498 research outputs found

    Systematic Reviews of Genetic Association Studies

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    Gurdeep S. Sagoo and colleagues describe key components of the methodology for undertaking systematic reviews and meta-analyses of genetic association studies

    Low radon exposures and lung cancer risk: joint analysis of the Czech, French, and Beaverlodge cohorts of uranium miners.

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    It is well established that high radon exposures increase the risk of lung cancer mortality. The effects of low occupational exposures and the factors that confound and modify this risk are not clear and are needed to inform current radiation protection of miners. The risk of lung cancer mortality at low radon exposures (< 100 working-level months) was assessed in the joint cohort analysis of Czech, French, and Canadian uranium miners, employed in 1953 or later. Statistical analysis was based on linear Poisson regression modeling with grouped cohort survival data. Two sensitivity analyses were used to assess potential confounding from tobacco smoking. A statistically significant linear relationship between radon exposure and lung cancer mortality was found. The excess relative risk per working-level month was 0.022 (95% confidence intervals: 0.013-0.034), based on 408 lung cancer deaths and 394,236 person-years of risk. Time since exposure was a statistically significant modifier; risk decreased with increasing time since exposure. A tendency for a decrease in risk with increasing attained age was observed, but this was not statistically significant. Exposure rate was not found to be a modifier of the excess relative risk. The potential confounding effect of tobacco smoking was estimated to be small and did not substantially change the radon-lung cancer mortality risk estimates. This joint cohort analysis provides strong evidence for an increased risk of lung cancer mortality from low occupational radon exposures. The results suggest that radiation protection measures continue to be important among current uranium miners

    The effect of performance-based financing interventions on out-of-pocket expenses intended to improve access to and utilization of maternal health services in sub-Saharan Africa: protocol for a systematic review and meta-analysis

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    Background: Out-of-pocket expenses have been reported as a major barrier to accessing antenatal care and skilled birth delivery in most of sub-Saharan Africa. Performance-based financing (PBF) is one of several strategies introduced in lower- and middle-income countries to strengthen a weak health system. This review aims to synthesize evidence on the effectiveness of PBF interventions implemented with the objective of reducing out-of-pocket expenses and improving access to and utilization of ANC and skilled birth delivery and family planning in sub-Saharan Africa. It will consider evidence across health sectors and identify gaps in the evidence. Methods and analysis: This protocol is reported according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guideline. The systematic review will apply a three-step strategy to search five databases (CINAHL, PubMed, Ovid Medline, EMBASE, Cochrane.) and grey literature with the help of a librarian. Two independent reviewers will conduct screening to determine eligibility and critical appraisal of selected studies using the risk of bias criteria developed by the Cochrane EPOC Group and the New Castle Ottawa Scale for observational studies. The certainty of evidence for the outcomes will be assessed using “Grades of Recommendation, Assessment, Development, and Evaluation” (GRADE) approach. This review will consider experimental and quasi-experimental study designs and observational studies. Studies published in English and French language(s) will be included. Studies published since the introduction of PBF in sub-Saharan Africa will be included. Data will be collected on each item that contributes to out-of-pocket expenses. This review will adopt the Multiple Dimensions of Access Framework to organize the findings. Discussion: This systematic review will support evidence-informed data for the performance-based financing community and government by identifying, describing, and assessing the impact of performance-based financing interventions on out-of-pocket expenses in promoting access and utilization of ANC, skilled birth delivery, and family planning across health sectors. Systematic review registration: This review has been registered with PROSPERO, Registration number CRD42020222893

    Adaptive Deep Brain Stimulation: From Experimental Evidence Toward Practical Implementation.

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    Closed-loop adaptive deep brain stimulation (aDBS) can deliver individualized therapy at an unprecedented temporal precision for neurological disorders. This has the potential to lead to a breakthrough in neurotechnology, but the translation to clinical practice remains a significant challenge. Via bidirectional implantable brain-computer-interfaces that have become commercially available, aDBS can now sense and selectively modulate pathophysiological brain circuit activity. Pilot studies investigating different aDBS control strategies showed promising results, but the short experimental study designs have not yet supported individualized analyses of patient-specific factors in biomarker and therapeutic response dynamics. Notwithstanding the clear theoretical advantages of a patient-tailored approach, these new stimulation possibilities open a vast and mostly unexplored parameter space, leading to practical hurdles in the implementation and development of clinical trials. Therefore, a thorough understanding of the neurophysiological and neurotechnological aspects related to aDBS is crucial to develop evidence-based treatment regimens for clinical practice. Therapeutic success of aDBS will depend on the integrated development of strategies for feedback signal identification, artifact mitigation, signal processing, and control policy adjustment, for precise stimulation delivery tailored to individual patients. The present review introduces the reader to the neurophysiological foundation of aDBS for Parkinson's disease (PD) and other network disorders, explains currently available aDBS control policies, and highlights practical pitfalls and difficulties to be addressed in the upcoming years. Finally, it highlights the importance of interdisciplinary clinical neurotechnological research within and across DBS centers, toward an individualized patient-centered approach to invasive brain stimulation. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

    An Epidemiological Reappraisal of the Familial Aggregation of Prostate Cancer: A Meta-Analysis

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    Studies on familial aggregation of cancer may suggest an overall contribution of inherited genes or a shared environment in the development of malignant disease. We performed a meta-analysis on familial clustering of prostate cancer. Out of 74 studies reporting data on familial aggregation of prostate cancer in unselected populations retrieved by a Pubmed search and browsing references, 33 independent studies meeting the inclusion criteria were used in the analysis performed with the random effects model. The pooled rate ratio (RR) for first-degree family history, i.e. affected father or brother, is 2.48 (95% confidence interval: 2.25–2.74). The incidence rate for men who have a brother who got prostate cancer increases 3.14 times (CI:2.37–4.15), and for those with affected father 2.35 times (CI:2.02–2.72). The pooled estimate of RR for two or more affected first-degree family members relative to no history in father and in brother is 4.39 (CI:2.61–7.39). First-degree family history appears to increase the incidence rate of prostate cancer more in men under 65 (RR:2.87, CI:2.21–3.74), than in men aged 65 and older (RR:1.92, CI:1.49–2.47), p for interaction = 0.002. The attributable fraction among those having an affected first-degree relative equals to 59.7% (CI:55.6–63.5%) for men at all ages, 65.2% (CI:57.7–71.4%) for men younger than 65 and 47.9% (CI:37.1–56.8%) for men aged 65 or older. For those with a family history in 2 or more first-degree family members 77.2% (CI:65.4–85.0%) of prostate cancer incidence can be attributed to the familial clustering. Our combined estimates show strong familial clustering and a significant effect-modification by age meaning that familial aggregation was associated with earlier disease onset (before age 65)

    Cost-Effectiveness of Pharmacotherapy to Reduce Obesity

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    Aims: Obesity causes a high disease burden in Australia and across the world. We aimed to analyse the cost-effectiveness of weight reduction with pharmacotherapy in Australia, and to assess its potential to reduce the disease burden due to excess body weight
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