Mining Relational Paths in Integrated Biomedical Data

Much life science and biology research requires an understanding of complex relationships between biological entities (genes, compounds, pathways, diseases, and so on). There is a wealth of data on such relationships in publicly available datasets and publications, but these sources are overlapped and distributed so that finding pertinent relational data is increasingly difficult. Whilst most public datasets have associated tools for searching, there is a lack of searching methods that can cross data sources and that in particular search not only based on the biological entities themselves but also on the relationships between them. In this paper, we demonstrate how graph-theoretic algorithms for mining relational paths can be used together with a previous integrative data resource we developed called Chem2Bio2RDF to extract new biological insights about the relationships between such entities. In particular, we use these methods to investigate the genetic basis of side-effects of thiazolinedione drugs, and in particular make a hypothesis for the recently discovered cardiac side-effects of Rosiglitazone (Avandia) and a prediction for Pioglitazone which is backed up by recent clinical studies

Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

ASSESSING THE IMPACT OF SCREENING, EARLY IDENTIFICATION AND INTERVENTION PROGRAMMES FOR CHRONIC KIDNEY DISEASE: PROTOCOL FOR A SCOPING REVIEW

Chronic kidney disease (CKD) is a major threat to public health, especially in low-income and lower middle-income countries, where resources for treating patients with advanced CKD are scarce. Although early CKD identification and intervention hold promise for reducing the burden of CKD and risk factors, it remains unclear if an uniform strategy can be applicable across all income groups. The aim of this scoping review is to synthesise available evidence on early CKD identification programmes in all world regions and income groups. The study will also identify efforts that have been made to use interventions and implementation of early identification programmes for CKD across countries and income groups. Methods and analysis This review will be guided by the methodological framework for conducting scoping studies developed by Arksey and O’Malley. Empirical (Medline, Embase, Cochrane Library, CINAHL, ISI Web of Science and PsycINFO) and grey literature references will be searched to identify studies on CKD screening, early identification and interventions across all populations. Two reviewers will independently screen references in consecutive stages of title/abstract screening and then full-text screening. We will use a general descriptive overview, tabular summaries and content analysis on extracted data. Ethics and dissemination The findings from our planned scoping review will enable us to identify items in early identification programmes that can be used in developing screening toolkits for CKD. We will disseminate our findings using traditional approaches that include open access peer-reviewed publication, scientific presentations and a white paper (call to action) report. Ethical approval will not be required for this scoping review as the data will be extracted from already published studie

EARLY IDENTIFICATION OF CKD—A SCOPING REVIEW OF THE GLOBAL POPULATIONS

Introduction: Decisions on whether to screen for chronic kidney disease (CKD) or not remain contentious in nephrology. This study provides a global overview of early CKD identification efforts. Methods: Guidelines for scoping reviews were followed and studies were identified by searching MEDLINE, EMBASE, Cochrane Library, CINAHL, ISI Web of Science, and PsycINFO. Data extracted from included studies focused on the following 4 themes: study population, measurement methods, interventions used, and available policies. Results: We identified 290 CKD screening and detection programs from 83 countries. Overall sample size was 3.72 million (North East Asia: 1.19 million), detection of CKD was the aim in 97.6%, 63.1% used populationbased screening methods, and only 12.4% were in rural populations. Reported CKD prevalence (stages 3– 5) was higher in targeted- (14.8%) than population-based studies (8.0%). Number of persons needed to screen (NNS) to identify 1 case was also lower in targeted studies (7 vs. 13). Single measurements (80%) and the combination of estimation of glomerular filtration rate with a urine test (albuminuria/proteinuria) (71.4%) were frequently used to detect CKD. Only 2.8% of studies included an intervention such as pharmacotherapy in identified cases. Policies on early identification were available in 30.1% of countries included. Conclusion: Methods for early CKD identification vary worldwide, often leading to wide variations in the reported prevalence. Efforts to standardize measurement methods for early detection focusing on highrisk populations and ensuring appropriate interventions are available to those identified with CKD will improve the value of programs and improve patient outcomes