Bmc Med
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The relationship between chemotherapy-related toxicities and prognosis is unclear. Previous studies have examined the association of myelosuppression parameters or neuropathy with survival and reported conflicting results. This study aims to investigate 13 common chemotherapy toxicities and their association with relapse-free survival and breast cancer-specific survival. ⋯ This large study shows a significant association between chemotherapy-induced neutropenia and increased survival. It also identifies a strong relationship between low/normal BMI and increased incidence of severe neutropenia. It provides evidence to support the development of neutropenia-adapted clinical trials to investigate optimal dose calculation and its impact on clinical outcome. This is important in populations where obesity may lead to sub-optimal chemotherapy doses.
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The declining efficacy of dihydroartemisinin-piperaquine against Plasmodium falciparum in Cambodia, along with increasing numbers of recrudescent cases, suggests resistance to both artemisinin and piperaquine. Available in vitro piperaquine susceptibility assays do not correlate with treatment outcome. A novel assay using a pharmacologically relevant piperaquine dose/time exposure was designed and its relevance explored in retrospective and prospective studies. ⋯ PSA adequately captures the piperaquine resistance/recrudescence phenotype, a mainstay to identify molecular marker(s) and evaluate efficacy of alternative drugs. Combined ex vivo PSA and K13 genotyping provides a convenient monitor for both artemisinin and piperaquine resistance where dihydroartemisinin-piperaquine is used.
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Individual participant data (IPD) from completed clinical trials should be responsibly shared to support efficient clinical research, generate new knowledge and bring benefit to patients. The Medical Research Council (MRC) Hubs for Trials Methodology Research (HTMR) has developed guidance to facilitate the sharing of IPD from publicly funded clinical trials. ⋯ Implementation of these principles will improve transparency, increase the coherent sharing of IPD from publicly funded trials, and help publicly funded trials to adhere to trial funder and journal requirements for data sharing.
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Randomized Controlled Trial
Randomized trial of primaquine hypnozoitocidal efficacy when administered with artemisinin-combined blood schizontocides for radical cure of Plasmodium vivax in Indonesia.
Safety and efficacy of primaquine against repeated attacks of Plasmodium vivax depends upon co-administered blood schizontocidal therapy in radical cure. We assessed primaquine (PQ) as hypnozoitocide when administered with dihydroartemisinin-piperaquine (Eurartesim®, DHA-PP) or artesunate-pyronaridine (Pyramax®, AS-PYR) to affirm its good tolerability and efficacy. A third arm, artesunate followed by primaquine, was not intended as therapy for practice, but addressed a hypothesis concerning primaquine efficacy without co-administration of blood schizontocide. ⋯ This trial offers evidence of good tolerability and efficacy of PQ against P. vivax relapse when administered concurrently with DHA-PP or AS-PYR. These offer alternative partner drugs for radical cure with primaquine. The AS arm demonstrated efficacy with a total dose of 7 mg/kg PQ without concurrently administered blood schizontocide, another option when primaquine therapy is removed in time from the treatment of the acute malaria or applied presumptively without an attack.
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Historical Article
Benchmarking health system performance across regions in Uganda: a systematic analysis of levels and trends in key maternal and child health interventions, 1990-2011.
Globally, countries are increasingly prioritizing the reduction of health inequalities and provision of universal health coverage. While national benchmarking has become more common, such work at subnational levels is rare. The timely and rigorous measurement of local levels and trends in key health interventions and outcomes is vital to identifying areas of progress and detecting early signs of stalled or declining health system performance. Previous studies have yet to provide a comprehensive assessment of Uganda's maternal and child health (MCH) landscape at the subnational level. ⋯ The MCH landscape in Uganda has, for the most part, improved between 1990 and 2011. Subnational benchmarking quantified the persistence of geographic health inequalities and identified regions in need of additional health systems strengthening. The tracking and analysis of subnational health trends should be conducted regularly to better guide policy decisions and strengthen responsiveness to local health needs.