Project description:Breast cancer exhibits significant molecular, pathological, and clinical heterogeneity. Current clinicopathological evaluation is imperfect for predicting outcome, which results in overtreatment for many patients, and for others, leads to death from recurrent disease. Therefore, additional criteria are needed to better personalize care and maximize treatment effectiveness and survival. To address these challenges, the Sweden Cancerome Analysis Network - Breast (SCAN-B) consortium was initiated in 2010 as a multicenter prospective study with longsighted aims to 1) analyze breast cancers with next-generation genomic technologies for translational research in a population-based manner and integrated with healthcare; 2) decipher fundamental tumor biology from these analyses; 3) utilize genomic data to develop and validate new clinically-actionable biomarker assays; and 4) build the infrastructure for real-time clinical implementation of molecular diagnostic, prognostic, and predictive tests. In the first phase, we focus on molecular profiling by next-generation RNA-sequencing on the Illumina platform. In the three years from August 30, 2010 through August 31, 2013, we have consented and enrolled 3,979 patients with primary breast cancer at the seven hospital sites in South Sweden, representing approximately 85% of eligible patients in the catchment area. Pre-operative blood samples have been collected for 3,942 (99%) patients and primary tumor specimens collected for 2,929 (74%) patients. Herein we describe the study infrastructure and present initial proof of concept results from prospective RNA-sequencing including tumor molecular subtyping and detection of driver gene mutations. We demonstrate that large-scale population-based collection and RNA-sequencing analysis of breast cancer is feasible. The SCAN-B Initiative should significantly reduce the time to discovery, validation, and clinical implementation of novel molecular diagnostic and predictive tests. We welcome the participation of additional comprehensive cancer treatment centers.

Project description:Breast cancer exhibits significant molecular, pathological, and clinical heterogeneity. Current clinicopathological evaluation is imperfect for predicting outcome, which results in overtreatment for many patients, and for others, leads to death from recurrent disease. Therefore, additional criteria are needed to better personalize care and maximize treatment effectiveness and survival. To address these challenges, the Sweden Cancerome Analysis Network - Breast (SCAN-B) consortium was initiated in 2010 as a multicenter prospective study with longsighted aims to 1) analyze breast cancers with next-generation genomic technologies for translational research in a population-based manner and integrated with healthcare; 2) decipher fundamental tumor biology from these analyses; 3) utilize genomic data to develop and validate new clinically-actionable biomarker assays; and 4) build the infrastructure for real-time clinical implementation of molecular diagnostic, prognostic, and predictive tests. In the first phase, we focus on molecular profiling by next-generation RNA-sequencing on the Illumina platform. In the three years from August 30, 2010 through August 31, 2013, we have consented and enrolled 3,979 patients with primary breast cancer at the seven hospital sites in South Sweden, representing approximately 85% of eligible patients in the catchment area. Pre-operative blood samples have been collected for 3,942 (99%) patients and primary tumor specimens collected for 2,929 (74%) patients. Herein we describe the study infrastructure and present initial proof of concept results from prospective RNA-sequencing including tumor molecular subtyping and detection of driver gene mutations. We demonstrate that large-scale population-based collection and RNA-sequencing analysis of breast cancer is feasible. The SCAN-B Initiative should significantly reduce the time to discovery, validation, and clinical implementation of novel molecular diagnostic and predictive tests. We welcome the participation of additional comprehensive cancer treatment centers. Due to privacy concerns, submitters were not allowed to release the actual sequencing reads

Project description:BackgroundThe implementation of new medical interventions into routine care involves healthcare professionals adopting new clinical behaviours and changing existing ones. Whilst theory-based approaches can help understand healthcare professionals' behaviours, such approaches often focus on a single behaviour and conceptualise its performance in terms of an underlying reflective process. Such approaches fail to consider the impact of non-reflective influences (e.g. habit and automaticity) and how the myriad of competing demands for their time may influence uptake. The current study aimed to apply a dual process theoretical approach to account for reflective and automatic determinants of healthcare professional behaviour while integrating a multiple behaviour approach to understanding the implementation and use of a new self-management tool by healthcare professionals in the context of diabetes care.MethodsFollowing Diabetes UK's national release of the 'Information Prescription' (DUK IP; a self-management tool targeting the management of cholesterol, blood pressure and HbA1c) in January 2015, we conducted semi-structured interviews with 13 healthcare professionals (general practitioners and nurses) who had started to use the DUK IP during consultations to provide self-management advice to people with type 2 diabetes. A theory-based topic guide included pre-specified constructs from a previously developed logic model. We elicited healthcare professionals' views on reflective processes (outcome expectations, self-efficacy, intention, action and coping planning), automatic processes (habit), and multiple behaviour processes (goal priority, goal conflict and goal facilitation). All interviews were audio recorded and transcribed verbatim and all transcripts were independently double coded and analysed using content analysis.ResultsThe majority of healthcare professionals interviewed reported strong intentions to use the DUK IP and having formed a habit of using them after a minimum of one month continuous use. Pop-up cues in the electronic patient records were perceived to facilitate the use of the tool. Factors that conflicted with the use of the DUK IP included existing pathways of providing self-management advice.ConclusionData suggests that constructs from dual process and multiple behaviour approaches are useful to provide supplemental understanding of the implementation of new self-management tools such as the DUK IP and may help to advance behavioural approaches to implementation science.

Project description:BACKGROUND:A new movement towards improved postpartum care calls for restructuring how that care is provided. As professional guidelines evolve, understanding how providers prioritize and practice postpartum care can offer insights about elements of care that may be currently performed more routinely than providers deem a priority to do so, as well as those that may warrant more routine practice. METHODS:We surveyed 600 randomly-sampled U.S. postpartum care providers about their priorities for and the frequency with which specific elements of care are provided, as well as the feasibility of remote delivery of postpartum care provision (i.e., telemedicine). RESULTS:The survey response rate was 43% across medical specialties. Providers reported an average of only 24.4 ± 11.7 min available to spend on the postpartum visit. Certain types of postpartum care were highly prioritized and routinely performed, such as depression screening. Yet, there were also noted discrepancies between prioritized and performed care, revealing competing demands on providers' time. For example, pelvic exams were performed more often than similarly prioritized care, whereas screening for intimate partner violence and substance use were performed less often than similarly-prioritized care. Certain types of care were identified as important that are not explicitly addressed by national practice guidelines (e.g. transitioning to parenthood). Approximately 25% of respondents regarded telemedicine as a feasible remote care delivery alternative to much of the care currently provided in-person. CONCLUSIONS:The time providers have available to offer comprehensive postpartum care is constrained. Understanding how certain elements of care may be competing with one another at a single postpartum visit highlights those elements of care, which may be currently underperformed, as well as those elements of care that may warrant evaluation for future inclusion in standard care. For some providers experiencing time constraints, complementary remote care represents a potentially viable approach to implementing recommendations for transitioning the traditional visit to a more frequent, ongoing postpartum care process. In calling for a new approach to postpartum care delivery, professional organizations should consider the practices and priorities of their constituency as they revise guidelines and shape future research about the value of specific postpartum services.

Project description:This paper studies inference for the average treatment effect in randomized controlled trials with covariate-adaptive randomization. Here, by covariate-adaptive randomization, we mean randomization schemes that first stratify according to baseline covariates and then assign treatment status so as to achieve "balance" within each stratum. Our main requirement is that the randomization scheme assigns treatment status within each stratum so that the fraction of units being assigned to treatment within each stratum has a well behaved distribution centered around a proportion π as the sample size tends to infinity. Such schemes include, for example, Efron's biased-coin design and stratified block randomization. When testing the null hypothesis that the average treatment effect equals a pre-specified value in such settings, we first show the usual two-sample t-test is conservative in the sense that it has limiting rejection probability under the null hypothesis no greater than and typically strictly less than the nominal level. We show, however, that a simple adjustment to the usual standard error of the two-sample t-test leads to a test that is exact in the sense that its limiting rejection probability under the null hypothesis equals the nominal level. Next, we consider the usual t-test (on the coefficient on treatment assignment) in a linear regression of outcomes on treatment assignment and indicators for each of the strata. We show that this test is exact for the important special case of randomization schemes with π = 1 2 , but is otherwise conservative. We again provide a simple adjustment to the standard errors that yields an exact test more generally. Finally, we study the behavior of a modified version of a permutation test, which we refer to as the covariate-adaptive permutation test, that only permutes treatment status for units within the same stratum. When applied to the usual two-sample t-statistic, we show that this test is exact for randomization schemes with π = 1 2 and that additionally achieve what we refer to as "strong balance." For randomization schemes with π ≠ 1 2 , this test may have limiting rejection probability under the null hypothesis strictly greater than the nominal level. When applied to a suitably adjusted version of the two-sample t-statistic, however, we show that this test is exact for all randomization schemes that achieve "strong balance," including those with π ≠ 1 2 . A simulation study confirms the practical relevance of our theoretical results. We conclude with recommendations for empirical practice and an empirical illustration·.

Project description:INTRODUCTION:There is considerable interest in triaging victims of large vessel occlusion (LVO) strokes to comprehensive stroke centers. Timely access to interventional therapy has been linked to improved stroke outcomes. Accurate triage depends upon the use of a validated screening tool in addition to several emergency medical system (EMS)-specific factors. This study examines the integration of a modified Rapid Arterial oCcclusion Evaluation (mRACE) score into an existing stroke treatment protocol. METHODS:We performed a retrospective review of EMS and hospital charts of patients transported to a single comprehensive stroke center. Adult patients with an EMS provider impression of "stroke/TIA," "CVA," or "neurological problem" were included for analysis. EMS protocols mandated the use of the Cincinnati Prehospital Stroke Score (CPSS). The novel protocol authorized the use of the mRACE score to identify candidates for triage directly to the comprehensive stroke center. We calculated specificity and sensitivity for various stroke screens (CPSS and a mRACE exam) for the detection of LVO stroke. The score's metrics were evaluated as a surrogate marker for a successful EMS triage protocol. RESULTS:We included 312 prehospital charts in the final analysis. The CPSS score exhibited reliable sensitivity at 85%. Specificity of CPSS for an LVO was calculated at 73%. For an mRACE score of five or greater, the sensitivity was 25%. Specificity for mRACE was calculated at 75%. The positive predictive value of the mRACE score for an LVO was estimated at 12.50%. CONCLUSION:In this retrospective study of patients triaged to a single comprehensive stroke center, the addition of an LVO-specific screening tool failed to improve accuracy. Reliable triage of LVO strokes in the prehospital setting is a challenging task. In addition to statistical performance of a particular stroke score, a successful EMS protocol should consider system-based factors such as provider education and training. Study limitations can inform future iterations of LVO triage protocols.

Dataset Information

Managing competing demands in the implementation of response-adaptive randomization in a large multicenter phase III acute stroke trial.

Publications

Managing competing demands in the implementation of response-adaptive randomization in a large multicenter phase III acute stroke trial.

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