PLoS medicine
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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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Postoperative periprosthetic femoral fracture (POPFF) after total hip replacement (THR) requires complex surgery and is associated with a high morbidity, mortality, and cost. Although the United Kingdom based National Joint Registry (NJR) captures over 95% of THRs treated with revision, before June 2023 it did not capture POPFF treated with fixation. We aimed to estimate the incidence and epidemiology of POPFF treated with either surgery in England. ⋯ To date, the incidence of POPFF may have been underestimated with over 50% of cases missed if the case identification in this study is correct. After including these cases, we observed that POPFF is the largest reason for major reoperation following THR and patients sustaining these injuries have a high risk of death. The prevention and treatment of POPFF and requires further resource allocation and research.
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Randomized Controlled Trial Multicenter Study
Cost-effectiveness of a patient-reported outcome-based remote monitoring and alert intervention for early detection of critical recovery after joint replacement: A randomised controlled trial.
While the effectiveness of patient-reported outcome measures (PROMs) as an intervention to impact patient pathways has been established for cancer care, it is unknown for other indications. We assessed the cost-effectiveness of a PROM-based monitoring and alert intervention for early detection of critical recovery paths following hip and knee replacement. ⋯ The intervention significantly improved patient outcomes at lower costs in patients with hip replacements when compared with standard care. Further it showed a nonsignificant cost reduction in knee replacement patients. This reinforces the notion that PROMs can be utilised as a cost-effective instrument for remote monitoring in standard care settings.
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Randomized Controlled Trial
Growth, physical, and cognitive function in children who are born HIV-free: School-age follow-up of a cluster-randomised trial in rural Zimbabwe.
Globally, over 16 million children were exposed to HIV during pregnancy but remain HIV-free at birth and throughout childhood by 2022. Children born HIV-free (CBHF) have higher morbidity and mortality and poorer neurodevelopment in early life compared to children who are HIV-unexposed (CHU), but long-term outcomes remain uncertain. We characterised school-age growth, cognitive and physical function in CBHF and CHU previously enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. ⋯ In this study, we found that CBHF had reductions in cognitive function compared to CHU at 7 years of age across multiple domains. Further research is needed to define the biological and psychosocial mechanisms underlying these differences to inform future interventions that help CBHF thrive across the life-course.
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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.