PLoS medicine
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Randomized Controlled Trial Observational Study
Long-term cognitive effects of menopausal hormone therapy: Findings from the KEEPS Continuation Study.
Findings from Kronos Early Estrogen Prevention Study (KEEPS)-Cog trial suggested no cognitive benefit or harm after 48 months of menopausal hormone therapy (mHT) initiated within 3 years of final menstrual period. To clarify the long-term effects of mHT initiated in early postmenopause, the observational KEEPS Continuation Study reevaluated cognition, mood, and neuroimaging effects in participants enrolled in the KEEPS-Cog and its parent study the KEEPS approximately 10 years after trial completion. We hypothesized that women randomized to transdermal estradiol (tE2) during early postmenopause would show cognitive benefits, while oral conjugated equine estrogens (oCEE) would show no effect, compared to placebo over the 10 years following randomization in the KEEPS trial. ⋯ In these KEEPS Continuation analyses, there were no long-term cognitive effects of short-term exposure to mHT started in early menopause versus placebo. These data provide reassurance about the long-term neurocognitive safety of mHT for symptom management in healthy, recently postmenopausal women, while also suggesting that mHT does not improve or preserve cognitive function in this population.
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The risk of re-operation, otherwise known as revision, following primary hip replacement depends in part on the prosthesis implant materials used. Current performance evidences are based on a broad categorisation grouping together different materials with potentially varying revision risks. We investigated the revision rate of primary total hip replacement (THR) reported in the National Joint Registry by specific types of bearing surfaces used. ⋯ Prosthesis revision is influenced by the prosthesis materials used in the primary procedure with the lowest risk for implants with delta ceramic or oxidised zirconium head and an HCLPE liner/cup. Further work is required to determine the association of implant bearing materials with the risk of rehospitalisation, re-operation other than revision, mortality, and the cost-effectiveness of these materials.
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This study estimated to what extent the number of measurements of cardiometabolic risk factors (e.g., blood pressure, cholesterol, glycated haemoglobin) were impacted by the COVID-19 pandemic and whether these have recovered to expected levels. ⋯ There was a substantial reduction in routine measurements of cardiometabolic risk factors following the COVID-19 pandemic, with variable recovery. The implications for missed diagnoses, worse prognosis, and health inequality are a concern.
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Measles outbreaks are still routine, even in countries where vaccination coverage exceeds the guideline of 95%. Therefore, achieving ambitions for measles eradication will require understanding of how unvaccinated children interact with others who are unvaccinated. It is well established that schools and homes are key settings for both clustering of unvaccinated children and for transmission of infection. In this study, we evaluate the potential for contacts between unvaccinated children in these contexts to facilitate measles outbreaks with a focus on the Netherlands, where large outbreaks have been observed periodically since the introduction of mumps, measles and rubella (MMR). ⋯ Our framework indicates that clustering of unvaccinated children in primary schools connected by unvaccinated children in related secondary schools lead to large, connected clusters of unvaccinated children. Using our approach, we could explain historical outbreaks on a spatial level. Our framework could be further developed to aid future outbreak response.
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Multicenter Study
Safety and tolerability of tegoprubart in patients with amyotrophic lateral sclerosis: A Phase 2A clinical trial.
The interaction of CD40L and its receptor CD40 on activated T cells and B cells respectively control pro-inflammatory activation in the pathophysiology of autoimmunity and transplant rejection. Previous studies have implicated signaling pathways involving CD40L (interchangeably referred to as CD154), as well as adaptive and innate immune cell activation, in the induction of neuroinflammation in neurodegenerative diseases. This study aimed to assess the safety, tolerability, and impact on pro-inflammatory biomarker profiles of an anti CD40L antibody, tegoprubart, in individuals with amyotrophic lateral sclerosis (ALS). ⋯ Tegoprubart appeared to be safe and well tolerated in adults with ALS demonstrating dose-dependent reduction in pro-inflammatory chemokines and cytokines associated with ALS. These results warrant further clinical studies with sufficient power and duration to assess clinical outcomes as a potential treatment for adults with ALS.