836 research outputs found

    Applying the estimands framework to non-inferiority trials: guidance on choice of hypothetical estimands for non-adherence and comparison of estimation methods

    Full text link
    A common concern in non-inferiority (NI) trials is that non adherence due, for example, to poor study conduct can make treatment arms artificially similar. Because intention to treat analyses can be anti-conservative in this situation, per protocol analyses are sometimes recommended. However, such advice does not consider the estimands framework, nor the risk of bias from per protocol analyses. We therefore sought to update the above guidance using the estimands framework, and compare estimators to improve on the performance of per protocol analyses. We argue the main threat to validity of NI trials is the occurrence of trial specific intercurrent events (IEs), that is, IEs which occur in a trial setting, but would not occur in practice. To guard against erroneous conclusions of non inferiority, we suggest an estimand using a hypothetical strategy for trial specific IEs should be employed, with handling of other non trial specific IEs chosen based on clinical considerations. We provide an overview of estimators that could be used to estimate a hypothetical estimand, including inverse probability weighting (IPW), and two instrumental variable approaches (one using an informative Bayesian prior on the effect of standard treatment, and one using a treatment by covariate interaction as an instrument). We compare them, using simulation in the setting of all or nothing compliance in two active treatment arms, and conclude both IPW and the instrumental variable method using a Bayesian prior are potentially useful approaches, with the choice between them depending on which assumptions are most plausible for a given trial

    Distribution and abundance of sei whales off the west coast of the Falkland Islands

    Get PDF
    The survey was funded by Falklands Conservation, the Royal Society for the Protection of Birds, and the Falkland Islands Government Environmental Studies Budget.Little information exists on the current status of Southern Hemisphere sei whales (Balaenoptera borealis). We assessed their distribution and abundance along the west coast of the Falkland Islands (southwest Atlantic) during February and March 2018, using line transect and nonsystematic surveys. Abundance estimates were generated for a single survey stratum using design- and model-based approaches. Sightings of sei whales and unidentified baleen whales (most, if not all, likely to be sei whales) occurred from the coast to the 100 m depth isobath that marked the offshore boundary of the stratum. The modeled distribution predicted highest whale densities in King George Bay and in the waters between Weddell Island and the Passage Islands. Sei whale abundance was estimated as 716 animals (CV = 0.22; 95% CI [448, 1,144]; density = 0.20 whales/km2) using the design-based approach, and 707 animals (CV = 0.11; 95% CI [566, 877]; density = 0.20 whales/km2) using the model-based approach. For sei whales and unidentified baleen whales combined, the equivalent estimates were 916 animals (CV = 0.19; 95% CI [606, 1,384]; density = 0.26 whales/km2) and 895 animals (CV = 0.074; 95% CI [777, 1,032]; density = 0.25 whales/km2). The data indicate that the Falkland Islands inner shelf region may support globally important seasonal feeding aggregations of sei whales, and potentially qualify as a Key Biodiversity Area.PostprintPeer reviewe

    A three-year prospective study of the presentation and clinical outcomes of major bleeding episodes associated with oral anticoagulant use in the UK (ORANGE study).

    Get PDF
    The outcomes of patients developing major bleeding while on oral anticoagulants remain largely unquantified. The objectives of this study were to: (i) describe the burden of major hemorrhage associated with all available oral anticoagulants in terms of proportion of bleeds which are intracranial hemorrhages, in-hospital mortality and duration of hospitalization following major bleeding; (ii) identify risk factors for mortality; and (iii) compare the characteristics of major hemorrhage between cases treated with warfarin and direct oral anticoagulants for the subgroups of patients with atrial fibrillation or venous thromboembolism. This was a multicenter, 3-year prospective cohort study of patients aged ≥18 years on oral anticoagulants who developed major hemorrhage leading to hospitalization. The patients were followed up for 30 days or until discharge or death, whichever occurred first. In total 2,192 patients (47% female, 81% on warfarin, median age 80 years) were reported between October 2013 and August 2016 from 32 hospitals in the UK. Bleeding sites were intracranial (44%), gastrointestinal (33%), and other (24%). The in-hospital mortality was 21% (95% CI: 19%-23%) overall, and 33% (95% CI: 30%-36%) for patients with intracranial hemorrhage. Intracranial hemorrhage, advanced age, spontaneous bleeding, liver failure and cancer were risk factors for death. Compared to warfarin-treated patients, patients treated with direct oral anticoagulants were older and had lower odds of subdural/epidural, subarachnoid and intracerebral bleeding. The mortality rate due to major bleeding was not different between patients being treated with warfarin or direct oral anticoagulants. Major bleeding while on oral anticoagulant therapy leads to considerable hospital stays and short-term mortality

    Four Butterflies: End of Life Stories of Transition and Transformation

    Get PDF
    In this article, the author discusses her experiences as an Artist In Residence in the Department of Palliative Care and Rehabilitation Medicine at the University of Texas M. D. Anderson Cancer Center. Emphasis is placed on the ways in which end of life images and narratives often unfold in the fragile yet powerful space where conceptions of aesthetics and spirituality intersect with critical issues in the medical humanities. Drawing on four vivid case studies, the author examines the ways in which end of life narratives shed valuable light on conceptions of the subtlety of human embodiment; issues of violation, sorrow, and forgiveness; the mystical dimensions of traditional cultural beliefs; and the capacity for perceiving the natural world as a living symbol of grace. In so doing, she explores how the themes of transition and transformation become invested with meaningful existential and symbolic dimensions in artworks that give voice and presence to some of the most vulnerable, and often invisible, members of our societyラpeople at the end of life

    Learning To Be Affected: Social suffering and total pain at life’s borders.

    Get PDF
    The practice of Live Sociology in situations of pain and suffering is the author’s focus. An outline of the challenges of understanding pain is followed by a discussion of Bourdieu’s ‘social suffering’ (1999) and the palliative care philosophy of ‘total pain’. Using examples from qualitative research on disadvantaged dying migrants in the UK, attention is given to the methods that are improvised by dying people and care practitioners in attempts to bridge intersubjective divides, where the causes and routes of pain can be ontologically and temporally indeterminate and/or withdrawn. The paper contends that these latter phenomena are the incitement for the inventive bridging and performative work of care and Live Sociological methods, both of which are concerned with opposing suffering. Drawing from the ontology of total pain, I highlight the importance of (i) an engagement with a range of materials out of which attempts at intersubjective bridging can be produced, and which exceed the social, the material, and the temporally linear; and (ii) an empirical sensibility that is hospitable to the inaccessible and non-relational
    corecore