-up . RESULTS Poorer grip strength was associated with increased mortality from all-causes , from cardiovascular disease , and from cancer in men , though not in women . After adjustment for potential confounding factors , including arm muscle area and BMI , the relative risk of death in men was 0.81 ( 95 % CI 0.700.95 ) from all-causes , 0.73 ( 95 % CI 0.600.89 ) from cardiovascular disease , and 0.81 ( 95 % CI 0.660.98 ) from cancer per SD increase in grip strength . These associations remained statistically significant after further adjustment for fat-free mass or % body fat . CONCLUSION Grip strength is a long-term predictor of mortality from all-causes , cardiovascular disease , and cancer in men . Muscle size and other indicators of body composition did not explain these associations OBJECTIVES To examine the association between strength , function , lean mass , muscle density , and risk of hospitalization . DESIGN Prospect i ve cohort study . SETTING Two U.S. clinical centers . PARTICIPANTS Adults aged 70 to 80 ( N=3,011 ) from the Health , Aging and Body Composition Study . MEASUREMENTS Measurements were of grip strength , knee extension strength , lean mass , walking speed , and chair st and pace . Thigh computed tomography scans assessed muscle area and density ( a proxy for muscle fat infiltration ) . Hospitalizations were confirmed by local review of medical records . Negative binomial regression models estimated incident rate ratios ( IRRs ) of hospitalization for race- and sex-specific quartiles of each muscle and function parameter separately . Multivariate models adjusted for age , body mass index , health status , and coexisting medical conditions . RESULTS During an average 4.7 years of follow-up , 1,678 ( 55.7 % ) participants experienced one or more hospitalizations . Participants in the lowest quartile of muscle density were more likely to be subsequently hospitalized ( multivariate IRR=1.47 , 95 % confidence interval (CI)=1.24 - 1.73 ) than those in the highest quartile . Similarly , participants with the weakest grip strength were at greater risk of hospitalization ( multivariate IRR=1.52 , 95 % CI=1.30 - 1.78 , Q1 vs. Q4 ) . Comparable results were seen for knee strength , walking pace , and chair st and s pace . Lean mass and muscle area were not associated with risk of hospitalization . CONCLUSION Weak strength , poor function , and low muscle density , but not muscle size or lean mass , were associated with greater risk of hospitalization . Interventions to reduce the disease burden associated with sarcopenia should focus on increasing muscle strength and improving physical function rather than simply increasing lean mass BACKGROUND Hospitalization represents a stressful and potentially hazardous event for older persons . We evaluated the value of the Short Physical Performance Battery ( SPPB ) in predicting rates of functional decline , rehospitalization , and death in older acutely ill patients in the year after discharge from the hospital . METHODS Prospect i ve cohort study of 87 patients aged 65 years and older who were able to walk and with a Mini-Mental State Examination score ≥ 18 and admitted to the hospital with a clinical diagnosis of congestive heart failure , pneumonia , chronic obstructive pulmonary disease , or minor stroke . Patients were evaluated with the SPPB at hospital admission , were reevaluated the day of hospital discharge , and 1 month later . Subsequently , they were followed every 3 months by telephone interviews to ascertain functional decline , new hospitalizations , and vital status . RESULTS After adjustment for potential confounders , including self-report activity of daily living and comorbidity , the SPPB score at discharge was inversely correlated with the rate of decline in activity of daily living performance over the follow-up ( p < .05 ) . In a multivariable discrete-time survival analysis , patients with poor SPPB scores at hospital discharge ( 0 - 4 ) had a greater risk of rehospitalization or death ( odds ratio : 5.38 , 95 % confidence interval : 1.82 - 15.9 ) compared with those with better SPPB scores ( 8 - 12 ) . Patients with early decline in SPPB score after discharge also had steeper increase in activity of daily living difficulty and higher risk of rehospitalization or death over the next year . CONCLUSIONS In older acutely ill patients who have been hospitalized , the SPPB provides important prognostic information . Lower extremity performance-based functional assessment might identify older patients at high risk of poor outcomes after hospital discharge AIM The purpose of the present study was to investigate whether sarcopenia was associated with future falls in the general Japanese older population . METHODS This study was a 2-year prospect i ve observational study . Participants were recruited from individuals who had an annual town-sponsored medical check-up and had not received nursing care . The inclusion criteria for participants in our study were : ( i ) agreement to participate ; ( ii ) living independently ; and ( iii ) the ability to walk to where the survey was carried out and to provide self-reported data . A total of 223 residents ( 82 men , 141 women ) participated in the baseline assessment in the study . Demographic information , previous fall history , locomotive syndrome , body function and structural measurements and pain at the knee and /or lumber spine were assessed . The Asian Working Group for Sarcopenia algorithm was used to classify the presence of sarcopenia , and assess the history of falling when the participant received their annual medical check-up . RESULTS A total of 162 participants had an annual follow-up assessment , 50 of whom ( 30.8 % ) fell at least once during the 2-year observational period after baseline assessment . Previous falling history , prevalence of locomotive syndrome , sarcopenia and pain were significantly higher in participants who had fallen compared with participants who had not . Multiple logistic regression analysis showed the prevalence of sarcopenia was a significant predictor of falling . CONCLUSION The key finding of the present study suggests that sarcopenia is a risk factor for falling in older adults who are living independently even after adjustment for previous falls and confounding factors . Geriatr Gerontol Int 2017 ; 17 : 2124 - 2130 OBJECTIVES To evaluate the predictive value of muscle strength and physical performance in the oldest old for all-cause mortality ; hospitalization ; and the onset of disability , defined as a decline in activities of daily living ( ADLs ) , independent of muscle mass , inflammatory markers , and comorbidities . DESIGN A prospect i ve , observational , population -based follow-up study . SETTING Three well-circumscribed areas of Belgium . PARTICIPANTS Five hundred sixty participants aged 80 and older were followed for 33.5 months ( interquartile range 31.1 - 35.6 months ) . MEASUREMENTS Grip strength , Short Physical Performance Battery ( SPPB ) score , and muscle mass were measured at baseline ; ADLs at baseline and after 20 months ; and all-cause mortality and time to first hospitalization from inclusion onward . Kaplan-Meier curves and Cox proportional hazards models were calculated for all-cause mortality and hospitalization . Logistic regression analysis was used to determine predictors of decline in ADLs . RESULTS Kaplan-Meier curves showed significantly higher all-cause mortality and hospitalization in subjects in the lowest tertile of grip strength and SPPB score . The adjusted Cox proportional hazards model showed that participants with high grip strength or a high SPPB score had a lower risk of mortality and hospitalization , independent of muscle mass , inflammatory markers , and comorbidity . A relationship was found between SPPB score and decline in ADLs , independent of muscle mass , inflammation , and comorbidity . CONCLUSION In people aged 80 and older , physical performance is a strong predictor of mortality , hospitalization , and disability , and muscle strength is a strong predictor of mortality and hospitalization . All of these relationships were independent of muscle mass , inflammatory markers , and comorbidity Abstract Background The aim of this study is to assess the prevalence of sarcopenia and investigate the associations between sarcopenia and long‐term mortality and readmission in a population of elderly in patients in acute care wards . Methods We conducted a prospect i ve observational study in the acute care wards of a teaching hospital in western China . The muscle mass was estimated according to a previously vali date d anthropometric equation . H and grip strength was measured with a h and held dynamometer , and physical performance was measured via a 4 m walking test . Sarcopenia was defined according to the recommended diagnostic algorithm of the Asia Working Group for Sarcopenia . The survival status and readmission information were obtained via telephone interviews at 12 , 24 , and 36 months during the 3 year follow‐up period following the baseline investigation . Results Two hundred and eighty‐eight participants ( mean age : 81.1 ± 6.6 years ) were included . Forty‐nine participants ( 17.0 % ) were identified as having sarcopenia . This condition was similar in men and women ( 16.9 % vs. 17.5 % , respectively , P = 0.915 ) . During the 3 year follow‐up period , 49 men ( 22.7 % ) and 9 women ( 16.4 % ) died ( P = 0.307 ) . The mortality of sarcopenic participants was significantly increased compared with non‐sarcopenic participants ( 40.8 % vs. 17.1 % , respectively , P < 0.001 ) . After adjusting for age , sex and other confounders , sarcopenia was an independent predictor of 3 year mortality ( adjusted hazard ratio : 2.49 ; 95 % confidential interval : 1.25–4.95 ) and readmission ( adjusted hazard ratio : 1.81 ; 95 % confidential interval : 1.17–2.80 ) . Conclusions Sarcopenia , which is evaluated by a combination of anthropometric measures , gait speed , and h and grip strength , is valuable to predict hospital readmission and long‐term mortality in elderly patients in acute care wards BACKGROUND Sarcopenia is prevalent in older population s with many causes and varying outcomes however information for use in clinical practice is still lacking . AIMS The aim of this report is to identify the clinical determinants and prognostic significance of sarcopenia in a cohort of hospitalized acutely ill older patients . METHODS Four hundred and thirty two r and omly selected patients had their baseline clinical characteristic data assessed within 72 h of admission , at 6 weeks and at 6 months . Nutritional status was assessed from anthropometric and biochemical data . Sarcopenia was diagnosed from low muscle mass and low muscle strength-h and grip using anthropometric measures based on the European Working Group criteria . RESULTS Compared with patients without sarcopenia , those diagnosed with sarcopenia 44 ( 10 % ) were more likely to be older , have more depression symptoms and lower serum albumin concentration . The length of hospital stay ( LOS ) was significantly longer in patients diagnosed with sarcopenia compared with patients without sarcopenia [ mean ( SD ) LOS 13.4 ( 8.8 ) versus 9.4 ( 7 ) days respectively , p = 0.003 ] . The risk of non-elective readmission in the 6 months follow up period was significantly lower in patients without sarcopenia compared with those diagnosed with sarcopenia ( adjusted hazard ratio .53 ( 95 % CI : .32 to .87 , p = 0.013 ) . The death rate was also lower in patients without sarcopenia 38/388 ( 10 % ) , compared with those with sarcopenia 12/44 ( 27 % ) , p-value = .001 . CONCLUSION Older people with sarcopenia have poor clinical outcome following acute illness compared with those without sarcopenia Summary In this study , we compare the extent to which seven available definitions of sarcopenia and two related definitions predict the rate of falling . Our results suggest that the definitions of Baumgartner and Cruz-Jentoft best predict the rate of falls among sarcopenic versus non-sarcopenic community-dwelling seniors . Introduction The purpose of the study is to compare the extent to which seven available definitions of sarcopenia and two related definitions predict the prospect i ve rate of falling . Methods We studied a cohort of 445 seniors ( mean age 71 years , 45 % men ) living in the community who were followed with a detailed fall assessment for 3 years . For comparing the rate of falls in sarcopenic versus non-sarcopenic individuals , we used multivariate Poisson regression analyses adjusting for gender and treatment ( original intervention tested vitamin D plus calcium against placebo ) . Of the seven available definitions , three were based on low lean mass alone ( Baumgartner , Delmonico 1 and 2 ) and four required both low muscle mass and decreased performance in a functional test ( Fielding , Cruz-Jentoft , Morley , Muscaritoli ) . The two related definitions were based on low lean mass alone ( Studenski 1 ) and low lean mass contributing to weakness ( Studenski 2 ) . Results Among 445 participants , 231 fell , sustaining 514 falls over the 3-year follow-up . The prospect i ve rate of falls in sarcopenic versus non-sarcopenic individuals was best predicted by the Baumgartner definition based on low lean mass alone ( RR = 1.54 ; 95 % CI 1.09–2.18 ) with 11 % prevalence of sarcopenia and the Cruz-Jentoft definition based on low lean mass plus decreased functional performance ( RR = 1.82 ; 95 % CI 1.24–2.69 ) with 7.1 % prevalence of sarcopenia . Consistently , fall rate was non-significantly higher in sarcopenic versus non-sarcopenic individuals based on the definitions of Delmonico 1 , Fielding , and Morley . Conclusion Among the definitions investigated , the Baumgartner definition and the Cruz-Jentoft definition had the highest validity for predicting the rate of falls OBJECTIVES To test the hypothesis that men and women with low bone mineral density ( BMD ) and sarcopenia have a higher risk of fracture than those with only one or neither conditions . DESIGN The Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures in women are prospect i ve observational studies with a mean follow up of 9 ( 2000 - 2012 ) and 8 years ( 1997 - 2009 ) , respectively . SETTING U.S. clinical centers . PARTICIPANTS Men ( n = 5,544 ; mean age 73.7 ) and women ( n = 1,114 ; mean age 77.6 ) aged 65 and older , able to walk without assistance , and without bilateral hip replacement . MEASUREMENTS Sarcopenia was defined as low appendicular lean mass plus slowness or weakness and low BMD according to the World Health Organization definition of a T-score less than -1.0 . Participants were classified as having normal BMD and no sarcopenia ( 3,367 men , 308 women ) , sarcopenia only ( 79 men , 48 women ) , low BMD only ( 1,986 men , 626 women ) , and low BMD and sarcopenia ( 112 men , 132 women ) . RESULTS Men with low BMD and sarcopenia ( hazard ratio (HR)=3.79 , 95 % confidence interval (CI)=2.65 - 5.41 ) and men with low BMD only ( HR=1.67 , 95 % CI=1.45 - 1.93 ) but not men with sarcopenia only ( HR=1.14 , 95 % CI=0.62 - 2.09 ) had greater risk of fracture than men with normal BMD and no sarcopenia . Women with low BMD and sarcopenia ( HR=2.27 , 95 % CI=1.37 - 3.76 ) and women with low BMD alone ( HR=2.62 , 95 % CI=1.74 - 3.95 ) , but not women with only sarcopenia , had greater risk of fracture than women with normal BMD and no sarcopenia . CONCLUSION Men with low BMD and sarcopenia are at especially high risk of fracture . Sarcopenia alone did not increase fracture risk in either group |
12,074 | 31,177,623 | Whilst most of the studies reported increased patient participation , those interventions which had provider or patient training in communication skills were found to be more effective .
CONCLUSION Interventions to improve patient participation , within the context of dyadic decision making , in non-Western countries can be feasible and effective if communication skills training is provided for health-care providers and /or patients | BACKGROUND Patients ' participation in medical decision making is an important aspect of patient-centred care .
However , there is often uncertainty about its applicability and feasibility in non-Western countries .
OBJECTIVE To provide an overview and assessment of interventions that aim ed to improve patients ' participation in decision making in non-Western countries . | Background Although a model for shared decision-making is important for patient-centered care , decisional conflict can emerge when patients participate in the decision-making . A decision aid is proposed to provide information and to involve patients more comfortably in the decision-making process . We aim ed to determine whether a decision aid helps patients with carpal tunnel syndrome ( CTS ) experience less decisional conflict regarding their decision-making for surgery . Methods Eighty patients with CTS were r and omized into two groups . The test group was given a decision aid in addition to regular information and the control group regular information only . The decision aid consisted of a 6-min videoclip that explains diagnosis and information regarding surgery for CTS with other treatment options . We evaluated patients ’ decisional conflict regarding surgery , knowledge about CTS , and symptom severity as measured by the Disabilities of Arm , Shoulder , and H and ( DASH ) Question naire . Results There was no difference in the decisional conflict scale ( DCS ) between both groups ( p = 0.76 ) . The test group had significantly better knowledge than the control group ( p = 0.04 ) . There was no correlation between the knowledge score and the DCS ( p = 0.76 ) . However , less severe symptoms were correlated with greater decisional conflict ( r = −0.29 , p = 0.02 ) . Conclusions We found that a decision aid does not reduce decisional conflict in patients with CTS , although it can help them be better informed . This study suggests that although a decision-aid is effective for patient education , doctor-patient communication should be more emphasized for patients with less severe symptoms , as they can have greater decisional conflict . Trial Registration SNUBH Registry 1510/317 - 003 Registered November 13 , OBJECTIVE We aim ed to evaluate the effect of a decision aid ( DA ) with patient narratives on decisional conflict in surgery choice for Japanese women with early-stage breast cancer . METHODS Two hundred ten women with early-stage breast cancer were r and omly assigned to an intervention or control group . Groups 1 and 2 received st and ard information and a DA , with or without patient narratives , and Group 3 received st and ard information ( control ) before surgery choice . At baseline , post-intervention ( Time 2 ) , and 1 month after surgery ( Time 3 ) , we evaluated decisional conflict as the primary outcome using a decisional conflict scale ( DCS ) . Sidak corrections for multiple comparisons in analysis of covariate were used to compare Time 2 and Time 3 DCS mean scores between each pair of groups . RESULTS At Time 3 , decisional conflict was significantly reduced for Group 1 vs control ( P=0.021 , Cohen 's d = 0.26 ) and Group 2 vs control ( P=0.008 , Cohen 's d=0.40 ) . CONCLUSION The DAs with and without patient narratives are equivalently effective at reducing postoperative decisional conflict in Japanese women with early-stage breast cancer . PRACTICE IMPLICATION S The DAs with and without patient narratives can be used in clinical practice for women with early-stage breast cancer Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more ABSTRACT In order to increase patient active engagement during patient – provider interactions , we developed and implemented patient training sessions in four antiretroviral therapy ( ART ) clinics in Namibia using a “ Patient Empowerment ” training curriculum . We examined the impact of these trainings on patient – provider interactions after the intervention . We tested the effectiveness of the intervention using a r and omized parallel group design , with half of the 589 enrolled patients r and omly assigned to receive the training immediately and the remaining r and omized to receive the training 6 months later . The effects of the training on patient engagement during medical consultations were measured at each clinic visit for at least 8 months of follow-up . Each consultation was audiotaped and then coded using the Roter Interaction Analysis System ( RIAS ) . RIAS outcomes were compared between study groups at 6 months . Using intention-to-treat analysis , consultations in the intervention group had significantly higher RIAS scores in doctor facilitation and patient activation ( adjusted difference in score 1.19 , p = .004 ) , doctor information gathering ( adjusted difference in score 2.96 , p = .000 ) , patient question asking ( adjusted difference in score .48 , p = .012 ) , and patient positive affect ( adjusted difference in score 2.08 , p = .002 ) . Other measures were higher in the intervention group but did not reach statistical significance . We have evidence that increased engagement of patients in clinical consultation can be achieved via a targeted training program , although outcome data were not available on all patients . The patient training program was successfully integrated into ART clinics so that the trainings complemented other services being provided Background Chronic conditions are a major source of morbidity , mortality and cost worldwide . Shared decision making is one way to improve care for patients with chronic conditions . Although it has been widely studied , the effect of shared decision making in the context of chronic conditions is unknown . Methods / Design We will perform a systematic review with the objective of determining the effectiveness of shared decision making interventions for persons diagnosed with chronic conditions . We will search the following data bases for relevant articles : PubMed , Scopus , Ovid MEDLINE , Ovid EMBASE , Ovid EBM Review s CENTRAL , CINAHL , and Ovid PsycInfo . We will also search clinical trial registries and contact experts in the field to identify additional studies . We will include r and omized controlled trials study ing shared decision making interventions in patients with chronic conditions who are facing an actual decision . Shared decision making interventions will be defined as any intervention aim ing to facilitate or improve patient and /or clinician engagement in a decision making process . We will describe all studies and assess their quality . After adjusting for missing data , we will analyze the effect of shared decision making interventions on outcomes in chronic conditions overall and stratified by condition . We will evaluate outcomes according to an importance ranking informed by a variety of stakeholders . We will perform several exploratory analyses including the effect of author contact on the estimates of effect . Discussion We anticipate that this systematic review may have some limitations such as heterogeneity and imprecision ; however , the results will contribute to improving the quality of care for individuals with chronic conditions and facilitate a process that allows decision making that is most consistent with their own values and preferences . Trial registration PROSPERO Registration Number : PURPOSE Breast cancer ( BC ) decision aid ( DA ) r and omized studies are limited to DA use in consultations among Western population s and for primary surgery . Their effectiveness beyond consultations , for reconstructive surgery and in other population s , has not been evaluated . We developed a DA administered after consultation for Chinese women deciding on BC surgery and , where relevant , immediate breast reconstruction , which was evaluated in this r and omized controlled trial ( RCT ) . PATIENTS AND METHODS Overall , 276 women considering BC surgery for early-stage BC were r and omly assigned to receive a DA ( take-home booklet ) or the st and ard information booklet ( control condition ) after the initial consultation , wherein surgeons disclosed the diagnosis and discussed treatment options with patients . Using block r and om assignment by week , 138 women were assigned to the DA arm and 138 to the control arm . Participants completed interview-based question naires 1 week after consultation and then 1 , 4 , and 10 months after surgery . Primary outcome measures were decisional conflict , decision-making difficulties , BC knowledge 1 week after consultation , and decision regret 1 month after surgery . Secondary outcome measures were treatment decision , decision regret 4 and 10 months after surgery , and postsurgical anxiety and depression . RESULTS The DA group reported significantly lower decisional conflict scores 1 week after consultation ( P = .016 ) compared with women in the control arm . Women receiving the DA had significantly lower decision regret scores 4 ( P = .026 ) and 10 months ( P = .014 ) after surgery and lower depression scores 10 months after surgery ( P = .001 ) . CONCLUSION This RCT demonstrated DAs may benefit Chinese patients in Hong Kong by reducing decisional conflict and subsequent regret and enhance clinical services for this population 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 OBJECTIVE The objective of this study was to evaluate the patients ' perception of the usefulness of a question prompt sheet ( QPS ) in facilitating the involvement of advanced cancer patients during consultation . METHODS Advanced cancer patients attending their first consultation after diagnosis were r and omly assigned to the intervention group ( received QPS and a hospital introduction sheet ( HIS ) ) or the control group ( received HIS only ) . Analysis was conducted on an intention-to-treat basis . The primary outcome measure was patient rating of the usefulness of the material ( s ) ( numerical rating scale of 0 - 10 ) . RESULTS Sixty-three advanced cancer patients ( 72.4 % response rate ) were enrolled and analyzed . Nearly three-quarters of patients in both groups read the material ( s ) before consultation . The rated usefulness of the material ( s ) for asking questions of physicians was significantly higher in the intervention group than in controls ( 4.4 ± 3.6 and 2.7 ± 2.8 , respectively ; p = 0.033 ) . The mean score of the usefulness of the material ( s ) for underst and ing the treatment plan tended to be higher in the intervention group than in the controls ( 4.9 ± 3.6 and 3.3 ± 2.8 ; p = 0.051 ) . The mean score of willingness to use the material ( s ) in the future was significantly higher in the intervention group than in the controls ( 5.3 ± 3.8 and 2.8 ± 2.8 ; p = 0.006 ) . There were no significant differences between the groups in the average total number of questions asked by patients ( median , 1.0 ; interquartile range in both groups , 2.0 ) . CONCLUSIONS QPS provided before oncology consultation may be useful for advanced cancer patients , on the other h and , it did not directly promote patient confidence to ask questions Paternalistic models of health care , social distance between patients and providers , and cultural norms discourage patients from playing an active role in health consultations . This study tested whether individual coaching can give family planning patients the confidence and communication skills to talk more openly and more vigorously with providers . Educators met with 384 Indonesian women in clinic waiting rooms and coached them on asking questions , expressing concerns , and seeking clarification . An analysis of audiotaped consultations found that patients who received coaching articulated significantly more questions and concerns than others . Coaching narrowed differentials in active communication by patient type , age , and assertiveness , but it widened differentials by patient education and socioeconomic class . The discontinuation rate at 8 months was lower in the intervention than the control condition , but the difference was only marginally significant Background A patient decision aid ( PDA ) is a tool for shared decision making ( SDM ) , which emphasises patient empowerment . It is useful in chronic diseases and when there are multiple , no best single treatment option . Although SDM is prevalent in Western countries , its use is limited in Chinese societies , where the adoption of a paternalistic approach is strong . Here , we report the development , acceptance and pilot test results of a PDA targeted at Chinese patients with primary open-angle glaucoma ( POAG ) . Methods We developed a PDA design ed for use in Chinese patients with POAG . Recruited subjects were given our PDA . Baseline evaluation included decision conflict scale ( DCS ) , vali date d glaucoma adherence question naires and glaucoma knowledge question naire . Subjects were briefed through the PDA and instructed to read it that day . Three to four weeks later , follow-up question naire as described above were conducted with the addition of acceptance question naires . Results Data from 65 subjects were available . The PDA was well received among subjects . DCS improved from 48.9±20.4 at baseline to 34.3±20.3 during follow-up , with P<0.01 . Vali date d medication adherence question naires and knowledge showed improvement from baseline , which was statistically significant . Conclusions The use of PDA among Chinese subjects with POAG demonstrated positive reception and acceptance . Evaluation of its initial effects shows improvement in DCS , medication adherence and glaucoma knowledge . The implementation of SDM and PDA among Chinese subjects with POAG is encouraged . Future studies with r and omised design and later evaluation time points can further reveal the impacts of PDA among Chinese subjects with POAG OBJECTIVE The Patient Activation Measure ( PAM ) is a 22-item measure that assesses patient knowledge , skill , and confidence for self-management . The measure was developed using Rasch analyses and is an interval level , unidimensional , Guttman-like measure . The current analysis is aim ed at reducing the number of items in the measure while maintaining adequate precision . STUDY METHODS We relied on an iterative use of Rasch analysis to identify items that could be eliminated without loss of significant precision and reliability . With each item deletion , the item scale locations were recalibrated and the person reliability evaluated to check if and how much of a decline in precision of measurement result ed from the deletion of the item . DATA SOURCES The data used in the analysis were the same data used in the development of the original 22-item measure . These data were collected in 2003 via a telephone survey of 1,515 r and omly selected adults . Principal Findings . The analysis yielded a 13-item measure that has psychometric properties similar to the original 22-item version . The scores for the 13-item measure range in value from 38.6 to 53.0 ( on a theoretical 0 - 100 point scale ) . The range of values is essentially unchanged from the original 22-item version . Subgroup analysis suggests that there is a slight loss of precision with some subgroups . CONCLUSIONS The results of the analysis indicate that the shortened 13-item version is both reliable and valid AIM To audit the extent of non-disclosure of cancer diagnosis ( NDD ) in South-East Asian patients referred to a Western trained oncologist , and determine the factors associated with this pattern of decision-making . METHODS Over a 12-month period , all new patients referred to a single radiation oncologist 's practice were prospect ively audited at time of the initial consultation . Data obtained included patient demographic features , tumour details , proposed treatment and decision-making process . A shared decision-making consultation was attempted but if there was a persistent request by family to avoid disclosure , then a family-centred model was adopted . Patient autonomy was maintained by formally asking desire to participate in decision-making process , and subsequent permission then sought to involve family members as surrogates . Treatment aim , predicted median survival and NDD was recorded at end of consultation . Endpoints of patient NDD and non- discussion of prognosis were audited over a 12-month period , and factors potentially associated with these endpoints were assessed . RESULTS Over a 12-month period 369 new patients were referred to the oncologist 's practice . Forty per cent were > 65 years , 84 % Chinese race , and 66 % non-English speaking . Lung ( 33 % ) and breast ( 32 % ) primaries were prominent . Forty-seven per cent were managed with palliative intent and 24 % had expected median survivals of < 6 months . NDD was recorded in 66 patients or 17 % of the patient group . Quantitative discussion of prognosis was avoided in 36.8 % of patients . On univariate analysis advanced patient age ( p<0.001 , OR=9.6 , 95 % CI 4.9 - 18.9 ) , female sex ( p=0.035 , OR=1.8 , 95 % CI 1.04 - 3.1 ) , non-English speaking ( p<0.001 , OR=21.4 , 95 % CI 5.1 - 89.1 ) , palliative treatment aim ( p<0.001 , OR=5.9 , 95 % CI 3.1 - 11.2 ) and short expected median survival ( p<0.001 , OR=4.0 , 95 % CI 2.3 - 7.1 ) were associated with NDD . Advanced patient age ( p<0.001 , OR=7.9 , 95 % CI 3.6 - 17.5 ) , female sex ( p<0.001 , OR=6.4 , 95 % CI 2.8 - 14.7 ) , non-English speaking ( p=0.010 , OR=7.4 , 95 % CI 1.6 - 33.3 ) and palliative treatment aim ( p=0.010 , OR=3.3 , 95 % CI 1.3 - 8.0 ) remained significantly associated with NDD on multivariate logistic regression analysis . CONCLUSIONS A high rate of desired NDD is evident in this Asian oncology population when a family-centred model to medical decision making is used . This data confirms that NDD and the model of decision making remains a significant ethical issue Patient autonomy and participation in treatment decision making have been encouraged in recent years . However , patients and physicians frequently disagree with regard to the patient 's needs and perceptions of their illness . To the authors ' knowledge to date only limited research has assessed physicians ' perceptions of patients ' decision‐making preferences . The purpose of the current prospect i ve study was to determine the agreement between patient decision‐making preferences and physician perceptions of those preferences OBJECTIVES To ascertain the expectations of Nepalese patients regarding aspects of doctor-patient communication and to review a model of patient-centred care for its appropriateness to Nepalese medical communication training . METHODS A cross-sectional survey , using an adapted version of the Patient-Practitioner Orientation Scale ( PPOS ) , was undertaken with a r and om sample of patients attending a general out patients department in rural Nepal . An alternative survey instrument , derived from the PPOS , was also used . RESULTS The following issues were most important to patients : being treated in a friendly and respectful manner ; being fully informed , and being given adequate consultation time . Patients were happy for the doctor to be in charge and did not want to seek information outside the doctor 's advice . They expressed a strong preference for receiving advice about preventative care . Patient responses were significantly more ' doctor-centred ' than those found in comparable studies in the USA . DISCUSSION Patients expressed strong preferences for some aspects of patient-centred communication ( PCC ) , but were not very concerned with sharing power and control . Models of PCC in Nepal require modification to reflect these local preferences . The importance of good communication techniques requires emphasis in clinical training and practice . Methods of disseminating information need to be enhanced in this low-literacy setting |
12,075 | 31,188,483 | The most common adverse events of riociguat were headache , dizziness , hypotension and nasopharyngitis .
CONCLUSIONS Our meta- analysis indicates that BPA might be associated with greater improvements in exercise tolerance and pulmonary hemodynamics except for cardiac output and cardiac index than riociguat therapy .
However , both of them were well tolerated | BACKGROUND S No previous meta-analyses have compared the efficacy and safety of BPA with riociguat therapy in inoperable CTEPH patients . | Chronic thromboembolic pulmonary hypertension ( CTEPH ) is a rare but potentially life-threatening disease of the pulmonary circulation [ 1 ] . The pathogenesis of CTEPH is not entirely clear . The most accepted scenario is that of aborted recanalisation of pulmonary arteries after a thromboembolic episode . While some post-embolic residua may persist in up to 50 % of survivors of acute pulmonary embolism ( aPE ) , only 0.5 % to 2 % will progress to CTEPH [ 2 , 3 ] . This is believed to occur in the presence of significant redistribution of flow to remaining unoccluded pulmonary bed with result ing elevation of intravascular pressure and shear stress . Remodelling of initially patent pulmonary arterioles leads to an increase in pulmonary vascular resistance similar to that observed in left-to-right shunting in congenital heart disease . Progressive uncoupling of pulmonary and right ventricular elastance results in a fall of pulmonary flow , left ventricular preload , systemic blood pressure , and right ventricular ( RV ) coronary perfusion leading to right heart failure with severe functional disability and eventually to death . Management of CTEPH requires precise differential diagnosis and qualification for surgical treatment by an experienced multidisciplinary team . Indeed , in operable patients pulmonary endarterectomy ( PEA ) is highly effective in restoring functional status and improving life expectancy . A surgical technique has been optimised and implemented worldwide by a group from San Diego – University of California [ 4 ] . Nevertheless , PEA performed in deep hypothermia and intermittent total cardiac arrest remains one of the most dem and ing cardiovascular interventions and is performed only in a limited number of highly dedicated centres . As an example , Papworth Hospital is the only centre performing PEA in the UK , while Marie-Lannelongue Hospital in Paris remains a referral centre for France for this type of surgery . Usually , individual cardiac surgeons are responsible for PEA in their centres , as the learning curve for this intervention has been well documented [ 5 ] . With growing experience of clinicians , radiologists , surgeons , and anaesthesiologists , an increasing proportion of patients with CTEPH may benefit from PEA despite distal , less accessible intravascular residua and /or advanced age and comorbidities . This is of paramount importance since the outcome of non-operated patients is drastically worse ( Figure 1 ) , despite identical baseline haemodynamic characteristics and significant perioperative mortality of 2–10 % in patients su bmi tted to PEA [ 6 ] . Nevertheless , even in the leading CTEPH referral centres almost 50 % patients remain on medical treatment alone , with grim perspectives regarding life quality and expectancy . Based on a large r and omised trial and promising long-term effects on exercise tolerance [ 7 , 8 ] direct guanylyl cyclase stimulator ( riociguat ) has been approved for treatment of inoperable CTEPH . Riociguat may protect patent pulmonary arterioles from progressive remodelling [ 9 ] but is unlikely to affect the culprit post-embolic residua . Recently , balloon pulmonary angioplasty ( BPA ) has emerged as a promising new interventional option in non-operable CTEPH . In 2001 , Feinstein et al. from Harvard Medical School described a group of 18 CTEPH patients treated with BPA [ 10 ] . Of these , 16 were excluded from PEA due to distal lesions , and two due to the presence of comorbidities increasing the risk associated with surgical treatment . In total , 47 procedures were performed , thus dilating or restoring the patency of 107 arteries . In the periprocedural period , 1 patient died of reperfusion pulmonary oedema and right ventricular failure . In total , reperfusion oedema occurred in 23 % of cases , and its presence correlated with the value of pulmonary artery pressure ( PAP ) prior to the procedure . Long-term follow-up ( mean , 34 months ) showed an increase in physical capacity , manifesting itself as an improvement in NYHA class from a mean value of 3.3 prior to the procedure to a mean value of 1.8 following the procedure . Figure 1 Survival curves for patients with CTEPH treated with PEA ( shadow line ) and who were treated by pharmacotherapy only ( solid line ) – reprinted from Wieteska et al. [ 6 ] The succeeding years saw the development of the BPA technique mainly in Japanese centres . Japanese research ers have refined the BPA technique by reducing the number of segments treated during one session [ 11 ] , by using smaller balloons [ 12 ] , and by wider use of intravascular imaging [ 13 , 14 ] . The experience of the Japanese centres shows that a series of BPA procedures performed in experienced centres has lead to regression of right ventricular dysfunction [ 15 , 16 ] and are associated with an annual mortality below 5 % – also in elderly patients [ 17 ] . However , it should be stressed that the population of Japanese patients with CTEPH differs from that observed in the European-American registry [ 18 ] . In a registry comprising 519 Japanese patients with CTEPH , lower median pretreatment mPAP ( 38 mm Hg vs. 47 mm Hg ) , more frequent use of PAH-like therapy ( 52 % vs. 38 % ) , and a significantly lower rate of cardiac surgical treatment used ( 14 % vs. 57 % ) was observed [ 19 ] . The only larger group of patients in Europe who underwent BPA is that described by And reassen et al. [ 20 ] . The Norwegian team treated 20 CTEPH patients , including 16 with distal lesions , 3 with proximal lesions who had refused PEA , and 1 patient with persistent pulmonary hypertension following surgical treatment . Prior to treatment , 85 % of the patients presented with NYHA class III and IV symptoms . During recruitment to a percutaneous treatment program in the same centre , 50 PEAs were performed . In total , 73 BPA procedures were carried out ( mean , 3.7 BPAs/patient ; range : 2–9 ) , thus performing angioplasty of 371 vessels – 118 segmental arteries and 253 subsegmental arteries . In the periprocedural period , two patients died , and treatment-requiring reperfusion oedema occurred in 7 cases . During 3-month follow-up , an improvement in the functional class ( 75 % of patients in NYHA class I – II ) , in VO2max in cardiopulmonary exercise test ( 13.6 ±5.6 vs. 17.0 ±6.5 , p < 0.001 ) , in mean pulmonary artery pressure ( 45 ±11 mm Hg vs. 33 ±10 mm Hg , p < 0.001 ) , in pulmonary vascular resistance ( 8.8 ±4.0 Wood Units vs. 5.9 ±3.6 Wood Units , p < 0.001 ) , and in NT-pro-BNP levels ( 194 ±182 ng/ml vs. 90 ±119 ng/ml , p = 0.007 ) was achieved . Follow-up angiography revealed no restenosis . In Pol and , the first BPA procedure was performed in 2013 [ 21 ] . Until now , the experience of our team includes 37 BPA procedures , which consisted of angioplasty of 105 vessels in 20 patients with CTEPH . Seventeen patients were excluded from surgical treatment by an experienced PEA cardiac surgery team , and in 3 patients persistent pulmonary hypertension persisted after PEA . Eighty-two percent of patients received PAH-like therapy – most frequently sildenafil . In the periprocedural period , two patients died of severe reperfusion oedema and severe hypoxaemia unresponsive to oxygen therapy ( including mechanical ventilation ) . Those 2 patients were disqualified from PEA due to the presence of extensive lung cavities related to previous mycobacterial infection and due to significant comorbidities and advanced age , respectively – but not because of distal localisation of thrombi . All patients who underwent BPA because of distal lesion localisation survived . In technical terms , BPA does not significantly differ from balloon angioplasty performed in other vessels ( Figure 2 ) . Nevertheless , the complicated anatomy of the pulmonary tree , the necessity to advance the instruments through enlarged right heart chambers , and the fact that pulmonary vessels can be easily damaged with the guide wire or balloon catheter requires specific experience . It is not recommended that BPA procedures be performed by cardiologists or interventional radiologists who have experience in other vascular regions but no experience in interventions within the pulmonary circulation . During one procedure , no more than two segmental arteries or their subsegmental equivalents should be dilated due to the risk of reperfusion oedema . Reperfusion oedema results from redistribution of blood flow to areas supplied by dilated vessels , in which vascular resistance has abruptly decreased . This may cause blood cells to migrate into the alveoli , excluding them from gas exchange . One way to prevent reperfusion oedema is to undersize the balloon catheter being used , on the basis of angiography , or by means of intravascular ultrasound ( IVUS ) or optical coherence tomography ( OCT ) . Also , pressure distal to a residual lesion and a gradient across the lesion can be measured by means of an fractional flow reserve ( FFR ) probe [ 22 ] . As there is no tendency towards restenosis , it is unnecessary to use stents . The results achieved in the group of patients who have completed a series of BPA procedures are very encouraging . A reduction in mean PAP from baseline 58 ±6 mm Hg to 41 ±9 mm Hg and in PVR from 11.7 ±4.3 Wood units to 6.6 ±2.2 Wood units was achieved in our series . The haemodynamic improvement corresponds with an improvement in exercise tolerance . Prior to BPA procedures , 95 % of patients were in NYHA class III and IV , and the rate of patients in class III and IV decreased to 35 % after treatment . A significant issue limiting growth in the number of such procedures performed in Pol and is that BPA is not reimbursed by the National Health Fund . Figure 2 Balloon pulmonary angioplasty in a 67-year-old patient with persistent form of CTEPH . Left panel ( A ) presents the angiogram of occluded segmental pulmonary artery of left lower lobe . The BPA results in reperfusion of the vessel – right panel ( To use cardiac magnetic resonance imaging ( MRI ) to investigate the effect of balloon pulmonary angioplasty ( BPA ) on interventricular dyssynchrony and its associations with ventricular interaction , which impairs LV function in patients with inoperable chronic thromboembolic pulmonary hypertension ( CTEPH ) . This prospect i ve observational study was approved by our institutional review board . Cardiac MRI and right heart catheterization were conducted before BPA sessions and at the follow up after BPA in 20 patients with CTEPH . We measured right ventricular ( RV ) and left ventricular ( LV ) end-diastolic volume ( EDV ) , end-systolic volume ( ESV ) , stroke volume ( SV ) , and ejection fraction ( EF ) using MRI . For the LV and RV free walls , the time to peak ( Tpeak ) of circumferential strain was calculated as a parameter for interventricular dyssynchrony . Following BPA , the RV-EDV and -ESV were significantly decreased , and the RVEF was significantly increased . Conversely , BPA led to significantly increased LV EDV and SV without changing LVESV . The left-to-right free wall delay ( L – R delay ) in Tpeak strain decreased from 105 ± 44 ms to 47 ± 67 ms ( p < 0.001 ) . Increased LV EDV ( r = 0.65 , p < 0.01 ) , SV ( r = 0.74 , p < 0.001 ) and 6-minute walk distance ( 6MWD ) ( r = 0.54 , p < 0.05 ) were correlated to the reduction in L – R delay . In patients with inoperable CPEPH , BPA improved interventricular dyssynchrony , which was strongly associated with increased SV and 6MWD . The assessment of interventricular dyssynchrony using cardiac MRI has an important role in evaluating ventricular interaction , which reduces LVSV and exercise tolerance BACKGROUND Although balloon pulmonary angioplasty ( BPA ) improves the hemodynamics and prognosis of patients with inoperable chronic thromboembolic pulmonary hypertension ( CTEPH ) , the mechanisms of improvement in oxygenation remain to be eluci date d. METHODS AND RESULTS From August 2013 to May 2015 , we performed a total of 113 BPA procedures in 24 patients with inoperable CTEPH ( mean 4.7 procedures per patient ) . Median age was 70 [ 60 , 74 ] years and 18 were female ( 75 % ) . We examined hemodynamics , respiratory functions , and intrapulmonary shunt before and after the BPA procedure . Mean pulmonary arterial pressure ( 37 [ 28 , 45 ] to 23[19 , 27 ] mmHg , P<0.01 ) , pulmonary vascular resistance ( 517 [ 389 , 696 ] to 268 [ 239 , 345 ] dyne/s/cm(5 ) ) and 6-min walk distance ( 390 [ 286 , 484 ] to 490 [ 411 , 617 ] m , P<0.01 ) were significantly improved after BPA therapy . Furthermore , arterial oxygen partial pressure ( PaO2 , 54.8 [ 50.0 , 60.8 ] to 65.2 [ 60.6 , 73.2 ] % , P<0.01 ) and intrapulmonary shunt ( 23.4±6.0 % to 19.3±5.0 % , P<0.01 ) were also significantly ameliorated . In the multivariate analysis , decrease in intrapulmonary shunt after BPA was significantly correlated with improvement of both PaO2(r(2)=0.26 , P<0.01 ) and SaO2(r(2)=0.49 , P<0.01 ) after BPA . CONCLUSIONS These results indicated that BPA improved not only pulmonary hemodynamics but also oxygenation with a result ant decrease in intrapulmonary shunt . ( Circ J 2016 ; 80 : 2227 - 2234 ) Balloon pulmonary angioplasty ( BPA ) is an emerging treatment for patients with inoperable chronic thromboembolic pulmonary hypertension ( CTEPH ) . We report on a prospect i ve series of 56 consecutive patients who underwent 266 BPA interventions ( median , five per patient ) at two German institutions . All patients underwent a comprehensive diagnostic work-up including right heart catheterisation at baseline and 24 weeks after their last intervention . BPA result ed in improvements in WHO functional class , 6 min walk distance ( mean change , + 33 m ) , right ventricular function and haemodynamics , including a decline in mean pulmonary artery pressure by 18 % and in pulmonary vascular resistance by 26 % . Procedure-related adverse events occurred in 9.4 % of the interventions . The most common complications were related to pulmonary vascular injury and consecutive pulmonary bleeding . Most of these events were asymptomatic and self-limiting , but one patient died from pulmonary bleeding , result ing in a mortality rate of 1.8 % . BPA result ed in haemodynamic and clinical improvements but was also associated with a considerable number of complications , including one fatal pulmonary bleeding . As the effects of BPA on survival are unknown , r and omised controlled outcome trials comparing BPA with approved medical therapies in patients with inoperable CTEPH are required to allow for appropriate risk – benefit assessment s. BPA improves haemodynamics and exercise capacity in patients with inoperable CTEPH but complications are not uncommon We assessed the therapeutic potential of riociguat , a novel soluble guanylate cyclase stimulator , in adults with chronic thromboembolic pulmonary hypertension ( CTEPH ; n = 42 ) or pulmonary arterial hypertension ( PAH ; n = 33 ) in World Health Organization ( WHO ) functional class II/III . In this 12-week , multicentre , open-label , uncontrolled phase II study , patients received oral riociguat 1.0–2.5 mg t.i.d . titrated according to systemic systolic blood pressure ( SBP ) . Primary end-points were safety and tolerability ; pharmacodynamic changes were secondary end-points . Riociguat was generally well tolerated . Asymptomatic hypotension ( SBP < 90 mmHg ) occurred in 11 patients , but blood pressure normalised without dose alteration in nine and after dose reduction in two . Median 6-min walking distance increased in patients with CTEPH ( 55.0 m from baseline ( 390 m ) ; p<0.0001 ) and PAH ( 57.0 m from baseline ( 337 m ) ; p<0.0001 ) ; patients in functional class II or III and bosentan pre-treated patients showed similar improvements . Pulmonary vascular resistance was significantly reduced by 215 dyn·s·cm−5 from baseline ( 709 dyn·s·cm−5 ; p<0.0001 ) . 42 ( 56 % ) patients were considered to have experienced drug-related adverse events ( AEs ; 96 % mild or moderate ) . Dyspepsia , headache and hypotension were the most frequent AEs . Study discontinuation because of AEs was 4 % . These preliminary data show that riociguat has a favourable safety profile and improves exercise capacity , symptoms and pulmonary haemodynamics in CTEPH and PAH . R and omised controlled trials are underway Background Following positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension ( CTEPH ) , the Phase IIIb CTEPH early access study ( EAS ) was design ed to assess the safety and tolerability of riociguat in real-world clinical practice , as well as to provide patients with early access to riociguat before launch . Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH . Methods We performed an open-label , uncontrolled , single-arm , early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily ( tid ) to a maximum of 2.5 mg tid . Patients switching from unsatisfactory prior pulmonary arterial hypertension (PAH)-targeted therapy ( n = 84 ) underwent a washout period of at least 3 days before initiating riociguat . The primary aim was to assess the safety and tolerability of riociguat , with World Health Organization functional class and 6-min walking distance ( 6MWD ) as exploratory efficacy endpoints . Results In total , 262 patients ( 87 % ) completed study treatment and entered the safety follow-up ( median treatment duration 47 weeks ) . Adverse events were reported in 273 patients ( 91 % ) . The most frequently reported serious adverse events were syncope ( 6 % ) , right ventricular failure ( 3 % ) , and pneumonia ( 2 % ) . There were five deaths , none of which was considered related to study medication . The safety and tolerability of riociguat was similar in patients switched from other PAH-targeted therapies and those who were treatment naïve . In patients with data available , mean ± st and ard deviation 6MWD had increased by 33 ± 42 m at Week 12 with no clinical ly relevant differences between the switched and treatment-naïve subgroups . Conclusions Riociguat was well tolerated in patients with CTEPH who were treatment naïve , and in those who were switched from other PAH-targeted therapies . No new safety signals were observed . Trial registration Clinical Trials.org NCT01784562 . Registered February 4 , 2013 BACKGROUND Riociguat , the first approved drug for patients with chronic thromboembolic pulmonary hypertension ( CTEPH ) , is a soluble guanylate cyclase ( sGC ) Stimulator . It directly stimulates sGC independently of nitric oxide ( NO ) and increases sGC sensitivity for NO . The safety and efficacy of transitioning from a phosphodiesterase 5 inhibitor ( PDE5i ) to riociguat is unknown . METHODS AND RESULTS Twenty-three patients were prospect ively enrolled : 8 symptomatic patients with inadequate clinical responses to PDE5i were changed to riociguat ( transitioned group ) ; 15 started riociguat anew ( new or add-on group ) . We analyzed the change from baseline to 6 - 12 months of riociguat treatment for the 6-minute walk distance ( 6MWD ) , mean pulmonary arterial pressure ( mPAP ) , pulmonary vascular resistance ( PVR ) , cardiac index ( CI ) , partial pressure of oxygen in arterial blood ( PaO2 ) , brain natriuretic peptide ( BNP ) , World Health Organization ( WHO ) functional class , safety and adverse events . The mPAP , BNP and WHO functional class significantly improved in total . In the transitioned group , BNP significantly decreased by -116.5±188.6pg/ml ( P=0.0156 ) . The 6MWD , mPAP , PVR , CI , and PaO2 improved but not significantly . The baseline condition was significantly more severe in the transitioned than in the new or add-on group . No patients discontinued riociguat . Relatively rapid transitioning from PDE5i to riociguat was safe under careful observation . CONCLUSIONS Transitioning to riociguat may be safe and effective in CTEPH patients with inadequate clinical responses to PDE5i AIMS To assess whether a strategy of invasive management without stents in selected acute coronary syndrome ( ACS ) patients with a large thrombus burden ( LTB ) might be feasible and safe . METHODS AND RESULTS We performed a prospect i ve non-r and omised observational cohort study of invasive treatment decisions guided by optical coherence tomography ( OCT ) in selected ACS patients with LTB . Among 852 ACS patients who had undergone invasive coronary angiography , 101 ( 11.8 % ) patients with large thrombus burden on initial angiography underwent thrombectomy to restore TIMI 3 flow without stenting . All of these patients then had repeat angiography with OCT ( days 0 - 2 [ Group 1 ] , days 3 - 6 [ Group 2 ] or days 7 - 30 [ Group 3 ] ) . No adverse events occurred between the initial and second angiograms . Residual thrombus was detected in 68 % of patients with OCT ( respectively , 94 % , 79 % and 32 % in Group 1 , Group 2 and Group 3 ) , and 20 % of cases with angiography . Plaque rupture was detected by OCT in 65 % of cases . Minimal lumen area was 2.81 mm2 , 3.40 mm2 and 4.89 mm2 in Group 1 , Group 2 and Group 3 , respectively . Sixty-two percent of patients were stented ( respectively , 76 % , 61 % and 50 % ) . During a minimum follow-up period of 12 months in all patients , one non-fatal MI occurred and one PCI was performed for angina . CONCLUSIONS Medical management without stents is safe and feasible in selected ACS patients with LTB . OCT revealed culprit lesion characteristics that were not disclosed by angiography and facilitated treatment decisions Objective To examine the effect of balloon pulmonary angioplasty ( BPA ) on chronic thromboembolic pulmonary hypertension ( CTEPH ) in patients with inoperable disease or persistent pulmonary hypertension after pulmonary endarterectomy . Design Observational cohort study . Setting Referred patients with inoperable or persistent CTEPH . Patients Twenty consecutive CTEPH patients ( 10 females ) , aged 60±10 years . Interventions BPA . Main outcome measures Right heart catheterisation , functional capacity ( cardiopulmonary exercise testing ( CPET ) and NYHA class ) and blood sample d biomarkers N-terminal pro-brain natriuretic peptide ( NT-proBNP ) and troponin T examined at the time of diagnosis and repeated in all patients 3 months after the last BPA . Results Seventy-three catheterisations were performed with 18.6±6.1 BPAs per patient on segmental and subsegmental arteries . Two deaths occurred following the first BPA , with an overall 10 % periprocedural death rate . Reperfusion oedema complicated seven procedures . Comparisons before and after BPA showed significant haemodynamic improvements , including decreased mean pulmonary artery pressure ( mPAP ) ( 45±11 mm Hg vs 33±10 mm Hg ; p<0.001 ) and increased cardiac output ( 4.9±1.6 L/min vs 5.4±1.9 L/min ; p=0.011 ) . Reduced right ventricular strain was indicated by significantly lower plasma levels of NT-proBNP and troponin T. Significant improvement in functional capacity was evident as assessed by NYHA class ( 3.0±0.5 vs 2.0±0.5 ; p<0.001 ) and CPET ( 13.6±5.6 mL/kg/min vs 17.0±6.5 mL/kg/min ; p<0.001 ) . Seventeen patients ( 85 % ) were alive after 51±30 months of follow-up . Conclusions BPA may offer an alternative form of treatment in selected CTEPH patients . While prognostic markers such as haemodynamics , functional capacity and biomarkers improve , significant periprocedural complications must be recognised . R and omised trials are warranted Objective We compared the haemodynamic effects of riociguat in patients with inoperable chronic thromboembolic pulmonary hypertension ( CTEPH ) or persistent/recurrent CTEPH after pulmonary endarterectomy in the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase – Stimulator Trial 1 study . Methods Patients with inoperable or persistent/recurrent CTEPH ( n=261 ; mean± SD age 59±14 years ; 66 % women ) were r and omised to riociguat ( up to 2.5 mg three times daily ) or placebo . Haemodynamic parameters were assessed at baseline and week 16 . Results Riociguat decreased pulmonary vascular resistance ( PVR ) in inoperable ( n=189 ; least-squares mean difference : −285 dyn s/cm5 ( 95 % CI −357 to −213 ) ; p<0.0001 ) and persistent/recurrent ( n=72 ; −131 dyn s/cm5 ( 95 % CI −214 to −48 ) ; p=0.0025 ) patients . Cardiac index improved in inoperable patients by a least-squares mean difference of + 0.6 L/min/m2 ( 95 % CI 0.4 to 0.7 ; p<0.0001 ) , while in persistent/recurrent patients the change was + 0.2 L/min/m2 ( 95 % CI −0.1 to 0.5 ; p=0.17 ) . Mean pulmonary artery pressure decreased in inoperable and persistent/recurrent patients ( −4.7 mm Hg ( 95 % CI −6.9 to −2.6 ; p<0.0001 and −4.8 mm Hg ( –8.2 to −1.5 ; p=0.0055 ) , respectively ) . For all patients , changes in 6 min walk distance correlated with changes in PVR ( r=−0.29 ( 95 % CI −0.41 to −0.17 ) ; p<0.0001 ) and cardiac index ( r=0.23 ( 95 % CI 0.10 to 0.35 ) ; p=0.0004 ) . Conclusions Riociguat improved haemodynamics in patients with inoperable CTEPH or persistent/recurrent CTEPH . Trial registration number NCT00855465 BACKGROUND Distal-type chronic thromboembolic pulmonary hypertension ( CTEPH ) is a fatal disease for which a new therapeutic strategy needs to be developed . We examined the effects of percutaneous transluminal pulmonary angioplasty ( PTPA ) . METHODS AND RESULTS We prospect ively enrolled 12 patients with distal-type CTEPH . After stabilizing their condition with pulmonary vasodilators , we then performed PTPA , which markedly improved pulmonary hemodynamics and pulmonary artery structure , as confirmed by angiography and optical coherence tomography , and also significantly improved their long-term prognosis compared with 39 historical controls . CONCLUSIONS PTPA is a promising therapeutic option for distal-type CTEPH Background — Chronic thromboembolic pulmonary hypertension , a rare complication of acute pulmonary embolism , is characterized by fibrothrombotic obstructions of large pulmonary arteries combined with small-vessel arteriopathy . It can be cured by pulmonary endarterectomy , and can be clinical ly improved by medical therapy in inoperable patients . A European registry was set up in 27 centers to evaluate long-term outcome and outcome correlates in 2 distinct population s of operated and not-operated patients who have chronic thromboembolic pulmonary hypertension . Methods and Results — A total of 679 patients newly diagnosed with chronic thromboembolic pulmonary hypertension were prospect ively included over a 24-month period . Estimated survival at 1 , 2 , and 3 years was 93 % ( 95 % confidence interval [ CI ] , 90–95 ) , 91 % ( 95 % CI , 87–93 ) , and 89 % ( 95 % CI , 86–92 ) in operated patients ( n=404 ) , and only 88 % ( 95 % CI , 83–91 ) , 79 % ( 95 % CI , 74–83 ) , and 70 % ( 95 % CI , 64–76 ) in not-operated patients ( n=275 ) . In both operated and not-operated patients , pulmonary arterial hypertension – targeted therapy did not affect survival estimates significantly . Mortality was associated with New York Heart Association functional class IV ( hazard ratio [ HR ] , 4.16 ; 95 % CI , 1.49–11.62 ; P=0.0065 and HR , 4.76 ; 95 % CI , 1.76–12.88 ; P=0.0021 ) , increased right atrial pressure ( HR , 1.34 ; 95 % CI , 0.95–1.90 ; P=0.0992 and HR , 1.50 ; 95 % CI , 1.20–1.88 ; P=0.0004 ) , and a history of cancer ( HR , 3.02 ; 95 % CI , 1.36–6.69 ; P=0.0065 and HR , 2.15 ; 95 % CI , 1.18–3.94 ; P=0.0129 ) in operated and not-operated patients , respectively . Additional correlates of mortality were bridging therapy with pulmonary arterial hypertension – targeted drugs , postoperative pulmonary hypertension , surgical complications , and additional cardiac procedures in operated patients , and comorbidities such as coronary disease , left heart failure , and chronic obstructive pulmonary disease in not-operated patients . Conclusions — The long-term prognosis of operated patients currently is excellent and better than the outcome of not-operated patients Background —Although pulmonary thromboendarterectomy is increasingly successful for the definitive treatment of chronic thromboembolic pulmonary hypertension ( CTEPH ) , not all patients have surgically accessible disease . Others are poor surgical c and i date s because of comorbid illness . Therefore , for selected patients , we defined and implemented an alternative interventional strategy of balloon pulmonary angioplasty ( BPA ) . Methods and Results —Eighteen patients ( mean age , 51.8 years ; range , 14 to 75 years ) with CTEPH underwent BPA ; they averaged 2.6 procedures ( range , 1 to 5 ) and 6 dilations ( range , 1 to 12 ) . Selection of pulmonary artery segments for dilation required ( 1 ) complete occlusion , ( 2 ) filling defects , or ( 3 ) signs of intravascular webs . After an average of 36 months of follow-up ( range , 0.5 to 66 months ) , the average New York Heart Association class improved from 3.3 to 1.8 ( P < 0.001 ) , and 6-minute walking distances increased from 209 to 497 yards ( P < 0.0001 ) . Pulmonary artery mean pressures decreased from 43.0±12.1 to 33.7±10.2 mm Hg ( P = 0.007 ) . Eleven patients developed reperfusion pulmonary edema ; 3 required mechanical ventilation . Conclusions —BPA reduces pulmonary artery hypertension in patients with CTEPH and is associated with long-term improvement in New York Heart Association class and 6-minute walking distances . BPA is a promising interventional technique that warrants r and omized comparison with medical therapy in CTEPH patients who are not surgical c and i date BACKGROUND Riociguat , a member of a new class of compounds ( soluble guanylate cyclase stimulators ) , has been shown in previous clinical studies to be beneficial in the treatment of chronic thromboembolic pulmonary hypertension . METHODS In this phase 3 , multicenter , r and omized , double-blind , placebo-controlled study , we r and omly assigned 261 patients with inoperable chronic thromboembolic pulmonary hypertension or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy to receive placebo or riociguat . The primary end point was the change from baseline to the end of week 16 in the distance walked in 6 minutes . Secondary end points included changes from baseline in pulmonary vascular resistance , N-terminal pro-brain natriuretic peptide ( NT-proBNP ) level , World Health Organization ( WHO ) functional class , time to clinical worsening , Borg dyspnea score , quality -of-life variables , and safety . RESULTS By week 16 , the 6-minute walk distance had increased by a mean of 39 m in the riociguat group , as compared with a mean decrease of 6 m in the placebo group ( least-squares mean difference , 46 m ; 95 % confidence interval [ CI ] , 25 to 67 ; P<0.001 ) . Pulmonary vascular resistance decreased by 226 dyn·sec·cm(-5 ) in the riociguat group and increased by 23 dyn·sec·cm(-5 ) in the placebo group ( least-squares mean difference , -246 dyn·sec·cm(-5 ) ; 95 % CI , -303 to -190 ; P<0.001 ) . Riociguat was also associated with significant improvements in the NT-proBNP level ( P<0.001 ) and WHO functional class ( P=0.003 ) . The most common serious adverse events were right ventricular failure ( in 3 % of patients in each group ) and syncope ( in 2 % of the riociguat group and in 3 % of the placebo group ) . CONCLUSIONS Riociguat significantly improved exercise capacity and pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension . ( Funded by Bayer HealthCare ; CHEST-1 and CHEST-2 Clinical Trials.gov numbers , NCT00855465 and NCT00910429 , respectively . BACKGROUND Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension . The microvasculopathy of chronic thromboembolic pulmonary hypertension ( CTEPH ) and pulmonary arterial hypertension are similar . METHODS The phase 2 , double-blind , r and omised , placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable . Patients identified as WHO functional class II-IV with a pulmonary vascular resistance ( PVR ) of at least 400 dyn·s/cm5 and a walk distance of 150 - 450 m in 6 min were r and omly assigned ( 1:1 ) , via an interactive voice/web response system , to receive oral macitentan ( 10 mg once a day ) or placebo . Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients . The primary endpoint was resting PVR at week 16 , expressed as percentage of PVR measured at baseline . Analyses were done in all patients who were r and omly assigned to treatment ; safety analyses were done in all patients who received at least one dose of the study drug . This study is registered with Clinical Trials.gov , number NCT02021292 . FINDINGS Between April 3 , 2014 , and March 17 , 2016 , we screened 186 patients for eligibility at 48 hospitals across 20 countries . Of these , 80 patients in 36 hospitals were r and omly assigned to treatment ( 40 patients to macitentan , 40 patients to placebo ) . At week 16 , geometric mean PVR decreased to 73·0 % of baseline in the macitentan group and to 87·2 % in the placebo group ( geometric means ratio 0·84 , 95 % CI 0·70 - 0·99 , p=0·041 ) . The most common adverse events in the macitentan group were peripheral oedema ( 9 [ 23 % ] of 40 patients ) and decreased haemoglobin ( 6 [ 15 % ] ) . INTERPRETATION In MERIT-1 , macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated . FUNDING Actelion Pharmaceuticals BACKGROUND / OBJECTIVES Balloon pulmonary angioplasty ( BPA ) is an emerging therapeutic method in CTEPH . We aim ed to prove the safety and efficacy of refined BPA driven by combined assessment of intra-arterial anatomy ( IVUS/OCT ) and physiology ( pulmonary pressure ratio , PPR ) in non-operable distal CTEPH . METHODS 11 pts ( mean age 76 , 59–84 , 7 males ) were enrolled in the BPA program according to the following inclusion criteria : 1 . Non-operable CTEPH ; 2 . RHC with mPAP > 30 mm Hg ; 3 . At least one segmental perfusion defect at lung scintigraphy ; 4 . WHO class > II . Overall , 9 pts underwent 27 BPA sessions ( mean 3 sessions per patient , range 1–5 ) , 50 pulmonary arteries were dilated ( mean 6 vessels per patient , range 3–9 ; 2.03 dilated arteries per session ) . All the angioplasties were performed according to an algorithm , which incorporated anatomical and functional assessment of targeted lesions . RESULTS We performed BPA of 32 web lesions , 5 ring-like stenosis and 13 complete obstructions . BPA result ed in clinical and hemodynamic improvement . WHO class improved from pre-BPA to post-BPA ( p = 0.018 ) , and 6 MWD increased from 304 m to 384 m ( p = 0.03 ) , NT-proBNP dropped from 1248 pg/ml to 730 pg/ml ( p < 0.001 ) . Mean PAP and PVR decreased ( p = 0.01 ) , while CO and CI increased ( p = 0.01 ) . All dilated arteries were patent at angiographic re assessment . No significant complications occurred and all treated patients are still alive . Insignificant transient reperfusion pulmonary oedema occurred in only 2 patients , who responded well to supplemental oxygen . CONCLUSIONS Refined BPA with assessment of intrapulmonary physiology using a pressure wire and precise evaluation of anatomy with IVUS and OCT provides hemodynamic and functional improvement , with minimal complications in distal non-operable CTEPH . This observation requires further validation in a large prospect i ve study |
12,076 | 25,900,902 | Our present meta- analysis indicates that the Aurora kinase A is an effective prognosticator in solid tumors patients . | OBJECTIVE The prognostic significance of Aurora kinase A expression in cancer patients is currently under debate .
Here , we conducted the first comprehensive meta- analysis of the prognostic relevance of Aurora kinase A associated with survival in solid tumors . | Previously , we and others showed that hypoxia‐inducible factor‐1α ( HIF‐1α ) and transcriptionally upregulated Aurora‐A were required for disease progression in several tumors . Here , we address the clinicopathologic value of Aurora‐A and HIF‐1α in locally advanced nasopharyngeal carcinoma ( NPC ) . Aurora‐A and HIF‐1α expression was semiquantitatively evaluated by immunohistochemistry staining in 144 cases from a r and omized controlled trial . Of these patients , 69 received neoadjuvant chemotherapy plus concurrent chemoradiotherapy , and acted as the training set , and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy were used as the testing set to vali date the prognostic effect of Aurora‐A and HIF‐1α . We found that Aurora‐A and HIF‐1α were highly expressed in NPC , but were deficient in normal adjacent epithelia . In the testing set , Aurora‐A overexpression predicted a shortened 5‐year overall survival ( 59.1 % vs 82.5 % , P = 0.024 ) , progression‐free survival ( 44.8 % vs 79.8 % , P = 0.004 ) , and distant metastasis‐free survival ( 43.0 % vs 17.3 % , P = 0.016 ) . Multivariate regression analysis confirmed that Aurora‐A was indeed an independent prognostic factor for death , recurrence , and distant metastasis both in the testing set and overall patients . Moreover , a positive correlation between Aurora‐A and HIF‐1α was detected ( P = 0.037 ) . Importantly , although HIF‐1α did not show any prognostic effect for patient outcome , the subset with Aurora‐A and HIF‐1α co‐overexpression had the poorest overall , progression‐free , and distant metastasis‐free survival ( all P < 0.05 ) . Our results confirmed that Aurora‐A was an independent prognostic factor for NPC . Aurora‐A combined with HIF‐1α refined the risk definition of the patient subset , thus potentially directing locally advanced NPC patients for more selective therapy . ( Cancer Sci , doi : 10.1111/j.1349‐7006.2012.02332.x , 2012 OBJECTIVES Aurora A kinase ( AAK ) , a key mitotic regulator , is implicated in the pathogenesis of several tumors , including ovarian cancer . This single-arm phase II study assessed single-agent efficacy and safety of the investigational AAK inhibitor MLN8237 ( alisertib ) , in patients with platinum-refractory or -resistant epithelial ovarian , fallopian tube , or primary peritoneal carcinoma . METHODS Adult women with malignant , platinum-treated disease received MLN8237 50 mg orally twice daily for 7 days plus 14 days ' rest ( 21-day cycles ) . The primary endpoint was combined objective tumor response rate per Response Evaluation Criteria in Solid Tumors ( RECIST ) and /or CA-125 criteria . Secondary endpoints included response duration , clinical benefit rate , progression-free survival ( PFS ) , time-to-progression ( TTP ) , and safety . RESULTS Thirty-one patients with epithelial ovarian ( n=25 ) , primary peritoneal ( n=5 ) , and fallopian tube carcinomas ( n=1 ) were enrolled . Responses of 6.9 - 11.1 month duration were observed in 3 ( 10 % ) patients with platinum-resistant ovarian cancer . Sixteen ( 52 % ) patients achieved stable disease with a mean duration of response of 2.86 months and which was durable for ≥3 months in 6 ( 19 % ) . Median PFS and TTP were 1.9 months . Most common drug-related grade ≥3 adverse events were neutropenia ( 42 % ) , leukopenia ( 23 % ) , stomatitis , and thrombocytopenia ( each 19 % ) ; 6 % reported febrile neutropenia . CONCLUSIONS These data suggest that MLN8237 has modest single-agent antitumor activity and may produce responses and durable disease control in some patients with platinum-resistant ovarian cancer . MLN8237 is currently undergoing evaluation in a phase I/II trial with paclitaxel in recurrent ovarian cancer Purpose : This phase I study evaluated the safety , pharmacokinetics , pharmacodynamics , and efficacy of the investigational oral drug MLN8237 ( alisertib ) , a small-molecule Aurora A kinase ( AAK ) inhibitor , in 87 adult patients with advanced solid tumors . Experimental Design : Sequential cohorts of patients received MLN8237 5 to 150 mg orally once daily or twice daily for 7 , 14 , or 21 days , followed by 14 days ' rest per cycle . MLN8237 pharmacokinetics was characterized , and the relative bioavailability of an enteric-coated tablet ( ECT ) formulation was evaluated in reference to the original powder-in-capsule ( PIC ) formulation . Pharmacodynamic effects of MLN8237 on inhibition of AAK activity were evaluated in skin biopsies . Tolerability and response to treatment were assessed . Results : Common toxicities included fatigue , nausea , and neutropenia . Plasma exposures increased dose proportionally ( 5–150 mg/d ) , and were similar for PIC and ECT . The terminal half-life was 23 hours . At the maximum tolerated dose of 50 mg twice daily on the 7-day schedule , the mitotic index of the skin basal epithelium was increased within 24 hours after MLN8237 administration on days 1 and 7 , a finding consistent with AAK inhibition . One ( 1 % ) patient achieved a partial response lasting for more than 1 year and received MLN8237 for 51 cycles ; 20 ( 23 % ) patients achieved stable disease for ≥3 months . Conclusions : This first-in-human trial of MLN8237 showed tolerability and favorable pharmacokinetics in this patient population . The recommended phase II dose of MLN8237 is 50 mg twice daily orally for 7 days in 21-day cycles , which is being evaluated further in the treatment of various solid tumors and hematologic malignancies . Clin Cancer Res ; 18(17 ) ; 4775–84 . © 2012 AACR BACKGROUND Alisertib is an investigational , oral , selective inhibitor of aurora kinase A. We aim ed to investigate the safety and activity of single-agent alisertib in patients with predefined types of advanced solid tumours . METHODS We did a multicentre phase 1/2 study at 40 centres in four countries ( Czech Republic , France , Pol and , and the USA ) . Here , we report results from phase 2 ; enrolment for the study began on Feb 16 , 2010 , and ended on May 3 , 2013 . Adult patients were eligible for the study if they had either breast cancer , small-cell lung cancer , non-small-cell lung cancer , head and neck squamous-cell carcinoma , or gastro-oesophageal adenocarcinoma that had relapsed or was refractory to chemotherapy . Patients had to have undergone two or fewer previous cytotoxic regimens ( four or fewer for breast cancer patients ) , not including adjuvant or neoadjuvant treatments . Enrolment followed a two-stage design : to proceed to the second stage , two or more objective responses were needed in the first 20 response-assessable patients in each of the five tumour cohorts . Alisertib was administered orally in 21-day cycles at the recommended phase 2 dose of 50 mg twice daily for 7 days followed by a break of 14 days . The protocol -specified primary endpoint was the proportion of patients with an objective response , assessed by Response Evaluation Criteria In Solid Tumors version 1.1 in the response-assessable population ( ie , patients with measurable disease who received at least one dose of alisertib and had undergone at least one post-baseline tumour assessment ) . This completed trial is registered with Clinical Trials.gov , NCT01045421 . FINDINGS By May 31 , 2013 , 249 patients had been treated , 53 with breast cancer , 60 with small-cell lung cancer , 26 with non-small-cell lung cancer , 55 with head and neck squamous-cell carcinoma , and 55 with gastro-oesophageal adenocarcinoma . Among response-assessable patients , an objective response was noted in nine ( 18 % , 95 % CI 9 - 32 ) of 49 women with breast cancer , ten ( 21 % , 10 - 35 ) of 48 participants with small-cell lung cancer , one ( 4 % , 0 - 22 ) of 23 patients with non-small-cell lung cancer , four ( 9 % , 2 - 21 ) of 45 people with head and neck squamous-cell carcinoma , and four ( 9 % , 2 - 20 ) of 47 individuals with gastro-oesophageal adenocarcinoma ; all were partial responses . Adverse events were similar across tumour types . The most frequent drug-related grade 3 - 4 adverse events included neutropenia ( n=107 [ 43 % ] ) , leukopenia ( 53 [ 21 % ] ) , and anaemia ( 26 [ 10 % ] ) . Serious drug-related adverse events were reported in 108 ( 43 % ) patients . INTERPRETATION These data support further clinical assessment of alisertib in patients with solid tumours , particularly those with breast cancer and small-cell lung cancer . FUNDING Millennium Pharmaceuticals , Inc , a wholly owned subsidiary of Takeda Pharmaceutical Company Limited |
12,077 | 22,895,949 | The results are promising for some outcomes ( perinatal death , stillbirth and neonatal death ) .
A lack of contrast in training in the intervention and control clusters may have contributed to the null result for stillbirths and an insufficient number of studies may have contributed to the failure to achieve significance for early neonatal deaths .
Despite the additional studies included in this up date d systematic review , there remains insufficient evidence to establish the potential of TBA training to improve peri-neonatal mortality | BACKGROUND Between the 1970s and 1990s , the World Health Organization promoted traditional birth attendant ( TBA ) training as one strategy to reduce maternal and neonatal mortality .
To date , evidence in support of TBA training is limited but promising for some mortality outcomes .
OBJECTIVES To assess the effects of TBA training on health behaviours and pregnancy outcomes . | Background Maternal and newborn mortality rates remain unacceptably high , especially where the majority of births occur in home setting s or in facilities with inadequate re sources . The introduction of emergency obstetric and newborn care services has been proposed by several organizations in order to improve pregnancy outcomes . However , the effectiveness of emergency obstetric and neonatal care services has never been proven . Also unproven is the effectiveness of community mobilization and community birth attendant training to improve pregnancy outcomes . Methods / Design We have developed a cluster-r and omized controlled trial to evaluate the impact of a comprehensive intervention of community mobilization , birth attendant training and improvement of quality of care in health facilities on perinatal mortality in low and middle-income countries where the majority of births take place in homes or first level care facilities . This trial will take place in 106 clusters ( 300 - 500 deliveries per year each ) across 7 sites of the Global Network for Women 's and Children 's Health Research in Argentina , Guatemala , India , Kenya , Pakistan and Zambia . The trial intervention has three key elements , community mobilization , home-based life saving skills for communities and birth attendants , and training of providers at obstetric facilities to improve quality of care . The primary outcome of the trial is perinatal mortality . Secondary outcomes include rates of stillbirth , 7-day neonatal mortality , maternal death or severe morbidity ( including obstetric fistula , eclampsia and obstetrical sepsis ) and 28-day neonatal mortality . Discussion In this trial , we are evaluating a combination of interventions including community mobilization and facility training in an attempt to improve pregnancy outcomes . If successful , the results of this trial will provide important information for policy makers and clinicians as they attempt to improve delivery services for pregnant women and newborns in low-income countries . Trial Registration Clinical Trials.gov OBJECTIVE : Changes in the ability of midwives to perform practical skills , after completion of the Maternal Care Manual of the Perinatal Education Program , were determined . STUDY DESIGN : A prospect i ve , controlled trial in a study town and two control towns . The practical skills of midwives caring for pregnant women in the towns were determined . Subsequently , the Maternal Care Manual was studied by midwives in the study town , and the skills of all midwives were subsequently evaluated . RESULTS : A total of 34 midwives in the study town and 39 midwives in the two control towns were studied . The marks showed a significant ( p ≤ 0.000 ) improvement in the study town when comparing the pre- and postintervention marks . The mean improvement in the study town was 36.6 % . DISCUSSION : The practical skills of midwives improved significantly . The Perinatal Education Program can be implemented with confidence as a distance learning program that is especially suited to the needs of health workers in remote regions The potential for traditional birth attendants ( TBAs ) to improve neonatal health outcomes has largely been overlooked during the current debate regarding the role of TBAs in improving maternal health . R and omly-selected TBAs ( n=93 ) were interviewed to gain a more thorough underst and ing of their knowledge , attitudes , and practice s regarding maternal and newborn care . Practice s , such as using a clean cord-cutting instrument ( 89 % ) and h and -washing before delivery ( 74 % ) , were common . Other beneficial practice s , such as thermal care , were low . Trained TBAs were more likely to wash h and s with soap before delivery , use a clean delivery-kit , and advise feeding colostrum . Although mustard oil massage was a universal practice , 52 % of the TBAs indicated their willingness to consider alternative oils . Low-cost , evidence -based interventions for improving neonatal outcomes might be implemented by TBAs in this setting where most births take place in the home and neonatal mortality risk is high . Continuing efforts to define the role of TBAs may benefit from an emphasis on their potential as active promoters of essential newborn care BACKGROUND Two recent trials have shown that women 's groups can reduce neonatal mortality in poor communities . We assessed the effectiveness of a scaled-up development programme with women 's groups to address maternal and neonatal care in three rural districts of Bangladesh . METHODS 18 clusters ( with a mean population of 27 953 [ SD 5953 ] ) in three districts were r and omly assigned to either intervention or control ( nine clusters each ) by use of stratified r and omisation . For each district , cluster names were written on pieces of paper , which were folded and placed in a bottle . The first three cluster names drawn from the bottle were allocated to the intervention group and the remaining three to control . All clusters received health services strengthening and basic training of traditional birth attendants . In intervention clusters , a facilitator convened 18 groups every month to support participatory action and learning for women , and to develop and implement strategies to address maternal and neonatal health problems . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study period ( Feb 1 , 2005 , to Dec 31 , 2007 ) . Neither study investigators nor participants were masked to treatment assignment . In a population of 229 195 people ( intervention clusters only ) , 162 women 's groups provided coverage of one group per 1414 population . The primary outcome was neonatal mortality rate ( NMR ) . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N54792066 . FINDINGS We monitored outcomes for 36 113 births ( intervention clusters , n=17 514 ; control clusters , n=18 599 ) in a population of 503 163 over 3 years . From 2005 to 2007 , there were 570 neonatal deaths in the intervention clusters and 656 in the control clusters . Cluster-level mean NMR ( adjusted for stratification and clustering ) was 33.9 deaths per 1000 livebirths in the intervention clusters compared with 36.5 per 1000 in the control clusters ( risk ratio 0.93 , 95 % CI 0.80 - 1.09 ) . INTERPRETATION For participatory women 's groups to have a significant effect on neonatal mortality in rural Bangladesh , detailed attention to programme design and context ual factors , enhanced population coverage , and increased enrolment of newly pregnant women might be needed . FUNDING Women and Children First , the UK Big Lottery Fund , Saving Newborn Lives , and the UK Department for International Development We compared the effects of lecture-style ( L ) and interactive problem-based ( I ) educational programs on knowledge , attitude , and practice s ( KAP ) of traditional birth attendants in the Philippines . Participants in two cities were r and omized to L and I teaching groups and completed a question naire pre- , immediately post- , and 6 months after education . Mothers reported practice s of the attendants . There was significant improvement in mean knowledge scores ( L 16.8 to 17.9 and I 16.4 to 19.3 ) in group I. Group I scores continued to improve 6 months later . Attitude scores significantly improved in both groups and decreased 6 months later , indicating a need for reinforcement . Certain undesirable practice s such as late cord clamping and holding the baby upside down following birth were changed in both groups . Actual practice s reported by mothers were carried out less frequently than indicated by providers , indicating a need for further education and possibly provision of adequate re sources . Interactive ( I ) learning is a preferred method for education of traditional birth attendants Background Birth attendance by trained health workers is low in rural Nepal . Local participation in improving health services and increased interaction between health systems and communities may stimulate dem and for health services . Significant increases in birth attendance by trained health workers may be affected through community mobilisation by local women 's groups and health management committee strengthening . We will test the effect of community mobilisation through women 's groups , and health management committee strengthening , on institutional deliveries and home deliveries attended by trained health workers in Makwanpur District . Design Cluster r and omised controlled trial involving 43 village development committee clusters . 21 clusters will receive the intervention and 22 clusters will serve as control areas . In intervention areas , Female Community Health Volunteers are supported in convening monthly women 's groups . The groups work through an action research cycle in which they consider barriers to institutional delivery , plan and implement strategies to address these barriers with their communities , and evaluate their progress . Health management committees participate in three-day workshops that use appreciative inquiry methods to explore and plan ways to improve maternal and newborn health services . Follow-up meetings are conducted every three months to review progress . Primary outcomes are institutional deliveries and home deliveries conducted by trained health workers . Secondary outcome measures include uptake of antenatal and postnatal care , neonatal mortality and stillbirth rates , and maternal morbidity . Trial registration numberIS RCT BACKGROUND Newborn deaths account for 57 % of deaths in children younger than 5 years in Pakistan . Although a large programme of trained lady health workers ( LHWs ) exists , the effectiveness of this training on newborn outcomes has not been studied . We aim ed to evaluate the effectiveness of a community-based intervention package , principally delivered through LHWs working with traditional birth attendants and community health committees , for reduction of perinatal and neonatal mortality in a rural district of Pakistan . METHODS We undertook a cluster r and omised trial between February , 2006 , and March , 2008 , in Hala and Matiari subdistricts , Pakistan . Catchment areas of primary care facilities and all affiliated LHWs were used to define clusters , which were allocated to intervention and control groups by restricted , stratified r and omisation . The intervention package delivered by LHWs through group sessions consisted of promotion of antenatal care and maternal health education , use of clean delivery kits , facility births , immediate newborn care , identification of danger signs , and promotion of careseeking ; control clusters received routine care . Independent data collectors undertook quarterly household surveillance to capture data for births , deaths , and household practice s related to maternal and newborn care . Data collectors were masked to cluster allocation ; those analysing data were not . The primary outcome was perinatal and all-cause neonatal mortality . Analysis was by intention to treat . This trial is registered , IS RCT N16247511 . FINDINGS 16 clusters were assigned to intervention ( 23,353 households , 12,391 total births ) and control groups ( 23,768 households , 11,443 total births ) . LHWs in the intervention clusters were able to undertake 4428 ( 63 % ) of 7084 planned group sessions , but were only able to visit 2943 neonates ( 24 % ) of a total 12,028 livebirths in their catchment villages . Stillbirths were reduced in intervention clusters ( 39·1 stillbirths per 1000 total births ) compared with control ( 48·7 per 1000 ; risk ratio [ RR ] 0·79 , 95 % CI 0·68 - 0·92 ; p=0·006 ) . The neonatal mortality rate was 43·0 deaths per 1000 livebirths in intervention clusters compared with 49·1 per 1000 in control groups ( RR 0·85 , 0·76 - 0·96 ; p=0·02 ) . INTERPRETATION Our results support the scale-up of preventive and promotive maternal and newborn interventions through community health workers and emphasise the need for attention to issues of programme management and coverage for such initiatives to achieve maximum potential . FUNDING WHO ; Saving Newborn Lives Program of Save the Children USA , funded by the Bill & Melinda Gates Foundation OBJECTIVES In a community r and omized trial , we aim ed to promote exclusive breastfeeding and appropriate complementary feeding practice s in under-twos to ascertain the feasibility of using available channels for nutrition counselling , their relative performance and the relationship between intensity of counselling and behaviour change . We also assessed whether using multiple opportunities to impart nutrition education adversely affected routine activities . METHODS We conducted a community r and omized , controlled effectiveness trial in rural Haryana , India , with four intervention and four control communities . We trained health and nutrition workers in the intervention communities to counsel mothers at multiple contacts on breastfeeding exclusively for 6 months and on appropriate complementary feeding practice s thereafter . The intervention was not just training health and nutrition workers in counselling but included community and health worker mobilization . FINDINGS In the intervention group , about 32 % of caregivers were counselled by traditional birth attendants at birth . The most frequent sources of counselling from birth to 3 months were immunization sessions ( 45.1 % ) and home visits ( 32.1 % ) , followed closely by weighing sessions ( 25.5 % ) ; from 7 to 12 months , home visits ( 42.6 % ) became more important than the other two . An increase in the number of channels through which caregivers were counselled was positively associated with exclusive breastfeeding prevalence at 3 months ( p = 0.002 ) , consumption of milk/cereal gruel or mix use at 9 months ( p = 0.004 ) and 18 months ( p = 0.003 ) , undiluted milk at 9 months ( p<0.0001 ) and 24 hour non-breast-milk energy intakes at 18 months ( p = 0.023 ) , after controlling for potential confounding factors . Intervention areas , compared with the control , had higher coverage for vitamin A ( 45 % vs. 11.5 % ) and iron folic acid ( 45 % vs. 0.4 % ) supplementation . CONCLUSIONS Using multiple available opportunities and workers for counselling caregivers was feasible , result ed in high coverage and impact , and instead of disrupting ongoing services , result ed in their improvement Background In many developing countries , the majority of births are attended by traditional birth attendants , who lack formal training in neonatal resuscitation and other essential care required by the newly born infant . In these countries , the major causes of neonatal mortality are birth asphyxia , infection , and low-birth-weight/prematurity . Death from these causes is potentially modifiable using low-cost interventions , including neonatal resuscitation training . The purpose of this study was to evaluate the effect on perinatal mortality of training birth attendants in a rural area of the Democratic Republic of Congo ( DRC ) using two established programs . Methods This study , a secondary analysis of DRC-specific data collected during a multi-country study , was conducted in two phases . The effect of training using the WHO Essential Newborn Care ( ENC ) program was evaluated using an active baseline design , followed by a cluster r and omized trial of training using an adaptation of a neonatal resuscitation program ( NRP ) . The perinatal mortality rates before ENC , after ENC training , and after r and omization to additional NRP training or continued care were compared . In addition , the influence of time following resuscitation training was investigated by examining change in perinatal mortality during sequential three-month increments following ENC training . Results More than two-thirds of deliveries were attended by traditional birth attendants and occurred in homes ; these proportions decreased after ENC training . There was no apparent decline in perinatal mortality when the outcome of all deliveries prior to ENC training was compared to those after ENC but before NRP training . However , there was a gradual but significant decline in perinatal mortality during the year following ENC training ( RR 0.73 ; 95 % CI : 0.56 - 0.96 ) , which was independently associated with time following training . The decline was attributable to a decline in early neonatal mortality . NRP training had no demonstrable effect on early neonatal mortality . Conclusion Training DRC birth attendants using the ENC program reduces perinatal mortality . However , a period of utilization and re-enforcement of training may be necessary before a decline in mortality occurs . ENC training has the potential to be a low cost , high impact intervention in developing countries . Trial registration This trial has been registered at http://www . clinical trials.gov ( identifier NCT00136708 ) Objective To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a re source poor country with limited access to healthcare . Design Prospect i ve , cluster r and omised and controlled effectiveness study . Setting Lufwanyama , an agrarian , poorly developed district located in the Copperbelt province , Zambia . All births carried out by study birth attendants occurred at mothers ’ homes , in rural village setting s. Participants 127 traditional birth attendants and mothers and their newborns ( 3559 infants delivered regardless of vital status ) from Lufwanyama district . Interventions Using an unblinded design , birth attendants were cluster r and omised to intervention or control groups . The intervention had two components : training in a modified version of the neonatal resuscitation protocol , and single dose amoxicillin coupled with facilitated referral of infants to a health centre . Control birth attendants continued their existing st and ard of care ( basic obstetric skills and use of clean delivery kits ) . Main outcome measures The primary outcome was the proportion of liveborn infants who died by day 28 after birth , with rate ratios statistically adjusted for clustering . Secondary outcomes were mortality at different time points ; and comparison of causes of death based on verbal autopsy data . Results Among 3497 deliveries with reliable information , mortality at day 28 after birth was 45 % lower among liveborn infants delivered by intervention birth attendants than control birth attendants ( rate ratio 0.55 , 95 % confidence interval 0.33 to 0.90 ) . The greatest reductions in mortality were in the first 24 hours after birth : 7.8 deaths per 1000 live births for infants delivered by intervention birth attendants compared with 19.9 per 1000 for infants delivered by control birth attendants ( 0.40 , 0.19 to 0.83 ) . Deaths due to birth asphyxia were reduced by 63 % among infants delivered by intervention birth attendants ( 0.37 , 0.17 to 0.81 ) and by 81 % within the first two days after birth ( 0.19 , 0.07 to 0.52 ) . Stillbirths and deaths from serious infection occurred at similar rates in both groups . Conclusions Training traditional birth attendants to manage common perinatal conditions significantly reduced neonatal mortality in a rural African setting . This approach has high potential to be applied to similar setting s with dispersed rural population s. Trial registration Clinical trials.gov NCT00518856 A r and omized , double blind , placebo-controlled community based trial of Maloprim ( pyrimethamine 12.5 mg+dapsone 100 mg ) administered to primigravid pregnant women by Traditional Birth Attendants was carried out in a rural area of The Gambia , West Africa . Placental histology showed less malaria infection in women who received chemoprophylaxis than in those who received placebo . The birth weight of children born to women who received chemoprophylaxis was increased by an average of 153 g. Within the treatment groups , there were no significant differences in the birthweights of babies born to women who had histological evidence of malaria infection of the placenta compared to those who had no malaria infection . This study confirms the beneficial effect of malaria prophylaxis for primigravid pregnant women but questions the mechanism by which malaria affects foetal development OBJECTIVE : To assess the ability of midwives to interpret antenatal cards and partograms correctly following completion of the Maternal Care Manual of the Perinatal Education Programme . STUDY DESIGN : We conducted a prospect i ve , controlled trial in a study town and two control towns in the Eastern Cape Province of South Africa . All 93 midwives caring for pregnant women in the three towns were included in the study . Sample s were compared using the two-tailed Student ’s t-test . RESULTS : The marks achieved by the study group for questions from the antenatal card and the partogram improved by 33.0 % ( p < 0.001 ) and 17.5 % ( p = 0.001 ) , respectively . No changes were observed in the control group . CONCLUSION : Midwives that studied the Maternal Care Manual significantly improved their ability to interpret clinical information and apply knowledge . If this ability is applied in clinical practice , a reduction in maternal and perinatal deaths is possible A r and omised , controlled trial was carried out to determine whether suckling immediately after birth reduces the frequency of post-partum haemorrhage ( PPH ) , the mean blood loss , and the frequency of retained placenta . The trial subjects were attended by traditional birth attendants ( TBAs ) , and r and omisation was by TBA and not by mother . 68 TBAs attended a course on third stage management and data collection ; 19 had to be excluded from the trial . 23 TBAs in the early suckling group and 26 in the control group recorded blood loss in 2104 and 2123 deliveries of liveborn singletons , respectively . The frequency of PPH ( loss greater than 500 ml ) was 7.9 % in the suckling group and 8.4 % in the control group and the mean blood loss 258 ml and 256 ml , respectively . Neither of these results differed significantly between the groups . Analysis of the results by individual TBA showed no significant difference between the groups . The frequency of PPH in women of higher parity and in those with multiple pregnancies and stillbirths was high , as expected , which seems to vali date the results . The frequency of retained placenta was too low to be analysed BACKGROUND Exclusive breastfeeding is recommended until age 6 months . We assessed the feasibility , effectiveness , and safety of an educational intervention to promote exclusive breastfeeding for this length of time in India . METHODS We developed the intervention through formative research , pair-matched eight communities on their baseline characteristics , and r and omised one of each pair to receive the intervention and the other to no specific intervention . We trained health and nutrition workers in the intervention communities to counsel mothers for exclusive breastfeeding at multiple opportunities . We enrolled 1115 infants born in the 9 months after training-552 in the intervention and 473 in the control communities . Feeding at age 3 months , and anthropometry and of diarrhoea prevalence at age 3 months and 6 months were assessed . All analyses were by intention to treat . FINDINGS We assessed 483 and 412 individuals at 3 months in the intervention and control groups , respectively , and 468 and 412 at 6 months . At 3 months , exclusive breastfeeding rates were 79 % ( 381 ) in the intervention and 48 % ( 197 ) in the control communities ( odds ratio 4.02 , 95 % CI 3.01 - 5.38 , p<0.0001 ) . The 7-day diarrhoea prevalence was lower in the intervention than in the control communities at 3 months ( 0.64 , 0.44 - 0.95 , p=0.028 ) and 6 months ( 0.85 , 0.72 - 0.99 , p=0.04 ) . The mean weights and lengths , and the proportion with weight-for-height or height-for-age Z scores of 2 or less , at age 3 months and 6 months did not differ much between groups . Intervention effect on exclusive breastfeeding , diarrhoeal morbidity , and anthropometry at age 6 months in the low-birthweight subgroup was similar to that for all births . INTERPRETATION Promotion of exclusive breastfeeding until age 6 months in a developing country through existing primary health-care services is feasible , reduces the risk of diarrhoea , and does not lead to growth faltering A r and omized , double-blind , placebo-controlled community-based trial of oral iron supplementation ( 200 mg ferrous sulphate daily ) administered to multigravid pregnant women by traditional birth attendants ( TBAs ) was carried out in a rural area of The Gambia . Iron supplementation led to a significant reduction in the prevalence of anaemia and of iron deficiency . Iron supplementation was not accompanied by increased susceptibility to malaria infection ; there was no difference in the prevalence and severity of peripheral blood or placental malaria infection between the 2 groups of women . The birth weight of children born to women who received iron prophylaxis was increased by an average of 56 g. It is concluded that oral iron prophylaxis can be successfully delivered through TBAs integrated into a primary health care programme . This simple intervention can produce significant beneficial effects on the health of the mother without inducing increased susceptibility to malaria and has the potential for reducing perinatal mortality by increasing birth weight OBJECTIVE To provide relevant details on how interventions in the Lufwanyama Neonatal Survival Project ( LUNESP ) were developed and how Zambian traditional birth attendants ( TBAs ) were trained to perform them . METHODS The study tested 2 interventions : a simplified version of the American Academy of Pediatrics ' neonatal resuscitation protocol ( NRP ) ; and antibiotics with facilitated referral ( AFR ) . RESULTS Key elements that enabled the positive study result were : focusing on common and correctible causes of mortality ; selecting a study population with high unmet public health need ; early community mobilization to build awareness and support ; emphasizing simplicity in the intervention technology and algorithms ; using a traditional training approach appropriate to students with low literacy rates ; requiring TBAs to demonstrate their competence before completing each workshop ; and minimizing attrition of skills by retraining and reassessing the TBAs regularly throughout the study . CONCLUSION An effective NRP training model was created that is suitable for community-based neonatal interventions , in research or programmatic setting s , and by practitioners with limited obstetric skills and low rates of literacy . Clinical trials.gov NCT00518856 BACKGROUND Of the 3.7 million neonatal deaths and 3.3 million stillbirths each year , 98 % occur in developing countries . An evaluation of community-based interventions design ed to reduce the number of these deaths is needed . METHODS With the use of a train-the-trainer model , local instructors trained birth attendants from rural communities in six countries ( Argentina , Democratic Republic of Congo , Guatemala , India , Pakistan , and Zambia ) in the World Health Organization Essential Newborn Care course ( which focuses on routine neonatal care , resuscitation , thermoregulation , breast-feeding , " kangaroo " [ skin-to-skin ] care , care of the small baby , and common illnesses ) and ( except in Argentina ) in a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program ( which teaches basic resuscitation in depth ) . The Essential Newborn Care intervention was assessed among 57,643 infants with the use of a before- and -after design . The Neonatal Resuscitation Program intervention was assessed as a cluster-r and omized , controlled trial involving 62,366 infants . The primary outcome was neonatal death in the first 7 days after birth . RESULTS The 7-day follow-up rate was 99.2 % . After birth attendants were trained in the Essential Newborn Care course , there was no significant reduction from baseline in the rate of neonatal death from all causes in the 7 days after birth ( relative risk with training , 0.99 ; 95 % confidence interval [ CI ] , 0.81 to 1.22 ) or in the rate of perinatal death ; there was a significant reduction in the rate of stillbirth ( relative risk with training , 0.69 ; 95 % CI , 0.54 to 0.88 ; P=0.003 ) . In clusters of births in which attendants had been r and omly assigned to receive training in the Neonatal Resuscitation Program , as compared with control clusters , there was no reduction in the rates of neonatal death in the 7 days after birth , stillbirth , or perinatal death . CONCLUSIONS The rate of neonatal death in the 7 days after birth did not decrease after the introduction of Essential Newborn Care training of community-based birth attendants , although the rate of stillbirths was reduced . Subsequent training in the Neonatal Resuscitation Program did not significantly reduce the mortality rates . ( Clinical Trials.gov number , NCT00136708 . OBJECTIVES Determine safety of household management of postpartum hemorrhage ( PPH ) with 1000 microg of rectal misoprostol , and assess possible reduction in referrals and the need for additional interventions . METHODS Traditional birth attendants ( TBAs ) in Kigoma , Tanzania were trained to recognize PPH ( 500 ml of blood loss ) . Blood loss measurement was st and ardized by using a local garment , the " kanga " . TBAs in the intervention area gave 1000 microg of misoprostol rectally when PPH occurred . Those in the non-intervention area referred the women to the nearest facility . RESULTS 454 women in the intervention and 395 in the non-intervention areas were eligible . 111 in the intervention area and 73 in the non-intervention had PPH . Fewer than 2 % of the PPH women in the intervention area were referred , compared with 19 % in the non-intervention . CONCLUSION Misoprostol is a low cost , easy to use technology that can control PPH even without a medically trained attendant The search for indicators for monitoring progress toward safe motherhood has prompted research into population -based measures of obstetric morbidity . One possible such measure is based on women 's reports of their past childbirth experiences . In this prospect i ve study in three hospitals in South Kalimantan , Indonesia , the accuracy of women 's reporting of severe birth-related complications was examined . The findings of this study suggest that poor agreement exists between the way women report their experience of childbirth and the way doctors diagnose obstetric problems , although the degree of agreement varies with the type of complication . Question naires relying on women 's experience of childbirth will tend to overestimate the prevalence of medically diagnosed obstetric problems such as those associated with excessive vaginal bleeding or dysfunctional labor . Questions suggestive of eclampsia may be more promising , although the small number of eclamptic women in this study precludes firm conclusions This study was design ed to assess the utility and impact on perinatal mortality of a model traditional birth attendant ( TBA ) training program in rural Mozambique by comparing birth attendance and outcomes in similar communities with and without trained TBAs . Birth attendants and pregnancy outcomes were compared in 1 ) communities with good access to trained TBAs , 2 ) r and omly selected , comparable communities with no access to trained TBAs , and 3 ) communities with good access to functioning maternities . Information was collected by interviews with women in r and omly selected households . A total of 4,169 women were interviewed who reported on 3,616 completed pregnancies , which result ed in a birth or fetal death . Among women with good access to trained TBAs , 33 % reported giving birth attended by a trained TBA , 43 % reported giving birth at a health facility , and 24 % reported giving birth attended by an untrained person . Among women without access to trained TBAs , 58 % reported giving birth at health facilities , and 42 % reported attendance by untrained persons . Among women with access to functioning maternity centers , 77 % reported giving birth at a health facility and 22 % said their birth was attended by an untrained person . There was no significant difference in perinatal or infant mortality among the groups . This study demonstrated a preference for health facility deliveries among rural Mozambican women with good access to trained TBAs . It also failed to demonstrate a reduction in perinatal or infant mortality associated with TBA training . Women said they preferred to deliver in health facilities because conditions were considered better and interventions could be performed if needed . The preference for health facility birth over home birth with a TBA may have been related to difficulties with TBA neighbors and their families or fear of potential witchcraft . Efforts to promote TBA training should be balanced with support for birthing services based in health facilities |
12,078 | 26,212,714 | MAIN RESULTS We included 14 studies ( 15 records ) with a total of 2275 participants ; although we included only 2272 participants in the final analyses as there were missing data for three participants from one included study .Regarding data equivalence , in both controlled and uncontrolled setting s , the included studies found no significant differences in the mean overall scores between apps and other delivery modes , and that all correlation coefficients exceeded the recommended thresholds for data equivalence .
Regarding adherence to the sampling protocol , apps may be better than paper but no different from SMS .
We identified multiple definitions of acceptability to respondents , with inconclusive results : preference ; ease of use ; willingness to use a delivery mode ; satisfaction ; effectiveness of the system informativeness ; perceived time taken to complete the survey question naire ; perceived benefit of a delivery mode ; perceived usefulness of a delivery mode ; perceived ability to complete a survey question naire ; maximum length of time that participants would be willing to use a delivery mode ; and reactivity to the delivery mode and its successful integration into respondents ' daily routine .
Our results , based on a narrative synthesis of the evidence , suggest that apps might not affect data equivalence as long as the intended clinical application of the survey question naire , its intended frequency of administration and the setting in which it was vali date d remain unchanged . | BACKGROUND Self-administered survey question naires are an important data collection tool in clinical practice , public health research and epidemiology .
They are ideal for achieving a wide geographic coverage of the target population , dealing with sensitive topics and are less re source -intensive than other data collection methods .
These survey question naires can be delivered electronically , which can maximise the scalability and speed of data collection while reducing cost .
In recent years , the use of apps running on consumer smart devices ( i.e. , smartphones and tablets ) for this purpose has received considerable attention .
However , variation in the mode of delivering a survey question naire could affect the quality of the responses collected .
OBJECTIVES To assess the impact that smartphone and tablet apps as a delivery mode have on the quality of survey question naire responses compared to any other alternative delivery mode : paper , laptop computer , tablet computer ( manufactured before 2007 ) , short message service ( SMS ) and plastic objects . | Adherence and accuracy of self-monitoring of dietary intake influences success in weight management interventions . Information technologies such as computers and smartphones have the potential to improve adherence and accuracy by reducing the burden associated with monitoring dietary intake using traditional paper-based food records . We evaluated the acceptability and accuracy of three different 7-day food record methods ( online accessed via computer , online accessed via smartphone , and paper-based ) . Young women ( N=18 ; aged 23.4±2.9 years ; body mass index 24.0±2.2 ) completed the three 7-day food records in r and om order with 7-day washout periods between each method . Total energy expenditure ( TEE ) was derived from resting energy expenditure ( REE ) measured by indirect calorimetry and physical activity level ( PAL ) derived from accelerometers ( TEE = REE × PAL ) . Accuracy of the three methods was assessed by calculating absolute ( energy intake [EI]-TEE ) and percentage difference ( EI/TEE × 100 ) between self-reported EI and TEE . Acceptability was assessed via question naire . Mean±st and ard deviation TEE was 2,185±302 kcal/day and EI was 1,729±249 kcal/day , 1,675±287kcal/day , and 1,682±352 kcal/day for computer , smartphone , and paper records , respectively . There were no significant differences between absolute and percentage differences between EI and TEE for the three methods : computer , -510±389 kcal/day ( 78 % ) ; smartphone , -456±372 kcal/day ( 80 % ) ; and paper , -503±513 kcal/day ( 79 % ) . Half of participants ( n=9 ) preferred computer recording , 44.4 % preferred smartphone , and 5.6 % preferred paper-based records . Most participants ( 89 % ) least preferred the paper-based record . Because online food records completed on either computer or smartphone were as accurate as paper-based records but more acceptable to young women , they should be considered when self-monitoring of intake is recommended to young women Introduction Electronic self-monitoring of affective symptoms using cell phones is suggested as a practical and inexpensive way to monitor illness activity and identify early signs of affective symptoms . It has never been tested in a r and omised clinical trial whether electronic self-monitoring improves outcomes in bipolar disorder . We are conducting a trial testing the effect of using a Smartphone for self-monitoring in bipolar disorder . Methods We developed the MONARCA application for And roid-based Smartphones , allowing patients suffering from bipolar disorder to do daily self-monitoring — including an interactive feedback loop between patients and clinicians through a web-based interface . The effect of the application was tested in a parallel-group , single-blind r and omised controlled trial so far including 78 patients suffering from bipolar disorder in the age group 18–60 years who were given the use of a Smartphone with the MONARCA application ( intervention group ) or to the use of a cell phone without the application ( placebo group ) during a 6-month study period . The study was carried out from September 2011 . The outcomes were changes in affective symptoms ( primary ) , social functioning , perceived stress , self-rated depressive and manic symptoms , quality of life , adherence to medication , stress and cognitive functioning ( secondary and tertiary ) . Analysis Recruitment is ongoing . Ethics Ethical permission has been obtained . Dissemination Positive , neutral and negative findings of the study will be published . Registration details The trial is approved by the Regional Ethics Committee in The Capital Region of Denmark ( H-2 - 2011 - 056 ) and The Danish Data Protection Agency ( 2013 - 41 - 1710 ) . The trial is registered at Clinical Trials.gov as NCT01446406 Background Refugees experience multiple health and social needs . This requires an integrated approach to care in the countries of resettlement , including Canada . Perhaps , interactive eHealth tools could build bridges between medical and social care in a timely manner . The authors developed and piloted a multi-risk Computer-assisted Psychosocial Risk Assessment ( CaPRA ) tool for Afghan refugees visiting a community health center . The iPad based CaPRA survey was completed by the patients in their own language before seeing the medical practitioner . The computer then generated individualized feedback for the patient and provider with suggestions about available services . Methods A pilot r and omized trial was conducted with adult Afghan refugees who could read Dari/Farsi or English language . Consenting patients were r and omly assigned to the CaPRA ( intervention ) or usual care ( control ) group . All patients completed a paper-pencil exit survey . The primary outcome was patient intention to see a psychosocial counselor . The secondary outcomes were patient acceptance of the tool and visit satisfaction . Results Out of 199 approached patients , 64 were eligible and 50 consented and one withdrew ( CaPRA = 25 ; usual care = 24 ) . On average , participants were 37.6 years of age and had lived 3.4 years in Canada . Seventy-two percent of participants in CaPRA group had intention to visit a psychosocial counselor , compared to 46 % in usual care group [ X2 (1)=3.47 , p = 0.06 ] . On a 5-point scale , CaPRA group participants agreed with the benefits of the tool ( mean = 4 ) and were ‘ unsure ’ about possible barriers to interact with the clinicians ( mean = 2.8 ) or to privacy of information ( mean = 2.8 ) in CaPRA mediated visits . On a 5-point scale , the two groups were alike in patient satisfaction ( mean = 4.3 ) . Conclusion The studied eHealth tool offers a promising model to integrate medical and social care to address the health and settlement needs of refugees . The tool ’s potential is discussed in relation to implication s for healthcare practice . The study should be replicated with a larger sample to generalize the results while controlling for potential confounders Background The electronic self report assessment - cancer ( ESRA-C ) , has been shown to reduce symptom distress during cancer therapy The purpose of this analysis was to evaluate aspects of how the ESRA-C intervention may have result ed in lower symptom distress ( SD ) . Methods Patients at two cancer centers were r and omized to ESRA-C assessment only ( control ) or the Web-based ESRA-C intervention delivered to patients ’ homes or to a tablet in clinic . The intervention allowed patients to self-monitor symptom and quality of life ( SxQOL ) between visits , receive self-care education and coaching to report SxQOL to clinicians . Summaries of assessment s were delivered to clinicians in both groups . Audio-recordings of clinic visits made 6 weeks after treatment initiation were coded for discussion s of 26 SxQOL issues , focusing on patients ’ /caregivers ’ coached verbal reports of SxQOL severity , pattern , alleviating/aggravating factors and requests for help . Among issues identified as problematic , two measures were defined for each patient : the percent SxQOL reported that included a coached statement , and an index of verbalized coached statements per SxQOL . The Wilcoxon rank test was used to compare measures between groups . Clinician responses to problematic SxQOL were compared . A mediation analysis was conducted , exploring the effect of verbal reports on SD outcomes . Results 517 ( 256 intervention ) clinic visits were audio-recorded . General discussion of problematic SxQOL was similar in both groups . Control group patients reported a median 75 % of problematic SxQOL using any specific coached statement compared to a median 85 % in the intervention group ( p = .0009 ) . The median report index of coached statements was 0.25 for the control group and 0.31 for the intervention group ( p = 0.008 ) . Fatigue , pain and physical function issues were reported significantly more often in the intervention group ( all p < .05 ) . Clinicians ' verbalized responses did not differ between groups . Patients ' verbal reports did not mediate final SD outcomes ( p = .41 ) . Conclusions Adding electronically-delivered , self-care instructions and communication coaching to ESRA-C promoted specific patient descriptions of problematic SxQOL issues compared with ESRA-C assessment alone . However , clinician verbal responses were no different and subsequent symptom distress group differences were not mediated by the patients ' reports . Trial registration NCT00852852 ; 26 Feb 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 Compared to females , males experience higher rates of chronic disease and mortality , yet few health promotion initiatives are specifically aim ed at men . Therefore , the aim of the ManUp Study is to examine the effectiveness of an IT-based intervention to increase the physical activity and nutrition behaviour and literacy in middle-aged males ( aged 35–54 years ) . Method / Design The study design was a two-arm r and omised controlled trial , having an IT-based ( applying website and mobile phones ) and a print-based intervention arm , to deliver intervention material s and to promote self-monitoring of physical activity and nutrition behaviours . Participants ( n = 317 ) were r and omised on a 2:1 ratio in favour of the IT-based intervention arm . Both intervention arms completed assessment s at baseline , 3 , and 9 months . All participants completed self-report assessment s of physical activity , sitting time , nutrition behaviours , physical activity and nutrition literacy , perceived health status and socio-demographic characteristics . A r and omly selected sub- sample in the IT-based ( n = 61 ) and print-based ( n = 30 ) intervention arms completed objective measures of height , weight , waist circumference , and physical activity as measured by accelerometer ( Actigraph GT3X ) . The average age of participants in the IT-based and print-based intervention arm was 44.2 and 43.8 years respectively . The majority of participants were employed in professional occupations ( IT-based 57.6 % , Print-based 54.2 % ) and were overweight or obese ( IT-based 90.8 % , Print-based 87.3 % ) . At baseline a lower proportion of participants in the IT-based ( 70.2 % ) group agreed that 30 minutes of physical activity each day is enough to improve health compared to the print-based ( 82.3 % ) group ( p = .026 ) . The IT-based group consumed a significantly lower number of serves of red meat in the previous week , compared to the print-based group ( p = .017 ) . No other significant between-group differences were observed at baseline . Discussion The ManUp Study will examine the effectiveness of an IT-based approach to improve physical activity and nutrition behaviour and literacy . Study outcomes will provide much needed information on the efficacy of this approach in middle aged males , which is important due to the large proportions of males at risk , and the potential reach of IT-based interventions .Trial registration BACKGROUND AND PURPOSE Epi Data and Epi Info are often used together by public health agencies around the world , particularly in developing countries , to meet their needs of low-cost public health data management ; however , the current open source data management technology lacks a mobile component to meet the needs of mobile public health data collectors . The goal of this project is to explore the opportunity of filling this gap through developing and trial of a personal digital assistant ( PDA ) based data collection /entry system . It evaluated whether such a system could increase efficiency and reduce data transcription errors for public surveillance data collection in developing countries represented by Fiji . METHODS A generic PDA-based data collection software eSTEPS was developed . The software and the data collected using it directly interfaces with Epi Data . A field trial was conducted to test the viability of public health surveillance data collection using eSTEPS . The design was a r and omised , controlled trial with cross-over design . 120 participants recruited from the Fiji School of Medicine were r and omly assigned to be interviewed by one of six interviewers in one of the two ways : ( 1 ) paper-based survey followed by PDA survey and ( 2 ) PDA survey followed by paper-based survey . Data quality was measured by error rates ( logical range errors/inconsistencies , skip errors , missing values , date or time field errors and incorrect data type ) . Work flow and cost were evaluated in three stages of the survey process : ( 1 ) preparation of data collection instrument , ( 2 ) data collection and ( 3 ) data entry , validation and cleaning . User acceptance was also evaluated in the two groups of participants : ( 1 ) data collectors and ( 2 ) survey participants . RESULTS None of the errors presented in 20.8 % of the paper question naires was found in the data set collected using PDA . Sixty-two percent of the participants perceived that the PDA-based question naire took less time to complete . Data entry , validation and cleaning for the PDA-based data collection from 120 participants took a total of 1.5h , a 93.26 % reduction of time from 20.5h required using paper and pen . The cost is also significantly reduced with PDA-based protocol . Both data collectors and participants prefer to use PDA instead of paper for data collection . The trial results prove that eSTEPS is a feasible solution for public health surveillance data collection in the field . Several deficiencies of the software were also identified and would be addressed in the next version . CONCLUSION eSTEPS offers the potential to meet the need for an effective mobile public health data collection tool for use in the field . The eSTEPS field trial proves that PDA was more efficient than paper for public health survey data collection . It also significantly reduced errors in data entry . The later benefit was derived from the software providing its users with the flexibility of building their own constraints to control the data type , range and logic of data entry The more consistently someone records their food intake the more likely they are to lose weight . We hypothesized that subjects who kept track via their preferred method would demonstrate higher adherence and therefore improved outcomes compared to those who used a non-preferred method . Participants were r and omly assigned to use a paper , PDA , or Web-based diary and classified as " Preferred " if they used their preferred method and " Non-Preferred " if they did not . Days adherent to diary use were collected for 12 weeks . Weight , % body fat , waist circumference , and self-efficacy scores were measured at baseline , 6 and 12 weeks . Thirty nine participants completed the 12 week study . Fifty nine percent were male . The mean age was 35 and mean baseline BMI was 33 kg/m(2 ) ( + /-3.5 ) . Forty four % ( n=17 ) used their " Preferred " diary method and 56 % ( n=22 ) did not . Participants who used their preferred diary were more adherent to recording both food intake ( 64.2 % vs. 43.4 % , p=.015 ) and exercise ( 60.6 % vs. 31.2 % , p=.001 ) . Though no difference was seen between groups on weight management outcomes , these results suggest that diary preference affects adherence to diary use 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 Background Mobile phone – based assessment may represent a cost-effective and clinical ly effective method of monitoring psychotic symptoms in real-time . There are several software options , including the use of native smartphone applications and text messages ( short message service , SMS ) . Little is known about the strengths and limitations of these two approaches in monitoring symptoms in individuals with serious mental illness . Objective The objective of this study was to compare two different delivery modalities of the same diagnostic assessment for individuals with non-affective psychosis — a native smartphone application employing a graphical , touch user interface against an SMS text-only implementation . The overall hypothesis of the study was that patient participants with sewrious mental illness would find both delivery modalities feasible and acceptable to use , measured by the quantitative post- assessment feedback question naire scores , the number of data points completed , and the time taken to complete the assessment . It was also predicted that a native smartphone application would ( 1 ) yield a greater number of data points , ( 2 ) take less time , and ( 3 ) be more positively appraised by patient participant users than the text-based system . Methods A r and omized repeated measures crossover design was employed . Participants with currently treated Diagnostic and Statistical Manual ( Fourth Edition ) schizophrenia or related disorders ( n=24 ) were r and omly allocated to completing 6 days of assessment ( four sets of questions per day ) with a native smartphone application or the SMS text-only implementation . There was then a 1-week break before completing a further 6 days with the alternative delivery modality . Quantitative feedback question naires were administered at the end of each period of sampling . Results A greater proportion of data points were completed with the native smartphone application in comparison to the SMS text-only implementation ( β = -.25 , SE=.11 , P=.02 ) , which also took significantly less time to complete ( β = .78 , SE= .09 , P<.001 ) . Although there were no significant differences in participants ’ quantitative feedback for the two delivery modalities , most participants reported preferring the native smartphone application ( 67 % ; n=16 ) and found it easier to use ( 71 % ; n=16 ) . 33 % of participants reported that they would be willing to complete mobile phone assessment for 5 weeks or longer . Conclusions Native smartphone applications and SMS text are both valuable methods of delivering real-time assessment in individuals with schizophrenia . However , a more streamlined graphical user interface may lead to better compliance and shorter entry times . Further research is needed to test the efficacy of this technology within clinical services , to assess validity over longer periods of time and when delivered on patients ’ own phones 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 ) BACKGROUND The primary form of treatment for obesity today is behavioral therapy . Self-monitoring diet and physical activity plays an important role in interventions targeting behavior and weight change . The SMART weight loss trial examined the impact of replacing the st and ard paper record used for self-monitoring with a personal digital assistant ( PDA ) . This paper describes the design , methods , intervention , and baseline sample characteristics of the SMART trial . METHODS The SMART trial used a 3-group design to determine the effects of different modes of self-monitoring on short- and long-term weight loss and on adherence to self-monitoring in a 24-month intervention . Participants were r and omized to one of three conditions ( 1 ) use of a st and ard paper record ( PR ) ; ( 2 ) use of a PDA with dietary and physical activity software ( PDA ) ; or ( 3 ) , use of a PDA with the same software plus a customized feedback program ( PDA + FB ) . RESULTS We screened 704 individuals and r and omized 210 . There were statistically but not clinical ly significant differences among the three cohorts in age , education , HDL cholesterol , blood glucose and systolic blood pressure . At 24 months , retention rate for the first of three cohorts was 90 % . CONCLUSIONS To the best of our knowledge , the SMART trial is the first large study to compare different methods of self-monitoring in a behavioral weight loss intervention and to compare the use of PDAs to conventional paper records . This study has the potential to reveal significant details about self-monitoring patterns and whether technology can improve adherence to this vital intervention component OBJECTIVE To compare users ' speed , number of entry errors and satisfaction in using two current devices for electronic data collection in clinical research : h and held and laptop computers . DESIGN The authors performed a r and omized cross-over trial using 160 different paper-based question naires and representing altogether 45,440 variables . Four data coders were instructed to record , according to a r and om predefined and equally balanced sequence , the content of these question naires either on a laptop or on a h and held computer . Instructions on the kind of device to be used were provided to data -coders in individual sealed and opaque envelopes . Study conditions were controlled and the data entry process performed in a quiet environment . MEASUREMENTS The authors compared the duration of the data recording process , the number of errors and users ' satisfaction with the two devices . The authors divided errors into two separate categories , typing and missing data errors . The original paper-based question naire was used as a gold-st and ard . RESULTS The overall duration of the recording process was significantly reduced ( 2.0 versus 3.3 min ) when data were recorded on the laptop computer ( p < 0.001 ) . Data accuracy also improved . There were 5.8 typing errors per 1,000 entries with the laptop compared to 8.4 per 1,000 with the h and held computer ( p < 0.001 ) . The difference was even more important for missing data which decreased from 22.8 to 2.9 per 1,000 entries when a laptop was used ( p < 0.001 ) . Users found the laptop easier , faster and more satisfying to use than the h and held computer . CONCLUSIONS Despite the increasing use of h and held computers for electronic data collection in clinical research , these devices should be used with caution . They double the duration of the data entry process and significantly increase the risk of typing errors and missing data . This may become a particularly crucial issue in studies where these devices are provided to patients or healthcare workers , unfamiliar with computer technologies , for self-reporting or research data collection processes Background Stress , depression , and anxiety affect 15 % to 25 % of pregnant women . However , substantial barriers to psychosocial assessment exist , result ing in less than 20 % of prenatal care providers assessing and treating mental health problems . Moreover , pregnant women are often reluctant to disclose their mental health concerns to a healthcare provider . Identifying screening and assessment tools and procedures that are acceptable to both women and service providers , cost-effective , and clinical ly useful is needed . Methods / Design The primary objective of this r and omized , parallel-group , superiority trial is to evaluate the feasibility and acceptability of a computer tablet-based prenatal psychosocial assessment ( e-screening ) compared to paper-based screening . Secondary objectives are to compare the two modes of screening on : ( 1 ) the level of detection of prenatal depression and anxiety symptoms and psychosocial risk ; ( 2 ) the level of disclosure of symptoms ; ( 3 ) the factors associated with feasibility , acceptability , and disclosure ; ( 4 ) the psychometric properties of the e-version of the assessment tools ; and ( 5 ) cost-effectiveness . A sample of 542 women will be recruited from large , primary care maternity clinics and a high-risk antenatal unit in an urban Canadian city . Pregnant women are eligible to participate if they : ( 1 ) receive care at one of the recruitment sites ; ( 2 ) are able to speak/read English ; ( 3 ) are willing to be r and omized to e-screening ; and ( 4 ) are willing to participate in a follow-up diagnostic interview within 1 week of recruitment . Allocation is by computer-generated r and omization . Women in the intervention group will complete an online psychosocial assessment on a computer tablet , while those in the control group will complete the same assessment in paper-based form . All women will complete baseline question naires at the time of recruitment and will participate in a diagnostic interview within 1 week of recruitment . Research assistants conducting diagnostic interviews and physicians will be blinded . A qualitative descriptive study involving healthcare providers from the recruitment sites and women will provide data on feasibility and acceptability of the intervention . We hypothesize that mental health e-screening in primary care maternity setting s and high-risk antenatal units will be as or more feasible , acceptable , and capable of detecting depression , anxiety , and psychosocial risk compared to paper-based screening . Trial registration Clinical Trials.gov Identifier : NCT01899534 We have design ed a flexible ecological momentary assessment /intervention smartphone ( EMA/EMI ) “ app ” . We examine the utility of this app for collecting real-time data , and assessing intra-subject variability , by using it to assess how freshman undergraduates spend their time . We also explore whether its use can promote greater self-awareness . Participants were r and omly divided into an experimental group , who used the app , and a control group , who did not . We used the app to collect both r and omized in-the-moment data as well as end-of-day data to assess time use . Using a posttest survey we asked participants questions about how they spent time throughout the school semester . We also asked the experimental group about their experience with the app . Among other findings , 80.49 % participants indicated that they became more aware of how they spent their time using the app . Corroborating this report , among the experimental group , end-of-semester self- assessment of time spent wasted , and time spent using electronics recreationally , predicted semester GPA at a strength comparable to high school GPA and ACT score ( two of the best single predictors for first semester college GPA ) , but had no correlation among controls . We discuss the advantages and limitations of using apps , such as ours , for EMA and /or EMI In healthcare , pain assessment is a key factor in effectively treating postoperative pain and reducing the risk of developing chronic pain . The overall aim of this study was to investigate whether a mobile phone support system can be used as a basis to continuously document patients ' health information in real time and provide conditions for optimal , individual pain management after cholecystectomy and hysterectomy procedures .In this pilot study , two r and omly selected groups of patients provided information about their pain for one week postoperatively . One group responded via cell phones , and the other , a control group , responded using paper-based question naires . The mobile phone system was found to provide a fast and safe basis for reporting pain postoperatively in real time . The results indicate that on days 3 and 4 the mobile phone group reported significantly higher levels of pain than the control group , and the cholecystectomy patients reported significantly more pain at movement on days 3 and 4 than the hysterectomy patients .The mobile phone approach is an adaptation to modern technology and the mobility of individuals . This technology is user friendly and requires minimal support . However , as the sample size was small ( n = 37 ) , further studies are needed before additional conclusions can be drawn Background Mathematical models of infection that consider targeted interventions are exquisitely dependent on the assumed mixing patterns of the population . We report on a pilot study design ed to assess three different methods ( one retrospective , two prospect i ve ) for obtaining contact data relevant to the determination of these mixing patterns . Methods 65 adults were asked to record their social encounters in each location visited during 6 study days using a novel method whereby a change in physical location of the study participant triggered data entry . Using a cross-over design , all participants recorded encounters on 3 days in a paper diary and 3 days using an electronic recording device ( PDA ) . Participants were r and omised to first prospect i ve recording method . Results Both methods captured more contacts than a pre- study question naire , but ascertainment using the paper diary was superior to the PDA ( mean difference : 4.52 ( 95 % CI 0.28 , 8.77 ) . Paper diaries were found more acceptable to the participants compared with the PDA . Statistical analysis confirms that our results are broadly consistent with those reported from large-scale European based surveys . An association between household size ( trend 0.14 , 95 % CI ( 0.06 , 0.22 ) , P < 0.001 ) and composition ( presence of child 0.37 , 95 % CI ( 0.17 , 0.56 ) , P < 0.001 ) and the total number of reported contacts was observed , highlighting the importance of sampling study population s based on household characteristics as well as age . New contacts were still being recorded on the third study day , but compliance had declined , indicating that the optimal number of sample days represents a trade-off between completeness and quality of data for an individual . Conclusions The study 's location-based reporting design allows greater scope compared to other methods for examining differences in the characteristics of encounters over a range of environments . Improved parameterisation of dynamic transmission models gained from work of this type will aid in the development of more robust decision support tools to assist health policy makers and planners Background Smartphone-based assessment may be a useful diagnostic and monitoring tool for patients . There have been many attempts to create a smartphone diagnostic tool for clinical use in various medical fields but few have demonstrated scientific validity . Objective The purpose of this study was to develop a smartphone application of the International Prostate Symptom Score ( IPSS ) and to demonstrate its validity and reliability . Methods From June 2012 to May 2013 , a total of 1581 male participants ( ≥40 years old ) , with or without lower urinary tract symptoms ( LUTS ) , visited our urology clinic via the health improvement center at Soonchunhyang University Hospital ( Republic of Korea ) and were enrolled in this study . A r and omized repeated measures crossover design was employed using a smartphone application of the IPSS and the conventional paper form of the IPSS . Paired t test under a hypothesis of non-inferior trial was conducted . For the reliability test , the intraclass correlation coefficient ( ICC ) was measured . Results The total score of the IPSS ( P=.289 ) and each item of the IPSS ( P=.157 - 1.000 ) showed no differences between the paper version and the smartphone version of the IPSS . The mild , moderate , and severe LUTS groups showed no differences between the two versions of the IPSS . A significant correlation was noted in the total group ( ICC=.935 , P<.001 ) . The mild , moderate , and severe LUTS groups also showed significant correlations ( ICC=.616 , .549 , and .548 respectively , all P<.001).There was selection bias in this study , as only participants who had smartphones could participate . Conclusions The validity and reliability of the smartphone application version were comparable to the conventional paper version of the IPSS . The smartphone application of the IPSS could be an effective method for measuring lower urinary tract symptoms Background The stepped-care approach , where people with early symptoms of depression are stepped up from low-intensity interventions to higher-level interventions as needed , has the potential to assist many people with mild depressive symptoms . Self-monitoring techniques assist people to underst and their mental health symptoms by increasing their emotional self-awareness ( ESA ) and can be easily distributed on mobile phones at low cost . Increasing ESA is an important first step in psychotherapy and has the potential to intervene before mild depressive symptoms progress to major depressive disorder . In this secondary analysis we examined a mobile phone self-monitoring tool used by young people experiencing mild or more depressive symptoms to investigate the relationships between self-monitoring , ESA , and depression . Objectives We tested two main hypotheses : ( 1 ) people who monitored their mood , stress , and coping strategies would have increased ESA from pretest to 6-week follow-up compared with an attention comparison group , and ( 2 ) an increase in ESA would predict a decrease in depressive symptoms . Methods We recruited patients aged 14 to 24 years from rural and metropolitan general practice s. Eligible participants were identified as having mild or more mental health concerns by their general practitioner . Participants were r and omly assigned to either the intervention group ( where mood , stress , and daily activities were monitored ) or the attention comparison group ( where only daily activities were monitored ) , and both groups self-monitored for 2 to 4 weeks . R and omization was carried out electronically via r and om seed generation , by an in-house computer programmer ; therefore , general practitioners , participants , and research ers were blinded to group allocation at r and omization . Participants completed pretest , posttest , and 6-week follow-up measures of the Depression Anxiety Stress Scale and the ESA Scale . We estimated a parallel process latent growth curve model ( LGCM ) using Mplus to test the indirect effect of the intervention on depressive symptoms via the mediator ESA , and calculated 95 % bias-corrected bootstrapping confidence intervals ( CIs ) . Results Of the 163 participants assessed for eligibility , 118 were r and omly assigned and 114 were included in analyses ( 68 in the intervention group and 46 in the comparison group ) . A parallel process LGCM estimated the indirect effect of the intervention on depressive symptoms via ESA and was shown to be statistically significant based on the 95 % bias-corrected bootstrapping CIs not containing zero ( –6.366 to –0.029 ) . The proportion of the maximum possible indirect effect estimated was κ2 = .54 ( 95 % CI .426–.640 ) . Conclusions This study supported the hypothesis that self-monitoring increases ESA , which in turn decreases depressive symptoms for young people with mild or more depressive symptoms . Mobile phone self-monitoring programs are ideally suited to first-step intervention programs for depression in the stepped-care approach , particularly when ESA is targeted as a mediating factor . Trial Registration Clinical Trials.gov NCT00794222 ; http:// clinical trials.gov/ct2/show/NCT00794222 ( Archived by WebCite at http://www.webcitation.org/65lldW34k Abstract . Aim : The capture , analysis and utilisation of health status information are attended by logistic considerations and interpretation challenges . We report a preliminary evaluation of cellular technology in capturing WOMAC ® NRS 3.1 Index data . Methods : A Java midlet for delivering the WOMAC ® NRS3.1 Index on Nokia-6300 , Motorola-V3 and Samsung-A711 mobile phones was developed by Exco InTouch . Following task orientation , patients completed the paper-based WOMAC ® ( p-WOMAC ® ) question naire , and then the three mobile phonebased WOMAC ® ( m-WOMAC ® ) applications , in r and om order . Results : All 12 patients ( age range = 55–82 years ) successfully completed the m-WOMAC ® Index on each of the three phones , and all were found acceptable by patients . With respect to m-WOMAC ® mean overall rank score , no significant difference was found between the 3 phones ( Friedman ’s chi square ( 2 df ) = 2.2 , p = 0.34 ) however , Motorola V3 was favoured with the best mean rank . Pearson correlation between the average p-WOMAC ® and average m-WOMAC ® score was 0.996 . Conclusions : Patient reported ratings indicated the m-WOMAC ® application performed well on all three phones . EDC provides unique opportunities for using quantitative measurement in both clinical practice and research PURPOSE Although tablet computers offer advantages in data collection over traditional paper- and -pencil methods , little research has examined whether the 2 formats yield similar responses , especially with underserved population s. We compared the 2 survey formats and tested whether participants ' responses to common health question naires or perceptions of usability differed by survey format . We also tested whether we could replicate established paper- and -pencil findings via tablet computer . METHODS We recruited a sample of low-income community members living in the rural southern United States . Participants were 170 residents ( black = 49 % ; white = 36 % ; other races and missing data = 15 % ) drawn from 2 counties meeting Florida 's state statutory definition of rural with 100 persons or fewer per square mile . We r and omly assigned participants to complete scales ( Center for Epidemiologic Studies Depression Inventory and Regulatory Focus Question naire ) along with survey format usability ratings via paper- and -pencil or tablet computer . All participants rated a series of previously vali date d posters using a tablet computer . Finally , participants completed comparisons of the survey formats and reported survey format preferences . FINDINGS Participants preferred using the tablet computer and showed no significant differences between formats in mean responses , scale reliabilities , or in participants ' usability ratings . CONCLUSIONS Overall , participants reported similar scales responses and usability ratings between formats . However , participants reported both preferring and enjoying responding via tablet computer more . Collectively , these findings are among the first data to show that tablet computers represent a suitable substitute among an underrepresented rural sample for paper- and -pencil methodology in survey research PURPOSE To determine whether electronic self-administration of the Disabilities of the Arm , Shoulder , and H and ( DASH ) question naire using a tablet computer increased completion rate compared with paper self-administration . METHODS We gave the DASH in self-administered paper form to 222 new patients in a single h and surgeon 's practice . After a washout period of 5 weeks , we gave the DASH in self-administered tablet computer form to 264 new patients . A maximum of 3 questions could be omitted before the question naire was considered unscorable . We review ed the su bmi tted surveys to determine the number of scorable question naires and the number of omitted questions in each survey . We completed univariate analysis and regression modeling to determine the influence of survey administration type on respondent error while controlling for patient age and sex . RESULTS Of the 486 total surveys , 60 ( 12 % ) were not scorable . A significantly higher proportion of the paper surveys ( 24 % ) were unscorable compared with electronic surveys ( 2 % ) , with significantly more questions omitted in each paper survey ( 2.6 ± 4.4 questions ) than in each electronic survey ( 0.1 ± 0.8 questions ) . Logistic regression analysis revealed survey administration mode to be significantly associated with DASH scorability while controlling for age and sex , with electronic survey administration being 14 times more likely than paper administration to yield a scorable DASH . CONCLUSIONS In our retrospective series , electronic self-administration of the DASH decreased the number of omitted questions and yielded a higher number of scorable question naires . Prospect i ve , r and omized evaluation is needed to better delineate the effect of survey administration on respondent error . CLINICAL RELEVANCE Administration of the DASH with a tablet computer may be beneficial for both clinical and research endeavors to increase completion rate and to gain other benefits from electronic data capture BACKGROUND Daily diaries are a useful way of measuring fluctuations in pain-related symptoms . However , traditional diaries do not assure the gathering of data in real time , not solving the problem of retrospective assessment . Ecological momentary assessment ( EMA ) by means of electronic diaries helps to improve repeated assessment . However , it is important to test its feasibility in specific population s in order to reach a wider number of people who could benefit from these procedures . METHODS The present study compares the compliance and acceptability of an electronic diary running on a smartphone using a crossover design for a sample with a specific pain condition , fibromyalgia and low familiarity with technology . Forty-seven participants were r and omly assigned to one of two conditions : ( 1 ) paper diary - smartphone diary and ( 2 ) smartphone diary - paper diary , using each assessment method for 1 week . RESULTS The findings of this study showed that the smartphone diary made it possible to gather more accurate and complete ratings . Besides , this method was well accepted by a sample of patients with fibromyalgia referred by a public hospital , with an important proportion of participants with low level of education and low familiarity with technology . CONCLUSIONS The findings of this study support the use of smartphones for EMA even in specific population s with a specific pain condition , fibromyalgia and with low familiarity with technology . These methods could help clinicians and research ers to gather more accurate ratings of relevant pain-related variables even in population s with low familiarity with technology Purpose We aim ed to investigate the effects of pretreatment with a small dose of dexmedetomidine on the cough caused by sufentanil during anesthetic induction . Methods Two hundred and forty patients undergoing elective gynecological surgery under general anesthesia were r and omly allocated to 4 groups ( n = 60 , each group ) . Dexmedetomidine 0 , 0.1 , 0.25 , and 0.5 μg/kg was administered in 5 min to groups I , II , III , and IV , respectively , followed by the induction of general anesthesia with intravenous propofol , at a target concentration of 5 μg/ml , and sufentanil 0.5 μg/kg . The incidences and severity of cough that occurred within 1 min after the injection of sufentanil were recorded , and the incidences of cardiovascular adverse events that occurred between the administration of the dexmedetomidine infusion and 1 min after tracheal intubation were recorded . Results The incidences of cough in group II , group III , and group IV were lower than that in group I ( 6.7 , 5.0 , and 6.7 vs. 26.7 % , P < 0.01 ) , while there were no significant differences between group II , group III , and group IV . The incidences of severe sinus bradycardia in group III and group IV were higher than that in group I ( 18.3 and 23.3 vs. 0.0 % , P < 0.01 ) , while there was no significant difference between group I and group II . There was no significant difference in the incidence of low blood pressure among the four groups . Conclusion Dexmedetomidine at 0.10 , 0.25 , and 0.50 μg/kg significantly reduced the incidence of sufentanil-induced cough during anesthetic induction , with the effect being most marked for 0.10 μg/kg dexmedetomidine Objectives : To assess ( 1 ) preference of parental use of an electronic diary ( e-diary ) over a paper diary to record continuous infant and caregiver behaviors over 7 days ; ( 2 ) whether e-diary recordings would differ in systematic ways from those obtained by paper diaries , and ( 3 ) frequency of diary entries when parents provide entries when convenient . Methods : Mothers of normal newborns were r and omized at 5 weeks infant age to a paper diary first ( n = 34 ) or e-diary first ( n = 35 ) group . With 3 days between , mothers completed 7-day recordings on both the paper Baby 's Day Diary and an analogous personal digital assistant e-diary for infant ( sleep , awake alert , feeding , fussing , crying , inconsolable crying ) and caregiver ( carrying/holding , moving ) behaviors , and completed post diary ease-of-use ratings and post study preference ratings . Results : Mothers found e-diaries less bothersome but similarly disruptive and enjoyable to paper diaries . At study end , more found e-diaries easier to use , less bothersome and more efficient . E-diary behaviors were consistently more frequent , but rarely different in duration , then paper diary behaviors . Time-stamped e-diary entries ( 1 ) generally declined across weeks , ( 2 ) were higher if e-diaries were used first , and ( 3 ) settled at a modal 2 to 3 entries/day by the second week . Conclusions : For behavioral recording of infant and caregiver behaviors , mothers generally expressed more approval for e-diaries than paper diaries , but neither was considered onerous . E-diaries consistently report more frequent but similar duration s of behaviors . If recording when convenient , daily diary entries trend toward 2 to 3 entries a day . The e-diary results provide convergent evidence that paper diary recordings of common infant and caregiver behavior duration s provide good estimates of duration s , but that behavioral frequencies may be underestimated OBJECTIVE This study used a two-group r and omized design to assess the validity of measuring self-reported alcohol consumption among college students using the H and held Assisted Network Diary ( H AND ) , a daily diary assessment administered using wireless mobile devices . METHOD A convenience sample of college students was recruited at a large , public university in the southeastern United States and r and omized into two groups . A r and omly assigned group of 86 students completed the daily H AND assessment during the 30-day study and a Timeline Followback ( TLFB ) at 30-day follow-up . A r and omly assigned group of 82 students completed the paper- and -pencil Daily Social Diary ( DSD ) over the same study period . Data from the daily H AND assessment were compared with the TLFB completed at follow-up by participants who completed the H AND using 95 % limits of agreement analysis . Furthermore , individual growth models were used to examine differences between the H AND and DSD by comparing the total drinks , drinking days , and drinks per drinking day captured by the two assessment s over the study period . RESULTS Results suggest that the H AND captured similar levels of alcohol use compared with the TLFB completed at follow-up by the same participants . In addition , comparisons of the two study groups suggest that , controlling for baseline alcohol use and demographics , the H AND assessment captured similar levels of total drinks , drinking days , and drinks per drinking day as the paper- and -pencil DSD . CONCLUSIONS The study findings support the validity of wireless mobile devices as a daily assessment of alcohol use among college students Purpose We investigated the feasibility and acceptance of electronic monitoring of symptoms and syndromes in oncological outpatient clinics using a PALM ( h and held computer ) . Methods The assessment of a combination of symptoms and clinical benefit parameters grouped in four pairs was tested in a pilot phase in advanced cancer patients . Based on these experiences , the software E-MOSAIC was developed , consisting of patient-reported symptoms and nutritional intake and objective assessment s ( weight , weight loss , performance status and medication for pain , fatigue , and cachexia ) . E-MOSAIC was then tested in four Swiss oncology centers . In order to compare the methods , patients completed the E-MOSAIC as a paper and a PALM version . Preferences of version and completion times were collected . Assessment s were compared using Wilcoxon signed-rank tests , and the test-retest reliability was evaluated . Results The pilot phase was completed by 22 patients . Most patients and physicians perceived the assessment as useful . Sixty-two patients participated in the feasibility study . Twelve patients reported problems ( underst and ing , optical , tactile ) , and five patients could not complete the assessment . The median time to complete the PALM-based assessment was 3 min . Forty-nine percent of patients preferred the PALM , 23 % preferred a paper version , and 28 % of patients had no preference . Paper vs. PALM revealed no significant differences in symptoms , but in nutritional intake ( p = 0.013 ) . Test-retest ( 1 h , n = 20 ) reliability was satisfactory ( r = 073–98 ) . Conclusion Electronic symptom and clinical benefit monitoring is feasible in oncology outpatient clinics and perceived as useful by patients , oncology nurses , and oncologists . E-MOSAIC is tested in a prospect i ve r and omized trial OBJECTIVES To test the impact of the method of administration ( MOA ) on score level , reliability , and validity of scales developed in the Patient Reported Outcomes Measurement Information System ( PROMIS ) . STUDY DESIGN AND SETTING Two nonoverlapping parallel forms each containing eight items from each of three PROMIS item banks ( Physical Function , Fatigue , and Depression ) were completed by 923 adults with chronic obstructive pulmonary disease , depression , or rheumatoid arthritis . In a r and omized crossover design , subjects answered one form by interactive voice response ( IVR ) technology , paper question naire ( PQ ) , personal digital assistant ( PDA ) , or personal computer ( PC ) and a second form by PC , in the same administration . Method equivalence was evaluated through analyses of difference scores , intraclass correlations ( ICCs ) , and convergent/discriminant validity . RESULTS In difference score analyses , no significant mode differences were found and all confidence intervals were within the prespecified minimal important difference of 0.2 st and ard deviation . Parallel-forms reliabilities were very high ( ICC = 0.85 - 0.93 ) . Only one across-mode ICC was significantly lower than the same-mode ICC . Tests of validity showed no differential effect by MOA . Participants preferred screen interface over PQ and IVR . CONCLUSION We found no statistically or clinical ly significant differences in score levels or psychometric properties of IVR , PQ , or PDA administration compared with PC 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 Background In the last 20 years , research ers have been using computer self-administered question naires to gather data on a wide range of adolescent health related behaviours . More recently , research ers collecting data in schools have started to use smaller h and -held computers for their ease of use and portability . The aim of this study is to describe a new technology with wi-fi enabled h and -held internet tablets and to compare adolescent preferences of laptop computers or h and -held internet tablets in administering a youth health and well-being question naire in a school setting . Methods A total of 177 students took part in a pilot study of a national youth health and wellbeing survey . Students were r and omly assigned to internet tablets or laptops at the start of the survey and were changed to the alternate mode of administration about half-way through the question naire . Students at the end of the question naire were asked which of the two modes of administration ( 1 ) they preferred , ( 2 ) was easier to use , ( 3 ) was more private and confidential , and ( 4 ) was easier to answer truthfully . Results Many students expressed no preference between laptop computers or internet tablets . However , among the students who expressed a preference between laptop computers or internet tablets , the majority of students found the internet tablets more private and confidential ( p < 0.001 ) and easier to answer questions truthfully ( p < 0.001 ) compared to laptop computers . Conclusion This study demonstrates that using wi-fi enabled h and -held internet tablets is a feasible methodology for school-based surveys especially when asking about sensitive information Background Maternal , Newborn , and Child Health ( MNCH ) household survey data are collected mainly with pen- and -paper . Smartphone data collection may have advantages over pen- and -paper , but little evidence exists on how they compare . Objective To compare smartphone data collection versus the use of pen- and -paper for infant feeding practice s of the MNCH household survey . We compared the two data collection methods for differences in data quality ( data recording , data entry , open-ended answers , and interrater reliability ) , time consumption , costs , interviewers ’ perceptions , and problems encountered . Methods We recruited mothers of infants aged 0 to 23 months in four village clinics in Zhaozhou Township , Zhao County , Hebei Province , China . We r and omly assigned mothers to a smartphone or a pen- and -paper question naire group . A pair of interviewers simultaneously question ed mothers on infant feeding practice s , each using the same method ( either smartphone or pen- and -paper ) . Results We enrolled 120 mothers , and all completed the study . Data recording errors were prevented in the smartphone question naire . In the 120 pen- and -paper question naires ( 60 mothers ) , we found 192 data recording errors in 55 question naires . There was no significant difference in recording variation between the groups for the question naire pairs ( P = .32 ) or variables ( P = .45 ) . The smartphone question naires were automatically uploaded and no data entry errors occurred . We found that even after double data entry of the pen- and -paper question naires , 65.0 % ( 78/120 ) of the question naires did not match and needed to be checked . The mean duration of an interview was 10.22 ( SD 2.17 ) minutes for the smartphone method and 10.83 ( SD 2.94 ) minutes for the pen- and -paper method , which was not significantly different between the methods ( P = .19 ) . The mean costs per question naire were higher for the smartphone question naire ( ¥ 143 , equal to US $ 23 at the exchange rate on April 24 , 2012 ) than for the pen- and -paper question naire ( ¥ 83 , equal to US $ 13 ) . The smartphone method was acceptable to interviewers , and after a pilot test we encountered only minor problems ( eg , the system halted for a few seconds or it shut off ) , which did not result in data loss . Conclusions This is the first study showing that smartphones can be successfully used for household data collection on infant feeding in rural China . Using smartphones for data collection , compared with pen- and -paper , eliminated data recording and entry errors , had similar interrater reliability , and took an equal amount of time per interview . While the costs for the smartphone method were higher than the pen- and -paper method in our small-scale survey , the costs for both methods would be similar for a large-scale survey . Smartphone data collection should be further evaluated for other surveys and on a larger scale to deliver maximum benefits in China and elsewhere OBJECTIVES To evaluate the validity , reliability , responsiveness , and mode preference of electronic data capture ( EDC ) using the Western Ontario and McMaster ( WOMAC ) numerical rating scale ( NRS ) 3.1 Osteoarthritis ( OA ) Index on Motorola V3 mobile phones . STUDY DESIGN AND SETTING Patients with OA undergoing hip or knee joint replacement were assessed preoperatively and 3 - 4 months postoperatively , completing the WOMAC Index in paper ( p-WOMAC ) and electronic ( m-WOMAC ) format in r and om order . RESULTS Data were successfully and securely transmitted from patients in Australia to a server in the United States . Pearson correlations between the summated total index scores ( TISs ) for the p-WOMAC and m-WOMAC pre- and postsurgery were 0.98 and 0.99 ( P<0.0001 ) . There were no clinical ly important or statistically significant between- method differences in the adjusted total summated scores , pre- and postsurgery ( adjusted mean differences=4.44 , P=0.474 and 1.73 , P=0.781 , respectively ) . Internal consistency estimates of m-WOMAC reliability were 0.87 - 0.98 . The m-WOMAC detected clinical ly important , statistically significant ( P<0.0001 ) improvements in pain , stiffness , function , and TIS . No statistically significant differences in mode preference were detected . CONCLUSIONS There was close agreement and no significant differences between m-WOMAC and p-WOMAC scores . This study confirms the validity , reliability , and responsiveness of the Exco InTouch-engineered , Java-based m-WOMAC Index application . EDC with the m-WOMAC Index provides unique opportunities for using quantitative measurement in clinical research and practice PURPOSE To compare the Disabilities of the Arm , Shoulder , and H and ( DASH ) patient-reported outcome measure as administered by tablet computer to the traditional paper format . METHODS In a prospect i ve , r and omized study design , 223 consecutive adult patients who presented to the clinic of a single h and surgeon at a tertiary medical center were r and omized by visit time to receive the DASH by either paper or tablet computer . Test completeness , time to completion , DASH score , and diagnostic and demographic data were collected and compared between the two cohorts . In total , 120 participants took the DASH using the tablet and 103 using paper . RESULTS 43 % of the paper surveys had at least one question that was omitted , compared with 13 % in the tablet group ; 14 % of the paper surveys were not scoreable ( < 27 questions answered ) compared with 4 % of the tablet surveys . The mean time to complete was 3.1 minutes for the paper version of the DASH and 4.3 minutes for the tablet version . Among our study population , there was no influence of age , sex , or diagnosis category on the time required to complete either version of the test . The mean DASH score was 45 for the paper version and 32 for the tablet version . CONCLUSIONS The use of digital data entry methods in the arena of health care outcomes research is increasing . Administration of the DASH via a tablet computer result ed in more complete data , slightly increased responder burden , and a lower DASH score . This finding may have important implication s for the use of this metric in an electronic format in future research endeavors . TYPE OF STUDY /LEVEL OF EVIDENCE Diagnostic II Accurate dietary assessment is an essential foundation of research in nutritional epidemiology . Due to the weaknesses in current methodology , attention is turning to strategies that automate the dietary assessment process to improve accuracy and reduce the costs and burden to participants and research ers . ' My Meal Mate ' ( MMM ) is a smartphone application design ed to support weight loss . The present study aim ed to vali date the diet measures recorded on MMM against a reference measure of 24 h dietary recalls . A sample of fifty volunteers recorded their food and drink intake on MMM for 7 d. During this period , they were contacted twice at r and om to conduct 24 h telephone recalls . Daily totals for energy ( kJ ) and macronutrients recorded on MMM were compared against the corresponding day of recall using t tests for group means and Pearson 's correlations . Bl and -Altman analysis was used to assess the agreement between the methods . Energy ( kJ ) recorded on MMM correlated well with the recalls ( day 1 : r 0·77 ( 95 % CI 0·62 , 0·86 ) , day 2 : r 0·85 ( 95 % CI 0·74 , 0·91 ) ) and had a small mean difference ( day 1 ( MMM - recall ) : -68 kJ/d ( 95 % CI -553 , 418 kJ ) ( -16 kcal/d , 95 % CI -127 , 100 kcal ) ; day 2 ( MMM - recall ) : -441 kJ/d ( 95 % CI -854 , -29 kJ ) ( -105 kcal/d , 95 % CI -204 , -7 kcal ) ) . Bl and -Altman analysis showed wide limits of agreement between the methods : -3378 to 3243 kJ/d ( -807 to 775 kcal/d ) on day 1 . At the individual level , the limits of agreement between MMM and the 24 h recall were wide ; however , at the group level , MMM appears to have potential as a dietary assessment tool Background Physical activity is associated with reduced risks of many chronic diseases . Data collected on physical activity in large epidemiological studies is often based on paper question naires . The validity of these question naires is debated , and more effective methods are needed . Objective This study evaluates repeated measures of physical activity level ( PAL ) and the feasibility of using a Java-based question naire downloaded onto cell phones for collection of such data . The data obtained were compared with reference estimates based on the doubly labeled water method and indirect calorimetry ( PALref ) . Method Using a Java-based cell phone application , 22 women reported their physical activity based on two short questions answered daily over a 14-day period ( PALcell ) . Results were compared with reference data obtained from the doubly labeled water method and indirect calorimetry ( PALref ) . Results were also compared against physical activity levels assessed by two regular paper question naires completed by women at the end of the 14-day period ( PALquest1 and PALquest2 ) . PALcell , PALquest1 , and PALquest2 were compared with PALref using the Bl and and Altman procedure . Results The mean difference between PALcell and PALref was small ( 0.014 ) with narrow limits of agreement ( 2SD = 0.30 ) . Compared with PALref , the mean difference was also small for PALquest1 and PALquest2 ( 0.004 and 0.07 , respectively ) ; however , the limits of agreement were wider ( PALquest1 , 2SD = 0.50 and PALquest2 , 2SD = 0.90 ) . The test for trend was statistically significant for PALquest1 ( slope of regression line = 0.79 , P = .04 ) as well as for PALquest2 ( slope of regression line = 1.58 , P < .001 ) when compared with PALref . Conclusion A Java-based physical activity question naire administered daily using cell phones produced PAL estimates that agreed well with PAL reference values . Furthermore , the limits of agreement between PAL obtained using cell phones , and reference values were narrower than for corresponding estimates obtained using paper question naires . Java-based question naires downloaded onto cell phones may be a feasible and cost-effective method of data collection for large-scale prospect i ve studies of physical activity 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 OBJECTIVE To examine the impact of 3 data collection modes on the number of questions answered , data quality , and student preference . METHODS 275 urban seventh- grade students were recruited and r and omly assigned to complete a paper survey ( SAQ ) , PDA survey ( PDA ) , or PDA survey with audio ( APDA ) . Students completed a paper debriefing survey . RESULTS APDA respondents completed significantly more questions compared to SAQ and PDA . PDA and APDA had significantly less missing data than did SAQ . No differences were found for student evaluation . CONCLUSIONS Strong benefits may be gained by the use of APDA for adolescent school-based data collection Background There is growing interest in the use of information communication technologies to treat obesity . An intervention delivered by smartphone could be a convenient , potentially cost-effective , and wide-reaching weight management strategy . Although there have been studies of texting-based interventions and smartphone applications ( apps ) used as adjuncts to other treatments , there are currently no r and omized controlled trials ( RCT ) of a st and -alone smartphone application for weight loss that focuses primarily on self-monitoring of diet and physical activity . Objective The aim of this pilot study was to collect acceptability and feasibility outcomes of a self-monitoring weight management intervention delivered by a smartphone app , compared to a website and paper diary . Methods A sample of 128 overweight volunteers were r and omized to receive a weight management intervention delivered by smartphone app , website , or paper diary . The smartphone app intervention , My Meal Mate ( MMM ) , was developed by the research team using an evidence -based behavioral approach . The app incorporates goal setting , self-monitoring of diet and activity , and feedback via weekly text message . The website group used an existing commercially available slimming website from a company called Weight Loss Re sources who also provided the paper diaries . The comparator groups delivered a similar self-monitoring intervention to the app , but by different modes of delivery . Participants were recruited by email , intranet , newsletters , and posters from large local employers . Trial duration was 6 months . The intervention and comparator groups were self-directed with no ongoing human input from the research team . The only face-to-face components were at baseline enrollment and brief follow-up sessions at 6 weeks and 6 months to take anthropometric measures and administer question naires . Results Trial retention was 40/43 ( 93 % ) in the smartphone group , 19/42 ( 55 % ) in the website group , and 20/43 ( 53 % ) in the diary group at 6 months . Adherence was statistically significantly higher in the smartphone group with a mean of 92 days ( SD 67 ) of dietary recording compared with 35 days ( SD 44 ) in the website group and 29 days ( SD 39 ) in the diary group ( P<.001 ) . Self-monitoring declined over time in all groups . In an intention-to-treat analysis using baseline observation carried forward for missing data , mean weight change at 6 months was -4.6 kg ( 95 % CI –6.2 to –3.0 ) in the smartphone app group , –2.9 kg ( 95 % CI –4.7 to –1.1 ) in the diary group , and –1.3 kg ( 95 % CI –2.7 to 0.1 ) in the website group . BMI change at 6 months was –1.6 kg/m2 ( 95 % CI –2.2 to –1.1 ) in the smartphone group , –1.0 kg/m2 ( 95 % CI –1.6 to –0.4 ) in the diary group , and –0.5 kg/m2 ( 95 % CI –0.9 to 0.0 ) in the website group . Change in body fat was –1.3 % ( 95 % CI –1.7 to –0.8 ) in the smartphone group , –0.9 % ( 95 % CI –1.5 to –0.4 ) in the diary group , and –0.5 % ( 95 % CI –0.9 to 0.0 ) in the website group . Conclusions The MMM app is an acceptable and feasible weight loss intervention and a full RCT of this approach is warranted . Trial Registration Clinical Trials.gov NCT01744535 ; http:// clinical trials.gov/ct2/show/NCT01744535 ( Archived by WebCite at http://www.webcitation.org/6FEtc3PVB Background : H and -held electronic devices may provide a simple reproducible means by which quality of life ( QOL ) may be documented in patients with cancer . However , the QOL scales that are routinely used were originally vali date d when used with paper and pencil data collection . Patient-reported outcomes acquired using h and -held electronic devices ( electronic patient-reported outcomes [ ePRO ] ) may not be the same as those acquired using paper and pencil , so validation of this method of data collection is needed . Objectives : This study aim ed to compare the results of e-PRO and paper and pencil collection of Functional Assessment of Cancer Therapy-Lung ( FACT-L ) and EuroQol-5 Dimension ( EQ-5D ) QOL data in patients with advanced non-small cell lung cancer ( NSCLC ) , and to ascertain patients ’ preferences for the different modes of collection . Methods : This r and omized , single-cohort , crossover study was performed in a tertiary referral hospital cancer center . Fifty patients with previously treated locally advanced or metastatic NSCLC were r and omized in a 1 : 1 ratio to complete either paper versions of the question naires ( FACT-L and EQ-5D ) followed by the e-PRO versions , or the e-PRO question naire followed by the paper versions . Results : The majority ( 88 % ) of the FACT-L and all ( 100 % ) of the EQ-5D individual question responses were within + 1 point of each other when data collection via e-PRO and via pencil and paper were compared . There was no significant difference between the mean total FACT-L scores obtained using the two methods ; however , 29 % of patients had a difference between FACT-L total scores obtained with the two methods that was greater than ±6 points . The mean completion time was shorter for the paper and pencil method than the e-PRO method ( p < 0.0001 ) . However , most patients stated that they preferred the e-PRO method over paper and pencil ( 60 % vs 12 % ) . Conclusion : This study suggests that the mode of administration of the FACT-L and EQ-5D had a relatively small effect on the mean responses given to the question naires in patients with advanced NSCLC . However , at the individual patient level , data varied considerably between the different modes of administration . Therefore , the group results obtained using the e-PRO should be similar to the originally vali date d paper method , with the advantages of improved patient acceptability and ease of reliable interfacing with trial data bases Objective : Patient-reported mood charts are frequently used in management of bipolar disorder . Although mood charts have recently been programmed in electronic devices such as mobile phones , little is known about the impact of the method of data capture on the psychometric properties and validity of these data . Methods : In an ongoing pilot study , a sample of out patients with bipolar disorder were r and omized to complete mood charts either on a mobile phone or with st and ard paper and pencil as part of a 12-week intervention ( primary outcomes for the trial await study completion ) . We compared these conditions across a single item rating of mood state , and we hypothesized that mobile phone-based data capture would produce greater compliance to mood ratings , variability between and within participants , and concurrent validity with blinded clinician-rated affective symptom severity . Results : A total of 56 participants were r and omized and 40 participants were included in the analyses . There were no significant differences between conditions on demographic or clinical variables . The rate of compliance was significantly higher in paper- and -pencil versus mobile phone ratings . Ratings demonstrated significantly more variability within individuals in the mobile phone condition . Mobile phone mood ratings were significantly correlated with clinician-rated depressive symptom severity across the study and with manic symptom severity at the week-6 assessment , whereas paper- and -pencil ratings were not significantly associated with clinician-rated depression or mania . Conclusions : Although preliminary , our results suggest a lower rate of compliance with mobile phones compared to paper- and -pencil daily mood rating in bipolar disorder , yet a greater ability to capture variability and concurrent validity in quantifying affective symptoms . This clinical trial is registered at www . clinical trials.gov as NCT01670123 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 Objective : To evaluate the capability of DietMatePro , a PDA-based dietary assessment program , to monitor dietary intake and to improve adherence to a dietary regimen . Design : R and omized controlled trial . Subjects . Overweight and obese ( Body Mass Index ( BMI ) 25–40 ) participants without dietary restrictions . Intervention : Participants ( n = 174 ) were r and omized to record usual dietary intake using either DietMatePro or a paper food diary for one week to compare concordance with 24-hr recall . At the week 1 visit , participants were individually counseled to follow the diet recommendations of the Ornish Prevention Diet for three weeks and continue monitoring food intake using the assigned method to estimate adherence to the intervention by monitoring condition . Outcome Measures : Spearman correlations between week 1 24-hr recall and the assigned recording method were compared to assess validity . Mean pre-post changes in intake measured by 24-hr recall were compared according to monitoring condition to measure adherence to the Ornish diet . Results : Correlations of energy and nutrient values reported on the food label ranged from 0.41 to 0.71 for the DietMatePro condition versus 0.63 to 0.83 for the paper-based diary . Diet adherence was higher among DietMatePro ( 43 % ) compared to the paper diary ( 28 % ) group ( p = 0.039 ) . Conclusions /Applications : DietMatePro does not appear to produce more valid data than paper-based approaches . DietMatePro may improve adherence to dietary regimens compared to paper-based methods OBJECTIVES The objective was to assess in a pediatric emergency department ( ED ) the reliability of the color analog scale ( CAS ) for acute pain assessment , overall and between traumatic and nontraumatic pain etiology . METHODS This was a prospect i ve study of children aged 5 to 16 years in the ED of a children 's hospital who had a complaint of pain . The CAS was administered to the patient at admission and at 30 minutes . To evaluate repeatability , a second measurement was obtained 1 minute following each assessment . This assumed there would be no substantial change in pain intensity within 1 minute . The authors used the intraclass correlation coefficient ( ICC ) to evaluate the repeatability of 1-minute interval measurements . RESULTS A total of 170 patients were enrolled . The origin of pain was traumatic in 81 cases ( 48 % ) . Regardless of pain etiology , the CAS scores were highly repeatable ( r = 0.97 , 95 % confidence interval [ CI ] = 0.95 to 0.98 ) . CONCLUSIONS The color analog scale is both a valid and a reliable self-reporting tool in the assessment of acute pain in children The Memory Orientation Screening Test ( MOST ® ) is a 29-point scale for identifying and following mild and major neurocognitive disorders in older patients . Previous research demonstrated validity in separating patients with normal vs. impaired cognition and high correlations with tests of memory and attention . This study compares the original paper-based MOST ® with a computerized ( iPad app ) version , the MOST ® -96120 , to determine the equivalence of formats . A total of 98 consecutive older patients were administered identical versions of the MOST and MOST-96120 in a r and om order , separated by 1 hour of interspersed testing , in a 3-hour neuropsychological evaluation . MOST and MOST-96120 scores were compared with each other , with global cognitive ratings , and with st and ardized tests of memory and attention . Both versions had equivalent means and st and ard deviations , very high inter-test correlation ( r = .92 , p < .001 ) , and equal correlations with outcome measures . Both versions separated patients into normal vs. mild NCD vs. major NCD categories with equal accuracy . ANOVA showed no significant difference between versions or presentation order . Both versions correlated very highly with cognitive level and neuropsychological endpoints , confirming previous research . The MOST-96120 is a computerized neuropsychological assessment device that demonstrates equivalence with its paper-based original , allowing for confident reliance on the findings of previous research In the 4 years between the Ministerial Forums on research and health held in Mexico in 2004 and Mali in 2008 , the l and scape of clinical trial registration changed significantly . When the ICMJE announced that they would no longer consider publishing the findings of clinical trials unless the research had been prospect ively registered , they were key to shifting the way the clinical trials community thinks about research transparency . The argument in favour of greater transparency had been building for more than 20 years . By 2004 there was consistent and convincing evidence of the existence of publication bias and the damage this does to people 's ability to make well informed decisions about health care . There is now increasing acceptance that the registration of clinical trials in a publicly accessible registry is a scientific , ethical and moral responsibility . In 2004 , less than 3000 clinical trials were registered on data bases meeting ICMJE criteria . There are now more than 19000 and , in some countries , prospect i ve registration in a publicly accessible registry is now a legal requirement . Further , since October 2008 , prospect i ve registration is required if research ers wish to comply with the Declaration of Helsinki . However , despite these advances and incentives , trial registration in many countries remains far from comprehensive and stronger enforcement mechanisms may be needed in those countries PURPOSE One potential strategy for improving voiding diary completion rates and data quality is use of a mobile electronic format . We evaluated the acceptability and feasibility of mobile voiding diaries for patients with nonneurogenic lower urinary tract dysfunction , and compared mobile and paper voiding diaries . MATERIAL S AND METHODS We prospect ively enrolled children presenting with daytime symptoms of lower urinary tract dysfunction between July 2012 and April 2013 . We enrolled an initial cohort of patients who were provided a paper voiding diary and a subsequent cohort who were provided a mobile voiding diary . We conducted in person interviews and assessed completion rates and quality , comparing paper and mobile voiding diary groups . RESULTS We enrolled 45 patients who received a paper voiding diary and 38 who received a mobile voiding diary . Completion rates were 78 % for paper voiding diaries and 61 % for mobile voiding diaries ( p = 0.10 ) . Data quality measures for patients completing paper vs mobile voiding diaries revealed a larger proportion ( 63 % vs 52 % ) providing a full 5 days of data and a smaller proportion ( 20 % vs 65 % ) with data gaps . However , the paper voiding diary also demonstrated a lower proportion ( 80 % vs 100 % ) that was completely legible and a lower proportion ( 40 % vs 65 % ) with completely prospect i ve data entry . CONCLUSIONS The use of a mobile voiding diary was acceptable and feasible for our patients with lower urinary tract dysfunction , although completion rates were somewhat lower compared to paper voiding diaries . Data quality was not clearly better for either version . The mobile voiding diary format may offer data quality advantages for select groups but it did not display significant superiority when provided universally PURPOSE We compared the completeness of data collection using paper forms and using electronic forms loaded on h and held computers in an office-based patient interview survey conducted within the American Academy of Family Physicians National Research Network . METHODS We asked 19 medical assistants and nurses in family practice s to administer a survey about pneumococcal immunizations to 60 older adults each , 30 using paper forms and 30 using electronic forms on h and held computers . By r and om assignment , the interviewers used either the paper or electronic form first . Using multilevel analyses adjusted for patient characteristics and clustering of forms by practice , we analyzed the completeness of the data . RESULTS A total of 1,003 of the expected 1,140 forms were returned to the data center . The overall return rate was better for paper forms ( 537 of 570 , 94 % ) than for electronic forms ( 466 of 570 , 82 % ) because of technical difficulties experienced with electronic data collection and stolen or lost h and held computers . Errors of omission on the returned forms , however , were more common using paper forms . Of the returned forms , only 3 % of those gathered electronically had errors of omission , compared with 35 % of those gathered on paper . Similarly , only 0.04 % of total survey items were missing on the electronic forms , compared with 3.5 % of the survey items using paper forms . CONCLUSIONS Although h and held computers produced more complete data than the paper method for the returned forms , they were not superior because of the large amount of missing data due to technical difficulties with the h and -held computers or loss or theft . Other hardware solutions , such as tablet computers or cell phones linked via a wireless network directly to a Web site , may be better electronic solutions for the future Currently , the use of electronic scales is increasing rapidly , which is not surprising considering its accuracy , the ease of use and the increased compliance . The value of Visual Analogue Scales as a mean to objectify subjective variables has long been recognised . The current study aim ed to vali date the electronic Visual Analogue Scale of Anxiety ( eVAAS ) . Seventy-one subjects , control subjects ( n=46 ) and Panic Disorder patients ( n=25 ) , filled out the paper VAAS and the eVAAS in a r and omised order . Panic was provoked using 35 % CO(2 ) inhalation allowing us to include maximal scores in our analyses . The correlation between eVAAS and pVAAS was very strong and highly significant ( r=0.98 , p<0.001 ) . pVAAS scores were slightly higher than eVAAS scores ( p<0.001 ) , but this difference is clinical ly unimportant . The VAAS established on a tablet PC is a useful and valid measure of anxiety and holds intrinsic benefits for anxiety assessment Background . Low health literacy has been identified as an independent predictor of poor asthma control . The Institute of Medicine considers the role of information technology ( IT ) as critical in providing “ safe , effective , patient centered , timely , efficient , and equitable ” care with the potential to reduce health disparities in underserved population s. The aim of this study was to design and evaluate an interactive computer-based question naire to assess asthma symptoms in children of parents with limited health literacy and /or limited English proficiency . Methods . Volunteer caregivers attending a mobile asthma clinic were r and omly assigned to complete the electronic or the paper- and -pencil version of an asthma screening question naire ( ASQ ) in their language of choice ( English or Spanish ) . In the electronic version , a tablet computer was used to present the ASQ questions as video clips and to collect information through the touchscreen . Participants also completed a demographic question naire , a brief health literacy question naire , and a system usability and satisfaction question naire . Reliability of the paper and electronic self- assessment s was evaluated by comparing each participant 's answers to information they provided during a nurse-guided structured interview ( gold st and ard ) . Results . A total of 48 parents participated in the study , 26 completed the electronic ASQ and 21 the paper- and -pencil form . Thirty-five percent of the children had well-controlled asthma ( n = 17 ) . Most participants were Spanish speaking ( 67 % ) Hispanic ( n = 44 ) mothers ( n = 43 ) with a median age of 32 years . More than half had ≤8 years of education ( n = 25 ) and earned < $ 20,000 per year ( n = 27 ) . The median health literacy score was 32 ( range 0–36 ) . The correlation between health literacy scores and years of education was significant ( ρ = .47 , p < .01 ) . Concordance between the electronic ASQ and the nurse interview was significantly higher than concordance between the paper ASQ and the nurse interview ( 68 % versus 54 % ; p < .01 ) . All parents who completed the electronic question naire reported being satisfied ; 96 % felt comfortable using it , and found it simple to use . Conclusions . By facilitating the assessment of asthma symptoms at manageable cost , interactive information technology tools may help reduce barriers to access due to inadequate levels of English proficiency and health literacy |
12,079 | 23,040,573 | Rb-82 PET is accurate for the detection of obstructive CAD and , despite advances in SPECT technology , remains superior .
More widespread use of Rb-82 PET may be beneficial to improve CAD detection | OBJECTIVES The purpose of this study was to evaluate the accuracy of rubidium (Rb)-82 positron emission tomography ( PET ) for the diagnosis of obstructive coronary artery disease ( CAD ) in comparison to single-photon emission tomography ( SPECT ) .
BACKGROUND Myocardial perfusion imaging is widely used in the assessment of patients with known or suspected CAD .
PET using Rb-82 has potential advantages over SPECT that may make it more accurate and that reduce radiation exposure compared with SPECT but has increased costs .
Comparisons of these technologies are highly relevant for policy makers and practice guidelines .
However , studies directly comparing Rb-82 PET with contemporary SPECT have been limited . | The coronary artery calcium ( CAC ) score is a readily and widely available tool for the noninvasive diagnosis of atherosclerotic coronary artery disease ( CAD ) . The aim of this study was to investigate the added value of the CAC score as an adjunct to gated SPECT for the assessment of CAD in an intermediate-risk population . Methods : Seventy-seven prospect ively recruited patients with intermediate risk ( as determined by the Framingham Heart Study 10-y CAD risk score ) and referred for coronary angiography because of suspected CAD underwent stress 99mTc-tetrofosmin SPECT myocardial perfusion imaging ( MPI ) and CT CAC scoring within 2 wk before coronary angiography . The sensitivity and specificity of SPECT alone and of the combination of the 2 methods ( SPECT plus CAC score ) in demonstrating significant CAD ( ≥50 % stenosis on coronary angiography ) were compared . Results : Forty-two ( 55 % ) of the 77 patients had CAD on coronary angiography , and 35 ( 45 % ) had abnormal SPECT results . The CAC score was significantly higher in subjects with perfusion abnormalities than in those who had normal SPECT results ( 889 ± 836 [ mean ± SD ] vs. 286 ± 335 ; P < 0.0001 ) . Similarly , with rising CAC scores , a larger percentage of patients had CAD . Receiver-operating-characteristic analysis showed that a CAC score of greater than or equal to 709 was the optimal cutoff for detecting CAD missed by SPECT . SPECT alone had a sensitivity and a specificity for the detection of significant CAD of 76 % and 91 % , respectively . Combining SPECT with the CAC score ( at a cutoff of 709 ) improved the sensitivity of SPECT ( from 76 % to 86 % ) for the detection of CAD , in association with a nonsignificant decrease in specificity ( from 91 % to 86 % ) . Conclusion : The CAC score may offer incremental diagnostic information over SPECT data for identifying patients with significant CAD and negative MPI results UNLABELLED In July 2009 , the Medical Advisory Secretariat ( MAS ) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease ( CAD ) , an evidence -based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD . This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities . After an initial review of the strategy and consultation with experts , MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD . Evidence -based analyses have been prepared for each of these five imaging modalities : cardiac magnetic resonance imaging , single photon emission computed tomography , 64-slice computed tomographic angiography , stress echocardiography , and stress echocardiography with contrast . For each technology , an economic analysis was also completed ( where appropriate ) . A summary decision analytic model was then developed to encapsulate the data from each of these reports ( available on the OHTAC and MAS website).The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports , which can be publicly accessed at the MAS website at : www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlSINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE : An Evidence -Based Analysis STRESS ECHOCARDIOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE : An Evidence -Based Analysis STRESS ECHOCARDIOGRAPHY WITH CONTRAST FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE : An Evidence -Based Analysis 64-Slice Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease : An Evidence -Based Analysis CARDIAC MAGNETIC RESONANCE IMAGING FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE : An Evidence -Based Analysis Pease note that two related evidence -based analyses of non-invasive cardiac imaging technologies for the assessment of myocardial viability are also available on the MAS website : POSITRON EMISSION TOMOGRAPHY FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY : An Evidence -Based Analysis MAGNETIC RESONANCE IMAGING FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY : an Evidence -Based Analysis The Toronto Health Economics and Technology Assessment Collaborative has also produced an associated economic report entitled : The Relative Cost-effectiveness of Five Non-invasive Cardiac Imaging Technologies for Diagnosing Coronary Artery Disease in Ontario [ Internet ] . Available from : http://theta.utoronto.ca/reports/?id=7 OBJECTIVE The objective of the analysis is to determine the diagnostic accuracy of single photon emission tomography ( SPECT ) in the diagnosis of coronary artery disease ( CAD ) compared to the reference st and ard of coronary angiography ( CA ) . The analysis is primarily meant to allow for indirect comparisons between non-invasive strategies for the diagnosis of CAD , using CA as a reference st and ard . SPECT : Cardiac SPECT , or myocardial perfusion scintigraphy ( MPS ) , is a widely used nuclear , non-invasive image acquisition technique for investigating ischemic heart disease . SPECT is currently appropriate for all aspects of detecting and managing ischemic heart disease including diagnosis , risk assessment /stratification , assessment of myocardial viability , and the evaluation of left ventricular function . Myocardial perfusion scintigraphy was originally developed as a two-dimensional planar imaging technique , but SPECT acquisition has since become the clinical st and ard in current practice . Cardiac SPECT for the diagnosis of CAD uses an intravenously administered radiopharmaceutical tracer to evaluate regional coronary blood flow usually at rest and after stress . The radioactive tracers thallium ( 201Tl ) or technetium-99 m ( 99mTc ) , or both , may be used to visualize the SPECT acquisition . Exercise or a pharmacologic agent is used to achieve stress . After the administration of the tracer , its distribution within the myocardium ( which is dependent on myocardial blood flow ) is imaged using a gamma camera . In SPECT imaging , the gamma camera rotates around the patients for 10 to 20 minutes so that multiple two-dimensional projections are acquired from various angles . The raw data are then processed using computational algorithms to obtain three-dimensional tomographic images . Since its inception , SPECT has evolved and its techniques/applications have become increasingly more complex and numerous . Accordingly , new techniques such as attenuation correction and ECG gating have been developed to correct for attenuation due to motion or soft-tissue artifact and to improve overall image clarity . RESEARCH QUESTIONS What is the diagnostic accuracy of SPECT for the diagnosis of CAD compared to the reference st and ard of CA?Is SPECT cost-effective compared to other non-invasive cardiac imaging modalities for the diagnosis of CAD?What are the major safety concerns with SPECT when used for the diagnosis of CAD ? METHODS A preliminary literature search was performed across OVID MEDLINE , MEDLINE In-Process and Other Non-Indexed Citations , EMBASE , the Cochrane Library , and the International Agency for Health Technology Assessment ( INAHTA ) for all systematic review s/meta- analysis published between January 1 , 2004 and August 22 , 2009 . A comprehensive systematic review was identified from this search and used as a basis for an up date d search . A second comprehensive literature search was then performed on October 30 , 2009 across the same data bases for studies published between January 1 , 2002 and October 30 , 2009 . Abstract s were review ed by a single review er and , for those studies meeting the eligibility criteria , full-text articles were obtained . Reference lists were also h and - search ed for any additional studies . Inclusion Criteria Exclusion Criteria Systematic review s , meta-analyses , controlled clinical trials , and observational studies Minimum sample size of 20 patients who completed coronary angiographyUse of CA as a reference st and ard for the diagnosis of CAD Data available to calculate true positives ( TP ) , false positives ( FP ) , false negatives ( FN ) and true negatives (TN)Accuracy data reported by patient not by segmentEnglish language Non- systematic review s , case reportsGrey literature and abstract sTrials using planar imaging onlyTrials conducted in patients with non-ischemic heart disease Studies done exclusively in special population s ( e.g. , patients with left branch bundle block , diabetics , minority population s ) unless insufficient data available SUMMARY OF FINDINGS Eighty-four observational studies , one non-r and omized , single arm controlled clinical trial , and one poorly reported trial that appeared to be a r and omized controlled trial ( RCT ) met the inclusion criteria for this review . All studies assessed the diagnostic accuracy of myocardial perfusion SPECT for the diagnosis of CAD using CA as a reference st and ard . Based on the results of these studies the following conclusions were made : According to very low quality evidence , the addition of attenuation correction to traditional or ECG-gated SPECT greatly improves the specificity of SPECT for the diagnosis of CAD although this improvement is not statistically significant . A trend towards improvement of specificity was also observed with the addition of ECG gating to traditional SPECT.According to very low quality evidence , neither the choice of stress agent ( exercise or pharmacologic ) nor the choice of radioactive tracer ( technetium vs. thallium ) significantly affect the diagnostic accuracy of SPECT for the diagnosis of CAD although a trend towards accuracy improvement was observed with the use of pharmacologic stress over exercise stress and technetium over thallium . Considerably heterogeneity was observed both within and between trials . This heterogeneity may explain why some of the differences observed between accuracy estimates for various subgroups were not statistically significant . More complex analytic techniques such as meta-regression may help to better underst and which study characteristics significantly influence the diagnostic accuracy of SPECT Background Although single photon emission computed tomography ( SPECT ) and positron emission tomography ( PET ) myocardial perfusion imaging ( MPI ) have evolved considerably over the last decade , there is no recent comparison of diagnostic performance . This study was design ed to assess relative image quality , interpretive confidence , and diagnostic accuracy by use of contemporary technology and protocol s. Methods and Results By consensus and without clinical information , 4 experienced nuclear cardiologists interpreted 112 SPECT technetium-99 m sestamibi and 112 PET rubidium-82 MPI electrocardiography (ECG)-gated rest/pharmacologic stress studies in patient population s matched by gender , body mass index , and presence and extent of coronary disease . The patients were categorized as having a low likelihood for coronary artery disease ( 27 in each group ) or had coronary angiography within 60 days . SPECT scans were acquired on a Cardio-60 system and PET scans on an ECAT ACCEL scanner . Image quality was excellent for 78 % and 79 % of rest and stress PET scans , respectively , versus 62 % and 62 % of respective SPECT scans ( both p < .05 ) . An equal percent of PET and SPECT gated images were rated excellent in quality . Interpretations were definitely normal or abnormal for 96 % of PET scans versus 81 % of SPECT scans ( p = .001 ) . Diagnostic accuracy was higher for PET for both stenosis severity thresholds of 70 % ( 89 % vs 79%,p = .03 ) and 50 % ( 87 % vs 71%,p = .003 ) and was higher in men and women , in obese and nonobese patients , and for correct identification of multivessel coronary artery disease . Conclusion In a large population of matched pharmacologic stress patients , myocardial perfusion PET was superior to SPECT in image quality , interpretive certainty , and diagnostic accuracy BACKGROUND The present study compared computed tomographic coronary angiography ( CTA ) and positron emission tomography ( PET ) for the detection of significant anatomical coronary artery stenosis as defined by conventional invasive coronary angiography ( CICA ) . METHODS The study protocol was approved by the local ethics board , and informed consent was obtained from all patients . Of the 26 patients ( mean age 57+/-9 years , 18 men ) who prospect ively underwent CTA and rubidium-82 PET before CICA , 24 patients had a history of chest pain . Images were interpreted by expert readers and assessed for the presence of anatomically significant coronary stenosis ( 50 % luminal diameter stenosis or greater ) or myocardial perfusion defects . Diagnostic test characteristics were analyzed using patient-based , territory-based , vessel-based and segment-based analyses . RESULTS In the 24 patients referred for chest pain , CTA had similar sensitivity to PET , but was more specific ( sensitivity 95 % [ 95 % CI 72 % to 100 % ] versus 95 % [ 95 % CI 72 % to 100 % ] , respectively ; specificity 100 % [ 95 % CI 46 % to 100 % ] versus 60 % [ 95 % CI 17 % to 93 % ] , respectively ) in the detection of patients with anatomical coronary artery stenosis of 50 % or greater . On a per-segment basis of all 26 patients , CTA had a sensitivity , specificity , positive predictive value and negative predictive value of 72 % , 99 % , 91 % and 95 % , respectively , in all coronary segments . CONCLUSIONS Coronary CTA has a similar sensitivity and specificity to rubidium-82 PET for the identification of patients with significant anatomical coronary artery disease Background Nonuniform attenuation artifacts cause suboptimal specificity of stress single photon emission computed tomography ( SPECT ) myocardial perfusion images . In phantoms , normal subjects , and patients suspected of having coronary artery disease ( CAD ) , we evaluated a new hybrid attenuation correction ( AC ) system that combines x-ray computed tomography ( CT ) with conventional stress SPECT imaging . Methods and Results The effect of CT-based AC was evaluated in phantoms by assessing homogeneity of normal cardiac inserts . AC improved homogeneity of normal cardiac phantoms from 11 % ± 2 % to 5 % ± 1 % ( P < .001 ) . Attenuation-corrected normal patient files were created from 37 normal subjects with a low likelihood ( <3 % ) of CAD . The diagnostic performance of AC for detection of CAD was evaluated in 118 patients who had stress technetium 99 m sestamibi or tetrofosmin stress SPECT imaging and coronary angiography . SPECT images with and without AC were interpreted by 4 blinded readers with different interpretative attitudes . Overall , AC improved the diagnostic performance of all readers , particularly the normalcy rate . The degree of improvement depended on interpretative attitude . Readers prone to high sensitivity or with less experience had the greatest gain in the normalcy rate , whereas a reader prone to higher specificity had improvements in sensitivity and specificity but not the normalcy rate . Importantly , improvement of one diagnostic variable was not associated with worsening of other variables . Conclusion CT-based AC of SPECT images consistently improved overall diagnostic performance of readers with different interpretive attitudes and experience . CT-based AC is well suited for routine use in clinical practice . ( J Nucl Cardiol 2005;12:676 - 86 . The purpose of the present study is to prospect ively compare myocardial perfusion imaging with rubidium-82 ( 82Rb ) by positron emission tomography ( PET ) with thallium-201 ( 201Tl ) imaging by single-photon emission tomography ( SPECT ) by recording both studies with a single dipyridamole h and grip stress , and reading both sets of images with the same display technique . In a series of 202 patients with previous coronary arteriography , the sensitivity , specificity , and accuracy of 82Rb PET were 93 % , 78 % , and 90 % and for 201Tl SPECT 76 % , 80 % , and 77 % , respectively . When 70 patients with previous therapeutic interventions were excluded , the remaining 132 patients showed a sensitivity , specificity , and accuracy of 95 % , 82 % and 92 % for 82Rb PET and 79 % , 76 % , and 78 % for 201Tl SPECT . The improved contrast resolution of PET result ed in markedly superior images and a more confident identification of defects Background Attenuation artifact remains a substantial limitation to confident interpretation of images and reduces laboratory efficiency by requiring comparison of stress and rest image sets . Attenuation-corrected stress-only imaging has the potential to ameliorate these limitations . Methods and Results Ten experienced nuclear cardiologists independently interpreted 90 stress-only electrocardiography (ECG)-gated technetium 99 m sestamibi images in a sequential fashion : myocardial perfusion imaging ( MPI ) alone , MPI plus ECG-gated data , and attenuation-corrected MPI with ECG-gated data . Images were interpreted for diagnostic certainty ( normal , probably normal , equivocal , probably abnormal , abnormal , and perceived need for rest imaging ) . With stress MPI data alone , only 37 % of studies were interpreted as definitely normal or abnormal , with a very high perceived need for rest imaging ( 77 % ) . The addition of gated data did not alter the interpretations . However , attenuation-corrected data significantly increased the number of studies characterized as definitely normal or abnormal ( 84 % , P < 005 ) and significantly reduced the perceived need for rest imaging ( 43 % , P < .005 ) . These results were confirmed by use of a nonsequential consensus interpretation of three readers . Conclusion Attenuation correction applied to studies with stress-only Tc-99 m ECG-gated single photon emission computed tomography images significantly increases the ability to interpret studies as definitely normal or abnormal and reduces the need for rest imaging . These findings may improve laboratory efficiency and diagnostic accuracy Background New iterative algorithms for scatter compensation ( SC ) , noise suppression , and depth-dependent collimator resolution ( RR ) can shorten rest and stress SPECT acquisitions by 50 % while maintaining quality and accuracy equivalent to conventional scans . Full-time stress-only myocardial perfusion SPECT is accurate and efficient when combined with line- source attenuation correction ( LSAC ) . We investigated the potential for half-time stress-only LSAC-SPECT by comparing this to conventional rest/stress SPECT in patients imaged for suspected CAD at three different centers . Methods One hundred and ten patients ( 58 % men , 53 % exercise ) had 64 projection rest/stress Tc-99 m ECG-gated SPECT with simultaneous Gd-153 LSAC : 18 had ≤5 % CAD likelihood and 92 had coronary angiography . The stress scans were retrospectively ‘ stripped ’ to create equally spaced 32 projection “ half-time ” ( HT ) scans for the emission and transmission ( TX ) projections . Astonish ( Philips , Milpitas , CA ) processing with AC , SC , and RR was applied to the HT data with the HT TX maps reconstructed using a Bayesian iterative method . The conventional rest/stress image sets processed using filtered back projection and without AC and the HT-AC stress-only images were interpreted in r and om sequence by consensus of two readers blinded to clinical information in separate reading sessions . Results Comparing rest/stress FBP and HT-LSAC , stress perfusion quality was excellent/good in 82 and 89 % ( P = .13 ) ; interpretive certainty ( definitely normal or abnormal ) was 88 and 95 % ( P = .14 ) ; sensitivity was 77 and 83 % ( P = .38 ) ; specificity was 67 and 71 % ( P = .65 ) ; normalcy was 94 and 100 % ( P = 1.0 ) ; SSS for CAD pts was 7.4 vs 7.8 and for non-CAD pts was 0.7 vs 0 ( P = .44 and .16 , respectively ) . Mean stress LVEF was 60 % in both groups . ConclusionS tress-only imaging with HT-LSAC using the Astonish acquisition/processing method provides results equivalent to conventional rest/stress scanning . This new approach has the potential to significantly improve operational efficiency without sacrificing accuracy OBJECTIVES This study sought to assess whether a transient ischemic dilation ratio , determined from automatically derived stress and rest left ventricular volumes during stress technetium-99 m ( Tc-99 m ) sestamibi/rest thallium-201 dual-isotope myocardial perfusion single-photon emission computed tomography ( SPECT ) , is useful for the identification of patients with severe and extensive coronary artery disease . BACKGROUND Transient ischemic dilation of the left ventricle on stress/redistribution thallium-201 scintigraphy has been shown to be a clinical ly useful marker of severe and extensive coronary artery disease . However , in practice , its assessment is highly subjective . This study automatically assessed the transient ischemic dilation ratio on the basis of a previously described algorithm to estimate three-dimensional ventricular boundaries . METHODS Normal limits for the transient ischemic dilation ratio were developed using data from 54 patients with a low likelihood ( < 5 % ) of coronary artery disease , and criteria for abnormality were developed based on data from 97 who under-went catheterization , of whom 34 had severe and extensive coronary artery disease , defined as > or = 90 % stenosis in the proximal left anterior descending coronary artery or in two or more coronary arteries , and 63 had no coronary artery disease ( 15 patients ) or mild to moderate coronary artery disease ( 48 patients ) . The criteria were then tested in a validation cohort of 77 additional patients who underwent catheterization , of whom 36 had severe and extensive coronary artery disease . The quantitative results of the dilation ratio were compared with the visual results of the dilation ratio and perfusion defect analysis . RESULTS For normal limits , receiver operating characteristic curve analysis showed that abnormal transient ischemic dilation ratio values corresponded to left ventricular endocardial volume ratios > 1.22 ( mean + /- 2 SD ) . Transient ischemic dilation assessment using these criteria for abnormality showed high sensitivity ( 24 [ 71 % ] of 34 ) and very high specificity ( 60 [ 95 % ] of 63 ) for severe and extensive coronary artery disease . When the analysis was applied to the prospect i ve catheterization group , similar sensitivity and specificity for severe and extensive coronary artery disease were observed ( 77 % and 92 % , respectively ) . Significant agreement ( p = 0.0001 ) was found between the degree of transient ischemic dilation and the Tc-99 m sestamibi defect extent , the latter assessed by semiquantitative visual analysis ( summed stress score ) . CONCLUSIONS The automatic measurement of transient ischemic dilation in dual-isotope myocardial perfusion SPECT is a clinical ly useful marker that is sensitive and highly specific for detection of severe and extensive coronary artery disease Purpose In clinical myocardial single photon emission computed tomography ( SPECT ) , attenuation artefacts may cause a loss of specificity in the identification of diseased vessels that can be corrected by means of gated SPECT ( GSPECT ) acquisition or CT attenuation correction ( AC ) . The purpose of this multicentre study was to assess the impact of GSPECT and AC on the diagnostic performance of myocardial scintigraphy , according to patient ’s sex , body mass index ( BMI ) and site of coronary artery disease ( CAD ) . Methods We studied a group of 104 patients who underwent coronary angiography within 1 month before or after the SPECT study . Patients with a BMI > 27 were considered “ overweight ” . Attenuation-corrected and st and ard GSPECT early images were r and omly interpreted by three readers blinded to the clinical data . Results In the whole group , GSPECT and AC showed a diagnostic accuracy of 86.5 % ( sensitivity 82 % , specificity 93 % ) and 77 % ( sensitivity 75.4 % , specificity 81.4 % ) , respectively ( p < 0.05 ) . In women , when anterior ischaemia was matched with CAD , AC failed to show any increase in specificity ( AC 63.6 % vs GSPECT 63.6 % ) with evident loss of sensitivity ( AC 72.7 % vs GSPECT 90.9 % ) . AC significantly improved SPECT specificity in the identification of right CAD in overweight men ( AC 100 % vs GSPECT 66.7 % , p < 0.05 ) . Conclusion AC improved specificity in the evaluation of right CAD in overweight men . In the other evaluable subgroups specificity was not significantly affected while sensitivity was frequently reduced Background Obesity is a growing problem in the United States , and attenuation artifacts are more prevalent in this patient group . This study evaluated the impact of attenuation correction in patients with a high body mass index ( BMI ) . Methods and Results Three readers interpreted gated attenuation-corrected and non-attenuation-corrected rest/stress technetium 99 m sestamibi myocardial perfusion imaging results in 116 patients ( BMI < 30 , n = 60 ; BMI ≥30 , n = 56 ) who had coronary angiography no more than 60 days after imaging . Readers were blinded to all clinical information and as to whether myocardial perfusion imaging was attenuation-corrected or non-attenuation-corrected . Sensitivity , specificity , and accuracy for detection of coronary artery disease of 70 % or greater for attenuation-corrected versus non-attenuation-corrected single photon emission computed tomography ( SPECT ) were 86 % versus 89 % , 79 % versus 50 % , and 84 % versus 79 % , respectively . Sensitivity , specificity , and accuracy for attenuation-corrected versus non-attenu-ation-corrected SPECT for patients with BMI less than 30 were 90 % versus 90 % , 82 % versus 64 % , and 88 % versus 85 % , respectively . For BMI of 30 or greater , the results were 82 % versus 87 % , 76 % versus 41 % , and 80 % versus 73 % , respectively . There was a significant difference in specificity overall ( P = .02 ) and for the category of BMI of 30 or greater ( P = .03 ) . Conclusions This study demonstrates that electrocardiography-gated attenuation-corrected Tc-99 m sestamibi SPECT myocardial perfusion imaging improves specificity compared with electrocardiography-gated non-attenuation-corrected SPECT myocardial perfusion imaging , especially in patients with BMI of 30 or greater The use of myocardial perfusion 82Rb PET/CT studies continues to increase but its accuracy using data base quantification methods for the diagnosis of coronary artery disease ( CAD ) has not been established . Methods : A sex-independent normal data base and criteria for abnormality for rest – stress 82Rb PET/CT myocardial perfusion imaging were developed and vali date d by evaluation of 281 patients ( 136 females : mean age ± SD , 63.3 ± 13.3 y ; 145 males : mean age ± SD , 63.9 ± 12.8 y ) who underwent a rest – adenosine stress 82Rb PET/CT study . These patients were divided into 3 groups : ( a ) healthy group : 30 patients , with < 5 % likelihood of CAD ( low likelihood [ LLK ] ) based on sequential Bayesian analysis ; these patients were used to generate the normal distribution ; ( b ) pilot group : 174 patients ; these patients were used to determine the optimal criteria for detecting and localizing the perfusion abnormality ; and ( c ) validation group : 76 patients ( 23 with LLK of CAD and 53 who underwent coronary angiography ; these patients were used for prospect i ve validation . Results : Of the 53 patients who underwent coronary angiography , 8 had < 50 % stenosis and 45 patients had at least one stenosis ≥50 % in one major artery . Fifteen patients had single-vessel disease , 17 had double-vessel disease , and 13 had triple-vessel disease . The prospect i ve validation shows a normalcy rate of 78 % ( 18/23 ) for global CAD . The analyses by individual arteries show a normalcy rate of 96 % ( 22/23 ) for the left anterior descending coronary artery , 96 % for the left circumflex coronary artery ( 22/23 ) , and 100 % for the right coronary artery ( 23/23 ) . The overall sensitivity for detection of CAD ( ≥50 % stenosis ) was 93 % ( 42/45 ) . The overall specificity for detection of the absence of CAD ( ≤50 % stenosis ) was 75 % ( 6/8 ) . Also , the positive predictive value for global CAD was 95 % ( 42/44 ) , the negative predictive value was 67 % ( 6/9 ) , and the accuracy was 91 % ( 48/53 ) . Conclusion : The quantitative 82Rb PET/CT data base created and vali date d in this study is highly accurate for the detection and localization of CAD . Physicians should consider using the quantitative output of these algorithms as decision support tools to aid with image interpretation |
12,080 | 29,447,720 | Use of the ultrasonographic technique review ed in this guideline may help identify women at risk of preterm birth and , in some circumstances , lead to interventions that may reduce the rate of preterm birth . | OBJECTIVES To review ( 1 ) the use of ultrasonographic-derived cervical length measurement in predicting preterm birth and ( 2 ) interventions associated with a short cervical length .
OUTCOMES Reduction in rates of prematurity and /or better identification of those at risk , as well as possible prevention of unnecessary interventions .
BENEFITS , HARMS , AND COSTS Preterm birth is a leading cause of perinatal morbidity and mortality . | OBJECTIVE The aim of this study was to compare perinatal outcomes of patients with second-trimester ultrasonographic evidence of preterm dilatation of the internal os treated with cerclage versus those of patients not treated with cerclage . STUDY DESIGN From May 1998 through June 1999 patients with ultrasonographic evidence of preterm dilatation of the internal os between 16 and 24 weeks ' gestation were r and omly assigned to receive a McDonald cerclage or no cerclage . Before r and om assignment all patients underwent amniocentesis and urogenital cultures and then received 48 hours of therapy with indomethacin and antibiotics . After treatment each patient was followed up as an outpatient with bed rest and weekly ultrasonographic evaluation . RESULTS Of the 61 patients 31 were r and omly assigned to cerclage and 30 were r and omly assigned to no cerclage . There were no differences between groups with respect to maternal demographic characteristics , risk factors for preterm birth , cervical measurements , rescue procedures , readmission , chorioamnionitis , and abruptio placentae . The mean gestational age at delivery ( 33.5 + /- 6.3 weeks ) and the perinatal death rate ( 12 . 9 % ) in the cerclage group were similar to the mean gestational age at delivery ( 34.7 + /- 4.7 weeks ; P = .4 ) and the perinatal death rate ( 10.0 % ; P = .9 ) in the no-cerclage group . CONCLUSION Treatment with McDonald cerclage of preterm dilatation of the cervix detected ultrasonographically during the second trimester did not improve perinatal outcomes OBJECTIVE Our purpose was to compare the accuracy of ultrasonographic and manual cervical examinations for the prediction of preterm delivery . STUDY DESIGN One hundred two singleton pregnancies at high risk for preterm delivery were followed up prospect ively from 14 to 30 weeks with both serial cervical ultrasonography measurements and manual examinations of the length of the cervix . The primary outcome studied was preterm ( < 35 weeks ) delivery . RESULTS Excluding six induced preterm deliveries , 96 pregnancies were analyzed . The mean cervical length measured by ultrasonography was 20.6 mm in pregnancies delivered preterm ( n = 17 ) and 31.3 mm in pregnancies delivered at term ( n = 79 ) ( p = 0.003 ) ; the mean cervical lengths measured by manual examination were 16.1 mm and 18.6 mm in the same preterm and term pregnancies , respectively ( not significant ) . The sixteenth- and twentieth-week ultrasonographic cervical lengths predicted preterm delivery most accurately ( p < 0.0005 ) . The 25th percentiles of ultrasonographic ( 25 mm ) and manual ( 16 mm ) cervical lengths showed relative risks for preterm delivery of 4.8 ( 95 % confidence interval 2.1 to 11.1 , p = 0.0004 ) and 2.0 ( 95 % confidence interval 0.5 to 4.7 , p = 0.1 ) , respectively ; sensitivity , specificity , and positive and negative predictive values were 59 % , 85 % , 45 % , 91 % , and 41 % , 77 % , 28 % , and 86 % , respectively . CONCLUSION Cervical length measured by ultrasonography is a better predictor of preterm delivery than is cervical length measured by manual examination . Cervical ultrasonography in patients at high risk for preterm birth seems to be most predictive of preterm delivery when it is performed between 14 and 22 weeks ' gestation OBJECTIVE To compare cervical length measurements obtained at 11 to 14 weeks and 22 to 24 weeks of gestation in an unselected group of pregnant women and to correlate the measurements with time of delivery . METHODS This was a prospect i ve study involving 529 pregnant women attending for routine antenatal care who underwent transvaginal scans at 11 - 14 weeks and 22 - 24 weeks for evaluation of cervical length . The mean cervical length was calculated at both stages of gestation and lengths were compared between groups which delivered at term or prematurely , this being defined as delivery before 37 completed weeks of gestation . RESULTS The mean cervical lengths at 11 - 14 and 22 - 24 weeks were , respectively , 42.4 mm and 38.6 mm . Cervical length at 11 - 14 weeks was not significantly different between the groups which delivered at term ( 42.7 mm ) and preterm ( 40.6 mm ) . However , at the 22 - 24-week evaluation , cervical length was significantly shorter in the group which had a preterm delivery than in that which had a term delivery ( 26.7 mm and 39.3 mm , respectively ; P = 0.0001 ) . In the group of women with a previous history of one or more preterm deliveries , there was a greater shortening in cervical length from the first to the second evaluation than there was in the group of women with no previous history of preterm delivery . This shortening was also more pronounced in the group which delivered prematurely ( from 40.6 mm to 26.7 mm ) than in that which delivered at term ( from 42.7 mm to 39.3 mm ) . CONCLUSION There is a spontaneous shortening in the pregnant cervix from the first to the second trimester of pregnancy . The shortening is more rapid in pregnant women who deliver prematurely and who have a history of previous preterm delivery BACKGROUND Measurement of mid-gestation cervix length has become a common screening tool for preterm birth . Our study was design ed to assess the value of cervix length and serum relaxin in the prediction of spontaneous preterm birth at < 35 and < 37 weeks ' gestation in a general obstetric population . METHODS A prospect i ve cohort of women with a singleton pregnancy had blood collected at 24 and 28 weeks ' gestation for determination of serum relaxin immediately before transvaginal ultrasound measurement of cervical length . Patients and referring physicians were blinded to cervix length and relaxin levels to preclude changes in management . The primary outcomes were spontaneous delivery at < 35 and < 37 weeks ' gestation . RESULTS A total of 1004 women entered the study . Delivery data were not available for 20 women who delivered elsewhere . Twenty women were excluded because preterm delivery was undertaken because of pregnancy abnormalities . Of the 964 women with known gestational age at delivery , 46 ( 4.8 % ) delivered at < 37 weeks and 16 ( 1.7 % ) at < 35 weeks ' gestation . Mean cervix length at 28 weeks ( 36.7 + /- 7.3 mm ) was significantly shorter than at 24 weeks ( 37.8 + /- 7.1 mm ) ( P < 0.001 ) . Cervix length at 24 and 28 weeks ' gestation was equally predictive of preterm birth . A cervix length of < or = 30 mm at 28 weeks had a sensitivity of 57.1 % , a specificity of 81.8 % , and a positive predictive value of 4.5 % for birth at < 35 weeks . Serum relaxin levels were not correlated with cervix length at either 24 or 28 weeks . Serum relaxin at 24 and 28 weeks ' gestation was not associated with preterm birth before or after controlling for patient characteristics and cervix length . CONCLUSION Serum relaxin levels at 24 and 28 weeks ' gestation are not associated with preterm birth . Although cervix length is associated with preterm birth , its positive predictive value is low . Given the lack of proven therapies for those at risk , cervix length does not appear to be a useful screening tool for preterm delivery in the general obstetric population OBJECTIVE To investigate the efficacy of vaginal progesterone to prevent early preterm birth in women with sonographic evidence of a short cervical length in the midtrimester . METHODS This was a planned , but modified , secondary analysis of our multinational , multicenter , r and omized , placebo-controlled trial , in which women were r and omized between 18 + 0 and 22 + 6 weeks of gestation to receive daily treatment with 90 mg of vaginal progesterone gel or placebo . Cervical length was measured with transvaginal ultrasound at enrollment and at 28 weeks of gestation . Treatment continued until either delivery , 37 weeks of gestation or development of preterm rupture of membranes . Maternal and neonatal outcomes were evaluated for the subset of all r and omized women with cervical length < 28 mm at enrollment . The primary outcome was preterm birth at < /= 32 weeks . RESULTS A cervical length < 28 mm was identified in 46 r and omized women : 19 of 313 who received progesterone and 27 of 307 who received the placebo . Baseline characteristics of the two groups were similar . In women with a cervical length < 28 mm , the rate of preterm birth at < /= 32 weeks was significantly lower for those receiving progesterone than it was for those receiving the placebo ( 0 % vs. 29.6 % , P = 0.014 ) . With progesterone , there were fewer admissions into the neonatal intensive care unit ( NICU ; 15.8 % vs. 51.9 % , P = 0.016 ) and shorter NICU stays ( 1.1 vs. 16.5 days , P = 0.013 ) . There was also a trend toward a decreased rate of neonatal respiratory distress syndrome ( 5.3 % vs. 29.6 % , P = 0.060 ) . CONCLUSION Vaginal progesterone may reduce the rate of early preterm birth and improve neonatal outcome in women with a short sonographic cervical length OBJECTIVES To assess the role of cervical sonography and to compare various sonographic cervical parameters in their ability to predict spontaneous preterm birth in high-risk singleton gestations . DESIGN A prospect i ve cohort of 469 high-risk gestations were longitudinally evaluated between 15 and 24 weeks ' gestation on 1265 occasions with transvaginal cervical sonography and transfundal pressure . The cervical parameters obtained were funnel width and length , cervical length , percent funneling and cervical index . The information obtained was used for patient management . Restriction of physical activities was initiated at cervical lengths of < or = 2.5 cm with cerclage as an option for cervical lengths of < or = 2.0 cm . RESULTS Receiver operating characteristic curve analyses showed that a cervical length of < or = 2.5 cm between 15 and 24 weeks ' gestation was equal to the other sonographic cervical parameters in its ability to predict spontaneous preterm birth . The sensitivities for delivery at < 28 , < 30 , < 32 and < 34 weeks ' gestation were 94 % , 91 % , 83 % and 76 % , respectively , while the negative predictive values were 99 % , 99 % , 98 % and 96 % , respectively . The placement of a cerclage did not influence the positive and negative predictive values . In comparison to women with other risk factors , cervical length was best in the prediction of preterm birth in women with a prior mid-trimester loss ; an optimal cut-off of < or = 1.5 cm had sensitivities for delivery at < 28 , < 30 , < 32 and < 34 weeks ' gestation of 100 % , 100 % 92 % and 81 % , respectively . The rate of preterm delivery at < 34 weeks ' gestation increased dramatically when the cervical length was < or = 1.5 cm . Cervical length was the only independent variable that entered the logistic regression model for the prediction of preterm delivery at < 34 weeks ' gestation . CONCLUSIONS In high-risk singleton gestations a cervical length of < or = 2.5 cm was equal to other sonographic cervical parameters in its ability to predict spontaneous preterm birth and was better for the prediction of earlier forms of prematurity ( at < 28 and < 30 weeks ) than later forms ( at < 32 and < 34 weeks ) . The optimal cervical lengths and their performance for predicting prematurity may be influenced by obstetric risk factors In a cohort of 43 women with viable , singleton pregnancies , cervical dilatation greater than 4 cm , and absent labor between 20 and 27 weeks gestation , 22 women who underwent emergency cerclage within six hours of admission , were compared prospect ively with 15 women who elected conservative bed rest treatment . The two groups were demographically similar . Emergency cervical cerclage result ed in a longer mean gestational age at delivery compared to bed rest ( p = 0.001 ) . Women treated with cerclage required a significantly shorter period of antepartum hospitalization ( p = 0.001 ) , required less tocolysis ( p = 0.005 ) , and experienced fewer preterm membrane ruptures compared to women in the bed rest group ( p = 0.01 ) , although the latency period , following preterm rupture of membranes was shorter in the cerclage group ( p = 0.005 ) . There was no statistical difference in the frequencies of chorioamnionitis , maternal morbidity and cesarean section between the two groups . Although the perinatal mortality in the two groups was not significantly different ( p = 0.3 ) , emergency cerclage result ed in a significantly higher mean birth weight compared to conservative bed rest treatment ( p = 0.02 ) . This study demonstrates the superiority of emergency cerclage to bed rest in women with advanced cervical dilatation and absent labor in late second-trimester of pregnancy OBJECTIVE To compare preterm delivery rates ( before 34 weeks of gestation ) and neonatal morbidity and mortality in patients with risk factors or symptoms of cervical incompetence managed with therapeutic McDonald cerclage and bed rest versus bed rest alone . STUDY DESIGN Cervical length was measured in patients with risk factors or symptoms of cervical incompetence . Risk factors for cervical incompetence included previous preterm delivery before 34 weeks of gestation that met clinical criteria for the diagnosis of cervical incompetence , previous preterm premature rupture of membranes before 32 weeks of gestation , history of cold knife conization , diethylstilbestrol exposure , and uterine anomaly . When a cervical length of < 25 mm was measured before a gestational age of 27 weeks , a r and omization for therapeutic cerclage and bed rest ( cerclage group ) or bed rest alone ( bed rest group ) was performed . The analysis is based on intention to treat . RESULTS Of the 35 women who met the inclusion criteria , 19 were allocated r and omly to the cerclage group and 16 to the bed rest group . Both groups were comparable for mean cervical length and mean gestational age at time of r and omization , mean overall 20 mm and 21 weeks . Preterm delivery before 34 weeks was significantly more frequent in the bed rest group than in the cerclage group ( 7 of 16 vs none , respectively ; P = .002 ) . There was no statistically significant difference in neonatal survival between the groups ( 13 neonates survived in the bed rest group vs all in the cerclage group ) . The compound neonatal morbidity , defined as admission to the neonatal intensive care unit or neonatal death , was significantly higher in the bed rest group than in the cerclage group ( 8 of 16 vs 1 of 19 , respectively ; P = .005 ; RR = 9.5 , 95 % CI , 1.3 - 68.1 ) . CONCLUSIONS Therapeutic cerclage with bed rest reduces preterm delivery before 34 weeks of gestation and compound neonatal morbidity in women with risk factors and /or symptoms of cervical incompetence and a cervical length of < 25 mm before 27 weeks of gestation Objective : Women with uterine anomalies have higher rates of preterm birth , but the reason for this has not been eluci date d. Transvaginal ultrasound examination has been shown to be an accurate test for the prediction of preterm birth but has not been studied specifically in this population . Methods : Pregnant women with uterine anomalies were followed prospect ively with transvaginal ultrasound examination of the cervix , performed between 14 and 23 6/7 weeks of gestation . A short cervical length was defined as less than 25 mm of cervical length . The primary outcome was spontaneous preterm birth , defined as birth at less than 35 weeks . Results : Of the 64 pregnancies available for analysis , there were 28 with a bicornuate uterus , 13 with a septate uterus , 11 with a uterine didelphys , and 12 with a unicornuate uterus . The overall incidence of spontaneous preterm birth at less than 35 weeks was 11 % . Of the 10 ( 16 % ) women with a short cervical length , 5 ( 50 % ) had spontaneous preterm birth . Of the 54 women without a short cervical length , only 2 ( 4 % ) had a spontaneous preterm birth . The sensitivity , specificity , and positive and negative predictive values of a short cervical length for spontaneous preterm birth were 71 % , 91 % , 50 % , and 96 % , respectively ( relative risk 13.5 , 95 % confidence interval 3.49–54.74 ) . Of the 7 women with both short cervical length and preterm birth , all uterine subtypes were represented except septate uterus . Conclusion : A short cervical length on transvaginal ultrasonography in women with uterine anomalies has a 13-fold risk for preterm birth . Unicornuate uterus had the highest rate of cervical shortening and preterm delivery . Level of Evidence : OBJECTIVE The purpose of this study was to assess cases of ultrasound-indicated cervical cerclage and to relate preoperative cervical length , operative findings , postoperative cervical length , and pregnancy outcome to establish the appropriate criteria to offer cervical cerclage . STUDY DESIGN A prospect i ve observational study comprised 380 women at high risk of preterm labor who underwent serial transvaginal ultrasonographic assessment of cervical length . Seventy-three women had criteria for and underwent cervical cerclage . Data concerning preoperative cervical length , operative findings , postoperative cervical length , and pregnancy outcome were collected . Statistical analysis was performed with Mann-Whitney and Fisher exact tests . RESULTS There was a significant increase in median cervical length after cerclage , 15.0 versus 25.0 mm ( P < .0001 ) . Preoperative cervical length and postoperative upper cervical length were independently better predictors of outcome than postoperative entire cervical length . Fetal membranes were visible in 18 % of cases at the time of suture insertion , which was associated with a significantly worse outcome , regardless of preoperative cervical length . Of those 41 women with a very short preoperative cervical length ( < or = 15 mm ) , outcome was significantly worse in those women with visible fetal membranes at the time of cerclage compared with those women with no visible fetal membranes at the time of cerclage : median gestational age at delivery , 23 weeks versus 37 weeks 4 days ( P = .002 ) ; suture insertion to delivery interval , 19 days versus 108 days ( P = .0004 ) ; and fetal survival rates , 50 % versus 86 % ( P = .03 ) . CONCLUSION In a high-risk population that undergoes serial transvaginal ultrasound surveillance of cervical length , the presence of visible fetal membranes at the time of suture insertion , regardless of preoperative cervical length , is associated with a poor outcome . Fetal membranes were not visible in any cases with a preoperative cervical length of > 15 mm . These findings lend support to a practice of offering cerclage at or above a cervical length of 15 mm PURPOSE A major advantage of transperineal sonography ( TPUS ) is its ability to evaluate the cervix without causing any distortion . This study was performed to compare transvaginal sonography ( TVUS ) and TPUS at 24 weeks of gestation in predicting preterm delivery in low-risk pregnancy . METHODS Three hundred fifty-seven pregnant women underwent TVUS and TPUS at 24 weeks of gestation . The relationship between cervical length and preterm delivery was assessed . Accuracy values of TVUS and TPUS at 24 weeks of gestation were compared in predicting preterm delivery . RESULTS Preterm delivery ( before 36 weeks of gestation ) occurred in 22 pregnancies ( 6.2 % ) . Mean cervical lengths measured by TVUS and TPUS were significantly different in preterm and term delivery groups ( P < 0.05 ) . Areas under the curves were 0.801 and 0.857 for the transvaginal and transperineal measurements , respectively . The coefficient of correlation between the transvaginal and transperineal cervical length measurements was 0.83 . TPUS had a sensitivity of 77 % in predicting preterm delivery , with a false-positive rate of 17 % and a relative risk of 4.5 at the 32.5-mm cutoff value . CONCLUSIONS When the cervix is well visualized , TPUS can predict preterm delivery as accurately as TVUS OBJECTIVE The purpose of this study was to determine whether selective use of fetal fibronectin detection after ultrasound measurement of cervical length predicts preterm delivery in symptomatic patients better than either indicator alone . STUDY DESIGN This prospect i ve blinded study performed both tests on 359 women hospitalized for preterm labor between 18 and 34 completed weeks ' gestation . The primary outcome was preterm delivery before 35 weeks'gestation . RESULTS Among the 359 women included , 48 ( 13.4 % ) delivered before 35 weeks ' gestation . The sensitivity , specificity , and positive and negative predictive values of cervical length < or = 25 mm were 75 % , 63 % , 24 % , and 94 % , respectively , and of fetal fibronectin > or = 50 ng/mL , 63 % , 81 % , 33 % , and 93 % . Fetal fibronectin detection was significantly ( P < .001 ) more specific than cervical length measurement . For selective use of fetal fibronectin detection after cervical length measurement , the test was considered positive if cervical length was < or = 15 mm or if cervical length was between 16 and 30 mm with fetal fibronectin > or = 50 ng/mL. The predictive values of this test were not significantly different from those of fetal fibronectin detection ( 67 % , 81 % , 36 % , and 94 % ) . This strategy could have avoided 200 fibronectin tests . CONCLUSION Selective use of fetal fibronectin detection after cervical length measurement is more specific than cervical length and as effective as fetal fibronectin assays in the entire population of women in preterm labor for predicting preterm birth OBJECTIVE The purpose of this study was to compare the diagnostic performance of ultrasonographic and digital examination of the cervix in the prediction of preterm delivery in patients presenting with preterm labor and intact membranes . STUDY DESIGN Endovaginal ultrasonography was performed in 59 patients admitted with preterm labor ( 20 to 35 weeks ) and cervical dilatation of < 3 cm . Cervical parameters evaluated included endocervical length , the presence of funneling , funnel length , funnel width , cervical index ( [ Funnel length + 1]/Endocervical length ) , and cervical dilatation and effacement as determined by digital examination . Outcome variables were the occurrence of preterm delivery ( < 36 weeks ) and the admission-to-delivery interval . RESULTS The prevalence of preterm delivery was 37.3 % ( 22/59 ) . Receiver-operator characteristic curve and logistic regression analyses indicated a significant relationship between the occurrence of preterm delivery and ultrasonographic cervical parameters ( p < 0.005 for each ) but not with the results of digital examination of the cervix . Survival analysis demonstrated a shorter admission-to-delivery interval for patients with an abnormal cervical index or endocervical length ( p < 0.005 for each ) . CONCLUSIONS Endovaginal ultrasonographic examination of the uterine cervix is more accurate than digital examination of the cervix in the assessment of the risk for preterm delivery in patients with preterm labor and intact membranes OBJECTIVE False positive diagnosis of preterm labor is common . As a consequence , medications including corticosteroids to promote fetal lung maturity and tocolysis are prescribed unnecessarily . We tested the hypothesis that management of threatened preterm labor based on measurement of cervical length by ultrasonography can reduce the number of women who receive inappropriate treatment . METHODS Forty-one women with threatened preterm labor for whom a clinical decision was made to prescribe antenatal corticosteroids and tocolysis were r and omized to have their cervical length measured by transvaginal ultrasound ( n=21 ) or to receive therapy as planned ( n=20 ) . Fourteen women in the ultrasound group had a cervix longer than 15 mm and the therapy was withheld , while the other seven with a short cervix were managed in the same way as the control group . RESULTS Three women ( 14 % ) in the ultrasound group were treated inappropriately with antenatal corticosteroids because they remained undelivered for more than a week . This compared favorably with the control group where 18 out of 20 ( 90 % ) received corticosteroids unnecessarily ( relative risk ( RR ) 0.16 ; 95 % confidence interval ( CI ) , 0.05 - 0.39 ) . Tocolysis was given to only seven women ( 33.3 % ) in the ultrasound group compared with 20 ( 100 % ) in the control group ( RR 0.3 ; 95 % CI , 0.15 - 0.54 ) . There were no babies in either group who were born prematurely without being given a full course of antenatal corticosteroid therapy . CONCLUSION Women with threatened preterm labor and cervical length more than 15 mm should not receive tocolysis . The issue of the safety of withholding corticosteroid therapy in this clinical scenario warrants further study Evaluation of the gravid cervix uteri is an important part of prenatal care , especially in the patient at risk for preterm birth . Seeking a method of cervical length measurement that could be used easily regardless of patient habitus , location of the cervix , and gestational age , we used a vaginal probe with a 240 ° scanning angle in gravidas at various gestational ages to test the theoretical advantages of the wide scanning angle . Among the first 201 examinations , cervical length was measured successfully in 99.5 % of cases . This success rate compares favorably with those of abdominal sonography and vaginal sonography using the st and ard 90 scanning angle sector probes . We also compared this method with digital examination in a double-blind fashion . Only a fair degree of association between sonographic cervical measurements and measurements obtained by digital examination was found , reflected in a correlation coefficient of 0.49 Objective . The aim of the study was to examine the clinical value of cervical assessment by transvaginal ultrasonography in women with symptoms of preterm labor . Methods . We prospect ively evaluated 172 women with singleton pregnancies and symptoms of preterm labor . Seventy of them were nulliparas , while 102 were multiparas . Gestational age ranged between 24 and 34 wks . All women underwent cervical assessment with transvaginal ultrasonography and were given intravenous tocolytics . The only parameter evaluated was cervical length . Women with multiple pregnancies , gestational age < 24 wks or > 34 wks , cervical dilatation > 2 cm , placenta praevia , premature rupture of membranes , or cervical cerclage were excluded from the study . The outcome measure was delivery before 34 wks gestation . Results . The preterm delivery rate before 34 wks was 37 % . The sensitivity and the specificity of a cervical length of less than 20 mm was 60 and 53.8 % and 97.7 and 95.2 % for nulliparas and multiparas , respectively . A cervical length < 20 mm was also 93.7 % predictive of preterm delivery in nulliparas and 87.5 % in multiparas , while the corresponding numbers for its negative predictive value ( NPV ) were 81.4 and 76.9 % , respectively . Conclusions . Cervical assessment in women with symptoms of preterm labor can distinguish those at high risk for preterm delivery . Cervical sonography can be a valuable adjunct to the clinical evaluation of these patients OBJECTIVE The purpose of this study was to determine whether a knowledge of fetal fibronectin results affects patient treatment and health care costs . STUDY DESIGN Women between 24 and 34 weeks of gestation with a singleton pregnancy and preterm uterine contractions were eligible for enrollment . Once informed consent was given , a fetal fibronectin specimen was obtained , and women were assigned r and omly into 2 groups . In 1 group , results of the fetal fibronectin test were available ; in the other group , results were not available . The use of inpatient and outpatient health care re sources subsequent to enrollment was ascertained through the use of medical records , hospital billing data , and patient interviews . This study was powered to allow the detection in the fetal fibronectin group of a 20 % reduction in total health care-related costs . RESULTS The 2 groups were similar with respect to maternal age , parity , race , cervical examination at admission , and estimated gestational age at enrollment and at delivery . Women who did not have fetal fibronectin results available were no different than those women who did with respect to initial length of labor and delivery observation ( median , 4 hours vs 3 hours ) , hospital admission ( 28 % vs 26 % ) , tocolysis ( 18 % vs 16 % ) , cessation of work ( 27 % vs 26 % ) , or total health care-related costs ( log mean + /- SD , 7.6 + /- 1.2 vs 7.5 + /- 1.1 ) . CONCLUSION In this study population , the use of fetal fibronectin did not affect physician behavior or health care costs related to preterm contractions OBJECTIVES We sought to determine the predictive accuracy for preterm delivery of transvaginal ultrasonography of the cervix between 14 and 24 weeks ' gestation in high-risk patients and to determine whether cerclage prevents preterm delivery in patients with ultrasonographic cervical changes . STUDY DESIGN Patients with asymptomatic singleton pregnancies at high risk for preterm delivery were followed prospect ively from 14 weeks ' to 23 weeks 6 days ' gestation with transvaginal ultrasonography of the cervix . The subgroup of patients with either a cervical length of < 25 mm or funneling of > 25 % or both was offered McDonald salvage cerclage , which was performed at the discretion of the patient and the obstetrician . The 2 groups ( with and without cerclage ) were compared for the primary outcome of preterm delivery at < 35 weeks ' gestation . RESULTS One hundred sixty-eight women were followed , including 97 ( 58 % ) with > /=1 prior 14- to 34-week preterm deliveries . Of 63 ( 37 . 5 % ) patients identified as having cervical changes , 23 ( 37 % ) had preterm delivery ; of 105 patients with no cervical changes , 8 ( 8 % ) had preterm delivery ( relative risk , 4.8 ; 95 % confidence interval , 2 . 3 - 10.1 ) . The sensitivity , specificity , and positive and negative predictive values of either a short cervix of < 25 mm or funneling of > 25 % or both were 74 % , 70 % , 37 % , and 92 % , respectively . Of 63 pregnancies in which there were cervical changes , 39 underwent cerclage and 24 did not . These 2 groups were similar for demographic characteristics , risk factors , and transvaginal ultrasonographic cervical length and funneling but dissimilar for gestational age at identification of cervical changes ( 18.3 vs 21.2 weeks ' gestation in the groups with and without cerclage , respectively ; P < .001 ) . Multivariate logistic regression analysis after adjustment for gestational age at cervical changes showed no difference in the rate of preterm delivery between the groups with and without cerclage ( odds ratio , 1.1 ; 95 % confidence interval , 0.3 - 4.6 ) . Stratified analysis of patients identified between 18 and 24 weeks revealed 22 pregnancies with cerclage and 22 pregnancies without cerclage , which was similar for all characteristics studied . The incidence of preterm delivery remained similar ( 27 % vs 23 % , respectively ; P = .7 ) , as did days from cervical changes to delivery ( 111 vs 96 , respectively ; P = .2 ) . CONCLUSIONS Transvaginal ultrasonography of the cervix between 14 and 24 weeks ' gestation is a good predictor of preterm delivery in high-risk pregnancies . Cerclage may not prevent preterm delivery in patients identified to be at high risk for this outcome by transvaginal ultrasonography OBJECTIVE This study was undertaken to determine the predictive accuracy for preterm birth of transvaginal ultrasound ( TVU ) of the cervix in women with a prior cone biopsy . STUDY DESIGN Pregnant patients with a history of cervical cone biopsy by cold knife , loop electrosurgical excision procedure ( LEEP ) , or laser were monitored prospect ively with TVU of the cervix between 16 and 24 weeks . The predictive value of TVU was evaluated by using less than 25 mm cervical length as criteria for the definition of a short cervix . The primary outcome was spontaneous preterm birth less than 35 weeks . RESULTS Of 109 women with prior cone biopsy identified , 55 had LEEP , 45 cold knife , and 9 laser cone biopsies . Thirty ( 28 % ) had a short cervix , with 9 ( 30 % ) having spontaneous preterm birth less than 35 weeks . Seventy-nine ( 72 % ) did not have a short cervix , with 5 ( 6 % ) having spontaneous preterm birth less than 35 weeks . The sensitivity , specificity , and positive and negative predictive values for spontaneous preterm birth were 64 % , 78 % , 30 % , and 94 % , respectively ( relative risk [ RR ] 4.7 , 95 % CI 1.6 - 15.3 ) . CONCLUSION TVU of the cervix is predictive of preterm birth in women with prior cone biopsy OBJECTIVE Shortening of the cervix that occurs early in gestation as determined by ultrasonography has been correlated with subsequent spontaneous preterm birth . Because previous studies have compared transperineal and endovaginal ultrasonographic assessment of the cervix over a wide gestational age range , we compared these methods in the midtrimester . STUDY DESIGN We performed a prospect i ve , blinded comparison of endovaginal and transperineal cervical ultrasonographic assessment . Unselected gravid women at 15 - 23 weeks ' gestation were sequentially examined by 2 experienced sonographers using an endovaginal probe and a curvilinear probe . For each patient the initial sonographer and examination method were r and omly assigned . The sonographer who performed the second examination was blinded to the results and images from the first examination . RESULTS One hundred two women were studied at a mean of 19.6 weeks ' gestation . The overall inter method correlation was poor ( R = 0.38 ) . In 12 cases a transperineal measurement could not be obtained because of poor visualization of the required l and marks . In 33 % of cases the inter method difference in cervical length was > /=20 % . There was no correlation in the identification of funneling at the internal os and very small correlation for the identification of a poorly developed lower uterine segment . CONCLUSION Transperineal ultrasonographic imaging of the cervix is an unsatisfactory alternative to an endovaginal assessment in the midtrimester BACKGROUND The role of the cervix in the pathogenesis of premature delivery is controversial . In a prospect i ve , multicenter study of pregnant women , we used vaginal ultrasonography to measure the length of the cervix ; we also documented the incidence of spontaneous delivery before 35 weeks ' gestation . METHODS At 10 university-affiliated prenatal clinics , we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies . We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery . RESULTS We examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks . Spontaneous preterm delivery ( at less than 35 weeks ) occurred in 126 of the women ( 4.3 percent ) examined at 24 weeks . The length of the cervix was normally distributed at 24 and 28 weeks ( mean [ + /- SD ] , 35.2 + /- 8.3 mm and 33.7 + /- 8.5 mm , respectively ) . The relative risk of preterm delivery increased as the length of the cervix decreased . When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile , the relative risks of preterm delivery among the women with shorter cervixes were as follows : 1.98 for cervical lengths at or below the 75th percentile ( 40 mm ) , 2.35 for lengths at or below the 50th percentile ( 35 mm ) , 3.79 for lengths at or below the 25th percentile ( 30 mm ) , 6.19 for lengths at or below the 10th percentile ( 26 mm ) , 9.49 for lengths at or below the 5th percentile ( 22 mm ) , and 13.99 for lengths at or below the 1st percentile ( 13 mm ) ( P < 0.001 for values at or below the 50th percentile ; P = 0.008 for values at or below the 75th percentile ) . For the lengths measured at 28 weeks , the corresponding relative risks were 2.80 , 3.52 , 5.39 , 9.57 , 13.88 , and 24.94 ( P < 0.001 for values at or below the 50th percentile ; P = 0.003 for values at the 75th percentile ) . CONCLUSIONS The risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy Objectives To establish the prevalence of cervicovaginal fetal fibronectin positivity at 23 weeks of gestation in a routine population of singleton pregnancies and determine the relative risk of spontaneous delivery before 33 weeks in women with a fibronectin positive result OBJECTIVE We hypothesized that shortened upper cervical segment length , measured by endovaginal ultrasonography , identifies patients with cervical cerclage at greater risk of preterm delivery . STUDY DESIGN A total of 121 endovaginal ultrasonographic examinations were performed on 32 patients after cervical cerclage . Ultrasonographic measurements included length of the closed cervical canal segments above and below the cerclage and dilatation of the internal cervical os ( funneling ) with and without fundal pressure . The risk of preterm delivery was tested by Fisher 's exact test ( two-tailed ) . RESULTS Development of funneling of the internal os and shortening of the upper cervical segment length were the most predictive of outcome in patients with cervical cerclage . Twelve patients had shortening of the upper cervical segment ( < or = 10 mm ) before 30 weeks ' gestation ( mean 22.6 + /- 2.7 weeks ) , whereas 20 patients continued to have upper cervical segment measurements > 10 mm . A short upper cervical segment before 30 weeks ' gestation was associated with a significantly higher risk of preterm delivery before 36 weeks ( 58 % vs 10 % , p = 0.006 ) and before 34 weeks ( 50 % vs 5 % , p = 0.006 ) . CONCLUSION Endovaginal ultrasonographic assessment of the cervix in patients with cervical cerclage is a useful adjunct for predicting outcome and for counseling the patient 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 ) OBJECTIVE : To estimate whether cervical length measured by transvaginal ultrasonography in women having had loop electrosurgical excision procedure ( LEEP ) , cold knife conization , or cryotherapy predicts spontaneous preterm birth . METHODS : Women with a history of LEEP , cold knife conization , or cryotherapy and who were subsequently pregnant with singleton gestations were prospect ively compared with both a low-risk control group and women with previous spontaneous preterm birth . A transvaginal ultrasonogram measuring cervical length was performed at 24 to 30 weeks of gestation . Primary outcomes included cervical length and spontaneous preterm birth less than 37 weeks . Secondary outcomes were spontaneous preterm birth less than 34 weeks , low birth weight , and maternal and neonatal outcomes . RESULTS : Women with previous LEEP ( N = 75 ) , cold knife conization ( N = 21 ) , and cryotherapy ( N = 36 ) had shorter cervical lengths ( 3.54 , 3.69 , and 3.75 cm respectively ) than the low-risk control group ( N = 81 , 4.21 cm ) ( P < .001 , P = .03 , P = .02 respectively ) and similar lengths to women with a previous spontaneous preterm birth ( N = 63 , 3.78 cm ) . Loop electrosurgical excision procedure and cold knife conization , but not cryotherapy , were associated with spontaneous preterm birth less than 37 weeks ( odds ratio 3.45 , 95 % confidence interval 1.28–10.00 , P = .02 ; and odds ratio 2.63 , 95 % confidence interval 1.28–5.56 , P = .009 , respectively ) . Using a cutoff of 3.0 cm , transvaginal ultrasonography had a positive predictive value of 53.8 % and negative predictive value of 95.2 % for spontaneous preterm birth less than 37 weeks in women with LEEP . CONCLUSION : Women with a history of LEEP , cold knife conization , and cryotherapy all independently have shorter cervical lengths than low-risk controls and similar lengths to women with previous spontaneous preterm birth . Loop electrosurgical excision procedure and cold knife conization are associated with spontaneous preterm birth less than 37 weeks , and transvaginal ultrasonography predicts preterm birth in women who have had LEEP . LEVEL OF EVIDENCE : OBJECTIVE The purpose of this study was to compare preterm delivery rates and neonatal morbidity/mortality rates for women with cervical incompetence with membranes at or beyond a dilated external cervical os that was treated with emergency cerclage , bed rest plus indomethacin , versus just bed rest . STUDY DESIGN Women with cervical incompetence with membranes at or beyond a dilated external cervical os , before 27 weeks of gestation , were treated with antibiotics and bed rest and r and omly assigned for emergency cerclage and indomethacin or bed rest only . RESULTS Twenty-three women were included ; 13 women were allocated r and omly to the emergency cerclage and indomethacin group , and 10 women were allocated r and omly to the bed rest-only group . Gestational age at time of r and omization was 22.2 weeks in the emergency cerclage and indomethacin group and 23.0 weeks in the bed rest-only group . Mean interval from r and omization until delivery was 54 days in the emergency cerclage and indomethacin group and 20 days in the bed rest-only group ( P=.046 ) . Mean gestational age at delivery was 29.9 weeks in the emergency cerclage and indomethacin group and 25.9 weeks in the bed rest-only group . Preterm delivery before 34 weeks of gestation was significantly lower in the emergency cerclage and indomethacin group , with 7 of 13 deliveries versus all 10 deliveries in the bed rest-only group ( P=.02 ) . CONCLUSIONS Emergency cerclage , indomethacin , antibiotics , and bed rest reduce preterm delivery before 34 weeks compared with bed rest and antibiotics alone OBJECTIVE To compare pregnancy outcome for women at risk of preterm delivery undergoing elective cervical cerclage in the first trimester or serial transvaginal assessment of cervical length with cerclage only if indicated ( control cases ) . DESIGN A matched case control study . SETTING Prematurity clinic at two London teaching hospitals . POPULATION Women at high risk for preterm delivery . METHODS Cases of elective cervical cerclage were matched for maternal age , ethnic group , previous cervical surgery , previous second trimester loss and early preterm delivery to women undergoing serial ultrasound surveillance of cervical length . Pregnancy outcome data was collected . Data was analysed using Fisher 's exact , Mann-Whitney and Student 's t-tests . MAIN OUTCOME MEASURES Gestation at delivery , rate of delivery < 24 , 24 - 32 and 32 - 37 weeks gestation . RESULTS Thirty-nine cases of elective cervical cerclage were matched to control cases . Both groups were similar for maternal age , ethnic group , previous cervical surgery , previous second trimester loss and early preterm delivery . Cervical cerclage was performed in 14 ( 36 % ) of the control cases due to cervical changes . There was no significant difference in median gestation at delivery ( 266 days versus 260 days P=0.9 ) , number delivering < 24 weeks ( 15 % versus 13 % P=0.9 ) , at 24 - 32 weeks ( 7.5 % versus 15 % P=0.6 ) and at 32 - 37 weeks ( 15 % versus 13 % P=0.9 ) . CONCLUSION Serial transvaginal ultrasound surveillance of cervical length in women at high risk of preterm delivery appears to reduce cerclage rates without compromising pregnancy outcome . A large multicentered r and omised trial is required to confirm these findings Abstract Objective : To determine pregnancy outcome in patients with short cervix on transvaginal ultrasound between 16 and 24 weeks ' gestation treated with McDonald cerclage compared to weekly intramuscular injections of 17 α-hydroxyprogesterone caproate ( 17OHP-C ) . Methods : From November 2003 through December 2006 , asymptomatic , singleton pregnancies were screened with transvaginal ultrasound between 16–24 weeks ' gestation . Patients with a cervical length ( CL ) ≤25 mm were offered enrollment . Patients were r and omly assigned to treatment with McDonald cerclage or weekly intramuscular injections of 17OHP-C. The primary outcome was spontaneous preterm birth ( PTB ) prior to 35 weeks ' gestation . Results : Seventy-nine patients met inclusion criteria ; 42 were r and omly assigned to the cerclage and 37 to 17OHP-C. Spontaneous PTB prior to 35 weeks ' gestation occurred in 16/42 ( 38.1 % ) of the cerclage group and in 16/37 ( 43.2 % ) of the 17OHP-C group ( relative risk , 1.14 95 % CI , 0.67 , 1.93 ) . A post hoc analysis of patients with a prior PTB showed no difference in spontaneous PTB < 35 weeks between groups . A similar analysis of patients with a CL≤15 mm showed a reduction in spontaneous PTB < 35 weeks in the cerclage group ( relative risk 0.48 , 0.24–0.97 ) . Conclusion : Women with CL ≤25 mm in the second-trimester appear to have similar risks of delivering prior to 35 weeks ' gestation when treated with 17OHP-C or McDonald cerclage . However , cerclage may be more effective in preventing spontaneous PTB in women with CL≤15 mm OBJECTIVE The purpose of this study was to estimate the effect of sonographic cervical length ( CL ) and fetal fibronectin ( FFN ) on length of evaluation and outcomes in women with preterm labor ( PTL ) . STUDY DESIGN Women with threatened PTL were r and omized to either a knowledge group ( results of CL and FFN available and used according to study protocol ) , or a st and ard group ( blinded to CL and FFN ) . Primary outcome was length of evaluation in triage . RESULTS One hundred women were r and omized . There was no significant difference between groups in length of evaluation , but in women with CL > or = 30 mm , the mean time for evaluation was significantly shorter in the knowledge group ( 1:58 h + /- 0:50 vs 2:53 h + /- 0:50 , P = .004 ) . Incidence of spontaneous preterm birth ( SPTB ) in the knowledge group was significantly reduced ( 13.0 vs 36.2 % , P = .01 ) . CONCLUSION The knowledge of CL and FFN was associated with reduction in length of evaluation in women with CL > or = 30 mm and in incidence of SPTB in all women with PTL OBJECTIVE We sought to compare history-indicated placement of cervical cerclage based on history- vs ultrasound-indicated placement in women at risk of preterm birth . STUDY DESIGN We conducted a r and omized controlled trial of history-indicated cervical cerclage suture based on history ( clinician preference ) vs ultrasound ( < 20 mm cervical length ) indicated in women at increased risk . RESULTS The incidence of the primary outcome , preterm delivery between 24(+0 ) and 33(+6 ) weeks , was similar : 19/125 ( 15 % ) in the history-indicated group vs 18/122 ( 15 % ) in the ultrasound-indicated group ( relative risk [ RR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.54 - 1.76 ) . Those women r and omized to the ultrasound-indicated arm were significantly more likely to receive a cerclage ( 32 % vs 19 % ; RR , 1.66 ; 95 % CI , 1.07 - 2.47 ) and progesterone ( 39 % vs 25 % ; RR , 1.55 ; 95 % CI , 1.06 - 2.25 ) . CONCLUSION Screening women at high risk with cervical ultrasound to determine cerclage placement results in more intervention but similar outcome compared with history-indicated placement OBJECTIVE To develop a clinical ly useful tool to predict the probability of preterm delivery in patients with threatened preterm labor . METHODS One hundred and seventy patients with preterm labor between 24 and 34 weeks of gestation were included . Preterm delivery < 37 weeks of gestation was the main endpoint of the study . The data were r and omized and split into an evaluation set ( n = 85 ) and a validation set ( n = 85 ) . The evaluation set was subjected to stepwise backward logistic regression analysis to quantify the relative impact of four potential risk factors , including individual patient factors , results of a rapid fetal fibronectin assay , and sonographic measurement of cervical length . Using the constant of the logistic regression analysis and the beta-coefficients for the identified risk factors the individual probability of preterm delivery for each woman of the validation data set was calculated . The area under a receiver-operating characteristics curve ( AUC ) was used to evaluate the discriminating power of the score . RESULTS The overall rate of preterm delivery was 27.1 % . The logistic regression analysis was performed for the potential predictors of spontaneous preterm delivery , identified by univariate analysis . These were positive fetal fibronectin , cervical length , previous preterm delivery and maternal age . Two risk factors were independent predictors of preterm delivery and were included in the CLEOPATRA I ( clinical evaluation of preterm delivery and theoretical risk assessment ) score : cervical length measurement and previous preterm delivery were associated with a higher risk of preterm delivery ( odds ratio , 7.65 and 6.74 , respectively ) . Since fetal fibronectin assay is not available at all institutions worldwide , it was excluded from the initial model . In the CLEOPATRA II model the risk factors fetal fibronectin and previous preterm delivery were associated with higher risk of preterm delivery , with odds ratios of 17.9 and 4.56 , respectively . The discrimination power ( AUC ) obtained from the models were : CLEOPATRA I , 0.69 ( 95 % CI , 0.56 - 0.82 ) ; CLEOPATRA II , 0.81 ( 95 % CI , 0.69 - 0.93 ) . CONCLUSION In symptomatic women the risk for preterm delivery can be predicted best with the CLEOPATRA II score based on fetal fibronectin and previous preterm delivery Objective To compare the efficacy of nifedipine with ritodrine in the management of preterm labor . Methods One hundred eighty-five singleton pregnancies with preterm labor were assigned r and omly to either ritodrine intravenously ( n = 90 ) or nifedipine orally ( n = 95 ) . The principal outcome assessed was delay of delivery . Results Ritodrine was discontinued in 12 patients because of severe maternal side effects , and their results were excluded from further analysis . More women in the ritodrine group delivered within 24 hours ( 22 versus 11 , P = .006 ) , within 48 hours ( 29 versus 21 , P = .03 ) , within 1 week ( 45 versus 36 , P = .009 ) , and within 2 weeks ( 52 versus 43 , P = .005 ) compared with those receiving nifedipine . There were significantly fewer maternal side effects in the nifedipine group . Apgar scores and umbilical artery and vein pHs were similar in both groups . The number of admissions to the neonatal intensive care unit ( NICU ) in the nifedipine group was significantly lower than in the ritodrine group ( 68.4 versus 82.1 % , P = .04 ) . Conclusion Nifedipine in comparison with ritodrine in the management of preterm labor is significantly associated with a longer postponement of delivery , fewer maternal side effects , and fewer admissions to the NICU OBJECTIVE To compare cervical length measurements at 10 - 14 and 20 - 24 weeks gestation in asymptomatic women with singleton pregnancies and to assess the measurements as a predictor of preterm delivery . STUDY DESIGN In this prospect i ve study , cervical length was measured in 152 asymptomatic women with singleton pregnancies using transvaginal ultrasonography at 10 - 14 and 20 - 24 weeks gestation . The primary outcome measure was spontaneous preterm delivery before 35 weeks of gestation . The mean cervical length was calculated at both stages , and lengths were compared between the term and preterm groups . RESULTS The rate of spontaneous preterm deliveries was 10.5 % . The mean cervical length at 10 - 14 and 20 - 24 weeks was 40.5 and 37.1 mm , respectively . The cervical length at 10 - 14 weeks was not significantly different between those who delivered at term ( 40.9 mm ) and those who delivered preterm ( 38.6 mm ) . By contrast , the cervical length at 20 - 24 weeks was significantly shorter in the group that had preterm deliveries ( 28.4 mm ) than in those who had term deliveries ( 37.8 mm ) ( P < 0.001 ) . The cervical shortening was more apparent in the group that delivered prematurely ( from 38.6 to 28.4 mm ) than in that which delivered at term ( from 40.9 to 37.8 mm ) . CONCLUSION Cervical length measurement used to predict preterm delivery was found to be more predictive at 20 - 24 weeks . Cervical length measurement at 10 - 14 weeks was not reliable for predicting preterm delivery . The mean cervical length tapered gradually from the first to the second scan , and the more rapid cervical shortening was found to be associated with increased risk for preterm delivery OBJECTIVE To evaluate the impact of ultrasound cervical length measurement on duration of hospital stay in patients admitted for threatened preterm labor . STUDY DESIGN This was a prospect i ve , comparative study in 294 patients with threatened preterm labor in three hospitalization units ( Units A , B and C ) . In the first phase of the study ( observational ) , cervical length was measured by transvaginal ultrasound , but managing physicians were blinded to the results . In the second phase ( interventional ) , physicians from Unit A remained blinded to cervical length information , but Units B and C incorporated these data into their clinical management protocol s. Early discharge was contemplated if the cervix measured 25 mm or more on admission ( Unit B ) or no changes were observed over 48 h ( Unit C ) . Duration of hospital stay and delivery rates within 7 days and before 37 weeks ' gestation were recorded . RESULTS Hospital stay was significantly reduced in Units B and C in the interventional phase , while no changes were observed in Unit A. Delivery rates within 7 days and before 37 weeks ' gestation were similar in the three units during the two stages of the study . CONCLUSION Routine use of ultrasound cervical length assessment in patients admitted with threatened preterm labor may reduce the duration of hospital stay without increasing the rate of preterm births . These data should be confirmed by means of an appropriately design ed r and omized clinical trial OBJECTIVE Our purpose was to compare the predictive values for preterm delivery of fetal fibronectin and cervical length measured by transvaginal ultrasonography and to determine whether performing both tests improves their separate predictive values . STUDY DESIGN This prospect i ve blinded study performed both tests on 76 patients hospitalized with signs of premature labor between 24 and 34 weeks of gestation . The outcome measure was delivery before 37 weeks ' gestation . RESULTS The rate of preterm bith was 26.3 % ( 20/76 ) . The predictive values of fetal fibronectin and of a cervical length of < or = 26 mm , considered separately , were approximately equal , and the negative predictive value of each was excellent ( 86.6 % and 89.1 % , respectively ) . This value improved slightly when positive fetal fibronectin , a cervical length < or = 26 mm , or both defined abnormality ( negative predictive value 94.4 % ) . The positive predictive values , although less helpful , were still useful ( 45.2 % and 50.0 % , respectively ) . Combining both indicators did not noticeably improve the positive predictive value ( 52.4 % ) . The risk of preterm delivery for a patient with a positive fetal fibronectin level and a short cervix was high ( odds ratio 13.9 , 95 % confidence interval 3.7 to 52.2 ) . CONCLUSION Fetal fibronectin and cervical length are approximately equivalent in their ability to distinguish between patients at high and low risk for preterm delivery . For physicians equipped to perform transvaginal ultrasonography , however , the additional information about the fibronectin level provides only slight benefits OBJECTIVE This study was conducted to evaluate the usefulness of testing for fetal fibronectin ( fFN ) to rule out the diagnosis of preterm labour in symptomatic patients in a Canadian setting . METHODS This was a prospect i ve , blinded clinical evaluation of fFN testing in women presenting with threatened preterm labour at between 24 and 34 weeks ' gestation at two Canadian tertiary care centres . RESULTS Of the 149 women tested , 32 had a positive fFN test . In the total patient population , 10.1 % delivered within seven days of testing , and 18.2 % delivered prior to 34 weeks . A negative fFN result was associated with a 97.4 % likelihood of delivering more than seven days after testing and with a 91.4 % chance of delivering after 34 weeks . CONCLUSION The fFN test appears to provide useful information in the risk assessment of Canadian women presenting with symptoms compatible with preterm labour . A negative test has a high predictive value for delivering more than seven days after presentation OBJECTIVE To examine the natural history of cervical length shortening in women who had experienced at least one prior spontaneous preterm birth at between 17 + 0 and 33 + 6 weeks ' gestation . METHODS This was an analysis of prer and omization data from the multicenter Vaginal Ultrasound Cerclage Trial . Serial cervical length was measured by transvaginal sonography in 1014 high-risk women at 16 + 0 to 22 + 6 weeks . We performed survival analyses in which the outcome was cervical length shortening<25 mm and data were censored if this did not occur before 22 + 6 weeks ' gestation . The incidence of cervical length shortening and the time to shortening were compared for women whose earliest prior preterm birth was in the mid-trimester , defined as < 24 weeks , vs. those at weeks 24 - 33 . Similar comparisons were performed based on each patient 's most recent birth history . RESULTS Time to cervical length shortening by survival analysis was significantly shorter ( hazard ratio (HR)=2.2 , P<0.0001 ) and the relative risk ( RR ) of shortening significantly higher ( RR=1.8 , P<0.0001 ) for women whose earliest prior spontaneous preterm birth was at < 24 weeks . A larger effect was observed for women whose most recent birth was at < 24 weeks ( HR=2.8 , P<0.0001 ; RR=2.1 , P<0.0001 ) . The observed hazard ratios remained significant after adjusting for confounders in a multivariable Cox proportional hazards model . CONCLUSION Women with a prior spontaneous preterm birth at < 24 weeks are at a higher risk of cervical shortening , and do so at a higher rate and at an earlier gestational age , than do women with a later preterm birth history |
12,081 | 27,075,482 | Conclusions Although supported by weak evidence , peers appear to influence children ’s eating behaviors and physical activity .
However , this influence may be moderated by the number of peers , gender , age and the perceived status of the role models . | Objectives Children learn by observing and imitating others , meaning that their eating behaviors and physical activity may be influenced by their peers .
This paper systematic ally review s how preschoolers ’ eating behaviors and physical activity relate to their peers ’ behaviors , and discusses avenues for future research . | Background Low levels of physical activity are characteristic in preschoolers . To effectively promote physical activity , it is necessary to underst and factors that influence young children 's physical activity . The present study aim ed to investigate how physical activity levels are influenced by environmental factors during recess in preschool . Methods Preschool playground observations and pedometry during recess were carried out in 39 r and omly selected preschools ( 415 boys and 368 girls ; 5.3 ± 0.4 years old ) . In order to examine the contribution of playground variables to physical activity levels , taking adjustment for clustering of subjects within preschools into account , multilevel analyses were conducted . Results During recess boys took significantly more steps per minute than girls ( 65 ± 36 versus 54 ± 28 steps/min ) . In both genders higher step counts per minute were significantly associated with less children per m2 and with shorter recess times . Only in boys a hard playground surface was a borderline significant predictor for higher physical activity levels . In girls higher step counts were associated with the presence of less supervising teachers . Playground markings , access to toys , the number of playing or aim ing equipment pieces and the presence of vegetation or height differences were not significant physical activity predictors in both genders . Conclusion In preschool children physical activity during outdoor play is associated with modifiable playground factors . Further study is recommended to evaluate if the provision of more play space , the promotion of continued activity by supervisors and the modification of playground characteristics can increase physical activity levels in preschoolers Objective : To investigate whether the distance covered in the six minute walk test was affected by walking with a group of others in comparison with performing the test alone . Methods : Eight healthy men ( mean ( SD ) age 21.0 ( 0.9 ) years ) and eight healthy women ( mean ( SD ) age 20.8 ( 2.0 ) years ) performed in r and om order two six minute walk tests either alone or in a group of four on two separate occasions one week apart . Results : Distance covered increased significantly from a mean of 653 ( 61 ) m in the individual male tests to 735 ( 79 ) m in the male group tests ( p<0.05 ) , and 616 ( 75 ) m in the individual female tests to 701 ( 54 ) m in the female group tests ( p<0.01 ) . The men increased the distance walked in six minutes by 12.5 % and the women by 13.7 % when they performed the test as a group . Conclusion : Performing the six minute walk test in a group facilitates its execution As part of the Harvard Cancer Prevention Program Project , we used a social context ual model of health behavior change to test an intervention targeting multiple risk-related behaviors in working-class , multiethnic population s. We examined the relationships between the social context ual factors in our conceptual model and changes in fruit and vegetable consumption from baseline to completion of intervention in health centers and small business studies . We analyzed change in fruit and vegetable consumption , measured at baseline and final assessment s by self-report , in 2 r and omized controlled prevention trials : 1 in small businesses ( n = 974 ) and 1 in health centers ( n = 1954 ) . Stronger social networks , social norms that were more supportive , food sufficiency , and less household crowding were associated with greater change in fruit and vegetable intake . We also observed differences between our intervention sites . Social context can play an important role in promoting changes in fruit and vegetable consumption Systematic review s that include nonr and omized studies ( NRS ) face a number of logistical challenges . However , the greatest threat to the validity of such review s arises from the differing susceptibility of r and omized controlled trials ( RCTs ) and NRS to selection bias . Groups compared in NRS are unlikely to be balanced because of the reasons leading study participants to adopt different health behaviours or to be treated differentially . Research ers can try to minimize the susceptibility of NRS to selection bias both at the design stage , for example , by matching participants on key prognostic factors , and during data analysis , for example , by regression modelling . However , because of logistical difficulties in matching , imperfect knowledge about the relationships between prognostic factors and between prognostic factors and outcome , and measurement limitations , it is inevitable that estimates of effect size derived from NRS will be confounded to some extent . Research ers , review ers and users of evidence alike need to be aware of the consequences of residual confounding . In poor quality RCTs , selection bias tends to favour the new treatment being evaluated . Selection bias need not necessarily lead to systematic bias in favour of one treatment but , even if it acts in an unpredictable way , it will still give rise to additional , nonstatistical uncertainty bias around the estimate of effect size . Systematic review s of NRS studies run the risk of compounding these biases . Nutritional choices and uptake of health education about nutrition are very likely to be associated with potential confounding factors . Therefore , pooled estimates of the effects of nutritional exposures and their confidence intervals are likely to be misleading ; review ers need to take into account both systematic and uncertainty bias OBJECTIVE The effects of positive- and negative peer modelling on children 's consumption of a novel blue food , presented in each of four snack meals during an " activity " day , were evaluated . It was predicted that : ( i ) novel food consumption would increase after positive modelling , but decrease after negative modelling ; ( ii ) modelling effects would generalise to a second novel blue food when participants were alone when they ate their snack ; ( iii ) that positive modelling would reverse the effects of negative modelling . DESIGN A mixed design was employed with r and om assignment to either Groups A , B , or C ( equal numbers of males and females per group ) . Within groups , each participant received the novel food on four snack occasions . Group A received positive modelling of blue food consumption on the first and third occasions , but were alone when they received the foods on the second and fourth occasions ; Group B had negative modelling on the first occasion , positive modelling on the third , and ate alone on the second and fourth ; Group C ate alone on all four occasions . To measure generalisation , an additional blue food was presented in all second and fourth " alone " occasions . PARTICIPANTS Thirty-five 5 - 7-year olds took part in Study 1 , and 44 3 - 4-year olds in Study 2 . RESULTS All main predictions were confirmed except that positive peer modelling did not reverse the effects of negative modelling in the 3 - 4-year olds . CONCLUSION Negative peer modelling inhibits novel food consumption , and its effects are particularly difficult to reverse in younger children Dietary patterns are useful in nutritional epidemiology , providing a comprehensive alternative to the traditional approach based on single nutrients . The Cardiovascular Risk in Young Finns Study is a prospect i ve cohort study with a 21-year follow-up . At baseline , detailed quantitative information on subjects ' food consumption was obtained using a 48 h dietary recall method ( n 1768 , aged 3 - 18 years ) . The interviews were repeated after 6 and 21 years ( n 1200 and n 1037 , respectively ) . We conducted a principal component analysis to identify major dietary patterns at each study point . A set of two similar patterns was recognised throughout the study . Pattern 1 was positively correlated with consumption of traditional Finnish foods , such as rye , potatoes , milk , butter , sausages and coffee , and negatively correlated with fruit , berries and dairy products other than milk . Pattern 1 type of diet was more common among male subjects , smokers and those living in rural areas . Pattern 2 , predominant among female subjects , non-smokers and in urban areas , was characterised by more health-conscious food choices such as vegetables , legumes and nuts , tea , rye , cheese and other dairy products , and also by consumption of alcoholic beverages . Tracking of the pattern scores was observed , particularly among subjects who were adolescents at baseline . Of those originally belonging to the uppermost quintile of pattern 1 and 2 scores , 41 and 38 % respectively , persisted in the same quintile 21 years later . Our results suggest that food behaviour and concrete food choices are established already in childhood or adolescence and may significantly track into adulthood This study investigates the effects of peer influence on the food intake of overweight and normal-weight children . A mixed factorial design was employed , with children 's weight status ( overweight vs. normal-weight ) as a between-subjects factor , and social context ( alone vs. group ) as a within-subjects factor . A total of 32 children ( n=17 overweight and n=15 normal-weight ) between the ages of 6 - 10 years participated in this study . Findings from the r and om regression model indicated that overweight children ate more when with others than when alone , while in contrast normal-weight ate more with others than they did when alone . Therefore , social context differentially impacts the eating behavior of overweight and normal-weight children . This study underscores differences in responses to the social environment between overweight and non-overweight youths , and suggests that social involvement may be an important tool in treatment and prevention programs for overweight and obesity PURPOSE The aim of the study was to investigate the tracking of physical activity ( PA ) from preschool age to adulthood in six age cohorts of males and females . METHODS A r and om sample of 3596 boys and girls age 3 - 18 yr participated in the Cardiovascular Risks in Young Finns Study in 1980 . The follow-up measurements were repeated in 1986 , 1992 , 2001 , and 2007 . The PA was measured by mother 's report in 3- and 6-yr-olds and self-report in 9-yr-olds and older . Tracking of PA was analyzed using the Spearman rank-order correlation and a simplex model . RESULTS Mother-reported PA at age 3 and 6 yr significantly predicted self-reported PA in youth and in young adulthood , and there was a significant indirect effect of mother report on adult PA 2007 in males . Simplex models that fitted the data very well produced higher stability coefficients than the Spearman rank-order correlations showing moderate or high tracking . The tracking was higher in males than that in females . CONCLUSION This study has shown that physically active lifestyle starts to develop very early in childhood and that the stability of PA is moderate or high along the life course from youth to adulthood Although Social Cognitive Theory ( B and ura , 1997 ) suggests that teacher modeling would be one of the most effective methods to encourage food acceptance by preschool children , opinions of experienced teachers have not yet been sample d , teacher modeling has rarely been examined experimentally , and it has produced inconsistent results . The present study considers opinions of teachers and conditions under which teacher modeling is effective . Study 1 was a question naire in which preschool teachers ( N=58 ) were found to rate modeling as the most effective of five teacher actions to encourage children 's food acceptance . Study 2 and Study 3 were quasi-experiments that found silent teacher modeling ineffective to encourage either familiar food acceptance ( N=34 ; 18 boys , 16 girls ) or new food acceptance ( N=23 ; 13 boys , 10 girls ) . Children 's new food acceptance was greatest in the first meal and then rapidly dropped , suggesting a " novelty response " rather than the expected neophobia . No gender differences were found in response to silent teacher modeling . Study 4 was a repeated- measures quasi-experiment that found enthusiastic teacher modeling ( " Mmm ! I love mangos ! " ) could maintain new food acceptance across five meals , again with no gender differences in response to teacher modeling ( N=26 ; 12 boys , 14 girls ) . Study 5 found that with the addition of a competing peer model , however , even enthusiastic teacher modeling was no longer effective to encourage new food acceptance and gender differences appeared , with girls more responsive to the peer model ( N=14 ; 6 boys , 8 girls ) . Thus , to encourage children 's new food acceptance , present results suggest that teachers provide enthusiastic modeling rather than silent modeling , apply such enthusiastic modeling during the first five meals before children 's " novelty response " to new foods drops , and avoid placing competing peer models at the same table with picky eaters , especially girls The purpose of this research was to compare the self-images of male and female children in order to determine whether females were at a particular disadvantage and , if so , why . A r and om sample of 1988 children from grade s 3–12 were interviewed in Baltimore in 1968 . Findings show more disturbance among White adolescent females than among White males or Black females : White girls become much more self-conscious and show greater self-image instability and somewhat lower self-esteem . Three sets of factors appear to explain part of these differences : ( 1 ) attitudes toward present and future sex role , ( 2 ) peer relationships in general and opposite sex relationships in particular , and ( 3 ) attitudes toward changing looks in adolescence The Scottish Intercollegiate Guidelines Network ( SIGN ) develops evidence based clinical guidelines for the NHS in Scotl and . The key elements of the methodology are ( a ) that guidelines are developed by multidisciplinary groups ; ( b ) they are based on a systematic review of the scientific evidence ; and ( c ) recommendations are explicitly linked to the supporting evidence and grade d according to the strength of that evidence . Until recently , the system for grading guideline recommendations was based on the work of the US Agency for Healthcare Research and Quality ( formerly the Agency for Health Care Policy and Research ) . 1 2 However , experience over more than five years of guideline development led to a growing awareness of this system 's weaknesses . Firstly , the grading system was design ed largely for application to questions of effectiveness , where r and omised controlled trials are accepted as the most robust study design with the least risk of bias in the results . However , in many areas of medical practice r and omised trials may not be practical or ethical to undertake ; and for many questions other types of study design may provide the best evidence . Secondly , guideline development groups often fail to take adequate account of the method ological quality of individual studies and the overall picture presented by a body of evidence rather than individual studies or they fail to apply sufficient judgment to the overall strength of the evidence base and its applicability to the target population of the guideline . Thirdly , guideline users are often not clear about the implication s of the grading system . They misinterpret the grade of recommendation as relating to its importance , rather than to the strength of the supporting evidence , and may therefore fail to give due weight to low grade recommendations . # # # # Summary points A revised system of determining levels of evidence and grade s Although most eating occurs in a social context , the effects of peer influence on child eating have not been the object of systematic experimental study . The present study assesses the effects of peer influence on lean and overweight pre-adolescent girls ' snack intake as a function of the co-eaters ' weight status . The weight status of the participants was varied by study ing weight discordant dyads ( i.e. , one lean and one overweight participant ) and weight concordant dyads ( i.e. , both members of the dyads were either lean or overweight ) . Results from the r and om regression model indicate that overweight girls eating with an overweight peer consumed more kilocalories than overweight participants eating with a normal-weight peer . Normal-weight participants eating with overweight peers ate similar amounts as those eating with lean eating companions . The regression model improved when the partners ' food intake was entered in the model , indicating that the peers ' intake was a significant predictor of participants ' snack consumption . This study underscores differences in responses to the social environment between overweight and non-overweight youths |
12,082 | 21,428,862 | The review revealed indication for decreased performance regarding visual scanning and visuoconstructional ability as well as some indication for verbal memory difficulties .
It is suggested that the decreased performance should be attributed to an increased level of situational anxiety , and an engagement in disorder-related , cognitively costly activities rather than trait-like cognitive dysfunctions . | BACKGROUND Over the past few years , there has been an increasing interest in the neuropsychological performance of patients with anxiety disorders , yet the literature does not provide a systematic review of the results concerning adult patients with social anxiety disorder ( SAD ) .
AIMS The primary aim of this paper is to review the literature on neuropsychological performance in adult patients with SAD . | An emerging literature has begun to document the affective consequences of emotion regulation . Little is known , however , about whether emotion regulation also has cognitive consequences . A process model of emotion suggests that expressive suppression should reduce memory for emotional events but that re appraisal should not . Three studies tested this hypothesis . Study 1 experimentally manipulated expressive suppression during film viewing , showing that suppression led to poorer memory for the details of the film . Study 2 manipulated expressive suppression and re appraisal during slide viewing . Only suppression led to poorer slide memory . Study 3 examined individual differences in typical expressive suppression and re appraisal and found that suppression was associated with poorer self-reported and objective memory but that re appraisal was not . Together , these studies suggest that the cognitive costs of keeping one 's cool may vary according to how this is done BACKGROUND The amygdala is believed to play a key role in processing emotionally salient , threat-relevant , events that require further online processing by cortical regions . Emotional disorders such as depression and anxiety have been associated with hyperactivity of the amygdala , but it is unknown whether antidepressant treatment directly affects amygdala responses to emotionally significant information . METHODS The current study assessed the effects of 7 days administration of the selective serotonin reuptake inhibitor ( SSRI ) , citalopram , on amygdala responses to masked presentations of fearful and happy facial expressions in never-depressed volunteers using blood oxygenation level-dependent ( BOLD ) functional magnetic resonance imaging . A double-blind , between-groups design was used with volunteers r and omized to 20 mg/day citalopram versus placebo . RESULTS Volunteers receiving citalopram showed decreased amygdala responses to masked presentations of threat compared with those receiving placebo . Citalopram also reduced responses within the hippocampus and medial prefrontal cortex ( mPFC ) specifically during the fear-relevant stimuli . These neural differences were accompanied by decreased recognition of fearful facial expressions assessed after the scan . By contrast , there was no effect of citalopram on the neural or behavioral response to the happy facial expressions . CONCLUSIONS These results suggest a direct effect of serotonin potentiation on amygdala response to threat-relevant stimuli in humans . Such effects may be important in the therapeutic actions of antidepressants in depression and anxiety A new cognitive therapy ( CT ) program was compared with an established behavioral treatment . Sixty-two patients meeting Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; American Psychiatric Association , 1994 ) criteria for social phobia were r and omly assigned to CT , exposure plus applied relaxation ( EXP = AR ) , or wait-list ( WAIT ) . CT and EXP = AR were superior to WAIT on all measures . On measures of social phobia , CT led to greater improvement than did EXP = AR . Percentages of patients who no longer met diagnostic criteria for social phobia at posttreatment-wait were as follows : 84 % in CT , 42 % in EXP = AR , and 0 % in WAIT . At the 1-year follow-up , differences in outcome persisted . In addition , patients in EXP = AR were more likely to have sought additional treatment . Therapist effects were small and nonsignificant . CT appears to be superior to EXP = AR in the treatment of social phobia Eyelid conditional discrimination learning ( ECDL ) is a test of discriminative aversive conditioning . It places minimal dem and s on motivation and was shown to selectively test temporal lobe function . Twenty-five unmedicated social phobia ( SP ) patients ( mean age 29.5 ± 7.0 years ) , diagnosed according to DSM-IV criteria , and 25 age- and gender-matched healthy controls ( HC , mean age 34.0 ± 8.6 years ) were examined with an ECDL paradigm . In the experiment two differently colored stimuli are r and omly presented . Only one of the stimuli ( reinforced trial ) is followed by an aversive airpuff to the cornea , as opposed to unreinforced trials not followed by an airpuff . Conditioned responses ( CRs ) consist of reflex eyelid closures already upon light presentation . HC as well as SP patients showed a significant difference between reinforced and unreinforced trials . In SP patients , CR frequency did not increase during the ECDL task , while HCs showed appropriate conditional discrimination ability . Thus the results indicate an impairment of adequate behavior modification in an aversive conditioning task in SP We have previously shown that a single dose of intravenous citalopram in healthy volunteers enhances the detection of fearful facial expressions , suggesting an effect of acute selective serotonin re-uptake inhibitor ( SSRI ) treatment on the processing of anxiety-related stimuli . The aim of the present study was to confirm and extend this finding by study ing the effects of a single dose of oral citalopram on a range of tasks design ed to assess different aspects of emotional processing . A total of 32 healthy volunteers were r and omly allocated to double-blind treatment with either citalopram 20 mg orally or placebo . Participants then completed a series of tasks assessing emotional aspects of attention ( visual-probe task ) , perception ( categorization of facial affect ) , memory ( emotional memory task ) and reactivity to threat ( emotion potentiated startle ) . Relative to placebo-treated subjects , participants treated with citalopram demonstrated improved recognition of fearful faces and increased baseline startle response . However , the citalopram group also showed an attentional bias towards positive words . Our data suggest that acute oral citalopram increases the processing of anxiety-related stimuli in healthy volunteers . This mechanism could underlie the known tendency of SSRIs to increase anxiety in patients early in treatment . Our data also suggests that some of the positive biases in emotional processing produced by SSRI treatment might be detectable at the beginning of treatment Information processing was examined in a sample of social phobic individuals using a revised version of the Stroop color-naming task . In the first of two experiments , the response latencies of social phobics and matched community controls were compared when color-naming socially threatening words , physically threatening words and color words . Social phobics demonstrated greater response latencies regardless of type of stimulus word and additional interference in color-naming social threat words compared to the control group . The second experiment examined the cognitive structural change that has been hypothesized to accompany successful treatment of individuals with an anxiety disorder . Social phobics who were treated with cognitive-behavioral group therapy , phenelzine or pill placebo were classified as treatment responders or nonresponders , and their latencies to color-naming on the Stroop task were compared . Treatment responders showed a significant reduction in latencies to color-name social threat words ( vs matched control words ) while nonresponders did not . This effect was not demonstrated with color words or physically threatening words . Clinical implication s and future research directions are discussed BACKGROUND This article presents results of the acute treatment phase of a 2-site study comparing cognitive behavioral group therapy ( CBGT ) and treatment with the monoamine oxidase inhibitor phenelzine sulfate for social phobia . METHODS One hundred thirty-three patients from 2 sites received 12 weeks of CBGT , phenelzine therapy , pill placebo administration , or educational-supportive group therapy ( an attention-placebo treatment of equal credibility to CBGT ) . The " allegiance effect , " ie , the tendency for treatments to seem most efficacious in setting s of similar theoretical orientation and less efficacious in theoretically divergent setting s , was also examined by comparing responses to the treatment conditions at both sites : 1 known for pharmacological treatment of anxiety disorders and the other for cognitive behavioral treatment . RESULTS After 12 weeks , phenelzine therapy and CBGT led to superior response rates and greater change on dimensional measures than did either control condition . However , response to phenelzine therapy was more evident after 6 weeks , and phenelzine therapy was also superior to CBGT after 12 weeks on some measures . There were few differences between sites , suggesting that these treatments can be efficacious at facilities with differing theoretical allegiances . CONCLUSIONS After 12 weeks , both phenelzine therapy and CBGT were associated with marked positive response . Although phenelzine therapy was superior to CBGT on some measures , both were more efficacious than the control conditions . More extended cognitive behavioral treatment and the combination of modalities may enhance treatment effect OBJECTIVES The present study examined whether social phobia is an anxiety disorder associated with a memory bias toward threat . DESIGN Social phobic ( N = 16 ) and non-anxious ( N = 17 ) individuals were compared on their recall of evaluative threat and neutral prose passage content . METHOD Participants were presented with two evaluative threat and two neutral prose passages and completed an immediate free recall task after each trial . RESULTS Contrary to expectation , individuals with social phobia recalled a smaller percentage of units from the evaluative threat passages than non-anxious individuals . CONCLUSION Consistent with the vigilance-avoidance theory , it is suggested that social phobia is an anxiety disorder characterized by the avoidance of elaborate processing of threatening material Specificity of neuropsychological dysfunction in obsessive-compulsive disorder ( OCD ) was assessed by comparing neuropsychological performance in 65 OCD patients , 17 social phobic patients , and 32 normal control subjects . Although both patient groups showed visual constructional impairment relative to normal subjects , only patients with social phobia showed executive dysfunction . Nonconcurrent state anxiety did not correlate with neuropsychological performance . Among anxiety disorders , neuropsychological dysfunction may not be specific to OCD , but the functions implicated may differ across patient groups |
12,083 | 23,940,407 | Where assessed , benefits to the child included improved mother-infant interaction , better cognitive development and growth , reduced diarrhoeal episodes and increased immunization rates .
CONCLUSION In LAMI countries , the burden of CPMDs can be reduced through mental health interventions delivered by supervised non-specialists . | OBJECTIVE To assess the effectiveness of interventions to improve the mental health of women in the perinatal period and to evaluate any effect on the health , growth and development of their offspring , in low- and middle-income ( LAMI ) countries . | Aims : To examine the associations between postnatal depression in mothers and diarrhoeal illness in their infants in the first year of life in a low-income country . Methods : Using a prospect i ve cohort design , 265 infants ( n = 130 of mothers having a depressive episode according to the International Classification of Diseases , 10th revision , at 3 months postnatal and n = 135 of psychologically well mothers ) living in rural Rawalpindi , Pakistan , were followed up for 1 year . Frequency of diarrhoeal episodes was measured fortnightly by health workers using a st and ard question naire . Results : Infants of depressed mothers had significantly more diarrhoeal episodes per year than those of controls ( mean 5.5 v 4.0 ; 95 % confidence interval ( CI ) 0.9 to 2.0 ) . The relative risk of having ⩾5 diarrhoeal episodes per year in infants of depressed mothers was 2.3 ( 95 % CI 1.6 to 3.1 ) . The association remained significant after adjustment for other risk factors by multivariate analysis . Conclusions : Maternal depression is associated with infant diarrhoeal morbidity in a low-income community setting . It is independent of the effects of known factors such as undernutrition , socioeconomic status and parental education . Preventive child health programmes targeting mothers must consider their mental health Combined psychosocial and nutrition interventions improve the development of infants . However , there is a paucity of studies examining the effectiveness of such interventions in humanitarian setting s. This article examines the impact of combining a group-based psychosocial intervention with an existing emergency feeding program for internally displaced mothers in Northern Ug and a. The intervention consisted of mother and baby group sessions and home visits for mothers attending 3 emergency feeding centers . Psychosocial outcomes were compared with a contrast group of mothers who received nutritional support alone . The outcomes investigated were infant stimulation and maternal mood . After controlling for the effects of interview site and baseline scores , mothers in the intervention group ( n = 70 ) showed greater involvement with their babies , more availability of play material s , and less sadness and worry at follow-up in comparison to the contrast group ( n = 77 ) . The intervention was acceptable to the mothers and easily taught . A proportion of the mothers chose to continue the intervention spontaneously with other mothers in their neighbourhoods . Further research needs to be done to vali date these preliminary findings and explore the longer term impact on child growth and intellectual development as well as maternal mood BACKGROUND Programmes that promote early psychological development of children in the developed world have been found to be beneficial . However , such programmes are rare in underprivileged parts of the developing world . We adapted one such parent-based programme ( Learning Through Play ) for a rural Pakistani population and aim ed to study if : ( 1 ) it was acceptable to community health workers ; ( 2 ) the programme led to an improvement , after a period of 6 months , in mothers ' knowledge and attitudes about early infant development ; ( 3 ) it led to a reduction in the levels of maternal mental distress in the post-natal period . METHODS Using a cluster r and omized design with villages as unit of r and omization , 163 mothers from 24 villages in a rural sub-district of Rawalpindi , Pakistan , received the ' Learning Through Play ' programme , whereas 146 mothers from 24 villages acted as controls . Twenty-four community health workers were trained to carry out the programme . Assessment s were conducted using a specially developed 15-item Infant Development Question naire and the 20-item Self-Reporting Question naire ( SRQ ) . RESULTS Over 80 % of the community health workers trained found the programme to be relevant and were able to integrate it into their routine work . There was a significant increase in mothers ' knowledge and positive attitudes about infant development in the intervention group , compared with the control group . Women in the intervention group answered correctly 4.3 ( 95 % CI 3.7 - 14.9 , P < 0.001 ) more questions than the control group . There was no difference in levels of mental distress measured by the SRQ . CONCLUSIONS The ' Learning Through Play ' programme was successfully integrated into the existing health system and accepted by community health workers . The programme succeeded in improving the knowledge and attitudes of mothers about infant development PURPOSE This study aim ed to study the effectiveness of an emotional self-management training program to antenatal women in the prevention of postnatal depression . DESIGN AND METHODS The sample comprised 240 women who were at 32 weeks antenatal . They were r and omly assigned into the intervention group and the control group . FINDINGS On completion of the program , the intervention group reported significantly lower mean Patient Health Question naire-9 and Edinburgh Postnatal Depression Scale scores than the control group . Fewer participants from the intervention group were diagnosed as having postnatal depression using the Structured Clinical Interview for DSM-IV . PRACTICE IMPLICATION S An antenatal emotional self-management training that may lower the risk of developing postnatal depression among Chinese women is recommended BACKGROUND The risk for emotional and behavioral problems is known to be high among children of depressed mothers , but little is known about the impact of prenatal and postnatal depression on the physical health of infants . OBJECTIVE To determine whether maternal depression is a risk factor for malnutrition and illness in infants living in a low-income country . DESIGN Prospect i ve cohort study . SETTING Rural community in Rawalpindi , Pakistan . PARTICIPANTS Six hundred thirty-two physically healthy women were assessed in their third trimester of pregnancy to obtain at birth a cohort of 160 infants of depressed mothers and 160 infants of psychologically well mothers . MAIN OUTCOME MEASURES All infants were weighed and measured at birth and at 2 , 6 , and 12 months of age , and they were monitored for episodes of diarrhea and acute respiratory infections . The mothers ' mental states were reassessed at 2 , 6 , and 12 months . Data were collected on potential confounders of infant outcomes , such as birth weight and socioeconomic status . RESULTS Infants of prenatally depressed mothers showed significantly more growth retardation than controls at all time points . The relative risks for being underweight ( weight-for-age z score of less than -2 ) were 4.0 ( 95 % confidence interval [ CI ] , 2.1 to 7.7 ) at 6 months of age and 2.6 ( 95 % CI , 1.7 to 4.1 ) at 12 months of age , and the relative risks for stunting ( length-for-age z score of less than -2 ) were 4.4 ( 95 % CI , 1.7 to 11.4 ) at 6 months of age and 2.5 ( 95 % CI , 1.6 to 4.0 ) at 12 months of age . The relative risk for 5 or more diarrheal episodes per year was 2.4 ( 95 % CI , 1.7 to 3.3 ) . Chronic depression carried a greater risk for poor outcome than episodic depression . The associations remained significant after adjustment for confounders by multivariate analyses . CONCLUSIONS Maternal depression in the prenatal and postnatal periods predicts poorer growth and higher risk of diarrhea in a community sample of infants . As depression can be identified relatively easily , it could be an important marker for a high-risk infant group . Early treatment of prenatal and postnatal depression could benefit not only the mother 's mental health but also the infant 's physical health and development Objective To assess the efficacy of an intervention design ed to improve the mother-infant relationship and security of infant attachment in a South African peri-urban settlement with marked adverse socioeconomic circumstances . Design R and omised controlled trial . Setting Khayelitsha , a peri-urban settlement in South Africa . Participants 449 pregnant women . Interventions The intervention was delivered from late pregnancy and for six months postpartum . Women were visited in their homes by previously untrained lay community workers who provided support and guidance in parenting . The purpose of the intervention was to promote sensitive and responsive parenting and secure infant attachment to the mother . Women in the control group received no therapeutic input from the research team . Main outcome measures Primary outcomes : quality of mother-infant interactions at six and 12 months postpartum ; infant attachment security at 18 months . Secondary outcome : maternal depression at six and 12 months . Results The intervention was associated with significant benefit to the mother-infant relationship . At both six and 12 months , compared with control mothers , mothers in the intervention group were significantly more sensitive ( 6 months : mean difference=0.77 ( SD 0.37 ) , t=2.10 , P<0.05 , d=0.24 ; 12 months : mean difference=0.42 ( 0.18 ) , t=−2.04 , P<0.05 , d=0.26 ) and less intrusive ( 6 months : mean difference=0.68 ( 0.36 ) , t=2.28 , P<0.05 , d=0.26 ; 12 months : mean difference=−1.76 ( 0.86 ) , t=2.28 , P<0.05 , d=0.24 ) in their interactions with their infants . The intervention was also associated with a higher rate of secure infant attachments at 18 months ( 116/156 ( 74 % ) v 102/162 ( 63 % ) ; Wald=4.74 , odds ratio=1.70 , P<0.05 ) . Although the prevalence of maternal depressive disorder was not significantly reduced , the intervention had a benefit in terms of maternal depressed mood at six months ( z=2.05 , P=0.04 ) on the Edinburgh postnatal depression scale ) . Conclusions The intervention , delivered by local lay women , had a significant positive impact on the quality of the mother-infant relationship and on security of infant attachment , factors known to predict favourable child development . If these effects persist , and if they are replicated , this intervention holds considerable promise for use in the developing world . Trial registration Current Controlled Trials IS RCT N25664149 BACKGROUND The optimum way to improve the recognition and treatment of postnatal depression in developing countries is uncertain . We compared the effectiveness of a multicomponent intervention with usual care to treat postnatal depression in low-income mothers in primary -care clinics in Santiago , Chile . METHODS 230 mothers with major depression attending postnatal clinics were r and omly allocated to either a multicomponent intervention ( n=114 ) or usual care ( n=116 ) . The multicomponent intervention involved a psychoeducational group , treatment adherence support , and pharmacotherapy if needed . Usual care included all services normally available in the clinics , including antidepressant drugs , brief psychotherapeutic interventions , medical consultations , or external referral for specialty treatment . The primary outcome measure was the Edinburgh postnatal depression scale ( EPDS ) score at 3 and 6 months after r and omisation . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00518830 . FINDINGS 208 ( 90 % ) of women r and omly assigned to treatment groups completed assessment s. The crude mean EPDS score was lower for the multicomponent intervention group than for the usual care group at 3 months ( 8.5 [ 95 % CI 7.2 - 9.7 ] vs 12.8 [ 11.3 - 14.1 ] ) . Although these differences between groups decreased by 6 months , EPDS score remained better in multicomponent intervention group than in usual care group ( 10.9 [ 9.6 - 12.2 ] vs 12.5 [ 11.1 - 13.8 ] ) . The adjusted difference in mean EPDS between the two groups at 3 months was -4.5 ( 95 % CI -6.3 to -2.7 ; p<0.0001 ) . The decrease in the number of women taking antidepressants after 3 months was greater in the intervention group than in the usual care group ( multicomponent intervention from 60/101 [ 59 % ; 95 % CI 49 - 69 % ] to 38/106 [ 36 % ; 27 - 46 % ] ; usual care from 18/108 [ 17 % ; 10 - 25 % ] to 11/102 [ 11 % ; 6 - 19 % ] ) . INTERPRETATION Our findings suggest that low-income mothers with depression and who have newly born children could be effectively helped , even in low-income setting s , through multicomponent interventions . Further refinements to this intervention are needed to ensure treatment compliance after the acute phase BACKGROUND Community mobilisation through participatory women 's groups might improve birth outcomes in poor rural communities . We therefore assessed this approach in a largely tribal and rural population in three districts in eastern India . METHODS From 36 clusters in Jharkh and and Orissa , with an estimated population of 228 186 , we assigned 18 clusters to intervention or control using stratified r and omisation . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study . In intervention clusters , a facilitator convened 13 groups every month to support participatory action and learning for women , and facilitated the development and implementation of strategies to address maternal and newborn health problems . The primary outcomes were reductions in neonatal mortality rate ( NMR ) and maternal depression scores . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N21817853 . FINDINGS After baseline surveillance of 4692 births , we monitored outcomes for 19 030 births during 3 years ( 2005 - 08 ) . NMRs per 1000 were 55.6 , 37.1 , and 36.3 during the first , second , and third years , respectively , in intervention clusters , and 53.4 , 59.6 , and 64.3 , respectively , in control clusters . NMR was 32 % lower in intervention clusters adjusted for clustering , stratification , and baseline differences ( odds ratio 0.68 , 95 % CI 0.59 - 0.78 ) during the 3 years , and 45 % lower in years 2 and 3 ( 0.55 , 0.46 - 0.66 ) . Although we did not note a significant effect on maternal depression overall , reduction in moderate depression was 57 % in year 3 ( 0.43 , 0.23 - 0.80 ) . INTERPRETATION This intervention could be used with or as a potential alternative to health-worker-led interventions , and presents new opportunities for policy makers to improve maternal and newborn health outcomes in poor population s. FUNDING Health Foundation , UK Department for International Development , Wellcome Trust , and the Big Lottery Fund ( UK ) Summary Background The treatment of perinatal depression is a public-health priority because of its high prevalence and association with disability and poor infant development . We integrated a cognitive behaviour therapy-based intervention into the routine work of community-based primary health workers in rural Pakistan and assessed the effect of this intervention on maternal depression and infant outcomes . Methods We r and omly assigned 40 Union Council clusters in rural Rawalpindi , Pakistan , in equal numbers to intervention or control . Married women ( aged 16–45 years ) in their third trimester of pregnancy with perinatal depression were eligible to participate . In the intervention group , primary health workers were trained to deliver the psychological intervention , whereas in the control group untrained health workers made an equal number of visits to the depressed mothers . The primary outcomes were infant weight and height at 6 months and 12 months , and secondary outcome was maternal depression . The interviewers were unaware of what group the participants were assigned to . Analysis was by intention to treat . The study is registered as IS RCT N65316374 . Findings The number of clusters per group was 20 , with 463 mothers in the intervention group and 440 in the control group . At 6 months , 97 ( 23 % ) of 418 and 211 ( 53 % ) of 400 mothers in the intervention and control groups , respectively , met the criteria for major depression ( adjusted odds ratio ( OR ) 0·22 , 95 % CI 0·14 to 0·36 , p<0·0001 ) . These effects were sustained at 12 months ( 111/412 [ 27 % ] vs 226/386 [ 59 % ] , adjusted OR 0·23 , 95 % CI 0·15 to 0·36 , p<0·0001 ) . The differences in weight-for-age and height-for-age Z scores for infants in the two groups were not significant at 6 months ( −0·83 vs −0·86 , p=0·7 and −2·03 vs −2·16 , p=0·3 , respectively ) or 12 months ( −0·64 vs −0·8 , p=0·3 and −1·10 vs −1·36 , p=0·07 , respectively ) . Interpretation This psychological intervention delivered by community-based primary health workers has the potential to be integrated into health systems in re source -poor setting s. Funding Wellcome Trust BACKGROUND This study aims to evaluate the effectiveness of an antenatal psycho-educational intervention to prevent postpartum depression in Mexican women . METHOD Pregnant women at high risk for depression were r and omized to intervention or a usual care condition . Assessment s of depression ( SCID , BDI-II ) occurred during pregnancy , 6 weeks and 4 - 6 months postnatally , and subjective impact of the intervention in the postpartum . RESULTS Of the 6484 women approached , 377 were eligible and consented to r and omization ( 250 intervention , 127 control ) . Sixty-eight intervention ( 27.2 % ) and 68 ( 53.5 % ) control participants completed the three assessment periods . The cumulative incidence of major depression over three time periods was significantly lower ( p<0.05 ) in the intervention ( 10.7 % ) than the control group ( 25 % ) . Repeated- measures analysis of variance showed a significant reduction of BDI-II in both groups , but no significant treatment effect . Even when controlling for initial levels of depressive and anxiety symptoms , a treatment effect on depressive symptoms could not be confirmed , although there was a trend demonstrating that intervention participants with high initial symptoms had a larger reduction of BDI-II . Most participants that completed the intervention reported that it had a medium to great influence on their well-being , depression , current problems , role as mothers and their relationship with the baby . LIMITATIONS Attrition was the most salient method ological problem in this study . CONCLUSIONS This is the first r and omized control depression prevention trial in high-risk pregnant Mexican women . Available data are consistent with the possibility that the incidence of depression may have been reduced by the intervention , but differential attrition makes interpretation of the findings difficult BACKGROUND Developing a sense of well-being and achieving maternal role competence are considered critical components of maternal adaptation . Given the growing evidence of postpartum depression and its devastating effects , effective childbirth psychoeducation programme to promote maternal role competence , psychological well-being and prevent postpartum depression is essential and of an urgent priority . OBJECTIVE To examine the effects of an interpersonal psychotherapy oriented childbirth education programme on social support , maternal role competence , postpartum depression and psychological well-being in Chinese first-time childbearing women at three-month postpartum . DESIGN , SETTING AND PARTICIPANTS R and omised controlled trial in a regional teaching hospital , Guangzhou , China with 194 first-time pregnant women , of whom 96 received interpersonal-psychotherapy-oriented childbirth education programme and 98 st and ard care . The intervention was developed from principles of interpersonal psychotherapy which consisted of two 90-min antenatal classes and a telephone follow-up within two weeks after delivery . Outcomes measurements included Perceived Social Support Scale , Parenting Sense of Competence Scale-Efficacy subscale , Edinburgh Postnatal Depression Scale and General Health Question naire , were compared over three-month follow up . RESULTS The study group had significantly better improvement on perceived social support ( p<0.01 ) , maternal role competence ( p<0.01 ) , postpartum depressive symptoms ( p<0.01 ) and psychological well-being ( p<0.01 ) when compared with the control group . The study group also had significantly higher level of social support ( t=2.33 , p=0.021 ) , maternal role competence ( t=2.43 , p=0.016 ) and less depressive symptoms ( t=-2.39 , p=0.018 ) at three-month postpartum when compared with the control group . DISCUSSION The childbirth psychoeducation programme can substantially benefit first time Chinese mothers . It could be implemented as a routine care with ongoing evaluation . Future studies could focus on women in lower social classes , with multiple pregnancy and complicated pregnancy OBJECTIVE This study investigated the effects of an interpersonal-psychotherapy-oriented childbirth psychoeducation programme on postnatal depression , psychological well-being and satisfaction with interpersonal relationships in Chinese first-time childbearing women . METHOD A r and omised , controlled trial was conducted in the maternity clinic of a regional hospital in China . The intervention was based on the principles of interpersonal psychotherapy , and consisted of two 90-min antenatal classes and a telephone follow-up within 2 weeks after delivery . One hundred and ninety-four first-time pregnant women were r and omly assigned to the intervention group ( n=96 ) or a control group ( n=98 ) . Outcomes of the study included symptoms of postnatal depression , psychological well-being and satisfaction with interpersonal relationships , which were measured by the Edinburgh Postnatal Depression Scale ( EPDS ) , General Health Question naire ( GHQ ) and Satisfaction with Interpersonal Relationships Scale ( SWIRS ) , respectively . RESULTS Women receiving the childbirth psychoeducation programme had significantly better psychological well-being ( t=-3.33 , p=0.001 ) , fewer depressive symptoms ( t=-3.76 , p=0.000 ) and better interpersonal relationships ( t=3.25 , p=0.001 ) at 6 weeks postpartum as compared with those who received only routine childbirth education . CONCLUSION An interpersonal-psychotherapy-oriented childbirth psychoeducation programme could be implemented as routine childbirth education with ongoing evaluation . Replication of this study with more diverse study groups , such as mothers with high risks to depression , those with multiple , complicated or multiparas pregnancies , would provide further information about the effects of the programme OBJECTIVE The effectiveness of a hospital discharge education program including information on postnatal depression was evaluated to reduce psychological morbidity after childbirth . METHODS A r and omized controlled trial ( RCT ) was conducted in a regional hospital in Taipei . Two hundred first-time mothers agreed to take part and were r and omly allocated to an intervention group ( n=100 ) or control group ( n=100 ) . The intervention group received discharge education on postnatal depression provided by postpartum ward nurses . The control group received general postpartum education . The main outcome measure was the Edinburgh Postnatal Depression Scale ( EPDS ) administered by postal question naire at six weeks and three months after delivery . RESULTS Women who received discharge education intervention on postnatal depression were less likely to have high depression scores when compared to the control group at three months postpartum . CONCLUSION A discharge educational intervention including postnatal depression information given to women during the postpartum stay benefits psychological well-being . PRACTICE IMPLICATION S A postpartum discharge education program including information on postnatal depression should be integrated into postpartum discharge care in general practice BACKGROUND A high rate of maternal depression and associated disturbance in the mother-infant relationship has been found in an indigent peri-urban South African community , Khayelitsha . The question arises whether a community-based intervention could be beneficial . AIMS To train community workers to deliver an intervention to mothers and infants in Khayelitsha , and to compare mothers and infants receiving this intervention with a sample receiving no such intervention . METHOD Four Khayelitsha women were trained in a mother-infant intervention , which they delivered to 32 women recruited in late pregnancy . At 6 months post-partum , maternal mood , the mother-infant relationship and infant growth were assessed . The findings were compared with a matched group of 32 mothers and infants . RESULTS There was no reliable impact of the intervention on maternal mood . However , compared with the comparison sample , the quality of mother-infant engagement was significantly more positive for those who had received the intervention . CONCLUSIONS The pilot study produced preliminary evidence of a benefit of a community-based mother-infant intervention delivered by trained , but otherwise unqualified , community workers , sufficient to warrant a formal controlled evaluation of this treatment |
12,084 | 26,824,220 | Depressive symptoms were common in medical in patients and are associated with an increased risk of adverse events postdischarge . | Depressive symptoms during a medical hospitalization may be an overlooked prognostic factor for adverse events postdischarge .
Our aim was to evaluate whether depressive symptoms predict 30-day readmission or death after medical hospitalization . | OBJECTIVE To determine the prevalence , correlates and recognition of depression among in patients of general hospitals in Wuhan , China . METHOD A total of 513 patients were r and omly selected from 1923 in patients from three general hospitals and evaluated with a Chinese version of the Structured Clinical Interview for Diagnostic and Statistical Manual-IV Axis I disorders by eight psychiatrists . Logistic regression was used to identify factors that were associated with depression . RESULTS The prevalence ( 95 % confidence interval ) of all current depressive disorders and major depressive disorder ( MDD ) was found to be 16.2 % ( 13.0 - 19.4 % ) and 9.4 % ( 6.8 - 11.9 % ) , respectively . The correlates for depression include higher hospital class , divorce/being widowed/separation , low family income , chronic diseases , lack of medical insurance , dwelling in rural area , suffering from severe illness and multiple hospitalization history . None of the patients with current MDD were detected , treated or referred to psychiatric consultation . CONCLUSIONS The prevalence of depression among in patients of general hospitals in Wuhan , China , was high . None of the depressive patients were recognized or treated for depression , indicating a serious neglect of depression in general hospitals . Our studies suggest an urgent need to improve clinicians ' ability to detect and treat depression BACKGROUND Rehospitalization occurs in approximately 20 % of medical in patients within 90 days of discharge . Rehospitalization accounts for considerable morbidity , mortality , and costs . Identification of risk factors could lead to interventions to reduce rehospitalization . The objective of the study was to determine if physical and mental health , substance abuse , and social support are risk factors for rehospitalization . METHOD This was a prospect i ve cohort study in an innercity population conducted from September 2002 to September 2004 . Participants included 144 adult in patients with at least 1 hospital admission in the past 6 months . Measurements included age , length of stay , number of admissions in the past year , and medical comorbidity as well as measures of depression , alcohol and drug abuse , social support , and health-related quality of life . The outcome studied was the rehospitalization status of participants within 90 days of the index hospitalization . RESULTS The mean age of the subjects was 54.8 years ; 48 % were black and 78 % spoke English as a primary language . Subjects were admitted a mean of 2.5 times in the year before the index admission . Sixty-four patients ( 44 % ) were subsequently rehospitalized within 90 days after the index admission . In bivariate analysis , rehospitalized patients had more prior admissions ( median of 3.0 vs. 2.0 admissions , p = .002 ) , greater medical comorbidity ( mean Charlson Comorbidity Index score of 2.6 vs. 2.0 , p = .04 ) , and poorer physical functional status ( mean SF-12 physical component score of 31.5 vs. 36.2 , p = .03 ) . A logistic regression model , including prior admissions in the last year , comorbidity , physical functional status , and depression , showed that depression tripled the odds of rehospitalization ( odds ratio = 3.3 , 95 % CI = 1.2 to 9.3 ) . This model had fair accuracy in identifying patients at greatest risk for rehospitalization ( c statistic = 0.72 ) . CONCLUSIONS Hospitalized patients with a history of prior hospitalization within 6 months who screen positive for depression are 3 times more likely to be rehospitalized within 90 days in this relatively high-risk population . Screening during hospitalization for depressive symptoms may identify those at risk for rehospitalization OBJECTIVES To identify variables associated with mortality in patients admitted to the hospital for acute exacerbation of COPD . DESIGN Prospect i ve cohort study . SETTING Acute-care hospital in Barcelona ( Spain ) . PATIENTS One hundred thirty-five consecutive patients hospitalized for acute exacerbation of COPD , between October 1996 and May 1997 . MEASUREMENTS AND RESULTS Clinical , spirometric , and gasometric variables were evaluated at the time of inclusion in the study . Socioeconomic characteristics , comorbidity , dyspnea , functional status , depression , and quality of life were analyzed . Mortality at 180 days , 1 year , and 2 years was 13.4 % , 22 % , and 35.6 % , respectively . Sixty-four patients ( 47.4 % ) were dead at the end of the study ( median follow-up duration , 838 days ) . Greater mortality was observed in the bivariate analysis among the oldest patients ( p < 0.0001 ) , women ( p < 0.01 ) , and unmarried patients ( p < 0.002 ) . Hospital admission during the previous year ( p < 0.001 ) , functional dependence ( Katz index ) [ p < 0.0004 ] , greater comorbidity ( Charlson index ) [ p < 0.0006 ] , depression ( Yesavage Scale ) [ p < 0.00001 ] ) , quality of life ( St. George 's Respiratory Question naire [ SGRQ ] ) [ p < 0.01 ] , and PCO(2 ) at discharge ( p < 0.03 ) were also among the significant predictors of mortality . In the multivariate analysis , the activity SGRQ subscale ( p < 0.001 ; odds ratio [ OR ] , 2.62 ; confidence interval [ CI ] , 1.43 to 4.78 ) , comorbidity ( p < 0.005 ; OR , 2.2 ; CI , 1.26 to 3.84 ) , depression ( p < 0.004 ; OR , 3.6 ; CI , 1.5 to 8.65 ) , hospital readmission ( p < 0.03 ; OR , 1.85 ; CI , 1.26 to 3.84 ) , and marital status ( p < 0.0002 ; OR , 3.12 ; CI , 1.73 to 5.63 ) were independent predictors of mortality . CONCLUSIONS Quality of life , marital status , depressive symptoms , comorbidity , and prior hospital admission provide relevant information of prognosis in this group of COPD patients Background The results of R and omized Controlled Trials ( RCTs ) on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio . These do not constitute the sufficient statistics required for meta- analysis or cost-effectiveness analysis , and their use in secondary analyses requires strong assumptions that may not have been adequately tested . In order to enhance the quality of secondary data analyses , we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated . Methods We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations , using where available information on number of events and numbers at risk . The reproducibility and accuracy of survival probabilities , median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics ( survival probabilities , medians and hazard ratios ) with statistics based on repeated reconstructions by multiple observers . Results The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics . Accuracy was excellent for survival probabilities and medians , for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported . Conclusion The algorithm is a reliable tool for meta- analysis and cost-effectiveness analyses of RCTs reporting time-to-event data . It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves Hospitalization is associated with a long-term increased risk for death , especially in older persons ( 1 - 4 ) . Although the mediators for this increased risk have not been fully eluci date d , depression may play an important role . Because depression is common in hospitalized older patients , an association between depression and mortality in this population would be of significant clinical importance ( 5 - 13 ) . The hypothesis that depression may be a mediator of death in hospitalized patients is supported by studies demonstrating that depressive symptoms are associated with increased mortality in community-dwelling patients and in highly selected groups of hospitalized older patients , such as those with acute myocardial infa rct ion ( 14 - 18 ) . These studies have often been limited by inadequate accounting for the complex interrelations between depressive symptoms and other predictors of death , such as acute physiologic impairment , chronic comorbid illness , functional impairment , and cognitive impairment . Because depressive symptoms are clearly correlated with and may partly be the result of these other factors ( 5 , 19 - 20 ) , improving our underst and ing of the relation between depression and death requires use of st and ardized methods to measure and adjust for confounders . We tested the hypothesis that depressive symptoms are associated with long-term mortality in hospitalized older patients . We demonstrated previously that depressive symptoms are strongly associated with adverse health status outcomes in hospitalized medical patients through 90 days after admission ( 21 ) . However , our initial study found no association between depressive symptoms and mortality during the first 90 days after admission ( 21 ) . In this report , we extend mortality follow-up to 3 years by merging our data with a national mortality data base . Furthermore , we adjusted for st and ard measures of physiologic impairment , comorbid illness , and functional impairment at hospital admission to control for the possibility that higher levels of these confounders in patients with more depressive symptoms affect the association between depressive symptoms and death . Methods Patients Patients were drawn from serial , prospect i ve longitudinal studies of functional change in older hospitalized patients on the general medical service of University Hospitals of Clevel and . The inclusion and exclusion criteria for these studies are described elsewhere ( 3 , 21 , 22 ) . The first study enrolled 206 patients 75 years of age or older who were admitted between March 1990 and July 1990 . The second study , a controlled trial of an intervention to improve functional outcomes , enrolled 651 patients 70 years of age or older who were admitted between November 1990 and March 1992 . The first study , which was a pilot study for the second study , enrolled consecutive patients . The second study r and omly assigned patients to an intervention design ed to improve functional outcomes in older persons or to usual care ( 22 ) . In each study , patients admitted to the intensive care unit , telemetry service , or oncology service were excluded . Data collection procedures in both studies were almost identical . Other than a slightly higher mean patient age in the first study cohort , the demographic , clinical , and functional characteristics of patients in the first study , the control group of the second study , and the intervention group of the second study were similar . Additional analyses that adjusted for whether patients were in the first study cohort or the control group compared with the intervention group of the second study cohort yielded results that were almost identical to the results reported here . Of 857 older patients enrolled in the two studies , 284 were excluded from the current study because they were too ill or confused to be interviewed about depressive symptoms at the time of admission ( n=164 ) , were admitted from nursing homes ( n=38 ) , were not available for interview ( n=37 ) , declined interview ( n=27 ) , or died before being approached ( n=18 ) . We excluded patients admitted from nursing homes because interview data were less consistently obtained from these patients . Thus , the analytic sample for this study comprised 573 patients . Assessment of Depressive Symptoms Within 48 hours of admission , patients were interviewed by using the 15-item Geriatric Depression Scale to assess depressive symptoms over the past week ( 23 , 24 ) . The Geriatric Depression Scale is well suited for use in acutely ill older persons because it focuses on symptoms of depression that are less likely to be directly influenced by somatic illness . Examples of items on this scale include feeling bored , dropping activities and interests , feeling helpless , feeling worthless , feeling that life is empty , feeling that others are better off , preferring to stay at home instead of doing new things , and feeling hopeless . We divided patients into those reporting five or fewer symptoms and those reporting six or more symptoms ; these are commonly recommended cutoffs on the 15-item Geriatric Depression Scale ( 24 - 26 ) . Measurement of Mortality We determined mortality and date of death during the 3 years after hospitalization by merging our files with the National Death Index , a data base of all deaths in the United States generated from state death certificates . Its sensitivity and specificity have been reported to be 98 % and 100 % , respectively ( 27 ) . Measurement of Potential Confounders Shortly after admission , we surveyed each patient 's primary nurse about the patient 's independence in six activities of daily living ( dressing , bathing , grooming , toileting , transferring , and eating ) based on the scale of Katz ( 28 ) . Within 48 hours of admission , we administered to patients the first 21 items of the 30-item Folstein Mini-Mental State Examination ( 29 ) . To minimize respondent burden , we used only the first 21 items . Scores on the 21-item instrument have previously been shown to correlate highly ( r=0.9 ) with scores on the 30-item instrument and to have construct validity on the basis of their strong association with functional outcomes ( 30 ) . Data gathered from medical records included the reason for admission , the components of the Acute Physiology and Chronic Health Evaluation ( APACHE ) II score ( 31 ) , and the components of the weighted Charlson comorbidity index of illness ( 32 ) . The APACHE II score is a commonly used measure of physiologic severity , and the Charlson score is often used as a measure of the burden of comorbid illness . Statistical Analysis For our primary set of analyses , we compared patients who had six or more depressive symptoms ( depressed patients ) with patients who had five or fewer symptoms ( nondepressed patients ) . We used the chi-square test or t-test to compare the characteristics of patients in each category at hospital admission . Survival curves describing mortality in the 3 years after hospitalization in each group were prepared by using the method of Kaplan and Meier . We used Cox regression to determine whether depressive symptoms were independently associated with mortality over 3 years . In the first model , we measured the unadjusted association between depressive symptoms and mortality . In the next four models , we determined the association between depressive symptoms and mortality after controlling for APACHE II scores , Charlson comorbidity index scores , dependence in activities of daily living , or cognitive function . In the sixth model , we controlled for all of these potential confounders as well as age , sex , ethnicity , and whether the patient lived alone . We did two secondary analyses . First , we modeled depression scores as the number of depressive symptoms on admission . We also determined the hazard ratio associated with multiple cut-points on the Geriatric Depression Scale . Results The mean age of the 573 patients was 79.9 years ; 67.8 % of patients were women and 39.4 % were African-American . About half were independent in all activities of daily living at hospital admission . Table 1 lists the 10 most common reasons for hospital admission , classified by using the method of Charlson ( 33 ) . The mean number of depressive symptoms at hospital admission was 4.5 , and 34 % of patients reported six or more symptoms . At admission , patients with six or more depressive symptoms had higher comorbidity scores , were more likely to have congestive heart failure or chronic obstructive pulmonary disease , had lower cognitive function scores , and were dependent in more activities of daily living ( Table 2 ) . Three years after admission ( Figure ) , the mortality rate was higher among patients with six or more depressive symptoms than among patients with five or fewer depressive symptoms ( 56 % compared with 40 % ; P<0.001 ) . Of the 376 patients with five or fewer depressive symptoms at admission , 78 ( 21 % ) died during the first year of follow-up , 121 ( 32 % ) died during the first 2 years , and 151 ( 40 % ) died during the 3 years . Of the 197 patients with six or more depressive symptoms on admission , 58 ( 29 % ) died in the first year , 88 ( 45 % ) died during the first 2 years , and 110 ( 56 % ) died during the 3 years . The unadjusted hazard ratio over 3 years of follow-up for patients with six or more depressive symptoms was 1.56 ( 95 % CI , 1.22 to 2.00 ) . Patients with six or more depressive symptoms were also slightly more likely than patients with five or fewer symptoms to be discharged to a nursing home ( 8.3 % compared with 4.9 % ; P=0.11 ) . Table 1 . Most Common Reasons for Hospital Admission ( n=573 ) Table 2 . Characteristics of Patients at Hospital Admission Figure . Mortality over 3 years ( 1095 days ) in patients who had six or more depressive symptoms compared with patients who had five or fewer symptoms . Although adjustment for physiologic severity , comorbid illness , dependence in activities of daily living , and cognitive function each reduced the strength of the association between depressive symptoms and mortality , in each case this association remained The impact of depressive symptoms on outcomes of acute exacerbations of chronic obstructive pulmonary disease ( AE COPD ) has not been thoroughly evaluated in prospect i ve studies . We prospect ively enrolled 230 consecutive patients hospitalised for AE COPD , without previous diagnosis of depression . Depressive symptoms were evaluated with Beck 's depression inventory . Pulmonary function tests , arterial blood gases , COPD assessment test ( CAT ) and Borg dyspnoea scale were recorded on admission and on days 3 , 10 and 40 . Patients were evaluated monthly for 1 year . Patients with depressive symptoms required longer hospitalisation ( mean±sd 11.6±3.7 versus 5.6±4.1 days , p<0.001 ) . Clinical variables improved during the course of AE COPD , but depressive symptoms on admission had a significant impact on dyspnoea ( p<0.001 ) and CAT score ( p=0.012 ) improvement . Patients with depressive symptoms presented more AE COPD ( p<0.001 ) and more hospitalisations for AE COPD ( p<0.001 ) in 1 year . In multivariate analysis , depressive symptoms were an independent predictor of mortality ( hazard ratio 3.568 , 95 % CI 1.302–9.780 ) and risk for AE COPD ( incidence rate ratio ( IRR ) 2.221 , 95 % CI 1.573–3.135 ) and AE COPD hospitalisations ( IRR 3.589 , 95 % CI 2.319–5.556 ) in 1 year . The presence of depressive symptoms in patients admitted for AE COPD has a significant impact on recovery and is related to worse survival and increased risk for subsequent COPD exacerbations and hospitalisations in 1 year BACKGROUND The accuracy of current models to predict the risk of unplanned readmission or death after a heart failure ( HF ) hospitalization is uncertain . METHODS We linked four administrative data bases in Alberta to identify all adults discharged alive after a HF hospitalization between April 1999 and 2009 . We r and omly selected one episode of care per patient and evaluated the accuracy of five administrative data -based models ( 4 already published , 1 new ) for predicting risk of death or unplanned readmission within 30 days of discharge . RESULTS Over 10 years , 59652 adults ( mean age 76 , 50 % women ) were discharged after a HF hospitalization . Within 30 days of discharge , 11199 ( 19 % ) died or had an unplanned readmission . All 5 administrative data models exhibited moderate discrimination for this outcome ( c-statistic between 0.57 and 0.61 ) . Neither Centers for Medicare and Medicaid Services (CMS)-endorsed model exhibited substantial improvements over the Charlson score for prediction of 30-day post-discharge death or unplanned readmission . However , a new model incorporating length of index hospital stay , age , Charlson score , and number of emergency room visits in the prior 6 months ( the LaCE index ) exhibited a 20.5 % net reclassification improvement ( 95 % CI , 18.4%-22.5 % ) over the Charlson score and a 19.1 % improvement ( 95 % CI , 17.1%-21.2 % ) over the CMS readmission model . CONCLUSIONS None of the administrative data base models are sufficiently accurate to be used to identify which HF patients require extra re sources at discharge . Models which incorporate length of stay such as the LaCE appear superior to current CMS-endorsed models for risk adjusting the outcome of " death or readmission within 30 days of discharge " OBJECTIVE To determine if the diagnosis of major depression in patients hospitalized following myocardial infa rct ion ( MI ) would have an independent impact on cardiac mortality over the first 6 months after discharge . DESIGN Prospect i ve evaluation of the impact of depression assessed using a modified version of the National Institute of Mental Health Diagnostic Interview Schedule for major depressive episode . Cox proportional hazards regression was used to evaluate the independent impact of depression after control for significant clinical predictors in the data set . SETTING A large , university-affiliated hospital specializing in cardiac care , located in Montreal , Quebec . PATIENTS All consenting patients ( N = 222 ) who met established criteria for MI between August 1991 and July 1992 and who survived to be discharged from the hospital . Patients were interviewed between 5 and 15 days following the MI and were followed up for 6 months . There were no age limits ( range , 24 to 88 years ; mean , 60 years ) . The sample was 78 % male . PRIMARY OUTCOME MEASURE Survival status at 6 months . RESULTS By 6 months , 12 patients had died . All deaths were due to cardiac causes . Depression was a significant predictor of mortality ( hazard ratio , 5.74 ; 95 % confidence interval , 4.61 to 6.87 ; P = .0006 ) . The impact of depression remained after control for left ventricular dysfunction ( Killip class ) and previous MI , the multivariate significant predictors of mortality in the data set ( adjusted hazard ratio , 4.29 ; 95 % confidence interval , 3.14 to 5.44 ; P = .013 ) . CONCLUSION Major depression in patients hospitalized following an MI is an independent risk factor for mortality at 6 months . Its impact is at least equivalent to that of left ventricular dysfunction ( Killip class ) and history of previous MI . Additional study is needed to determine whether treatment of depression can influence post-MI survival and to assess possible underlying mechanisms Background : Pseudomonas aeruginosa ( PA ) is isolated in advanced stages of chronic obstructive pulmonary disease ( COPD ) . Objectives : The aim of our study was to determine whether PA isolation during hospitalization for COPD exacerbation was associated with a poorer prognosis after discharge . Methods : We prospect ively studied all patients with COPD exacerbation admitted between June 2003 and September 2004 . A sputum culture was obtained at admission . Comorbidity , functional dependence , hospitalizations during the previous year , dyspnea , quality of life and other variables previously associated with mortality in COPD were studied . Spirometry and a 6-min walking test were performed 1 month after discharge . Mortality was evaluated 3 years after discharge . Results : A total of 181 patients were included in the study . Of these , 29 ( 16 % ) had PA in the sputum . The mean age was 72 years , and mean basal postbronchodilator forced expiratory volume in 1 s was 45.2 % predicted ( SD 14.4 ) . The mean point value on the BODE index was 5.1 ( SD 2.5 ) . At 3 years , 17 of 29 patients ( 58.6 % ) in the PA group had died , compared to 53 of the 152 non-PA patients [ 34.9 % ; p < 0.004 ; hazard ratio ( HR ) 2.23 , 95 % confidence interval ( CI ) 1.29–3.86 ] . In the multivariate analysis , PA remained statistically related to posthospital mortality ( p = 0.02 ; HR 2.2 , 95 % CI 1.2–4.2 ) after adjustment for age ( p < 0.02 ; HR 1.04 , 95 % CI 1.007–1.07 ) , BODE index ( p < 0.02 ; HR 1.15 , 95 % CI 1.02–1.3 ) and comorbidity ( p < 0.02 ; HR 1.24 , 95 % CI 1.03–1.5 ) . Conclusions : PA isolation in sputum in patients hospitalized for acute exacerbation of COPD is a prognostic marker of 3-year mortality . Poor prognosis is independent of other significant predictors of mortality such as BODE index , age and comorbidity , as measured by the Charlson index The course of depression and the economic consequences in the 6-month period after hospitalization for congestive heart failure were examined in a prospect i ve observational cohort study involving 203 older adults ( mean age=76.8 years , SD=7.8 ) . At discharge , 73 of 203 subjects ( 36 % ) were depressed according to the screening criteria of the Geriatric Depression Scale , and 44 ( 22 % ) were depressed according to the Structured Clinical Interview for DSM-III-R-Non-Patient Edition . The proportions were 33 % and 20 % of 166 subjects , respectively , at 4 weeks and 26 % and 17 % of 113 subjects , respectively , at 24 weeks . Depressed patients used more medical re sources after discharge than nondepressed patients . Additional research is required to determine whether the optimal time to identify and treat depressed older adults with congestive heart failure is during a hospital stay or after discharge Although attention has recently been focused on the role of psychosocial factors in patients with cardiovascular disease ( CVD ) , the factors that have the greatest influence on prognosis have not yet been eluci date d. The aim of this study was to evaluate the effects of depression , anxiety , and anger on the prognosis of patients with CVD . Four hundred fourteen consecutive patients hospitalized with CVD were prospect ively enrolled . Depression was evaluated using the Patient Health Question naire , anxiety using the Generalized Anxiety Disorder Question naire , and anger using the Spielberger Trait Anger Scale . Cox proportional-hazards regression was used to examine the individual effects of depression , anxiety , and anger on a combined primary end point of cardiac death or cardiac hospitalization and on a combined secondary end point of all-cause death or hospitalization during follow-up ( median 14.2 months ) . Multivariate analysis showed that depression was a significant risk factor for cardiovascular hospitalization or death after adjusting for cardiac risk factors and other psychosocial factors ( hazard ratio 2.62 , p = 0.02 ) , whereas anxiety was not significantly associated with cardiovascular hospitalization or death after adjustment ( hazard ratio 2.35 , p = 0.10 ) . Anger was associated with a low rate of cardiovascular hospitalization or death ( hazard ratio 0.34 , p < 0.01 ) . In conclusion , depression in hospitalized patients with CVD is a stronger independent risk factor for adverse cardiac events than either anxiety or anger . Anger may help prevent adverse outcomes . Routine screening for depression should therefore be performed in patients with CVD , and the potential effects of anger in clinical practice should be reconsidered BACKGROUND Evidence suggests depression increases hospital readmission risk . OBJECTIVE Determine whether depressive symptoms are associated with unplanned readmission within 30 days of discharge of general medical patients . DESIGN Secondary analysis of the Project Re-Engineered Discharge ( RED ) r and omized controlled trials . SETTING Urban academic safety-net hospital . PATIENTS A total of 1418 hospitalized adult English-speaking patients . INTERVENTION The 9-Item Patient Health Question naire ( PHQ-9 ) was used to screen patients for depressive symptoms . MEASUREMENTS Hospital readmission within 30 days of discharge . Poisson regression was used to control for confounding variables . RESULTS There were 225 ( 16 % ) patients who screened positive for mild depressive symptoms ( 5 ≤PHQ-9 ≤ 9 ) and 336 ( 24 % ) for moderate or severe depressive symptoms ( PHQ-9 ≥ 10 ) . After controlling for confounders , a higher rate of readmission was observed in subjects with mild depressive symptoms compared to subjects with PHQ-9 < 5 , incidence rate ratio ( IRR ) 1.49 ( 95 % confidence interval [ CI ] : 1.11 - 2.00 ) . The adjusted IRR of readmission for those with moderate-to-severe symptoms was 1.96 ( 95 % CI : 1.51 - 2.49 ) compared to those with no depression . CONCLUSIONS Screening positive for mild and moderate-to-severe depressive symptoms during a hospitalization on a general medical service is associated with an increased dose-dependent readmission rate within 30 days of discharge in an urban , academic , safety-net hospital . Further research is needed to determine whether treatments targeting the reduction of depressive symptoms reduce the risk of readmission The authors evaluated a consecutive sample of 542 elderly hospital patients for depression ; of these , 160 depressed and 171 nondepressed patients were followed up for a median of 47 weeks after discharge . A subset of 113 depressed patients had significant physical disability . Depressed patients saw physicians more frequently , particularly during the 9- to 12-month period after hospital discharge . Depressed patients also had higher rates of rehospitalization and spent more days in the nursing home . These findings persisted after physical health status was controlled . Patients who remained both depressed and physically disabled during the follow-up period used the most general-medical services during the year after hospital discharge , but did not see mental health specialists any more frequently than those whose depression and physical disability improved . These results underscore the importance of diagnosing and treating depression during and after hospital discharge to increase quality of life and possibly reduce health service use OBJECTIVE The purpose of this study was to assess gender differences in the impact of depression on 1-year cardiac mortality in patients hospitalized for an acute myocardial infa rct ion ( MI ) . METHODS Secondary analysis was performed on data from two studies that used the Beck Depression Inventory ( BDI ) to assess depression symptoms during hospitalization : a prospect i ve study of post-MI risk and a r and omized trial of psychosocial intervention ( control group only ) . The sample included 896 patients ( 283 women ) who survived to discharge and received usual posthospital care . Multivariate logistic regression analysis was used to assess the risk of 1-year cardiac mortality associated with baseline BDI scores . RESULTS There were 290 patients ( 133 women ) with BDI scores > or = 10 ( at least mild to moderate symptoms of depression ) ; 8.3 % of the depressed women died of cardiac causes in contrast to 2.7 % of the nondepressed . For depressed men , the rate of cardiac death was 7.0 % in contrast to 2.4 % of the nondepressed . Increased BDI scores were significantly related to cardiac mortality for both genders [ the odds ratio for women was 3.29 ( 95 % confidence interval ( CI ) = 1.02 - 10.59 ) ; for men , the odds ratio was 3.05 ( 95 % CI = 1.29 - 7.17 ) ] . Control for other multivariate predictors of mortality in the data set ( age , Killip class , the interactions of gender by non-Q wave MI , gender by left ventricular ejection fraction , and gender by smoking ) did not change the impact of the BDI for either gender . CONCLUSIONS Depression in hospital after MI is a significant predictor of 1-year cardiac mortality for women as well as for men , and its impact is largely independent of other post-MI risks BACKGROUND Little evidence exists to determine whether depression predicts hospital utilization following discharge among adult in patients on a general medical service . OBJECTIVE We aim ed to determine whether a positive depression screen during hospitalization is significantly associated with an increased rate of returning for hospital services . DESIGN A secondary analysis was performed using data from 738 English-speaking , hospitalized adults from the Project RED r and omized controlled trial ( clinical trials.gov Identifier : NCT00252057 ) conducted at an urban academic safety-net hospital . MEASUREMENTS We used the nine-item Patient Health Question naire ( PHQ-9 ) depression screening tool to identify patients with depressive symptoms . The primary endpoint was hospital utilization , defined as the number of emergency department ( ED ) visits plus readmissions within 30 days of discharge . Poisson regression was used to control for confounding variables . RESULTS Of the 738 subjects included in the analysis , 238 ( 32 % ) screened positive for depressive symptoms . The unadjusted hospital utilization within 30 days of discharge was 56 utilizations per 100 depressed patients compared with 30 utilizations per 100 non-depressed patients , incident rate ratio ( IRR ) ( confidence interval [ CI ] ) , 1.90 ( 1.51 - 2.40 ) . After controlling for potential confounders , a higher rate of post-discharge hospital utilization was observed in patients with depressive symptoms compared to patients without depressive symptoms ( IRR [ CI ] , 1.73 [ 1.27 - 2.36 ] ) . CONCLUSIONS A positive screen for depressive symptoms during an inpatient hospital stay is associated with an increased rate of readmission within 30 days of discharge in an urban , academic , safety-net hospital population AIMS To examine the impact of depressive symptoms on rehospitalisation for heart failure exacerbation in patients with preserved systolic function . BACKGROUND Depressive symptoms associated with higher risk of rehospitalisation have been primarily demonstrated in heart failure patients with systolic dysfunction ( ejection fraction < 40 % ) and the factors influencing rehospitalisation of patients with preserved systolic function ( ejection fraction > or = 40 % ) remain unclear . DESIGN A prospect i ve , descriptive study design was used . METHODS The following baseline data were collected from 165 patients with preserved systolic function during an index hospitalisation for heart failure in South Korea : age , gender , body mass index , New York Heart Association functional class , the ratio of mitral velocity to early diastolic velocity of the mitral annulus , comorbidities , history of prior admission and depressive symptoms . Patients were followed monthly for six months after discharge to collect date on all rehospitalisation for heart failure exacerbation . Hierarchical Cox proportional hazards regression was used to identify independent predictors of rehospitalisation . Kaplan-Meier survival curves with log-rank test were used to determine differences in time to rehospitalisation according to severity of depressive symptoms . RESULTS Almost half of the patients ( 48 % ) had moderate to severe depressive symptoms . The ratio of mitral velocity to early diastolic velocity of the mitral annulus ( hazard ratio = 1.06 , 95 % confidence interval = 1.02 - 1.10 ) and depressive symptoms ( hazard ratio = 1.05 , 95 % confidence interval = 1.02 - 1.08 ) independently predicted rehospitalisation after controlling for other risk factors . Moderate and severe depressive symptoms were associated with both a higher rate and shorter time to rehospitalisation . CONCLUSIONS Moderate to severe depressive symptoms predict early rehospitalisation for heart failure exacerbations in patients with preserved systolic function . RELEVANCE TO CLINICAL PRACTICE Nurses should assess for depressive symptoms in patients with heart failure and refer those with depressive symptoms for treatment to improve outcomes CONTEXT Medicare expenditures of patients with chronic illnesses might be reduced through improvements in care , patient adherence , and communication . OBJECTIVE To determine whether care coordination programs reduced hospitalizations and Medicare expenditures and improved quality of care for chronically ill Medicare beneficiaries . DESIGN , SETTING , AND PATIENTS Eligible fee-for-service Medicare patients ( primarily with congestive heart failure , coronary artery disease , and diabetes ) who volunteered to participate between April 2002 and June 2005 in 15 care coordination programs ( each received a negotiated monthly fee per patient from Medicare ) were r and omly assigned to treatment or control ( usual care ) status . Hospitalizations , costs , and some quality -of-care outcomes were measured with cl aims data for 18 309 patients ( n = 178 to 2657 per program ) from patients ' enrollment through June 2006 . A patient survey 7 to 12 months after enrollment provided additional quality -of-care measures . INTERVENTIONS Nurses provided patient education and monitoring ( mostly via telephone ) to improve adherence and ability to communicate with physicians . Patients were contacted twice per month on average ; frequency varied widely . MAIN OUTCOME MEASURES Hospitalizations , monthly Medicare expenditures , patient-reported and care process indicators . RESULTS Thirteen of the 15 programs showed no significant ( P<.05 ) differences in hospitalizations ; however , Mercy had 0.168 fewer hospitalizations per person per year ( 90 % confidence interval [ CI ] , -0.283 to -0.054 ; 17 % less than the control group mean , P=.02 ) and Charlestown had 0.118 more hospitalizations per person per year ( 90 % CI , 0.025 - 0.210 ; 19 % more than the control group mean , P=.04 ) . None of the 15 programs generated net savings . Treatment group members in 3 programs ( Health Quality Partners [ HQP ] , Georgetown , Mercy ) had monthly Medicare expenditures less than the control group by 9 % to 14 % ( -$84 ; 90 % CI , -$171 to $ 4 ; P=.12 ; -$358 ; 90 % CI , -$934 to $ 218 ; P=.31 ; and -$112 ; 90 % CI , -$231 to $ 8 ; P=.12 ; respectively ) . Savings offset fees for HQP and Georgetown but not for Mercy ; Georgetown was too small to be sustainable . These programs had favorable effects on none of the adherence measures and only a few of many quality of care indicators examined . CONCLUSIONS Viable care coordination programs without a strong transitional care component are unlikely to yield net Medicare savings . Programs with substantial in-person contact that target moderate to severe patients can be cost-neutral and improve some aspects of care . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00627029 |
12,085 | 24,920,437 | RESULTS CPP is associated with central changes similar to those identified in other pain conditions .
Specifically these include , alterations in the behavioural and central response to noxious stimulation , changes in brain structure ( both increases and decreases in the volume of specific brain regions ) , altered activity of both the hypothalamic-pituitary-adrenal axis and the autonomic nervous system ( ANS ) and psychological distress .
CONCLUSIONS The evidence review ed in this paper demonstrates that CPP is associated with significant central changes when compared with healthy pain-free women .
Moreover , the presence of these changes has the potential to both exacerbate symptoms and to predispose these women to the development of additional chronic conditions . | BACKGROUND Chronic pelvic pain ( CPP ) is a significant public health problem with 1 million affected women in the UK .
Although many pathologies are associated with CPP , the pain experienced is often disproportionate to the extent of disease identified and frequently no pathology is found ( chronic pelvic pain syndrome ) .
The central nervous system ( CNS ) is central to the experience of pain and chronic pain conditions in general are associated with alterations in both the structure and function of the CNS .
This review describes the available evidence for central changes in association with conditions presenting with CPP . | Summary BACKGROUND : The aim of this study was to compare the efficacy and side effects of gabapentin , amitriptyline , and their combination in women with chronic pelvic pain . METHODS : In this open-label , prospect i ve , r and omized trial , 56 women with chronic pelvic pain were investigated with a two-year follow-up at the Vienna Medical University Hospital . If pain intensity assessed by a visual analog scale ( VAS ) was 5 or more ( 0 , no pain ; 10 , maximal pain ) , despite analgesic therapy using the nonopioid drug metamizol together with weak opioids , patients were r and omized to receive gabapentin ( n = 20 ) , amitriptyline ( n = 20 ) , or a combination of both drugs ( n = 16 ) . Doses of gabapentin and amitriptyline were increased to maximum daily doses of 3600 mg and 150 mg , respectively , until sufficient pain relief or the occurrence of side effects . VAS and side effects were evaluated before treatment and at 1 , 3 , 6 , 12 and 24 months afterwards . RESULTS : All patients experienced significant pain relief during the observation period . However , after 6 , 12 and 24 months , pain relief was significantly better in patients receiving gabapentin either alone or in combination with amitriptyline than in patients receiving monotherapy with amitriptyline ( gabapentin : 0 months , 7.7 ± 1.5 ; 6 months , 1.6 ± 0.9 ; 12 months , 1.5 ± 0.9 ; 24 months , 1.9 ± 0.9 ; amitriptyline : 0 months , 7.3 ± 1.5 ; 6 months , 2.2 ± 1.6 ; 12 months , 2.2 ± 1.6 ; 24 months ; 3.4 ± 0.9 ; amitriptyline-gabapentin : 0 months , 7.6 ± 0.8 ; 6 months , 1.3 ± 0.9 ; 12 months , 1.7 ± 1.0 ; 24 months , 2.3 ± 0.9 ) . Side effects were lower in the gabapentin group than in the two other groups , the difference reaching statistical significance after three months ( P < 0.05 ) . CONCLUSION : Gabapentin alone or in combination with amitriptyline is better than amitriptyline alone in the treatment of female chronic pelvic pain . ZusammenfassungEINLEITUNG : Gegenst and der Studie war der Vergleich der Wirksamkeit und Verträglichkeit von Gabapentin bzw . Amitriptylin allein mit der Kombination der beiden Medikamente bei chronischen Unterbauchschmerzen ( chronic pelvic pain , CPP ) . METHOD EN : 56 weibliche Patientinnen mit chronischen Unterbauschmerzen wurden bei der prospektiven , r and omisierten Open-label-Studie mit einem 2-jährigem Follow-up an der Schmerzambulanz der Universitätsklinik Wien , Österreich , eingeschlossen . Wenn die Schmerzintensität trotz analgetischer Therapie mit dem Nichtopioid Metamizol und einem schwachen Opioid gemessen auf der visuellen Analogskala ( VAS ) bei 5 oder darüber lag ( 0 , kein Schmerz ; 10 , schlimmster vorstellbarer Schmerz ) , wurden die Patientinnen r and omisiert einem der drei Beh and lungsarme zugeteilt ( Gabapentin , n = 20 ; Amitriptylin , n = 20 , oder beides , n = 16 ) . Die Medikamentengaben von Gabapentin bzw . Amitriptylin wurden auf eine tägliche Dosis von 3600 mg bzw . 150 mg gesteigert , bis eine suffiziente Schmerzerleichterung erreicht war oder unerwünschte Nebenwirkungen auftraten . VAS-Werte wurde vor Beginn der Beh and lung und 1 , 3 , 6 , 12 und 24 Monate danach erhoben . ERGEBNISSE : Alle Patientinnen erfuhren während des Beobachtungszeitraumes eine signifikante Schmerzreduktion . Dennoch war die Schmerzreduktion bei Patientinnen , die Gabapentin allein oder in Kombination mit Amitriptylin erhalten hatten , signifikant höher als unter Monotherapie mit Amitriptylin ( Gabapentin : 0 , 7,7 ± 1,5 ; 6 , 1,6 ± 0,9 ; 12 , 1,5 ± 0,9 ; 24 , 1,9 ± 0,9 ; Amitriptylin : 0 , 7,3 ± 1,5 ; 6 , 2,2 ± 1,6 ; 12 , 2,2 ± 1,6 ; 24 , 3,4 ± 0,9 ; Amitriptylin-Gabapentin : 0 , 7,6 ± 0,8 ; 6 , 1,3 ± 0,9 ; 12 , 1,7 ± 1,0 ; 24 , 2,3 ± 0,9 ) . Unerwünschte Nebenwirkungen traten signifikant seltener in der Gabapentin-Gruppe auf als in den beiden and eren Gruppen ( P < 0,05 ) . KONKLUSION : Diese Ergebnisse legen nahe , dass die Pharmakotherapie mit dem Antikonvulsivum Gabapentin die Beh and lung von chronischen Unterbauchschmerzen bei ambulanten Patientinnen verbessert OBJECTIVE To examine the prevalence of migraine in women with chronic pelvic pain with and without endometriosis . DESIGN Prospect i ve study of headache , pelvic pain , and quality of life before laparoscopic surgery for pelvic pain . Endometriosis was diagnosed pathologically . Headaches were classified as migraine or non-migraine using International Headache Society criteria . SETTING Clinical research hospital . PATIENT(S ) 108 women in a clinical trial for chronic pelvic pain ( NCT00001848 ) . INTERVENTION(S ) Laparoscopy to diagnose endometriosis , assessment by neurologist to assess headaches . MAIN OUTCOME MEASURE(S ) Prevalence of migraine and other headaches in women with chronic pelvic pain with or without endometriosis . Headache frequency , severity and relationship to pelvic pain and endometriosis . RESULT ( S ) Lifetime prevalence of definite or possible migraine was 67 % of women with chronic pelvic pain . An additional 8 % met criteria for possible migraine . Migraine was no more likely in women with endometriosis than those without . Women with the most severe headaches had a lower quality of life compared with those with pelvic pain alone . CONCLUSION ( S ) Migraine headache is common in women with chronic pelvic pain , regardless of endometriosis , and contributes to disability in those with both conditions . The strong association suggests a common pathophysiology Chronic pelvic pain ( CPP ) in women is often debilitating and isolating . Problems with diagnosis continue to make CPP one of the most perplexing conditions in gynaecology , and one of the most difficult to treat BACKGROUND Chronic pelvic pain has often been described as a major women 's health issue , but no information exists on the extent of the problem in the United Kingdom . AIM To investigate the community prevalence of chronic pelvic pain and its effect on the lives of consulting and non-consulting women . DESIGN OF STUDY Postal question naire survey . SETTING Women aged 18 to 49 ( n = 3916 ) r and omly selected from the Oxfordshire Health Authority Register . METHOD The question naire response rate ( adjusted for non-deliveries ) was 74 % ( 2304/3106 ) . Chronic pelvic pain was defined as recurrent or constant pelvic pain of at least six months ' duration , unrelated to periods , intercourse , or pregnancy . Case subgroups comprised recent consulters , past consulters , and non-consulters . Women who reported dysmenorrhoea alone formed a comparison group . RESULTS The three-month prevalence of chronic pelvic pain was 24.0 % ( 95 % CI = 22.1 % to 25.8 % ) . One-third of women reported pain that started more than five years ago . Recent consulters ( 32 % of cases ) were most affected by their symptoms in terms of pain severity , use of health care , physical and mental health scores , sleep quality , and pain-related absence from work . Non-consulters ( 41 % of cases ) did not differ from women with dysmenorrhoea in terms of symptom-related impairment . Irrespective of consulting behaviour , a high rate of symptom-related anxiety was found in women with chronic pelvic pain ( 31 % ) compared with women with dysmenorrhoea ( 7 % ) . CONCLUSIONS This study showed a high community prevalence of chronic pelvic pain in women of reproductive age . Cases varied substantially in the degree to which they were affected by their symptoms . The high symptom-related anxiety in these women emphasises the need for more information about chronic pelvic pain and its possible causes Vulvar vestibulitis syndrome ( VVS ) is a common cause of dyspareunia in pre‐menopausal women . Recent evidence points to the importance of the sensory component in VVS , particularly the heightened processing of tactile and pain sensation in the vulvar vestibule . The goal of the present study was to examine the neural basis of heightened sensitivity to touch ( i.e. allodynia ) in women with VVS . Using functional magnetic resonance imaging , we compared regions of neural activity in 14 women with VVS and 14 age‐ and contraceptive‐matched control women in response to the application of mild and moderate pressure to the posterior portion of the vulvar vestibule . Intensity and unpleasantness ratings were recorded after each scan ; these ratings were significantly higher for women with VVS than controls . All women with VVS described moderate pressure as painful and unpleasant , and 6 of the 14 women with VVS described mild pressure as painful and unpleasant . In contrast , none of the stimuli was painful for control women . Correspondingly , women with VVS showed more significant activations during pressure levels that they found to be either painful or non‐painful than did controls during comparable pressure levels . During pressure described as painful by women with VVS , they had significantly higher activation levels in the insular and frontal cortical regions than did control women . These results suggest that women with VVS exhibit an augmentation of genital sensory processing , which is similar to that observed for a variety of syndromes causing hypersensitivity , including fibromyalgia , idiopathic back pain , irritable bowel syndrome , and neuropathic pain Abstract Pain symptoms of many disorders are reported to vary with menstrual stage . This study investigated how pain thresholds to electrical stimulation of the skin , subcutis and muscle tissue varied with menstrual stage in normal women and compared these variations with those in women with dysmenorrhea and in healthy men at matched intervals . Thresholds of the three tissues were measured four times during the course of one menstrual cycle at four sites . Two of the sites were on the abdomen within the uterine viscerotome ( abdomen‐rectus abdominis , left and right ) and two were outside it on the limbs ( leg‐quadriceps , arm‐deltoid ) . Calculated from the beginning of menstruation ( day 0 ) , the menstrual phases studied were menstrual ( days 2–6 ) , periovulatory ( days 12–16 ) , luteal ( days 17–22 ) and premenstrual ( days 25–28 ) . Spontaneous pain associated with menstruation was measured from diary estimates on a VAS scale . Menstrual phase , dysmenorrhea and tissue : Whereas the highest thresholds always occurred in the luteal phase regardless of segmental site or stimulus depth , the lowest thresholds occurred in the periovulatory stage for skin , whereas those for muscle/subcutis occurred perimenstrually . Dysmenorrhea accentuated the impact of menstrual phase . For non‐dysmenorrheic women menstrual trends were significant only in abdominal muscle and subcutis , but for dysmenorrheic women the trends were also significant in abdominal skin and in limb muscle and subcutis . Dysmenorrhea also lowered thresholds mainly in muscle and sometimes in subcutis , but never in skin , with the greatest hyperalgesic effects in left abdominis muscle . Segmental site : Abdominal sites were more vulnerable to menstrual influences than limb sites . Muscle thresholds , but not skin or subcutis thresholds , were significantly lower in abdomen than in limbs , particularly in dysmenorrheic women . The amount of abdominal muscle hyperalgesia correlated significantly with the amount of spontaneous menstrual pain . Sex differences : Only minor sex differences were observed for pain thresholds of the arm and leg , but there was a unanimous refusal by men , but not by women , to be tested at abdominal sites . These results indicate that menstrual phase , dysmenorrhea status , segmental site , tissue depth and sex all have unique interacting effects on pain thresholds , thus adding more items to the lengthy and still‐growing list of biological factors that enter into an individual 's judgment of whether or not a stimulus is painful Introduction Chronic pelvic pain ( CPP ) affects > 1 million UK women . Annual healthcare costs are estimated at > £ 150 million . Proven interventions for CPP are limited , and treatment is often unsatisfactory . Gabapentin is increasingly prescribed due to reports of effectiveness in other chronic pain conditions , but there are insufficient data supporting value in CPP specifically . The mechanism by which gabapentin exerts its analgesic action is unknown . Given the prevalence and costs of CPP , the authors believe that a large , multicentre , placebo-controlled , double-blind r and omised controlled trial to evaluate the efficacy of gabapentin in management of CPP is required . The focus of this study is a pilot to inform planning of a future r and omised controlled trial . Methods and analysis The authors plan to perform a two-arm , parallel , r and omised controlled pilot trial . The authors aim to recruit 60 women with CPP in NHS Lothian and NHS Grampian ( UK ) and r and omise them to gabapentin or placebo . Response to treatment will be monitored by question naire compared at 0 , 3 and 6 months . The primary objective is to assess recruitment and retention rates . The secondary objectives are to determine the effectiveness and acceptability to participants of the proposed methods of recruitment , r and omisation , drug treatments and assessment tools and to perform a pretrial cost-effectiveness assessment of treatment with gabapentin . Ethics and dissemination Ethical approval has been obtained from the Scotl and A Research Ethics Committee ( LREC 12/SS/0005 ) . Data will be presented at international conferences and published in peer- review ed journals . Trial registration number IS RCT N70960777 Abstract Dysregulations of the hypothalamus – pituitary – adrenal ( HPA ) axis have been discussed as a physiological substrate of chronic pain and fatigue . The aim of the study was to investigate possible dysregulations of the HPA axis in chronic whiplash‐associated disorder ( WAD ) . In 20 patients with chronic WAD and 20 healthy controls , awakening cortisol responses as well as a short circadian free cortisol profile were assessed before and after administration of 0.5 mg dexamethasone . In comparison to the controls , chronic WAD patients had attenuated cortisol responses to awakening , normal cortisol levels during the day , and showed enhanced and prolonged suppression of cortisol after the administration of 0.5 mg dexamethasone . Dysregulations of the HPA axis in terms of reduced reactivity and enhanced negative feedback suppression exist in chronic WAD . The observed endocrine abnormalities could serve as a systemic mechanism of symptoms experienced by chronic WAD patients It is common clinical experience that anxiety about pain can exacerbate the pain sensation . Using event-related functional magnetic resonance imaging ( FMRI ) , we compared activation responses to noxious thermal stimulation while perceived pain intensity was manipulated by changes in either physical intensity or induced anxiety . One visual signal , which reliably predicted noxious stimulation of moderate intensity , came to evoke low anxiety about the impending pain . Another visual signal was followed by the same , moderate-intensity stimulation on most of the trials , but occasionally by discriminably stronger noxious stimuli , and came to evoke higher anxiety . We found that the entorhinal cortex of the hippocampal formation responded differentially to identical noxious stimuli , dependent on whether the perceived pain intensity was enhanced by pain-relevant anxiety . During this emotional pain modulation , entorhinal responses predicted activity in closely connected , affective ( perigenual cingulate ) , and intensity coding ( mid-insula ) areas . Our finding suggests that accurate preparatory information during medical and dental procedures alleviates pain by disengaging the hippocampus . It supports the proposal that during anxiety , the hippocampal formation amplifies aversive events to prime behavioral responses that are adaptive to the worst possible outcome CONTEXT Until recently , the reproductive health agenda has focused on a restricted number of morbidity indicators , particularly those associated with life-threatening diseases . However , gynecologic morbidities that are a source of pelvic pain , although not life-threatening , do impose a substantial burden because of their potential to reduce women 's overall well-being . METHODS In 2005 , a cross-sectional population -based study was conducted in Hermosillo , Mexico , to assess self- reported pelvic pain conditions in a r and om sample of 1,307 women aged 25 - 54 . The 12-month prevalence of each condition was calculated , and logistic regression was used to assess the association between pelvic pain and social , demographic , anthropometric and reproductive characteristics , and other medical conditions . RESULTS The 12-month prevalence of pelvic pain during menstruation among 1,007 menstruating women was 40 % . Pelvic pain during or after sexual intercourse was reported by 12 % of the 1,183 sexually active respondents . Among 1,201 nonpregnant women , 6 % reported chronic pelvic pain . In adjusted analyses , younger age ( 25 - 34 years ) and having a history of STIs or pelvic inflammatory disease ( PID ) were associated with an increased risk of pain during menstruation and chronic pelvic pain ( odds ratios , 1.6 - 3.1 ) . An interaction term for younger age and history of STIs or PID was associated with an elevated risk of intercourse-related pelvic pain ( 6.4 ) . Chronic pelvic pain and pain during menstruation were more frequently reported as interfering with daily activities than was intercourse-related pelvic pain . The proportion of women who had talked with a physician about their condition was highest among those with chronic pelvic pain ( 40 % ) . CONCLUSION Pelvic pain associated with menstruation , pelvic pain during or after sexual intercourse , and chronic pelvic pain are common complaints among Mexican women of reproductive age . Health care providers should pay greater attention to these conditions & NA ; Cutaneous response to capsaicin has been used to assess central sensitization in pain research . This study compared the response to intradermal capsaicin in the forearm and foot of vulvar vestibulitis (vestibulodynia)‐afflicted cases and controls . We hypothesized that cases will experience greater spontaneous pain , larger cutaneous areas of punctate hyperalgesia and dynamic allodynia , and greater vascular flow than controls . We also hypothesized enhanced post‐injection pain in the foot compared to the forearm based on dermatome proximity of the foot and vulva . Methods . Ten vulvar vestibulitis syndrome ( VVS ) cases and 10 age and ethnically matched controls underwent two r and omized , cross‐over trials with intra‐dermal injections of capsaicin or a saline placebo in the forearm and foot . Outcome measures included spontaneous pain level , surface area of punctate hyperalgesia , surface area of dynamic allodynia , cutaneous blood flow , regional skin temperature and vital signs . Results . VVS cases experienced greater spontaneous pain , punctate hyperalgesia and dynamic allodynia than pain‐free controls . Within the VVS group , post‐capsaicin spontaneous pain , punctate hyperalgesia and dynamic allodynia were similar in the forearm and foot . Post‐capsaicin blood flow did not differ between cases and controls by anatomic site . Measures of depression and anxiety correlated with spontaneous pain intensity but did not correlate with measures of hyperalgesia , allodynia , or blood flow . VVS cases had higher resting pulse rates and lower resting systolic blood pressures than in controls . Conclusion . VVS patients show enhancement of post‐capsaicin pain response extending far beyond the anatomic location of the primary complaint Objectives To examine whether generalized pain sensitivity in women with vulvar vestibulitis syndrome ( VVS ) is increased , suggestive of altered pain processing at the level of the central nervous system , and to investigate pain history and other pain measures in women with VVS . Methods Sixteen women with VVS and 16 age-matched ( ±3 years ) and oral contraceptive status-matched ( yes or no ) control women participated in this cross-sectional study . The TP examination , typically used in the diagnosis of FMS , consists of the palpation of 9 bilateral nonvulvar areas by a blinded rheumatologist and was the main measure of generalized sensitivity . Pain intensity and unpleasantness rating ( 0 to 10 ) were recorded after each palpation . In addition , nonvulvar pain history , pain interference , catastrophizing , and anxiety were assessed via question naires . Results Women with VVS had significantly more painful TPs than nonaffected women ; they reported significantly higher pain intensity and unpleasantness ratings and displayed more pain behaviors than controls ( P<0.05 ) . Furthermore , VVS patients reported having experienced more pain problems and associated interference , they catastrophized more in response to vulvar and nonvulvar pain , and they had higher levels of trait anxiety than controls ( P<0.05 ) . Discussion These results are consistent with recent findings of generalized sensitivity and heightened responses to pain in women with VVS . These results suggest that the mechanisms involved in VVS may include those that are genital specific in addition to those that are more generalized , and possibly central ly mediated & NA ; Visceral pain processing is abnormal in a majority of irritable bowel syndrome ( IBS ) patients . Aberrant endogenous nociceptive modulation and anticipation are possible underlying mechanisms investigated in the current study . Twelve IBS patients and 12 matched healthy controls underwent brain fMRI scanning during the following r and omised stimuli : sham and painful rectal distensions by barostat without and with simultaneous activation of endogenous descending nociceptive inhibition using ice water immersion of the foot for heterotopic stimulation . Heterotopic stimulation decreased rectal pain scores from 3.7 ± 0.2 to 3.1 ± 0.3 ( mean ± SE , scale 0–5 ) in controls ( p < 0.01 ) , but not significantly in IBS . Controls differed from IBS patients in showing significantly greater activation bilaterally in the anterior insula , SII and putamen during rectal stimulation alone compared to rectal plus heterotopic stimulation . Greater activation during rectal plus heterotopic versus rectal stimulation was seen bilaterally in SI and the right superior temporal gyrus in controls and in the right inferior lobule and bilaterally in the superior temporal gyrus in IBS . Rectal pain scores were similarly low during sham stimulation in both groups , but brain activation patterns differed . In conclusion , IBS patients showed dysfunctional endogenous inhibition of pain and concomitant aberrant activation of brain areas involved in pain processing and integration . Anticipation of rectal pain was associated with different brain activation patterns in IBS involving multiple interoceptive , homeostatic , associative and emotional areas , even though pain scores were similar during sham distension . The aberrant activation of endogenous pain inhibition appears to involve circuitry relating to anticipation as well as pain processing itself BACKGROUND / AIMS Intestinal distention induces perception and gut reflexes via sympathetic and vagal pathways , but the modulatory mechanisms of such responses remain obscure . The aim of this study was to determine the effects of sympathetic nervous activity on sympathetic and vagal reflexes as well as on intestinal and somatic perception . METHODS In 9 healthy volunteers , proximal duodenal distentions were produced in 4-mL increments and h and transcutaneous electrical nerve stimulation was produced in 3-mA increments . Increasing stimuli of 1-minute duration were r and omly performed at 10-minute intervals both with and without sympathetic activation ( induced by means of lower body negative pressure ) . Intestinal and somatic perception was scored by specific question naires ; vagal enterogastric and sympathetic intestinointestinal relaxatory reflexes were simultaneously measured by gastric and distal duodenal barostats . RESULTS Sympathetic activation significantly heightened perception of intestinal distention without modifying perception of somatic stimuli ( perception scores increased by 41 % and -2 % , respectively ) . The reflex responses to duodenal distention significantly increased during sympathetic activation both in the stomach and in the intestine ( relaxation increased by 91 % and 69 % , respectively ; P < 0.05 for both ) . CONCLUSIONS Activation of the sympathetic nervous system selectively increases visceral but not somatic sensitivity and enhances both vagally and sympathetically driven reflexes in the gut OBJECTIVE : To assess both regional ( vulvar ) and overall ( generalized ) pain sensitivity in women with vulvodynia to determine whether both are increased , suggestive of altered central pain processing . METHODS : Seventeen patients ( aged 18–60 years ) with vulvodynia and 23 age-matched control subjects were included in this cross-sectional study . Pressure pain thresholds in the vulvar area were evaluated in 23 defined locations using a newly developed vulvodolorimeter . Peripheral pressure pain sensitivity was assessed by applying 1 ) continuously ascending pressures to 3 bilateral locations ( thumb , deltoid , and shin ) , and 2 ) discrete pressure stimuli to the thumb using both an ascending and r and om sequence of varying pressures . RESULTS : Pain thresholds at all vulvar locations were lower in the women with vulvodynia than in pain-free control subjects . Similarly , peripheral pain thresholds were lower at the thumb in women with vulvodynia when obtained by discrete ascending or r and om staircase paradigms , as well as at the thumb , deltoid , and shin when tested by dolorimeter ( P < .05 ) . Findings were similar in both those with generalized vulvar dysesthesia and those with localized vestibulodynia . The quantitative results obtained with the vulvodolorimeter and with the more subjective cotton-tipped swab testing routinely used in diagnosis were strongly correlated . CONCLUSION : Women with vulvodynia displayed significantly increased pressure pain sensitivity in both the vulvar region and in peripheral body regions , suggesting a “ central ” component to the mechanisms mediating this disorder . Both the novel vulvodolorimeter and the thumb pressure stimulator may assist in future experimental tests of this and related hypotheses . LEVEL OF EVIDENCE : OBJECTIVE To assess depressive symptoms , anxiety and quality of life in women with pelvic endometriosis . STUDY DESIGN A prospect i ve study of 104 women diagnosed with pelvic endometriosis . The Beck Depression Inventory ( BDI ) and the Hamilton Rating Scale for Depression ( HAM-D ) were used to evaluate depressive symptoms ; the Spielberger State-Trait Anxiety Inventory ( STAI ) and the Hamilton Rating Scale for Anxiety ( HAM-A ) to evaluate anxiety symptoms ; and the short ( 26-item ) version of the World Health Organization Quality Of Life instrument ( WHOQOL-BREF ) to evaluate quality of life . RESULTS Of the patients evaluated , 86.5 % presented depressive symptoms ( mild in 22.1 % , moderate in 31.7 % , and severe in 32.7 % ) and 87.5 % presented anxiety ( minor in 24 % and major in 63.5 % ) . Quality of life was found to be subst and ard . Age correlated positively with depressive symptoms , as determined using the BDI ( P=0.013 ) and HAM-D ( P=0.037 ) . There was a positive correlation between current pain intensity and anxiety symptoms , as assessed using the STAI ( state , P=0.009 ; trait , P=0.048 ) and HAM-A ( P=0.0001 ) . The complaints related to physical limitations increased in parallel with the intensity of pain ( P=0.017 ) . There was an inverse correlation between duration of treatment and quality of life ( P=0.017 ) . There was no correlation between psychiatric symptoms and endometriosis stage . CONCLUSIONS A rational approach to endometriosis should include an evaluation of the emotional profile and quality of life . That approach would certainly reduce the functional damage caused by the endometriosis Endometriosis is a pain syndrome representing a major cause of pelvic pain in women of reproductive age . The aim of this study was to test the hypothesis that persistent nociceptive input from endometriotic tissues leads to central sensitization manifested by somatic hyperalgesia and increased referred pain areas to experimental saline-induced muscle pain in patients with endometriosis , compared to healthy control subjects . Ten women with laparoscopically confirmed endometriosis and 10 healthy , age-matched women participated in the study . Hypertonic saline ( 0.5 mL , 5.8 % ) was injected intramuscularly , in r and om succession , into 1 site of menstrual pain referral ( the multifidus muscle at the low back ) and into 1 non-pain control site ( first dorsal interosseous muscle [ FDI ] of the h and ) . The post-saline pain intensity and pain areas at the FDI were significantly greater in patients with endometriosis than in control subjects ( P < .05 ) but were not different between the groups for the back . An absence of enhancement of post-saline pain responses at the back in the endometriosis group suggests that saline-induced pain at the back appears to activate segmental inhibitory systems in patients with endometriosis . Manifestation of central sensitization in women with endometriosis is demonstrated by increased muscle nociceptor input in the form of increased post-saline pain intensity , pain areas at the FDI , and hypersensitivity to pressure stimulation . These findings provide new insights into the complex pain mechanisms associated with endometriosis & NA ; Co‐existing algogenic conditions in two internal organs in the same patient may mutually enhance pain symptoms ( viscero‐visceral hyperalgesia ) . The present study assessed this phenomenon in different models of visceral interaction . In a prospect i ve evaluation , patients with : ( a ) coronary artery disease ( CAD ) + gallstone ( Gs ) ( common sensory projection : T5 ) ; ( b ) irritable bowel syndrome ( IBS ) + dysmenorrhea ( Dys ) ( T10‐L1 ) ; ( c ) dysmenorrhea/endometriosis + urinary calculosis (Cal)(T10‐L1 ) ; and ( d ) gallstone + left urinary calculosis ( Gs + LCal ) ( unknown common projection ) were compared with patients with CAD , Gs , IBS , Dys or Cal only , for spontaneous symptoms ( number/intensity of pain episodes ) over comparable time periods and for referred symptoms ( muscle hyperalgesia ; pressure/electrical pain thresholds ) from each visceral location . In patients ’ subgroups , symptoms were also re‐assessed after treatment of each condition or after no treatment . ( a ) CAD + Gs presented more numerous/intense angina/biliary episodes and more referred muscle chest/abdominal hyperalgesia than CAD or Gs ; cardiac revascularization or cholecystectomy also reduced biliary or cardiac symptoms , respectively ( 0.001 < p < 0.05 ) . ( b ) IBS + Dys had more intestinal/menstrual pain and abdomino/pelvic muscle hyperalgesia than IBS or Dys ; hormonal dysmenorrhea treatment also reduced IBS symptoms ; IBS dietary treatment also improved dysmenorrhea ( 0.001 < p < 0.05 ) while no treatment of either conditions result ed in no improvement in time of symptoms from both . ( c ) Cal + Dys had more urinary/menstrual pain and referred lumbar/abdominal hyperalgesia than Cal or Dys ; hormonal dysmenorrhea treatment/laser treatment for endometriosis also improved urinary symptoms ; lithotripsy for urinary stone also reduced menstrual symptoms ( 0.001 < p < 0.05 ) . ( d ) In Gs + LCal , cholecystectomy or urinary lithotripsy did not improve urinary or biliary symptoms , respectively . Mechanisms of viscero‐visceral hyperalgesia between organs with documented partially common sensory projection probably involve sensitization of viscero‐viscero‐somatic convergent neurons |
12,086 | 26,068,957 | We are unable to provide evidence to establish whether steroid-eluting sinus stents have potential advantages and disadvantages for patients with CRS undergoing FESS .
Future , high- quality RCTs are needed to assess whether or not steroid-eluting sinus stents confer any beneficial effects , over those of surgery alone , when compared to non-steroid sinus stents | BACKGROUND Functional endoscopic sinus surgery ( FESS ) has become a well-established approach for treating patients with chronic rhinosinusitis ( CRS ) refractory to medical management .
However , the surgical outcome may be compromised by postoperative inflammation , polyposis and adhesions , which often require subsequent intervention .
Bioabsorbable , steroid-eluting sinus stents are inserted into the nose , sinuses or both following surgery to prevent stenosis of the sinus openings during the postoperative healing period .
The slow release of corticosteroid aims to decrease mucosal oedema and expedite wound healing .
Whether a steroid-eluting stent offers any beneficial effects in terms of improving sinonasal symptoms has not been systematic ally review ed .
OBJECTIVES To assess the safety and efficacy of steroid-eluting sinus stent placement in CRS patients after FESS . | Background Steroid-infused absorbable nasal dressings after endoscopic sinus surgery ( ESS ) have been used to improve wound healing and to reduce the recurrence of polyps . However , their systemic effects are not well known . The purpose of this study was to evaluate the systemic effects and safety of steroid-impregnated absorbable nasal packing after ESS . Methods Patients who underwent bilateral ESS for chronic rhinosinusitis were recruited and r and omized into two groups . Ten patients in the triamcinolone ( TA ) group received a TA ( 20 mg)-soaked bioabsorbable dressing in both nasal cavities while 10 patients in the control group took saline-impregnated dressing in both nasal cavities . Nasal dressings were not removed until postoperative day 10 . Serum cortisol , 12-hour urine cortisol , serum adrenal-corticotropic hormone ( ACTH ) , and serum osteocalcin were measured preoperatively and on postoperative days 2 and 10 . Serum cortisol levels were checked 1 day after surgery additionally , while urine cortisol levels were not checked at postoperative day 10 . Results All 20 patients completed this study . The serum cortisol levels were significantly suppressed at postoperative days 1 and 2 in the TA group . Serum ACTH and 12-hour urine cortisol levels were lower 2 days after surgery in the TA group , although these changes were not statistically significant . There were no differences in all other parameters between the TA and control groups on postoperative day 10 . Conclusions TA-impregnated nasal dressings suppress serum cortisol levels during the early postoperative period . This systemic effect was recovered gradually and normalized 10 days after the operation Objective . Endoscopic sinus surgery ( ESS ) for chronic rhinosinusitis ( CRS ) may be compromised by postoperative inflammation , polyposis , and adhesions , often requiring subsequent intervention . To address this issue , the authors investigated the safety and effectiveness of controlled delivery of mometasone furoate to the sinus mucosa via bioabsorbable implants deployed at the time of ESS . Study Design . Prospect i ve , multicenter , r and omized , controlled , double-blind trial using an intrapatient control design . Setting . Otolaryngology – head and neck surgery centers ; both academic and private practice s. Subjects and Methods . The study enrolled 105 patients with CRS undergoing bilateral ethmoidectomy to compare the effect of drug-releasing to non-drug-releasing implants using an intrapatient control design . Postoperative interventions , polyposis , and adhesions were assessed postoperatively . Efficacy was determined through independent analysis of r and omized video-endoscopies by 3 blinded sinus surgeons . Safety assessment s included ocular examinations . Results . Implants were successfully deployed in all 210 ethmoid sinuses . Compared with control sinuses with non-drug-releasing implants , the drug-releasing implant provided a 29.0 % relative reduction in postoperative interventions ( P = .028 ) and a 52 % ( P = .005 ) decrease in lysis of adhesions . The relative reduction in frank polyposis was 44.9 % ( P = .002 ) . Similar reductions were observed in real-time grading performed by the clinical investigators . No clinical ly significant changes from baseline in intraocular pressure or cataracts were observed . Conclusion . This study provides a high level of evidence that use of steroid-releasing implants that apply a sustained release of corticosteroid improves surgical outcomes by reducing synechiae formation , polyposis , and the need for postoperative interventions , with no observable ocular safety risk Background Nasal packing is usually performed to control bleeding after endoscopic sinus surgery ( ESS ) . Although new packing material s have been developed , they still cause pain . This study was design ed to evaluate the effect of lidocaine-soaked packs on pain after ESS . Methods A prospect i ve , r and omized , double-blind controlled trial was conducted in 63 patients with CRS undergoing ESS . At the conclusion of the operation , 2 % lidocaine-soaked biodegradable synthetic polyurethane foam and saline-soaked polyurethane foam were inserted in both nasal cavities of 31 patients and 32 control patients , respectively . The same lidocaine or saline was reapplied into the nasal packs at postoperative 8 hours . Pain was evaluated using a visual analog scale at postoperative 1 , 4 , 8 , 16 , 20 , and 24 hour(s ) . The number of gauze that cleaned the blood around the nose was counted . Heart rate , rhythm , and blood pressures were checked preoperatively and postoperatively to evaluate the influence of lidocaine on vital signs . Results Postoperative pain decreased in lidocaine group at all of the postoperative time periods ( p < 0.05 ) . Lidocaine reduced postoperative bleeding at postoperative 8 and 24 hours . Changes of blood pressure from preoperative values in the lidocaine group were not different from those in the control group ( p > 0.05 ) . Heart rate in the lidocaine group was more stable than that in the control group ( p < 0.05 ) . Conclusion Lidocaine-soaked packs significantly reduced postoperative pain without serious changes on vital sign . These findings suggest that topical lidocaine application to nasal packs could be a useful method to reduce pain during the early postoperative period after ESS OBJECTIVES We sought to determine the efficacy of MeroGel , an absorbable hyaluronic acid nasal dressing ( HA ) in reducing synechia after functional endoscopic sinus surgery ( FESS ) compared with Merocel , a nonabsorbable packing ( NAP ) requiring removal . METHODS We conducted a blinded , r and omized , controlled trial of 37 patients requiring bilateral FESS for chronic sinusitis . Patients were r and omized to placement of HA within the right or left middle meatus and NAP on the other side . Patients were evaluated at 2 , 4 , 6 , and 8 weeks postoperatively . RESULTS Blinded evaluation revealed 5 patients ( 14 % ) with synechia at last follow-up : 3 sides ( 8 % ) with HA and 3 ( 8 % ) with NAP . Thirteen patients ( 35 % ) had synechia at any visit , 10 sides ( 27 % ) with HA and 9 ( 24 % ) with NAP . Seven patients ( 19 % ) required lysis of synechia , 5 sides ( 14 % ) with HA and 3 ( 8 % ) with NAP . CONCLUSION We found no statistically significant difference between HA and NAP dressings Background The aim of this study was to determine whether there was any benefit or detrimental consequences of placing a hyaluronic acid pack ( Merogel ) into the middle meatus after endoscopic sinus surgery ( ESS ) . Methods A r and omized controlled blinded study was performed in 42 patients with chronic sinusitis undergoing ESS . The patients were r and omized to receive Merogel on one side and no packing on the other side . Patients were assessed at 2 , 4 , and 6–8 weeks after surgery and the presence of synechia , edema , and infection was noted with the observer blinded to the side that had received the Merogel . Results At 2 weeks the side packed with Merogel had 35 % synechiae , 83 % edema , and 30 % mucopurulent discharge and on the control side the figures were similar with 22.5 % synechiae , 83 % edema , and 28 % mucopurulent discharge . In both groups these figures improved over the observation period but percentages in the groups remained similar . At no time point was the difference between the packed and unpacked sides statistically significant for any of the measures when assessed with Fisher 's exact test . Conclusion Merogel nasal packing has no significant beneficial or detrimental effect in terms of synechia , edema , or infection when placed in the middle meatus after ESS OBJECTIVES /HYPOTHESIS Disease recurrence and adverse wound healing in the form of inflammation , polyposis , adhesions , and middle turbinate lateralization may induce suboptimal outcomes following sinus surgery . The study objective was to assess the safety and effectiveness of a bioabsorbable , steroid-eluting implant used following functional endoscopic sinus surgery in patients with chronic rhinosinusitis ( CRS ) . STUDY DESIGN Prospect i ve , multicenter , single-cohort trial enrolling 50 patients . METHODS The study allowed bilateral or unilateral steroid-eluting implant placement . Oral and topical steroids were withheld for 60 days postoperatively . Endoscopic follow-up was performed to 60 days . Patient-reported outcomes ( Sino-Nasal Outcome Test-22 Question naire , Rhinosinusitis Disability Index ) were collected to 6 months . Efficacy was assessed by grading inflammation , polyp formation , adhesions , and middle turbinate position . Safety assessment included ocular exams at baseline and 30 days . RESULTS Implants were successfully placed in all 90 sinuses . Mean inflammation scores were minimal at all time points . At 1 month , the prevalence of polypoid edema was 10.0 % , significant adhesions 1.1 % , and middle turbinate lateralization 4.4 % . Changes from baseline in patient-reported outcomes were statistically significant ( P < .0001 ) . No clinical ly significant changes from baseline in intraocular pressure occurred . CONCLUSIONS This consecutive case series provides clinical evidence of the safety , effectiveness , and clinical utility of a bioabsorbable steroid-eluting implant for use in CRS patients . The implant was associated with favorable rates of sinus patency . At 1 month , minimal degrees of inflammation and adhesions were observed , suggesting a positive clinical impact of local steroid delivery without evidence of ocular risk Nasal packings can aid in control of postoperative bleeding and healing following functional endoscopic sinus surgery ( FESS ) , but traditional non-resorbable stents have several inherent drawbacks . We performed a r and omized , controlled , multicenter clinical trial to assess efficacy of resorbable nasal packing in patients undergoing FESS for chronic rhinosinusitis . A total of 66 patients for 88 nasal cavities were r and omized to receive either hyaluronan resorbable packing ( MeroGel ® ) or st and ard non-resorbable nasal dressing after FESS . All underwent preoperative rhinoscopy , CT of sinuses , and , after surgery , were reassessed by rhinoscopy at 2 , 4 , and 12 weeks in blinded fashion . A total of 44 nasal cavities ( MeroGel ® -group ) received resorbable packing , whereas the remaining 44 were packed with non-resorbable nasal dressing . At follow-up endoscopic visit , the presence of nasal synechia was evaluated as primary outcome . Moreover , the tolerability and surgical h and ling properties of MeroGel ® and its comfort were assessed by surgeons and patients . Preoperative severity of rhinosinusitis was similar in both groups . No significant adverse events were observed in all patients . Follow-up endoscopy showed a lower proportion of nasal adhesions in MeroGel ® -group at both 4 ( P = 0.041 ) and 12 weeks ( P < 0.001 ) . Moreover , an improvement of other endoscopic nasal findings such as re-epithelialization , presence of granulation tissue , and appearance of nasal mucosa of nasal cavities after FESS was observed in the MeroGel ® -group . Tolerability and surgical h and ling properties of MeroGel ® were positively rated by clinicians and the overall patient judged comfort of MeroGel ® was favorable . In conclusion , MeroGel ® can be considered a valid alternative to st and ard non-resorbable nasal dressings . It is safe , well-accepted , well-tolerated , and has significant advantage of being resorbable . Moreover , it may favor improved healing in patients undergoing FESS and reduce formation of adhesions Background This study investigated the efficacy of glove finger – coated polyvinyl acetate ( PA ) pack on hemostasis , pain levels , and wound healing after endoscopic sinus surgery ( ESS ) . Methods A prospect i ve , r and omized , double-blinded controlled study was performed in 30 patients who underwent bilateral ESS for chronic rhinosinusitis . Fifteen patients ( control group ) had both nasal cavities packed with PA pack ( Merocel ; Medtronic Xomed , Jacksonville , FL ) and another 15 subjects ( experimental group ) had their nasal cavities packed with PA in a glove finger . Pain levels were assessed by patients on a visual analog scale 12 hours after surgery and at the time of packing removal . The amount of bleeding on removal were quantified by weighing it after removal . Lund-Kennedy score and synechiae formation were assessed at 4 , 8 , and 12 weeks after surgery . The use of analgesics and oral steroid was compared between the two groups . Results The experimental group showed lower levels of pain and lessened bleeding during packing removal than the control group . There were no differences in pain levels at 12 hours after surgery , use of analgesics and oral steroid between the two groups . One ( 6 % ) of each group had postoperative bleeding and required additional packing for hemostasis . Lower Lund-Kennedy score at postoperative 4 weeks was documented in the experimental group . In addition , two ( 13 % ) control subjects developed a synechiae between the middle turbinate and the lateral wall . Conclusion PA packing in a glove finger is advantageous in terms of pain , bleeding on packing removal , and postoperative wound healing , compared with PA pack only Background Chronic rhinosinusitis ( CRS ) is an inflammatory process that causes different clinical symptoms : nasal blockage and congestion , posterior and anterior nasal drip , and smell disorder ranging from reduced olfaction ( hyposmia ) to complete loss of smell ( anosmia ) . It has been suggested that mechanical blockage of olfactory clef after polypectomy is responsible for the persistent impairment of olfaction in some cases . The aim of this study was to evaluate the efficacy of application of steroids at the olfactory cleft in improving olfactory function in patients who underwent sinus surgery . Methods A double-blind , r and omized controlled trial was conducted in Yazd , Iran , between March and December 2012 . Eligible patients who had CRS with polyposis and underwent functional endoscopic sinus surgery were recruited . An absorbable gelatin dressing combined with triamcinolone ( case ) or normal saline ( control ) was applied at the site of surgery . Olfaction was assessed by butanol threshold tests before and 8 weeks after surgery . Results A total of 60 patients were enrolled into the study and were equally divided into triamcinolone and control groups . Subjects in both arms of trial experienced augmentation of smell function throughout the study ; however , patients who received triamcinolone had better improvement after 8 weeks ( p = 0.007 ) . Complete remission rate was 100 % in the triamcinolone group and the corresponding figure was 76 % in the control group . Conclusion We suggest that application of triamcinolone at the olfactory cleft can boost the effect of surgery in restoring olfactory function Objective Steroid-eluting spacers can improve local drug delivery immediately following endoscopic sinus surgery and reduce the recurrence of inflammation warranting systemic corticosteroids . For chronic rhinosinusitis with nasal polyposis , the need for systemic corticosteroids immediately following endoscopic sinus surgery when using a steroid-eluting spacer has not been studied . Study Design A r and omized , double-blind , placebo-controlled trial . Setting Academic rhinology practice . Subjects and Methods Chronic rhinosinusitis patients with nasal polyposis who failed medical therapy and elected endoscopic sinus surgery were enrolled . Patients were r and omized into either the treatment arm ( postoperative prednisone 30 mg daily × 7 days ; n = 18 ) or placebo arm ( postoperative placebo pill daily × 7 days ; n = 18 ) . Outcomes were evaluated at 1 week , 3 weeks , and 2 months postoperatively . Primary outcome was endoscopic grading at postoperative month 2 using the Lund – Kennedy system . Secondary outcome included disease-specific quality of life using the Sinonasal Outcome Test ( SNOT-22 ) survey . Patient enrolment occurred from January 2012 through February 2013 ( NCT01564355 ) . Results Both arms received significant improvement in endoscopic grading and disease-specific quality of life from baseline compared to 2-month follow-up ( P < .001 ) . There were no significant differences in mean endoscopic scores between the postoperative prednisone and control groups at 1 week ( P = .715 ) , 3 weeks ( P = .883 ) , or 2 months ( P = .343 ) . There were no significant differences in SNOT-22 scores between groups at all follow-up points ( all P > .119 ) . Conclusion Minimizing systemic corticosteroid use in patients with chronic rhinosinusitis with nasal polyposis may avoid adverse events . Results from this study suggest that postoperative systemic corticosteroids immediately following endoscopic sinus surgery may not provide improved outcomes when utilizing a steroid-eluting spacer OBJECTIVES /HYPOTHESIS The aim of this study was to evaluate the effects of a nonabsorbable packing ( NAP ) in the middle meatus ( MM ) for 5 days after sinus surgery . STUDY DESIGN A r and omized , partly blinded , controlled clinical trial . METHODS Sixty-one patients ( M/F = 30/31 , mean age 42 , range 18 - 72 ) with chronic or acute recurrent rhinosinusitis were included . Fifty-nine underwent surgery . Thirty-one had NAP in the MM for 5 days , and 28 served as controls with daily saline irrigations postoperatively . Primary outcome variables were nasal congestion , nasal pain , and headache the first 2 weeks rated on visual analogue scales ( VAS ; 0 - 100 ) and the amount of postoperative bleeding recorded on an ordinal scale ( 1 - 4 ) . Secondary outcome variable was the extent of adhesions in MM 10 to 14 weeks after surgery judged by blinded evaluation of endoscopic video recordings . RESULTS Fifty-eight patients completed a diary . No significant differences in primary outcome variables between the groups were found . Nasal congestion decreased most the first 5 to 7 days postoperatively . Removal of the NAP caused little pain ( mean 23 on VAS ) . Temporary bleeding occurred in three patients . Bilateral adhesions were observed in 10 control patients but in none with NAP . Unilateral adhesions were found in nine control patients and in seven with NAP ( exact P < .001 ) . CONCLUSIONS NAP in the MM for 5 days significantly reduced the extent of adhesions in MM compared with saline irrigation alone . NAP did not cause additional discomfort Although serious sequelae of endoscopic sinus surgery are infrequent , more commonplace surgical management often involves the control of mucosal bleeding . This study was conducted to assess the efficacy of an elastoviscous hylan gel as a postsurgical wound dressing for promotion of hemostasis . Twenty patients with a diagnosis of chronic sinusitis were evaluated . In r and omized fashion , the gel dressing was placed into one operated cavity while the contralateral side served as the control . The results indicated that hylan gel was effective in stilling postsurgical bleeding , particularly in the fulminant polyposis cases who had a larger and more exposed cavity . These early results indicate a potential benefit of a gel dressing for hemostasis when used at the conclusion of the operative procedure . In addition , other parameters were evaluated in this study , including prevention of postoperative adhesions and the effect on mucosal healing . These parameters showed a positive result compared with the control group Background This study was design ed to evaluate the safety and efficacy of a novel , self – cross-linked hyaluronic acid ( HA ) hydrogel compared with carboxymethylcellulose ( CMC ) viscous foam in promoting healing when applied after ethmoidectomy . A prospect i ve , r and omized , controlled , blinded clinical trial was performed . The study was performed by four surgeons operating in two community hospitals . Methods Thirty patients with bilateral chronic rhinosinusitis underwent bilateral total ethmoidectomy . Intraoperatively , each patient received 5 mL of HA hydrogel in one ethmoid cavity and 5 mL of CMC contralaterally . The material applied within each ethmoid cavity was r and omly assigned before surgery . An independent surgeon , blinded to the material used to treat each ethmoid cavity , evaluated postoperative endoscopic video at 1 and 2 weeks for edema , crusting , and mucopurulence and at 6 and 12 weeks for remucosalization and scarring/synechiae . Twenty-item Sino-Nasal Outcome Test SNOT-20 data were collected at each visit . A small sample underwent endoscopic mucosal biopsy . Results Twenty-nine of 30 patients completed the protocol . The difference in edema , crusting , and mucopurulence at 1 and 2 weeks was not statistically significant ; however , at 6 and 12 weeks , the HA hydrogel showed statistically significant reduction in both overall endoscopic grade ( p < 0.05 ) , as well as synechiae formation ( p < 0.05 ) , with a trend toward superiority in remucosalization ( p = 08 ) . Histological analysis of six subjects at 12 weeks showed a nonsignificant trend toward a greater amount of regenerated cilia present with the HA hydrogel ( p = 0.23 ) . SNOT-20 scores declined 78.8 % from preoperative scores . Conclusion Self – cross-linked HA hydrogel provides superior wound healing to CMC after ethmoidectomy OBJECTIVES /HYPOTHESIS To evaluate the impact of steroid-impregnated absorbable nasal dressing on wound healing and surgical outcomes after endoscopic sinus surgery ( ESS ) . STUDY DESIGN A prospect i ve , r and omized , double-blinded , placebo-controlled trial . METHODS Chronic rhinosinusitis patients with polyposis who were to undergo bilateral endoscopic sinus surgery were recruited and r and omized to receive triamcinolone-impregnated bioresorbable dressing ( Nasopore ; Stryker Canada , Hamilton , Ontario , Canada ) in one nasal cavity and saline-impregnated dressing contralaterally . Postoperative healing assessment s of edema , crusting , secretions , and scarring were done at postoperative days 7 , 14 , 28 and at 3 and 6 months using vali date d Lund-Kennedy and Perioperative Sinus Endoscopy ( POSE ) scores . RESULTS Analysis of 19 enrolled patients having completed observation shows no significant difference between the cavity scores preoperatively using both the POSE and Lund-Kennedy scores . There was , however , a statistically significant difference at day 7 and 14 in both the Lund-Kennedy ( P = .04 and P = .03 , respectively ) and POSE scores ( P = .03 and P = .001 , respectively ) for the treatment and control groups , and a significant difference was also detected between the groups at 3- and 6-month observations ( Lund-Kennedy , P = .007 and P = .02 , respectively ; POSE , P = .049 and P = .01 , respectively ) . CONCLUSIONS Data analysis suggests a significant improvement in early postoperative healing in nasal cavities receiving triamcinolone-impregnated absorbable nasal packing following ESS and is also associated with improved healing up to 6 months postoperatively Objective The aim of this study was to find out the efficacy of a polyvinyl alcohol ( PVA ) sponge ( Merocel Kennedy ; Medtronic Xomed , Jacksonville , Florida ) sinus pack soaked with levobupivacaine hydrochloride to control postoperative pain and analgesic need following functional endoscopic sinus surgery ( FESS ) . Study Design The study was design ed as a prospect i ve , double-blind , r and omized , controlled study . Forty-one patients who underwent FESS were included in the analysis . Setting A tertiary referral hospital in Turkey . Material s and Methods Patients who underwent FESS were divided into 2 groups . The PVA sponge sinus packs were soaked with 5 mL of levobupivacaine hydrochloride ( chirocaine 25 mg/10 mL ; Abbott , Nycomed Pharma AS , Elverum , Norway ) in group I and with 5 mL of saline in group II . Main Outcome Measures Postoperative pain levels were recorded using a visual analog scale ( VAS score , 0 - 100 ) at 30 minutes and 1 , 2 , 8 , 12 , and 24 hours . Results There were no statistically significant differences between groups regarding age , sex , and American Society of Anesthesiologists status . Postoperative VAS values at 30 minutes and 1 , 2 , 8 , 12 , and 24 hours were significantly lower in group I than in group II ( P < .05 ) . Supplemental analgesia amount was significantly lower in group I than in group II ( P = .003 ) . Conclusion Using levobupivacaine-soaked PVA sponge sinus packs after FESS is an effective , easy , and quick method to control postoperative pain , and it improves patient comfort and tolerability OBJECTIVE To determine if patients undergoing revision endoscopic sinus surgery ( ESS ) for chronic rhinosinusitis obtain significant symptomatic benefit from surgery . DESIGN Prospect i ve controlled clinical trial . METHODS Adult patients undergoing revision ESS were evaluated preoperatively with a computed tomographic scan and the Rhinosinusitis Symptom Inventory . After the revision ESS , patients were reevaluated with the Rhinosinusitis Symptom Inventory . Data were analyzed for symptom score changes and effect sizes , changes in medication , and economic variables . Improvements in sinonasal symptom scores , medication use , and economic variables were compared with those of a contemporaneous control group of patients undergoing primary ESS and matched for age , sex , and Lund score . RESULTS The 21 patients ( mean age , 44.8 years ) who completed evaluation after revision ESS had a mean follow-up of 12.4 months . Mean preoperative Lund score was 12.6 . Large effect sizes indicating significant symptom improvements were noted for nasal obstruction ( effect size , -1.9 ) , hyposmia ( -0.9 ) , and headache ( -0.6 ) , as well as nasal ( -1.1 ) and total symptom domains ( -0.9 ; P<.05 in all cases ) . Nasal steroid and nonsedating antihistamine use did not decrease significantly after ESS , but oral antibiotic use showed a downward trend ( net change , - 2.9 wk/y ; P = .23 ) . Improvements in clinical symptoms were statistically similar to corresponding improvements in the matched cohort of patients undergoing primary ESS . CONCLUSIONS The symptomatic relief that revision ESS can provide for patients with refractory chronic rhinosinusitis is similar to that following a primary ESS . However , many patients undergoing revision ESS require continued intense medical management of their chronic rhinosinusitis OBJECTIVE To compare NasoPore ( Stryker Canada , Hamilton , ON , Canada ) and a traditional middle meatal spacer ( MMS ) composed of Merocel ( ( Medtronic Xomed , Mississauga , ON , Canada ) placed in a vinyl glove finger in functional endoscopic sinus surgery ( FESS ) with regard to postoperative bleeding , wound healing , and patient comfort . DESIGN A prospect i ve , double-blind , r and omized trial of 30 consecutive adults ( age > 16 years ) with chronic or recurrent acute rhinosinusitis undergoing bilateral FESS , excluding patients with significant difference in their sinus disease bilaterally using preoperative computed tomographic scan assessment ( Lund-McKay scores > 2 ) . SETTING Tertiary hospital , Vancouver , British Columbia . METHODS Preoperatively , all patients were r and omized and blinded to receive NasoPore ( Stryker Canada ) on one side and Merocel on the other . Patients completed a question naire during their first postoperative week relating to their subjective assessment of pain , pressure , nasal blockage , swelling , and bleeding . Patients were evaluated 1 week postoperatively for packing removal and debridement , and associated discomfort and bleeding with the removal , as well as overall preference for either pack . A clinician blinded to the r and omization process objective ly assessed the healing status of the nasal cavities at 4 and 12 weeks postoperatively . MAIN OUTCOME MEASURES Patient satisfaction , bleeding , and wound healing postoperatively . RESULTS Thirty patients were enrolled . There was no significant difference between the Lund-Mackay scores in both groups preoperatively ( p = .80 ) . Postoperatively , there was no significant difference between both groups with regard to patients ' pain , pressure , blockage , swelling , bleeding , or discomfort on packing removal ( p > .05 ) . There was no statistical difference in the amount of bleeding associated with packing removal ( p = .32 ) . Mucosal grading at 4 weeks was significantly better for the traditional MMS ( p = .03 ) , but this difference disappeared at the 12-week visit ( p = 1.00 ) . CONCLUSIONS The absorbable pack did not significantly reduce the risk of bleeding or patient discomfort compared with a traditional nonabsorbable MMS and was associated with significantly slower mucosal healing initially , an effect that disappeared after 3 months postoperatively . There was no significant patient preference for either pack OBJECTIVES Evaluate causes of surgical failure at time of revision endoscopic sinus surgery . STUDY DESIGN Prospect i ve review of 682 cases that had endoscopic sinus surgery performed between 1991 and 1995 . METHODS In all cases , variables of age , sex , asthma , allergy , computed tomography stage , associated procedures , complications , and operative findings were collected . Those cases that had a failure after a previous endoscopic sinus procedure and not an intranasal procedure or an external procedure were evaluated . RESULTS Fifty-two patients ( 7.6 % ) were identified . The age range was 24 to 70 years . The most common cause of failure was residual air cells and adhesions in the ethmoid area ( 30.7 % ) , followed by maxillary sinus ostium stenosis in 27 % , frontal sinus ostium stenosis in 25 % , and a separate maxillary sinus ostium stenosis in 15 % of the cases . CONCLUSION Review of surgical causes of failure in endoscopic sinus surgery patients revealed that residual air cells and stenotic maxillary or frontal sinus ostium were the most common causes of failures |
12,087 | 28,524,907 | Transmucosal immediate‐release fentanyl ( TIRF ) was found to have the most evidence for BtCP . | BACKGROUND : Breakthrough cancer pain ( BtCP ) , defined as a transient exacerbation of pain that occurs in conjunction with well‐controlled background pain , is a common and burdensome problem in patients with cancer .
OBJECTIVES : The aim of this systematic review is to identify evidence ‐based pharmacologic modalities for adequate management of BtCP . | Background : Fentanyl buccal soluble film ( FBSF ) has been developed as a treatment of breakthrough pain in opioid-tolerant patients with cancer . The objective of this study was to evaluate the efficacy of FBSF at doses of 200–1200 μg in the management of breakthrough pain in patients with cancer receiving ongoing opioid therapy . Patients and methods : This was a multicenter , r and omized , double-blind , placebo-controlled , multiple-crossover study that included opioid-tolerant adult patients with chronic cancer pain who experienced one to four daily episodes of breakthrough pain . The primary efficacy assessment was the sum of pain intensity differences at 30 min ( SPID30 ) postdose . Results : The intent-to-treat population consisted of 80 patients with ≥1 post-baseline efficacy assessment . The least-squares mean ( LSM ± SEM ) of the SPID30 was significantly greater for FBSF-treated episodes of breakthrough pain than for placebo-treated episodes ( 47.9 ± 3.9 versus 38.1 ± 4.3 ; P = 0.004 ) . There was statistical separation from placebo starting at 15 min up through 60 min ( last time point assessed ) . There were no unexpected adverse events ( AEs ) or clinical ly significant safety findings . Conclusions : FBSF is an effective option for control of breakthrough pain in patients receiving ongoing opioid therapy . In this study , FBSF was well tolerated in the oral cavity , with no reports of treatment-related oral AEs Purpose Instanyl ® ( intranasal fentanyl spray ) is a novel treatment for breakthrough pain ( BTP ) in cancer patients . It has shown a rapid onset of pain relief in clinical trials . This study examines the use of Instanyl ® in real-life setting s. Methods A 3-month observational , prospect i ve , cohort study of cancer patients with BTP receiving Instanyl ® ( 50 , 100 , or 200 μg ) under routine clinical practice . Data were collected at three time points corresponding with routine clinic visits – baseline , Week 4 , and Week 13 . Primary outcomes : success of titration and maintenance dose after titration . Secondary outcomes : change in maintenance dose of Instanyl ® and level of background pain medication ; Brief Pain Inventory — Short Form ( BPI-SF ) and Patient Treatment Satisfaction Scale ( PTSS ) scores ; adverse drug reactions ( ADRs ) . Results Titration with Instanyl ® was successful in 84.5 % of 309 patients ; most patients were titrated at the lowest dose ( 50 μg ) . The majority showed no change in maintenance dose , with little change in the level of background pain medication . BPI-SF and PTSS scores significantly improved from baseline to Week 4 . The main reason for terminating Instanyl ® was death , as expected due to the underlying disease ; incidence of ADRs was low and no fatal ADRs were reported . Conclusions In a real-life group of cancer patients with disease progression , Instanyl ® was titrated successfully at doses < 200 μg in the majority of patients , requiring only one dose , with no further change in maintenance dose . Pain severity , impact of pain on daily life , and treatment satisfaction significantly improved with Instanyl ® treatment . No unexpected ADRs occurred & NA ; Oral transmucosal fentanyl citrate ( OTFC ® ; Actiq ® ) is a drug delivery formulation used for management of breakthrough cancer pain . Previous studies with open‐label comparisons indicated OTFC was more effective than patients ’ usual opioid for breakthrough pain . The objective of this study was to compare OTFC and morphine sulfate immediate release ( MSIR ® ) for management of breakthrough pain in patients receiving a fixed scheduled opioid regimen . This double‐blind , double‐dummy , r and omized , multiple crossover study was conducted at 19 US university‐ and community‐based hospitals and clinics and comprised 134 adult ambulatory cancer patients . Patients were receiving a fixed scheduled opioid regimen equivalent to 60–1000 mg/day oral morphine or 50–300 & mgr;g/h transdermal fentanyl , were using a ‘ successful ’ MSIR dose ( 15–60 mg ) as defined by entry criteria , and were experiencing 1–4 episodes of breakthrough pain per day . In open‐label fashion , OTFC was titrated such that a single unit ( 200–1600 & mgr;g ) provided adequate pain relief with acceptable side effects . Successfully titrated patients entered the double‐blind phase of the study and received ten prenumbered sets of r and omized capsules and oral transmucosal units . Five sets were the successful OTFC dose paired with placebo capsules , and five sets were placebo OTFC paired with capsules containing the successful MSIR dose . Patients took one set of study medication for each episode of target breakthrough pain . Pain intensity ( PI ) , pain relief ( PR ) and global performance of medication ( GP ) scores were recorded . Pain intensity differences ( PID ) were calculated and 15‐min PID was the primary efficacy variable . Adverse events were recorded . Sixty‐nine percent of patients ( 93/134 ) found a successful dose of OTFC . OTFC yielded outcomes ( PI , PID , and PR ) at all time points that were significantly better than MSIR . GP also favored OTFC and more patients opted to continue with OTFC than MSIR following the study . Somnolence , nausea , constipation , and dizziness were the most common drug‐associated side effects . In conclusion , OTFC was more effective than MSIR in treating breakthrough cancer pain Abstract Background and objectives : Breakthrough cancer pain ( BTcP ) represents an important clinical challenge in the care of patients with cancer . This trial evaluated the efficacy and long-term tolerability of a sublingual formulation of the fast-acting opioid fentanyl , for the treatment of BTcP in opioid-tolerant patients with cancer . Research design and methods : This was a r and omized , placebo-controlled , multi-center , phase III trial , conducted in opioid-tolerant male and female patients ( aged ≥17 years ) with BTcP. The study was conducted at 36 centers across the USA . The study comprised a 2-week open-label titration phase , followed by a double-blind efficacy phase , during which patients received sublingual fentanyl citrate orally disintegrating tablet ( sublingual fentanyl ODT ) or placebo , in a r and om order . The primary efficacy endpoint was the sum of pain intensity difference ( SPID ) over 30 min post-administration . Secondary efficacy endpoints included pain intensity difference ( PID ) and pain relief ( PR ) throughout the 60-min post-dose assessment period . Following efficacy evaluation , patients entered a long-term safety phase of up to 12 months . Adverse events were recorded throughout the study . [ Clinical trial registration : NCT00262678 ] Results : A total of 131 patients entered the titration phase , of whom 61 were included in the primary efficacy analysis . Sublingual fentanyl ODT provided significant improvements in SPID relative to placebo at 30 min ( 49.5 vs. 36.6 , p = 0.0004 ) and 60 min post-administration ( 143.0 vs. 104.5 , p = 0.0002 ) . Furthermore , sublingual fentanyl ODT provided significant improvements in PID and PR compared to placebo , from 10 min post-dose ( p = 0.0055 and p = 0.049 for PID and PR , respectively ) . Patient recruitment was stopped early , due to positive interim analysis results ( significant at prespecified level , p ≤ 0.0414 ) . Overall , sublingual fentanyl ODT was well-tolerated both systemically and sublingually , with 41 patients experiencing ≥1 study drug-related adverse event ( AE ) . The most common AEs included nausea ( 12.2 % ) , vomiting ( 5.3 % ) and somnolence ( 4.6 % ) . One serious AE ( mild affect lability ) was considered possibly related to study medication . The observed pattern of AEs was consistent with that previously observed with fentanyl . Conclusions : Sublingual fentanyl ODT was efficacious and well-tolerated for the treatment of BTcP in opioid-tolerant patients with cancer . Sublingual fentanyl ODT provided significant improvements in pain intensity compared to placebo , from 10 min post-administration and throughout the 60-min post-dose assessment period . Sublingual fentanyl ODT was well tolerated over 12 months of treatment Abstract Objective : The efficacy of intranasal fentanyl spray ( INFS ) was compared with that of oral transmucosal fentanyl citrate ( OTFC ) for the relief of cancer-related breakthrough pain ( BTP ) in an open-label , crossover trial . Methods : Adult cancer patients receiving stable background opioid treatment and experiencing BTP episodes were recruited from 44 study centres in seven European countries ( Austria , France , Germany , Italy , Pol and , Spain and the United Kingdom ) ; of the 196 patients enrolled , 139 were r and omised to receive INFS followed by OTFC , or vice versa . Patients were titrated to an effective dose of one agent ( 50 , 100 or 200 µg INFS ; 200 , 400 , 600 , 800 , 1200 or 1600 µg OTFC ) to treat six BTP episodes , then titration and treatment were repeated with the other agent . The primary outcome was patient-recorded time to onset of ‘ meaningful ’ pain relief . Secondary outcomes included pain intensity difference ( PID ) at 10 and 30 minutes ( PID10 , PID30 ) , sum of PID at 15 and 60 minutes ( SPID0–15 , SPID0–60 ) , ease of administration , treatment preference and relationship between background opioid dose and effective INFS dose . Additional outcome measures included proportions of episodes with ≥33 % and ≥50 % pain intensity ( PI ) reduction , and PID at additional time points . Clinical trial registration number : NCT00496392 . Results : Among the intention-to-treat population ( n = 139 ) , median time to onset of ‘ meaningful ’ pain relief was 11 minutes with INFS versus 16 minutes with OTFC ; 65.7 % of patients attained faster time to ‘ meaningful ’ pain-relief onset with INFS ( p < 0.001 ) . PID was statistically significantly greater for INFS than OTFC from 5 minutes post-dosing . Significantly more INFS-treated breakthrough pain episodes achieved clinical ly important pain relief ( ≥33 % and ≥50 % PI reduction ) up to 30 minutes post-dosing . The proportions of episodes treated with INFS and OTFC achieving a PI reduction of ≥33 % at 5 minutes were 25.3 % versus 6.8 % ( p < 0.001 ) , and at 10 minutes were 51.0 % versus 23.6 % ( p < 0.001 ) , respectively ; the proportions of episodes treated with INFS and OTFC achieving a ≥50 % PI reduction at 5 minutes were 12.8 % versus 2.1 % ( p < 0.001 ) , and at 10 minutes were 36.9 % versus 9.7 % ( p < 0.001 ) , respectively . Higher SPID0–15 and SPID0–60 scores were achieved with INFS ( p < 0.001 ) . More patients preferred INFS than OTFC ( p < 0.001 ) and more patients found it very easy/easy to use . Both treatments were well tolerated . In the safety population ( n = 139 ) , 56.8 % ( n = 79 ) of patients experienced ≥1 AE during the trial . The only AE that occurred in ≥5 % of patients in either treatment group was nausea . Among those patients who experienced serious AEs ( 13.7 % , n = 19 ) , none were considered to be related to either study medication . There was a weak correlation between effective INFS doses and background opioid doses . Conclusion : In this open-label , r and omised , crossover trial , significantly more patients attained faster ‘ meaningful ’ pain relief with INFS than OTFC , and more patients preferred INFS to OTFC Objectives To determine the efficacy and safety of different opioids used in doses proportional to the basal opioid regimen for the management of breakthrough pain ( BP ) . Methods In 66 patients consecutive patients admitted to a pain relief and palliative care unit , the efficacy and safety of different opioids used in doses proportional to the basal opioid regimen for the management of breakthrough pain ( BP ) were assessed . The choice of the opioid to be administered as rescue medication was based on the characteristics of patients , clinical stability , compliance , preference , and so on . For each episode , nurses were instructed to routinely collect changes in pain intensity and emerging problems when pain became severe ( T0 ) , and to re-assess the patient 15 minutes after the opioid given as a rescue medication ( T15 ) . Results Six hundred twenty four episodes of BP were recorded during admission . Intravenous morphine ( IV-MO ) and oral transmucosal fentanyl ( OTFC ) were most frequently administered . Of 503 events available , 427 episodes were defined as successfully treated , while 76 episodes required a further administration of opioids . Pain intensity significantly decreased at T15 in all the groups ( P<0.001 ) . In 97.2 % and 90.7 % of cases treated with IV-MO , BP events had a reduction in pain intensity of more than 33 % and 50 % , respectively . In 99.2 % and 97.6 % patients receiving OTFC , BP events had a reduction in pain intensity of more than 33 % and 50 % , respectively . Discussion This survey suggests that doses of opioids for BP proportional to the basal opioid regimen , are very effective and safe in clinical practice , regardless the opioid and modality used Introduction Breakthrough cancer pain ( BTcP ) is recognized as a clinical ly significant complication of chronic cancer pain with most BTcP episodes peaking in intensity within a few minutes and lasting for approximately 30 min . Although a number of rapid-onset fentanyl preparations have been developed in the last decade , BTcP is still typically managed through the use of rescue doses of oral morphine but a comparative study of sublingual fentanyl and oral morphine is still lacking . The aim of this study was to determine the efficacy , tolerability , and patient satisfaction of sublingual fentanyl citrate ( SLF ) and oral morphine solution ( OM ) in the treatment of BTcP. Methods In this prospect i ve , longitudinal , controlled- study , 40 patients with BTcP were allocated to receive oral morphine ( OM ) or sublingual fentanyl ( SLF ) . Pain intensity level on a 0–10 numerical rating visual analog scale ( VAS ) , frequency of BTcP throughout the day , onset of relief ( 0–5 , 6–10 , 11–15 , or over 16 min ) , time required for dose titration , patient satisfaction and adverse effects were assessed at 3 , 7 , 15 , and 30 days after starting the treatment . Results Mean doses of opioids for BTcP were 235 ± 23.4 μg ( SLF ) and 38 ± 5.2 mg ( OM ) . The mean pain intensity levels were significantly lower with SLF than OM at 3 days ( 6.0 vs. 6.95 ; p = 0,001 ) , 7 days ( 4.15 vs. 6.25 , p < 0.001 ) , 15 days ( 3.45 vs. 5.35 , p < 0.001 ) , and 30 days ( 3.05 vs. 4.45 , p < 0.001 ) . SLF provided significantly faster relief for BTcP than OM ( p < 0.001 ) with a shorter dose titration period ( mean 6.6 ± 3.3 vs. 13.3 ± 4.9 days ; p < 0.001 ) and better satisfaction scores and with a very good safety profile . Conclusions Administration of SLF might provide a more effective treatment option than oral morphine for Fentanyl buccal tablet ( FBT ) is a new opioid formulation providing rapid-onset analgesia for the treatment of breakthrough pain ( BTP ) . This study evaluated FBT for BTP in opioid-tolerant patients with chronic cancer pain . The study had a r and omized , double-blind , placebo-controlled design and was conducted at 30 outpatient treatment centers in the United States . Following open-label titration , patients were r and omly assigned to 1 of 18 double-blind dose sequences ( 7 FBT tablets , 3 placebo ) to treat 10 BTP episodes . Pain intensity was measured on an 11-point scale ( 0 = no pain ; 10 = worst pain ) . The primary efficacy measure was the sum of pain intensity differences ( PIDs ) for the first 60 minutes ( SPID60 ) ; secondary efficacy measures included PIDs and pain relief ( PR ) measured from 5 minutes through 2 hours . Adverse events ( AEs ) were recorded . Of 129 patients enrolled , 87 entered the double-blind phase . SPID60 significantly favored FBT versus placebo ( mean + /- SE , 9.7 + /- 0.63 vs 4.9 + /- 0.50 ; P < 0.0001 ) . Secondary measures also favored FBT : PIDs and PR showed significant differences versus placebo at 10 minutes ( 0.9 vs 0.5 ; 0.815 vs 0.606 , respectively , P < 0.0001 ) and all subsequent time points ( P < 0.0001 ) . AEs were typical of opioids ( eg , nausea , dizziness , fatigue ) . In conclusion , in this study of opioid-tolerant patients with chronic cancer pain and BTP , FBT was efficacious , well tolerated , demonstrated rapid onset of analgesia ( within 10 minutes ) , and had a sustained effect The aim of this prospect i ve cohort study was to confirm the safety of intravenous morphine ( IV-M ) used in doses proportional to the basal opioid regimen for the management of breakthrough pain and to record the nurse compliance on regularly recording data regarding breakthrough pain treated by IV-M. Over a one-year period , 99 patients received IV-M for breakthrough pain during 116 admissions . The IV-M dose was 1/5 of the oral daily dose , converted using an equianalgesic ratio of 1/3 ( IV/oral ) . For each episode , nurses were instructed to routinely collect changes in pain intensity and emerging problems when pain became severe ( T0 ) , and to reassess the patient 15minutes after IV-M injection ( T15 ) . Nurses were unaware of the aim of the study and just followed department policy . In total , 945 breakthrough events treated by IV-M were recorded and the mean number of events per patient per admission was eight ( 95 % confidence interval ( CI ) 6.9 - 9.5 ) . The mean dose of IV-M was 12 mg ( 95 % CI 9 - 14 mg ) . In the 469 events ( 49.6 % ) with a complete assessment , a decrease in pain of more than 33 % and 50 % was observed in 287 ( 61.2 % ) and 115 ( 24.5 % ) breakthrough events , respectively . The mean pain intensity decreased from 7.2 ( T0 ) to 2.7 ( T15 ) . In eight episodes , no changes in pain intensity were observed and a further dose of IV-M was given . The remaining patients did not require further interventions . No clinical events requiring medical intervention were recorded . In this confirmatory study , IV-M was administered for the management of breakthrough pain in doses proportional to the basal opioid regimen to all patients , including older patients and those requiring relatively large doses . This did not result in life-threatening adverse effects in a large number of patients and was effective in most cases . The role of nurses is of paramount importance in monitoring and collecting data and gathering information for audit purpose s on the unit Abstract Background and objectives : A number of transmucosal fentanyl formulations have been developed for the management of breakthrough cancer pain ( BTCP ) . Sublingual delivery of fentanyl , formulated as fentanyl sublingual spray , offers the potential for more rapid and greater absorption of fentanyl and associated onset of analgesic effect compared with other formulations . The objective of this study was to assess the efficacy and safety of fentanyl sublingual spray for the treatment of BTCP . Research design and methods : This was a r and omized , double-blind , placebo-controlled phase III trial conducted in opioid-tolerant patients with BTCP . An open-label titration period was followed by a double-blind treatment period during which patients received fentanyl sublingual spray ( 100–1600 mcg ) or placebo . Clinical trial registration : Trial registration : Clinical Trials.gov identifier : NCT00538850 . Main outcome measures : The primary efficacy measure was summed pain intensity difference at 30 minutes ( SPID30 ) . Secondary efficacy measures included total pain relief at 30 minutes ( TOTPAR30 ) and patient global evaluation of study medication at 30 minutes . Efficacy measures were also assessed at various time points from 5–60 minutes postdose . Adverse events were monitored throughout the study . Results : A total of 130 patients were treated during the titration period , of whom 98 ( 75.4 % ) entered the double-blind period . Relative to placebo , fentanyl sublingual spray significantly improved mean SPID scores from 5 minutes ( p = 0.0219 ) through 60 minutes ( p < 0.0001 ) , including the primary endpoint at 30 minutes ( p < 0.0001 ) . Fentanyl sublingual spray produced significantly greater pain relief ( expressed in terms of TOTPAR ) from 5 through 60 minutes ( p < 0.0001 ) , and significantly greater global evaluation of treatment effectiveness ( p < 0.0001 ) , compared with placebo . During double-blind treatment , the most frequently reported adverse events were nausea ( 7.1 % ) , hyperhidrosis ( 5.1 % ) , and peripheral edema ( 5.1 % ) . Serious adverse events occurred in seven patients ( 5.4 % ) during titration and six ( 6.1 % ) during double-blind treatment ; none were considered related to treatment . Conclusions : These findings indicate that treatment with fentanyl sublingual spray results in effective relief of BTCP , with a rapid onset of action , and is well tolerated Purpose The aim of the present study was to assess the long-term tolerability and efficacy of intranasal fentanyl ( INFS ) in opioid-tolerant patients with breakthrough cancer pain ( BTP ) . Patients and methods A 6 months , observational , prospect i ve , cohort study design was employed to follow advanced cancer patients with BTP receiving INFS under routine clinical practice . Eligible adult cancer patients suffering from BTP had been prescribed INFS at effective doses . Data were collected at T0 and at month intervals for six months . The principal outcomes were the evaluation of possible serious adverse effects with prolonged use of INFS , the efficacy of BTP treatment with INFS , the quality of sleep , the rate of INFS discontinuation , and reasons for that . Results Seventy-five patients were surveyed . Thirty-four patients ( 45.3 % ) had a follow-up at 3 months , and twelve patients ( 16 % ) were followed up at 6 months . The mean opioid doses , expressed as oral morphine equivalents , ranged 111–180 mg/day , while the mean INFS doses were 87–119 μg . Adverse effects were reported in a minority of patients and were considered to be associated with opioid therapy used for background pain . The quality of sleep significantly improved during the first 3–4 months . Finally , efficacy based on a general impression regarding the efficacy of INFS was good-excellent in most patients and statistically improved in time up to the third month . Conclusion The long-term use of INFS in advanced cancer patients is effective and safe . No serious adverse effects were found up to six months of assessment . The level of quality of sleep and patients ’ satisfaction was relatively good , considering the advanced stage of disease PURPOSE The aims of this study were to explore the efficacy of intranasal fentanyl spray * ( INFS ) 400 μg to evaluate 12-week tolerability of the nasal mucosa and to explore safety data for all dose strengths of INFS in patients with cancer-related breakthrough pain ( BTP ) . METHODS Patients received a test dose of INFS 50 μg , followed by a titration phase . Those patients with doses titrated to 200 or 400 μg entered a r and omized , double-blind , cross-over efficacy phase , in which 8 episodes of BTP were r and omly treated with INFS 400 μg ( 6 episodes ) and placebo ( 2 episodes ) , followed by a tolerability phase . Patients with doses titrated to 50 or 100 μg entered the tolerability phase directly . Primary outcome was measured by pain intensity difference at 10 minutes , analyzed using ANCOVA , and presented as least square mean difference . Examination of the nasal cavity was conducted at inclusion and after 12 weeks of treatment by an otorhinolaryngologist . FINDINGS Forty-six patients were included . Thirty-eight patients ' doses were titrated to an effective dose of INFS ; 50 μg ( n = 8) , 100 μg ( n = 9 ) , 200 μg ( n = 9 ) , and 400 μg ( n = 12 ) ; 15 patients entered the efficacy phase and 31 entered the tolerability phase . In the efficacy phase , 88 and 29 episodes of BTP were treated with INFS 400 μg and placebo , respectively . Pain intensity difference at 10 minutes least square mean for INFS 400 μg was 2.5 ( 95 % CI , 1.42 - 3.49 ) ( P < 0.001 ) and least square mean difference between INFS 400 μg and placebo was 1.1 ( 95 % CI , 0.41 - 1.79 ) ( P = 0.002 ) . Runny nose ( 10 % ) and change in color of the mucosa ( 9 % ) were the most frequent findings of nasal examination , and nausea and dizziness were the most frequent treatment-related adverse events . One serious adverse event ( ie , respiratory depression ) was considered related to INFS . IMPLICATION S INFS 400 μg is effective and nasal tolerability and overall safety profile is acceptable during 12 weeks of use . Clinical Trials.gov identifier : NCT01429051 Abstract Background and objectives : Breakthrough cancer pain ( BTcP ) is a transient exacerbation of cancer pain in patients with otherwise stable , persistent background pain . This study evaluated the long-term effectiveness and tolerability of sublingual fentanyl orally disintegrating tablet ( sublingual fentanyl ODT ) , for the treatment of BTcP in opioid-tolerant patients with cancer . Research design and methods : This was a non-r and omized , open-label , multi-center , Phase III study conducted in opioid-tolerant patients ( aged ≥17 years ) with BTcP. The study comprised a 2-week titration phase , followed by a maintenance phase of up to 12 months . Patients self-administered sublingual fentanyl ODT for episodes of BTcP. Effectiveness was assessed using patients ’ global evaluation of medication ( PGEM ) , the brief pain inventory ( BPI ) and the depression , anxiety and positive outlook scale ( DAPOS ) . Adverse events were recorded throughout . Clinical trial registration : NCT00263575 ( http://www . clinical trials.gov/ ) . Results : Of 139 recruited patients , 69 % identified an effective dose of sublingual fentanyl ODT ( a dosage that successfully treated all episodes of BTcP over two consecutive days ) and entered the maintenance phase , during which they were treated for a median of 149.0 days ( mean dose 507.5 µg ) . The study recorded a significant increase in reported satisfaction with pain medication at the 6-month and end-of- study visits , compared to screening ( p ≤ 0.01 ) . Evaluation of quality of life using BPI and DAPOS identified no deterioration in scores and significant improvements in certain parameters ( p < 0.05 ) . Sublingual fentanyl ODT was well tolerated , with no study drug-related deaths , and 49 patients ( 35.3 % ) experiencing ≥1 study drug-related adverse event . The most common of these included nausea ( 8.6 % ) , constipation ( 5.8 % ) and somnolence ( 5.8 % ) . There was no evidence of sublingual mucosal irritation due to the study medication . The pattern of adverse events was similar to that previously observed with transmucosal fentanyl . Conclusions : Sublingual fentanyl ODT was effective and well tolerated for the long-term treatment of BTcP in opioid-tolerant cancer patients . There was an increase in satisfaction with pain medication during the study , and sublingual fentanyl ODT showed an acceptable safety profile over 12 months of treatment Background Breakthrough cancer pain typically has a rapid onset and relatively short duration . Due to this temporal profile , it may not be adequately relieved by oral opioid analgesics . The sublingual fentanyl orally disintegrating tablet is a formulation by which fentanyl can be rapidly absorbed across the oral mucosa producing rapid-onset analgesia , and which may be effective for breakthrough pain treatment . Methods A multicenter , r and omized , placebo-controlled , double-blind comparative study was conducted to evaluate the efficacy and safety of the sublingual fentanyl tablet at optimized doses for breakthrough pain treatment in cancer patients treated with strong opioid analgesics at fixed intervals . The optimal dose was determined by open-label dose titration . The efficacy and safety of a 12-week extended treatment were also evaluated . Results Eleven of 42 subjects who received the sublingual fentanyl tablet experienced adverse drug reactions . Common reactions were somnolence , constipation , nausea , and vomiting . No serious adverse reactions occurred . Sublingual fentanyl tablets at optimal doses and placebo were administered to 37 subjects in a double-blinded manner . A significant analgesic effect of the sublingual fentanyl tablet was present compared to placebo at 30 min after administration . The sublingual fentanyl tablet was also effective and safe during extended treatment , in which changes in basal opioid doses as well as sublingual fentanyl tablet doses were made as needed . ConclusionS ublingual fentanyl tablets at doses determined by titration were effective and safe for breakthrough pain treatment in cancer patients treated with strong opioid analgesics at fixed intervals . Extended treatment up to 12 weeks was also effective and safe Background Data on the treatment of beakthrough cancer pain ( BTcP ) in patients receiving methadone therapy are lacking . Whether methadone produces tolerance to other opioids , other opioids should be less effective when administered as a BTcP medication . Aim The aim of this preliminary study was to assess the efficacy of fentanyl buccal tablets ( FBT ) for the treatment of BTcP in patients who receive methadone as a background analgesic . Patients and methods A prospect i ve study was carried out for a period of 1 year in a consecutive sample of 13 advanced cancer patients admitted to an acute pain relief and palliative care unit— patients who were receiving stable doses of oral methadone for their background analgesia . The dose of FBT was 100 μg for patients who were receiving 12 mg of oral methadone . For higher doses of methadone , proportional doses of FBT were given . For each episode , trained nurses collected changes in pain intensity ( on numerical scale 0–10 ) and emerging problems when called for pain increases considered to be severe in intensity by patients ) ( T0 ) and 15 min after FBT administration ( T15 ) . Results The mean age was 58.1 ( SD 9.9 ) , and nine patients were males . Sixty-four events were treated with FBT ( 4.9 ± 3.1 for each patient , on average ) . Patients were receiving mean doses of oral methadone of 68 mg ( range 15–240 ) . In the majority of events , a decrease in pain intensity > 33 % and > 50 % was observed ( n = 20 and n = 26 , respectively ) , 15 min after the administration of FBT . Data on ten episodes were unavailable . Nine events were unsuccessfully treated . In all the patients , the level of adverse effects after FBT administration was mild and undistinguishable from that associated with basal opioid analgesia . Conclusion FBT was effective as breakthrough pain medication in patients receiving methadone for their background analgesia , confirming that this group of patients are not inevitably resistant to other opioids Aim : To compare the efficacy and safety of oral transmucosal fentanyl citrate ( OTFC ) and oral morphine in Indian patients with breakthrough episodes of cancer pain . Material s and Methods : In this r and omized , open label , active controlled , clinical study , total 186 patients who regularly experienced 1 - 4 episodes of breakthrough cancer pain ( BTCP ) daily , over the persistent pain controlled by taking oral morphine 60 mg/day or its equivalent were r and omized to receive either OTFC 200 mcg or oral morphine 10 mg for the treatment of BTCP for 3 days . Improvement in pain as determined by numerical rating scale ( NRS ) at 5 , 15 , 30 , and 60 minutes of drug administration and percentage of BTCP episodes showing reduction in pain intensity by > 33 % at 15 minutes were primary efficacy endpoints . Secondary efficacy endpoints were requirement for rescue analgesia and global assessment by physician and patient . Data of both treatment groups were analysed by appropriate statistical test using software , STATISTICA , version 11 . Results : Patients treated with OTFC experienced significantly greater improvement in pain intensity of breakthrough episodes compared to those treated with oral morphine at all assessment time points ( P < 0.0001 ) . 56 % of breakthrough pain episodes treated with OTFC showed a greater than 33 % reduction in pain intensity from baseline at 15 minutes compared to 39 % episodes treated with oral morphine ( P < 0.0001 ) . Patient 's and physician 's global assessment favoured OTFC than oral morphine ( P < 0.0001 ) . Requirement of rescue analgesia in both the study groups was similar ( P > 0.05 ) . Both study drugs were well tolerated . Conclusions : OTFC was found to provide faster onset of analgesic effect than immediate release oral morphine in management of breakthrough cancer pain The objective of this study was to demonstrate the efficacy , safety and patient acceptability of the use of intranasal sufentanil for cancer-associated breakthrough pain . This was a prospect i ve , open label , observational study of patients in three inpatient palliative care units in Australia . Patients on opioids with cancer-associated breakthrough pain and clinical evidence of opioid responsiveness to their breakthrough pain were given intranasal ( IN ) Sufentanil via a GO Medical ™ patient controlled IN analgesia device . The main outcome measures were pain scores , need to revert to previous breakthrough opioid after 30 min , number of patients who chose to continue using IN sufentanil , and adverse effects . There were 64 episodes of use of IN sufentanil for breakthrough pain in 30 patients . There was a significant reduction in pain scores at 15 ( P < 0.0001 ) and 30 min ( P < 0.0001 ) . In only 4/64 ( 6 % ) episodes of breakthrough pain did the participants choose to revert to their pre study breakthrough medication . Twenty-three patients ( 77 % ) rated IN sufentanil as better than their pre study breakthrough medication . The incidence of adverse effects was low and most were mild . Our study showed that IN sufentanil can provide relatively rapid onset , intense but relatively short lasting analgesia and in the palliative care setting it is an effective , practical , and safe option for breakthrough pain In this study we evaluated the efficacy and tolerability of sublingual fentanyl ( SLF ) for breakthrough pain ( BTP ) in adult opioid-tolerant cancer patients . Patients received one dose of placebo , SLF 100 , 200 and 400 μg in r and om order at four pain episodes . The primary efficacy endpoint was pain intensity difference ( PID ) from baseline . Twenty-seven patients received study medication . Overall PID increased significantly with SLF 400 μg versus placebo ( 8.57 mm , p < 0.0001 ) . Improvements were statistically different from placebo at 15 min ( p = 0.005 ) . SLF 100 and 200 μg showed a numerical trend towards improved pain relief . A dose that gave a clinical ly important reduction in pain ( PID > 20 mm ) was identified by 95 % of patients . Reduced use of rescue medication ( p < 0.001 , SLF 400 μg ) and improved global assessment of treatment ( p = 0.0146 , SLF 400 μg ) confirmed these differences as clinical ly important . Nausea and dizziness were the most common treatment-related adverse effects . SLF appears to be a fast , effective and well-tolerated treatment for BTP Abstract Background and objectives : Breakthrough cancer pain ( BTcP ) affects more than half of patients with cancer pain and has severe detrimental impacts on quality of life ( QoL ) . This study evaluated the efficacy , QoL impact and safety of sublingual fentanyl orally disintegrating tablet ( sublingual fentanyl ODT ) , for the treatment of BTcP in a clinical setting . Research design and methods : This was a prospect i ve , multi-center phase IV study . Opioid-tolerant adult patients with BTcP received sublingual fentanyl ODT in the course of routine clinical practice , and completed question naires over a 28-day observation period . Efficacy was assessed using measures of maximum BTcP intensity and the times to first effect and maximum effect of sublingual fentanyl ODT . Changes in QoL were evaluated using the modified pain disability index ( mPDI ) and the hospital anxiety and depression scale ( HADS ) . Adverse events were recorded throughout . Results : Of 217 enrolled patients , 181 ( 83.4 % ) completed the observation period . During the study , 3163 episodes were treated with a mean dose of 401.4 μg per episode . The study recorded a significant improvement in maximum BTcP intensity with sublingual fentanyl ODT , compared with baseline ( p < 0.0001 ) . Patients reported experiencing the first effects of the study drug within 5 minutes of administration in 67.7 % of episodes , and maximum effect within 30 minutes in 63.2 % of episodes . mPDI and HADS scores significantly improved during the observation period ( p < 0.0001 ) . Sublingual fentanyl ODT was well-tolerated , with 12 patients ( 5.5 % ) experiencing ≥1 study drug-related adverse event . Study limitations include a modest size and duration , and the single-arm design . Conclusions : Under the conditions of a phase IV study , sublingual fentanyl ODT was effective and well-tolerated for the treatment of BTcP in opioid-tolerant cancer patients . Study treatment was associated with significant improvements in BTcP intensity and QoL scores , and patients reported rapid onset of action in the majority of episodes CONTEXT Rapid-onset opioids for treating breakthrough pain ( BTP ) in patients with cancer are needed in the Japanese care setting . OBJECTIVES To examine the efficacy and safety of fentanyl buccal tablets ( FBTs ) for treating BTP in Japanese cancer patients . METHODS This was a r and omized , double-blinded , placebo-controlled study . In subjects receiving around-the-clock ( ATC ) opioids at doses of 30 mg or more to less than 60 mg or 60 - 1000 mg of oral morphine equivalents ( low and high ATC groups ) , dose titration was started from 50 to 100 μg FBT , respectively . Subjects whose effective dose was identified were r and omly allocated to a prearranged administration order of nine tablets ( six FBTs and three placebos ) , one tablet each for nine episodes of BTP ( double blinded ) . Efficacy and safety of FBT were assessed for patients overall , and also for the low and high ATC groups . RESULTS A significant difference was observed between FBT and placebo for the primary endpoint of pain intensity difference at 30 minutes . The analgesic onset of FBT was observed from 15 minutes in several secondary variables ( e.g. , pain relief ) . Adverse events were somnolence and other events associated with opioids were mostly mild or moderate . Of the low and high ATC group subjects , an effective FBT dose was identified in 72.2 % and 73.1 % , respectively . CONCLUSION The safety of FBT and its analgesic effect on BTP were confirmed in Japanese cancer patients receiving opioids . Our findings suggest that analgesic onset may occur from 15 minutes after FBT , and that FBT can be administered to patients with low doses of ATC opioids CONTEXT Fentanyl products have shown superiority to oral opioids for the management of breakthrough cancer pain ( BTcP ) . However , these studies did not use appropriate patient selection , and drugs have been compared by using different rationale s. OBJECTIVES The aim of this r and omized , crossover , controlled study was to compare efficacy and safety of fentanyl buccal tablets ( FBTs ) and oral morphine ( OM ) , given in doses proportional to opioid daily doses . METHODS Cancer patients with pain receiving ≥60 mg or more of oral morphine equivalents per day and presenting with ≤3 episodes of BTcP per day were included . In a r and omized , crossover manner , patients received FBT or OM at doses proportional to the daily opioid regimen in four consecutive episodes of BTcP. Pain intensity was measured before ( T0 ) and 15 ( T15 ) and 30 minutes ( T30 ) , after study drugs . RESULTS In total , 263 episodes of BTcP were treated . A statistical difference in changes in pain intensity-decrease of ≥33 % and ≥50%-between the two groups was observed at T15 and T30 ( P < 0.0005 ) . No severe adverse effects after study drug administration were observed . CONCLUSION When used in doses proportional to the basal opioid regimen , FBT showed a clear superiority and was well tolerated when compared with OM during the first 30 minutes , which is the approximate target for a timely intervention required for a BTcP medication BACKGROUND Immediate-release morphine sulfate ( IRMS ) remains the st and ard treatment for breakthrough cancer pain ( BTCP ) , but its onset of effect does not match the rapid onset and short duration of most BTCP episodes . OBJECTIVE This study will evaluate the efficacy/tolerability of fentanyl pectin nasal spray ( FPNS ) compared with IRMS for BTCP . METHODS Patients ( n = 110 ) experiencing one to four BTCP episodes/day while taking ≥ 60 mg/day oral morphine ( or equivalent ) for background cancer pain entered a double-blind , double-dummy ( DB/DD ) , multiple-crossover study . Patients completing a titration phase ( n = 84 ) continued to a DB/DD phase : 10 episodes of BTCP were r and omly treated with FPNS and oral capsule placebo ( five episodes ) or IRMS and nasal spray placebo ( 5 episodes ) . The primary end point was pain intensity ( P < .05 FPNS vs. IRMS ) difference from baseline at 15 minutes ( PID(15 ) ) . Secondary end points were onset of pain intensity ( PI ) decrease ( ≥ 1-point ) and time to clinical ly meaningful pain relief ( CMPR , ≥ 2-point PI decrease ) . Safety and tolerability were evaluated by adverse events ( AEs ) and nasal assessment s. By-patient and by-episode analyses were completed . RESULTS Compared with IRMS , FPNS significantly improved mean PID(15 ) scores . 57.5 % of FPNS-treated episodes significantly demonstrated onset of PI improvement by 5 minutes and 95.7 % by 30 minutes . CMPR ( ≥ 2-point PI decrease ) was seen in 52.4 % of episodes by 10 minutes . Only 4.7 % of patients withdrew from titration ( 2.4 % in DB/DD phase ) because of AEs ; no significant nasal effects were reported . CONCLUSION FPNS was efficacious and well tolerated in the treatment of BTCP and provided faster onset of analgesia and attainment of CMPR than IRMS This study assessed the long‐term safety and tolerability of fentanyl buccal tablet ( FBT ) in opioid‐tolerant patients with cancer and breakthrough pain ( BTP ) who were either naive to FBT or had completed 1 of 2 previous double‐blind , placebo‐controlled FBT studies ( rollover patients ) OBJECTIVE This trial investigated the efficacy and long-term tolerability of intranasal fentanyl spray ( INFS ) 50 to 200 microg in the treatment of breakthrough pain in opioid-tolerant patients with cancer . METHODS This Phase III , double-blind , r and omized , placebo-controlled , crossover trial was conducted at pain centers , anesthesiology departments , palliative care units , and oncology clinics in Austria , Denmark , France , Germany , and Pol and . Eligible patients were adults with cancer receiving a stable dose of long-term opioid treatment for the control of background pain . Patients were treated at home with their effective dose of INFS ( 50 , 100 , or 200 microg ) or inactive spray ( placebo ) in a r and omized sequence for 3 weeks , followed by a 10-month , open-label tolerability phase during which they received their effective dose of INFS . Throughout the study , patients were allowed to use their usual rescue medication , which was recorded in patient diaries . The primary efficacy end point was the pain intensity difference at 10 minutes after study drug administration ( PID(10 ) ) , as assessed using an 11-point numeric rating scale ( 0 = no pain to 10 = worst pain imaginable ) . An effect size of 0.5 for PID was considered clinical ly relevant . The rate of response , defined as PID(10 ) > 2 , was also assessed . Adverse events ( AEs ) were recorded in patient diaries during the efficacy period and reported in monthly clinic visits and follow-up weekly telephone contacts during the extension period . RESULTS In all , 120 patients were enrolled and achieved an effective dose ; 113 were r and omized and 111 were included in the intent-to-treat analysis set ( 56 men , 55 women ; mean [ SD ] age , 60.6 [ 9.45 ] years ; mean weight , 70.3 kg [ men ] and 65.3 kg [ women ] ; white race , 107 [ 96.4 % ] ; INFS 50 microg , 18 ; INFS 100 microg , 48 ; INFS 200 microg , 45 ; placebo , 110 ) . PID(10 ) with INFS was 2-fold that with placebo ( adjusted means , 2.36 vs 1.10 ; adjusted difference , 1.26 [ greater than the clinical ly relevant difference of 0.5 ] ; P < 0.001 ) . Additional analysis revealed that the mean response rate with all 3 doses of INFS was 51.1 % versus 20.9 % with placebo . The prevalence of AEs was 22/111 ( 19.8 % ) during the efficacy period , during which the most frequently reported AEs were nausea ( 5 [ 4.5 % ] ) and vertigo ( 2 [ 1.8 % ] ) . No serious AEs were considered related to the study drugs . In all , 108 patients entered the extension period , with a mean duration of exposure to INFS of 134.9 days . Progression of underlying malignant disease was the most common AE reported during this period ( 55 [ 50.9 % ] ) ; this event was not considered treatment related . CONCLUSIONS In these opioid-tolerant patients with cancer , INFS at doses of 50 , 100 , and 200 microg was associated with an onset of activity at 10 minutes and effective treatment of breakthrough pain compared with placebo . All doses were generally well tolerated and clinical ly efficacious |
12,088 | 29,982,151 | Incidence of stroke , hypertension , dyslipidaemia , asthma , and coronary heart disease were reduced .
Conclusions : Greenspace exposure is associated with numerous health benefits in intervention and observational studies .
These results are indicative of a beneficial influence of greenspace on a wide range of health outcomes .
Green prescriptions involving greenspace use may have substantial benefits .
HighlightsGreenspace exposure is associated with wide ranging health benefits across 143 included studies .Meta‐ analysis showed statistically significant reductions in diastolic blood pressure , salivary cortisol and heart rate .
Meta‐ analysis found statistically significant decreases in incidence of diabetes , all‐cause and cardiovascular mortality . | Background : The health benefits of greenspaces have dem and ed the attention of policymakers since the 1800s .
Although much evidence suggests greenspace exposure is beneficial for health , there exists no systematic review and meta‐ analysis to synthesis e and quantify the impact of greenspace on a wide range of health outcomes .
Objective : To quantify evidence of the impact of greenspace on a wide range of health outcomes . | BACKGROUND Access to local parks can affect walking levels . Neighborhood environment and park use may influence relationships between neighborhood socioeconomic status ( SES ) and walking . METHODS Self-report data on perceived park features , neighborhood environment , park use , neighborhood walking and sociodemographics were obtained from a sample of Australian adults , living in high/low SES areas . Surveys were mailed to 250 r and omly selected households within 500 m of 12 matched parks . Mediating effects of perceived environment attributes and park use on relationships between area-SES and walking were examined . RESULTS Mean frequency of local park use was higher for high-SES residents ( 4.36 vs 3.16 times/wk , P < .01 ) , who also reported higher levels of park safety , maintenance , attractiveness , opportunities for socialization , and neighborhood crime safety , aesthetics , and traffic safety . Safety and opportunity for socialization were independently positively related to monthly frequency of visits to a local park which , in turn , was positively associated with walking for recreation and total walking . Residents of higher SES areas reported an average 22 % ( 95 % CI : 5 % , 37 % ) more weekly minutes of recreational walking than their low SES counterparts . CONCLUSION Residents of high-SES areas live in environments that promote park use , which positively contributes to their weekly amounts of overall and recreational walking Purpose of review This review highlights recent work evaluating the relationship between exercise , physical activity and physical and mental health . Both cross-sectional and longitudinal studies , as well as r and omized clinical trials , are included . Special attention is given to physical conditions , including obesity , cancer , cardiovascular disease and sexual dysfunction . Furthermore , studies relating physical activity to depression and other mood states are review ed . The studies include diverse ethnic population s , including men and women , as well as several age groups ( e.g. adolescents , middle-aged and older adults ) . Recent findings Results of the studies continue to support a growing literature suggesting that exercise , physical activity and physical-activity interventions have beneficial effects across several physical and mental-health outcomes . Generally , participants engaging in regular physical activity display more desirable health outcomes across a variety of physical conditions . Similarly , participants in r and omized clinical trials of physical-activity interventions show better health outcomes , including better general and health-related quality of life , better functional capacity and better mood states . Summary The studies have several implication s for clinical practice and research . Most work suggests that exercise and physical activity are associated with better quality of life and health outcomes . Therefore , assessment and promotion of exercise and physical activity may be beneficial in achieving desired benefits across several population s. Several limitations were noted , particularly in research involving r and omized clinical trials . These trials tend to involve limited sample sizes with short follow-up periods , thus limiting the clinical implication s of the benefits associated with physical activity . Abbreviations CAD : coronary artery disease ; COPD : chronic obstructive pulmonary disease ; CRP : cardiac rehabilitation program ; CVD : cardiovascular disease ; GMCB : group-mediated cognitive – behavioural ; HRQOL : health-related quality of life Seasonal affective disorder ( SAD ) is a syndrome characterized by recurrent depressions that occur annually at the same time each year . We describe 29 patients with SAD ; most of them had a bipolar affective disorder , especially bipolar II , and their depressions were generally characterized by hypersomnia , overeating , and carbohydrate craving and seemed to respond to changes in climate and latitude . Sleep recordings in nine depressed patients confirmed the presence of hypersomnia and showed increased sleep latency and reduced slow-wave ( delta ) sleep . Preliminary studies in 11 patients suggest that extending the photoperiod with bright artificial light has an antidepressant effect OBJECTIVE To investigate the effects of short-term forest bathing on human health . METHODS Twenty healthy male university students participated as subjects and were r and omly divided into two groups of 10 . One group was sent on a two-night trip to a broad-leaved evergreen forest , and the other was sent to a city area . Serum cytokine levels reflecting inflammatory and stress response , indicators reflecting oxidative stress , the distribution of leukocyte subsets , and plasma endothelin-1 ( ET-1 ) concentrations were measured before and after the experiment to evaluate the positive health effects of forest environments . A profile of mood states ( POMS ) evaluation was used to assess changes in mood states . RESULTS No significant differences in the baseline values of the indicators were observed between the two groups before the experiment . Subjects exposed to the forest environment showed reduced oxidative stress and pro-inflammatory level , as evidence d by decreased malondialdehyde , interleukin-6 , and tumor necrosis factor a levels compared with the urban group . Serum cortisol levels were also lower than in the urban group . Notably , the concentration of plasma ET-1 was much lower in subjects exposed to the forest environment . The POMS evaluation showed that after exposure to the forest environment , subjects had lower scores in the negative subscales , and the score for vigor was increased . CONCLUSION Forest bathing is beneficial to human health , perhaps through preventive effects related to several pathological factors Background : Green , natural environments may ameliorate adverse environmental exposures ( e.g. , air pollution , noise , and extreme heat ) , increase physical activity and social engagement , and lower stress . Objectives : We aim ed to examine the prospect i ve association between residential greenness and mortality . Methods : Using data from the U.S.-based Nurses ’ Health Study prospect i ve cohort , we defined cumulative average time-varying seasonal greenness surrounding each participant ’s address using satellite imagery [ Normalized Difference Vegetation Index ( NDVI ) ] . We followed 108,630 women and observed 8,604 deaths between 2000 and 2008 . Results : In models adjusted for mortality risk factors ( age , race/ethnicity , smoking , and individual- and area-level socioeconomic status ) , women living in the highest quintile of cumulative average greenness ( accounting for changes in residence during follow-up ) in the 250-m area around their home had a 12 % lower rate of all-cause nonaccidental mortality [ 95 % confidence interval ( CI ) ; 0.82 , 0.94 ] than those in the lowest quintile . The results were consistent for the 1,250-m area , although the relationship was slightly attenuated . These associations were strongest for respiratory and cancer mortality . The findings from a mediation analysis suggested that the association between greenness and mortality may be at least partly mediated by physical activity , particulate matter < 2.5 μm , social engagement , and depression . Conclusions : Higher levels of green vegetation were associated with decreased mortality . Policies to increase vegetation may provide opportunities for physical activity , reduce harmful exposures , increase social engagement , and improve mental health . Planting vegetation may mitigate the effects of climate change ; in addition , evidence of an association between vegetation and lower mortality rates suggests it also might be used to improve health . Citation : James P , Hart JE , Banay RF , Laden F. 2016 . Exposure to greenness and mortality in a nationwide prospect i ve cohort study of women . Environ Health Perspect 124:1344–1352 ; Forest bathing trip is a short , leisurely visit to forest . In this study we determined the health effects of forest bathing trip on elderly patients with chronic obstructive pulmonary disease ( COPD ) . The patients were r and omly divided into two groups . One group was sent to forest , and the other was sent to an urban area as control . Flow cytometry , ELISA , and profile of mood states ( POMS ) evaluation were performed . In the forest group , we found a significant decrease of perforin and granzyme B expressions , accompanied by decreased levels of pro-inflammatory cytokines and stress hormones . Meanwhile , the scores in the negative subscales of POMS decreased after forest bathing trip . These results indicate that forest bathing trip has health effect on elderly COPD patients by reducing inflammation and stress level We previously reported that the forest environment enhanced human natural killer ( NK ) cell activity , the number of NK cells , and intracellular anti-cancer proteins in lymphocytes , and that the increased NK activity lasted for more than 7 days after trips to forests both in male and female subjects . To explore the factors in the forest environment that activated human NK cells , in the present study we investigate the effect of essential oils from trees on human immune function in twelve healthy male subjects , age 37–60 years , who stayed at an urban hotel for 3 nights from 7.00p.m . to 8.00a.m . Aromatic volatile substances ( phytoncides ) were produced by vaporizing Chamaecyparis obtusa ( hinoki cypress ) stem oil with a humidifier in the hotel room during the night stay . Blood sample s were taken on the last day and urine sample s were analysed every day during the stay . NK activity , the percentages of NK and T cells , and granulysin , perforin , granzyme A/B-expressing lymphocytes in blood , and the concentrations of adrenaline and noradrenaline in urine were measured . Similar control measurements were made before the stay on a normal working day . The concentrations of phytoncides in the hotel room air were measured . Phytoncide exposure significantly increased NK activity and the percentages of NK , perforin , granulysin , and granzyme A/B-expressing cells , and significantly decreased the percentage of T cells , and the concentrations of adrenaline and noradrenaline in urine . Phytoncides , such as α-pinene and β-pinene , were detected in the hotel room air . These findings indicate that phytoncide exposure and decreased stress hormone levels may partially contribute to increased NK activity |
12,089 | 30,059,147 | Whilst the women 's subjective impression of cure seemed similar for both procedures , in the short- and medium-term follow-up , there was some evidence of poorer results of laparoscopic colposuspension on objective outcomes .
The results showed trends towards fewer perioperative complications , less postoperative pain and shorter hospital stay for laparoscopic compared with open colposuspension , however , laparoscopic colposuspension was more costly .
We observed no significant differences for postoperative voiding dysfunction and perioperative complications .
Laparoscopic colposuspension had a significantly longer operation time and hospital stay .
Currently available evidence suggests that laparoscopic colposuspension may be as good as open colposuspension at two years post surgery .
However , the newer vaginal sling procedures appear to offer even greater benefits , better objective outcomes in the short term and similar subjective outcomes in the longer term .
If laparoscopic colposuspension is performed , the use of two paravaginal sutures appears to be the most effective method . | BACKGROUND Stress urinary incontinence ( SUI ) imposes significant health and economic burden on society and the women affected .
Laparoscopic colposuspension was one of the first minimal access operations for the treatment of women with SUI , with the presumed advantages of avoiding major incisions , shorter hospital stays and quicker return to normal activities .
OBJECTIVES To determine the effects of laparoscopic colposuspension for urinary incontinence in women . | Objective To compare 1-year cure rates after laparoscopic Burch colposuspension using one double-bite or two single-bite sutures on each side of the urethra . Methods Consecutive women with primary stress urinary incontinence at one university hospital were included . Pre-operative clinical and urodynamic evaluation included cystoscopy , cystouretrometry at rest and stress , and a st and ardized pad test . Immediately before surgery , the patients were r and omized to have one or two polytetrafluoroethylene ( GoreTex CV 2 ; W. L. Gore Inc. , Flagstaff , AZ ) sutures placed on each side of the urethra . During surgery , access to the space of Retzius was achieved by transperitoneal videolaparoscopic technique . Women were scheduled for postoperative interview and pad test 1 year after surgery . Results We included 161 women in the study ; 78 were r and omized to one suture ( group A ) and 83 to two sutures ( group B ) . Median time for surgery was significantly shorter for group A than for group B ( 60 compared with 77 minutes ; P < .001 ) . We examined 158 women 1 year after surgery , at which time 148 performed a pad test . Objective cure rate was significantly higher in group B than in group A ( 83 % compared with 58 % ; P = .001 ) . Conclusion Two single-bite sutures result ed in a significantly higher objective short-term cure rate than one double-bite suture on each side of the urethra Introduction and hypothesisThe aim of this study is to provide long-term outcome data , at least 10 years , following laparoscopic colposuspension . Methods The study includes a control group who underwent open colposuspension . A consecutive series of 139 women who had undergone laparoscopic colposuspension were review ed and compared to 52 women who had an open colposuspension in the same unit . Subjects were contacted by telephone , at least 10 years post-operatively , at which time a structured interview was performed which included the short-form Bristol Female Lower Urinary Tract Symptom question naire . Results There was deterioration in subjective cure rates from 71 % and 67 % at 6 months to 52 % and 36 % at 10 years for the laparoscopic and open procedures , respectively . Conclusion This study provides evidence that laparoscopic colposuspension is probably as durable as open colposuspension . However , cure rates for both procedures appear to deteriorate over time , emphasising the importance of long-term follow-up Background . Evaluation of cost‐effectiveness of new surgical techniques is important . As the data on incontinence procedures are scarce , we evaluated the cost‐effectiveness of tension‐free vaginal tape procedure and laparoscopic mesh colposuspension as a primary surgical treatment for female stress urinary incontinence . Methods . In four university teaching hospitals and two central hospitals 128 stress incontinent women were r and omized to tension‐free vaginal tape procedure ( n = 70 ) or laparoscopic mesh colposuspension ( n = 51 ) in order to investigate the clinical performance of these two procedures . Primary objective clinical outcome measures were : stress test and 48‐h pad test . Secondary subjective outcome measures were health‐related quality of life measured in terms of visual analogue scale and Urinary Incontinence Severity Score . Alongside the clinical trial , a cost‐effectiveness analysis for the main outcome measures was performed . Results . The changes in the 48‐h pad test result did not reach statistical significance ( p = 0.105 ) . When the visual analogue scale or Urinary Incontinence Severity Score are used as the outcome measure , the tension‐free vaginal tape is more cost‐effective than laparoscopic mesh colposuspension over a follow‐up period of one year ( p<0.000 ) . Conclusion . The clinical and economic data of the present study suggest that over a follow‐up period of one year the tension‐free vaginal tape procedure is more cost‐effective than laparoscopic mesh colposuspension as a primary treatment for female stress urinary incontinence Background . The aim of this study was to compare laparoscopic colposuspension with tension‐free vaginal tape ( TVT ) in terms of costs to the county Objective : We compared the success of laparoscopic Burch colposuspension with the laparotomic Burch colposuspension for the treatment of genuine stress incontinence ( GSI ) concomitant with gynecologic operations . Material s and Methods : Fifty-two women with symptoms of GSI , also requiring additional gynecologic operations , were r and omly assigned to undergo laparoscopic ( n = 26 ) or laparotomic ( n = 26 ) Burch colposuspension . For all patients complete histories were taken and physical examination , urinalysis , urine culture , multi-channel urodynamics with cystometry , uroflowmetry , and measurement of Valsalva leak-point pressure were performed . Variables analyzed included : age , surgical time , length of catheterization , number of days in hospital , and complications . Results : Both groups were similar in age , parity and menopausal status . Valsalva leak-point pressure significantly increased in the laparoscopy group after the operation . There were no statistical differences in other urodynamics in both groups . The mean operating time in the laparoscopy group was longer than in the laparotomy group . The laparoscopy group required a significantly shorter hospitalization and catheterization than the laparotomy group . The success and complication rates did not differ significantly for both groups . Conclusion : The laparoscopic approach for the treatment of GSI in patients requiring additional gynecologic procedures is associated with a shorter duration of hospital stay compared with the abdominal approach OBJECTIVE To compare the efficacy , safety , complications , and short-term outcome of laparoscopic and open colposuspension in women with genuine stress incontinence . DESIGN R and omised controlled trial . SETTING Urogynaecology unit in a public hospital , Hong Kong . SUBJECTS AND METHODS Ninety patients with urodynamically proven genuine stress incontinence . Forty-three patients were r and omly allocated to receive open colposuspension and 47 to undergo laparoscopy . All patients had re assessment within 1 year of the operation . MAIN OUTCOME MEASURES Objective and subjective measures and complication rates . RESULTS There was no significant difference in the duration of stress incontinence , mean preoperative pad test results , or proportion with pre-existing detrusor instability . Among patients in the laparoscopic group , the mean operating time was significantly longer ( 42.0 minutes versus 29.3 minutes ; P<0.0001 ) , while the mean blood loss was significantly less ( 124.7 mL versus 326.9 mL ; P=0.001 ) . Subjective and objective success rates within 1 year were similar for patients in the open and laparoscopic groups ( 86.0 % versus 80.9 % ; P=0.58 , and 86.0 % versus 85.1 % ; P=1.00 , respectively ) . There was no significant difference in the rate of complications , including de novo detrusor instability and an obstructive voiding pattern , enterocele , or dyspareunia . CONCLUSION Laparoscopic colposuspension is a feasible alternative to the open approach . The operating time is longer but the short-term cure rate is comparable with that of the open approach The technical feasibility of the laparoscopic and extraperitoneal approach to the Burch colposuspension for treatment of grade II and III ( moderate to severe ) stress incontinence was examined in a r and omised prospect i ve study . Irrespective of the endoscopic access , two suspension techniques , namely conventional suture and stapler fixation of alloplastic material s , were compared . A total of 20 patients entered this preliminary evaluation . Three complications occurred ; a bladder perforation ( during laparoscopic dissection of the space of Retzius ) , a postoperative detrusor instability and transient urinary retention . Both the endoscopic approaches and the suspension procedures employed proved feasible and safe , and presented the advantages of a " minimal access " procedure , with short hospitalisation and rapid recovery . Short-term follow-up ( 6 - 12 months ) showed subjective and objective results comparable to those of the conventional abdominal Burch colposuspension . Detailed evaluation of the subgroups is not yet feasible , as the number of patients in this preliminary evaluation was too small and follow-up too short . Final evaluation of the entire study population and long-term follow-up will be necessary before these procedures can be generally offered as a therapeutic alternative OBJECTIVE : To estimate costs for incontinence management , health-related quality of life , and willingness to pay for incontinence improvement in women electing surgery for stress urinary incontinence . METHODS : A total of 655 incontinent women enrolled in the Stress Incontinence Surgical Treatment Efficacy Trial , a r and omized surgical trial . Baseline out-of-pocket costs for incontinence management were calculated by multiplying self-report of re sources used ( supplies , laundry , dry cleaning ) by national re source costs ( $ 2006 ) . Health-related quality of life was estimated with the Health Utilities Index Mark 3 . Participants estimated willingness to pay for 100 % improvement in incontinence . Potential predictors of these outcomes were examined by using multivariable linear regression . RESULTS : Mean age was 52±10 years , and mean number of weekly incontinence episodes was 22±21 . Mean and median ( 25 % , 75 % interquartile range ) estimated personal costs for incontinence management among all women were $ 14±$24 and $ 8 ( interquartile range $ 3 , $ 18 ) per week , and 617 ( 94 % ) women reported any cost . Costs increased significantly with incontinence frequency and mixed compared with stress incontinence . The mean and median Health Utilities Index Mark 3 scores were 0.73±0.25 and 0.84 ( interquartile range 0.63 , 0.92 ) . Women were willing to pay a mean of $ 118±$132 per month for complete resolution of incontinence , and willingness to pay increased significantly with greater expected incontinence improvement , household income , and incontinent episode frequency . CONCLUSION : Urinary incontinence is associated with substantial costs . Women spent nearly $ 750 per year out of pocket for incontinence management , had a significant decrement in quality of life , and were willing to pay nearly $ 1,400 per year for cure . LEVEL OF EVIDENCE : STUDY OBJECTIVE To compare laparoscopic Burch colposuspension and tension-free vaginal tape ( TVT ) procedure in women with genuine stress incontinence . DESIGN R and omized clinical study ( Canadian Task Force classification I ) . SETTING Tertiary care university hospital . PATIENTS Forty-six consecutive women . INTERVENTION Laparoscopic Burch colposuspension ( 23 ) and TVT procedure ( 23 ) . MEASUREMENTS AND MAIN RESULTS Valsalva leak-point pressure increased after surgery in both groups , but TVT substantially decreased maximum urinary flow rate . Other urodynamic studies showed no statistical differences . The groups did not differ significantly with respect to intraoperative complications or objective and subjective cure rates . Operating time was significantly longer for laparoscopic Burch ( p = 0.001 ) , and three patients in that group required conversion to laparotomy . Length of hospital stay ( p = 0.003 ) and duration of catheterization ( p = 0.003 ) were shorter in the TVT group . CONCLUSION TVT holds promise in women with genuine stress incontinence , with several advantages over laparoscopic Burch Introduction and hypothesisBefore the introduction of the tension-free vaginal tape ( TVT ) procedure for the treatment of female stress urinary incontinence , the colposuspension operation was regarded as the “ gold st and ard ” procedure . The laparoscopic variant of the colposuspension was introduced as a less invasive operation . The aim of the present trial was to compare the new minimally invasive TVT procedure with laparoscopic mesh colposuspension ( LCM ) . Methods A multicenter r and omized clinical trial conducted in six public hospitals in Finl and including primary cases of stress incontinence . Objective treatment success criteria were a negative stress test and no retreatment for stress incontinence . Patient satisfaction was assessed by Patients Global Impression of Improvement , a visual analog scale , and the Urinary Incontinence Severity Score . Results Of 128 r and omized patients , 121 underwent the allocated operation . At the 5-year follow-up 77 % in the TVT group and 84 % in the LCM group could be assessed according to the protocol . The objective cure rate was significantly higher in the TVT group ( 94 % ) than in the LCM group ( 78 % ) . Subjective treatment satisfaction ( completely satisfied with the procedure ) was significantly higher in the TVT group ( 64 % ) than in the LCM group ( 51 % ) . Conclusions By per protocol analysis both objective and subjective cure rates were significantly higher in the TVT group than in the LCM group . If cases that were lost to follow-up were regarded as failures , the intension-to-treat analysis found no difference between the groups STUDY OBJECTIVE To compare results of laparoscopic Burch colposuspension with those of classic Burch colposuspension , and to assess complications , results , and morbidity associated with each procedure . DESIGN Prospect i ve , r and omized study ( Canadian Task Force classification I ) . SETTING Minimal access surgery unit . PATIENTS Seventy-four women with genuine stress incontinence . INTERVENTION Laparoscopic and classic Burch colposuspensions . MEASUREMENTS AND MEAN RESULTS : Mean operating times for laparoscopic and open surgery were 70.18 + /- 16.54 and 53+/- 10.05 minutes , respectively ( p < 0.001 ) . Mean blood loss was 42.75 + /- 7.2 and 240.5 + /- 35.5 ml , respectively ( p < 0.001 ) . Postoperative analgesia requirement was significantly less with laparoscopy ( p < 0.001 ) . Mean postoperative hospital stay was 36 + /- 6.3 hours for the laparoscopic group and 76+/- 10.4 hours for the open group p<0.001 ) . Average time to return to light work was 8.5 and 31.5 days , respectively . Success rates were 90.9 % at 6 months and 87.9 % at 18 months in the laparoscopic group , compared with 90 % and 85 % , respectively , in the open group . CONCLUSION Given equal efficacy of the two procedures , we prefer the laparoscopic approach since it is associated with lower morbidity , shorter hospital stay , and fewer complications . ( J Am Assoc Gynecol Laparosc 8(1):99 - 106 , 2001 OBJECTIVES Stress urinary incontinence affects between 10 percent and 50 percent of women . Surgery is commonly recommended for troublesome incontinence that does not respond to nonsurgical management . Tension-free vaginal tape ( TVT ) is a newer , minimal access surgical sling procedure , which is being increasingly adopted worldwide . The cost-effectiveness of TVT in comparison with other surgical procedures , particularly open colposuspension , is assessed . METHODS Effectiveness estimates came from a systematic review of TVT compared with other surgical procedures ( open and laparoscopic colposuspension , traditional slings , and injectables ) . Deterministic and probabilistic analyses were used to assess the likelihood of TVT being cost-effective . Sensitivity analyses assessed the impact of changing assumptions about cure rates and costs for TVT , cure rates for retreatment open colposuspension , and proportions of women who choose retreatment . RESULTS Reliable estimates of relative effectiveness were difficult to derive because the few r and omized controlled comparisons had not been optimally analyzed or fully reported . Results of the economic model suggested that TVT dominates open colposuspension ( lower cost and same quality of life years [ QALYs ] ) within 5 years after surgery . Stochastic analysis indicated that the likelihood of TVT being cost-effective was 100 percent if decision-makers are unwilling to pay for additional QALYs . TVT 's dominance depended on the assumption fact that retreatment open colposuspension has lower cure rates than a first colposuspension . CONCLUSIONS Analysis based on current short-term data indicates dominance of TVT over open colposuspension from approximately 5 years . There is a need for longer-term follow-up data from method ologically rigorous r and omized trials to provide a sounder basis for estimating the relative benefits and cost implication STUDY OBJECTIVE To determine if outpatient laparoscopic Burch procedure performed with mesh and staples is as effective as that done with the suture technique . DESIGN Prospect i ve , r and omized study . SETTING Community hospital . PATIENTS Sixty-nine women with genuine stress incontinence ( GSI ) r and omly assigned to either the suture group ( group 1 ) or the mesh-staple group ( group 2 ) . INTERVENTIONS Before surgery each patient had a complete history , physical and neurologic examinations , 24-hour urolog , urology question naire , urine culture and sensitivity , Q-Tip test , transperineal ultrasound , cough stress test , cystourethroscopy , and cystometrogram . Stress incontinence was diagnosed by positive Q-Tip , ultrasound , and cough stress tests and a negative cystometrogram for detrusor contraction . The laparoscopic Burch procedures were performed with either sutures for bladder neck elevation or with mesh and staples . Clinical and , if necessary , urodynamic studies were repeated at 6 weeks and 1 year postoperatively . MEASYRENEBTS AND MAIN RESULTS : The cure rate at 1 year was 91 % in group 1 and 94 % in group 2 . Only objective cures by urologic testing are reported . The hypermobile urethra , as tested by transperineal ultrasound , was cured by both procedures . Of the 69 women , 68 were able to void spontaneously within 24 hours . CONCLUSIONS Early results suggest that laparoscopic Burch colposuspension is effective in curing GSI . Both sutures and mesh with staples yield good outcomes OBJECTIVE To determine the method ological quality of studies evaluating surgery for stress incontinence , the effectiveness of different procedures and the frequency of complications associated with each procedure . MATERIAL S AND METHODS Eleven r and omized controlled trials , 20 non-r and omized trials/ prospect i ve cohort studies and 45 retrospective cohort studies were review ed systematic ally . RESULTS The method ological quality of the 31 prospect i ve studies was generally poor . The considerable variation in inclusion criteria , surgical management and assessment of outcome precluded any statistical meta- analysis . Evidence as to the effectiveness of surgery for stress incontinence is weak ; therefore , any conclusions are speculative . It appears that colposuspension may be more effective and the effect more long-lasting than that following anterior colporrhaphy and needle suspension . There is little information on the value of sling procedures . Comparisons of different ways of performing each procedure show no significant differences in outcome but this may reflect the method ological weaknesses of the studies . Valid and reliable data on the frequency of complications following surgery are lacking so the safety of the procedures is unclear . Repeat operations to correct stress incontinence are less successful than first procedures but this finding may be subject to confounding . CONCLUSIONS There is an urgent need for some large , rigorous , prospect i ve studies of high quality . Until such studies have been completed , recommendations as to the best clinical practice can not be based on scientific evidence . Studies need to define cases according to widely accepted criteria , including st and ard measures of the severity of stress incontinence , and surgical terminology for the procedures performed needs to be st and ardized and outcomes need to be clearly defined , valid and reliable , not confined to short-term assessment and include patients ' views along with the surgeon 's assessment STUDY OBJECTIVE To compare two techniques of transperitoneal laparoscopic urethropexy . DESIGN Prospect i ve , r and omized , open trial ( Canadian Task Force classification I ) . SETTING University-affiliated department of gynecology and obstetrics . PATIENTS Sixty women with genuine stress incontinence . INTERVENTIONS Transperitoneal laparoscopic retropubic urethropexy using nonabsorbable sutures ( group A ) and polypropylene mesh fixed with tacks or staples ( group B ) . MEASUREMENTS AND MAIN RESULTS Failure was assessed subjectively and objective ly . Subjective evaluation was performed asking patients if they had urine loss and having them describe symptomatology on a visual analog scale before surgery and at each follow-up visit . Objective evaluation was by clinical examination and /or multichannel urodynamic studies . No significant differences in intraoperative and postoperative complications were observed between groups . The subjective failure rate was not significantly different between groups 3 , 6 , and 12 months after surgery . At 3 and 6 months the objective failure rate was not significantly different ; however , at 12 months it was significantly lower in group A than in group B. CONCLUSION Transperitoneal laparoscopic retropubic urethropexy is more effective with sutures than with mesh AIMS To compare direct health care costs of treatment for stress urinary incontinence in Sweden with four different procedures : ( i ) open Burch colposuspension ( OBC ) ; ( ii ) laparoscopic colposuspension with sutures ( LCS ) ; ( iii ) laparoscopic colposuspension with mesh and staples ( LCM ) , and ( iv ) Tension-free Vaginal Tape ( TVT ) . MATERIAL AND METHODS A model was constructed representing a hospital with st and ardized surgical equipment , staff and average unit costs in 2003 Euros . The time used for anesthesia and surgery was calculated . Clinical data was collected from three different sources , a multicenter , r and omized , prospect i ve study comparing OBC with LCM with 1 year follow-up , a three-armed , prospect i ve study where women were r and omized to either OBC , LCM , or LCS with 1 year follow-up and a descriptive study reporting results of TVT with 5 year follow-up . Data collected from the studies and hospital cost data were put into the model to create the different cost elements . RESULTS The total cost per individual , showed a lower cost for TVT compared to the other alternatives . The direct costs for a TVT , euro1,366 were only 56 % of the costs for an OBC , euro2,431 ( P < 0.001 ) and 59 % of the costs for a LCS , euro2,310 ( P < 0.001 ) . CONCLUSIONS When using a model and comparing health care costs for surgical treatment of female stress urinary incontinence in Sweden , the TVT procedure generated a lower direct cost than both open and laparoscopic colposuspension BACKGROUND To compare two different transperitoneal laparoscopic urethropexy procedures . METHODS In this prospect i ve r and omized open trial , 60 women affected by genuine stress incontinence were enrolled and r and omized in two groups of surgical technique . Group A was treated with transperitoneal laparoscopic retropubic urethropexy using non absorbable sutures , and group B with prolene meshes fixed with tackers or staplers . The failure rate was defined subjectively and objective ly . The subjective evaluation was performed asking the patients if they had urine loss and expressing the symptomatology using a visual analog scale before surgery and after each follow-up visit . The objective evaluation was performed with clinical evaluation and /or with the use of multichannel urodynamic studies . RESULTS No significant differences in intra- operative and postoperative complications between the two groups were observed . The subjective failure rate was not significantly different between the two groups at 3 , 6 , and 12 months from surgery . At 3 and 6 months follow-up , the objective failure rate was not significantly different between the two groups . Moreover , at 12 months from surgical procedure the objective failure rate was significantly lower in group A than in group B. CONCLUSIONS Transperitoneal laparoscopic retropubic urethropexy performed using sutures is more effective than the mesh technique The open Burch colposuspension , first described in 1961 had been widely employed for the surgical treatment of women with stress urinary incontinence ( SUI ) caused by urethral hypermobility . We evaluated the long-term efficacy of laparoscopic Burch colposuspension ( LBC ) for SUI in women . A r and omized prospect i ve trial was conducted from September 2010 to January 2013 . The extraperitoneal laparoscopic Burch colposuspension was performed by an operator on 96 women , mean age was 54,3 ± 3,7 years all of whom suffered from SUI or mixed urinary incontinence . Patients completed a self-administered the Short Form-36 ( SF-36 ) , the Physical Component Summary ( PCS ) and Mental Component Summary ( MCS ) , the Short Urinary Distress Inventory ( SUDI ) and Short Incontinence Impact Question naire ( SIIQ ) . at both baseline and follow up(6 weeks , 6 months , 18 months postoperatively ) . The Genito-Urinary Treatment Satisfaction Scale ( GUTSS ) was used to assess satisfaction with surgery . After follow up was recorded an improvement of question naries scores . The general health score is improved after surgery ( 2,60 ± 1.02 versus 2,76 ± 1.06 ) with p = 0.09 . The PCS baseline score is 46.29 ± 10.95 versus 49.54 ± 10.41 after treatment with p = 0.01 , so there was a significant baseline to follow up improvement . The MCS improved also , infact baseline score is 42.19 ± 12.57 versus 42.70 ± 13.03 with p = 0.87 . The SUDI baseline score is 50.22 ± 20.73 versus 23.92 ± 17.90 , while SIIQ score is 49.98 ± 23.90 versus 31.40 ± 23.83 with p < 0.01 . In both question naires there is an improvement . Satisfaction with treatment outcomes from the GUTSS at 6-month follow up is 29.5 ± 6.3 with p = 0.46 . The LBC has significant advantages , without any apparent compromise in short-term and long term outcomes OBJECTIVE : To compare objective and subjective outcomes after the tension-free vaginal tape procedure ( TVT ) with laparoscopic mesh colposuspension as a primary treatment for female stress urinary incontinence . Objective outcome measures were stress test and 48-hour pad test . METHODS : In 6 departments of gynecology in Finl and , including 4 university teaching hospitals and 2 central hospitals , 128 women with urodynamic stress incontinence were r and omly allocated to 2 treatment groups . Seventy were treated with TVT and 51 by means of laparoscopic mesh colposuspension . There were 7 dropouts . Inclusion criteria were history of stress incontinence , positive stress test , and urodynamic conformation of stress incontinence . Exclusion criteria were age older than 70 years , previous incontinence surgery , more than 3 episodes of urinary tract infection within the last 2 years , coincident other gynecological surgery , body mass index more than 32 kg/m2 , urethral closure pressure less than 20 cm H2O , and residual volume more than 100 mL in preoperative urodynamic evaluation . Assessment took place before treatment and at 12 months postoperatively with the cough stress test , Urge Score , 48-hour pad test , King 's College Health Question naire , Visual Analog Scale , and Urinary Incontinence Severity Score . RESULTS : When negative stress test was used as criteria for cure , 85.7 % of women in the TVT group and 56.9 % in the laparoscopic mesh colposuspension group were objective ly cured . Subject satisfaction was significantly better after the TVT procedure than after laparoscopic mesh colposuspension . CONCLUSION : Treatment with TVT results in higher objective and subjective cure rates at 1 year than treatment by means of laparoscopic mesh colposuspension . LEVEL OF EVIDENCE : AIMS The aim of the study was to further vali date three patient-based outcome measures ( PBOM ) used to assess the outcome of surgery for stress urinary incontinence and to compare their psychometric properties with a view to determining the most appropriate measure for clinical use . METHODS The work was embedded within a r and omized controlled trial of laparoscopic and open colposuspension . The trial recruited 291 women from six centers . The three instruments compared were Bristol Female Lower Urinary Tract Symptom Question naire ( BFLUTS ) , Kings Health Question naire ( KHQ ) , and the Symptom Severity Index and Symptom Impact Index ( SSI/SII ) . The International Consultation on Incontinence ( ICI ) ABC grading system of psychometric propertie 's reliability , validity , and responsiveness was used to evaluate the instruments . RESULTS From the analysis of the psychometric properties of the three instruments , the SSI/SII appeared to have the best psychometric profile ; Grade A , BFLUTS was of grade A , and KHQ was of grade B. SSI/SII had a good degree of internal consistency ( Cronbach 's alpha 0.74 - 0.78 ) . BFLUTS and KHQ both had domains in which the internal consistency was < 0.7 . The SSI domain of the SSI/SII was the only domain to correlate to the 1-hr pad test . All domains of the SSI/SII were able to distinguish those cured from not cured and it was most responsive to change . Unlike the KHQ , the SSI/SII had no significant ceiling or floor effects . CONCLUSIONS This study has demonstrated that when instruments are used in different population s their psychometric properties may change . All three instruments analyzed had limitations when used as an outcome measure for surgery for stress urinary incontinence Abstract : For 285 subjects referred to a menopause clinic data were prospect ively collected on the time elapsed since the onset of menopause ( menopausal age ) , sexual activity , dyspareunia , smoking , chronic cough and constipation . Prolapse and atrophy were sought on examination . FSH assay confirmed menopausal status . We found an anterior wall prolapse in 51 % of the subjects , of which 6 % were protruding beyond the introitus . Posterior wall prolapse was present in 27 % and apical prolapse in 20 % ; none was protruding beyond the introitus . No trend was noted between prolapse and menopausal age . Atrophy was evident in 34 % of the women , and this was related to menopausal age ( P<0.001 ) . Forty per cent of the sexually active women admitted to dyspareunia , of which 2/3 were superficial . This correlated with advancing menopausal age ( P<0.02 ) . In conclusion , genital prolapse was frequent in the population of postmenopausal women , predominantly cystocele , but the prevalence did not correlate with menopausal age OBJECTIVE ( S ) To compare the long-term effectiveness of two different laparoscopic colposuspension procedures . STUDY DESIGN Sixty women affected by genuine stress incontinence ( GSI ) were enrolled in a prospect i ve r and omized controlled trial ( RCT ) and treated by transperitoneal laparoscopic colposuspension using nonabsorbable sutures ( group A ) or prolene mesh fixed with tackers or staplers ( group B ) . In each group the subjective and objective failure rates were evaluated at 12 , 24 , and 36 months after surgery . For the subjective evaluation patients were asked whether they had experienced urine leakage and any urine loss they reported was recorded on a visual analogue scale ( VAS ) . The objective evaluation was performed by means of a clinical examination and multichannel urodynamic studies . The data were analyzed by the intention-to-treat method . RESULTS The subjective failure rate was significantly ( P < 0.05 ) lower in group A than in group B at 12 months ( 3.3 % versus 13.3 % , respectively ) , 24 months ( 20.0 % versus 36.7 % , respectively ) , and 36 months ( 33.3 % versus 53.3 % , respectively ) after surgery . The objective failure rate also differed significantly ( P < 0.05 ) between the two groups after 12 ( 10.7 % versus 25.0 % for group A and group B , respectively ) , 24 ( 29.6 % versus 57.7 % , respectively ) , and 36 ( 42.3 % versus 61.5 % , respectively ) months of follow-up . CONCLUSION ( S ) Laparoscopic colposuspension performed with sutures is more effective than laparoscopic colposuspension accomplished with the use of prolene meshes in the long term , and the use of prolene meshes should be avoided in treatment of GSI OBJECTIVE To compare the effectiveness of two transperitoneal laparoscopic Burch procedures . METHODS The sample size required was 30 subjects per group to detect a statistically significant estimated difference of 15 % between two surgical procedures with an & agr ; = 0.05 and a power of 0.7 . Sixty women affected by genuine stress incontinence ( GSI ) were enrolled and r and omly assigned to two groups of 30 women each . All women were treated with the transperitoneal laparoscopic Burch procedure using nonabsorbable sutures ( group A ) or Prolene mesh ( Ethicon , Somerville , NJ ) fixed with tacks or staples ( group B ) . The failure rate was defined subjectively and objective ly . The subjective evaluation was performed by asking the women to rate their urine loss on a visual analog scale . The objective evaluation was a clinical evaluation using multichannel urodynamic studies . RESULTS The subjective failure rate was not significantly different between the two groups at 3 months ( 0 % for both groups ) , 6 months ( 3.7 % versus 3.8 % for groups A and B , respectively ) , and 12 months ( 7.4 % versus 15.4 % for groups A and B , respectively ) after surgery . At 3 months ( 3.7 % versus 3.8 % for groups A and B , respectively ) and 6 months ( 7.4 % versus 15.4 % for groups A and B , respectively ) follow‐up , the objective failure rate was not significantly different between the two groups . However , at 12 months after the surgical procedure , the objective failure rate was significantly lower in group A than in group B ( 11.1 % versus 26.9 % , respectively ; P < .05 ) . CONCLUSION Transperitoneal laparoscopic Burch colposuspension performed using sutures was more effective than the mesh technique Objective To assess specific parturition and reproductive variables as potential risk factors for urinary incontinence in later life . Methods a mail survey was conducted with a r and om sample of 1922 women members of a large health maintenance organization . Multivariate analysis was used to estimate the independent association between parturition factors , husterectomy , hormone use , and incontinence . Results Completed surveys were returned by 939 women ( 49 % ) , 682 of whom reported at least one episode of incontinence in the past 12 months or ever having been treated for incontinence . On univariate analysis , women with incontinence were more likely to be white and heavier and to have had a hysterectomy before age 45 , at least one live birth , a post date ( at least 42 weeks ' gestation ) birth , alabor lasting longer than 24 hours , and exposure to oxytocin . The risk of incontinence increased significantly with the number of exposures to oxytocin . In a multivariate model including age , there was a significant association between incontinence and white race ( odds ratio [ OR ] 1.8 , 95 % confidence interval [ CI ] 1.2 , 2.8 ) , body mass ( OR for fourth quartile 3.0 , 95 % CI 1.8 , 5.0 ) , estrogen replacement ( OR 1.9 , 95 % CI 1.3 , 2.8 ) and oxytocin ( OR 1.9 , 95 % CI 1.0 , 3.6 ) . Parity was also associated with incontinence ( P < .05 ) . Conclusion This study supports previous findings of a positive association between urinary incontinence and body mass , parity , and use of estrogen . In addition , we found a significant independent association between exposure to oxytocin during labor and incontinence in later life |
12,090 | 30,128,683 | There was no difference in the side effects between patients with AT and the control group .
AT in OA patients is not useless because there is evidence that a subgroup of patients with non-traumatic flap tears of the medial meniscus or patients with crystal arthropathy benefit from arthroscopy . | Purpose The purpose of this study was to perform a systematic review of prospect i ve r and omized controlled trials comparing arthroscopic treatment for knee osteoarthritis ( OA ) with either other therapeutic interventions or sham treatment . | In this prospect i ve r and omised study two treatments after non-traumatic medial meniscal tear diagnosed with radiological examination and magnetic resonance imaging were compared ; arthroscopic partial meniscectomy followed by supervised exercise or supervised exercise alone . The aim was to evaluate knee function and physical activity . Ninety patients ( mean age 56 years ) were evaluated using the Knee Injury and Osteoarthritis Outcome Score , the Lysholm Knee Scoring Scale , the Tegner Activity Scale and a Visual Analogue Scale for knee pain prior to the intervention , after 8 weeks of exercise and after 6 months . According to the outcome scores arthroscopic partial medial meniscectomy combined with exercise did not lead to greater improvement than exercise alone . After the intervention both groups reported decreased knee pain , improved knee function and a high satisfaction ( P < 0.0001 ) . Forty-one per cent of the patients returned to their pre-injury activity level after 6 months . In conclusion , when evaluated with outcome scores , arthroscopic partial medial meniscectomy followed by supervised exercise was not superior to supervised exercise alone in terms of reduced knee pain , improved knee function and improved quality of life Background — Arthroscopic meniscal surgery is the most common orthopedic procedure , and the incidence has increased in Denmark over the last 10 years . Concomitantly , several r and omized controlled trials have shown no benefit of arthroscopic procedures including arthroscopic partial meniscectomy in middle-aged and older individuals suffering from knee pain with or without knee osteoarthritis . We examined the annual incidence of meniscal procedures together with age , sex , and diagnosis for patients who underwent meniscal procedures in the period 2000–2011 in Denmark . Methods — Data on age , sex , diagnosis , and surgical procedures were extracted from the Danish National Patient Register for the years 2000–2011 , for all records containing meniscal surgery as a primary or secondary procedure . Results — The overall annual incidence of meniscal procedures per 100,000 persons in Denmark doubled from 164 in 2000 to 312 in 2011 ( i.e. 8,750 procedures to 17,368 procedures ) . A 2-fold increase was found for patients aged between 35 and 55 , and a 3-fold increase was found for those older than 55 . Middle-aged and older patients accounted for 75 % of all 151,228 meniscal procedures carried out between 2000 and 2011 . Interpretation — The incidence of meniscal procedures performed in Denmark doubled from 2000 to 2011 , with the largest increase in middle-aged and older patients . This increase contrasts with the mounting evidence showing no added benefit of arthroscopic partial meniscectomy over non-surgical treatments . Our observations illustrate the long delay in the dissemination , acceptance , and implementation of research evidence into the practice of arthroscopic surgery PURPOSE To determine whether preoperative magnetic resonance ( MR ) imaging could help identify factors associated with poor clinical outcome after arthroscopic partial meniscectomy ( APM ) in middle-aged and elderly patients with meniscal tears . MATERIAL S AND METHODS The prospect i ve , institutional review board-approved , HIPAA-compliant study was performed with informed consent in 53 men and 47 women ( average ages , 54.5 and 56.6 years , respectively ) . Patients underwent knee MR imaging before APM ; clinical symptoms were evaluated preoperatively and 1 year postoperatively with International Knee Documentation Committee ( IKDC ) question naire . Overall severity of knee joint degeneration and severity of each feature of joint degeneration were assessed with Boston Leads Osteoarthritis Knee ( BLOK ) scoring system . Tear length was measured , and type of meniscal tear was classified . Spearman correlation coefficients and relative risks showed the relationship between clinical outcome after APM ( difference between preoperative and postoperative IKDC scores ) and severity of joint degeneration . RESULTS Seventy-four patients with isolated medial APM had a significant ( P < .05 ) inverse correlation between clinical outcome and severity of cartilage loss and bone marrow edema in the medial femoral condyle and medial tibial plateau . Fifteen patients with isolated lateral APM had a significant ( P < .05 ) inverse correlation between clinical outcome and severity of cartilage loss in the lateral femoral condyle and lateral tibial plateau and bone marrow edema in the lateral femoral condyle . One hundred patients with APM had a significant ( P < .05 ) inverse correlation between clinical outcome and severity of meniscal extrusion , total BLOK score , and meniscal tear length . A significantly ( P < .05 ) increased relative risk that a patient would not definitely improve after APM was observed if a meniscal root tear was present . CONCLUSION Poorer clinical outcome after APM was associated with greater severity of cartilage loss and bone marrow edema in the same compartment as the meniscal tear , greater severity of meniscal extrusion , greater overall severity of joint degeneration , a meniscal root tear , and a longer meniscal tear at preoperative MR imaging Introduction Arthroscopic partial meniscectomy ( APM ) to treat degenerative meniscus injury is the most common orthopaedic procedure . However , valid evidence of the efficacy of APM is lacking . Controlling for the placebo effect of any medical intervention is important , but seems particularly pertinent for the assessment of APM , as the symptoms commonly attributed to a degenerative meniscal injury ( medial joint line symptoms and perceived disability ) are subjective and display considerable fluctuation , and accordingly difficult to gauge objective ly . Methods and analysis A multicentre , parallel r and omised , placebo surgery controlled trial is being carried out to assess the efficacy of APM for patients from 35 to 65 years of age with a degenerative meniscus injury . Patients with degenerative medial meniscus tear and medial joint line symptoms , without clinical or radiographic osteoarthritis of the index knee , were enrolled and then r and omly assigned ( 1 : 1 ) to either APM or diagnostic arthroscopy ( placebo surgery ) . Patients are followed up for 12 months . According to the prior power calculation , 140 patients were r and omised . The two r and omised patient groups will be compared at 12 months with intention-to-treat analysis . To safeguard against bias , patients , healthcare providers , data collectors , data analysts , outcome adjudicators and the research ers interpreting the findings will be blind to the patients ’ interventions ( APM/placebo ) . Primary outcomes are Lysholm knee score ( a generic knee instrument ) , knee pain ( using a numerical rating scale ) , and WOMET score ( a disease-specific , health-related quality of life index ) . The secondary outcome is 15D ( a generic quality of life instrument ) . Further , in one of the five centres recruiting patients for the r and omised controlled trial ( RCT ) , all patients scheduled for knee arthroscopy due to a degenerative meniscus injury are prospect ively followed up using the same protocol as in the RCT to provide an external validation cohort . In this article , we present and discuss our study design , focusing particularly on the internal and external validity of our trial and the ethics of carrying out a placebo surgery controlled trial . Ethics and dissemination The protocol has been approved by the institutional review board of the Pirkanmaa Hospital District and the trial has been duly registered at Clinical Trials.gov . The findings of this study will be disseminated widely through peer- review ed publications and conference presentations . Trial registration Clinical Trials.gov , number NCT00549172 OBJECTIVE To determine if visually-guided arthroscopic irrigation is an effective therapeutic intervention in patients with early knee osteoarthritis . DESIGN Ninety patients with knee osteoarthritis were r and omized in a double-blind fashion to receive either arthroscopic irrigation with 3000 ml of saline ( treatment group ) or the minimal amount of irrigation ( 250 ml ) required to perform arthroscopy ( placebo group ) . The primary outcome variable was aggregate WOMAC score . RESULTS The study did not demonstrate an effect of irrigation on arthritis severity as measured by aggregate WOMAC scores , the primary outcome variable ; the mean change in aggregate WOMAC score at 12 months was 15.5 ( 95 % CI 7.7 , 23.4 ) for the full irrigation group compared to 8.9 ( 95 % CI 4.9 , 13.0 ) for the minimal irrigation group ( P=0.10 ) . Full irrigation did have a statistically significant effect on patients ' self-reported pain as measured by the WOMAC pain subscale and by a visual analog scale ( VAS ) ( the secondary outcome variables ) . Mean change in WOMAC pain scores decreased by 4.2 ( 95 % CI -0.9 , 9.4 ) for the full irrigation group compared with a mean decrease of 2.3 ( 95 % CI -0.1 , 4.7 ) in the minimal irrigation group ( P=0.04 ) . Mean VAS pain scores decreased by 1.47 ( 95 % CI -1.2 , 4.1 ) in the full irrigation group compared to a mean decrease of 0.12 ( 95 % CI 0.0 , 0.3 ) in the minimal irrigation group ( P=0.02 ) . A hypothesis-generating post-hoc analysis of the effect of positively birefrigent intraarticular crystals showed that patients with and without intraarticular crystals had statistically significant improvements in pain assessment s and aggregate WOMAC scores at 12 months ; patients with crystals had statistically greater improvements in pain . CONCLUSIONS Visually-guided arthroscopic irrigation may be a useful therapeutic option for relief of pain in a subset of patients with knee OA , particularly in those who have occult intraarticular crystals Background : It is still debated whether a degenerative horizontal tear of the medial meniscus should be treated with surgery . Hypothesis : The clinical outcomes of arthroscopic meniscectomy will be better than those of nonoperative treatment for a degenerative horizontal tear of the medial meniscus . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 102 patients with knee pain and a degenerative horizontal tear of the posterior horn of the medial meniscus on magnetic resonance imaging were included in this study between January 2007 and July 2009 . The study included 81 female and 21 male patients with an average age of 53.8 years ( range , 43 - 62 years ) . Fifty patients underwent arthroscopic meniscectomy ( meniscectomy group ) , and 52 patients underwent nonoperative treatment with strengthening exercises ( nonoperative group ) . Functional outcomes were compared using a visual analog scale ( VAS ) for pain , Lysholm knee score , Tegner activity scale , and patient subjective knee pain and satisfaction . Radiological evaluations were performed using the Kellgren-Lawrence classification to evaluate osteoarthritic changes . Results : In terms of clinical outcomes , meniscectomy did not provide better functional improvement than nonoperative treatment . At the final follow-up , the average VAS scores were 1.8 ( range , 1 - 5 ) in the meniscectomy group and 1.7 ( range , 1 - 4 ) in the nonoperative group ( P = .675 ) . The average Lysholm knee scores at 2-year follow-up were 83.2 ( range , 52 - 100 ) and 84.3 ( range , 58 - 100 ) in the meniscectomy and nonoperative groups , respectively ( P = .237 ) . In addition , the average Tegner activity scale and subjective satisfaction scores were not significantly different between the 2 groups . Although most patients initially had intense knee pain with mechanical symptoms , both groups reported a relief in knee pain , improved knee function , and a high level of satisfaction with treatment ( P < .05 for all values ) . Two patients in the meniscectomy group and 3 in the nonoperative group with Kellgren-Lawrence grade 1 progressed to grade 2 at the 2-year follow-up . Conclusion : There were no significant differences between arthroscopic meniscectomy and nonoperative management with strengthening exercises in terms of relief in knee pain , improved knee function , or increased satisfaction in patients after 2 years of follow-up OBJECTIVES Patients with knee osteoarthritis ( OA ) often suffer pain that is not fully controlled by analgesics and often require intra-articular therapies . The aim of this study was to compare the benefits of intra-articular corticosteroid injections ( CSIs ) and tidal irrigation ( TI ) in patients with OA of the knee . METHODS We performed a dual-centre , single blind , r and omised , parallel group trial comparing TI and CSI . Patients with knee OA were r and omised to either irrigation using a 3.2 mm arthroscope under local anaesthesia or an intra-articular injection of 40 mg triamcinolone acetonide and 1 % lidocaine . Patients were followed for 6 months . The primary outcome measure was the Western Ontario and McMaster Universities OA Index total pain score ( visual analogue scale , VAS ) . RESULTS One hundred and fifty patients were recruited of whom 71 received TI and 79 CSI . In both treatment groups , over 80 % of patients reported improvement at 2 and 4 weeks . After this time , the benefit of CSI decreased whereas that of TI was maintained : at 26 weeks the pain relief afforded by TI was significantly greater than that of CSI . At 26 weeks 29 % of the CSI group reported improvement vs 64 % of the TI group ( P<0.001 ) . Patients with a knee effusion responded better to both treatments , however , this was most apparent for CSI . Patients with less severe radiographic OA also obtained the greatest improvement from both treatments . CONCLUSION Both procedures lead to significant short-term pain relief of at least 4 weeks , however , TI displayed a significantly greater duration of benefit . Patients with effusions and milder radiographic change obtained the best response to treatment BACKGROUND Arthroscopic partial meniscectomy is one of the most common orthopedic procedures , yet rigorous evidence of its efficacy is lacking . METHODS We conducted a multicenter , r and omized , double-blind , sham-controlled trial in 146 patients 35 to 65 years of age who had knee symptoms consistent with a degenerative medial meniscus tear and no knee osteoarthritis . Patients were r and omly assigned to arthroscopic partial meniscectomy or sham surgery . The primary outcomes were changes in the Lysholm and Western Ontario Meniscal Evaluation Tool ( WOMET ) scores ( each ranging from 0 to 100 , with lower scores indicating more severe symptoms ) and in knee pain after exercise ( rated on a scale from 0 to 10 , with 0 denoting no pain ) at 12 months after the procedure . RESULTS In the intention-to-treat analysis , there were no significant between-group differences in the change from baseline to 12 months in any primary outcome . The mean changes ( improvements ) in the primary outcome measures were as follows : Lysholm score , 21.7 points in the partial-meniscectomy group as compared with 23.3 points in the sham-surgery group ( between-group difference , -1.6 points ; 95 % confidence interval [ CI ] , -7.2 to 4.0 ) ; WOMET score , 24.6 and 27.1 points , respectively ( between-group difference , -2.5 points ; 95 % CI , -9.2 to 4.1 ) ; and score for knee pain after exercise , 3.1 and 3.3 points , respectively ( between-group difference , -0.1 ; 95 % CI , -0.9 to 0.7 ) . There were no significant differences between groups in the number of patients who required subsequent knee surgery ( two in the partial-meniscectomy group and five in the sham-surgery group ) or serious adverse events ( one and zero , respectively ) . CONCLUSIONS In this trial involving patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear , the outcomes after arthroscopic partial meniscectomy were no better than those after a sham surgical procedure . ( Funded by the Sigrid Juselius Foundation and others ; Clinical Trials.gov number , NCT00549172 . ) Purpose A degenerative meniscus lesion is a slowly developing process typically involving a horizontal cleavage in a middle-aged or older person . When the knee is symptomatic , arthroscopic partial meniscectomy has been practised for a long time with many case series reporting improved patient outcomes . Since 2002 , several r and omised clinical trials demonstrated no additional benefit of arthroscopic partial meniscectomy compared to non-operative treatment , sham surgery or sham arthroscopic partial meniscectomy . These results introduced controversy in the medical community and made clinical decision-making challenging in the daily clinical practice . To facilitate the clinical decision-making process , a consensus was developed . This initiative was endorsed by ESSKA . Methods A degenerative meniscus lesion was defined as a lesion occurring without any history of significant acute trauma in a patient older than 35 years . Congenital lesions , traumatic meniscus tears and degenerative lesions occurring in young patients , especially in athletes , were excluded . The project followed the so-called formal consensus process , involving a steering group , a rating group and a peer- review group . A total of 84 surgeons and scientists from 22 European countries were included in the process . Twenty questions , their associated answers and an algorithm based on extensive literature review and clinical expertise , were proposed . Each question and answer set was grade d according to the scientific level of the corresponding literature . Results The main finding was that arthroscopic partial meniscectomy should not be proposed as a first line of treatment for degenerative meniscus lesions . Arthroscopic partial meniscectomy should only be considered after a proper st and ardised clinical and radiological evaluation and when the response to non-operative management has not been satisfactory . Magnetic resonance imaging of the knee is typically not indicated in the first-line work-up , but knee radiography should be used as an imaging tool to support a diagnosis of osteoarthritis or to detect certain rare pathologies , such as tumours or fractures of the knee . Discussion The present work offers a clear framework for the management of degenerative meniscus lesions , with the aim to balance information extracted from the scientific evidence and clinical expertise . Because of biases and weaknesses of the current literature and lack of definition of important criteria such as mechanical symptoms , it can not be considered as an exact treatment algorithm . It summarises the results of the “ ESSKA Meniscus Consensus Project ” ( http://www.esska.org/education/projects ) and is the first official European consensus on this topic . The consensus may be up date d and refined as more high- quality evidence emerges . Level of evidence Purpose The aim of this prospect i ve r and omized intervention study was to evaluate the outcome at a 2 and 5 year follow-up whether combined arthroscopic surgery followed by exercise therapy was superior to the same exercise therapy alone when treating non-traumatic , degenerative medial meniscal tears . Methods Ninety-six middle-aged patients with MRI-verified degenerative medial meniscus tear and radiographic osteoarthritis grade ≤1 ( Ahlbäck ) participated in the study . Radiographic examination was done before r and omization and after 5 years . The patients were r and omly assigned to either arthroscopic treatment followed by exercise therapy for 2 months or to the same exercise therapy alone . At the start of the study and at the follow-ups at 24 and 60 months the patients answered three question naires KOOS , Lysholm Knee Scoring Scale and Tegner Activity Scale and made pain ratings on the Visual Analogue Scale ( VAS ) . Results Both groups showed highly significant clinical improvements from baseline to the follow-ups at 24 and 60 months on all subscales of KOOS , Lysholm Knee Scoring Scale and VAS ( p < 0.0001 ) . No group differences were found at any of the testing occasions . One third of the patients that were treated with exercise therapy alone did not feel better after the treatment but were improved after arthroscopic surgery . According to radiographic findings two patients from each group had a slight progression of their osteoarthritis after 5 years . Conclusion The findings indicate that arthroscopic surgery followed by exercise therapy was not superior to the same exercise therapy alone for this type of patients . Consequently , exercise therapy can be recommended as initial treatment . However , one third of the patients from the exercise group still had disabling knee symptoms after exercise therapy but improved to the same level as the rest of the patients after arthroscopic surgery with partial meniscectomy . Level of evidence This paper presents the rationale and design features of the MeTeOR Trial ( Meniscal Tear in Osteoarthritis Research ; Clinical Trials.gov NCT00597012 ) . MeTeOR is an NIH-funded seven-center prospect i ve r and omized controlled trial ( RCT ) design ed to establish the efficacy of arthroscopic partial meniscectomy combined with a st and ardized physical therapy program as compared with a st and ardized physical therapy program alone in patients with a symptomatic meniscal tear in the setting of mild to moderate knee osteoarthritic change ( OA ) . The design and execution of a trial that compares surgery with a nonoperative treatment strategy presents distinctive challenges . The goal of this paper is to provide the clinical rationale for MeTeOR and to highlight salient design features , with particular attention to those that present clinical and method ologic challenges Thirty-five patients with limited extent of degenerative osteoarthritis of the femorotibial joint treated by arthroscope-guided surgery were compared after 1 - 3 years with 38 patients with a similar condition treated conservatively . In selecting a patient for arthroscope-guided surgery , the most important considerations were a normal mechanical axis , a limited extent of the degenerative process , and a femorotibial pain of sudden onset or that had been present for < 6 months . Clinical evaluation was undertaken using a modification of the Hospital for Special Surgery Knee Rating Score . The surgical procedure included partial meniscectomy , limited debridement of loose articular cartilage and removal of loose bodies . In the operated group , 26 patients ( 75 % ) showed improvement , five ( 14 % ) remained unchanged , and four ( 11 % ) were worse than before surgery . The average age of patients was 57 years . In the nonoperated group , six patients ( 16 % ) were improved , 12 ( 31 % ) unchanged , and 20 ( 53 % ) worse than before treatment . The average age of patients was 56 years . Arthroscope-guided surgery for limited degenerative osteoarthritis of the femorotibial joint with normal limb alignment or for degenerative meniscal tears has proven to be a useful technique Thirty-eight patients with symptomatic knee osteoarthritis without mechanical symptoms were r and omised after informed consent to receive either a course of intra-articular Hyalgan injections or an arthroscopic washout . The patients were prospect ively assessed pre-intervention , 6 weeks , 3 months , 6 months and 1 year using a 10 cm visual analogue pain score , the Knee Society function score and the Lequesne index . There was no significant difference between the two groups at 6 weeks , 3 months , 6 months or 1 year . The use of intra-articular Hyalgan injections in patients with knee osteoarthritis without mechanical symptoms gives results comparable with arthroscopic washout . Hyalgan is an alternative to arthroscopy in this patient group . Further study is needed to confirm these findings and improve patient selection OBJECTIVE There is no evidence that a knee arthroscopy is more beneficial to middle-aged patients with meniscal symptoms compared to other treatments . This r and omised controlled trial aim ed to determine whether an arthroscopic intervention combined with a structured exercise programme would provide more benefit than a structured exercise programme alone for middle-aged patients with meniscal symptoms that have undergone physiotherapy . METHOD 150 out of 179 eligible patients , aged 45 to 64 ( mean:54 ± 5 ) , symptom duration more than 3 months and st and ing X-ray with Ahlbäck grade 0 , were r and omised to : ( 1 ) a physiotherapy appointment within 2 weeks of inclusion that included instructions for a 3-month exercise programme ( non-surgery group ) ; or ( 2 ) the same as ( 1 ) plus , within 4 weeks of inclusion , knee arthroscopy for resection of any significant meniscal injuries ( surgery group ) . The primary outcome was change in pain at 12 months , assessed with the Knee Injury and Osteoarthritis Outcome Score ( KOOSPAIN ) . RESULTS In the Intention-To-Treat analysis , pain at 12 months was significantly lower in the surgery than in the non-surgery group . The change in KOOSPAIN was significantly larger in the surgery than in the non-surgery group ( between-group difference was 10.6 points of change ; 95 % CI : 3.4 to 17.7 , P = 0.004 ) . The As-Treated analysis results were consistent with the Intention-To-Treat analysis results . CONCLUSION Middle-aged patients with meniscal symptoms may benefit from arthroscopic surgery in addition to a structured exercise programme . Patients ' age or symptom history ( i.e. , mechanical symptoms or acute onset of symptoms ) did n't affect the outcome . TRIAL REGISTRATION NCT01288768 OBJECTIVE To compare arthroscopic surgery and closed-needle joint lavage for patients with non-end-stage osteoarthritis ( OA ) of the knee under controlled , experimental conditions . METHODS Thirty-two subjects who met specific clinical , radiologic , medical , and rehabilitation criteria were r and omized to receive arthroscopic surgery ( n = 18 ) or joint lavage ( n = 14 ) . Outcome measures evaluated at baseline and at 3 and 12 months of followup included 3 st and ard clinical parameters , self-reported pain and functional status ( by the Arthritis Impact Measurement Scales ) , 50-foot walk time , 2 global scales , and direct and indirect medical costs . RESULTS At 3 months of followup , there were no significant between-group differences in pain , self-reported and observed functional status , and patient and " blinded " physician global assessment s. The arthroscopic procedure cost $ 3,840 more than did closed-needle joint lavage . After 1 year , there were no between-group differences in medication costs , utilization of medical services , or indirect costs related to employment or use of household help . After 1 year , 44 % of subjects who underwent arthroscopy reported improvement and 58 % of subjects who underwent joint lavage improved . Patients with tears of the anterior two-thirds of the medial meniscus or any lateral meniscus tear had a higher probability of improvement ( by " blinded " physician assessment ) after arthroscopic surgery ( 0.63 ) than did patients with other intraarticular pathology ( 0.20 ) . CONCLUSION The search for and removal of soft tissue abnormalities via arthroscopic surgery does not appear justified for all patients with non-end-stage OA of the knee who fail to respond to conservative therapy , but it may be beneficial for certain subgroups BACKGROUND Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis , but it is unclear how the procedure achieves this result . We conducted a r and omized , placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee . METHODS A total of 180 patients with osteoarthritis of the knee were r and omly assigned to receive arthroscopic débridement , arthroscopic lavage , or placebo surgery . Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope . Patients and assessors of outcome were blinded to the treatment-group assignment . Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores -- three on scales for pain and two on scales for function-- and one objective test of walking and stair climbing . A total of 165 patients completed the trial . RESULTS At no point did either of the intervention groups report less pain or better function than the placebo group . For example , mean ( + /-SD ) scores on the Knee-Specific Pain Scale ( range , 0 to 100 , with higher scores indicating more severe pain ) were similar in the placebo , lavage , and débridement groups : 48.9+/-21.9 , 54.8+/-19.8 , and 51.7+/-22.4 , respectively , at one year ( P=0.14 for the comparison between placebo and lavage ; P=0.51 for the comparison between placebo and débridement ) and 51.6+/-23.7 , 53.7+/-23.7 , and 51.4+/-23.2 , respectively , at two years ( P=0.64 and P=0.96 , respectively ) . Furthermore , the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinical ly meaningful difference . CONCLUSIONS In this controlled trial involving patients with osteoarthritis of the knee , the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure In a prospect i ve r and omised trial 76 knees with isolated degenerative changes in the medial femoral condyle of grade s 3 or 4 were treated by either arthroscopic debridement ( 40 ) or washout ( 36 ) . All knees were followed up for at least one year and 58 for five years . The mean follow-up time was 4.5 years in the debridement group and 4.3 years in the washout group . At one year 32 of the debridement group and five of the washout group were painfree and at five years 19 of a total of 32 survivors in the debridement group and three of the 26 in the washout group were also free from pain . The mean improvement in a modified Lysholm score was 28 for the debridement group at one year and 21 at five years . In the washout group it was only 5 at one year and 4 at five years . For knees with lesions of the medial femoral condyle of grade s 3 or 4 , arthroscopic debridement appears to be the treatment of choice with over half the patients free from pain after five years OBJECTIVE According to prevailing consensus , patients with mechanical symptoms are those considered to most likely benefit from arthroscopic surgery . The aim of this study was to determine the value of using patients ' pre-operative self-reports of mechanical symptoms as a justification surgery in patients with degenerative meniscus tear/knee disease . DESIGN Pragmatic prospect i ve cohort of 900 consecutive patients with symptomatic degenerative knee disease and meniscus tear undergoing arthroscopic partial meniscectomy ( APM ) was collected from one public orthopedic referral center specialized in arthroscopic surgery during 2007 - 2011 . The patients ' subjective satisfaction , self-rated improvement , change in Western Ontario Meniscal Evaluation Tool ( WOMET ) score , and patients ' ratings of the knee using a numerical rating scale ( NRS ) was assessed at 1 year postoperatively . Multivariable regression models , adjusted for possible confounders and intermediates , were used to compare the outcomes in those with and without preoperative mechanical symptoms . RESULTS The proportion of patients satisfied with their knee 12 months after arthroscopy was significantly lower among those with preoperative mechanical symptoms than among those without ( 61 % vs 75 % , multivariable adjusted risk ratio [ RR ] 0.84 ; 95 % confidence interval [ CI ] 0.76 , 0.92 ) . Similarly , the proportion reporting improvement was lower ( RR 0.91 ; 95 % CI 0.85 , 0.97 ) . No statistically significant difference was found in change in WOMET or NRS between the two groups . Of those with preoperative mechanical symptoms , 47 % reported persistent symptoms at 12 months postoperatively . CONCLUSIONS Our observational data contradicts the current tenet of using patients ' self-report of mechanical symptoms as a justification for performing arthroscopic surgery on patients with degenerative meniscus tear BACKGROUND Whether arthroscopic partial meniscectomy for symptomatic patients with a meniscal tear and knee osteoarthritis results in better functional outcomes than nonoperative therapy is uncertain . METHODS We conducted a multicenter , r and omized , controlled trial involving symptomatic patients 45 years of age or older with a meniscal tear and evidence of mild-to-moderate osteoarthritis on imaging . We r and omly assigned 351 patients to surgery and postoperative physical therapy or to a st and ardized physical-therapy regimen ( with the option to cross over to surgery at the discretion of the patient and surgeon ) . The patients were evaluated at 6 and 12 months . The primary outcome was the difference between the groups with respect to the change in the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) physical-function score ( ranging from 0 to 100 , with higher scores indicating more severe symptoms ) 6 months after r and omization . RESULTS In the intention-to-treat analysis , the mean improvement in the WOMAC score after 6 months was 20.9 points ( 95 % confidence interval [ CI ] , 17.9 to 23.9 ) in the surgical group and 18.5 ( 95 % CI , 15.6 to 21.5 ) in the physical-therapy group ( mean difference , 2.4 points ; 95 % CI , -1.8 to 6.5 ) . At 6 months , 51 active participants in the study who were assigned to physical therapy alone ( 30 % ) had undergone surgery , and 9 patients assigned to surgery ( 6 % ) had not undergone surgery . The results at 12 months were similar to those at 6 months . The frequency of adverse events did not differ significantly between the groups . CONCLUSIONS In the intention-to-treat analysis , we did not find significant differences between the study groups in functional improvement 6 months after r and omization ; however , 30 % of the patients who were assigned to physical therapy alone underwent surgery within 6 months . ( Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases ; METEOR Clinical Trials.gov number , NCT00597012 . ) BACKGROUND The efficacy of arthroscopic surgery for the treatment of osteoarthritis of the knee is unknown . METHODS We conducted a single-center , r and omized , controlled trial of arthroscopic surgery in patients with moderate-to-severe osteoarthritis of the knee . Patients were r and omly assigned to surgical lavage and arthroscopic débridement together with optimized physical and medical therapy or to treatment with physical and medical therapy alone . The primary outcome was the total Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) score ( range , 0 to 2400 ; higher scores indicate more severe symptoms ) at 2 years of follow-up . Secondary outcomes included the Short Form-36 ( SF-36 ) Physical Component Summary score ( range , 0 to 100 ; higher scores indicate better quality of life ) . RESULTS Of the 92 patients assigned to surgery , 6 did not undergo surgery . Of the 86 patients assigned to control treatment , all received only physical and medical therapy . After 2 years , the mean ( + /-SD ) WOMAC score for the surgery group was 874+/-624 , as compared with 897+/-583 for the control group ( absolute difference [ surgery-group score minus control-group score ] , -23+/-605 ; 95 % confidence interval [ CI ] , -208 to 161 ; P=0.22 after adjustment for baseline score and grade of severity ) . The SF-36 Physical Component Summary scores were 37.0+/-11.4 and 37.2+/-10.6 , respectively ( absolute difference , -0.2+/-11.1 ; 95 % CI , -3.6 to 3.2 ; P=0.93 ) . Analyses of WOMAC scores at interim visits and other secondary outcomes also failed to show superiority of surgery . CONCLUSIONS Arthroscopic surgery for osteoarthritis of the knee provides no additional benefit to optimized physical and medical therapy . ( Clinical Trials.gov number , NCT00158431 . |
12,091 | 31,193,395 | Results A low skinfold thickness , body fat and large forearm volume were anthropometric traits in successful climbers .
Well-trained forearm flexors with high aerobic capacities lead to an efficient style .
H and grip strength and endurance , postural stability and optimized kinematic motions were favourable .
Elite climbers had long finger and bent-arm hang times .
Psychologically , an " iceberg profile " was typical .
Constant training with fingerboard and dynamic eccentric-concentric training helped to push the " red-point grade " .
Conclusion H and , forearm strength and endurance are highly important elements in elite climbers .
An efficient climbing style with perpetual focus and accuracy , high speed and low exhaustion due to adaption to repeated isometric exercise is helpful in the ascent , while low body fat and a large bone-to-tip pulp make it easier . | Background The number of athletes engaged in climbing sports has risen .
Specific physical and psychological skills are required .
The objective of this review was to determine factors for high climbing performance .
We evaluated physiological , biomechanical and psychological characteristics that simplify the ascent .
We also assessed training and recovery strategies . | We studied which physiological and kinanthropometric characteristics determine climbing performance in 16 high-level sports climbers aged 29.9 ± 4.9 years . Body composition parameters were measured with dual energy X-ray absorptiometry scanner . We also measured kinanthropometric and physical fitness parameters . The sex-specific 75th percentile value of onsight climbing ability was used to divide the sample into expert ( < 75th ) and elite ( ≥75th ) climbers . All the analyses were adjusted by sex . The 75th percentile value of onsight climbing ability was 7b in women and 8b in men . There were no differences between expert and elite climbers in the studied variables , except in climbing time to exhaustion and bone mineral density . Elite climbers had a significantly higher time to exhaustion than the expert group ( 770.2 ± 385 vs. 407.7 ± 150 s , respectively , P = 0.001 ) . These results suggest that , among climbers with a high level of performance , as those analysed in this study , climbing time to exhaustion is a major determinant of climbing performance White , DJ and Olsen , PD . A time motion analysis of bouldering style competitive rock climbing . J Strength Cond Res 24(5 ) : 1356 - 1360 , 2010-Limited research has been performed on competitive bouldering . The aim of this study was to quantify the movement dynamics of elite boulder climbers . Six climbers were filmed during a national competition consisting of 5 novel climbing problems or routes . Two problems were r and omly selected and film footage was analyzed using K and le Swinger Pro software to determine type and duration ( seconds ) of bouldering movements . All subjects provided consent , and the study had ethical approval . The mean ± SD were determined for number of attempts per problem , duration of attempt , time on hold , and time to reach between holds . Exercise : recovery ratios were also calculated . On average , climbers attempted a problem 3.0 ± 0.5 times , with an attempt lasting 28.9 ± 10.8 seconds and rest periods of 114 ± 31 seconds between attempts . Average time gripping holds was 7.9 ± 1.3 seconds , with approximately 0.5 ± 0.1 seconds recovery between reaching for holds . The exercise-to-recovery ratio was ∼1:4 for attempting a problem and ∼13:1 for forearm muscles during climbing . The exercise-to-recovery ratios allow sufficient time for recovery during and after a problem . However , the prolonged contraction of forearm muscles indicates the importance of strength and endurance in these muscles . Video analysis was found to be a useful tool for the quantification of movement characteristics of competitive elite boulders . Data collected could be utilized in the design of sport-specific tests and training programs . Future research could examine a larger number of athletes and problems and help develop performance tests and training interventions for bouldering OBJECTIVES To assess oxygen uptake ( VO2 ) , blood lactate concentration ( [ La(b ) ] ) , and heart rate ( HR ) response during indoor and outdoor sport climbing . METHODS Seven climbers aged 25 ( SE 1 ) years , with a personal best ascent without p review or fall ( on sight ) ranging from 6b to 7a were assessed using an indoor vertical treadmill with artificial rock h and /foot holds and a discontinuous protocol with climbing velocity incremented until voluntary fatigue . On a separate occasion the subjects performed a 23.4 m outdoor rock climb grade d 5c and taking 7 min 36 s ( SE 33 s ) to complete . Cardiorespiratory parameters were measured using a telemetry system and [ La(b ) ] collected at rest and after climbing . RESULTS Indoor climbing elicited a peak oxygen uptake ( VO2climb-peak ) and peak HR ( HRpeak ) of 43.8 ( SE 2.2 ) ml/kg/min and 190 ( SE 4 ) bpm , respectively and increased blood lactate concentration [ La(b ) ] from 1.4 ( 0.1 ) to 10.2 ( 0.6 ) mmol/l ( p < 0.05 ) . During outdoor climbing VO2 and HR increased to about 75 % and 83 % of VO2climb-peak and HRpeak , respectively . [ La(b ) ] increased from 1.3 ( 0.1 ) at rest to 4.5 mmol/l ( p < 0.05 ) at 2 min 32 s ( 8 s ) after completion of the climb . CONCLUSIONS The results suggest that for elite climbers outdoor sport rock climbs of five to 10 minutes ' duration and moderate difficulty require a significant portion of the VO2climb-peak . The higher HR and VO2 for outdoor climbing and the increased [ La(b ) ] could be the result of repeated isometric contractions , particularly from the arm and forearm muscles Abstract Medernach , JPJ , Kleinöder , H , Lötzerich , HHH . Fingerboard in competitive bouldering : Training effects on grip strength and endurance . J Strength Cond Res 29(8 ) : 2286–2295 , 2015—Bouldering ( BL ) is an independent discipline of sport climbing , with grip strength and endurance as key factors . Although the sport has grown increasingly popular and competitive , limited research has been conducted on commonly used training methods to maximize BL performance . The purpose of this study was to investigate the training effects of 4 weeks of fingerboarding ( FB ) on grip strength and endurance in competitive BL . Twenty-three highly advanced male boulderers ( 25.6 ± 4.4 y ; 1.78 ± 0.05 m ; 70.1 ± 5.4 kg ; 6.2 ± 2.8 y climbing ; 7b+ Fb mean ability ) were r and omly allocated to a 4-week FB ( n = 11 ) or BL ( n = 12 ) training regimen . Pretests and posttests ( 50-min duration ) involved ( a ) h and held dynamometry ( GS ) to assess grip strength , ( b ) dead hangs ( DH ) , and ( c ) intermittent finger hangs ( IFH ) to assess grip endurance . After the 4-week regimen , GS increased significantly in the FB group ( 2.5 ± 1.4 kg , p < 0.001 ) but not in the BL group ( 1.4 ± 2.8 kg , p = 0.109 ) . The mean increase in DH ranged from 5.4 to 6.7 seconds in the FB group and was significantly ( p ⩽ 0.05 ) higher than that in the BL group ( 3.0–3.9 seconds ) . Finally , significantly higher IFH gains were observed in the FB group ( p = 0.004 ) , with a mean gain of 26 seconds , but not in the BL group ( p = 0.168 ) . These results suggest that FB is highly effective in increasing grip strength and endurance in competitive BL Performing intra-session recovery is important in rock climbing due to the multiple efforts that climbers are required to make in competitions , as well as repeated climbing trials that they carry out during training sessions . Active recovery has been shown to be a better option than passive recovery . However , the type of active recovery that should be done and the influence of the type and quantity of muscle mass activated are not clear . The aim of this study was to compare the effects of recovering with easy climbing ( CR ) or walking ( WR ) on markers of fatigue and climbing performance . For this purpose , 14 subjects participated in this r and omly assigned crossover protocol completing three two-minute climbing trials separated by two minutes of active recovery with the assigned method . Seven days later participants carried out the same protocol with the other recovery method . Blood lactate ( La(- ) ) , rating of perceived exertion ( RPE ) , and heart rate ( HR ) were analyzed as markers of fatigue and recovery , while meters climbed ( MC ) and h and grip force ( HF ) were analyzed for performance . La- values before the last climbing trial ( p < 0.05 ; d = 0.69 ) and Peak La- values ( p < 0.05 ; d = 0.77 ) were lower for CR than for WR . Climbers were able to ascend more meters in the set time when following the CR protocol ( p < 0.01 ; d = 0.6 ) , which shows the important role of the active recovery method carried out on climbing performance . There were no differences in HR , HF or RPE between protocol s. A more sport-specific recovery protocol , in addition to moving great muscle mass ( e.g. lower limbs ) , seems to enhance recovery and to facilitate lactate removal . For this reason , CR appears to be a more effective active recovery method than WR in sport rock climbing . Key pointsClimbing recovery improved lactate removal in comparison with walking recovery . Subjects were able to climb more meters in a determined time when easy climbing instead of walking during recoveries . Activating both great muscle mass like that of the lower limbs as well as the main fatigue producing muscles ( forearms in climbing ) seems more effective for recovering than activating just great muscle mass One of the main objectives of the experiment reported in this article was to analyze the arrangement of the forces applied to the holds accompanying a voluntary right foot release in the hanging rock climber . The three dimensional reaction forces applied to the holds were measured using four holds equipped with strain gauges . The force arrangement after the release consisted of a tripedal stance on the three remaining holds for the vertical forces , and of a bipedal stance on two laterally opposite holds ( left foot and left holds ) for the horizontal forces . The general significance of the results was analyzed with respect to the mechanism of static equilibrium . However , before conclusions can be drawn , other climbing movements and positions must be analyzed There is limited information on the anthropometry , strength , endurance and flexibility of female rock climbers . The aim of this study was to compare these characteristics in three groups of females : Group 1 comprised 10 elite climbers aged 31.3 ± 5.0 years ( mean ± s ) who had led to a st and ard of ‘ hard very severe ’ ; Group 2 consisted of 10 recreational climbers aged 24.1 ± 4.0 years who had led to a st and ard of ‘ ; severe ’ ; and Group 3 comprised 10 physically active individuals aged 28.5 ± 5.0 years who had not previously rock-climbed . The tests included finger strength ( grip strength , finger strength measured on climbing-specific apparatus ) , flexibility , bent arm hang and pull-ups . Regression procedures ( analysis of covariance ) were used to examine the influence of body mass , leg length , height and age . For finger strength , the elite climbers recorded significantly higher values ( P < 0.05 ) than the recreational climbers and non-climbers ( four fingers , right h and : elite 321 ± 18 N , recreational 251 ± 14 N , non-climbers 256 ± 15 N ; four fingers , left h and : elite 307 ± 14 N , recreational 248 ± 12 N , non-climbers 243 ± 11 N ) . For grip strength of the right h and , the elite climbers recorded significantly higher values than the recreational climbers only ( elite 338 ± 12 N , recreational 289 ± 10 N , non-climbers 307 ± 11 N ) . The results suggest that elite climbers have greater finger strength than recreational climbers and non-climbers PURPOSE Considering the development of rock climbing as a competitive sport , we aim ed at investigating the influence of four recovery methods on subsequent maximal climbing performance . METHODS In a r and omly assigned crossover design , 13 female well-trained climbers ( 27.1 + /- 8.9 yr ) came to the climbing center on four occasions separated by 1 wk . On each occasion , they had to perform two climbing tests ( C1 and C2 ) until volitional exhaustion on a pre practice d route ( overhanging wall , level 6b ) . These two tests were separated by 20 min of recovery . Four recovery methods were used in r and omized order : passive recovery , active recovery ( cycle ergometer , 30 - 40 W ) , electromyostimulation on the forearm muscles ( bisymmetric TENS current ) , or cold water immersion of the forearms and arms ( three periods of 5 min at 15 + /- 1 degrees C ) . Climbing tests ' performance was reflected by the number of arm movements and climb duration . RESULTS Using active recovery and cold water immersion , performance at C2 was maintained in comparison with C1 , whereas C2 performance was impaired compared with C1 ( P < 0.01 ) using electromyostimulation and passive recovery ( recovery method -by-climb interaction , P < 0.05 ) . Blood lactate decreased during recovery , with the greatest decrease occurring during active recovery ( time-by-recovery method interaction , P < 0.001 ) . Arms and forearms ' skin temperatures were lower throughout the cold water immersion compared with the other three methods ( P < 0.001 ) . CONCLUSION Active recovery and cold water immersion are two means of preserving performance when repeating acute exhausting climbing trails in female climbers . These positive effects are accompanied by a greater lactate removal and a decrease in subcutaneous tissues temperatures , respectively The aim of the present work was to characterize the modifications of the postural adjustments during a climbing task as a function of postural and /or movement constraints . The variations of the horizontal and vertical forces and momentum were analyzed for different movement amplitudes and types of holds . The results show that the horizontal momentum is influenced by all experimental conditions before the onset of movement . By contrast , the vertical momentum is only influenced by the amplitude of the movement , after its onset . These results confirm the hypothesis of a dual function of the anticipatory postural adjustments . The horizontal momentum is mainly involved in the control of equilibrium . The vertical momentum contributes to the movement initiation Abstract Three studies examined the effort and performance of rock climbers in the context of processing efficiency theory . Anxiety was manipulated by different means in the three studies . In each study , the effort due only to the physical exertion of climbing was controlled for . Anxiety , effort , and performance were measured via self-report , an integrated heart rate measure , and belayer observation . Consistent with processing efficiency theory , the results showed that higher levels of anxiety were usually associated with higher levels of effort and commensurately higher levels of performance . However , the results also suggested that cognitive anxiety may not be the prime determinant of the effort and performance changes observed . Finally , the results suggested that other individual difference variables may play an important part in determining the extent to which individuals may be able to make use of anxiety-induced effort Abstract Deyhle , MR , Hsu , H-S , Fairfield , TJ , Cadez-Schmidt , TL , Gurney , BA , and Mermier , CM . Relative importance of four muscle groups for indoor rock climbing performance . J Strength Cond Res 29(7 ) : 2006–2014 , 2015—Little research is available to guide training programs for rock climbers . To help meet this need , we sought to determine the relative importance of 4 muscle groups for rock climbing performance . Eleven male climbers were familiarized with an indoor climbing route before 5 separate days of testing . On testing days , subjects were r and omly assigned to climb with no prefatiguing exercise ( control climb ) or after a prefatiguing exercise design ed to specifically target the digit flexors ( DF ) , shoulder adductors ( SA ) , elbow flexors ( EF ) , or lumbar flexors ( LF ) . Immediately after the prefatiguing exercise , the subject climbed the route as far as possible without rest until failure . The number of climbing moves was recorded for each climb . Surface electromyography of the target muscles was recorded during the prefatigue . Fewer climbing moves were completed after prefatigue of the DF ( 50 ± 18 % ) and EF ( 78 ± 22 % ) ( p ⩽ 0.05 ) compared with the control climb . The number of moves completed after prefatigue of the LF and SA were not statistically significant compared with the control climb ( p > 0.05 ) . The short time lapse between the end of prefatiguing exercise and the start of climbing ( transit time ) , which may have allowed for some recovery , was not different among trials ( p > 0.05 ) . Electromyography median frequency was reduced from beginning to end of each prefatiguing exercise . These results suggest that among the muscle groups studied in men , muscular endurance of DF and EF muscle groups is especially important for rock climbing on 40 ° overhanging terrain Abstract The aim of the study was to compare the effects of different strength training intensities on climbing performance , climbing-specific tests and a general strength test . Thirty lower grade and intermediate-level climbers participated in a 10-week training programme . The participants were r and omized into three groups : high resistance – few repetitions training groups ( HR-FR ) , low resistance – high repetitions training groups ( LR-HR ) and a control group ( CON ) which continued climbing/training as usual . Post-testing results demonstrated statistical tendencies for climbing performance improvements in the HR-FR and LR-HR ( p = 0.088–0.090 , effect size = 0.55–0.73 ) , but no differences were observed between the groups ( p = 0.950 ) . For the climbing-specific tests , no differences were observed between the groups ( p = 0.507–1.000 ) , but the HR-FR and LR-HR improved their time in both Dead-hang ( p = 0.004–0.026 ) and Bent-arm hang ( p < 0.001–0.002 ) . The HR-FR and LR-HR improved their 12RM strength in pull-down ( p ≤ 0.001 ) , but not the CON group ( p = 0.250 ) . No differences were observed in the CON group in any of the tests ( p = 0.190–0.596 ) with the exception of improvement in Bent-arm Hang ( p = 0.018 ) . The training groups reduced their climbing sessions during the intervention compared to the CON group ( p = 0.057–0.074 ) . In conclusion , HR-FR and LR-HR training programmes demonstrated an 11 % and 12 % non-significant improvement in climbing performance despite a 50 % reduction in climbing sessions , but improved the results in strength and climbing-specific tests . None of the training intensities was superior compared to the others The aim of this study was to compare the climbing-specific finger endurance of climbers , rowers and aerobically leg trained athletes . Twenty-seven males aged 21.2±2.2 years ( mean±s ) volunteered for the study . The participants were intermediate rock climbers ( n = 9 ) , rowers ( n = 9 ) and leg trained athletes ( n = 9 ) . Maximal voluntary contraction ( MVC ) was determined on climbing-specific finger apparatus . Endurance isometric exercise was performed at 40 % MVC in three tests performed in a r and om order : ( 1 ) sustained exercise ; ( 2 ) 6 s exercise , 4 s rest ; and ( 3 ) 18 s exercise , 12 s rest . Pre- and post-exercise blood pressure and blood lactate concentration , together with post-exercise pain perception , were measured . The climbers had a significantly greater MVC ( 383±35.6 N ) than the rowers ( 321±49.5 N , P = 0.007 ) and aerobically leg trained athletes ( 288±60.6 N , P = 0.001 ) . There were no significant differences between the groups in terms of endurance times for any of the tests . In the test with 18 s exercise and 12 s rest , the climbers showed a significantly higher increase in blood lactate concentration , on average , than the rowers by 0.01 - 0.89 mmol · l−1 ( P = 0.006 ) ; there were no significant differences , on average , in the comparisons of climbers and the leg trained athletes and rowers and the leg trained athletes . There were no significant differences in the average changes in blood pressure from rest to post-exercise between any of the groups . Although the climbers had greater MVC on average than the other two groups , there were no significant differences in average endurance times among the groups . These findings suggest that training for rock climbing and participation in rock climbing may result in some specific adaptations . However , we acknowledge that this study is descriptive and there is the possibility that differences between groups could be attributed to self- selection PURPOSE To quantify the cardiorespiratory responses to indoor climbing during two increasingly difficult climbs and relate them to whole-body dynamic exercise . It was hypothesized that as climbing difficulty increased , oxygen consumption ( [ V02 ] and heart rate would increase , and that climbing would require utilization of a significant fraction of maximal cycling values . METHODS Elite competitive sport rock climbers ( 6 male , 3 female ) completed two data collection sessions . The first session was completed at an indoor climbing facility , and the second session was an incremental cycle test to exhaustion . During indoor climbing subjects were r and omly assigned to climb two routes design ated as " harder " or " easier " based on their previous best climb . Subjects wore a portable metabolic system , which allowed measurement of oxygen consumption [ V02 ] , minute ventilation ( [V02]E ) , respiratory exchange ratio ( RER ) , and heart rate . During the second session , maximal values for [ V02 ] , [V02]E , RER , and heart rate were determined during an incremental cycle test to exhaustion . RESULTS Heart rate and [ VO2 ] , expressed as percent of cycling maximum , were significantly higher during harder climbing compared with easier climbing . During harder climbing , % HR(max ) was significantly higher than % [ V02 ] ( 2max ) ( 89.6 % vs 51.2 % ) , and during easier climbing , % HR(max ) was significantly higher than % [ V02 ] ( 2max ) ( 66.9 % vs 45.3 % ) . CONCLUSIONS With increasing levels of climbing difficulty , there is a rise in both heart rate and [ V02 ] . However , there is a disproportional rise in heart rate compared with [ V02 ] , which we attribute to the fact that climbing requires the use of intermittent isometric contractions of the arm musculature and the reliance of both anaerobic and aerobic metabolism The aim of this study was to investigate how the affordances of an indoor climbing wall changed for intermediate climbers following a period of practice during which hold orientation was manipulated within a learning and transfer protocol . The learning protocol consisted of four sessions , in which eight climbers r and omly ascended three different routes of fixed absolute difficulty ( 5c on the French scale ) , as fluently as possible . All three routes were 10.3 m in height and composed of 20 h and -holds at the same locations on an artificial climbing wall ; only hold orientations were altered : ( i ) a horizontal-edge route ( H ) was design ed to afford horizontal hold grasping , ( ii ) a vertical-edge route ( V ) afforded vertical hold grasping , and ( iii ) , a double-edge route ( D ) was design ed to afford both horizontal and vertical hold grasping . Five inertial measurement units ( IMU ) ( 3D accelerometer , 3D gyroscope , 3D magnetometer ) were attached to the hip , feet and forearms to analyze the vertical acceleration and direction ( 3D unitary vector ) of each limb and hip in ambient space during the entire ascent . Segmentation and classification processes supported detection of movement and stationary phases for each IMU . Depending on whether limbs and /or hip were moving , a decision tree distinguished four states of behavior : stationary ( absence of limb and hip motion ) , hold exploration ( absence of hip motion but at least one limb in motion ) , hip movement ( hip in motion but absence of limb motion ) and global motion ( hip in motion and at least one limb in motion ) . Results showed that with practice , the learners decreased the relative duration of hold exploration , suggesting that they improved affordance perception of hold grasp-ability . The number of performatory movements also decreased as performance increased during learning sessions , confirming that participants ' climbing efficacy improved as a function of practice . Last , the results were more marked for the H route , while the D route led to longer relative stationary duration and a shorter relative duration of performatory states . Together , these findings emphasized the benefit of manipulating task constraints to promote safe exploration during learning , which is particularly relevant in extreme sports involving climbing tasks |
12,092 | 31,637,485 | No evidence showed that patients with MDS will benefit from using HMAs before HSCT in long-term survival ( OS and RFS ) compared to chemotherapy or best supportive therapy , though older patients were more likely to benefit from pre-transplantation HMAs treatment in terms of long-term survival . | The use of hypomethylating agents ( HMAs ) prior to hematopoietic stem cell transplantation ( HSCT ) in patients with myelodysplastic syndromes ( MDS ) was still controversial .
Therefore , we sought to evaluate the impact of hypomethylation therapy before HSCT , with a special focus on long-term outcome . | Background Allogeneic stem-cell transplantation ( HSCT ) is the only curative treatment in myelodysplastic syndromes ( MDS ) . Azacitidine ( AZA ) is increasingly used prior to HSCT , however in Europe it is only approved for patients who are not eligible for HSCT . Patients and methods We conducted a phase II multicenter study to prospect ively evaluate the feasibility of HSCT after treatment with AZA in 70 patients with a myelodysplastic syndrome ( MDS ) , 19 with acute myeloid leukemia ( AML ) , and 8 with chronic myelomonocytic leukemia ( CMML ) . After a median of four cycles ( range 1 - 11 ) : 24 % of patients achieved complete remission , 14 % partial remission , 8 % hematologic improvement , 32 % had stable and 22 % progressive disease . Ten patients discontinued treatment before the planned four cycles , due to an adverse event in nine cases . Results A HSC donor was identified in 73 patients , and HSCT was performed in 54 patients ( 74 % of patients with a donor ) . Main reasons for turning down HSCT were lack of a donor , an adverse event , or progressive disease ( 9 , 12 , and 16 patients , respectively ) . At a median follow-up of 20.5 months from enrolment , response to AZA was the only independent prognostic factor for survival . Compared to baseline assessment , AZA treatment did not affect patients ' comorbidities at HSCT : the HCT-CI remained stable in 62 % patients , and worsened or improved in 23 % and 15 % of patients , respectively . Conclusions Our study shows that HSCT is feasible in the majority of patients with HR-MDS/AML/CMML-2 after AZA treatment . As matched unrelated donor was the most frequent source of donor cells , the time between diagnosis and HSCT needed for donor search could be ' bridged ' using azacitidine . These data show that AZA prior to HSCT could be a better option than intensive chemotherapy in higher-risk MDS . The trial has been registered with the EudraCT number 2010 - 019673 - 1 Cytoreduction before allogeneic stem cell transplantation ( allo-SCT ) for patients with myelodysplastic syndromes remains a debatable issue . After excluding patients who had received preconditioning induction chemotherapy , we analyzed 128 consecutive patients with myelodysplastic syndrome who received reduced-intensity or nonmyeloablative conditioning ( RIC/NMA ) allo-SCT . Among them , 40 received azacitidine ( AZA ) before transplant ( AZA group ) and 88 were transplanted up front ( best supportive care [ BSC ] group ) . At diagnosis , 55 patients had intermediate 2 or high-risk scores per the International Prognostic Scoring System and 33 had a high cytogenetic risk score . Progression to a more advanced disease before allo-SCT was recorded in 22 patients . Source of stem cells were blood ( n = 112 ) or marrow ( n = 16 ) from sibling ( n = 78 ) or HLA-matched unrelated ( n = 50 ) donors . With a median follow-up of 60 months , 3-year overall survival , relapse-free survival , cumulative incidence of relapse , and nonrelapse mortality were , respectively , 53 % versus 53 % ( P = .69 ) , 37 % versus 42 % ( P = .78 ) , 35 % versus 36 % ( P = .99 ) , and 20 % versus 23 % ( P = .74 ) , for the AZA group and BSC group , respectively . Multivariate analysis confirmed the absence of statistical differences in outcome between the AZA and BSC groups , after adjusting for potential confounders using the propensity score approach . The absence of cytoreduction before RIC/NMA allo-SCT did not seem to alter the outcome . However , our results emphasize the need to perform prospect i ve protocol s to delineate the role of debulking strategy and to identify subsets of patients who may benefit from this approach This analysis compared azacitidine ( AZA ) to conventional care regimens ( CCR ) and their associated overall survival ( OS ) and tolerability in the subset of 87 elderly ( ≥ 75 years ) patients with higher-risk MDS ( FAB : RAEB , RAEB-t , CMML and IPSS : Int-2 or High ) from the AZA-001 trial . Patients were r and omized to AZA ( 75 mg/m(2)/daysubcutaneously × 7 days every 28 days ) ( n=38 ) or CCR ( n=49 ) and had median ages of 78 and 77 years , respectively . AZA significantly improved OS vs CCR ( HR : 0.48 [ 95%CI : 0.26 , 0.89 ] ; p=0.0193 ) and 2-year OS rates were 55 % vs 15 % ( p<0.001 ) , respectively . AZA was generally well tolerated compared with CCR , which was primarily best supportive care ( 67 % ) . Grade 3 - 4 anemia , neutropenia , and thrombocytopenia with AZA vs CCR were 13 % vs 4 % , 61 % vs 17 % , and 50 % vs 30 % , respectively . Given this efficacy and tolerability , AZA should be considered the treatment of choice in patients aged ≥ 75 years with good performance status and higher-risk MDS Aberrant DNA methylation , which results in leukemogenesis , is frequent in patients with myelodysplastic syndromes ( MDS ) and is a potential target for pharmacologic therapy . Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters In a study of elderly AML patients treated with the hypomethylating agent decitabine ( DAC ) , we noted a surprisingly favorable outcome in the ( usually very unfavorable ) subgroup with two or more autosomal monosomies ( MK2 + ) within a complex karyotype ( Lübbert et al. , Haematologica 97:393 - 401 , 2012 ) . We now analyzed 206 myelodysplastic syndrome ( MDS ) patients ( 88 % of 233 patients r and omized in the EORTC/GMDSSG phase III trial 06011 , 61 of them with RAEBt , i.e. AML by WHO ) with cytogenetics informative for MK status .. Endpoints are the following : complete/partial ( CR/PR ) and overall response rate ( ORR ) and progression-free ( PFS ) and overall survival ( OS ) . Cytogenetic subgroups are the following : 63 cytogenetically normal ( CN ) patients , 143 with cytogenetic abnormalities , 73 of them MK-negative ( MK− ) , and 70 MK-positive ( MK+ ) . These MK+ patients could be divided into 17 with a single autosomal monosomy ( MK1 ) and 53 with at least two monosomies ( MK2 + ) . ORR with DAC in CN patients : 36.1 % , in MK− patients : 16.7 % , in MK+ patients : 43.6 % ( MK1 : 44.4 % , MK2 + 43.3 % ) . PFS was prolonged by DAC compared to best supportive care ( BSC ) in the CN ( hazard ratio ( HR ) 0.55 , 99 % confidence interval ( CI ) , 0.26 ; 1.15 , p = 0.03 ) and MK2 + ( HR 0.50 ; 99 % CI , 0.23 ; 1.06 , p = 0.016 ) but not in the MK− , MK+ , and MK1 subgroups . OS was not improved by DAC in any subgroup . In conclusion , we demonstrate for the first time in a r and omized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC Background Few studies thus far have compared head-to-head different non-myelooablative conditioning regimens for allogeneic hematopoietic cell transplantation ( allo-HCT ) . Methods Here , we report the results of a phase II multicenter r and omized study comparing non-myeloablative allo-HCT from HLA-identical siblings ( n = 54 ) or from 10/10 HLA-matched unrelated donors ( n = 40 ) with either fludarabine plus 2 Gy total body irradiation ( Flu-TBI arm ; n = 49 ) or 8 Gy TLI + anti-thymocyte globulin ( TLI-ATG arm ; n = 45 ) conditioning . Results The 180-day cumulative incidences of grade II-IV acute GVHD ( primary endpoint ) were 12.2 % versus 8.9 % in Flu-TBI and TLI-ATG patients , respectively ( P = 0.5 ) . Two-year cumulative incidences of moderate/severe chronic GVHD were 40.8 % versus 17.8 % in Flu-TBI and TLI-ATG patients , respectively ( P = 0.017 ) . Five Flu-TBI patients and 10 TLI-ATG patients received pre-emptive DLI for low donor chimerism levels , while 1 Flu-TBI patient and 5 TLI-ATG patients ( including 2 patients given prior pre-emptive DLIs ) received a second HCT for poor graft function , graft rejection , or disease progression . Four-year cumulative incidences of relapse/progression were 22 % and 50 % in Flu-TBI and TLI-ATG patients , respectively ( P = 0.017 ) . Four-year cumulative incidences of nonrelapse mortality were 24 % and 13 % in Flu-TBI and TLI-ATG patients , respectively ( P = 0.5 ) . Finally , 4-year overall ( OS ) and progression-free survivals ( PFS ) were 53 % and 54 % , respectively , in the Flu-TBI arm , versus 54 % ( P = 0.9 ) and 37 % ( P = 0.12 ) , respectively , in the TLI-ATG arm . Conclusions In comparison to patients included in the Flu-TBI arm , patients included in the TLI-ATG arm had lower incidence of chronic GVHD , higher incidence of relapse and similar OS.Trial registration The study was registered on Clinical Trial.gov ( NCT00603954 ) and EUDRACT ( 2010 - 024297 - 19 ) Background The treatment of acute myeloid leukemia of older , medically non-fit patients still poses a highly unmet clinical need , and only few large , prospect i ve studies have been performed in this setting . Given the established activity of hypomethylating agents such as 5-aza-2'-deoxycytidine ( decitabine ) in myelodysplastic syndromes and acute myeloid leukemia with 20–30 % bone marrow blasts , we investigated whether this drug is also active in patients with more than 30 % blasts . Design and Methods To evaluate the efficacy and toxicity of decitabine in patients over 60 years old with untreated acute myeloid leukemia ineligible for induction chemotherapy , 227 patients ( median age , 72 years ) , many with comorbidities , adverse cytogenetics and /or preceding myelodysplastic syndrome were treated with this hypomethylating agent . During the initial decitabine treatment ( 135 mg/m2 total dose infused intravenously over 72 hours every 6 weeks ) , a median of two cycles was administered ( range , 1–4 ) . All-trans retinoic acid was administered to 100 patients during course 2 . Fifty-two patients who completed four cycles of treatment subsequently received a median of five maintenance courses ( range , 1–19 ) with a lower dose of decitabine ( 20 mg/m2 ) infused over 1 hour on 3 consecutive days every 4–6 weeks . Results The complete and partial remission rate was 26 % , 95 % CI ( 20 % , 32 % ) , and an antileukemic effect was noted in 26 % of patients . Response rates did not differ between patients with or without adverse cytogenetics ; patients with monosomal karyotypes also responded . The median overall survival from the start of decitabine treatment was 5.5 months ( range , 0–57.5 + ) and the 1-year survival rate was 28 % , 95%CI ( 22%,34 % ) . Toxicities were predominantly hematologic . Conclusions Decitabine is well tolerated by older , medically non-fit patients with acute myeloid leukemia ; myelosuppression is the major toxicity . The response rate and overall survival were not adversely influenced by poor-risk cytogenetics or myelodysplastic syndrome . Because of these encouraging results , r and omized studies evaluating single-agent decitabine versus conventional treatment are warranted . The study is registered with the German Clinical Trials Registry , number DRKS00000069 BACKGROUND The molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia ( AML ) or myelodysplastic syndromes ( MDS ) are unclear . METHODS We enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses . Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles . We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients . An extension cohort included 32 additional patients who received decitabine in different protocol s. RESULTS Of the 116 patients , 53 ( 46 % ) had bone marrow blast clearance ( < 5 % blasts ) . Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile ( 29 of 43 patients [ 67 % ] vs. 24 of 71 patients [ 34 % ] , P<0.001 ) and among patients with TP53 mutations than among patients with wild-type TP53 ( 21 of 21 [ 100 % ] vs. 32 of 78 [ 41 % ] , P<0.001 ) . Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes . However , in this study of 10-day courses of decitabine , neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles . CONCLUSIONS Patients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk , TP53 mutations , or both had favorable clinical responses and robust ( but incomplete ) mutation clearance after receiving serial 10-day courses of decitabine . Although these responses were not durable , they result ed in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine . ( Funded by the National Cancer Institute and others ; Clinical Trials.gov number , NCT01687400 . ) Novel , non-intensive treatment options in older MDS/AML patients planned for allografting , with the goal of down-staging the underlying disease and bridging time to transplantation , are presently being developed . 5-azacytidine and decitabine ( DAC ) are of particular interest , as they can be given repetitively , with very limited non-hematologic toxicity and result in responses both in MDS and AML even at low doses . We describe 15 consecutive patients ( median age 69 years , range 60–75 years ) with MDS ( n=10 ) or AML ( n=5 ) who all received first-line treatment with DAC and subsequent allografting ( from sibling donor in four patients , unrelated donor in 11 ) after reduced-intensity conditioning with the FBM regimen . Successful engraftment was attained in 14/15 patients , all of whom achieved a CR , with a median duration of 5 months ( range 1 + to 51 + ) . Six of these 14 patients are alive ( 4 with complete donor chimerism ) , 8 have died either from relapse ( n=4 ) or treatment-related complications while in CR ( n=4 ) . We conclude that allografting after low-dose DAC and subsequent conditioning with FBM is feasible , with no unexpected toxicities and appears as a valid alternative to st and ard chemotherapy ( ‘ InDACtion instead of induction ’ ) in elderly patients with MDS/AML Although allogeneic hematopoietic cell transplantation ( HCT ) has proven curative potential for myelodysplastic syndrome , relapse after HCT remains a problem . Pretransplantation cytoreduction with induction chemotherapy ( IC ) has been used to reduce relapse rates but is associated with significant toxicity and mortality . Hypomethylating agents may achieve cytoreduction with limited toxicity ; however , data on the effect of pre-HCT hypomethylation on post-HCT outcomes are limited . We retrospectively review ed results in 68 patients who underwent allogeneic HCT for myelodysplastic syndrome or acute myeloid leukemia transformed from MDS . Thirty-five patients had received cytoreduction with azacitidine before HCT with either a high-dose ( 40 % ) or a reduced-intensity ( 60 % ) conditioning regimen , and 33 had undergone IC before HCT with high-dose conditioning . The estimated 1-year overall survival ( OS ) was 57 % in the azacitidine group and 36 % in the IC group . The risk of post-HCT mortality ( hazard ratio , 0.68 ; 95 % confidence interval , 0.35 - 1.30 ) , nonrelapse mortality ( hazard ratio , 0.99 ; 95 % confidence interval , 0.41 - 2.34 ) , and relapse ( hazard ratio , 0.34 ; 95 % confidence interval , 0.41 - 2.34 ) were lower in the azacitidine group compared to the IC group , but only the hazard for relapse was significantly lower . After adjustment for cytogenetic risk , International Prognostic Scoring System , and donor , the rates of post-HCT relapse for the 2 cohorts were similar . Although the current study was retrospective and nonr and omized and needs to be interpreted in this context , the results add to the growing evidence that pre-HCT therapy with azacitidine is associated with less toxicity than IC and may allow for similar post-HCT outcomes Transplant outcome was analyzed in 150 patients with myelodysplastic syndrome ( MDS ) or acute myelogenous leukemia transformed from MDS ( tAML ) conditioned with nonmyeloablative or myeloablative regimens . A total of 38 patients received nonmyeloablative regimens of 2 Gy total body irradiation alone ( n=2 ) or with fludarabine ( n=36 ) , 90 mg/m2 . A total of 112 patients received a myeloablative regimen of busulfan , 16 mg/kg ( targeted to 800–900 ng/ml ) , and cyclophosphamide 120 mg/kg . Nonmyeloablative patients were older ( median age 62 vs 52 years , P<0.001 ) , more frequently had progressed to tAML ( 53 vs 31 % , P=0.06 ) , had higher risk disease by the International Prognostic Scoring System ( 53 vs 30 % , P=0.004 ) , had higher transplant specific comorbidity indices ( 68 vs 42 % , P=0.01 ) and more frequently had durable complete responses to induction chemotherapy ( 58 vs 14 % ) . Three-year overall survival ( 27%/48 % ( P=0.56 ) ) , progression-free survival ( 28%/44 % , ( P=0.60 ) ) , and nonrelapse mortality ( 41%/34 % , ( P=0.94 ) ) did not differ significantly between nonmyeloblative/myeloablative conditioning . Overall ( HR=0.9 , P=0.84 ) and progression-free survivals ( HR=1 , P=0.93 ) were similar for patients with chemotherapy-induced remissions irrespective of conditioning intensity . Graft vs leukemia effects may be more important than conditioning intensity in preventing progression in patients in chemotherapy-induced remissions at the time of transplantation . R and omized prospect i ve studies are needed to further address the optimal choice of transplant conditioning intensity in myeloid neoplasms PURPOSE In a phase III r and omized trial , azacitidine significantly prolonged overall survival ( OS ) compared with conventional care regimens ( CCRs ) in patients with intermediate-2- and high-risk myelodysplastic syndromes . Approximately one third of these patients were classified as having acute myeloid leukemia ( AML ) under current WHO criteria . This analysis compared the effects of azacitidine versus CCR on OS in this subgroup . PATIENTS AND METHODS Patients were r and omly assigned to receive subcutaneous azacitidine 75 mg/m(2)/d or CCR ( best supportive care [ BSC ] only , low-dose cytarabine ( LDAC ) , or intensive chemotherapy [ IC ] ) . RESULTS Of the 113 elderly patients ( median age , 70 years ) r and omly assigned to receive azacitidine ( n = 55 ) or CCR ( n = 58 ; 47 % BSC , 34 % LDAC , 19 % IC ) , 86 % were considered unfit for IC . At a median follow-up of 20.1 months , median OS for azacitidine-treated patients was 24.5 months compared with 16.0 months for CCR-treated patients ( hazard ratio = 0.47 ; 95 % CI , 0.28 to 0.79 ; P = .005 ) , and 2-year OS rates were 50 % and 16 % , respectively ( P = .001 ) . Two-year OS rates were higher with azacitidine versus CCR in patients considered unfit for IC ( P = .0003 ) . Azacitidine was associated with fewer total days in hospital ( P < .0001 ) than CCR . CONCLUSION In older adult patients with low marrow blast count ( 20 % to 30 % ) WHO-defined AML , azacitidine significantly prolongs OS and significantly improves several patient morbidity measures compared with CCR BACKGROUND Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage . In this trial , we aim ed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens . METHODS In a phase III , international , multicentre , controlled , parallel-group , open-label trial , patients with higher-risk myelodysplastic syndromes were r and omly assigned one-to-one to receive azacitidine ( 75 mg/m(2 ) per day for 7 days every 28 days ) or conventional care ( best supportive care , low-dose cytarabine , or intensive chemotherapy as selected by investigators before r and omisation ) . Patients were stratified by French-American-British and international prognostic scoring system classifications ; r and omisation was done with a block size of four . The primary endpoint was overall survival . Efficacy analyses were by intention to treat for all patients assigned to receive treatment . This study is registered with Clinical Trials.gov , number NCT00071799 . FINDINGS Between Feb 13 , 2004 , and Aug 7 , 2006 , 358 patients were r and omly assigned to receive azacitidine ( n=179 ) or conventional care regimens ( n=179 ) . Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis . After a median follow-up of 21.1 months ( IQR 15.1 - 26.9 ) , median overall survival was 24.5 months ( 9.9-not reached ) for the azacitidine group versus 15.0 months ( 5.6 - 24.1 ) for the conventional care group ( hazard ratio 0.58 ; 95 % CI 0.43 - 0.77 ; stratified log-rank p=0.0001 ) . At last follow-up , 82 patients in the azacitidine group had died compared with 113 in the conventional care group . At 2 years , on the basis of Kaplan-Meier estimates , 50.8 % ( 95 % CI 42.1 - 58.8 ) of patients in the azacitidine group were alive compared with 26.2 % ( 18.7 - 34.3 ) in the conventional care group ( p<0.0001 ) . Peripheral cytopenias were the most common grade 3 - 4 adverse events for all treatments . INTERPRETATION Treatment with azacitidine increases overall survival in patients with higher-risk myelodysplastic syndromes relative to conventional care Allogeneic hematopoietic cell transplantation ( allo HCT ) is the only curative therapy for the myelodysplastic syndromes ( MDS ) and myeloproliferative neoplasms ( MPN ) , but treatment toxicity has been a barrier to its more widespread use . The nonmyeloablative regimen of total lymphoid irradiation ( TLI ) and antithymocyte globulin ( ATG ) permits the establishment of donor hematopoiesis necessary for the graft-versus-malignancy effect and is protective against acute graft-versus-host disease ( aGVHD ) , but it has minimal direct cytotoxicity against myeloid diseases . We explored the use of TLI-ATG conditioning to treat 61 patients with allo HCT for MDS ( n = 32 ) , therapy-related myeloid neoplasms ( n = 15 ) , MPN ( n = 9 ) , and chronic myelomonocytic leukemia ( n = 5 ) . The median age of all patients was 63 years ( range , 50 to 73 ) . The cumulative incidence of aGVHD grade s II to IV was 14 % ( 95 % confidence interval [ CI ] , 4 % to 23 % ) and for grade s III to IV , 4 % ( 95 % CI , 0 to 9 % ) , and it did not differ between patients who received allografts from related or unrelated donors . The cumulative incidence of nonrelapse mortality ( NRM ) at 100 days , 12 months , and 36 months was 0 % , 7 % , and 11 % . Overall survival and progression-free survival were 41 % ( 95 % CI , 29 % to 53 % ) and 35 % ( 95 % CI , 23 % to 48 % ) , respectively . The safety and tolerability of TLI-ATG , as exemplified by its low NRM , provides a foundation for further risk-adapted or prophylactic interventions to prevent disease progression Decitabine is a hypomethylating agent with activity in myelodysplastic syndrome ( MDS ) . It is largely unknown whether treatment with this drug before allo-SCT will increase the toxicity of the preparative regimen or otherwise affect the results of the transplant . We report the outcome of 17 patients with MDS with a median age of 55.5 years ( range , 36–66 years ) who underwent an allo-SCT ( 12 siblings , 5 unrelated ) after prior therapy with decitabine . Preparative regimens consisted of fludarabine in combination with BU ( n=8 ) or melphalan ( n=9 ) . The source of stem cells was marrow in four patients and peripheral blood ( PB ) in 13 patients . Thirteen patients were in CR within 100 days of transplant . With a median follow-up of 12 months ( range , 3–35 months ) , 11 patients are alive ; eight in CR and three with progressive disease . Prior therapy with hypomethylating agents did not increase toxicity and may improve the outcome of allogeneic transplant in MDS and should be evaluated in a prospect i ve trial PURPOSE Patients with high-risk myelodysplastic syndrome ( MDS ) have high mortality from bone marrow failure or transformation to acute leukemia . Supportive care is st and ard therapy . We previously reported that azacitidine ( Aza C ) was active in patients with high-risk MDS . PATIENTS AND METHODS A r and omized controlled trial was undertaken in 191 patients with MDS to compare Aza C ( 75 mg/m(2)/d subcutaneously for 7 days every 28 days ) with supportive care . MDS was defined by French-American-British criteria . New rigorous response criteria were applied . Both arms received transfusions and antibiotics as required . Patients in the supportive care arm whose disease worsened were permitted to cross over to Aza C. RESULTS Responses occurred in 60 % of patients on the Aza C arm ( 7 % complete response , 16 % partial response , 37 % improved ) compared with 5 % ( improved ) receiving supportive care ( P < .001 ) . Median time to leukemic transformation or death was 21 months for Aza C versus 13 months for supportive care ( P = .007 ) . Transformation to acute myelogenous leukemia occurred as the first event in 15 % of patients on the Aza C arm and in 38 % receiving supportive care ( P = .001 ) . Eliminating the confounding effect of early cross-over to Aza C , a l and mark analysis after 6 months showed median survival of an additional 18 months for Aza C and 11 months for supportive care ( P = .03 ) . Quality -of-life assessment found significant major advantages in physical function , symptoms , and psychological state for patients initially r and omized to Aza C. CONCLUSION Aza C treatment results in significantly higher response rates , improved quality of life , reduced risk of leukemic transformation , and improved survival compared with supportive care . Aza C provides a new treatment option that is superior to supportive care for patients with the MDS subtypes and specific entry criteria treated in this study Prognostic factors for response and survival in higher-risk myelodysplastic syndrome patients treated with azacitidine ( AZA ) remain largely unknown . Two hundred eighty-two consecutive high or intermediate-2 risk myelodysplastic syndrome patients received AZA in a compassionate , patient-named program . Diagnosis was RA/RARS/RCMD in 4 % , RAEB-1 in 20 % , RAEB-2 in 54 % , and RAEB-t ( AML with 21%-30 % marrow blasts ) in 22 % . Cytogenetic risk was good in 31 % , intermediate in 17 % , and poor in 47 % . Patients received AZA for a median of 6 cycles ( 1 - 52 ) . Previous low-dose cytosine arabinoside treatment ( P = .009 ) , bone marrow blasts > 15 % ( P = .004 ) , and abnormal karyotype ( P = .03 ) independently predicted lower response rates . Complex karyotype predicted shorter responses ( P = .0003 ) . Performance status ≥ 2 , intermediate- and poor-risk cytogenetics , presence of circulating blasts , and red blood cell transfusion dependency ≥ 4 units/8 weeks ( all P < 10(-4 ) ) independently predicted poorer overall survival ( OS ) . A prognostic score based on those factors discriminated 3 risk groups with median OS not reached , 15.0 and 6.1 months , respectively ( P < 10(-4 ) ) . This prognostic score was vali date d in an independent set of patients receiving AZA in the AZA-001 trial ( P = .003 ) . Achievement of hematological improvement in patients who did not obtain complete or partial remission was associated with improved OS ( P < 10(-4 ) ) . In conclusion , routine tests can identify subgroups of patients with distinct prognosis with AZA treatment |
12,093 | 18,006,773 | The use of biomarkers in phase I trials has increased over the period from 1991 to 2002 .
To date , biomarker utilization has made a limited and primarily supportive contribution to dose selection , the primary end point of phase I studies . | PURPOSE There has been interest in using biomarkers that aid the evaluation of new anticancer agents .
We evaluated trends in the use of biomarkers and their contribution to the main goals of phase I trials . | Investigations using intermediate end points as cancer surrogates are quicker , smaller , and less expensive than studies that use malignancy as the end point . We present a strategy for determining whether a given biomarker is a valid intermediate end point between an exposure and incidence of cancer . C and i date intermediate end points may be selected from case series , ecologic studies , and animal experiments . Prospect i ve cohort and sometimes case-control studies may be used to quantify the intermediate end point-cancer association . The most appropriate measure of this association is the attributable proportion . The intermediate end point is a valid cancer surrogate if the attributable proportion is close to 1.0 , but not if it is close to 0 . Usually , the attributable proportion is close to neither 1.0 nor 0 ; in this case , valid surrogacy requires that the intermediate end point mediate an established exposure-cancer relation . This would in turn imply that the exposure effect would vanish if adjusted for the intermediate end point . We discuss the relative advantages of intervention and observational studies for the validation of intermediate end points . This validation strategy also may be applied to intermediate end points for adverse reproductive outcomes and chronic diseases other than cancer |
12,094 | 25,597,420 | Our meta-analyses indicate that optical biopsy with NBI , exceeds the NPV threshold for adenomatous polyp histology , supporting a " diagnose- and -leave " strategy for diminutive predicted nonneoplastic polyps in the rectosigmoid colon . | In vivo real-time assessment of the histology of diminutive ( ≤5 mm ) colorectal polyps detected at colonoscopy can be achieved by means of an " optical biopsy " by using currently available endoscopic technologies .
This systematic review and meta- analysis was performed by the American Society for Gastrointestinal Endoscopy ( ASGE ) Technology Committee to specifically assess whether acceptable performance thresholds outlined by an ASGE Preservation and Incorporation of Valuable endoscopic Innovations ( PIVI ) document for clinical adoption of these technologies have been met . | BACKGROUND Investigators have proposed " predict , resect , and discard " strategies for diminutive ( ≤ 5 mm ) or small ( 6 - 9 mm ) polyps to reduce screening colonoscopy costs . Advanced histological features such as villous histology , high- grade dysplasia , and /or cancer in these polyps could deter adoption of these strategies . OBJECTIVE Determine the prevalence of advanced histological features in diminutive and small colon polyps . DESIGN Retrospective analysis of data from 3 prospect i ve clinical trials . SETTING Two tertiary-care referral centers . PATIENTS This study involved patients undergoing screening or surveillance colonoscopy . INTERVENTION The location , size , and morphology of each polyp detected was documented . Each polyp was then resected , placed in a unique specimen jar , and sent for histopathological evaluation . MAIN OUTCOME MEASUREMENTS Rates of advanced histological features ( villous histology , high- grade dysplasia , and cancer ) . RESULTS A total of 2361 polyps were detected , removed , and retrieved . Both diminutive and small polyps had a lower frequency of any advanced histological features compared with large polyps ( 0.5 % and 1.5 % , respectively vs 15.0 % ; P < .001 for both comparisons ) . Polyps < 10 mm in size had a lower frequency of advanced histology compared with polyps ≥ 10 mm ( 0.8 % vs 15.0 % ; P < .001 ) . During sensitivity analysis , the frequency of advanced histological features varied from 0.2 % to 0.7 % within diminutive polyps , 1.5 % to 3.6 % within small polyps , and 0.8 % to 1.2 % within polyps < 10 mm . LIMITATIONS Retrospective analysis from tertiary-care referral centers ; predominantly white , male , veteran patient population result ing in limited generalizability of results . CONCLUSION The prevalence of advanced histological features in colon polyps ≤ 5 mm is very low ( 0.5 % ) . This has important implication s for the potential practice of " predicting , resecting , and discarding " diminutive colon polyps Objective : Colonoscopy is the accepted gold st and ard for screening of neoplastic colorectal lesions , but the substantial miss rate remains a challenge . Computed virtual chromoendoscopy with the Fujinon intelligent colour enhancement ( FICE ) system is a new dyeless imaging technique that might allow higher rates of adenoma detection . Methods : This is a prospect i ve r and omised five tertiary care centre trial of colonoscopy in the FICE mode versus st and ard colonoscopy with targeted indigocarmine chromoscopy ( control group ) in consecutive patients attending for routine colonoscopy . Histopathology of detected lesions was confirmed by evaluation of endoscopic resection or biopsy specimens . Results : 871 patients were enrolled , and 764 patients ( 344 female , mean age 64 years ) were subjected to final analysis ( 368 in the FICE group , 396 in the control group ) . In total , 236 adenomas ( mean of 0.64 per case ) were detected in the FICE group and 271 adenomas ( mean of 0.68 per case ) in the control group ( p = 0.92 ) . There was no statistically significant difference in the percentage of patients with ⩾1 adenoma between the control group ( 35.4 % ) and the FICE group ( 35.6 % ) ( p = 1.0 ) . For the differential diagnosis of adenomas and non-neoplastic polyps , the sensitivity of FICE ( 92.7 % ) was comparable with that of indigocarmine ( 90.4 % ) ( p = 0.44 ) . Conclusions : At colonoscopy , adenoma detection rates are not improved by virtual chromoendoscopy with the FICE system compared with white light endoscopy with targeted indigocarmine spraying . However , FICE can effectively substitute for chromoscopy concerning the differentiation of neoplastic and non-neoplastic lesions BACKGROUND Probe-based confocal laser endomicroscopy ( pCLE ) is an emerging tool for in vivo imaging of the GI tract that requires the endoscopist to interpret microscopic images . The learning curve for interpretation of pCLE images is unknown . OBJECTIVE To examine the learning curve of correctly identifying benign and neoplastic colorectal lesions by using pCLE and to evaluate the learning curve of obtaining high- quality images . DESIGN Prospect i ve , double-blind review of pCLE images of 76 colorectal lesions by using corresponding polypectomies as the reference st and ard . A training set of 20 images with known histology was first review ed to st and ardize image interpretation , followed by blinded review of 76 unknown images . SETTING Eleven endoscopists from 3 different endoscopy centers evaluated the images obtained by 1 endoscopist using the high-definition confocal probe . PATIENTS Patients undergoing screening and surveillance colonoscopies . INTERVENTION Intravenous fluorescein pCLE imaging of colorectal lesions followed by polypectomies . MAIN OUTCOME MEASUREMENTS Accuracy of image interpretation with constructing learning curve for pCLE image interpretation and acquisition . RESULTS Of the 76 colorectal lesions , 51 ( 67 % ) were neoplastic and 25 ( 33 % ) were benign , based on histopathology . Accuracy for the overall group was 63 % for lesions 1 to 20 , 64 % for lesions 21 to 40 , 79 % for lesions 41 to 60 , and 86 % for lesions 61 to 76 . The ability to obtain high- quality images was stable over the 76 cases . LIMITATIONS Small sample size and use of offline video sequences . CONCLUSIONS Accurate interpretation of pCLE images for predicting neoplastic lesions can be learned rapidly by a wide range of GI specialists . Furthermore , the ability to acquire high- quality pCLE images is also quickly learned BACKGROUND The EPKi system ( Pentax , Japan ) enables resolution above HDTV . Aim of the study was to test the efficacy of HD+ alone and with the new post-processing digital filter i-Scan or chromoendoscopy ( Methylene blue 0.1 % ) in screening for colorectal cancer . We focused on lesions less than 5 mm as a surrogate marker for the optical possibilities of the EPKi system . METHODS The last 30 cm of the colon in a screening population were inspected with HD+ alone , in combination with i-Scan ( 2:1 r and omisation ) and subsequently with chromoendoscopy . All lesions were characterized and targeted biopsies were performed . RESULTS i-Scan augmented in 69 patients the identification of lesions from 176 to 335 ( p<0.001 ) and chromoendoscopy to 646 ( p<0.001 ) . The additional lesions were mainly flat ( type IIb , 74 % ) , which were only recognized using i-Scan or chromoendoscopy . The amount of neoplasias was not significantly different ( HD+ : 5 , i-Scan : 11 , Chromoendoscopy : 11 ) , but all could correctly be predicted using i-Scan or chromoendoscopy . CONCLUSIONS HD+ colonoscopy with and without i-Scan unmask a plethora of small lesions but chromoendoscopy can even advance the number . However , i-Scan was able to predict neoplasia as precisely as chromoendoscopy and might shortly replace chromoendoscopy as a more time efficient tool BACKGROUND AND STUDY AIMS Narrow-b and imaging ( NBI ) has shown promising results in discriminating adenomatous from non-adenomatous colonic polyps . In patients with small polyps ( < 10 mm ) , the application of NBI within a " resect and discard " strategy , might allow post-polypectomy surveillance intervals to be determined independently from histopathology . The aim of the present study was to assess the feasibility and safety of this approach in routine clinical practice . PATIENTS AND METHODS Consecutive colonoscopy out patients with one or more polyps smaller than 10 mm were prospect ively included . Each polyp was categorized by the endoscopist as adenoma or non-adenoma according to simplified NBI criteria , and future post-polypectomy surveillance interval was assigned accordingly . Following histopathology , post-polypectomy surveillance interval was subsequently re-assigned , and the accordance between endoscopy- and histology-directed surveillance strategies was calculated . RESULTS Among 942 colonoscopy patients , 286 ( 30.4 % ) with only small polyps were included . In total , 511 small polyps were evaluated ; 350 ( 68.5 % ) were adenomas and 18 of these ( 5.1 % ) had histologic features of advanced neoplasia . For the in vivo diagnosis of adenoma , NBI sensitivity , specificity , accuracy , and positive and negative likelihood ratios were 94.9 % , 65.8 % , 85.7 % , 2.80 , and 0.08 , respectively . The endoscopy-directed surveillance strategy was in accordance with the histology-directed strategy in 237 of 286 patients ( 82.9 % ) . In 9.8 % and 7.3 % patients , the endoscopy-directed approach would have result ed in early and delayed surveillance , respectively . CONCLUSIONS The resect and discard strategy seems to be a viable , safe , and cost-effective approach for the management of patients with small polyps . However , caution in the application of the strategy should be advocated for patients with polyps 6 - 9 mm in size and those with right-sided lesions , due to their malignant potential . The study was registered on Clinical trials.gov ( NCT01462123 ) Background and study aims Magnifying colonoscopy with indigo carmine dye and the analysis of the capillary and the pit patterns by computed virtual chromoendoscopy ( Fujinon Intelligent Color Enhancement , FICE ) with magnification are effective for the differential diagnosis of neoplastic and non-neoplastic lesions . This study aim ed to compare the accuracy of virtual and real chromoendoscopy in differentiating neoplastic and non-neoplastic colorectal lesions . Patients and methods A prospect i ve r and omized trial of magnification colonoscopy with targeted FICE ( Group I – 72 patients /111 lesions ) versus magnification colonoscopy with targeted indigo carmine dye ( Group II – 72 patients /137 lesions ) was performed in consecutive patients with lesions 1 cm or less . Histopathology of the specimens was regarded as the gold st and ard . Results In group I , 86 ( 77.5 % ) lesions showed an intense vascular pattern ( positive capillary meshwork ) , of which 80 ( 93 % ) were histologically confirmed as adenomas . From 25 lesions with negative capillary meshwork , 23 ( 92 % ) were non-neoplastic . Sensitivity , specificity , accuracy , positive and negative predictive values of the capillary meshwork for the differential diagnosis of these lesions was 97.8 , 79.3 , 92.8 , 93 and 92 % , respectively . The same parameters for pit pattern analysis by FICE were 92.7 , 82.3 , 90.1 , 93.8 and 80 % , respectively . Indigo carmine magnified chromoscopy showed sensitivity , specificity , accuracy , positive and negative predictive values of 97 , 88.9 , 94.9 , 96.1 and 91.4 % , respectively in the discrimination between neoplastic and non-neoplastic lesions . Conclusion Magnified virtual chromoendoscopy is as accurate as indigo carmine magnified chromoendoscopy in distinguishing between neoplastic from non-neoplastic small colorectal lesions BACKGROUND Digital chromoendoscopy ( DCE ) has the potential for the in vivo optical diagnosis of colon polyps . However , no comparison of different DCE technologies currently exists . OBJECTIVE To compare the diagnostic efficacies of narrow-b and imaging ( NBI ) with those of I-Scan for the real-time histological prediction of diminutive colonic polyps ( DCPs ) ( ≤5 mm ) by using the simple unified endoscopic classification . DESIGN Prospect i ve cohort study . SETTING Academic hospital . PATIENTS In total , 296 DCPs from 142 patients undergoing screening or surveillance colonoscopy were assessed . INTERVENTIONS All DCPs detected during withdrawal were evaluated for the surface details by using high-definition white-light colonoscopy , and thereafter by using DCE ( NBI or I-Scan ) without optical magnification . The histology of all polyps was predicted in real-time and confirmed through the evaluation of biopsy or polypectomy specimens . MAIN OUTCOME MEASUREMENTS Diagnostic efficacies of NBI and I-Scan . RESULTS NBI and I-Scan displayed a significantly higher sensitivity and improved accuracy compared with high-definition white-light colonoscopy for the prediction of adenomas ( P < .05 ) . No significant differences were evident between the NBI and I-Scan ( sensitivity , 88.8 % vs 94.6 % ; specificity , 86.8 % vs 86.4 % ; accuracy , 87.8 % vs 90.7 % , respectively ; P > .05 ) . Additionally , substantial levels of intra- and interobserver agreement between the NBI and I-Scan were measured ( κ values > 0.7 ) . LIMITATIONS No r and omized or crossover design . CONCLUSIONS NBI and I-Scan displayed a similar efficacy for the real-time histological prediction of DCPs . The simple unified endoscopic classification can be used for the interpretation of DCE , regardless of the type of technology . ( CLINICAL TRIAL REGISTRATION NUMBER NCT1133041 . ) BACKGROUND Experts can accurately characterize the histology of diminutive polyps with narrow-b and imaging ( NBI ) . There are limited data on the performance of non-experts . OBJECTIVE To assess the impact of a computer-based teaching module on the accuracy of predicting polyp histology with NBI by non-experts ( in academics and community practice ) by using video clips . DESIGN Prospect i ve , observational study . SETTING Academic and community practice . PARTICIPANTS A total of 15 gastroenterologists participated-5 experts in NBI , 5 non-experts in academic practice , and 5 non-experts in community practice . INTERVENTION Participants review ed a 20-minute , computer-based teaching module outlining the different NBI features for hyperplastic and adenomatous polyps . MAIN OUTCOME MEASUREMENTS Performance characteristics in characterizing the histology of diminutive polyps with NBI by using short video clips before ( pretest ) and after ( posttest ) review ing the teaching module . RESULTS Non-experts in academic practice showed a significant improvement in the sensitivity ( 54 % vs 79 % ; P < .001 ) , accuracy ( 64 % vs 81 % ; P < .001 ) , and proportion of high-confidence diagnoses ( 49 % vs 69 % ; P < .001 ) in the posttest . Non-experts in community practice had significantly higher sensitivity ( 58 % vs 75 % ; P = .004 ) , specificity ( 76 % vs 90 % ; P = .04 ) , accuracy ( 64 % vs 81 % ; P < .001 ) , and proportion of high-confidence diagnoses ( 49 % vs 72 % ; P < .001 ) in the posttest . Performance of experts in NBI was significantly better than non-experts in both academic and community practice . LIMITATIONS Selection bias in selecting good quality videos . Performance not assessed during live colonoscopy . CONCLUSION Academic and community gastroenterologists without prior experience in NBI can achieve significant improvements in characterizing diminutive polyp histology after a brief computer-based training . The durability of these results and applicability in everyday practice are uncertain BACKGROUND In vivo prediction of colorectal polyp histology by narrow-b and imaging ( NBI ) could potentially avoid post-polypectomy histologic examination or resection of diminutive lesions , thereby reducing costs and risk . OBJECTIVE To assess whether NBI is able to predict colonoscopy surveillance intervals and histology of distal diminutive polyps according to American Society for Gastrointestinal Endoscopy ( ASGE ) criteria . DESIGN Prospect i ve , multicenter study . SETTING Five endoscopic centers . PATIENTS Consecutive patients undergoing colonoscopy in 5 centers were included . INTERVENTION Participating endoscopists were required to pass a before- study qualifying examination . Histology of polyps that were < 10 mm was predicted at NBI and assigned a design ation of high or low confidence . MAIN OUTCOME MEASUREMENTS Accuracy of high-confidence NBI prediction for polyps ≤5 mm in predicting surveillance intervals and negative predictive value ( NPV ) for adenomatous histology in the rectosigmoid colon were compared with the ASGE thresholds ( 90 % agreement , 90 % NPV ) . RESULTS A total of 278 patients ( mean age , 63 years ; 58 % male ) were enrolled . At colonoscopy , 574 ( 97.3 % ) polyps < 10 mm ( 429 ≤5 mm , 60 % adenomatous ) were retrieved for histologic analysis . Sensitivity , specificity , positive and negative predictive values , and accuracy of high confidence-NBI predictions for adenomatous histology in lesions ≤5 mm were 90 % , 88 % , 89 % , 89 % , and 89 % , respectively . High-confidence characterization of polyps ≤5 mm predicted the correct surveillance interval in 92 % to 99 % of cases , according to the American and European guidelines . NPV of high-confidence NBI for adenomatous histology for the rectosigmoid colon lesions ≤5 mm was 92 % . LIMITATIONS Only experienced endoscopists were included . CONCLUSION High-confidence prediction of histology for polyps ≤5 mm appears to be sufficiently accurate to avoid post-polypectomy histologic examination of the resected lesions as well as to allow rectosigmoid hyperplastic polyps to be left in place without resection . ( CLINICAL TRIAL REGISTRATION NUMBER NCT01675752 . ) The National Polyp Study ( NPS ) , a r and omized clinical trial to evaluate effective surveillance of patients discovered to have one or more colorectal adenomas , was the framework for this statistical analysis which used a multiple logistic model to assess the independent risk factors of patient and polyp characteristics associated with high- grade dysplasia in adenomas . The data base included 3371 adenomas from 1867 patients . Adenoma size and the extent of the villous component were found to be the major independent polyp risk factors associated with high- grade dysplasia ( p less than 0.0001 ) . The adjusted odds ratios were 3.3 for medium-sized adenomas and 7.7 for large adenomas relative to small adenomas and 2.7 for villous A adenomas , 3.4 for villous B adenomas , and 8.1 for villous C and D adenomas relative to tubular adenomas . Increased frequency of high- grade dysplasia in adenomas located distal to the splenic flexure was attributable mainly to increased size and villous component rather than to location per se . The adjusted odds ratio was 1.4 ( p less than 0.11 ) for left-sided location . Multiplicity of adenomas affected the risk for high- grade dysplasia in patients but was dependent on adenoma size and villous component and was not an independent factor . The adjusted odds ratio was 1.3 ( p less than 0.17 ) for multiplicity . Increasing age was associated with risk for high- grade dysplasia in patients , and this effect was independent of the effect of adenoma size and histological type . The adjusted odds ratio was 1.8 ( p less than 0.0016 ) for age greater than or equal to 60 yr . Gender was not associated with high- grade dysplasia . The adjusted odds ratio was 1.0 ( p less than 0.95 ) for men . The size of the patient series , the prospect i ve nature of the data collection , the completeness of information on all patients , the requirements of complete examination of the entire colon and pathological examination of all lesions encountered , and the exclusion of patients with previously diagnosed adenomas are , collectively , features unique to this study . The detailed model provided by the analysis integrates multiple patient and adenoma factors associated with high- grade dysplasia in colorectal adenomas Introduction . To compare the accuracy of digital and real-time chromoendoscopy for the differential diagnosis of diminutive ( < 5 mm ) neoplastic and nonneoplastic colorectal lesions . Material s and Methods . This is a prospect i ve r and omized study comparing the Fujinon intelligent color enhancement ( FICE ) system ( 65 patients /95 lesions ) and indigo carmine ( 69 patients /120 lesions ) in the analysis of capillary meshwork and pit pattern , respectively . All lesions were less than 5 mm in diameter , and magnification was used in both groups . Histopathology was the gold st and ard examination . Results . Of 215 colorectal lesions , 153 ( 71.2 % ) were adenomas , and 62 were hyperplastic polyps ( 28.8 % ) . Morphological analysis revealed 132 ( 61.4 % ) superficial lesions , with 7 ( 3.3 % ) depressed lesions , and 83 ( 38.6 % ) protruding lesions . Vascular meshwork analysis using FICE and magnification result ed in 91.7 % sensitivity , 95.7 % specificity , and 92.6 % accuracy in differentiating neoplastic from nonneoplastic lesions . Pit pattern analysis with indigo carmine and magnification showed 96.5 % sensitivity , 88.2 % specificity , and 94.2 % accuracy for the same purpose . Conclusion . Both magnifying virtual chromoendoscopy and indigo carmine chromoendoscopy showed high accuracy in the histopathological diagnosis of colorectal lesions less than 5 mm in diameter BACKGROUND & AIMS Colorectal cancer surveillance guidelines rely on clinicohistologic features of adenomas . Unfortunately , in common practice , recording of these features lacks precision and uniformity , which might hamper appropriate follow-up decisions . Confocal laser endomicroscopy ( CLE ) is a novel technology that allows real-time in vivo microscopy of the mucosa and provides accurate histopathology . The aims of this study were ( 1 ) to define and vali date differential features of adenomatous and nonadenomatous colorectal polyps by chromoendoscopy-guided CLE ( C-CLE ) and ( 2 ) to assess predictive value of this technique for diagnosis of colorectal neoplasia . METHODS Patients at risk for colorectal cancer were prospect ively investigated by using CLE . During extubation , fluorescein 10 % was used in conjunction with acriflavine hydrochloride 0.05 % to characterize global tissue architecture as well as cytonuclear features of colorectal epithelium . Ex vivo histology was used as gold st and ard . Reproducibility tests were performed . RESULTS In total , 116 colorectal polyps from 72 patients were examined . Ex vivo histology showed 68 adenomas , 6 invasive carcinomas , 30 hyperplastic polyps , and 12 inflammatory polyps . C-CLE of adenomas revealed lack of epithelial surface maturation , crypt budding , altered vascular pattern , and loss of cell polarity . In contrast , C-CLE of nonadenomatous polyps revealed epithelial surface maturation , and minor abnormalities of crypt architecture and of vascular pattern , and maintained cell polarity . Adenoma dysplasia score reliably discriminated high- grade dysplasia from low- grade dysplasia ( accuracy , 96.7 % ) . Interobserver agreement was high ( K coefficients : pathologist , 0.92 ; endomicroscopist , 0.88 ) . In vivo histology predicted ex vivo data with sensitivity of 97.3 % , specificity of 92.8 % , and accuracy of 95.7 % . CONCLUSIONS C-CLE accurately discriminates adenomatous from nonadenomatous colorectal polyps and enables evaluation of degree of dysplasia during ongoing endoscopy . This technology might offer considerable potential to ultimately fine-tune surveillance programs , particularly in high-risk groups Purpose Aim of the study was the evaluation of high-definition white light ( HDWL ) i-Scan endoscopy for diagnostic prediction of histology , inter- and intraobserver agreement for colorectal polyps . Methods In this prospect i ve single-center cohort study , a skilled endoscopist , with HDWL i-Scan , predicted on real-time the histology of 150 polyps from 78 patients undergoing colonoscopy . Subsequently , four endoscopists , not involved in the collection of cases , predicted the polyps ' histology ( neoplastic vs nonneoplastic ) and repeated the assessment after 6 months . Results Real-time assessment of the lesions predicted a correct histology in 138/150 cases with a sensitivity , specificity , and accuracy of 95 , 82 , and 92 % , respectively . Sensitivity , specificity , and accuracy of post-acquisition evaluation were 87.7 , 61.7 , and 82.2 % , respectively . The κ values of inter- and intraobserver agreement of prediction of histology were 0.462 ( 0.373–0.537 ) and 0.657 ( 0.523–0.917 ) . Among the subset of polyps ( n = 82 ) with good/excellent quality image , sensitivity and accuracy of HDWL i-Scan improved ( 97 % , p = 0.003 and 94 % , p = 0.002 , respectively ) as well as κ value of interobserver agreement ( 0.699 ) . Conclusions HDWL i-Scan technology helps for characterization of polyps of the colon with good accuracy even if it can not replace , at the moment , the histopathological examination . Reproducibility among operators is supported by a moderate substantial interobserver and intraobserver agreement BACKGROUND AND STUDY AIM The real-time identification and removal of adenomas is a cost-effective strategy to improve the prognosis of colorectal cancer . Confocal laser endomicroscopy ( CLE ) could provide real-time histological-level observation . We aim ed to evaluate the efficacy of CLE diagnosis using a simple classification system that differentiates adenomas from non-neoplastic polyps with intravenous fluorescein staining alone . PATIENTS AND METHODS An endoscope integrated confocal laser microscopy system was used in this study . CLE images of 35 colonic polyps , including 15 hyperplastic polyps and 20 adenomas confirmed by histology , were first evaluated to develop criteria for diagnosis of neoplastic and non-neoplastic polyps . The diagnostic criteria included goblet cell depletion , villous architecture , and microvascular alterations . We then performed a prospect i ve study of colonic polyps found during CLE and classified them according to the established criteria . A total of 115 patients with 115 colonic polyps were included . The real-time CLE diagnosis was compared with that from histology . The stored CLE images were evaluated later by a blinded observer . RESULTS The sensitivity , specificity , positive predictive value , and negative predictive value of real-time CLE in identifying colonic adenomas were 93.9 % ( 95 % confidence interval [ CI ] 85.4 - 97.6 ) , 95.9 % ( 95 % CI 86.2 - 98.9 ) , 96.9 % ( 95 % CI 89 - 99 ) , and 92.2 % ( 95 % CI 81 - 97 ) , respectively , compared with histological results . Interobserver agreement between real-time and post-CLE still-image evaluation was excellent ( kappa = 0.929 ) . Goblet cell depletion alone had a sensitivity of 84.9 % ( 95 % CI 73 - 92 ) and a specificity of 87.8 % ( 95 % CI 75 - 95 ) , as well as excellent interobserver agreement ( kappa = 0.824 ) . CONCLUSIONS Endoscope integrated CLE with fluorescein staining may reliably assist in the real-time identification of colonic adenomas . Among three diagnostic categories , goblet cell depletion can be used to distinguish adenomas and hyperplastic polyps BACKGROUND Colonoscopy with narrow-b and imaging can allow real-time determination of polyp histology . OBJECTIVE To determine whether physicians with varying levels of experience can learn and apply endoscopic criteria to distinguish between adenomas and hyperplastic polyps . DESIGN Prospect i ve observational study . SETTING University teaching hospital . PARTICIPANTS This study involved 37 physicians ( medical residents , N = 12 ; gastroenterology fellows , N = 12 ; and gastroenterology faculty , N = 13 ) . INTERVENTION Small-group , 20-minute , didactic teaching sessions in which the endoscopic criteria for determining polyp histology by using narrow-b and imaging were described and demonstrated . MAIN OUTCOME MEASUREMENTS Learning outcomes were evaluated by using written pretests and posttests in which participants scored pathologically verified , high-definition polyp photographs as adenomas or hyperplastic polyps . RESULTS The mean overall scores increased significantly from 47.6 % correct on the pretest to 90.8 % correct on the posttest ( P = .0001 ) . The overall mean percentage of responses answered do n't know was significantly lower on the posttest ( 0.6 % ) compared with the pretest ( 20.5 % , P < .0001 ) . After training , the level of agreement was substantial ( kappa = 0.69 for all participants , kappa = 0.79 for fellows ) . LIMITATIONS Our study did not assess for sustained improvement with time or in vivo accuracy of histological prediction during live colonoscopy . Further validation in a sample of community physicians is required . CONCLUSION A short , didactic teaching session can achieve high accuracy and good interobserver agreement in the use of narrow-b and imaging for determining the histology of colorectal polyps BACKGROUND Computed virtual chromoendoscopy ( CVC ) enables high-definition imaging of mucosal lesions with improved tissue contrast . Previous studies have shown that CVC yields an improved detection rate of colorectal lesions . However , the learning curve for interpretation of CVC images is unknown . OBJECTIVE To examine the learning curve of correctly identifying hyperplastic and adenomatous colorectal lesions by using CVC . DESIGN Prospect i ve , 2-center study . PATIENTS Consecutive patients undergoing screening colonoscopy were included . CVC images were analyzed by using corresponding polypectomies as the reference st and ard followed by a prospect i ve , double-blind review of i-scan images . METHODS A training set containing 20 images with known histology was review ed to st and ardize image interpretation , followed by a blind review of 110 unknown images . Overall , 4 endoscopists from 2 different endoscopy centers evaluated the images , which were obtained by 1 endoscopist using high-definition endoscopy with CVC . RESULTS Patients were included in a prospect i ve fashion . Seventy-seven of 110 colorectal lesions were adenomas and 33 were hyperplastic lesions . Mean diameter of colonic polyps was 4 mm ( range , 2 - 20 mm ) . Overall accuracy for the group was 73.9 % for lesions 1 to 22 , 79.6 % for lesions 23 to 44 , 84.1 % for lesions 45 to 66 , 87.5 % for lesions 67 to 88 , and 94.3 % for lesions 89 to 110 . Accuracy of i-scan for prediction of polyp histology was not dependent on polyp size ( ≤5 mm , 6 - 10 mm , or > 10 mm ) . The ability to obtain high- quality images was stable over time , and high- quality images were constantly produced . LIMITATION Post-hoc assessment . CONCLUSION Accurate interpretation of CVC images for prediction of hyperplastic and adenomatous colorectal lesions follows a learning curve but can be learned rapidly BACKGROUND Accurate colonoscopic assessment of colorectal polyp histology could avoid resection of distal nonadenomatous polyps and reduce costs and risk . OBJECTIVE To assess the accuracy of predicting histology by using narrow-b and imaging ( NBI ) in real time for distal colorectal polyps . DESIGN Prospect i ve observational study . SETTING University hospital and ambulatory surgery center . PATIENTS This study involved 225 consecutive adults undergoing elective screening or surveillance colonoscopy . INTERVENTION We evaluated real-time histology of 235 distal ( rectosigmoid ) colorectal polyps from 31 patients by using high-definition colonoscopy and NBI without optical magnification . For each polyp , the endoscopist described size , Paris classification , and surface characteristics ( vascular and pit pattern , color , pseudodepression ) . Before resection , histology was predicted , and a level of confidence ( high or low ) was assigned . MAIN OUTCOME MEASUREMENTS Sensitivity and negative predictive value of high-confidence endoscopic predictions of adenomatous versus hyperplastic histology for polyps ≤ 5 mm . RESULTS The accuracy of a high-confidence endoscopic prediction was 97.7 % , sensitivity for adenomatous histology 93.9 % , specificity 98.4 % , negative predictive value 97.9 % , and positive predictive value 75.6 % . The performance characteristics for predicting diminutive distal polyps ( ≤ 5 mm ) with high confidence were sensitivity 96.0 % , specificity 99.4 % , negative predictive value 99.4 % , and positive predictive value 96.0 % . LIMITATIONS Single-center study with a single endoscopist . CONCLUSION NBI without optical magnification is sufficiently accurate to allow distal hyperplastic polyps to be left in place without resection and small , distal adenomas to be discarded without pathologic assessment . These findings vali date NBI criteria based on color , vessels , and pit characteristics for predicting real-time colorectal polyp histology BACKGROUND AND AIMS For colonoscopic examinations , the narrow-b and imaging ( NBI ) system is more convenient and timesaving than magnifying chromoendoscopy ( MCE ) . However , the time-saving aspects of NBI techniques have not been assessed . The present study compared interpretation times between NBI and MCE techniques in distinguishing between neoplastic and non-neoplastic small colorectal lesions . METHODS Between January and March 2010 , 693 consecutive patients who underwent colonoscopy at the National Cancer Center Hospital , Tokyo , Japan , were enrolled . When the first lesion was detected by conventional white-light observation , the patient was r and omly assigned to undergo a sequence of NBI and MCE observations ( group A : NBI-MCE , group B : MCE-NBI ) . The time to diagnosis with each modality ( NBI , from changing to NBI until diagnosis ; MCE , from the start of indigo carmine solution spraying until diagnosis ) was recorded by an independent observer . The sensitivity , specificity , and diagnostic accuracy of the first modality used in each group ( NBI or MCE ) were assessed by referring to the histopathological data . RESULTS Seventy-one patients with 137 lesions were r and omized to group A , and 80 patients with 163 lesions to group B. The median interpretation times were 12 s ( interquartile range [ IQR ] : 7 - 19 s ) in group A , and 17 s ( IQR : 12 - 24 s ) in group B , the difference being significant ( P < 0.001 ) . No significant differences were observed between NBI and MCE in terms of sensitivity , specificity , and diagnostic accuracy . CONCLUSIONS NBI reduces the interpretation times for distinguishing between neoplastic and non-neoplastic small lesions during colonoscopies , without loss of diagnostic accuracy BACKGROUND & AIMS When small colorectal lesions are accurately characterized , adenomas can be removed and discarded without formal histopathology analysis . Previous studies in an academic setting showed that many lesions can be managed accurately on the basis of their endoscopic image ( optical diagnosis ) . We performed a prospect i ve study to assess the accuracy of optical diagnosis of small colorectal polyps in a nonacademic setting ( the DISCOUNT trial ) by using high-resolution endoscopy ( HRE ) and narrow-b and imaging ( NBI ) . METHODS During colonoscopy , 1 of 3 nonacademic endoscopists characterized small lesions and declared whether this was done with low or high confidence . In cases of high confidence , the endoscopists decided whether lesions should be removed and discarded or whether they could be left in situ . A surveillance interval was then recommended on-site . RESULTS Of 215 patients in the study , 108 were found to have 281 small lesions . Of these lesions , 231 were characterized with high confidence by using HRE or NBI ; the level of corresponding sensitivity was 77.0 % ( 95 % confidence interval , 68.4 - 83.8 ) , and specificity was 78.8 % ( 95 % confidence interval , 70.6 - 85.2 ) . Of these lesions , 164 were assigned for removal , and 67 were assigned to remain in situ , including 9 adenomas . In 54 patients , a surveillance interval could be recommended on-site that was in line with Dutch guidelines for 44 patients . CONCLUSIONS Even though many lesions were characterized by HRE or NBI with high confidence , optical diagnosis in a nonacademic setting proved to be disappointing , with a sensitivity of 77.0 % and a specificity of 78.8 % . Many lesions were accurately assigned to be removed or remain in situ , although few adenomas were assigned to remain in situ . Also , 19 % of on-site recommendations for a surveillance interval proved to be inaccurate BACKGROUND The presence of meshed capillary ( MC ) vessels is highly sensitive ( 96 % ) and specific ( 92 % ) for diagnosing colorectal neoplasia on colonoscopy by using narrow-b and imaging ( NBI ) with optical magnification , which is not available in North America . However , the efficacy of NBI to identify an MC pattern without optical magnification has not been determined . OBJECTIVE To determine the diagnostic capabilities of NBI colonoscopy without optical magnification in differentiating neoplastic from non-neoplastic colorectal polyps by using the MC pattern . DESIGN Retrospective comparison of prospect ively collected colorectal polyp data . SETTING Large , academic medical center . PATIENTS This study involved 126 consecutive colorectal polyps ( median size 3 mm ) that were found in 52 patients ( 33 men ) with a median age of 59.5 years . INTERVENTION All lesions identified by white-light colonoscopy were prospect ively diagnosed in real-time by using the MC pattern as determined on high-definition NBI , with 1.5x zoom but without true optical magnification , and then endoscopically excised . Surgical pathology was used as the criterion st and ard . MAIN OUTCOME MEASUREMENTS Sensitivity , specificity , positive predictive value , negative predictive value , and accuracy of identifying neoplastic polyps were calculated . RESULTS NBI without optical magnification was found to have a sensitivity of 93 % , specificity of 88 % , positive predictive value of 90 % , negative predictive value of 91 % , and diagnostic accuracy of 91 % when all polyp sizes were considered . For lesions < or = 5 mm , sensitivity was 87 % , specificity was 93 % , positive predictive value was 89 % , negative predictive value was 91 % , and diagnostic accuracy was 90 % . LIMITATIONS Single-center , single-endoscopist experience . CONCLUSION Use of the MC pattern on NBI colonoscopy without optical magnification effectively distinguishes neoplastic from non-neoplastic colorectal polyps . NBI colonoscopy without optical magnification for neoplastic polyp diagnosis appears to be comparable with NBI with optical magnification when the MC pattern is used . A large , prospect i ve trial is needed for further validation BACKGROUND & AIMS A confocal laser endoscopy system has recently been developed that may allow subsurface imaging of living cells in colonic tissue in vivo . The aim of the present study was to assess its potential for prediction of histology during screening colonoscopy for colorectal cancer . METHODS Twenty-seven patients underwent colonoscopy with the confocal endoscope using acriflavine hydrochloride or fluorescein sodium with blue laser illumination . Furthermore , 42 patients underwent colonoscopy with this system using fluorescein sodium . St and ardized locations and circumscript lesions were examined by confocal imaging before taking biopsy specimens . Confocal images were grade d according to cellular and vascular changes and correlated with conventional histology in a prospect i ve and blinded fashion . RESULTS Acriflavine hydrochloride and fluorescein sodium both yielded high- quality images . Whereas acriflavine hydrochloride strongly labeled the superficial epithelial cells , fluorescein sodium offered deeper imaging into the lamina propria . Fluorescein sodium was thus used for the prospect i ve component of the study in which 13,020 confocal images from 390 different locations were compared with histologic data from 1038 biopsy specimens . Subsurface analysis during confocal laser endoscopy allowed detailed analysis of cellular structures . The presence of neoplastic changes could be predicted with high accuracy ( sensitivity , 97.4 % ; specificity , 99.4 % ; accuracy , 99.2 % ) . CONCLUSIONS Confocal laser endoscopy is a novel diagnostic tool to analyze living cells during colonoscopy , thereby enabling virtual histology of neoplastic changes with high accuracy . These newly discovered diagnostic possibilities may be of crucial importance in clinical practice and lead to an optimized rapid diagnosis of neoplastic changes during ongoing colonoscopy BACKGROUND & AIMS Accurate optical analysis of colorectal polyps ( optical biopsy ) could prevent unnecessary polypectomies or allow a " resect and discard " strategy with surveillance intervals determined based on the results of the optical biopsy ; this could be less expensive than histopathologic analysis of polyps . We prospect ively evaluated real-time optical biopsy analysis of polyps with narrow b and imaging ( NBI ) by community-based gastroenterologists . METHODS We first analyzed a computerized module to train gastroenterologists ( N = 13 ) in optical biopsy skills using photographs of polyps . Then we evaluated a practice -based learning program for these gastroenterologists ( n = 12 ) that included real-time optical analysis of polyps in vivo , comparison of optical biopsy predictions to histopathologic analysis , and ongoing feedback on performance . RESULTS Twelve of 13 subjects identified adenomas with > 90 % accuracy at the end of the computer study , and 3 of 12 subjects did so with accuracy ≥90 % in the in vivo study . Learning curves showed considerable variation among batches of polyps . For diminutive rectosigmoid polyps assessed with high confidence at the end of the study , adenomas were identified with mean ( 95 % confidence interval [ CI ] ) accuracy , sensitivity , specificity , and negative predictive values of 81 % ( 73%-89 % ) , 85 % ( 74%-96 % ) , 78 % ( 66%-92 % ) , and 91 % ( 86%-97 % ) , respectively . The adjusted odds ratio for high confidence as a predictor of accuracy was 1.8 ( 95 % CI , 1.3 - 2.5 ) . The agreement between surveillance recommendations informed by high-confidence NBI analysis of diminutive polyps and results from histopathologic analysis of all polyps was 80 % ( 95 % CI , 77%-82 % ) . CONCLUSIONS In an evaluation of real-time optical biopsy analysis of polyps with NBI , only 25 % of gastroenterologists assessed polyps with ≥90 % accuracy . The negative predictive value for identification of adenomas , but not the surveillance interval agreement , met the American Society for Gastrointestinal Endoscopy-recommended thresholds for optical biopsy . Better results in community practice must be achieved before NBI-based optical biopsy methods can be used routinely to evaluate polyps ; Clinical Trials.gov number , NCT01638091 BACKGROUND & AIMS Endoscopic trimodal imaging ( ETMI ) incorporates high-resolution endoscopy ( HRE ) and autofluorescence imaging ( AFI ) for adenoma detection , and narrow-b and imaging ( NBI ) for differentiation of adenomas from nonneoplastic polyps . The aim of this study was to compare AFI with HRE for adenoma detection and to assess the diagnostic accuracy of NBI for differentiation of polyps . This was a r and omized trial of t and em colonoscopies . The study was performed at the Academic Medical Center in Amsterdam . METHODS One hundred patients underwent colonoscopy with ETMI . Each colonic segment was examined twice for polyps , once with HRE and once with AFI , in r and om order per patient . All detected polyps were assessed with NBI for pit pattern and with AFI for color , and subsequently removed . Histopathology served as the gold st and ard for diagnosis . The main outcome measures of this study were adenoma miss-rates of AFI and HRE , and diagnostic accuracy of NBI and AFI for differentiating adenomas from nonneoplastic polyps . RESULTS Among 50 patients examined with AFI first , 32 adenomas were detected initially . Subsequent inspection with HRE identified 8 additional adenomas . Among 50 patients examined with HRE first , 35 adenomas were detected initially . Successive AFI yielded 14 additional adenomas . The adenoma miss-rates of AFI and HRE therefore were 20 % and 29 % , respectively ( P = .351 ) . The sensitivity , specificity , and overall accuracy of NBI for differentiation were 90 % , 70 % , and 79 % , respectively ; corresponding figures for AFI were 99 % , 35 % , and 63 % , respectively . CONCLUSIONS The overall adenoma miss-rate was 25 % ; AFI did not significantly reduce the adenoma miss-rate compared with HRE . Both NBI and AFI had a disappointing diagnostic accuracy for polyp differentiation , although AFI had a high sensitivity BACKGROUND The newly developed i-SCAN application can theoretically maximize the effectiveness of colonoscopy . However , the practical usefulness of the i-SCAN application during screening colonoscopy has not been assessed . OBJECTIVE To assess the efficacy of the i-SCAN application during screening colonoscopy . DESIGN A prospect i ve , r and omized trial that used a modified , back-to-back colonoscopy . SETTING Academic hospital . PATIENTS This study involved 389 asymptomatic , consecutive , average-risk patients who underwent screening colonoscopy . INTERVENTION The patients were r and omized to the first withdrawal with either conventional high-definition white light ( HDWL group ; n = 119 ) , i-SCAN contrast/surface enhancement ( CE/SE ) mode ( i-SCAN1 group ; n = 115 ) , or i-SCAN CE/SE/tone enhancement-colorectal mode ( i-SCAN2 group ; n = 118 ) . All patients underwent a second examination with HDWL as the criterion st and ard . MAIN OUTCOME MEASUREMENTS The primary outcome measurement was the adenoma detection rate and adenoma miss rate . The secondary outcome measurement was the accuracy of the histologic prediction of neoplastic and nonneoplastic polyps . RESULTS The adenoma detection rates during the first withdrawal of HDWL , i-SCAN1 , and i-SCAN2 were 31.9 % , 36.5 % , and 33.1 % , respectively ( P = .742 ) , and the adenoma miss rates of each group were 22.9 % , 19.3 % , and 15.9 % , respectively ( P = .513 ) . Based on the multivariate analysis , the application of i-SCAN was not associated with an improvement in adenoma detection and the prevention of missed polyps . However , the prediction of neoplastic and nonneoplastic colorectal lesions was more precise in the i-SCAN2 group compared with the HDWL group ( accuracy 79.3 % vs 75.5 % , P = .029 ; sensitivity 86.5 % vs 72.6 % , P = .020 ; and specificity 91.4 % vs 80.6 % , P = .040 ) . LIMITATIONS Single-center trial . CONCLUSION i-SCAN during the screening colonoscopy may fail to improve adenoma detection and the prevention of missed polyps , but i-SCAN appears to be effective for real-time histologic prediction of polyps compared with conventional HDWL colonoscopy . ( CLINICAL TRIAL REGISTRATION NUMBER NCT01417611 . ) Background As screening colonoscopy becomes more widespread , the costs for histopathological assessment of resected polyps are rising correspondingly . Reference centres have published highly accurate results for endoscopic polyp classification . Therefore , it has been proposed that , for smaller polyps , the differential diagnosis that guides follow-up recommendations could be based on endoscopy alone . Objective The aim was to prospect ively assess whether the high accuracy for endoscopic polyp diagnosis as reported by reference centres can be reproduced in routine screening colonoscopy . Design Ten experienced private practice endoscopists had initial training in pit patterns . Then they assessed all polyps detected during 1069 screening colonoscopies . Patients ( 46 % men ; mean age 63 years ) were r and omly assigned to colonoscopy with conventional or latest generation HDTV instruments . The main outcome measure was diagnostic accuracy of in vivo polyp assessment ( adenomatous vs hyperplastic ) . Secondary outcome measures were differences between endoscopes and reliability of image-based follow-up recommendations ; a blinded post hoc analysis of polyp photographs was also performed . Results 675 polyps were assessed ( 461 adenomatous , 214 hyperplastic ) . Accuracy , sensitivity and specificity of in vivo diagnoses were 76.6 % , 78.1 % and 73.4 % ; size of adenomas and endoscope withdrawal time significantly influenced accuracy . Image-based recommendations for post-polypectomy surveillance were correct in only 69.5 % of cases . Post hoc analysis of polyp photographs did not improve accuracy . Conclusions In everyday practice , endoscopic classification of polyp type is not accurate enough to ab and on histopathological assessment and use of latest generation colonoscopes does not improve this . Image-based surveillance recommendations after polypectomy would consequently not meet guideline requirements . TrialRegNo NCT01297712 BACKGROUND AND STUDY AIMS Probe-based confocal laser endomicroscopy ( pCLE ) is a new imaging modality that enables histological examination of gastrointestinal mucosa during endoscopic procedures . Most studies have evaluated offline interpretation of pCLE images . In clinical practice , real-time interpretation is necessary to assist decision-making during the procedure . The aim of this pilot study was to compare the accuracy of real-time pCLE diagnosis made during the procedure with that of blinded offline interpretation to provide accuracy estimates that will aid the planning of future studies . PATIENTS AND METHODS pCLE was performed in patients undergoing screening and surveillance colonoscopy . Once a polyp had been identified , one endoscopist analyzed pCLE images during the procedure and made a provisional " real-time " diagnosis . Saved video recordings were de-identified , r and omized , and review ed " offline " 1 month later by the same endoscopist , who was blinded to the original diagnoses . RESULTS Images from a total of 154 polyps were recorded ( 80 neoplastic , 74 non-neoplastic ) . The overall accuracy of real-time pCLE diagnosis ( accuracy 79 % , sensitivity 81 % , specificity 76 % ) and offline pCLE diagnosis ( 83 % , 88 % , and 77 % , respectively ) for all 154 polyps were similar . Among polyps < 10 mm in size , the accuracy of real-time interpretation was significantly lower ( accuracy 78 % , sensitivity 71 % , specificity 83 % ) than that of offline pCLE interpretation ( 81 % , 86 % , 78 % , respectively ) . For polyps ≥ 10 mm , the accuracy of pCLE diagnosis in real-time was better ( accuracy 85 % , sensitivity 90 % , specificity 75 % ) than offline pCLE diagnosis ( 81 % , 97 % , and 50 % , respectively ) . CONCLUSIONS These results suggest that real-time and offline interpretations of pCLE images are moderately accurate . Real-time interpretation is slightly less accurate than offline diagnosis , but overall both are comparable . Additionally , there was contrasting accuracy between the two methods for small and large polyps BACKGROUND & AIMS There are limited data describing the performance of Fuji Intelligent Color Enhancement ( FICE , EC 590 ZW ; Fujinon Inc , Saitama , Japan ) for differentiating polyp histologies during screening colonoscopy . We evaluated the ability of an endoscopist to diagnose small polyp histology during a screening colonoscopy using FICE . METHODS A prospect i ve study was performed on 763 consecutive , asymptomatic subjects who were undergoing screening colonoscopy . Pit patterns and vascular patterns were used to predict the histology of 525 polyps ( mean size , 4.5 ± 2.2 mm , 315 adenomas ) of less than 10 mm using FICE with high magnification and without . The performances of the FICE analyses were calculated and compared with the results from the histopathology . RESULTS The overall accuracy achieved by FICE with high magnification in the diagnosis of adenomas of less than 10 mm ( 87.0 % ) was significantly greater than that achieved without high magnification ( 80.4 % ; P < .05 ) . Moreover , the improvement of accuracy attained when using high-magnification FICE was most pronounced and significant compared without using high-magnification FICE in the diagnosis for diminutive polyps ( ≤5 mm ; 85.4 % vs 79.1 % ; P < .05 ) . Among all types of adenomas , the sensitivity of FICE was lowest for sessile serrated adenomas ( 38.5 % vs 89.4 % ; P < .01 ) , even when FICE was used with high magnification . CONCLUSIONS FICE with high magnification is better for differentiating the histology of small polyps during screening colonoscopy than FICE without high magnification , especially for diminutive polyps . Large-scale studies are needed to improve the identification of serrated adenomas and small diminutive polyps using FICE BACKGROUND There is no widely adopted , easily applied method for distinguishing between adenomatous and nonadenomatous polyps during real-time colonoscopy . OBJECTIVE To compare white light ( WL ) with narrow-b and imaging ( NBI ) for the differentiation of colorectal polyps in vivo and to assess for a learning curve . DESIGN A prospect i ve polyp series . PATIENTS AND SETTING A total of 302 patients referred for colonoscopy , between August 2006 and July 2007 , to a single tertiary-referral center in the United States . INTERVENTION St and ard WL colonoscopy was performed with Olympus 180-series colonoscopes . Each detected polyp was first characterized by WL and then by NBI . Modified Kudo pit pattern and vascular color intensity ( VCI ) were recorded , and the histology was predicted . Endoscopists were given feedback every 2 weeks . MAIN OUTCOME MEASUREMENTS Overall accuracy and sensitivity and specificity of endoscopic diagnosis by using WL alone and with NBI , as well as improvement in endoscopists ' performance . RESULTS A total of 265 polyps were found in 131 patients . Diagnostic accuracy was 80 % with NBI and 77 % with WL ( P = .35 ) . NBI performed better than WL in diagnosing adenomas ( sensitivity 80 % vs 69 % , P < .05 ) . Nonadenomatous polyps were more likely to have a " light " VCI compared with adenomas ( 71 % vs 29 % , P < .001 ) . During the second half of the study , NBI accuracy improved , from 74 % to 87 % , and outperformed an unchanged WL accuracy of 79 % ( P < .05 ) . CONCLUSIONS Overall , NBI was not more accurate than WL in differentiating colorectal polyps in vivo ; however , once a learning curve was achieved , NBI performed significantly better . Further refinements of an NBI pit-pattern classification and VCI scale are needed before broad application to clinical decisions regarding the necessity of polypectomy BACKGROUND Accurate optical diagnosis of small ( < 10 mm ) colorectal polyps in vivo , without formal histopathology , could make colonoscopy more efficient and cost effective . The aim of this study was to assess whether optical diagnosis of small polyps is feasible and safe in routine clinical practice . METHODS Consecutive patients with a positive faecal occult blood test or previous adenomas undergoing surveillance at St Mark 's Hospital ( London , UK ) , from June 19 , 2008 , to June 16 , 2009 , were included in this prospect i ve study . Four colonoscopists with different levels of experience predicted polyp histology using optical diagnosis with high-definition white light , followed by narrow-b and imaging without magnification and chromoendoscopy , as required . The primary outcome was accuracy of polyp characterisation using optical diagnosis compared with histopathology , the current gold st and ard . Accuracy of optical diagnosis to predict the next surveillance interval was also assessed and compared with surveillance intervals predicted by current guidelines using histopathology . This study is registered with Clinical Trials.gov , NCT00888771 . FINDINGS 363 polyps smaller than 10 mm were detected in 130 patients , of which 278 polyps had both optical and histopathological diagnosis . By histology , 198 of these polyps were adenomas and 80 were non-neoplastic lesions ( of which 62 were hyperplastic ) . Optical diagnosis accurately diagnosed 186 of 198 adenomas ( sensitivity 0.94 ; 95 % CI 0.90 - 0.97 ) and 55 of 62 hyperplastic polyps ( specificity 0.89 ; 0.78 - 0.95 ) , with an overall accuracy of 241 of 260 ( 0.93 , 0.89 - 0.96 ) for polyp characterisation . Using optical diagnosis alone , 82 of 130 patients could be given a surveillance interval immediately after colonoscopy , and the same interval was found after formal histopathology in 80 patients ( 98 % ) using British guidelines and in 78 patients ( 95 % ) using US multisociety guidelines . INTERPRETATION For polyps less than 10 mm in size , in-vivo optical diagnosis seems to be an acceptable strategy to assess polyp histopathology and future surveillance intervals . Dispensing with formal histopathology for most small polyps found at colonoscopy could improve the efficiency of the procedure and lead to substantial savings in time and cost . FUNDING Leigh Family Trust , London , UK BACKGROUND Previous reports assessing diagnostic skill using narrow-b and imaging ( NBI ) and pit pattern analysis for colorectal polyps involved only highly experienced endoscopists . OBJECTIVE To evaluate diagnostic skills of less-experienced endoscopists ( LEE group ) for differentiation of diminutive colorectal polyps by using NBI and pit pattern analysis with and without magnification after an exp and ed training program . DESIGN Prospect i ve study . PATIENTS This study involved 32 patients with 44 colorectal polyps ( 27 adenomas and 17 hyperplastic polyps ) of < or = 5 mm that were identified and analyzed by using conventional colonoscopy as well as non-magnification and magnification NBI and chromoendoscopy followed by endoscopic removal for histopathological analysis . INTERVENTION Before a training course , 220 endoscopic images were distributed in r and omized order to residents with no prior endoscopy experience ( NEE group ) and to the LEE group , who had performed colonoscopies for more than 5 years but had never used NBI . The 220 images were also distributed to highly experienced endoscopists ( HEE group ) who had routinely used NBI for more than 5 years . The images were distributed to the NEE and LEE groups again after a training class . Magnification NBI and chromoendoscopy images were assessed by using the Sano and Kudo classification systems , respectively . MAIN OUTCOME MEASUREMENTS Diagnostic accuracy and interobserver agreement for each endoscopic modality in each group . RESULTS Diagnostic accuracy was significantly higher , and kappa ( kappa ) values improved in the LEE group for NBI with high magnification after exp and ed training . Diagnostic accuracy and kappa values when using high-magnification NBI were highest among endoscopic techniques for the LEE group after such training and the HEE group ( accuracy 90 % vs 93 % ; kappa = 0.79 vs 0.85 , respectively ) . LIMITATIONS Study involved only polyps of < or = 5 mm . CONCLUSION Using high-magnification NBI increased the differential diagnostic skill of the LEE group after exp and ed training so that it was equivalent to that of the HEE group BACKGROUND Recent technological advances in miniaturisation have allowed for a confocal scanning microscope to be integrated into trans-endoscopic probes enabling endoscopists to collect in vivo virtual biopsies of the gastrointestinal mucosa during endoscopy . AIMS The aim of the present study was to assess prospect ively the clinical applicability and predictive power of a probe-based confocal laser endomicroscopy for the in vivo diagnosis of colorectal neoplasia . METHODS Patients with evidence of colorectal superficial neoplasia at routine endoscopy , were included prospect ively in this study . Lesions were identified using white-light endoscopy followed by pCLE imaging recorded by a Coloflex UHD-type probe . The images were interpreted as either neoplastic or not according to vascular and cellular changes . pCLE readings were then compared with histopathological results from endoscopically resected lesions and /or targeted biopsy specimens . RESULTS A total of 32 lesions were identified in 20 consecutive patients . Histopathology diagnosis was of adenomas in 19 cases , hyperplastic polyps in 11 cases and adenocarcinoma in 2 cases . For the detection of neoplastic tissue pCLE had a sensitivity of 100 % , a specificity of 84.6 % , an accuracy of 92.3 , a PPV of 90.5 % and a NPV of 100 % . CONCLUSIONS pCLE permits high- quality imaging , enabling prediction of intraepithelial neoplasia with a high level of accuracy INTRODUCTION Colonoscopy is the accepted gold st and ard for the detection of colorectal cancer . The aim of the current study was to prospect ively compare high definition plus ( HD+ ) colonoscopy with I-Scan functionality ( electronic staining ) vs. st and ard video colonoscopy . The primary endpoint was the detection of patients having colon cancer or at least one adenoma . METHODS A total of 220 patients due to undergo screening colonoscopy , postpolypectomy surveillance or with a positive occult blood test were r and omized in a 1 : 1 ratio to undergo HD+ colonoscopy in conjunction with I-Scan surface enhancement ( 90i series , Pentax , Tokyo , Japan ) or st and ard video colonoscopy ( EC-3870FZK , Pentax ) . Detected colorectal lesions were judged according to type , location , and size . Lesions were characterized in the HD+ group by using further I-Scan functionality ( p- and v-modes ) to analyze pattern and vessel architecture . Histology was predicted and biopsies or resections were performed on all identified lesions . RESULTS HD+ colonoscopy with I-Scan functionality detected significantly more patients with colorectal neoplasia ( 38 % ) compared with st and ard resolution endoscopy ( 13 % ) ( 200 patients finally analyzed ; 100 per arm ) . Significantly more neoplastic ( adenomatous and cancerous ) lesions and more flat adenomas could be detected using high definition endoscopy with surface enhancement . Final histology could be predicted with high accuracy ( 98.6 % ) within the HD+ group . CONCLUSIONS HD+ colonoscopy with I-Scan is superior to st and ard video colonoscopy in detecting patients with colorectal neoplasia based on this prospect i ve , r and omized , controlled trial BACKGROUND The American Society for Gastrointestinal Endoscopy ( ASGE ) recently developed thresholds for the performance characteristics of technologies for real-time assessment of histology of diminutive ( ≤ 5 mm ) colon polyps . Narrow-b and imaging ( NBI ) has been shown to predict polyp histology with moderate to high accuracy in several studies . OBJECTIVE To determine whether in vivo optical diagnosis of polyp histology by using NBI can reach the 2 benchmarks set forth by the ASGE . DESIGN Retrospective analysis of data from 3 prospect i ve clinical trials . SETTING Two tertiary referral centers . PATIENTS Subjects undergoing screening or surveillance colonoscopy . INTERVENTIONS In vivo optical diagnosis of polyp histology by using NBI . MAIN OUTCOME MEASUREMENT Accuracy in predicting colonoscopy surveillance intervals , negative predictive value ( NPV ) for diagnosing adenomatous histology in the rectosigmoid . RESULTS A total of 410 patients met the inclusion /exclusion criteria and had at least 1 polyp seen and resected during colonoscopy . Using in vivo optical diagnosis instead of histopathology for all diminutive polyps predicted the correct colonoscopy surveillance interval in 86 % to 94 % patients . When optical diagnosis was limited to diminutive polyps in the rectosigmoid only , the NPV for diagnosing adenomatous histology with NBI was 95 % . LIMITATIONS Retrospective analysis from tertiary referral centers . CONCLUSIONS The threshold NPV for diagnosing adenomatous histology in diminutive rectosigmoid polyps recently set forth by the ASGE can be achieved by using NBI . The threshold accuracy rate for predicting surveillance interval recommendations can be reached by using NBI , but only if patients with 1 to 2 small adenomas without advanced features have a repeat colonoscopy in 10 years Real‐time optical diagnosis of colorectal polyps may lead to substantial time and cost savings and could potentially reduce complications associated with polypectomy . We prospect ively assessed the utility of a novel narrow‐b and imaging ( NBI ) system with dual focus magnification ( DF ) in differentiating colorectal polyps in consecutive patients undergoing colonoscopy BACKGROUND & AIMS The ability to determine colorectal polyp pathology by endoscopy could reduce the risks of polypectomy and the cost of pathologic evaluation . This study evaluated the ability of the Olympus Exera 180 high-definition colonoscope ( Olympus America , Inc , Center Valley , PA ) , with narrow-b and imaging , to predict colorectal polyp histology . METHODS A library of 320 endoscopic photographs with correlated histologic information was used to identify endoscopic features associated with adenomatous and hyperplastic histology . These features were tested in a prospect i ve study of 451 consecutively identified colorectal polyps . Polyps were observed endoscopically and assigned a design ation of high or low confidence . The primary end points were the predictive value of high-confidence endoscopic interpretations of adenoma and hyperplastic histology for polyps 5 mm and smaller in size . RESULTS Endoscopic predictions of adenoma and hyperplastic histology were made with high confidence for 80 % and 83 % of cases , respectively . High-confidence predictions were more likely than low-confidence predictions to be correct ( P<.001 ) . High-confidence predictions of adenoma and hyperplastic histology were correct for 91 % and 95 % , respectively , of polyps 5 mm and smaller in size . CONCLUSIONS Introduction of confidence levels to the endoscopic interpretation of colorectal polyp histology allows sufficient accuracy for the use of the Exera narrow-b and imaging system in the identification of distal hyperplastic polyps that do not need resection , as well as to plan postpolypectomy surveillance without pathologic evaluation of polyps 5 mm in size or smaller BACKGROUND AND STUDY AIMS The resolution of endoscopes has increased in recent years . Modern Fujinon colonoscopes have a charge-coupled device ( CCD ) pixel density of 650,000 pixels compared with the 410,000 pixel CCD in st and ard-definition scopes . Acquiring high-definition scopes represents a significant capital investment and their clinical value remains uncertain . The aim of the current study was to investigate the impact of high-definition endoscopes on the in vivo histology prediction of colonic polyps . PATIENTS AND METHODS Colonoscopy procedures were performed using Fujinon colonoscopes and EPX-4400 processor . Procedures were r and omized to be performed using either a st and ard-definition EC-530 colonoscope or high-definition EC-530 and EC-590 colonoscopes . Polyps of < 10 mm were assessed using both white light imaging ( WLI ) and flexible spectral imaging color enhancement ( FICE ) , and the predicted diagnosis was recorded . Polyps were removed and sent for histological analysis by a pathologist who was blinded to the endoscopic diagnosis . The predicted diagnosis was compared with the histology to calculate the accuracy , sensitivity , and specificity of in vivo assessment using either st and ard or high-definition scopes . RESULTS A total of 293 polyps of < 10 mm were examined–150 polyps using the st and ard-definition colonoscope and 143 polyps using high-definition colonoscopes . There was no difference in sensitivity , specificity or accuracy between the two scopes when WLI was used ( st and ard vs. high : accuracy 70 % [ 95 % CI 62–77 ] vs. 73 % [ 95 % CI 65–80 ] ; P=0.61 ) . When FICE was used , high-definition colonoscopes showed a sensitivity of 93 % compared with 83 % for st and ard-definition colonoscopes ( P=0.048 ) ; specificity was 81 % and 82 % , respectively . CONCLUSIONS There was no difference between high- and st and ard-definition colonoscopes when white light was used , but FICE significantly improved the in vivo diagnosis of small polyps when high-definition scopes were used compared with st and ard definition Objectives At present , all colonic polyps are removed and sent for histopathological evaluation , result ing in laboratory and reporting costs . Recent American Society for Gastrointestinal Endoscopy ( ASGE ) guidelines have set st and ards for in-vivo diagnosis in place of conventional histopathology , and all future technologies will have to be tested against these st and ards . Data on flexible spectral imaging color enhancement ( FICE ) were very limited . This study aims to evaluate the accuracy of FICE and indigo carmine ( IC ) for in-vivo histology prediction for polyps of less than 10 mm in size and to assess the economic impact of this strategy . Methods In a screening population , polyps of less than 10 mm were assessed using white light ( WLI ) by FICE , by IC , and the predicted diagnosis was recorded . Polyps were then removed and sent for histological analysis . Accuracy of the predicted rescope interval was calculated using British Society of Gastroenterology and ASGE guidelines . Two models for using in-vivo diagnosis were proposed and savings in terms of histopathology costs calculated . Results A total of 232 polyps of less than 10 mm were examined . FICE improved the accuracy of in-vivo diagnosis of adenoma to 88 % compared with 75 % with WLI ( P<0.0001 ) . IC after FICE improved this further to 94 % . Rescope interval could be set correctly using FICE or IC in 97 % of cases by British Society of Gastroenterology guidelines or 97 % with FICE and 99 % with IC using ASGE guidelines . A saving of £ 678 253 ( & OV0556;762767 ) per annum could be made within the UK national screening population . Conclusion FICE and IC significantly improves the in-vivo diagnosis of colonic polyps over WLI and can lead to significant cost savings BACKGROUND Discriminating neoplastic from non-neoplastic polyps can significantly reduce the cost of colonoscopy . The American Society for Gastrointestinal Endoscopy ( ASGE ) recently set threshold levels for optical diagnostic accuracy to be acceptable for clinical use . OBJECTIVE In this study , we compare a novel colonoscope capable of dual-focus imaging with st and ard colonoscopy with respect to the ASGE guidelines . SETTING An academic medical center ambulatory surgical center . PATIENTS AND INTERVENTIONS Patients at average risk were r and omized to st and ard colonoscopy ( Olympus CF-H180 and Exera II 180 colonoscopes , Olympus America , Center Valley , Pa ) or dual-focus colonoscopy ( Olympus CF-HQ190 and Exera III 190 colonoscopes , Olympus America ) . All polyps were given an optical diagnosis and compared with histology . RESULTS A total of 600 patients were consented and 522 completed all aspects of the procedure . A total of 927 polyps were analyzed . Optical diagnostic accuracy was 79 % ( 95 % confidence interval , 74%-83 % ) for the 190 and 77 % ( 95 % confidence interval , 73%-81 % ) for the 180 colonoscope . Adenoma detection rates were also similar between the 2 groups ( 50 % for the 190 vs 52 % for the 180 colonoscope ) . For small distal rectosigmoid polyps with a high confidence diagnosis , the negative predictive value for adenoma was 96 % ( range 89%-99 % ) for the 180 in the narrow-b and imaging ( NBI ) mode and 97 % ( range 88%-99 % ) for the 190 colonoscope in NBI mode . Agreement of surveillance intervals by using optical diagnosis was 94 % to 95 % for all modalities ( 180 and 190 colonoscopes , white light imaging , NBI ) . LIMITATIONS Our study evaluated the accuracy of the 180 and 190 colonoscopes at a center with already-established expertise in endoscopic imaging . CONCLUSIONS Both traditional and new dual-focus colonoscopes provide highly accurate optical polyp discrimination . There was no difference between the 2 systems in terms of discrimination or adenoma detection . Both systems are consistent with ASGE guidelines for optical diagnosis of selected colorectal polyps without histological confirmation BACKGROUND Although microvascular vessels on the surface of colorectal polyps are observed by narrow-b and imaging ( NBI ) with magnification , its clinical usefulness is still uncertain . OBJECTIVE Our purpose was to evaluate the usefulness of meshed capillary ( MC ) vessels observed by NBI magnification for differentiating between nonneoplastic and neoplastic colorectal lesions . DESIGN Prospect i ve polyp study . SETTING National Cancer Center Hospital East , Chiba , Japan . PATIENTS A total of 702 consecutive patients who underwent total colonoscopy between September and December 2004 were prospect ively evaluated . Patients with polyps > 10 mm and those with polyps previously evaluated by histologic examination or colonoscopy were excluded . INTERVENTION Lesions were classified into 2 groups : polyps with invisible or faintly visible MC vessels as nonneoplastic and polyps with clearly visible MC vessels as neoplastic . Lesions judged as nonneoplastic were subjected to biopsy and those as neoplastic were removed endoscopically . Histologic analysis was performed in all lesions . MAIN OUTCOME MEASUREMENT Visible or invisible surface MC vessels , prediction of histologic diagnosis . RESULTS Of 92 eligible patients enrolled in this study , 150 lesions , including 39 ( 26 % ) hyperplastic polyps and 111 ( 74 % ) adenomatous polyps , were detected . Observation of MC vessels detected 107 of 111 neoplastic polyps and 36 of 39 nonneoplastic polyps . The overall diagnostic accuracy , sensitivity , and specificity were 95.3 % , 96.4 % , and 92.3 % , respectively . LIMITATIONS MC vessel judgment performed by a single colonoscopist with extensive experience in magnifying NBI . CONCLUSION Observation of surface MC vessels by magnifying NBI is a useful and simple method for differentiating colorectal nonneoplastic and neoplastic polyps BACKGROUND AND STUDY AIMS Narrow b and imaging ( NBI ) can accurately characterize colonic polyps using microvascular appearances . We aim ed to assess whether the Kudo pit pattern classification is accurate when used with NBI ( without dye-spray ) , and if microvascular appearances or NBI pit patterns maintain accuracy for polyp characterization at sizes < 10 mm . PATIENTS AND METHODS 116 polyps < 10 mm in size were detected in 62 patients undergoing surveillance colonoscopy . The polyps were prospect ively assessed using NBI and magnification for Kudo pit pattern ( III-V neoplastic , I-II non-neoplastic ) and vascular pattern intensity ( VPI ) , a measure of microvascular density ( strong VPI , neoplastic ; normal or weak VPI , non-neoplastic ) . Sensitivity , specificity , and accuracy were calculated and compared with results from histopathology . RESULTS The mean polyp size was 3.4 mm ( range 1 - 9 mm ) . Overall , NBI pit pattern sensitivity , specificity , and accuracy were 0.88 , 0.91 , and 89.6 % , respectively . Equivalent values for VPI were 0.94 , 0.89 , and 91.4 % . Results were similar when polyps were subdivided into diminutive polyps ( size < or= 5 mm ) and flat polyps . Combining both pit pattern and VPI improved the sensitivity ( 0.98 , P = 0.06 versus NBI pit pattern alone ) . There was very good agreement between NBI pit pattern and VPI for prediction of dysplasia ( kappa = 0.83 ) . No evidence of a learning curve for VPI was found . The NBI pit pattern was better than the VPI at subclassifying hyperplastic from other non-neoplastic polyps ( sensitivity 0.79 versus 0.56 , respectively , P = 0.02 ) , but accuracy was poor . CONCLUSION The NBI pit pattern and VPI are both highly accurate in characterizing neoplastic colonic polyps of < 10 mm , with VPI appearing to be simple to learn . NBI has the potential to replace conventional histology for small polyps BACKGROUND The diagnostic accuracy of conventional endoscopy for small colonic polyps is not satisfactory . Optimal b and imaging ( OBI ) enhances the contrast of the mucosal surface without the use of dye . OBJECTIVE To evaluate the diagnostic accuracy for the differentiation of neoplastic and non-neoplastic colorectal polyps by using magnified OBI colonoscopy . DESIGN An open prospect i ve study . SETTING Jichi Medical University , Japan . PATIENTS A total of 133 colonoscopy cases . MAIN OUTCOME MEASUREMENT A comparative study of the overall accuracy , sensitivity , and specificity for the differentiation of neoplastic and non-neoplastic colorectal polyps < or = 5 mm in size by capillary-pattern diagnosis by using conventional colonoscopy , capillary-pattern diagnosis in OBI , and pit-pattern diagnosis in chromoendoscopy with low magnification . RESULTS A total of 107 polyps , composed of 80 neoplastic and 27 non-neoplastic polyps , were evaluated . OBI clearly showed the capillary network of the surface mucosa of neoplastic polyps at low magnification , whereas the surface mucosa of non-neoplastic polyps showed up as a pale lesion . The capillary pattern in conventional colonoscopy had 74 % accuracy , 71 % sensitivity , and 81 % specificity for neoplastic polyps . The accuracy and sensitivity were significantly lower than those that used the capillary pattern in OBI ( accuracy 87 % and sensitivity 93 % ) and the pit pattern in chromoendoscopy ( accuracy 86 % and sensitivity 90 % ) . There were no significant differences in specificity ( OBI 70 % and chromoendoscopy 74 % ) . The kappa analysis indicated good agreement in both OBI and chromoendoscopy . CONCLUSIONS Capillary-pattern diagnosis in OBI is superior to that in conventional endoscopy and is not significantly different from pit-pattern diagnosis for predicting the histology of small colorectal polyps BACKGROUND & AIMS Probe-based confocal laser endomicroscopy ( pCLE ) allows in vivo imaging of tissue at micron resolution . Virtual chromoendoscopy systems , such as Fujinon intelligent color enhancement and narrow b and imaging , also have potential to differentiate neoplastic colorectal lesions . The accuracy of these systems in clinical practice is , however , unknown . Our primary aim was to compare sensitivity and specificity of pCLE to virtual chromoendoscopy for classification of colorectal polyps using histopathology as a gold st and ard . A secondary aim was to compare sensitivity and specificity of pCLE to virtual chromoendoscopy using a modified gold st and ard that assumed that all polyps > /=10 mm had malignant potential and were considered neoplastic or high risk . METHODS Patients underwent colonoscopy using high-resolution colonoscopes . The surface pit pattern was determined with NBI or FICE in all patients . Confocal images were recorded and subsequently analyzed offline , blinded to the endoscopic characteristics and histopathology . Each polyp was diagnosed as benign or neoplastic based on confocal features according to modified Mainz criteria . RESULTS A total of 119 polyps ( 81 neoplastic , 38 hyperplastic ) from 75 patients was assessed . The pCLE had higher sensitivity compared to virtual chromoendoscopy when considering histopathology as gold st and ard ( 91 % vs 77 % ; P = .010 ) and modified gold st and ard ( 88 % vs 76 % ; P = .037 ) . There was no statistically significant difference in specificity between pCLE and virtual chromoendoscopy when considering histopathology or modified gold st and ard . CONCLUSIONS Confocal endomicroscopy demonstrated higher sensitivity with similar specificity in classification of colorectal polyps . These new methods may replace the need for ex vivo histological confirmation of small polyps , but further studies are warranted |
12,095 | 27,497,794 | Conclusions : Weak evidence suggests that infobuttons can help providers answer clinical questions . | Objective : Infobuttons appear as small icons adjacent to electronic health record ( EHR ) data ( e.g. , medications , diagnoses , or test results ) that , when clicked , access online knowledge re sources tailored to the patient , care setting , or task .
Infobuttons are required for “ Meaningful Use ” certification of US EHRs .
We sought to evaluate infobuttons ’ impact on clinical practice and identify features associated with improved outcomes . | OBJECTIVE Infobuttons are message-based content search and retrieval functions embedded within other applications that dynamically return information relevant to the clinical task at h and . The objective of this study was to determine whether infobuttons effectively answer providers ' questions about medications or affect patient care decisions . DESIGN The authors implemented and evaluated a medication infobutton application called KnowledgeLink . Health care providers at 18 outpatient clinics were r and omized to one of two versions of KnowledgeLink , one that linked to information from Micromedex ( Thomson Micromedex , Greenwood Village , Co ) and the other to material from SkolarMD ( Wolters Kluwer Health , Palo Alto , CA ) . MEASUREMENTS Data were collected about the frequency of use and demographics of users , patients , and drugs that were queried . Users were periodically surveyed with short question naires and then with a more extensive survey at the end of one year . RESULTS During the first year , KnowledgeLink was used 7,972 times by 359 users to look up information about 1,723 medications for 4,961 patients . Clinicians used KnowledgeLink twice a month on average , and during an average of 1.2 % of patient encounters . KnowledgeLink was used by a wide variety of medical staff , not just physicians and nurse practitioners . The frequency of usage and the questions asked varied with user role ( primary care physician , specialist physician , nurse practitioner ) . Although the median KnowledgeLink session was brief ( 21 seconds ) , KnowledgeLink answered users ' queries 84 % of the time , and altered patient care decisions 15 % of the time . Users rated KnowledgeLink favorably on multiple scales , recommended extending KnowledgeLink to other content domains , and suggested enhancing the interface to allow refinement of the query and selection of the target re source . CONCLUSION An infobutton can satisfy information needs about medications . Although used infrequently and for brief sessions , KnowledgeLink was positively received , answered most users ' questions , and had a significant impact on medical decision making . The next steps would be to broaden the domains that KnowledgeLink covers to more specifically tailor results to the user type , to provide options when queries are not immediately answered , and to implement KnowledgeLink within other electronic clinical applications OBJECTIVE Authors evaluated whether displaying context sensitive links to infrequently accessed educational material s and patient information via the user interface of an inpatient computerized care provider order entry ( CPOE ) system would affect access rates to the material s. DESIGN The CPOE of V and erbilt University Hospital ( VUH ) included " baseline " clinical decision support advice for safety and quality . Authors augmented this with seven new primarily educational decision support features . A prospect i ve , r and omized , controlled trial compared clinicians ' utilization rates for the new material s via two interfaces . Control subjects could access study -related decision support from a menu in the st and ard CPOE interface . Intervention subjects received active notification when study -related decision support was available through context sensitive , visibly highlighted , selectable hyperlinks . MEASUREMENTS Rates of opportunities to access and utilization of study -related decision support material s from April 1999 through March 2000 on seven VUH Internal Medicine wards . RESULTS During 4,466 intervention subject-days , there were 240,504 ( 53.9/subject-day ) opportunities for study -related decision support , while during 3,397 control subject-days , there were 178,235 ( 52.5/subject-day ) opportunities for such decision support , respectively ( p = 0.11 ) . Individual intervention subjects accessed the decision support features at least once on 3.8 % of subject-days logged on ( 278 responses ) ; controls accessed it at least once on 0.6 % of subject-days ( 18 responses ) , with a response rate ratio adjusted for decision support frequency of 9.17 ( 95 % confidence interval 4.6 - 18 , p < 0.0005 ) . On average , intervention subjects accessed study -related decision support material s once every 16 days individually and once every 1.26 days in aggregate . CONCLUSION Highlighting availability of context -sensitive educational material s and patient information through visible hyperlinks significantly increased utilization rates for study -related decision support when compared to " st and ard " VUH CPOE methods , although absolute response rates were low Abstract Objectives : To characterise the information needs of family doctors by collecting the questions they asked about patient care during consultations and to classify these in ways that would be useful to developers of knowledge bases . Design : Observational study in which investigators visited doctors for two half days and collected their questions . Taxonomies were developed to characterise the clinical topic and generic type of information sought for each question . Setting : Eastern Iowa . Participants : R and om sample of 103 family doctors . Main outcome measures : Number of questions posed , pursued , and answered ; topic and generic type of information sought for each question ; time spent pursuing answers ; information re sources used . Results : Participants asked a total of 1101 questions . Questions about drug prescribing , obstetrics and gynaecology , and adult infectious disease were most common and comprised 36 % of all questions . The taxonomy of generic questions included 69 categories ; the three most common types , comprising 24 % of all questions , were “ What is the cause of symptom X ? ” “ What is the dose of drug X ? ” and “ How should I manage disease or finding X ? ” Answers to most questions ( 702 , 64 % ) were not immediately pursued , but , of those pursued , most ( 318 , 80 % ) were answered Doctors spent an average of less than 2 minutes pursuing an answer , and they used readily available print and human re sources Only two questions led to a formal literature search . Conclusions : Family doctors in this study did not pursue answers to most of their questions . Questions about patient care can be organised into a limited number of generic types , which could help guide the efforts of knowledge base developers . Key messages Questions that doctors have about the care of their patients could help guide the content of medical information sources and medical training In this study of US family doctors , participants frequently had questions about patient care but did not pursue answers to most questions ( 64 % ) On average , participants spent less than 2 minutes seeking an answer to a question The most common re sources used to answer questions included textbooks and colleagues ; formal literature search es were rarely performed The most common generic questions were “ What is the cause of symptom X ? ” “ What is the dose of drug X ? ” and “ How should I manage disease or finding X ? OBJECTIVE Infobuttons are decision support tools that provide links within electronic medical record systems to relevant content in online information re sources . The aim of infobuttons is to help clinicians promptly meet their information needs . The objective of this study was to determine whether infobutton links that direct to specific content topics ( " topic links " ) are more effective than links that point to general overview content ( " nonspecific links " ) . DESIGN R and omized controlled trial with a control and an intervention group . Clinicians in the control group had access to nonspecific links , while those in the intervention group had access to topic links . MEASUREMENTS Infobutton session duration , number of infobutton sessions , session success rate , and the self-reported impact that the infobutton session produced on decision making . RESULTS The analysis was performed on 90 subjects and 3,729 infobutton sessions . Subjects in the intervention group spent 17.4 % less time seeking for information ( 35.5 seconds vs. 43 seconds , p = 0.008 ) than those in the control group . Subjects in the intervention group used infobuttons 20.5 % ( 22 sessions vs. 17.5 sessions , p = 0.21 ) more often than in the control group , but the difference was not significant . The information seeking success rate was equally high in both groups ( 89.4 % control vs. 87.2 % intervention , p = 0.99 ) . Subjects reported a high positive clinical impact ( i.e. , decision enhancement or knowledge up date ) in 62 % of the sessions . Limitations The exclusion of users with a low frequency of infobutton use and the focus on medication-related information needs may limit the generalization of the results . The session outcomes measurement was based on clinicians ' self- assessment and therefore prone to bias . CONCLUSION The results support the hypothesis that topic links are more efficient than nonspecific links regarding the time seeking for information . It is unclear whether the statistical difference demonstrated will result in a clinical ly significant impact . However , the overall results confirm previous evidence that infobuttons are effective at helping clinicians to answer questions at the point of care and demonstrate a modest incremental change in the efficiency of information delivery for routine users of this tool |
12,096 | 25,347,280 | There is no evidence to determine whether the use of antihistamines , decongestants or nasal irrigation is efficacious in children with acute sinusitis . | BACKGROUND The efficacy of decongestants , antihistamines and nasal irrigation in children with clinical ly diagnosed acute sinusitis has not been systematic ally evaluated .
OBJECTIVES To determine the efficacy of decongestants , antihistamines or nasal irrigation in improving symptoms of acute sinusitis in children . | 60 patients , aged 15 - 51 years , with chronic allergic or bacterial maxillary sinusitis , were entered in a controlled , double-blind study comparing the efficacy of endonasal irrigations of tixocortol pivalate (Pivalone)-neomycin and neomycin . The treatment lasted 11 days and was administered once daily . A ventilometric measurement of sinus pressure was performed every two endonasal irrigations to assess treatment efficacy . The percentage of nasal deobstruction was significantly higher with tixocortol pivalate-neomycin than with neomycin alone by the fifth examination ( 9th day ) regardless of the etiology of the sinusitis ( allergic or bacterial ) . After 11 days of treatment , significantly better results were obtained in cases of bacterial sinusitis ( 94 % deobstruction with tixocortol pivalate-neomycin versus 74 % with neomycin ) than in cases of allergic sinusitis ( 69 % deobstruction with tixocortol pivalate-neomycin versus 36 % with neomycin ) BACKGROUND Chronic sinusitis ( CS ) is a common disease in children , especially those with allergies , that is caused by impaired drainage from the sinuses . Hypertonic NaCl solution has been shown to increase mucociliary clearance and ciliary beat frequency . OBJECTIVE We performed a r and omized double blind study to compare the effect of nasal wash with hypertonic saline ( HS ) ( 3.5 % ) versus normal saline ( NS ) ( 0.9 % ) on CS . METHODS Thirty patients with CS aged 3 to 16 years were studied . They were r and omly divided into two treatment groups matched by age and severity of the disease . Each individual was treated with either HS or NS for 4 weeks . All patients were evaluated by two clinical scores ( cough and nasal secretions/postnasal drip [ PND ] ) and by a radiology score at the beginning of the study and after 4 weeks . RESULTS The HS group improved significantly in all scores ( average + /- SD ) : cough score , from 3.6 + /- 0.51 to 1.6 + /- 0.74 ; nasal secretion/PND score , from 2.86 + /- 0.35 to 1.6 + /- 0.74 ; and radiology score , from 8.06 + /- 1.28 to 2.66 + /- 1.04 . The NS treatment group showed significant improvement only in the PND score ( from 2.66 + /- 0.49 to 1.53 + /- 0.83 ) but no significant change in both the cough score ( from 3.53 + /- 0.52 to 3.33 + /- 0.49 ) and the radiology score ( from 8.13 + /- 1.25 to 7.86 + /- 0.91 ) . Clinical observation 1 month after the end of the study showed no change compared with the end of the study in both groups . CONCLUSION HS nasal wash is an efficient treatment of CS OBJECTIVES To test whether daily hypertonic saline nasal irrigation improves sinus symptoms and quality of life and decreases medication use in adult subjects with a history of sinusitis . STUDY DESIGN R and omized controlled trial . Experimental subjects used nasal irrigation daily for 6 months . POPULATION Seventy-six subjects from primary care ( n=70 ) and otolaryngology ( n=6 ) clinics with histories of frequent sinusitis were r and omized to experimental ( n=52 ) and control ( n=24 ) groups . OUTCOMES MEASURED Primary outcome measures included the Medical Outcomes Survey Short Form ( SF-12 ) , the Rhinosinusitis Disability Index ( RSDI ) , and a Single-Item Sinus-Symptom Severity Assessment ( SIA ) ; all 3 were completed at baseline , 1.5 , 3 , and 6 months . Secondary outcomes included daily assessment of compliance and biweekly assessment of symptoms and medication use . At 6 months , subjects reported on side effects , satisfaction with nasal irrigation , and the percentage of change in their sinus-related quality of life . RESULTS No significant baseline differences existed between the 2 groups . Sixty-nine subjects ( 90.8 % ) completed the study . Compliance averaged 87 % . Experimental group RSDI scores improved from 58.4 -/+ 2.0 to 72.8 -/+ 2.2 ( P < or = .05 ) compared with those of the control group ( from 59.6 -/+ 3.0 to 60.4 -/+ 1.1 ) ; experimental group SIA scores improved from 3.9 -/+ 0.1 to 2.4 -/+ 0.1 ( P < or = .05 ) compared with those of the control group ( from 4.08 -/+ 0.15 to 4.07 -/+ 0.27 ) . The number needed to treat to achieve 10 % improvement on RSDI at 6 months was 2.0 . Experimental subjects reported fewer 2-week periods with sinus-related symptoms ( P < .05 ) , used less antibiotics ( P < .05 ) , and used less nasal spray ( P = .06 ) . On the exit question naire 93 % of experimental subjects reported overall improvement of sinus-related quality of life , and none reported worsening ( P < .001 ) ; on average , experimental subjects reported 57 -/+ 4.5 % improvement . Side effects were minor and infrequent . Satisfaction was high . We found no statistically significant improvement on the SF-12 . CONCLUSIONS Daily hypertonic saline nasal irrigation improves sinus-related quality of life , decreases symptoms , and decreases medication use in patients with frequent sinusitis . Primary care physicians can feel comfortable recommending this therapy BACKGROUND Nasal irrigation has been used as an adjunctive therapy of sinonasal disease including acute/chronic sinusitis and allergic rhinitis . Several published articles reported it also improves clinical sinus symptoms . OBJECTIVE To evaluate the effectiveness of normal saline nasal irrigation in the management of acute sinusitis in children . DESIGN This was a r and omized , prospect i ve placebo-controlled study . METHODS We included 69 participants with acute sinusitis . 30 of 69 participants underwent normal saline nasal irrigation . 39 of 69 participants were not receiving nasal irrigation . All participants performed nasal peak expiratory flow rate ( nPEFR ) test , nasal smear examination , radiography ( Water 's projection ) and requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Question naires ( PRQLQ ) at the baseline visit . All participants were requested to record the symptom diary card every day and were followed-up every 1 week during this period . A physical examination , nasal smear and nPEFR were performed at each visit , and all daily diary cards collected . At the final visit , the symptoms diaries were review ed and participants were requested to complete the PRQLQ again . The nPEFR , radiography ( Water 's projection ) and nasal smear were also repeated . RESULTS Normal saline irrigation group significantly improved mean PRQLQ values and nPEFR values at medium ( T=2.816 , P<0.05 ) and final period ( T=2.767 , P<0.05 ) compared with the other group . Although there were no statically significant improving rate of radiography ( Water 's projection ) in among two groups ( T=0.545 , P>0.05 ) , but normal saline irrigation group was better than the other group . The improval rate of mean TSS in the irrigation group significantly improved all symptoms compared with the placebo group , in which rhinorrhea , nasal congestion , throat itching , cough and sleep quality improved . 27 of 66 ( 40.9 % ) participants with atopy , 16 of 27 ( 53.33 % ) participants underwent normal saline irrigation . Normal saline irrigation atopy group significantly improved rhinorrhea , nasal congestion , throat itching and sleep quality symptoms compared with non-irrigation atopy group . Normal saline irrigation atopy group significantly improved nPEFR values at final period ( Z=2.53 , P<0.05 ) . CONCLUSION This study evidence that normal saline nasal irrigation improves Pediatric Rhinoconjunctivitis Quality of Life and decreases acute sinusitis symptoms . Nasal irrigation is an effective adjunctive treatment for pediatric acute sinusitis . Normal saline nasal irrigation in atopy children also improves allergic-related symptoms . We may need larger , longer and extended study to assess the conclusion Antibiotic abuse for treating rhinopharyngitis induces the occurrence of resistant bacteria . As topical drugs might reduce this phenomenon , the aims of our study are to evaluate inhaled thiamphenicol associated with acetylcysteine in children with acute bacterial rhinopharyngitis and to compare it with the use of saline solution . The trial was conducted as r and omized , parallel group , and single blind . Children , aged 3–6 years , with acute bacterial rhinopharyngitis were treated with aerosolized thiamphenicol associated with acetylcysteine ( 250 mg : ½ vial in the morning and ½ vial in the evening ) ( Group A ) or saline solution twice daily ( Group B ) , both of them for 5 days . Both treatments were administered using a new device : Rinowash . The following parameters were assessed : nasal obstruction , mucopurulent rhinorrhea , post-nasal drip , cough , sore throat , fever , and cultures . Of 104 patients screened , 90 children , median age 3.7 years ( 44 females and 46 males ) , completed the study : 60 in Group A and 30 in Group B. Actively-treated children achieved a significant improvement of all parameters , but fewer than the control group . In conclusion , inhaled thiamphenicol associated with acetylcysteine may represent a valid treatment for acute bacterial rhinopharyngitis in children , as it is effective , safe , economic , and simple to use BACKGROUND The role of topical corticosteroids in the treatment of acute sinusitis has not been established in children . OBJECTIVE An attempt was made to determine the impact of topical corticosteroids as an adjunct to antibiotic treatment in the management of childhood sinusitis . METHODS In a double-blind , placebo-controlled study , 151 children with sinusitis were recruited from a general pediatric outpatient clinic and 89 completed a 3-week trial . Treatment consisted of amoxicillin-clavulanate potassium , 40 mg/kg/d tid , combined with bid nasal spray of either budesonide , 50 micrograms , to each nostril ( n = 43 ) or placebo ) n = 46 _ for 3 weeks . Patients maintained daily symptom cards throughout the study and were examined by the same physician each week . RESULTS Clinical symptoms and signs decreased significantly in both treatment groups in comparison to baseline ( P < .01 ) . We detected a significant improvement in the scores of the cough and nasal discharge at the end of second week in the budesonide group when compared with placebo ( P < .05 ) . Friedman nonparametric repeated measures ANOVA test revealed a significant decrease in the total weekly scores of cough during the second week of budesonide treatment ( P < .001 ) in contrast to continuous decline during the second and third weeks in the placebo group ( P < .001 and P < .05 , respectively ) . While the nasal discharge score decreased significantly during the second week in the budesonide group ( P < .01 ) , no significant effect on the nasal discharge score was observed in the placebo group . CONCLUSION These data suggest that topical corticosteroids may be a useful ancillary treatment to antibiotics in childhood sinusitis and effective in reducing the cough and nasal discharge earlier in the course of acute sinusitis OBJECTIVE The objective of this r and omized , prospect i ve , double-blind study was to compare nasal irrigation using hypertonic Dead Sea salt ( DSS ) solution with hypertonic saline in the treatment of chronic rhinosinusitis and improvement of quality of life ( QOL ) . METHODS With Institutional Review Board approval , 42 adults seeking treatment for chronic rhinosinusitis in a tertiary university-affiliated medical center were studied . After history and endonasal examination , computed tomography imaging , and QOL survey ( St and ardized Rhinoconjunctivitis Quality of Life Question naire [ RQLQ(S ) ] ) , patients were r and omized to self-administered hypertonic saline spray and irrigation twice daily or hypertonic DSS spray and irrigation . Patients were reassessed weekly and at 1 month . RESULTS Both groups had similar symptoms and RQLQ(S ) scores before treatment and had significant improvement after treatment . However , the DSS patients had significantly better symptom relief and only the DSS group showed improved RQLQ(S ) scores . CONCLUSIONS We present a short-term study providing level I evidence on the superiority of DSS over saline nasal irrigation for treatment of chronic rhinosinusitis preparation , and phenylephrine plus nitrofurazone 0.02 per cent solution t as the test preparation . Each was dispensed in a plastic dropping container marked only with a code number ; neither patient nor physician knew to which group the patient had been assigned . All 100 patients ---541 in each group-were from a general practice in pediatrics and had purulent rhinitis . Each patient was provided Purulent nasal discharge ( discharge that is thick , opaque and colored ) is a common clinical symptom in pediatrie patients . Although it may occur at any age it is probably most problematic and most common in children between birth and 2 to 3 years of age . This article review s the differential diagnosis , evaluation and management of purulent nasal discharge in children Objective . Although antimicrobial treatment for children with acute sinusitis is used commonly , it is unclear whether it offers significant clinical benefit . The purpose of this study was to evaluate the effectiveness of antimicrobial treatments for acute sinusitis as they are used in community pediatric practice . Methods . We conducted a r and omized , placebo-controlled trial in 3 community pediatric practice s in St Louis , Missouri . A total of 188 patients who were between the ages of 1 and 18 years and who had had 10 to 28 days of persistent sinus symptoms and a clinical diagnosis of acute sinusitis were r and omized to receive 14 days of amoxicillin ( 40 mg/kg/d in 3 daily doses ) , amoxicillin-clavulanate ( amoxicillin 45 mg/kg/d in 2 daily doses ) , or placebo . Change in sinus symptoms was assessed both by a quantitative symptom score ( the S5 score ) and subjectively by the parent . Secondary outcomes included adverse effects of treatment and recurrence or relapse of sinus symptoms . Outcomes were assessed by telephone interviews over a 2-month period . Results . Of the 161 patients who were included in the analysis , 58 received amoxicillin , 48 received amoxicillin-clavulanate , and 55 received placebo . Day 14 improvement rates were 79 % , 81 % , and 79 % , respectively . There were no differences in the 14-day change in S5 score among treatment groups . The rates of adverse events ( amoxicillin , 19 % ; amoxicillin-clavulanate , 11 % ; placebo , 10 % ) , relapse ( amoxicillin , 12 % ; amoxicillin-clavulanate , 13 % ; placebo , 13 % ) , and recurrence ( amoxicillin , 9 % ; amoxicillin-clavulanate , 13 % ; placebo , 13 % ) of sinus symptoms were similar among treatment groups . Conclusion . Neither amoxicillin nor amoxicillin-clavulanate offered any clinical benefit compared with placebo for children with clinical ly diagnosed acute sinusitis Acute sinusitis is a common childhood illness . If it is overlooked or undertreated , suppurative and intracranial complications may develop . Amoxicillin has traditionally been the antibiotic of choice for treatment of acute sinusitis . However , the efficacy of amoxicillin has been reduced because of the emergence of bacteria producing b-lactamase and altered penicillin-binding proteins . This study compares the effectiveness of 10 , 15 , and 20 days of ceftibuten therapy with 14 days of erythromycin-sulfisoxazole therapy in treating acute sinusitis . The results indicate that both treatment regimens are effective in treating acute sinusitis ( 96 % clinical response for erythromycin-sulfisoxazole vs 92 % for a 10-or 15-day course of ceftibuten vs 100 % for a 20-day course of ceftibuten ) . Longer treatment periods may be more effective in resolving the acute illness Abstract In a prospect i ve , r and omized , controlled , double-blind trial we compared the effectiveness of endonasal irrigations with Ems salt solution to that with sodium chloride solution in the treatment of adult patients with chronic paranasal sinus disease . Subjects ( n = 40 ) were r and omly allocated to treatment either with isotonic Ems salt solution or with isotonic sodium chloride solution . The treatment consisted of endonasal irrigation twice daily and additional nasal spray as required . Nasal endoscopy , plain radiography of the paranasal sinuses , olfactometry , anterior rhinomanometry , and a saccharin-clearance test were carried out on days 1 and 7 . Patients recorded rating scales of general discomfort , nasal airway obstruction , agreeableness of the irrigation , duration of improved nasal resistance after each irrigation , and the amount of additional nasal spray in a diary . Nasal air flow was not improved significantly . Subjective complaints , endonasal endoscopy , and radiography results revealed a significant improvement in both groups ( P = 0.0001 ) . In comparison , the two groups were not significantly different in outcome . Endonasal irrigations with salt solutions are effective in the treatment of chronic sinusitis , and a significant difference between Ems salt and sodium chloride was not observed Aim : To evaluate the efficacy of antibiotic treatment in children who presented in medical care with respiratory infection and had imaging evidence of sinusitis . Methods : Eighty‐two children ( 4–10 y ) with acute respiratory symptoms and ultrasonography findings suggestive of acute rhinosinusitis were enrolled in a r and omized , double‐blind trial . The sinus findings were confirmed with plain radiographs . The children received either cefuroxime axetil in 125‐mg capsules twice a day for 10 d or placebo . Main outcome measures were complete cure in 2 wk and absence of prolonged symptoms or complications . Results : A total of 72 children ( 88 % ) completed follow‐up . The sinusitis findings in the ultrasound could be confirmed with plain radiographs in 65 of the 72 patients ( 90 % ) . The proportion of children completely cured by day 14 was similar in both groups ( difference 6 % , 95 % confidence interval −16 % to 29 % ) . Similarly , there was no significant difference in the proportions of children who escaped prolonged disease and complications between the groups ( difference 7 % , −9 % to 24 % ) OBJECTIVES To determine whether the adjunctive drugs antihistamine and corticosteroid improve immediate and long-term outcomes of acute otitis media ( AOM ) . STUDY DESIGN Children with AOM ( 3 mos-6 y ) were enrolled in a r and omized , double-blind , placebo-controlled trial . All 179 children received one dose of intramuscular ceftriaxone and were assigned to receive either chlorpheniramine maleate ( 0.35 mg/kg/d ) and /or prednisolone ( 2 mg/kg/day ) or placebo for 5 days . Main outcome measures were rate of treatment failure during the first 2 weeks , duration of middle ear effusion , and rate of recurrences of AOM to 6 months . RESULTS Clinical outcomes and recurrence rates did not differ significantly with treatment . Children who received antihistamine alone had significantly longer duration of middle ear effusion ( median , 73 days ) than subjects in other treatment groups ( median , 23 to 36 days , P=.04 ) . Temporary normalization of tympanometric findings on day 5 occurred more frequently in the corticosteroid-treated group ( P=.04 ) . CONCLUSIONS Five-day treatment with antihistamine or corticosteroid , in addition to antibiotic , did not improve AOM outcomes . Antihistamine use during an acute episode of OM should be avoided , since the drug may prolong the duration of middle ear effusion . The efficacy of 7- to 10-day treatment of AOM with corticosteroid , in addition to antibiotic , deserves further investigation OBJECTIVES Nasal irrigations are mentioned among the adjunctive measures for treating several sinonasal conditions . Hyperchromatic supranuclear stria ( HSS ) in the ciliated cells ( CCs ) has recently been suggested as a potential cytological marker of the anatomofunctional integrity of nasal mucosa . The aim of this study was to compare the effects of nasal irrigations with sulfurous , salty , bromic , iodic ( SSBI ) thermal water or isotonic sodium chloride solution ( ISCS ) in patients with nonallergic chronic rhinosinusitis , considering the endoscopic , functional , microbiological , and cytological evidence ( including the ratio of HSS-positive CCs to total CCs [ the HSS+ rate ] ) . METHODS In a prospect i ve , r and omized , double-blind setting , 80 patients were recruited for nasal irrigations with SSBI water or ISCS for 1 month . RESULTS An endoscopically assessed significant clinical improvement was seen after both SSBI thermal water and ISCS irrigations . Before treatment , Staphylococcus aureus was isolated in 5 patients in the SSBI thermal water group and 4 in the ISCS group . After the nasal irrigations , there was no sign of the bacteria in either group . Only the SSBI water irrigations significantly reduced total nasal resistance , as determined by rhinomanometry . Mild nasal irritation ( 6 cases ) and episodes of extremely limited epistaxis ( 5 cases ) were only reported after SSBI thermal water irrigations . Neither type of nasal irrigation significantly increased the mean HSS+ rate at cytological control after 1 month . CONCLUSIONS Both types of nasal irrigation improved the endoscopic and microbiological features of patients with nonallergic chronic rhinosinusitis , whereas only SSBI irrigations significantly reduced total nasal resistance . Further investigations are needed based on longer treatments and follow-up periods to establish whether the HSS+ rate is useful for monitoring clinical improvements in chronic rhinosinusitis treated with nasal irrigations In a prospect i ve , r and omised , double-blinded controlled study , we compared the efficacy and safety of two different treatment options with the herbal medicines cineole and a combination of five different components for acute viral rhinosinusitis . One hundred and fifty patients with acute and viral rhinosinusitis ( 75 patients in each treatment group ) were enrolled . The diagnosis rhinosinusitis was made according to a defined symptoms-sum-score which was based on rhinoscopic and clinical signs which are characteristic for rhinosinusitis . The primary endpoint was the amelioration of the symptoms-sum-score , which includes all relevant characteristics for rhinosinusitis as headache on bending , frontal headache , sensitivity of pressure points of trigeminal nerve , impairment of general condition , nasal obstruction , rhino-secretion , secretion quantity , secretion viscosity and fever in a treatment period of 7 days . The mean reduction of the symptoms-sum-score after 4 days was 6.7 ( ±3.4 ) and after 7 days 11.0 ( ±3.3 ) in the cineole group and 3.6 ( ±2.8 ) after 4 days and 8.0 ( ±3.0 ) after 7 days in the control group . The differences between both groups were clinical ly relevant and statistically significant after 4 and 7 days ( P < 0.0001 ) . This result is vali date d by the amelioration of the secondary endpoints headache on bending , frontal headache , sensitivity of pressure points of trigeminal nerve , impairment of general condition , nasal obstruction and rhino-secretion . These findings correlate with the statistically significant difference of the estimation of B-scan ultrasonography . It is safe to use both medications for 7 days in patients with acute viral rhinosinusitis . Treatment with cineole is clinical ly relevant and statistically significant , more effective in comparison to the alternative herbal preparation with five different components We studied the effectiveness of nasal decongestant-antihistamine in treating acute sinusitis in children . All subjects received oral amoxicillin for 14 days . Subjects r and omized to the decongestant-antihistamine group received nasal oxymetazolone and oral syrup containing brompheniramine and phenylpropanolamine . Controls received placebo nasal saline and oral syrup . In both groups symptoms resolved quickly , and radiographs improved significantly . Responses to treatment were similar between the two groups . Water 's radiographs of the maxillary sinuses proved reliable in the assessment of the degree of sinus involvement . We conclude that decongestant-antihistamine need not be given to the child with acute maxillary sinusitis The diagnosis and treatment of non-purulent rhinitis in the pediatric population poses a challenge to the clinician . In this r and omized double blind study , the authors conclude that rhinometry is more effective than cytologic or symptomologic assessment in children with non-purulent rhinitis treated with either intranasal beclomethasone or placebo spray . Intranasal beclomethasone spray produced significant reductions in nasal airflow resistance values compared to the placebo-treated group OBJECTIVE : The role of antibiotic therapy in managing acute bacterial sinusitis ( ABS ) in children is controversial . The purpose of this study was to determine the effectiveness of high-dose amoxicillin/potassium clavulanate in the treatment of children diagnosed with ABS . METHODS : This was a r and omized , double-blind , placebo-controlled study . Children 1 to 10 years of age with a clinical presentation compatible with ABS were eligible for participation . Patients were stratified according to age ( < 6 or ≥6 years ) and clinical severity and r and omly assigned to receive either amoxicillin ( 90 mg/kg ) with potassium clavulanate ( 6.4 mg/kg ) or placebo . A symptom survey was performed on days 0 , 1 , 2 , 3 , 5 , 7 , 10 , 20 , and 30 . Patients were examined on day 14 . Children 's conditions were rated as cured , improved , or failed according to scoring rules . RESULTS : Two thous and one hundred thirty-five children with respiratory complaints were screened for enrollment ; 139 ( 6.5 % ) had ABS . Fifty-eight patients were enrolled , and 56 were r and omly assigned . The mean age was 66 ± 30 months . Fifty ( 89 % ) patients presented with persistent symptoms , and 6 ( 11 % ) presented with nonpersistent symptoms . In 24 ( 43 % ) children , the illness was classified as mild , whereas in the remaining 32 ( 57 % ) children it was severe . Of the 28 children who received the antibiotic , 14 ( 50 % ) were cured , 4 ( 14 % ) were improved , 4 ( 14 % ) experienced treatment failure , and 6 ( 21 % ) withdrew . Of the 28 children who received placebo , 4 ( 14 % ) were cured , 5 ( 18 % ) improved , and 19 ( 68 % ) experienced treatment failure . Children receiving the antibiotic were more likely to be cured ( 50 % vs 14 % ) and less likely to have treatment failure ( 14 % vs 68 % ) than children receiving the placebo . CONCLUSIONS : ABS is a common complication of viral upper respiratory infections . Amoxicillin/potassium clavulanate results in significantly more cures and fewer failures than placebo , according to parental report of time to resolution of clinical symptoms H1‐blockers are often added to the st and ard treatment of acute sinusitis , but this is not supported by a controlled study . A multicentric , r and omized , double‐blind , placebo‐controlled , parallel‐group study was done in 139 allergic patients ( 15–65 years ) to assess the adjunct efficacy of loratadine in acute exacerbation of rhinosinusitis . Sinusitis was diagnosed by symptoms and confirmed by rhinoscopy and sinus radiograph . Allergy was characterized by skin tests , RAST , and history . Patients were treated with antibiotics ( 14 days ) , oral corticosteroids ( 10 days ) , and loratadine ( 10 mg OD ) or placebo ( 28 days ) . Treatment efficacy was assessed over 28 days by symptom scores quoted daily by patients . Physicians also rated total symptom scores at entry and at day 28 . At entry , both groups had similar symptoms . Placebo‐treated patients improved significantly , but patients who received loratadine had a significantly greater improvement in sneezing ( P=0.003 ) after 14 days , and in nasal obstruction ( P=0.002 ) after 28 days . Physicians found that patients receiving loratadine were significantly improved compared to placebo patients ( P=0 . 0125 ) . Loratadine in addition to st and ard therapy was found to improve the control of some symptoms of sinusitis Abstract We investigated the clinical value of intranasal budesonide in acute sinusitis in 52 children with acute maxillary sinusitis . We r and omly divided them into two groups : group 1 received oral pseudoephedrine ( 2 × 30 mg ) and cefaclor ( 40 mg/kg ) for 10 days , and group 2 received intranasal budesonide ( 2 × 100 μg ) and cefaclor ( 40 mg/kg ) for 10 days . Symptoms of headache , cough , and nasal stuffiness and signs of nasal discharge were grade d before and after treatment . The patients whose symptoms and signs completely normalized after treatment were considered to have recovered , and those with persisting symptoms and signs after treatment as having not recovered . The results of the two treatment groups were compared . The recovery rate of the children in group 2 were significantly higher than those in group 1 ( P < 0.05 ) . No adverse drug effects were determined during the study period . These findings suggest that topical steroids may be a useful adjunctive agent in the treatment of acute sinusitis of children without apparent side effects and can possibly hasten the resolution of symptoms BACKGROUND To compare the efficiency of isotonic and hypertonic seawater solutions used for nasal lavage and quality of life of the patients with chronic rhinosinusitis . METHODS A r and om and controlled clinical study was performed . The study included 60 patients with history of chronic rhinosinusitis . At the beginning of the study , each subject was given a Patient Logbook , which needed to be filled out daily during the 15-day study period . There were three visits per each patient during the study . RESULTS Results Patient Logbook notes showed significant statistical differences in all symptoms in the group of patients using hypertonic seawater solution . However , while the notes showed significant statistical differences in congestion and rhinorrhea , in the group of patients using isotonic seawater solution , other symptoms showed no major changes during the study period . CONCLUSIONS Hypertonic seawater solution has been proven to be better than isotonic seawater solution in eliminating the symptoms of nasal congestion , rhinorrhea , cough , headache and waking up during the night This study was undertaken to compare prospect ively the frequency , nature , and severity of infections experienced by children in three types of child care arrangements : home care , group care ( two to six children ) , and day care ( seven or more children ) . Children were enrolled at birth and observed for 12 to 18 months . At entry there were 159 children in home care , 40 in group care , and 45 in day care . The families were telephoned every 2 weeks to record on a st and ardized form the type and severity of illnesses experienced during the previous interval . Severe illnesses were defined by high fever , duration exceeding 10 days , or physician visit . Children remaining in their original child care group for at least 1 year were compared with regard to the frequency and severity of illness . Children in group care and day care were more likely than children in home care to experience at least six respiratory infections , more than 60 days of illness , and more than four severe illnesses ( P less than 0.01 ) . Similarly , life table analyses showed that children in home care had fewer episodes of infection than did children in day care ( P less than 0.01 ) . Although no children were hospitalized because of acute infections during the first year of study , hospitalization for myringotomy and tube placement occurred in 21 % of children in day care and 3 % of children in home care ( P less than 0.01 ) This study compared the relative effectiveness of two antimicrobial preparations , amoxicillin and amoxicillin-clavulanate potassium ( Augmentin ) , in the treatment of acute maxillary sinusitis in children 2 to 16 years of age . Of 171 children with persistent ( ten to 30 days ' duration ) nasal discharge or daytime cough or both , 136 ( 80 % ) had abnormal maxillary sinus radiographs . These children were stratified by age and severity of symptoms and r and omly assigned to receive either amoxicillin , amoxicillin-clavulanate potassium , or placebo . After the exclusion of 28 children with throat cultures positive for group A Streptococcus and 15 who did not complete their medication , the remaining 93 children were evaluated : 30 received amoxicillin , 28 received amoxicillin-clavulanate potassium , and 35 received placebo . Clinical assessment was performed at three and ten days . On each occasion , children treated with an antibiotic were more likely to be cured than children receiving placebo ( P less than .01 at three days , P less than .05 at ten days ) . The overall cure rate was 67 % for amoxicillin , 64 % for amoxicillin-clavulanate potassium , and 43 % for placebo OBJECTIVES /HYPOTHESIS To compare efficacy and outcome of daily saline irrigation versus saline/gentamicin for treating chronic rhinosinusitis ( CRS ) . STUDY DESIGN Prospect i ve , r and omized , double-blinded study . METHODS Forty children diagnosed with CRS were enrolled . Patients were r and omized to once-daily irrigation with saline or saline/gentamicin for 6 weeks . Treatment outcomes were measured using 1 ) Lund-Mackay scoring system of pre- and post-treatment computer tomography ( CT ) ; and 2 ) Sinonasal Quality -of-Life Survey ( SN-5 ) completed at baseline , and after 3 weeks and 6 weeks of irrigation . RESULTS Thirty-four patients completed the study and follow-up . There were statistically significant improvements in quality -of-life ( QoL ) scores after 3 weeks of irrigation within both groups . However , there were no statistically significant differences in the SN-5 scores between the two treatment groups after 3 and 6 week ( P = .067 ) . CT scores for each sinus and total scores were reduced for both groups after 6 weeks , and the differences in scores were statistically significant within each group after treatment , but there were no differences between the two treatment groups . Only one patient required functional endoscopic sinus surgery due to persistent symptoms . Compliance was over 90 % for once daily irrigation over the 6 week treatment period . CONCLUSIONS Once-daily intranasal irrigation for 6 weeks is safe and equally effective in the treatment of pediatric CRS using saline or saline plus gentamicin , and QoL was significantly improved after 3 weeks of irrigation in both groups . High tolerance , compliance , and effectiveness of irrigation support its use as a first-line treatment for pediatric CRS before considering surgical intervention OBJECTIVE To determine whether hypertonic saline nasal spray relieves nasal symptoms and shortens illness duration in patients with the common cold or acute rhinosinusitis . DESIGN R and omized trial with 2 control groups . SETTING Two family practice clinics . PARTICIPANTS One hundred forty-three adult patients with a cold or sinus infection . Patients with allergic rhinitis , symptoms for more than 3 weeks , or other respiratory diagnoses were excluded , as were those who had used topical decongestants . INTERVENTION Hypertonic saline or normal saline spray 3 times a day or observation . Subjects completed a 7-day symptom checklist that included a well-being question ( " Do you feel back to normal ? " ) . MAIN OUTCOME MEASURES Nasal symptom score ( sum of scores for nasal congestion , rhinorrhea , and headache ) on day 3 and day of well-being ( day of symptom resolution ) . RESULTS Data were collected for 119 subjects . No difference was found in either primary outcome when hypertonic saline was compared with either normal saline or observation . Mean day of well-being was 8.3 ( 95 % confidence interval [ CI ] , 6.9 - 9.7 ) , 9.2 ( 95 % CI , 6.9 - 11.43 ) , and 8.0 ( 95 % CI , 6.7 - 9.3 ) days in the hypertonic saline , normal saline , and observation groups , respectively . Day 3 mean nasal symptom score was 3.8 ( 95 % CI , 3.0 - 4.5 ) for hypertonic saline , 3.7 ( 95 % CI , 2.9 - 4.5 ) for normal saline , and 4.1 ( 95 % CI , 3.5 - 4.7 ) for observation . Only 44 % of the patients would use the hypertonic saline spray again . Thirty-two percent noted burning , compared with 13 % of the normal saline group ( P = .05 ) . CONCLUSION Hypertonic saline does not improve nasal symptoms or illness duration in patients with the common cold or rhinosinusitis OBJECTIVE : To determine the effect of nasal irrigation on sinonasal symptoms . STUDY DESIGN AND SETTING : A total of 150 adult subjects with chronic sinusitis symptoms were recruited from the community and assigned to 1 of 3 treatment groups : nasal irrigation with bulb syringe , nasal irrigation with nasal irrigation pot , or control treatment with reflexology massage . Groups 1 and 2 performed daily hypertonic saline irrigation with 1 device for 2 weeks and then with the other device for 2 weeks . Group 3 performed reflexology massage daily for 2 weeks . Prospect i ve data collected included pretreatment Medical Outcomes Study Short Form , pretreatment and posttreatment Rhinosinusitis Outcomes Measure , daily medication use , subjective treatment efficacy , and preference of irrigation method . RESULTS : There was a significant and equivalent improvement in Rhinosinusitis Outcomes Measure 31 score after 2 weeks of intervention in each treatment group ; 35 % of subjects reported decreased use of sinus medication . CONCLUSION : Daily nasal irrigation using either a bulb syringe , nasal irrigation pot , and daily reflexology massage were equally efficacious and result ed in improvement in the symptoms of chronic sinusitis in over 70 % of subjects . Medication usage was decreased in approximately one third of participants regardless of intervention Brodimoprim is a long acting broad spectrum antibacterial agent . It is a new selective inhibitor of bacterial dihydrofolate reductase , structurally related to trimethoprim . The aim of the present study was to investigate the efficacy and tolerability of brodimoprim ( 10 mg/kg on the first day , 5 mg/kg/die onward ) in the treatment of upper respiratory tract infections in children ( age range : 2 - 14 years ) . This open group comparative study was performed either in 68 children affected by bacterial pharyngotonsillitis ( 37 treated with brodimoprim , 31 with erythromycin 560 mg/kg/8 hours ) or in 50 patients affected by otitis media ( 25 treated with brodimoprim , 25 with amoxicillin/clavulanic acid 50 mg/kg/12 hours ) or in 52 patients affected by acute sinusitis ( 25 treated with brodimoprim , 27 with amoxicillin/clavulanic acid 50 mg/kg/12 hours ) . All patients were clinical ly evaluated before admission , during the trial and 48 hours after the last dose of antibiotic . At the same time blood and secretion sample s were collected for hematology/biochemistry and microbiological assays . A total of 170 subjects were treated and 141 patients demonstrated a clinical recovery/improvement following the treatment period , with approximately the same recovery rate ( 83 % ) among the groups . The bacteriological response was evaluated in 169 subjects . Eradication of pathogens was documented in 27 subjects treated with brodimoprim and 28 with erythromycin in the pharyngotonsillitis group , in 22 subjects treated with brodimoprim and 16 with amoxicillin/clavulanic acid in the otitis group and in 17 subjects treated with brodimoprim and 20 with amoxicillin/clavulanic acid in the sinusitis group . The overall eradication in brodimoprim treated patients was 77 % in comparison with 76 % of eradication obtained in the control groups . ( ABSTRACT TRUNCATED AT 250 WORDS |
12,097 | 24,819,480 | COMT genotypes could be related with a modest modification in the age at onset of PD , but its possible genotypes in excessive daytime somnolence , impulse control disorders , cognitive impairment , and neuropharmacological or neurochemical variables are unclear .
The results of the meta- analysis suggest that the COMT rs4680 polymorphism is not a major determinant of either the risk for PD or clinical , neuropharmacological and neurochemical features of PD .
Data on other COMT polymorphisms are scarce but do not suggest association with PD | BACKGROUND / AIMS Several single-nucleotide polymorphisms ( SNPs ) in the catechol-O-methyltransferase ( COMT ) gene have been associated with the risk of developing Parkinson 's disease ( PD ) . | The catechol-O-methyltranferase ( COMT ) is one of the main enzymes that metabolise dopamine in the brain . The Val158Met polymorphism in the COMT gene ( rs4680 ) causes a trimodal distribution of high ( Val/Val ) , intermediate ( Val/Met ) and low ( Met/Met ) enzyme activity . We tested whether the Val158Met polymorphism is a modifier of the age at onset ( AAO ) in Parkinson 's disease ( PD ) . The rs4680 was genotyped in a total of 16 609 subjects from five independent cohorts of European and North American origin ( 5886 patients with PD and 10 723 healthy controls ) . The multivariate analysis for comparing PD and control groups was based on a stepwise logistic regression , with gender , age and cohort origin included in the initial model . The multivariate analysis of the AAO was a mixed linear model , with COMT genotype and gender considered as fixed effects and cohort and cohort-gender interaction as r and om effects . COMT genotype was coded as a quantitative variable , assuming a codominant genetic effect . The distribution of the COMT polymorphism was not significantly different in patients and controls ( p=0.22 ) . The Val allele had a significant effect on the AAO with a younger AAO in patients with the Val/Val ( 57.1±13.9 , p=0.03 ) than the Val/Met ( 57.4±13.9 ) and the Met/Met genotypes ( 58.3±13.5 ) . The difference was greater in men ( 1.9 years between Val/Val and Met/Met , p=0.007 ) than in women ( 0.2 years , p=0.81 ) . Thus , the Val158Met COMT polymorphism is not associated with PD in the Caucasian population but acts as a modifier of the AAO in PD with a sexual dimorphism : the Val allele is associated with a younger AAO in men with idiopathic PD Patients with Parkinson 's Disease ( PD ) have a variable response to tolcapone , a catechol-O-methyltransferase ( COMT ) inhibitor . In addition , a subset of patients develop severe diarrhea as a side effect . Two codominant alleles for the COMT gene exist , coding for low and high activity , result ing in low- , medium- , and high-activity genotypes . This study investigates the relationship between this variation in genotype and clinical effects in patients with PD taking tolcapone . To investigate the relationship between COMT polymorphism and clinical response , 24 patients who completed tolcapone clinical trials provided blood sample s for COMT genotype analysis . Change in levodopa dose and United Parkinson Disease Rating Scale ( UPDRS ) Part III ( motor subscale ) were analyzed at baseline , at 1–2 weeks , and 6 months after initiation of tolcapone . Genotype analysis was performed on seven patients who had diarrhea as a side effect . There was no significant correlation between genotype and improvement in UPDRS score ( p = 0.29 ) according to a linear models approach that adjusted for the subject 's severity of PD , tolcapone dose ( either 100 or 200 mg three times daily ) and initial differences in baseline scores . No significant difference was seen in change in daily levodopa intake and genotype . There was also no relation between diarrhea and COMT genotype . These results indicate that , in the treatment of Parkinson 's disease , COMT genotype is not a major contributor to the clinical response to tolcapone Background A polymorphism ( G to A transition ) in intron 13 of the mitochondrial enzyme monoamine oxidase B ( MAOB ) gene may modify , alone or by interacting with the catechol-O-methyltransferase ( COMTLL ) genotype ( low enzymatic activity ) , the risk of idiopathic PD . Also , the association between never smoking and PD risk may be present only in people with the MAOB G allele . Methods The authors studied two ongoing prospect i ve cohorts — the Nurses ’ Health Study ( 121,700 women aged 30 to 55 in 1976 ) and the Health Professionals ’ Follow-up Study ( 51,529 men aged 40 to 75 in 1986 ) . They identified new PD cases through 1996 , selected r and om control subjects matched on age and study cohort , and obtained DNA sample s from blood or buccal smears from 85 % of the eligible cases and 84 % of the control subjects . They included genotypes from 214 cases and 449 control subjects , all Caucasian . Results The odds ratio of PD was 1.2 ( 95 % CI 0.9 , 1.7 ) for MAOB genotypes G/GG/GA compared with genotypes A/AA , and 1.1 ( 0.7 , 1.8 ) for COMT genotypes LL compared with HH . The odds ratio ( 95 % CI ) was 1.7 ( 0.7 , 3.9 ) for those with MAOB G/GG and COMTLL genotypes compared with those with MAOB A/AA and COMTHH . There was a strong association between never smoking and PD risk in all groups defined by MAOB and COMT genotypes . Conclusion The findings do not support a major role of the MAOB intron 13 polymorphism in the development of PD , either by itself or by interacting with smoking A single nucleotide polymorphism at the nucleotide 1947 in the catechol-O-methyltransferase ( COMT ) gene encodes the high and low activity forms of the enzyme . We investigated COMT genotypes of 73 Korean patients with Parkinson 's disease ( PD ) , 29 with multiple system atrophy ( MSA ) , and 49 controls , and analyzed the response to levodopa challenge in the PD patients . We found no significant difference in the distribution of the COMT genotypes among the three groups . The frequencies of the G- and A-alleles in the total population were 75 and 25 % , respectively . The levodopa response was determined by a single oral levodopa challenge test with Sinemet ( 25/250 mg ) in the patients with PD . The motor response evaluated by the time to peak response , the duration and magnitude of the response in the motor part of the Unified Parkinson 's Disease Rating Scale ; tapping or walking times showed no significant difference between the genotypes . Thus , pharmacokinetic or pharmacodynamic factors other than the investigated genetic variant of the COMT enzyme seem to determine the response to levodopa in PD The role of genetic factors in cognitive decline associated with Parkinson 's disease ( PD ) is unclear . We examined whether variations in apolipoprotein E ( APOE ) , microtubule-associated protein tau ( MAPT ) , or catechol-O-methytransferase ( COMT ) genotypes are associated with cognitive decline in PD . We performed a prospect i ve cohort study of 212 patients with a clinical diagnosis of PD . The primary outcome was change in Mattis Dementia Rating Scale version 2 score . Linear mixed-effects models and survival analysis were used to test for associations between genotypes and change in cognitive function over time . The ε4 allele of APOE was associated with more rapid decline ( loss of 2.9 ; 95 % confidence interval [ CI ] : 1.7 - 4.1 ) of more points per year ; P < 0.001 ) in total score and an increased risk of a ≥ 10 point drop during the follow-up period ( hazard ratio , 2.8 ; 95 % CI : 1.4 - 5.4 ; P = 0.003 ) . MAPT haplotype and COMT genotype were associated with measures of memory and attention , respectively , over the entire follow-up period , but not with the overall rate of cognitive decline . These results confirm and extend previously described genetic associations with cognitive decline in PD and imply that individual genes may exert effects on specific cognitive domains or at different disease stages . Carrying at least one APOE ε4 allele is associated with more rapid cognitive decline in PD , supporting the idea of a component of shared etiology between PD dementia and Alzheimer 's disease . Clinical ly , these results suggest that genotyping can provide information about the risk of future cognitive decline for PD patients Pyridoxal‐5‐phosphate , the biological active form of pyridoxine , is a cofactor for dopa‐decarboxylase ( DDC ) enzyme . Pyridoxine may augment the conversion of levodopa to dopamine in the periphery and therefore decrease availability of levodopa to the brain . However , this effect can be negated in the presence of a DDC inhibitor , which potentiates plasma levodopa level . A single nucleotide polymorphism at the nucleotide 1947 in the catechol‐O‐methyltransferase ( COMT ) gene encodes the high ( COMTH ) and low activity ( COMTL ) forms of the enzyme . In this study , we examined the effect of the COMTL allele on the clinical response to pyridoxine in Parkinson 's disease ( PD ) patients . PD patients who were on stable and optimized dose of levodopa were included in this study . Their mean motor and activities of living score improved after high dose pyridoxine ( P = 0.09 , P = 0.04 ) , and worsened after a washout period ( P = 0.005 , P = 0.001 ) . Using a multivariate model , the presence of the COMTL allele predicted response to pyridoxine , with the best outcome observed in COMTL/L homozygotes . Our observational study suggests that the status the functional COMTL variant may be potentially useful to select PD patients for high dose pyridoxine therapy . © 2005 Wiley‐Liss , Catechol-O-methyltransferase ( COMT ) is an enzyme that inactivates catecholamines such as adrenaline , noradrenaline , dopamine , and levodopa . Recently an amino acid change ( Val-108-Met ) of the COMT protein was found to determine high and low activity alleles of the COMT gene . We genotyped 109 Japanese patients with Parkinson 's disease ( PD ) and 153 controls by using polymerase chain reaction ( PCR ) amplification and digestion by the restriction enzyme NlaIII . The frequency of low activity allele in the controls was 0.29 , which was significantly different from that reported in Caucasians ( 0.50 ) . When comparison was made between patients with PD and controls , homozygosity for the low activity allele was significantly more common among the patients than among the controls ( P = 0.017 ; odds ratio , 2.8 , 95 % CI 1.2 - 6.5 ) , suggesting that homozygosity for the low activity allele may increase susceptibility to PD We explored the potential effect of catechol-O-methyltransferase ( COMT ) genetic polymorphism on the pharmacokinetics and pharmacodynamics of a st and ard oral dose of levodopa in patients with Parkinson 's disease ( PD ) . We prospect ively collected blood sample s for COMT genotyping from a population of 104 PD patients . Each patient was examined by a st and ard oral levodopa/benserazide test , based on simultaneous serial measurements of plasma levodopa concentrations , finger-tapping motor effects and dyskinesia ratings , up to 4 hours after dosing . The main levodopa pharmacokinetic outcome variables were time to peak and peak plasma concentration , plasma elimination half-life , and the area under the plasma concentration-time curve . The main outcome levodopa pharmacodynamic variables were latency , duration , and magnitude of the motor effect elicited by the levodopa test dose , the area under the tapping effect-time curve , and the presence of dyskinesias . Nineteen patients ( 18 % ) harbored the low-activity homozygous COMT genotype ( A/A ) , 63 patients ( 61 % ) carried the intermediate-activity heterozygous COMT genotype ( A/G ) and 22 patients ( 21 % ) had the high-activity homozygous COMT genotype ( G/G ) . The three groups were comparable for vital and clinical characteristics . No significant difference was found in levodopa main pharmacokinetic-pharmacodynamic variables and dyskinesia incidence among the three subgroups of patients . We failed to identify clinical ly relevant levodopa pharmacokinetic-pharmacodynamic response patterns associated with the COMT polymorphism in PD patients Objective To investigate the relationship between the catechol-O-methyltransferase ( COMT ) genotype and the therapeutic efficacy of entacapone . Methods The efficacy of 2 months of entacapone treatment in 65 patients with PD with end-of-dose deterioration was studied . The efficacy of entacapone was assessed using the Unified Parkinson ’s Disease Rating Scale ( UPDRS ) score , the daily levodopa dosage , and the patients ’ diary card . Results Thirty-six patients ( 55.4 % ) had a high-activity COMT gene ( COMTHH ) , 22 ( 33.8 % ) had an intermediate-activity COMT gene ( COMTHL ) , and 7 patients ( 10.8 % ) had a low-activity COMT gene ( COMTLL ) . Two months of entacapone treatment result ed in a significant increase in “ on ” time , a reduction in “ off ” time , and a reduction in the total UPDRS score , but these results were independent of the COMT genotype of the patient . There was no significant difference in the frequency or severity of dyskinesias between the patients with different COMT genotypes . Conclusion The COMT genotype seems to be a minor factor in judging the beneficial effects of entacapone administration We report -108Met/Val polymorphism of the COMT gene in Japanese patients with Parkinson 's disease ( PD ) . The allele frequency for -108Val was higher in PD patients compared with controls , although the differences did not reach the statistical significance . However , the frequency of -108Val homozygotes was significantly higher in PD patients ( 56.8 % ) than in control subjects ( 44.2 % ) , and heterozygotes of -108Met/Val were less in PD . COMT gene polymorphism may constitute a genetic risk factor for PD among Japanese |
12,098 | 11,434,793 | Treatment efficacy for these 5 outcomes was greatest early , in the first few days of treatment , declining after the first week .
Patients receiving cyclobenzaprine also experienced more adverse effects , the most common being drowsiness .
CONCLUSIONS Cyclobenzaprine is more effective than placebo in the management of back pain ; the effect is modest and comes at the price of greater adverse effects .
The effect is greatest in the first 4 days of treatment , suggesting that shorter courses may be better . | BACKGROUND Back pain is a common problem for which cyclobenzaprine hydrochloride is frequently prescribed .
OBJECTIVE To perform a systematic review of cyclobenzaprine 's effectiveness in the treatment of back pain . | A double-blind , 18-center , balanced trial of diflunisal vs. cyclobenzaprine HCl vs. these two drugs combined vs. placebo produced complete results from 175 patients . They had sought treatment at the cooperating centers for acute painful spasms of the back within a day or two of trauma or strain . Global results over the 7 to 10 days of observations revealed a clinical ly and statistically significant superiority of the combined therapy by Day 4 ( P=0.006 ) and almost all patients recovered within a week to 10 days . A combination therapy with an effective safe analgesic and a true muscle relaxant for less than a week appears to be an excellent relief measure for acute back problems The reduction of pain by two antidepressants , clomipramine and mianserin , was , in this study on 253 patients with chronic idiopathic pain syndrome , found to be not better than a placebo when all patients were compared independently of the classification of pain . The improvement rate was around 40 % after 6 weeks of treatment when using a 50 % or better reduction in pain level . However , in patients who fulfilled a checklist definition of minor to major depression ( 30 % of the total patient material ) clomipramine was superior to mianserin and placebo with an improvement rate of 75 % after 6 weeks . Using pain curves over time as outcome measure in the various clinical pain categories it was found that both mianserin and clomipramine seemed superior to placebo in patients with tension headache , but in patients with low back pain syndrome placebo was superior to the two antidepressants . No difference among the three treatments was found in patients with burning mouth syndrome or in patients with abdominal pain . These differences underline the importance of study ing specific pain syndromes rather than composite groups of patients with idiopathic pain . The clinical significance of these pain curves needs further placebo controlled investigations & NA ; To assess the efficacy of nortriptyline , a tricyclic antidepressant , as an analgesic in chronic back pain without depression , we conducted a r and omized , double‐blind , placebo‐controlled , 8‐week trial in 78 men recruited from primary care and general orthopedic setting s , who had chronic low back pain ( pain at T‐6 or below on a daily basis for 6 months or longer ) . Of these 57 completed the trial ; of the 21 who did not complete , four were withdrawn because of adverse effects . The intervention consisted of inert placebo or nortriptyline titrated to within the therapeutic range for treating major depression ( 50–150 ng/ml ) . The main outcome endpoints were pain ( Descriptor Differential Scale ) , disability ( Sickness Impact Profile ) , health‐related quality of life ( Quality of Well‐Being Scale ) , mood ( Beck Depression Inventory , Spielberger State Anxiety Inventory , Hamilton Anxiety/Depression Rating Scales ) , and physician rated outcome ( Clinical Global Impression ) . Reduction in pain intensity scores was significantly greater for participants r and omized to nortriptyline ( difference in mean change 1.68 , 95 % −0.001 , CI −3.36 , P=0.050 ) , with a reduction of pain by 22 % compared to 9 % on placebo . Reduction in disability marginally favored nortriptyline ( P=0.055 ) , but health‐related quality of life , mood , and physician ratings of overall outcome did not differ significantly between treatments . Subgroup analyses of study completers supported the intent‐to‐treat analysis . Also , completers with radicular pain on nortriptyline ( n=5 ) had significantly ( P<0.05 ) better analgesia and overall outcome than did those on placebo ( n=6 ) . The results suggest noradrenergic mechanisms are relevant to analgesia in back pain . This modest reduction in pain intensity suggests that physicians should carefully weigh the risks and benefits of nortriptyline in chronic back pain without depression Thirty-seven patients with chronic back pain were entered into a r and omised , 3-way , double-blind , cross-over comparison of naproxen sodium 550 mg twice daily , diflunisal 500 mg twice daily , and placebo . Each treatment was given for 14 days after a preadmission wash-out week during which only paracetamol was allowed . Patients were assessed on admission and at the end of each treatment with respect to global pain , night pain , pain on movement , and pain on st and ing . Both visual analogue scales and simple descriptive scales were used to measure pain . Side effects were elicited by a nonleading question . Both methods of pain measurement gave similar results and were highly correlated . Naproxen sodium was superior to placebo in relieving global pain and depending on the method of measurement , in relieving night pain and pain on movement . Diflunisal showed no significant differences from placebo . Side effects were similar on all 3 treatments . The final preference of the patients was significantly in favour of the active treatments This report describes a double-blind between-group comparison of Tofranil and placebo in fifty-nine patients admitted to the Joint Service Medical Rehabilitation Unit suffering from low back pain . Patients were given 25 mg of either Tofranil or placebo three times a day for four weeks . Fifteen patients were not included in the analysis , nine dropping out for non-trial related reasons , two dropping out complaining of lost libido and four not taking the tablets , or taking additional drugs . One of the patients complaining of lost libido was taking Tofranil and the other was taking placebo . Over the whole sample there was no significant benefit for Tofranil over placebo as regards physical measurements . Both Tofranil and placebo groups showed a significant improvement during the trial on straight leg raise and backward flexion . For lateral flexion the Tofranil group was significantly worse than the placebo group on entering the trial , and during the trial the Tofranil group improved to match the placebo group . The clinician 's pain and stiffness assessment s and the patients ' pain and stiffness assessment s show a significant improvement for both the Tofranil and placebo groups during the trial . However , no difference is shown between Tofranil and placebo . The psychological tests show no difference between Tofranil and placebo and only a marinal improvenmet over initial condition . Further analysis according to initial diagnosis showed nothing conclusive . Numerically , the use of Tofranil produced a marked improvement in pain and stiffness in patients with ' disc lesion only ' diagnoses , whereas placebo did not produce an improvement . However , this observation was far from reaching statistical significance . Side-effects were not severe for either drug . Additional medication was rarely used The effectiveness of cyclobenzaprine hydrochloride , a new tricyclic skeletal muscle relaxant , was shown in patients with long-term intractable pain of cervical and lumbar origin aggravated by skeletal muscle spasm and tenderness . The investigation was double-blind and r and omized , comparing cyclobenzaprine hydrochloride ( 10 mg three times a day ) with diazepam ( 5 mg three times a day ) and with placebo . After two weeks of treatment , the 16 patients in the cyclobenzaprine group showed an overall improvement in pain variables as did the 16 patients in the diazepam group . No serious adverse reactions to cyclobenzaprine were observed in the study . However , dry mouth due to cyclobenzaprine 's anticholinergic action and mild degrees of drowsiness were encountered more often than with diazepam or placebo Thirty-nine patients with acute low back pain were treated with amitriptyline ( 150 mg/d ) or acetaminophen ( 2,000 mg/d ) in a controlled double-blind design for 5 weeks . Both groups revealed mild depression , normal coping , and increased anxiety at the beginning , with significant improvement in anxiety state and pain at the end of treatment . A repeated measures analysis of variance demonstrated that amitriptyline was more effective than acetaminophen in reducing pain intensity from the second week of treatment . Age and depression were the only significant pretreatment predictors of posttreatment pain . The study evaluates the significance of these findings Health status measures are being used with increasing frequency in clinical research . Up to now the emphasis has been on the reliability and validity of these measures . Less attention has been given to the sensitivity of these measures for detecting clinical change . As health status measures are applied more frequently in the clinical setting , we need a useful way to estimate and communicate whether particular changes in health status are clinical ly relevant . This report considers effect sizes as a useful way to interpret changes in health status . Effect sizes are defined as the mean change found in a variable divided by the st and ard deviation of that variable . Effect sizes are used to translate “ the before and after changes ” in a “ one group ” situation into a st and ard unit of measurement that will provide a clearer underst and ing of health status results . The utility of effect sizes is demonstrated from four different perspectives using three health status data sets derived from arthritis population s administered the Arthritis Impact Measurement Scales ( AIMS ) . The first perspective shows how general and instrument-specific benchmarks can be developed and how they can be used to translate the meaning of clinical change . The second perspective shows how effect sizes can be used to compare traditional clinical measures with health status measures in a st and ard clinical drug trial . The third application demonstrates the use of effect sizes when comparing two drugs tested in separate drug trials and shows how they can facilitate this type of comparison . Finally , our health status results show how effect sizes can supplement st and ard statistical testing to give a more complete and clinical ly relevant picture of health status change . We conclude that effect sizes are an important tool that will facilitate the use and interpretation of health status measures in clinical research in arthritis and other chronic diseases Twenty-seven investigators participated in a double-blind , parallel placebo-controlled trial of piroxicam involving 278 patients with acute low back pain . Therapy commenced within 48 hours of the injury and continued for 7 days . The drug was given in the recommended regimen of 40 mg once daily for the first 2 days and 20 mg once daily thereafter . After 3 days of therapy , piroxicam patients showed a statistically greater amount of pain relief in the lying ( P<0.001 ) , sitting ( P<0.01 ) , and st and ing ( P<0.01 ) positions , but after 7 days the difference between treatments was no longer significant . After 1 week 's therapy , however , the requirement for additional analgesic was significantly lower in the piroxicam group ( P<0.05 ) , and more piroxicam than placebo patients ( 42 versus 28 ) had returned to work ( P<0.05 ) . Toleration was excellent in most patients , with only 13 % of the piroxicam and 17 % of the placebo group reporting adverse effects of mainly mild or moderate severity . The profile of the adverse effects was similar for both treatments . Piroxicam can provide effective relief of acute low-back pain with good toleration ; it should be considered for use in the initial treatment of this condition A new drug , Cyclobenzaprine hydrochloride ( Flexeril ) , was compared with diazepam ( Valium ) and placebo in double-blind trials for efficacy in treating spasms and pain in the neck and low back . Complex recording methods involving clinical evaluations ( grade d ) , patient self-ratings , goniometry , motion analysis by computer , electromyography of controlled motions and detailed statistical analysis were used . Clinical improvement over two weeks was statistically significant in all treatment groups with a statistically significant preference for Cyclobenzaprine hydrochloride . The most striking improvements recorded were in the electromyographic findings , which showed statistically significant changes for the Cyclobenzaprine group . Clinical muscle spasms are not accompanied by increased myoelectric activity ; the reverse is true . With improvement , myoelectric activity in back muscles is augmented during prescribed stressful movements as measured by electromyography and computer analysis combined with complex electrogoniometry Chronic low back pain is a common problem that has been noted in several studies to exist as a component of masked depression . To determine the usefulness of imipramine in the treatment of chronic low back pain , either by a direct action or indirectly via resolution of a depressive equivalent , 50 consecutive patients were entered into a controlled trail that employed serum imipramine and desipramine levels and Beck depression question naires . Forty-one patients completed the study , and 48 were used in the statistical analysis . Imipramine had a statistically significant effect over placebo in most , but not all , of the clinical parameters that were measured . A linear relationship between serum drug levels and reported symptoms was not noted . Only 10 of the 50 patients entered into the study were judged clinical ly depressed and , of these , 7 were depressed according to st and ard criteria . There was no statistically significant difference noted in either the initial or the change in Beck depression scores between those on imipramine and those on placebo . However , among those on the active drug , the patients with a greater symptomatic response had a simultaneous change in the total Beck depression scores ( toward less depression ) that approached statistical significance when compared with those with a less symptomatic response . Although the results are not conclusive , imipramine may possibly be useful in the treatment of chronic low back pain , especially so when it exists as a component of masked depression Two groups of 20 patients each , with mild to moderate acute low back pain with associated muscle spasm of ten days ' duration or less , were treated with a combination of cyclobenzaprine and naproxen or naproxen alone in a r and omized , 14-day open-label trial . Cyclobenzaprine was added to the naproxen regimen as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute , painful , musculoskeletal conditions . The clinical characteristics of each study group , including the number of worker 's compensation patients , were comparable . Combination therapy was associated with less objective muscle spasm and tenderness and greater motion of the lumbosacral spine ( P less than 0.05 ) . There were trends toward faster resolution of functional deficits and pain with combined therapy . Combination therapy was associated with more side effects , due primarily to drowsiness from the cyclobenzaprine . The results of this study demonstrated that patients with muscle spasm associated with acute low back strain benefited from the use of combination therapy consisting of a nonsteroidal anti-inflammatory agent ( naproxen ) and a muscle relaxant ( cyclobenzaprine ) The effect of antidepressant medication on chronic low-back pain patients was studied in a r and omized blind crossover study . Among those patients who completed the study , there was a 46 % decrease in the use of analgesics while on amitriptyline when compared to placebo ( P < 0.005 ) . There was also improvement in affect , but no measurable change in activity level . The MMPI profile of those patients who were unable to comply with the study protocol differed from that of patients who completed the study . The noncompliers demonstrated an elevation of the F , Pd , Pt ( P < 0.05 ) and Mf ( P < 0.01 ) scales . Although the interpretation of such a profile is left open to speculation , it may serve as an indicator of noncompliant individuals Patients with chronic low-back pain and depression were treated double blind with desipramine or doxepin . During this treatment several hypotheses regarding the modes of action of these drugs were examined . A low serotonin hypothesis was supported by the fact that patients who had pain relief following an acute challenge with fenfluramine , a relatively pure releaser of serotonin , were significantly more likely to have pain relief on either antidepressant . The antidepressants did not change cerebrospinal fluid ( CSF ) beta-endorphin levels , acute pain tolerance , or electromyogram ( EMG ) levels . The nonsedating antidepressant desipramine was as effective as doxepin ; 60 % of patients had significant pain relief . Pain relief was associated with depression relief , but several patients had only pain or depression relief . Patients who had a substantial physical basis for their pain responded as well as those who did not |
12,099 | 27,160,267 | Meta- analysis demonstrated that NSRH was associated with less bladder and anorectal dysfunction than RH .
The time to bladder and anorectal function recovery after NSRH was shorter than RH .
Patients undergoing NSRH also scored higher than patients undergoing RH at Female Sexual Function Index ( FSFI ) .
On the other h and , the local recurrence and overall recurrence rate were similar between NSRH and RH .
Conclusion : NSRH may be an effective technique for lowering pelvic organ dysfunction and improving the function recovery without increasing the recurrence rate of cervical cancer | Background / Aims : Radical hysterectomy ( RH ) for the treatment of cervical cancer frequently caused pelvic organ dysfunctions .
This study aim ed to compare the results of pelvic organ function and recurrence rate after Nerve sparing radical hysterectomy ( NSRH ) and RH treatment through systematic review and meta- analysis . | OBJECTIVES The objectives of this study were to describe our laparoscopic nerve-sparing radical hysterectomy ( LNSRH ) technique and to assess the feasibility and safety of the procedure , as well as its impact on voiding function . We introduce a fascia space dissection technique in order to preserve the pelvic splanchnic nerve , the hypogastric nerve and the bladder branch of the inferior hypogastric plexus under magnification ( ×10.5 ) during laparoscopic radical hysterectomy ( LRH ) with pelvic lymphadenectomy . METHODS From October 2006 to November 2009 , 163 consecutive patients with cervical cancer underwent laparoscopic radical hysterectomy ( LRH ) and pelvic lymphadenectomy , with 82 women undergoing LNSRH with fascia space dissection technique ( LNSRH group ) and 81 undergoing LRH ( LRH group ) . Data from 163 patients were prospect ively collected and compared . Post-operative assessment of bladder function included the following : the time to recover the ability to void spontaneously and to achieve a post-void residual urine ( PVR ) volume of less than 50 ml , with urination function grade d. RESULTS The laparoscopic nerve-sparing radical hysterectomy procedure was completed successfully and was conducted safely in all of the patients . There were no conversions to open surgery in the two groups . The median operative duration in the LNSRH and the LRH groups were 163.52±34.47 min and 132.13±31.42 min , respectively . Blood loss was 142.12±62.38 ml and 187.69±68.63 ml , respectively . The time taken to obtain a post-void residual urine volume of less than 50 ml after removal of the urethral catheter was 7.42±2.35 d ( 5 - 18 d ) in LNSRH group and was 16.75±7.73 d ( 5 - 35 d ) in LRH group ( P<0.05 ) . The bladder void function recovery to Grade s 0-I was 76 ( 92.7 % ) for the LNSRH group and 59 ( 72.8 % ) for the LRH group . A mean follow-up of 22.3 ( 5 - 42 ) months was adhered to , and no patient had a recurrence or metastasis . CONCLUSIONS The technique described in this preliminary study appears to be safe , feasible , and easy in our population , with satisfactory recovery of voiding function OBJECTIVE To investigate bladder and intestinal function recovery and quality of sexual life after laparoscopic nerve-sparing radical hysterectomy ( LNRH ) for treatment of early invasive cervical carcinoma . METHODS Subjects included patients who underwent radical hysterectomy by laparotomy who were r and omly assigned to 2 groups : 30 patients who underwent LNRH and 35 classical laparoscopic radical hysterectomy ( LRH ) . We assessed the patients general clinical information , surgical characteristics , pathological findings , and adjuvant therapies . A urodynamic study was used to assess bladder function . Intestinal function recovery and quality of sexual life were evaluated by question naire . RESULTS No significant differences were found in age , surgery characteristics , pathological findings , adjuvant therapies , and main adverse effects between the 2 groups . The mean duration of the postoperative catheterization ( DPC ) in group LNRH was shorter than that in group LRH ( P < 0.001 ) . The maximum flow rate , maximum cystometric capacity , maximum detrusor pressure and urinary complications in group LNRH were better than those in group LRH . The quality of sexual life evaluated according to the female sexual function index ( FSFI ) was better in group LNRH than in those who underwent LRH . The intestinal function of patients in group LNRH also recovered better compared with patients in group LRH The objective of this study is to describe a technique for preserving the autonomic nerve systematic ally , including the hypogastric nerves , pelvic splanchnic nerves , and pelvic plexus and its vesical branches , based on anatomic considerations for the autonomic nerves innervating the urinary bladder , in radical hysterectomies and to assess postsurgical bladder function . A nerve-sparing radical hysterectomy was carried out on 27 consecutive patients with uterine cervical cancer treated between 2000 and 2002 . The FIGO stages of the disease consisted of 10 stage Ib1 , 6 stage Ib2 , 3 stage IIa , and 8 stage IIb . The nerve-sparing procedure was successfully completed in 22 of the 27 patients ( 81.5 % ) in the study . At 1 year after the operation , bladder symptoms were significantly improved in the nerve-sparing group compared to the non – nerve-sparing group . Urinary incontinence and abnormal ( diminished ) bladder sensation were observed in three of the five patients ( two patients had both symptoms ) , for whom the nerve-sparing procedure could not be performed , but none of the 22 patients for whom the nerve-sparing procedure was performed had incontinence , and only two patients had abnormal ( increased ) bladder sensation ( P = 0.0034 for incontinence and P = 0.030 for abnormal bladder sensation ) . The patients ' survival was not adversely affected by the nerve-sparing procedure . Although it is still preliminary , the surgical technique described in this report is thought to be effective for preserving bladder function , and thus , the quality of life could be improved for patients with cervical cancer who are treated with a radical hysterectomy . For further evaluation of the efficacy of nerve-sparing radical hysterectomy , a prospect i ve r and omized trial needs to be performed Objective Conventional radical hysterectomy with pelvic lymphadenectomy ( RHL ) for early-stage cervical cancer is associated with significant bladder , anorectal , and sexual dysfunction . Nerve-sparing modification of RHL ( NS-RHL ) has been developed with the aim to reduce surgical treatment-related morbidity . Postoperative radiation therapy ( RT ) is offered to patients with unfavorable prognostic features to improve local control . The aim of the study was to assess self-reported morbidity of various types of treatment in cervical cancer patients . Methods Self-reported symptoms were prospect ively assessed before and 1 and 2 years after treatment by the Dutch Gynaecologic Leiden Question naire . Results Included were 229 women ( 123 NS-RHL and 106 conventional RHL ) . Ninety-four ( 41 % ) received RT . Up to 2 years ( response rate , 81 % ) , women reported significantly more bowel , bladder , and sexual symptoms compared with the pretreatment situation . No significant difference was found between the conventional RHL and NS-RHL with the exception of the unexpected finding that a smaller percentage in the NS-RHL group ( 34 % vs 68 % ) complained about numbness of the labia and / or thigh . Radiation therapy had a negative impact on diarrhea , urine incontinence , lymphedema , and sexual symptoms ( especially a narrow/short vagina ) . Conclusions In the current longitudinal cohort study , treatment for early-stage cervical cancer was associated with worse subjective bladder , anorectal , and sexual functioning , irrespective of the surgical procedure used . Postoperative RT result ed in a significant deterioration of these functions . The results have to be interpreted with caution in view of the study design and method used Introduction : The present study compares for the first time the st and ard therapy for cervical cancer in FIGO-stages IB-IIB , radical hysterectomy according to the Wertheim-Meigs operation , with the newly developed , nerve-sparing surgical technique , total mesometrial resection ( TMMR ) with regard to postoperative , health-related quality of life . Method : In the framework of a multicentre , retrospective cohort study a total of 110 cervical cancer patients were interviewed once by means of the European Organisation for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) and the cervical cancer module ( EORTC QLQ-CX24 ) . The influence of the surgical method was investigated by analysis of covariance under control of age and the time elapsed between treatment and interview . Results : An influence of the therapeutic method was demonstrated in the EORTC scales physical function ( p = 0.047 ) , role function ( p = 0.016 ) , fatigue ( p = 0.028 ) , pain ( p = 0.018 ) , shortness of breath ( p = 0.034 ) , lack of appetite ( p = 0.006 ) and diarrhoea ( p = 0.012 ) in favour of the 74 women treated by TMMR . With regard to cognitive , emotional and social functioning as well as cervical cancer-specific symptoms , no significant differences between the therapy groups were found . Conclusion : The findings presented in this study suggest a superiority of TMMR in comparison to the previously employed radical hysterectomy according to Wertheim-Meigs with regard to the postoperative quality of life , especially in the fields of physical activity and fatigue . This needs to be vali date d in the course of prospect i ve , multicentre studies . In addition , it must be clarified as to what extent the found effects are , in particular , due to the omission of an additional radiotherapy OBJECTIVE Surgical therapy for cervical carcinoma carries a significant risk of functional impairment to the bladder . This study evaluates the feasibility and complications of nerve-sparing radical hysterectomy ( NRH ) in Taiwan . METHODS Between March 2010 and March 2011 , consecutive patients diagnosed with early stage cervical cancer ( FIGO stage Ia2 to Ib1 ) and tumor size < 3 cm were recruited prospect ively to undergo NRH or conventional radical hysterectomy ( RH ) . Patients with histories of urinary stress incontinence or bladder dysfunction disease were excluded . A modified Tokyo nerve-sparing radical hysterectomy was performed . RESULTS A total of 30 patients were enrolled . Among these , 18 patients underwent NRH with successful bilaterally nerve-sparing procedures in 15 cases ( 83 % ) , unilaterally nerve-sparing procedures in 2 cases ( 11 % ) , and a failure in 1 case ( 6 % ) . The indwelling catheter was removed on postoperative day 6 . The mean±SD duration from operation to spontaneous voiding was 6.8 ± 1.5 days for women who underwent NRH ; the corresponding duration for women who underwent RH or failed NRH was 20.6 ± 3 days . None of the patients who underwent NRH required intermittent catheterization . All 12 patients who underwent RH needed self-catheterization after discharge . There was a significant reduction in the incidence of postoperative self-catheterization ( p<0.01 ) and bladder dysfunction ( p<0.006 ) . Average satisfaction score analyzed by the Likert-scale question naire was 4.5 for the NRH group and 1.9 for RH group ( p<0.0001 ) . CONCLUSIONS We concluded that the new technique of NRH can reduce postoperative bladder dysfunctions OBJECTIVE To assess the nerve-sparing radical hysterectomy ( NSRH ) technique and its impact on postoperative voiding function . METHODS Forty-four patients with International Federation of Gynecology and Obstetrics ( FIGO ) stage I b1-IIa cervical cancer were enrolled and r and omized into NSRH group ( study group , n = 22 ) and conventional radical hysterectomy ( CRH ) group ( control group , n = 22 ) . The pelvic autonomic nerve pathway ( including hypogastric nerve , pelvic splanchnic nerve , inferior hypogastric plexus and bladder branch ) was completely preserved in the NSRH group . Related parameters were compared between the two groups . RESULTS The estimated blood loss in NSRH group and CRH group were ( 550 + /- 241 ) ml and ( 475 + /- 284 ) ml , respectively , with no significant difference ( P > 0.05 ) . The mean operation time in NSRH group and CRH group were ( 329 + /- 43 ) min and ( 272 + /- 56 ) min , respectively , with a significant difference ( P < 0.01 ) . More patients in NSRH group had post-void residual urine volume ( PVR ) < 100 ml than that in CRH group on day 8 after surgery ( 68 % vs. 18 % , P < 0.01 ) . The median duration of postoperative catheterization was significantly shorter in NRSH group ( 8 - 23 days , median 8 days ) than that in CRH group ( 8 - 32 days , median 20 days ; P < 0.01 ) . Neither surgery-related injury nor pathologically positive margin was reported in either of the groups . CONCLUSIONS NSRH is a feasible and safe technique for preserving bladder function . Larger prospect i ve studies are needed to confirm the efficacy of this technique Objective : To investigate the bladder function recovery and quality of life ( QOL ) using nerve-sparing radical hysterectomy ( NSRH ) in treating early invasive cervical carcinoma . Methods : Subjects included patients who underwent radical hysterectomy by laparotomy for early-stage cervical carcinoma . Thirty-one patients were r and omly assigned to 2 groups : group A , 15 patients who underwent NSRH ; and group B , 16 patients who underwent classical radical hysterectomy . We observed the patients ' general clinical information , surgical characteristics , postoperative vital signs , pathological findings , adjuvant therapies , and adverse effects . A urodynamic study was used to assess the bladder function . The patients ' QOL was evaluated by Functional Assessment of Cervical Cancer Therapy ( FACT-Cx ) . Results : Twenty-nine patients completed the study . No significant differences were found in age , body mass index , surgery characteristics , pathological findings , adjuvant therapies , and main adverse effects between the 2 groups ( P > 0.05 ) . The postoperative time of bladder function recovery in group A was obviously earlier than that in group B ( P < 0.05 ) . The urodynamic study showed that the extent of bladder function recovery in group A was better than that in group B ( P < 0.05 ) . The QOL in group A evaluated 1 year after operation was improved compared with that in group B ( P < 0.05 ) . The QOL analysis showed that group A did much better than group B in social and family life , emotional well-being , working status , and the symptom correlated with the operation ( P < 0.05 ) . No significant differences were found in basic bodily functions ( P > 0.05 ) . Conclusions : Nerve-sparing radical hysterectomy is a safe and reliable technique for early invasive cervical carcinoma . The postoperative bladder function recovery and the patients ' QOL were improved after NSRH compared with the control group . Therefore , NSRH could be an alternative management to modify the classical surgery for cervical carcinoma with International Federation of Gynecology and Obstetrics stages IB1 to IIA INTRODUCTION Although growing evidence suggests the beneficial effects of a nerve-sparing ( NS ) approach to surgery in cervical cancer patients , only limited data on NS laparoscopic radical hysterectomy ( LRH ) are available , and no studies have investigated the effects of NS-LRH on sexual function . AIM This study aims to determine whether the implementation of NS-LRH impacts on sexual function in cervical cancer patients . METHODS Sexually active cervical cancer patients undergoing type C ( class III ) LRH between 2004 and 2013 were enrolled in this prospect i ve study . MAIN OUTCOME MEASURES Preoperative and postoperative sexual function were assessed using a vali date d question naire , the Female Sexual Function Index ( FSFI ) . The FSFI evaluates desire , arousal , lubrication , orgasm , satisfaction , and pain . RESULTS Forty patients undergoing radical hysterectomy ( 20 conventional LRH vs. 20 NS-LRH ) represented the study group . Baseline characteristics were similar between groups ( P > 0.05 ) . No differences in preoperative FSFI scores were recorded ( P > 0.05 ) . We observed that both LRH and NS-LRH worsened postoperative FSFI scores ( P < 0.001 ) . However , patients undergoing NS-LRH had higher postoperative FSFI scores than patients undergoing LRH ( 21.3 ± 9.4 vs. 14.2 ± 12.5 ; P = 0.04 ) . Considering postoperative domain scores , we observed that desire , arousal , orgasm , and pain scores were similar between groups ( P > 0.05 ) , while patients undergoing NS-LRH experienced higher lubrication ( 3.4 ± 2.3 vs. 1.7 ± 2.2 ; P = 0.02 ) and satisfaction ( 4.6 ± 3.9 vs. 2.8 ± 2.2 ; P = 0.004 ) scores in comparison with patients undergoing conventional LRH . No between-group differences in survival outcomes were found . CONCLUSIONS Both conventional LRH and NS-LRH impact negatively on patients ' sexual function . However , the NS approach impairs sexual function less , minimizing the effects of radical surgery Background : Radical hysterectomy has been the treatment of choice for early-stage cervical cancer . Since its introduction in oncology , modifications to the original technique were made to enhance feasibility , improve cure rate , and decrease postoperative complications . Among these are the identification and preservation of pelvic autonomic nerves , known as the nerve-sparing radical hysterectomy ( RH ) . This retrospective study was conducted to compare the nerve-sparing with the conventional RH in terms of feasibility and safety , including bladder dysfunction and perioperative and postoperative complications and morbidities . Methods : Patients with biopsy-proven early-stage cervical carcinoma , cervical carcinoma with central tumor recurrence or persistence after primary radiotherapy , and endometrial carcinoma with cervical involvement treated with RH with or without nerve-sparing technique were included . The perioperative and postoperative complications and bladder function of these patients were analyzed . Results : Ninety-seven patients with early-stage cervical cancer and 24 patients with clinical stage II endometrial cancer underwent RH with or without nerve-sparing technique in a nonr and omized fashion . There was no statistically significant difference between the 2 procedures in terms of duration of surgery , intraoperative blood loss , duration of hospitalization , and morbidity . Patients who underwent the nerve-sparing approach had a statistically significant earlier return of bladder function , with a mean of 9.4 days for the cervical cancer cases ( vs 21 days in the non-nerve-sparing group ) and a mean of 8.5 days for the endometrial cancer cases ( vs 22.6 days in the non-nerve-sparing group ) . Conclusions : The technique of sparing the pelvic autonomic nerves during RH for early-stage cervical cancer and clinical stage II endometrial cancer is comparable to the conventional method in terms of perioperative complications and morbidity , but is more favorable in terms of return of bladder function The objective of this study was to assess the postsurgical bladder function by urodynamic study in patients with cervical cancer treated with nerve-sparing radical hysterectomy . A total of 27 consecutive patients were included in the study . Of the 27 patients , autonomic nerves had been completely preserved at least on one side in 22 patients ( group A ) , and autonomic nerves could not be successfully preserved in five patients ( group B ) . In group A , there was no significant difference in compliance at the moment of strong desire to void , maximum flow rate , and residual urine volume between before the operation and at 12 months after the operation . However , abdominal pressure at maximum flow had significantly increased in patients of group B than of group A. Detrusor contraction pressure at maximum flow had significantly decreased in patients of group B than of group A. Bladder sensation was diminished in three cases ( 60 % ) of group B but preserved in all the patients of group A. Although it is still preliminary , our surgical technique described in this report is thought to be effective for preservation of bladder function . For further evaluation of the efficacy of nerve-sparing radical hysterectomy in terms of quality of life and survival of patients , a prospect i ve r and omized trial needs to be performed STUDY OBJECTIVE To compare perioperative and long-term outcomes related to laparoscopic and open abdominal surgical management of cervical cancer . DESIGN Propensity-matched comparison of prospect ively collected data ( Canadian Task Force classification II-1 ) . SETTING University teaching hospital . PATIENTS Sixty-five propensity-matched patient pairs ( 130 patients ) undergoing either laparoscopy or open abdominal surgical procedures to treat cervical cancer . INTERVENTION Radical hysterectomy plus lymphadenectomy was performed via the laparoscopic ( LRH ) or open abdominal approach ( RAH ) . MEASUREMENT AND MAIN RESULTS Baseline characteristics of the study population s were similar . In the LRH group the procedure was converted to open surgery in 2 patients ( 2 % ) . Compared with the RAH group , patients undergoing LRH experienced less blood loss ( 200 vs 500 mL ; p < .001 ) , a lower transfusion rate ( 6 % vs 22 % ; p = .02 ) , similar operative time ( 245 vs 259.5 minutes ; p = .26 ) , and shorter length of hospital stay ( 4 vs 8 days ; p < .001 ) . No between-group differences in intraoperative complications were recorded ( p = 1.0 ) ; however , a trend toward a lower postoperative complication rate ( Accordion system grade ≥ 3 ) was observed for LRH compared with RAH ( 4 patients [ 6 % ] ) vs 12 patients [ 18 % ] ; p = .06 ) . Five-year disease-free survival ( p = .6 , log-rank test ) and overall survival ( p = .31 , log-rank test ) did not differ statistically between women undergoing LRH or RAH . CONCLUSION Laparoscopy ensures the same results as open surgery insofar as radicality and long-term survival . Use of the laparoscopic approach is associated with improved short-term results , minimizing the occurrence of severe postoperative complications |
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