158 research outputs found

    Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence

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    Objectives: To reanalyse SmithKline Beecham’s Study 329 (published by Keller and colleagues in 2001), the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The reanalysis under the restoring invisible and abandoned trials (RIAT) initiative was done to see whether access to and reanalysis of a full dataset from a randomised controlled trial would have clinically relevant implications for evidence based medicine. Design: Double blind randomised placebo controlled trial. Setting: 12 North American academic psychiatry centres, from 20 April 1994 to 15 February 1998. Participants: 275 adolescents with major depression of at least eight weeks in duration. Exclusion criteria included a range of comorbid psychiatric and medical disorders and suicidality. Interventions: Participants were randomised to eight weeks double blind treatment with paroxetine (20-40 mg), imipramine (200-300 mg), or placebo. Main outcome measures: The prespecified primary efficacy variables were change from baseline to the end of the eight week acute treatment phase in total Hamilton depression scale (HAM-D) score and the proportion of responders (HAM-D score ≀8 or ≄50% reduction in baseline HAM-D) at acute endpoint. Prespecified secondary outcomes were changes from baseline to endpoint in depression items in K-SADS-L, clinical global impression, autonomous functioning checklist, self-perception profile, and sickness impact scale; predictors of response; and number of patients who relapse during the maintenance phase. Adverse experiences were to be compared primarily by using descriptive statistics. No coding dictionary was prespecified. Results: The efficacy of paroxetine and imipramine was not statistically or clinically significantly different from placebo for any prespecified primary or secondary efficacy outcome. HAM-D scores decreased by 10.7 (least squares mean) (95% confidence interval 9.1 to 12.3), 9.0 (7.4 to 10.5), and 9.1 (7.5 to 10.7) points, respectively, for the paroxetine, imipramine and placebo groups (P=0.20). There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and cardiovascular problems in the imipramine group. Conclusions: Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base.Joanna Le Noury, John M Nardo, David Healy, Jon Jureidini, Melissa Raven, Catalin Tufanaru, Elia Abi-Jaoud

    Measuring financial risk protection in health benefits packages: scoping review protocol to inform allocative efficiency studies

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    INTRODUCTION: To progress towards Universal Health Coverage (UHC), countries will need to define a health benefits package of services free at the point of use. Financial risk protection is a core component of UHC and should therefore be considered a key dimension of health benefits packages. Allocative efficiency modelling tools can support national analytical capacity to inform an evidence-based selection of services, but none are currently able to estimate financial risk protection. A review of existing methods used to measure financial risk protection can facilitate their inclusion in modelling tools so that the latter can become more relevant to national decision making in light of UHC. METHODS AND ANALYSIS: This protocol proposes to conduct a scoping review of existing methods used to measure financial risk protection and assess their potential to inform the selection of services in a health benefits package. The proposed review will follow the methodological framework developed by Arksey and O'Malley and the subsequent recommendations made by Levac et al. Several databases will be systematically searched including: (1) PubMed; (2) Scopus; (3) Web of Science and (4) Google Scholar. Grey literature will also be scanned, and the bibliography of all selected studies will be hand searched. Following the selection of studies according to defined inclusion and exclusion criteria, key characteristics will be collected from the studies using a data extraction tool. Key characteristics will include the type of method used, geographical region of focus and application to specific services or packages. The extracted data will then be charted, collated, reported and summarised using descriptive statistics, a thematic analysis and graphical presentations. ETHICS AND DISSEMINATION: The scoping review proposed in this protocol does not require ethical approval. The final results will be disseminated via publication in a peer-reviewed journal, conference presentations and shared with key stakeholders

    Improving Allocative Efficiency in Zimbabwe’s Health Sector: Results from the Health Interventions Prioritization Tool

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    The country of Zimbabwe has seen some important improvements in key health outcomes since 2009. However, despite progress in some areas of the health sector, the country did not meet its Millennium Development Goals (MDGs) and current progress falls short of the Sustainable Development Goals (SDGs) milestones. As is often the case, the poor and rural populations in Zimbabwe bear a disproportionate burden of disease and health risks. The situation is compounded by national economic challenges and health sector spending inefficiencies that have resulted in households bearing an increasing share of health sector financing, mainly through out-of-pocket expenditures. Households provide approximately 25 percent of health sector financing in Zimbabwe. Again, the poor and rural populations are hardest hit by this economic reality. Zimbabwe was one of the few countries in which HIPtool was piloted at the proof of concept stage. HIPtool enables the mathematical prioritization of interventions based on existing data and a set of criteria. It provides a technical foundation to further develop an essential health benefits package. However, HIPtool, at this stage in development, still has strong limitations, which are outlined along with results in this report

    The Role of Radiotherapy In the Management of Massive Intrahepatic Cholangiocarcinoma

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    https://openworks.mdanderson.org/sumexp21/1005/thumbnail.jp

    Modeling of the effect of a thermoelectric magnetic force onto conducting particles immersed in the liquid metal

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    International audienceSimulation of a thermo-electromagnetic force which acts on a conducting particle immersed into liquid metal is performed using multi-gird multi-physics software AEQUATIO. To verify numerical solutions a model thermoelectric problem is solved using two methods. In the first one a phase function is used to indicate the phase transition whereas in the second the solid particle is described with a real frontier of a simplified shape. Numerical and analytical solutions for a model problem qualitatively agree but strong oscillations are observed in a numerical solution with a phase function. Further AEQUQTIO is applied for calculation of the velocity of a dendrite fragment observed in-situ in experiment of solidification of AlCu alloy. Numerical solution gives a good agreement with the experimental observation

    Using allocative efficiency analysis to inform health benefits package design for progressing towards Universal Health Coverage: Proof-of-concept studies in countries seeking decision support

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    Background: Countries are increasingly defining health benefits packages (HBPs) as a way of progressing towards Universal Health Coverage (UHC). Resources for health are commonly constrained, so it is imperative to allocate funds as efficiently as possible. We conducted allocative efficiency analyses using the Health Interventions Prioritization tool (HIPtool) to estimate the cost and impact of potential HBPs in three countries. These analyses explore the usefulness of allocative efficiency analysis and HIPtool in particular, in contributing to priority setting discussions. / Methods and findings: HIPtool is an open-access and open-source allocative efficiency modelling tool. It is preloaded with publicly available data, including data on the 218 cost-effective interventions comprising the Essential UHC package identified in the 3rd Edition of Disease Control Priorities, and global burden of disease data from the Institute for Health Metrics and Evaluation. For these analyses, the data were adapted to the health systems of Armenia, Cîte d’Ivoire and Zimbabwe. Local data replaced global data where possible. Optimized resource allocations were then estimated using the optimization algorithm. In Armenia, optimized spending on UHC interventions could avert 26% more disability-adjusted life years (DALYs), but even highly cost-effective interventions are not funded without an increase in the current health budget. In Cîte d’Ivoire, surgical interventions, maternal and child health and health promotion interventions are scaled up under optimized spending with an estimated 22% increase in DALYs averted–mostly at the primary care level. In Zimbabwe, the estimated gain was even higher at 49% of additional DALYs averted through optimized spending. / Conclusions: HIPtool applications can assist discussions around spending prioritization, HBP design and primary health care transformation. The analyses provided actionable policy recommendations regarding spending allocations across specific delivery platforms, disease programs and interventions. Resource constraints exacerbated by the COVID-19 pandemic increase the need for formal planning of resource allocation to maximize health benefits

    Public health benefits of shifting from inpatient to outpatient TB care in Eastern Europe: optimising TB investments in Belarus, the Republic of Moldova, and Romania

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    Background: High rates of drug-resistant tuberculosis (DR TB) continue to threaten public health, especially in Eastern Europe. Costs for treating DR TB are substantially higher than treating drug-susceptible TB, and higher yet if DR TB services are delivered in hospital. Therefore, countries are encouraged to transition from inpatient to ambulatory-focused TB care, which has been shown to have non-inferior health outcomes. / Methods: Allocative efficiency analyses were conducted for three countries in Eastern Europe, Belarus, the Republic of Moldova, and Romania to minimise a combination of active TB cases, prevalence of active TB, and TB-related deaths by 2035. These mathematical optimisations were carried out using Optima TB, a dynamical compartmental model of TB transmission. The focus of this study was to project the health and financial gains that could be realised if TB service delivery shifted from hospital to ambulatory-based care. / Findings: These analyses show that transitioning from inpatient to ambulatory TB care could reduce treatment costs by 5%−31% or almost 35 million US dollars across these three countries without affecting the quality of care. Improved TB outcomes could be achieved without additional spending by reinvesting these potential savings in cost-effective prevention and diagnosis interventions. / Conclusions: National governments should examine barriers delaying the adoption of outpatient DR TB care and consider the lost opportunities caused by delays in switching to more efficient and effective treatment modes
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