Pixantrone dimaleate in combination with fludarabine, dexamethasone, and rituximab in patients with relapsed or refractory indolent non‐Hodgkin lymphoma Re-orientation of clinical research in traumatic brain injury: report of an international workshop on comparative effectiveness research. Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center. Interventions aimed at increasing research use in nursing: a systematic review Strategies to Promote Physical Activity During Pregnancy Clinical research in implant dentistry: study design, reporting and outcome measurements: consensus report of Working Group 2 of the VIII European Workshop on Periodontology. A protocol for developing, disseminating, and implementing a core outcome set for pre-eclampsia. A systematic review and development of a classification framework for factors associated with missing patient-reported outcome data Self-help interventions for depressive disorders and depressive symptoms: a systematic review Adapting and testing a brief intervention to reduce maternal anxiety during pregnancy (ACORN): study protocol for a randomised controlled trial
Pixantrone dimaleate ( pixantrone ) has been shown to have antitumor activity in leukemia and lymphoma in vitro models and to lack delayed cardiotoxicity associated with mitoxantrone in animal models . FND‐R , a combination regimen of fludarabine , mitoxantrone , dexamethasone , and rituximab , has been shown to be an effective regimen for low‐ grade lymphomas During the National Neurotrauma Symposium 2010 , the DG Research of the European Commission and the National Institutes of Health/National Institute of Neurological Disorders and Stroke ( NIH/NINDS ) organized a workshop on  comparative effectiveness research  ( CER ) in traumatic brain injury ( TBI ) . This workshop review ed existing approaches to improve outcomes of TBI patients . It had two main outcomes : First , it initiated a process of re-orientation of clinical research in TBI . Second , it provided ideas for a potential collaboration between the European Commission and the NIH/NINDS to stimulate research in TBI . Advances in provision of care for TBI patients have result ed from observational studies , guideline development , and meta-analyses of individual patient data . In contrast , r and omized controlled trials have not led to any identifiable major advances . Rigorous protocol s and tightly selected population s constrain generalizability . The workshop addressed additional research approaches , summarized the greatest unmet needs , and highlighted priorities for future research . The collection of high- quality clinical data bases , associated with systems biology and CER , offers substantial opportunities . Systems biology aims to identify multiple factors contributing to a disease and addresses complex interactions . Effectiveness research aims to measure benefits and risks of systems of care and interventions in ordinary setting s and broader population s. These approaches have great potential for TBI research . Although not new , they still need to be introduced to and accepted by TBI research ers as instruments for clinical research . As with therapeutic targets in individual patient management , so it is with research tools : one size does not fit all PURPOSE Advanced-stage follicular lymphoma is considered incurable . The pace of improvements in treatment has been slow . This article analyzes five sequential cohorts of patients with stage IV follicular lymphoma treated between 1972 and 2002 . METHODS Five consecutive studies ( two were r and omized trials ) involving 580 patients were analyzed for overall survival ( OS ) , failure-free survival ( FFS ) , and survival after first relapse . A proportional hazards analysis , and subset analyses using the follicular lymphoma international prognostic index ( FLIPI ) score were performed . Treatment regimens included : cyclophosphamide , doxorubicin , vincristine , prednisone , bleomycin ( CHOP-Bleo ) ; CHOP-Bleo followed by interferon alfa ( IFN-alpha ) ; a rotation of three regimens ( alternating triple therapy ) , followed by IFN-alpha ; fludarabine , mitoxantrone , dexamethasone ( FND ) followed by IFN-alpha ; and FND plus delayed versus concurrent rituximab followed by IFN-alpha . RESULTS Improvements in 5-year OS ( from 64 % to 95 % ) and FFS ( from 29 % to 60 % ) indicate steady progress , perhaps partly due to more effective salvage therapies , but the FFS data also indicate improved front-line therapies ; these observations held true after controlling for differences in prognostic factors among the cohorts . The FLIPI model adds rigor to and facilitates comparisons among the different cohorts . An unexpected finding in this study was a trend toward an apparent FFS plateau . CONCLUSION Evolving therapy , including the incorporation of biologic agents , has led to stepwise significant outcome improvements for patients with advanced-stage follicular lymphoma . The apparent plateau in the FFS curve , starting approximately 8 to 10 years from the beginning of treatment , raises the issue of the potential curability of these patients Background There has been considerable interest recently in developing and evaluating interventions to increase research use by clinicians . However , most work has focused on medical practice s ; and nursing is not well represented in existing systematic review s. The purpose of this article is to report findings from a systematic review of interventions aim ed at increasing research use in nursing . Objective To assess the evidence on interventions aim ed at increasing research use in nursing . Methods A systematic review of research use in nursing was conducted using data bases ( Medline , CINAHL , Healthstar , ERIC , Cochrane Central Register of Controlled Trials , and Psychinfo ) , grey literature , ancestry search ing ( Cochrane Data base of Systematic Review s ) , key informants , and manual search ing of journals . R and omized controlled trials and controlled before- and after- studies were included if they included nurses , if the intervention was explicitly aim ed at increasing research use or evidence -based practice , and if there was an explicit outcome to research use . Method ological quality was assessed using pre-existing tools . Data on interventions and outcomes were extracted and categorized using a pre-established taxonomy . Results Over 8,000 titles were screened . Three r and omized controlled trials and one controlled before- and after- study met the inclusion criteria . The method ological quality of included studies was generally low . Three investigators evaluated single interventions . The most common intervention was education . Investigators measured research use using a combination of surveys ( three studies ) and compliance with guidelines ( one study ) . Research er-led educational meetings were ineffective in two studies . Educational meetings led by a local opinion leader ( one study ) and the formation of multidisciplinary committees ( one study ) were both effective at increasing research use . Conclusion Little is known about how to increase research use in nursing , and the evidence to support or refute specific interventions is inconclusive . To advance the field , we recommend that investigators : ( 1 ) use theoretically informed interventions to increase research use , ( 2 ) measure research use longitudinally using theoretically informed and psychometrically sound measures of research use , as well as , measuring patient outcomes relevant to the intervention , and ( 3 ) use more robust and method ologically sound study design s to evaluate interventions . If investigators aim to establish a link between using research and improved patient outcomes they must first identify those interventions that are effective at increasing research use Physical activity during pregnancy has been associated with significant health benefits ; however , most women in the United States do not meet the current guidelines . This systematic review evaluates evidence for interventions to improve physical activity during pregnancy in order to identify best practice s and inform future research . Electronic data bases ( PubMed , CINAHL , SportD ISCUS , Embase , ERIC , Psych Info , and ISI Web of Science ) were search ed in July 2011 for peer- review ed journal articles . Studies were included if they were English- language r and omized control trials that measured the efficacy of an intervention targeted at pregnant women and were design ed to change physical activity as a primary or secondary outcome . Out of 777 studies identified through the systematic search , 9 interventions were selected for inclusion by multiple review ers . Data were abstract ed using an abstract ion form modeled after the “ Guide to Community Preventive Services . ” Of the 9 interventions included in the review , 3 reported statistically significant positive results for physical activity . Although the interventions included a variety of strategies and techniques , none were uniquely associated with positive outcomes . Overall , this review suggests that little is known about the efficacy of interventions for physical activity during pregnancy . This study provides several recommendations for future research and intervention design AIMS The objective of this working group was to assess and make specific recommendations to improve the quality of reporting of clinical research in implant dentistry and discuss ways to reach a consensus on choice of outcomes . MATERIAL AND METHODS Discussion s were informed by three systematic review s on quality of reporting of observational studies ( case series , case-control and cohort ) and experimental research ( r and omized clinical trials ) . An additional systematic review provided information on choice of outcomes and analytical methods . In addition , an open survey among all workshop participants was utilized to capture a consensus view on the limits of currently used survival and success-based outcomes as well as to identify domains that need to be captured by future outcome systems . RESULTS The Workshop attempted to clarify the characteristics and the value in dental implant research of different study design s. In most areas , measurable quality improvements over time were identified . The Workshop recognized important aspects that require continued attention by clinical research ers , funding agencies and peer review ers to decrease potential bias . With regard to choice of outcomes , the limitations of currently used systems were recognized . Three broad outcome domains that need to be captured by future research were identified : ( i ) patient reported outcome measures , ( ii ) peri-implant tissue health and ( iii ) performance of implant supported restorations . Peri-implant tissue health can be measured by marginal bone level changes and soft tissue inflammation and can be incorporated in time to event analyses . CONCLUSIONS The Workshop recommended that collaboration between clinicians and epidemiologists/ clinical trials specialists should be encouraged . Aspects of design aim ed at limitation of potential bias should receive attention by clinical research ers , funding agencies and journal editors . Adherence to appropriate reporting guidelines such as STROBE and CONSORT are necessary st and ards . Research on outcome measure domains is an area of top priority and should urgently inform a proper process leading to a consensus on outcome measures in dental implant research BACKGROUND Pre-eclampsia is a serious complication of pregnancy and contributes to maternal and offspring mortality and morbidity . R and omised controlled trials evaluating therapeutic interventions for pre-eclampsia have reported many different outcomes and outcome measures . Such variation contributes to an inability to compare , contrast , and combine individual studies , limiting the usefulness of research to inform clinical practice . The development and use of a core outcome set would help to address these issues ensuring outcomes important to all stakeholders , including patients , will be collected and reported in a st and ardised fashion . METHODS An international steering group including healthcare professionals , research ers , and patients , has been formed to guide the development of this core outcome set . Potential outcomes will be identified through a comprehensive literature review and semi-structured interviews with patients . Potential core outcomes will be entered into an international , multi-perspective online Delphi survey . All key stakeholders , including healthcare professionals , research ers , and patients will be invited to participate . The modified Delphi method encourages whole and stakeholder group convergence towards consensus ' core ' outcomes . Once core outcomes have been agreed upon it is important to determine how they should be measured . The truth , discrimination , and feasibility assessment framework will assess the quality of potential outcome measures . High quality outcome measures will be associated with core outcomes . Mechanisms exist to disseminate and implement the result ing core outcome set within an international context . DISCUSSION Embedding the core outcome set within future clinical trials , systematic review s , and clinical practice guidelines could make a profound contribution to advancing the usefulness of research to inform clinical practice , enhance patient care , and improve maternal and offspring outcomes . The infrastructure created by developing a core outcome set for pre-eclampsia could be leveraged in other setting s , for example selecting research priorities and clinical practice guideline development . PROSPECT IVE REGISTRATION : [ 1 ] Core Outcome Measures in Effectiveness Trials ( COMET ) registration number : 588 . [ 2 ] International Prospect i ve Register of Systematic Review s ( PROSPERO ) registration number : CRD42015015529 Background / aims : Missing patient-reported outcome data can lead to biased results , to loss of power to detect between-treatment differences , and to research waste . Awareness of factors may help research ers reduce missing patient-reported outcome data through study design and trial processes . The aim was to construct a Classification Framework of factors associated with missing patient-reported outcome data in the context of comparative studies . The first step in this process was informed by a systematic review . Methods : Two data bases ( MEDLINE and CINAHL ) were search ed from inception to March 2015 for English articles . Inclusion criteria were ( a ) relevant to patient-reported outcomes , ( b ) discussed missing data or compliance in prospect i ve medical studies , and ( c ) examined predictors or causes of missing data , including reasons identified in actual trial data sets and reported on cover sheets . Two review ers independently screened titles and abstract s. Discrepancies were discussed with the research team prior to finalizing the list of eligible papers . In completing the systematic review , four particular challenges to synthesizing the extracted information were identified . To address these challenges , operational principles were established by consensus to guide the development of the Classification Framework . Results : A total of 6027 records were screened . In all , 100 papers were eligible and included in the review . Of these , 57 % focused on cancer , 23 % did not specify disease , and 20 % reported for patients with a variety of non-cancer conditions . In total , 40 % of the papers offered a descriptive analysis of possible factors associated with missing data , but some papers used other methods . In total , 663 excerpts of text ( units ) , each describing a factor associated with missing patient-reported outcome data , were extracted verbatim . Redundant units were identified and sequestered . Similar units were grouped , and an iterative process of consensus among the investigators was used to reduce these units to a list of factors that met the guiding principles . The list was organized on a framework , using an iterative consensus-based process . The result ant Classification Framework is a summary of the factors associated with missing patient-reported outcome data described in the literature . It consists of 5 components ( instrument , participant , centre , staff , and study ) and 46 categories , each with one or more sub-categories or examples . Conclusion : A systematic review of the literature revealed 46 unique categories of factors associated with missing patient-reported outcome data , organized into 5 main component groups . The Classification Framework may assist research ers to improve the design of new r and omized clinical trials and to implement procedures to reduce missing patient-reported outcome data . Further research using the Classification Framework to inform quantitative analyses of missing patient-reported outcome data in existing clinical trials and to inform qualitative inquiry of research staff is planned Background Research suggests that depressive disorders exist on a continuum , with subthreshold symptoms causing considerable population burden and increasing individual risk of developing major depressive disorder . An alternative strategy to professional treatment of subthreshold depression is population promotion of effective self-help interventions that can be easily applied by an individual without professional guidance . The evidence for self-help interventions for depressive symptoms is review ed in the present work , with the aim of identifying promising interventions that could inform future health promotion campaigns or stimulate further research . Methods A literature search for r and omised controlled trials investigating self-help interventions for depressive disorders or depressive symptoms was performed using PubMed , PsycINFO and the Cochrane Data base of Systematic Review s. Reference lists and citations of included studies were also checked . Studies were grouped into those involving participants with depressive disorders or a high level of depressive symptoms , or non- clinical ly depressed participants not selected for depression . A number of exclusion criteria were applied , including trials with small sample sizes and where the intervention was adjunctive to antidepressants or psychotherapy . Results The majority of interventions search ed had no relevant evidence to review . Of the 38 interventions review ed , the ones with the best evidence of efficacy in depressive disorders were S-adenosylmethionine , St John 's wort , bibliotherapy , computerised interventions , distraction , relaxation training , exercise , pleasant activities , sleep deprivation , and light therapy . A number of other interventions showed promise but had received less research attention . Research in non- clinical sample s indicated immediate beneficial effects on depressed mood for distraction , exercise , humour , music , negative air ionisation , and singing ; while potential for helpful longer-term effects was found for autogenic training , light therapy , omega 3 fatty acids , pets , and prayer . Many of the trials were poor quality and may not generalise to self-help without professional guidance . Conclusion A number of self-help interventions have promising evidence for reducing subthreshold depressive symptoms . Other forms of evidence such as expert consensus may be more appropriate for interventions that are not feasible to evaluate in r and omised controlled trials . There needs to be evaluation of whether promotion to the public of effective self-help strategies for subthreshold depressive symptoms could delay or prevent onset of depressive illness , reduce functional impairment , and prevent progression to other undesirable outcomes such as harmful use of substances Background National guidelines in the UK , United States of America , Canada , and Australia have recently stressed the importance of identifying and treating antenatal anxiety and depression . However , there is little research into the most effective and acceptable ways of helping women manage their symptoms of anxiety and stress during pregnancy . Research indicates the necessity to consider the unique needs and concerns of perinatal population s to ensure treatment engagement , highlighting the need to develop specialised treatments which could be integrated within routine antenatal healthcare services . This trial aims to develop a brief intervention for antenatal anxiety , with a focus on embedding the delivery of the treatment within routine antenatal care . Methods / Design This study is a two-phase feasibility trial . In phase 1 we will develop and pilot a brief intervention for antenatal anxiety , blended with group support , to be led by midwives . This intervention will draw on cognitive behavioural principles and wider learning from existing interventions that have been used to reduce anxiety in expectant mothers . The intervention will then be tested in a pilot r and omised controlled trial in phase 2 . The following outcomes will be assessed : ( 1 ) number of participants meeting eligibility criteria  , ( 2 ) number of participants consenting to the study , ( 3 )  number of participants r and omised  , ( 4 ) number of sessions completed by those in the intervention arm , and ( 5 ) number of participants completing the post-intervention outcome measures . Secondary outcomes comprise : detailed feedback on acceptability , which will guide further development of the intervention ; and outcome data on symptoms of maternal and paternal anxiety and depression , maternal quality of life , quality of couple relationship , mother-child bonding , infant temperament and infant sleep . Discussion The study will provide important data to inform the design of a future full-scale r and omised controlled trial of a brief intervention for anxiety during pregnancy . This will include information on its acceptability and feasibility regarding implementation within current antenatal services , which will inform whether ultimately this provision could be rolled out widely in healthcare setting s . Trial registration Current Controlled Trials IS RCT N95282830 . Registered on 29 October 2014
No single measure was identified for use across the range of FND symptoms in adults .
Across r and omised controlled trials ( k=40 ) and observational treatment studies ( k=40 ) , outcome measures most often assessed core FND symptom change .
Other domains measured commonly were additional physical and psychological symptoms , life impact ( ie , quality of life , disability and general functioning ) and health economics/cost-utility ( eg , healthcare re source use and quality -adjusted life years ) .
CONCLUSIONS There are few well-vali date d FND-specific outcome measures .
OBJECTIVES We aim ed to identify existing outcome measures for functional neurological disorder ( FND ) , to inform the development of recommendations and to guide future research on FND outcomes .