The Beck depression inventory as a measure of subjective well-being:A cross-national study

The present study examined the question whether the Beck Depression Inventory (BDI), which is one of the most widely used instruments to assess depression, can be used to measure differences in subjective well-being at national level. In order to establish the meaning of depression scores at country level, the functional equivalence (i.e., similarity of meaning) of depression scores at individual and country level was examined. Studies using the BDI in normal populations from 28 countries were collected. Depression showed the same correlates at individual and country level, which supports the functional equivalence of the BDI at the two levels. BDI scores and subjective well-being were then correlated with a number of country characteristics in order to test three theories of cross-national differences in subjective well-being. Livability theory stresses the importance of objective living conditions, comparison theory focuses on relative living conditions, and folklore theory states that cross-national differences can be explained by some national trait (e.g., beliefs and values concerning happiness). Cross-national differences in depression and subjective well-being could be explained by livability theory and folklore theory. BDI scores were negatively correlated with subjective well-being and other happiness-related variables. These findings suggest that depression had the same meaning at individual and country level and that depression is an adequate measure of (a lack of) subjective well-being at country level.

UK Public Sector Information and Re-use Policy – A 2008 Analysis

INTRODUCTION: Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR. METHODS: We develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10-year period. We then compare the impact on TDR and cost-effectiveness of: (1) introduction of pre-therapy genotyping; (2) doubling use of second-line treatment to 80% (50-90%) of patients with confirmed virological failure on first-line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost-effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda. RESULTS: The prevalence of TDR is predicted to rise from 6.7$1612 to $2234 (IQR$450-dominated) per QALY gained. CONCLUSIONS: While earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug-resistant HIV, the absolute numbers of patients infected with drug-resistant HIV is predicted to decrease. Increasing use of second-line treatment to all patients with confirmed failure on first-line therapy is a cost-effective approach to reduce TDR. Improving access to second-line ART is therefore a major priority

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials.

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding: Bill & Melinda Gates Foundation