70 research outputs found

    Causal assessment of income inequality on self-rated health and all-cause mortality: a systematic review and meta-analysis

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    Context: Whether income inequality has a direct effect on health or is only associated because of the effect of individual income has long been debated. We aimed to understand the association between income inequality and self-rated health (SRH) and all-cause mortality (mortality) and assess if these relationships are likely to be causal. Methods: We searched Medline, ISI Web of Science, Embase, and EconLit (PROSPERO: CRD42021252791) for studies considering income inequality and SRH or mortality using multilevel data and adjusting for individual-level socioeconomic position. We calculated pooled odds ratios (ORs) for poor SRH and relative risk ratios (RRs) for mortality from random-effects meta-analyses. We critically appraised included studies using the Risk of Bias in Nonrandomized Studies – of Interventions tool. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework and causality using Bradford Hill (BH) viewpoints. Findings: The primary meta-analyses included 2,916,576 participants in 38 cross-sectional studies assessing SRH and 10,727,470 participants in 14 cohort studies of mortality. Per 0.05-unit increase in the Gini coefficient, a measure of income inequality, the ORs and RRs (95% confidence intervals) for SRH and mortality were 1.06 (1.03-1.08) and 1.02 (1.00-1.04), respectively. A total of 63.2% of SRH and 50.0% of mortality studies were at serious risk of bias (RoB), resulting in very low and low certainty ratings, respectively. For SRH and mortality, we did not identify relevant evidence to assess the specificity or, for SRH only, the experiment BH viewpoints; evidence for strength of association and dose–response gradient was inconclusive because of the high RoB; we found evidence in support of temporality and plausibility. Conclusions: Increased income inequality is only marginally associated with SRH and mortality, but the current evidence base is too methodologically limited to support a causal relationship. To address the gaps we identified, future research should focus on income inequality measured at the national level and addressing confounding with natural experiment approaches

    Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer.

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    While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP-CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20-1.79, P=1.68x10−4). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92-1.18, P=0.49), 0.94 (95% CI: 0.84-1.05, P= 0.27), and 0.98 (95% CI: 0.85-1.12, P=0.75) respectively. A genetic risk score for 3-hydoxy-3-methylglutaryl-coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR=0.69, 95% CI: 0.49-0.99, P=0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia. This article is protected by copyright. All rights reserved

    Changes in daily mental health service use and mortality at the commencement and lifting of COVID-19 ‘lockdown’ policy in 10 UK sites: a regression discontinuity in time design

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    Objectives: To investigate changes in daily mental health (MH) service use and mortality in response to the introduction and the lifting of the COVID-19 ‘lockdown’ policy in Spring 2020. Design: A regression discontinuity in time (RDiT) analysis of daily service-level activity. Setting and participants: Mental healthcare data were extracted from 10 UK providers. Outcome measures: Daily (weekly for one site) deaths from all causes, referrals and discharges, inpatient care (admissions, discharges, caseloads) and community services (face-to-face (f2f)/non-f2f contacts, caseloads): Adult, older adult and child/adolescent mental health; early intervention in psychosis; home treatment teams and liaison/Accident and Emergency (A&E). Data were extracted from 1 Jan 2019 to 31 May 2020 for all sites, supplemented to 31 July 2020 for four sites. Changes around the commencement and lifting of COVID-19 ‘lockdown’ policy (23 March and 10 May, respectively) were estimated using a RDiT design with a difference-in-difference approach generating incidence rate ratios (IRRs), meta-analysed across sites. Results: Pooled estimates for the lockdown transition showed increased daily deaths (IRR 2.31, 95% CI 1.86 to 2.87), reduced referrals (IRR 0.62, 95% CI 0.55 to 0.70) and reduced inpatient admissions (IRR 0.75, 95% CI 0.67 to 0.83) and caseloads (IRR 0.85, 95% CI 0.79 to 0.91) compared with the pre lockdown period. All community services saw shifts from f2f to non-f2f contacts, but varied in caseload changes. Lift of lockdown was associated with reduced deaths (IRR 0.42, 95% CI 0.27 to 0.66), increased referrals (IRR 1.36, 95% CI 1.15 to 1.60) and increased inpatient admissions (IRR 1.21, 95% CI 1.04 to 1.42) and caseloads (IRR 1.06, 95% CI 1.00 to 1.12) compared with the lockdown period. Site-wide activity, inpatient care and community services did not return to pre lockdown levels after lift of lockdown, while number of deaths did. Between-site heterogeneity most often indicated variation in size rather than direction of effect. Conclusions: MH service delivery underwent sizeable changes during the first national lockdown, with as-yet unknown and unevaluated consequences

    Safety of bendamustine for the treatment of indolent non-Hodgkin lymphoma: a UK real-world experience

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    Introduction: Bendamustine is among the most effective chemotherapeutics for indolent B-cell non-Hodgkin lymphomas (iNHL), but trial reports of significant toxicity, including opportunistic infections and excess deaths, led to prescriber warnings. We conducted a multicentre observational study evaluating bendamustine toxicity in real-world practice. Methods: Patients receiving at least one dose of bendamustine (B) +/- rituximab (R) for iNHL were included. Demographics, lymphoma and treatment details and grade 3-5 adverse events (AEs) were analysed. Results: 323 patients were enrolled from 9 NHS hospitals. Most patients (96%) received BR and 46% R maintenance. 21.7% experienced serious AEs (SAE) related to treatment, including infections in 12%, with absolute risk highest during induction (63%), maintenance (20%), and follow-up (17%), and the relative risk highest during maintenance (54%), induction (34%) and follow-up (28%). Toxicity led to permanent treatment discontinuation in 13% of patients, and 2.8% died of bendamustine-related infections (n=5), myelodysplastic syndrome (n=3), and cardiac disease (n=1). More SAEs per patient were reported in patients with mantle cell lymphoma, poor pre-induction PS, poor pre-maintenance PS, abnormal pre-induction total globulins and in those receiving growth factors. Use of antimicrobial prophylaxis was variable, and 3/10 opportunistic infections occurred despite prophylaxis. Conclusion: In this real-world analysis, bendamustine-related deaths and treatment discontinuation were similar to trial populations of younger, fitter patients. Poor PS, mantle cell histology and maintenance rituximab were potential risk factors. Infections, including late onset events, were the most common treatment-related SAE and cause of death warranting extended antimicrobial prophylaxis and infectious surveillance, especially in maintenance-treated patients

    Drivers of soil microbial and detritivore activity across global grasslands

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    DATA AVAILABILITY : The source data that support the findings of this study can be found in the supplementary data (Figs. 1a, b, 2 and 4 were created with Data 1, Fig. 1c and Fig. 3 with Data 2). All other data are available from the corresponding author on reasonable request.CODE AVAILABILITY : The code is available from the corresponding author upon request.Covering approximately 40% of land surfaces, grasslands provide critical ecosystem services that rely on soil organisms. However, the global determinants of soil biodiversity and functioning remain underexplored. In this study, we investigate the drivers of soil microbial and detritivore activity in grasslands across a wide range of climatic conditions on five continents. We apply standardized treatments of nutrient addition and herbivore reduction, allowing us to disentangle the regional and local drivers of soil organism activity. We use structural equation modeling to assess the direct and indirect effects of local and regional drivers on soil biological activities. Microbial and detritivore activities are positively correlated across global grasslands. These correlations are shaped more by global climatic factors than by local treatments, with annual precipitation and soil water content explaining the majority of the variation. Nutrient addition tends to reduce microbial activity by enhancing plant growth, while herbivore reduction typically increases microbial and detritivore activity through increased soil moisture. Our findings emphasize soil moisture as a key driver of soil biological activity, highlighting the potential impacts of climate change, altered grazing pressure, and eutrophication on nutrient cycling and decomposition within grassland ecosystems.Open Access funding enabled and organized by Projekt DEAL.http://www.nature.com/commsbioam2024Mammal Research InstituteNoneSDG-15:Life on lan

    Drivers of soil microbial and detritivore activity across global grasslands

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    Covering approximately 40% of land surfaces, grasslands provide critical ecosystem services that rely on soil organisms. However, the global determinants of soil biodiversity and functioning remain underexplored. In this study, we investigate the drivers of soil microbial and detritivore activity in grasslands across a wide range of climatic conditions on five continents. We apply standardized treatments of nutrient addition and herbivore reduction, allowing us to disentangle the regional and local drivers of soil organism activity. We use structural equation modeling to assess the direct and indirect effects of local and regional drivers on soil biological activities. Microbial and detritivore activities are positively correlated across global grasslands. These correlations are shaped more by global climatic factors than by local treatments, with annual precipitation and soil water content explaining the majority of the variation. Nutrient addition tends to reduce microbial activity by enhancing plant growth, while herbivore reduction typically increases microbial and detritivore activity through increased soil moisture. Our findings emphasize soil moisture as a key driver of soil biological activity, highlighting the potential impacts of climate change, altered grazing pressure, and eutrophication on nutrient cycling and decomposition within grassland ecosystems
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