Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

The impact of COVID-19 lockdown announcements on mental health: quasi-natural experiment in Lombardy, Italy

Abstract Background Evidence showed that mental health problems have risen markedly during COVID-19. It is unclear if part of the mental sufferings relates to the climate of uncertainty and confusion originated from rough communication by health officials and politicians. Here, we test the impact of unanticipated policy announcements of lockdown policies on mental health of the older population. Methods We used a representative telephone-based survey of 4400 people aged 65 years or older in Italy’s Lombardy region to compare information on self-reported symptoms of anxiety, depression and poor-quality sleep of subjects interviewed on the days of the policy announcement with that of subjects interviewed on other days. We used regression models adjusting for potential socio-demographic confounders as well study design with inverse probability weighting. Results On days when policymakers announced to extend the lockdown, mental health deteriorated on average by 5.5 percentage points [95% confidence interval (CI): 1.1–9.8] for self-reported anxiety symptoms and 5.1 percentage points (95% CI: 2.7–7.4) for self-reported depressive symptoms. The effect of the announcement to shorten the lockdown is more moderate but statistically significant. These associations were short term in duration; after just 1 day, self-reported mental health and sleep quality return to levels better than pre-announcement until a new policy change. Conclusions Our research shows that lockdown policy announcements are associated with short-term worsening in mental distress, highlighting the importance of appropriate communication strategies and political determinations in crisis times. </jats:sec

Survival and Health Care Burden of Children With Retinoblastoma in Europe

Importance: Studies on the epidemiology of retinoblastoma (RB) could lead to improvement in management. Objective: To estimate the incidence and survival of RB in European children and the occurrence of second primary tumors (other than RB) in these patients. Design, setting, and participants: This cohort study used population-based data from 81 cancer registries in 31 European countries adhering to the European Cancer Registries (EUROCARE-6) project. Data collection took place between January 2000 and December 2013. European children aged 0 to 14 years diagnosed with RB were included. Data were analyzed from May to November 2023. Exposures: Diagnosis of RB with International Classification of Diseases for Oncology, Third Edition (ICD-O-3), morphology coded 9510-9514 (retinoblastoma) and malignant behavior (fifth digit of morphology code, 3). Main outcome and measures: Annual incidence (per million children aged 0-14 years), 5-year survival (%), and the standardized incidence ratio (SIR) of subsequent malignant neoplasms. Results: The study included 3262 patients (mean [SD] age, 1.27 [1.63] years; 1706 [52%] male and 1556 [48%] female) from 81 registries. Of these, 3098 patients were considered in trend analysis after excluding registries with incomplete time coverage: 940 in 2000 to 2003, 703 in 2004 to 2006, 744 in 2007 to 2009, and 856 in 2010 to 2013. The estimated overall European incidence rate was 4.0 (95% CI, 3.9-4.1). Rates among countries varied from less than 2 million to greater than 6 million per year. No time trend of incidence was observed in any area. The overall European 5-year survival was 97.8% (95% CI, 95.5-98.9; 3180 cases). Five-year survival was lower in Estonia and Bulgaria (&lt;80%) and 100% in several countries. Twenty-five subsequent malignant neoplasms were recorded during follow-up (up to 14 years), with an SIR of 8.2 and with cases occurring at mean ages between 1.3 and 8.9 years across different sites. An increased risk was found for hematological tumors (SIR, 5) and bone and soft tissue sarcomas (SIR, 29). Conclusions and relevance: This study showed RB incidence remained stable at 4.0 per 1 000 000 European children aged 0 to 14 years from 2000 to 2013, but estimates varied among countries and differences in survival across countries persist. These data might be used to monitor RB management and occurrences of second tumors. The findings suggest future registry studies should aim to collect standardized RB stage at diagnosis and treatment to interpret disparities and potentially improve surveillance