Lancet
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Randomized Controlled Trial Multicenter Study Pragmatic Clinical Trial
The clinical and cost-effectiveness of total versus partial knee replacement in patients with medial compartment osteoarthritis (TOPKAT): 5-year outcomes of a randomised controlled trial.
Late-stage isolated medial knee osteoarthritis can be treated with total knee replacement (TKR) or partial knee replacement (PKR). There is high variation in treatment choice and little robust evidence to guide selection. The Total or Partial Knee Arthroplasty Trial (TOPKAT) therefore aims to assess the clinical effectiveness and cost-effectiveness of TKR versus PKR in patients with medial compartment osteoarthritis of the knee, and this represents an analysis of the main endpoints at 5 years. ⋯ National Institute for Health Research Health Technology Assessment Programme.
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Randomized Controlled Trial Multicenter Study
Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial.
Rimegepant, a small molecule calcitonin gene-related peptide receptor antagonist, has shown efficacy in the acute treatment of migraine using a standard tablet formulation. The objective of this trial was to compare the efficacy, safety, and tolerability of a novel orally disintegrating tablet formulation of rimegepant at 75 mg with placebo in the acute treatment of migraine. ⋯ Biohaven Pharmaceuticals.
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Alcohol use disorders consist of disorders characterised by compulsive heavy alcohol use and loss of control over alcohol intake. Alcohol use disorders are some of the most prevalent mental disorders globally, especially in high-income and upper-middle-income countries; and are associated with high mortality and burden of disease, mainly due to medical consequences, such as liver cirrhosis or injury. ⋯ Primary health care should be responsible for most treatment, with routine screening for alcohol use, and the provision of a staggered treatment response, from brief advice to pharmacological treatment. Clinical interventions for these disorders should be embedded in a supportive environment, which can be bolstered by the creation of alcohol control policies aimed at reducing the overall level of consumption.
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Antibody-drug conjugates (ADCs) are immunoconjugates comprised of a monoclonal antibody tethered to a cytotoxic drug (known as the payload) via a chemical linker. The ADC is designed to selectively deliver the ultratoxic payload directly to the target cancer cells. ⋯ In this Therapeutics paper, we review recent clinical experience with the approved ADCs and other promising late-stage candidates on the horizon, following an overview of the biology and chemistry of ADCs and how the individual components of an ADC (antibody [or target], linker and conjugation chemistry, and cytotoxic payload) influence its activity. We briefly discuss opportunities for enhancing ADC efficacy, drug resistance, and future perspectives for this novel antibody-based molecular platform, which has great potential to make a paradigm shift in cancer chemotherapy.
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Multicenter Study
Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study.
Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. ⋯ Bill & Melinda Gates Foundation.