Population-based analysis of POT1 variants in a cutaneous melanoma case-control cohort.

Pathogenic germline variants in the protection of telomeres 1 gene (POT1) have been associated with predisposition to a range of tumour types, including melanoma, glioma, leukaemia and cardiac angiosarcoma. We sequenced all coding exons of the POT1 gene in 2928 European-descent melanoma cases and 3298 controls, identifying 43 protein-changing genetic variants. We performed POT1-telomere binding assays for all missense and stop-gained variants, finding nine variants that impair or disrupt protein-telomere complex formation, and we further define the role of variants in the regulation of telomere length and complex formation through molecular dynamics simulations. We determine that POT1 coding variants are a minor contributor to melanoma burden in the general population, with only about 0.5% of melanoma cases carrying germline pathogenic variants in this gene, but should be screened in individuals with a strong family history of melanoma and/or multiple malignancies.

Accuracy and economic evaluation of screening tests for undiagnosed COPD among hypertensive individuals in Brazil.

In Brazil, prevalence of diagnosed COPD among adults aged 40 years and over is 16% although over 70% of cases remain undiagnosed. Hypertension is common and well-recorded in primary care, and frequently co-exists with COPD because of common causes such as tobacco smoking, therefore we conducted a cross-sectional screening test accuracy study in nine Basic Health Units in Brazil, among hypertensive patients aged ≥40 years to identify the optimum screening test/combinations to detect undiagnosed COPD. We compared six index tests (four screening questionnaires, microspirometer and peak flow) against the reference test defined as those below the lower limit of normal (LLN-GLI) on quality diagnostic spirometry, with confirmed COPD at clinical review. Of 1162 participants, 6.8% (n = 79) had clinically confirmed COPD. Peak flow had a higher specificity but lower sensitivity than microspirometry (sensitivity 44.3% [95% CI 33.1, 55.9], specificity 95.5% [95% CI 94.1, 96.6]). SBQ performed well compared to the other questionnaires (sensitivity 75.9% [95% CI 65.0, 84.9], specificity 59.2% [95% CI 56.2, 62.1]). A strategy requiring both SBQ and peak flow to be positive yielded sensitivity of 39.2% (95% CI 28.4, 50.9) and specificity of 97.0% (95% CI 95.7, 97.9). The use of simple screening tests was feasible within the Brazilian primary care setting. The combination of SBQ and peak flow appeared most efficient, when considering performance of the test, cost and ease of use (costing £1690 (5554 R$) with 26.7 cases detected per 1,000 patients). However, the choice of screening tests depends on the clinical setting and availability of resources.ISRCTN registration number: 11377960.

Health outcomes, utilization, and equity in Chile: an evolution from 1990 to 2015 and the effects of the last health reform.

OBJECTIVE: Chile is an attractive case study because of the deep political changes that it underwent over a short period of time: from a universal health service (60s), through a neoliberal reform (70s) and onto a series of legislative reforms (80s-90s). This article aims to explore and assess the evolution of health outcomes, equity, and utilization in Chile through the last period of these reforms (1990-2015). STUDY DESIGN: Standardized health equity analysis. METHODS: We conducted a standardized economic analysis on health equity and healthcare utilization using the ADePT software (by the World Bank) and using data from the Chilean National Socio-economic Survey. We evaluated trends of health equity and examined concentration curves of health utilization of healthcare services and health outcomes such as children/elder/pregnant nutritional status, self-reported health, and physical limitations. RESULTS: Health outcomes such as nutritional problems in children and pregnant women were concentrated among the poor, while others such as high-relevance health conditions were similar for poorest and richest households. The concentration indexes for health outcomes suggested that income makes the distribution pro-poor. However, the opposite was true for age, in which the probability of health problems among rich individuals increased with age. The concentration curves for utilization of healthcare services showed that dental visits, laboratory exams, specialty visits, and hospitalizations were concentrated on the richest households, while the use of emergency services and preventive medicine were highly concentrated among poor individuals. CONCLUSIONS: Although a positive trend in the increase of healthcare service use among income groups was observed, a significant impact of the latest health reform was not observed.

Case Report Unicentric Castleman disease located in the anterior mediastinum misdiagnosed as invasive thymoma: a case report.

Castleman disease is a rare lymphoproliferative disorder of unknown etiology. The localized form, which usually presents as a slow-growing mass, is most commonly located in the mediastinum. Invasion of the vena anonyma by a mass has rarely been reported. We herein describe a case of initially misdiagnosed invasive thymoma in a 72-year-old woman, but postoperatively proven to have anterior mediastinal Castleman disease with invasion of the vena anonyma.