Prevention of cisplatin-induced hearing loss in children: Informing the design of future clinical trials.

Cisplatin is an essential chemotherapeutic agent in the treatment of many pediatric cancers. Unfortunately, cisplatin-induced hearing loss (CIHL) is a common, clinically significant side effect with life-long ramifications, particularly for young children. ACCL05C1 and ACCL0431 are two recently completed Childrens Oncology Group studies focused on the measurement and prevention of CIHL. The purpose of this paper was to gain insights from ACCL05C1 and ACCL0431, the first published cooperative group studies dedicated solely to CIHL, to inform the design of future pediatric otoprotection trials. Use of otoprotective agents is an attractive strategy for preventing CIHL, but their successful development must overcome a unique constellation of methodological challenges related to translating preclinical research into clinical trials that are feasible, evaluate practical interventions, and limit risk. Issues particularly important for children include use of appropriate methods for hearing assessment and CIHL severity grading, and use of trial designs that are well-informed by preclinical models and suitable for relatively small sample sizes. Increasing interest has made available new funding opportunities for expanding this urgently needed research

The Roadmap for Implementing Value-Based Healthcare in European University Hospitals—Consensus Report and Recommendations

Expert recommendation; Patient-reported outcomes; Quality in healthcareRecomendación experta; Resultados informados por el paciente; Calidad en la asistencia sanitariaRecomanació experta; Resultats informats pel pacient; Qualitat en l'assistència sanitàriaObjectives Value-based healthcare (VBHC) aims at improving patient outcomes while optimizing the use of hospitals’ resources among medical personnel, administrations, and support services through an evidence-based, collaborative approach. In this article, we present a blueprint for the implementation of VBHC in hospitals, based on our experience as members of the European University Hospital Alliance. Methods The European University Hospital Alliance is a consortium of 9 large hospitals in Europe and aims at increasing the quality and efficiency of care to ultimately drive better outcomes for patients. Results The blueprint describes how to prepare hospitals for VBHC implementation; analyzes gaps, barriers, and facilitators; and explores the most effective ways to turn patient pathways into a process that results in high-value care. Using a patient-centric approach, we identified 4 core minimum components that must be established as cornerstones and 7 organizational enablers to waive the barriers to implementation and ensure sustainability. Conclusion The blueprint guides through pathway implementation and establishment of key performance indicators in 6 phases, which hospitals can tailor to their current status on their way to implement VBHC

Plasmodium malariae infections as a cause of febrile disease in an area of high Plasmodium falciparum transmission intensity in Eastern Uganda.

BACKGROUND: Plasmodium falciparum is responsible for the vast majority of (severe) clinical malaria cases in most African settings. Other Plasmodium species often go undiagnosed but may still have clinical consequences. CASE PRESENTATION: Here, five cases of Plasmodium malariae infections from Eastern Uganda (aged 2-39 years) are presented. These infections were all initially mistaken for P. falciparum, but Plasmodium schizonts (up to 2080/µL) were identified by microscopy. Clinical signs included history of fever and mild anaemia. CONCLUSION: These findings highlight the importance of considering non-falciparum species as the cause of clinical malaria. In areas of intense P. falciparum transmission, where rapid diagnostic tests that detect only P. falciparum antigens are commonly used, non-falciparum malaria cases may be missed

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Methane emissions from oil and gas production sites in Alberta, Canada

We performed ground-based measurements (downwind, site-wide characterization) of methane emissions from older light oil and natural gas production sites in Alberta, Canada (Red Deer region, 60 measured sites). We developed a distribution of site-based methane emissions and as previously found in production regions in the United States, a small fraction of the sites account for the majority of methane emissions: 20% of the sites emit three quarters of the methane from oil and gas production. Using empirically derived emission factors, we compared an estimate of regional methane emissions, to a top-down airborne-based measurement of the same region. The airborne measurement was 35% lower, though not statistically different (4,800 ± 3,200 vs. 3,100 ± 2,200 kg CH4 h–1). In Alberta, the majority of these oil and gas emissions go unreported under current reporting requirements. Effective mitigation will most likely require frequent monitoring to identify high-emitting sites as well as leaky components that we hypothesize are also a major contributor to emissions

Effect of COVID-19 lock down on teenage pregnancies in Northern Uganda: an interrupted time series analysis

Abstract Background Pregnancy and childbirth complications are the leading cause of death among girls aged 15–19 years globally, with low- and middle-income countries (LMICs) accounting for 99% of global maternal deaths of women aged 15–49 years. Despite teenage pregnancies declining in many developing countries in recent years, the COVID-19 period intensified the problem and altered the trend for most countries. We determined the effect of the COVID-19 lockdown on the teenage pregnancy trend in Pakwach district, Uganda, to understand its magnitude in our study population. Methods Using interrupted time series analysis (ITS), sometimes known as quasi-experimental time series analysis. We constructed a time series of the first ANC service utilization records for girls aged 10–19 years in Pakwach district, Uganda, and conducted an interrupted series analysis. We compared the two periods of March 2019 to March 2020 and March 2020 to March 2021. We used Stata 15 to conduct our analysis, performed OLS, and plotted the results. Results The teenage pregnancy trend before the lockdown was decreasing by − 0.203 pregnancies per month, but in the first month after the institution of the lockdown (March 20, 2020), there was an increase in the teenage pregnancy rate of 13.9 pregnancies [95% CI: − 33.6 to 61.5], which corresponds to an increase in the monthly trend in teenage pregnancies (relative to the period before the COVID-19 lockdown trend) of 1.53 girls per month. Conclusion Teenage pregnancies increased during the lockdown. This slight increase depicted the impact of the pandemic on the teenage pregnancy trend associated with the COVID-19 outbreak. The government needs to focus on intervention to reduce this trend and avoid any further increases

The Roadmap for Implementing Value-Based Healthcare in European University Hospitals—Consensus Report and Recommendations

Objectives: Value-based healthcare (VBHC) aims at improving patient outcomes while optimizing the use of hospitals’ resources among medical personnel, administrations, and support services through an evidence-based, collaborative approach. In this article, we present a blueprint for the implementation of VBHC in hospitals, based on our experience as members of the European University Hospital Alliance. Methods: The European University Hospital Alliance is a consortium of 9 large hospitals in Europe and aims at increasing the quality and efficiency of care to ultimately drive better outcomes for patients. Results: The blueprint describes how to prepare hospitals for VBHC implementation; analyzes gaps, barriers, and facilitators; and explores the most effective ways to turn patient pathways into a process that results in high-value care. Using a patient-centric approach, we identified 4 core minimum components that must be established as cornerstones and 7 organizational enablers to waive the barriers to implementation and ensure sustainability. Conclusion: The blueprint guides through pathway implementation and establishment of key performance indicators in 6 phases, which hospitals can tailor to their current status on their way to implement VBHC