Evaluating the influence of taxation and social security policies on psychological distress: A microsimulation study of the UK during the COVID-19 economic crisis.

Economic determinants are important for population health, but actionable evidence of how policies can utilise these pathways remains scarce. This study employs a microsimulation framework to evaluate the effects of taxation and social security policies on population mental health. The UK economic crisis caused by the COVID-19 pandemic provides an informative context involving an economic shock accompanied by one of the strongest discretionary fiscal responses amongst OECD countries. The analytical setup involves a dynamic, stochastic, discrete-time microsimulation model (SimPaths) projecting changes in psychological distress given predicted economic outcomes from a static tax-benefit microsimulation model (UKMOD) based on different policy scenarios. We contrast projections of psychological distress for the working-age population from 2017 to 2025 given the observed policy environment against a counterfactual scenario where pre-crisis policies remained in place. Levels of psychological distress and potential cases of common mental disorders (CMDs) were assessed with the 12-item General Health Questionnaire (GHQ-12). The UK policy response to the economic crisis is estimated to have prevented a substantial fall (over 12 percentage points, %pt) in the employment rate in 2020 and 2021. In 2020, projected psychological distress increased substantially (CMD prevalence increase >10%pt) under both the observed and the counterfactual policy scenarios. Through economic pathways, the policy response is estimated to have prevented a further 3.4%pt [95%UI 2.8%pt, 4.0%pt] increase in the prevalence of CMDs, approximately 1.2 million cases. Beyond 2021, as employment levels rapidly recovered, psychological distress returned to the pre-pandemic trend. Sustained preventative effects on poverty are estimated, with projected levels 2.1%pt [95%UI 1.8%pt, 2.5%pt] lower in 2025 than in the absence of the observed policy response. The study shows that policies protecting employment during an economic crisis are effective in preventing short-term mental health losses and have lasting effects on poverty levels. This preventative effect has substantial public health benefits.

Short-term impacts of Universal Basic Income on population mental health inequalities in the UK: A microsimulation modelling study.

BACKGROUND: Population mental health in the United Kingdom (UK) has deteriorated, alongside worsening socioeconomic conditions, over the last decade. Policies such as Universal Basic Income (UBI) have been suggested as an alternative economic approach to improve population mental health and reduce health inequalities. UBI may improve mental health (MH), but to our knowledge, no studies have trialled or modelled UBI in whole populations. We aimed to estimate the short-term effects of introducing UBI on mental health in the UK working-age population. METHODS AND FINDINGS: Adults aged 25 to 64 years were simulated across a 4-year period from 2022 to 2026 with the SimPaths microsimulation model, which models the effects of UK tax/benefit policies on mental health via income, poverty, and employment transitions. Data from the nationally representative UK Household Longitudinal Study were used to generate the simulated population (n = 25,000) and causal effect estimates. Three counterfactual UBI scenarios were modelled from 2023: "Partial" (value equivalent to existing benefits), "Full" (equivalent to the UK Minimum Income Standard), and "Full+" (retaining means-tested benefits for disability, housing, and childcare). Likely common mental disorder (CMD) was measured using the General Health Questionnaire (GHQ-12, score ≥4). Relative and slope indices of inequality were calculated, and outcomes stratified by gender, age, education, and household structure. Simulations were run 1,000 times to generate 95% uncertainty intervals (UIs). Sensitivity analyses relaxed SimPaths assumptions about reduced employment resulting from Full/Full+ UBI. Partial UBI had little impact on poverty, employment, or mental health. Full UBI scenarios practically eradicated poverty but decreased employment (for Full+ from 78.9% [95% UI 77.9, 79.9] to 74.1% [95% UI 72.6, 75.4]). Full+ UBI increased absolute CMD prevalence by 0.38% (percentage points; 95% UI 0.13, 0.69) in 2023, equivalent to 157,951 additional CMD cases (95% UI 54,036, 286,805); effects were largest for men (0.63% [95% UI 0.31, 1.01]) and those with children (0.64% [95% UI 0.18, 1.14]). In our sensitivity analysis assuming minimal UBI-related employment impacts, CMD prevalence instead fell by 0.27% (95% UI -0.49, -0.05), a reduction of 112,228 cases (95% UI 20,783, 203,673); effects were largest for women (-0.32% [95% UI -0.65, 0.00]), those without children (-0.40% [95% UI -0.68, -0.15]), and those with least education (-0.42% [95% UI -0.97, 0.15]). There was no effect on educational mental health inequalities in any scenario, and effects waned by 2026. The main limitations of our methods are the model's short time horizon and focus on pathways from UBI to mental health solely via income, poverty, and employment, as well as the inability to integrate macroeconomic consequences of UBI; future iterations of the model will address these limitations. CONCLUSIONS: UBI has potential to improve short-term population mental health by reducing poverty, particularly for women, but impacts are highly dependent on whether individuals choose to remain in employment following its introduction. Future research modelling additional causal pathways between UBI and mental health would be beneficial.

Causal Assessment of Income Inequality on Self-Rated Health and All-Cause Mortality: A Systematic Review and Meta-Analysis.

Policy Points Income is thought to impact a broad range of health outcomes. However, whether income inequality (how unequal the distribution of income is in a population) has an additional impact on health is extensively debated. Studies that use multilevel data, which have recently increased in popularity, are necessary to separate the contextual effects of income inequality on health from the effects of individual income on health. Our systematic review found only small associations between income inequality and poor self-rated health and all-cause mortality. The available evidence does not suggest causality, although it remains methodologically flawed and limited, with very few studies using natural experimental approaches or examining income inequality at the national level. 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.

OPTIMA: An Open-Label, Noncomparative Pilot Trial of Inhaled Molgramostim in Pulmonary Nontuberculous Mycobacterial Infection.

Rationale: Inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) has been proposed as a potential immunomodulatory treatment for nontuberculous mycobacterial (NTM) infection.Objectives: This open-label, noncomparative pilot trial investigated the efficacy and safety of inhaled GM-CSF (molgramostim nebulizer solution) in patients with predominantly treatment-refractory pulmonary NTM infection (Mycobacterium avium complex [MAC] and M. abscessus [MABS]), either in combination with ongoing guideline-based therapy (GBT) or as monotherapy in patients who had stopped GBT because of lack of efficacy or intolerability.Methods: Thirty-two adult patients with refractory NTM infection (MAC, n = 24; MABS, n = 8) were recruited into two cohorts: those with (n = 16) and without (n = 16) ongoing GBT. Nebulized molgramostim 300 µg/d was administered over 48 weeks. Sputum cultures and smears and clinical assessments (6-min-walk distance, symptom scores, Quality of Life-Bronchiectasis Questionnaire score, and body weight) were collected every 4 weeks during treatment and 12 weeks after the end of treatment. The primary endpoint was sputum culture conversion, defined as three consecutive monthly negative cultures during the treatment period.Results: Eight patients (25%) achieved culture conversion on treatment (seven [29.2%] patients with MAC infection, one [12.5%] patient with MABS infection); in four patients, this was durable after the end of treatment. Of the 24 patients with MAC infection, an additional 4 patients had a partial response, converting from smear positive at baseline to smear negative at the end of treatment, and time to positivity in liquid culture media increased. Two of these patients sustained negative cultures from the end of treatment. Other clinical endpoints were unchanged. Serious adverse events were mainly pulmonary exacerbations or worsening NTM infection. Three deaths, not treatment related, were reported.Conclusions: In this population of patients with severe NTM disease, molgramostim was safe and well tolerated. Sputum culture conversion rates for patients with MAC infection (29.2%) were greater than reported for similar refractory MAC cohorts managed with GBT alone. Less benefit was seen for MABS infection. No serious safety concerns were identified. Further evaluation in a larger cohort is warranted.Clinical trial registered with www.clinicaltrials.gov (NCT03421743).

Social media use and health risk behaviours in young people: systematic review and meta-analysis.

OBJECTIVES: To examine the association between social media use and health risk behaviours in adolescents (defined as those 10-19 years). DESIGN: Systematic review and meta-analysis. DATA SOURCES: EMBASE, Medline, APA PsycINFO, SocINDEX, CINAHL, SSRN, SocArXic, PsyArXiv, medRxiv, and Google Scholar (1 January 1997 to 6 June 2022). METHODS: Health risk behaviours were defined as use of alcohol, drugs, tobacco, electronic nicotine delivery systems, unhealthy dietary behaviour, inadequate physical activity, gambling, and anti-social, sexual risk, and multiple risk behaviours. Included studies reported a social media variable (ie, time spent, frequency of use, exposure to health risk behaviour content, or other social media activities) and one or more relevant outcomes. Screening and risk of bias assessments were completed independently by two reviewers. Synthesis without meta-analysis based on effect direction and random-effects meta-analyses was used. Effect modification was explored using meta-regression and stratification. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations). RESULTS: Of 17 077 studies screened, 126 were included (73 included in meta-analyses). The final sample included 1 431 534 adolescents (mean age 15.0 years). Synthesis without meta-analysis indicated harmful associations between social media and all health risk behaviours in most included studies, except inadequate physical activity where beneficial associations were reported in 63.6% of studies. Frequent (v infrequent) social media use was associated with increased alcohol consumption (odds ratio 1.48 (95% confidence interval 1.35 to 1.62); n=383 068), drug use (1.28 (1.05 to 1.56); n=117 646), tobacco use (1.85, 1.49 to 2.30; n=424 326), sexual risk behaviours (1.77 (1.48 to 2.12); n=47 280), anti-social behaviour (1.73 (1.44 to 2.06); n=54 993), multiple risk behaviours (1.75 (1.30 to 2.35); n=43 571), and gambling (2.84 (2.04 to 3.97); n=26 537). Exposure to content showcasing health risk behaviours on social media (v no exposure) was associated with increased odds of use of electronic nicotine delivery systems (1.73 (1.34 to 2.23); n=721 322), unhealthy dietary behaviours (2.48 (2.08 to 2.97); n=9892), and alcohol consumption (2.43 (1.25 to 4.71); n=14 731). For alcohol consumption, stronger associations were identified for exposure to user generated content (3.21 (2.37 to 4.33)) versus marketer generated content (2.12 (1.06 to 4.24)). For time spent on social media, use for at least 2 h per day (v <2 h) increased odds of alcohol consumption (2.12 (1.53 to 2.95); n=12 390). GRADE certainty was moderate for unhealthy dietary behaviour, low for alcohol use, and very low for other investigated outcomes. CONCLUSIONS: Social media use is associated with adverse health risk behaviours in young people, but further high quality research is needed to establish causality, understand effects on health inequalities, and determine which aspects of social media are most harmful. STUDY REGISTRATION: PROSPERO, CRD42020179766.

A systematic review of the clinical impact of small colony variants in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a life-limiting disorder that is characterised by respiratory tract inflammation that is mediated by a range of microbial pathogens. Small colony variants (SCVs) of common respiratory pathogens are being increasingly recognised in CF. The aim of this systematic review is to investigate the prevalence of SCVs, clinical characteristics and health outcomes for patients with CF, and laboratory diagnostic features of SCVs compared to non-small colony variants (NCVs) for a range of Gram-positive and Gram-negative respiratory pathogens. METHODS: A literature search was conducted (PubMed, Web of Science, Embase and Scopus) in April 2020 to identify articles of interest. Data pertaining to demographic characteristics of participants, diagnostic criteria of SCVs, SCV prevalence and impact on lung function were extracted from included studies for analysis. RESULTS: Twenty-five of 673 studies were included in the systematic review. Individuals infected with SCVs of Staphylococcus aureus (S. aureus) were more likely to have had prior use of the broad-spectrum antibiotic trimethoprim sulfamethoxazole (p < 0.001), and the prevalence of SCVs in patients infected with S. aureus was estimated to be 19.3% (95% CI: 13.5% to 25.9%). Additionally, patients infected with SCVs of Gram-negative and Gram-positive pathogens were identified to have a lower forced expiratory volume in one second percentage predicted (-16.8, 95% CI: -23.2 to -10.4) than those infected by NCVs. Gram-positive SCVs were commonly described as small and non-haemolytic, grown on Mannitol salt or blood agar for 24 h at 35°C and confirmed using tube coagulase testing. CONCLUSION: The findings of this systematic review demonstrate that SCVs of S. aureus have a high prevalence in the CF community, and that the occurrence of SCVs in Gram-positive and Gram-negative pathogens is linked to poorer respiratory function. Further investigation is necessary to determine the effect of infection by SCVs on the CF population.

Systems science methods in public health: what can they contribute to our understanding of and response to the cost-of-living crisis?

BACKGROUND: Many complex public health evidence gaps cannot be fully resolved using only conventional public health methods. We aim to familiarise public health researchers with selected systems science methods that may contribute to a better understanding of complex phenomena and lead to more impactful interventions. As a case study, we choose the current cost-of-living crisis, which affects disposable income as a key structural determinant of health. METHODS: We first outline the potential role of systems science methods for public health research more generally, then provide an overview of the complexity of the cost-of-living crisis as a specific case study. We propose how four systems science methods (soft systems, microsimulation, agent-based and system dynamics models) could be applied to provide more in-depth understanding. For each method, we illustrate its unique knowledge contributions, and set out one or more options for studies that could help inform policy and practice responses. RESULTS: Due to its fundamental impact on the determinants of health, while limiting resources for population-level interventions, the cost-of-living crisis presents a complex public health challenge. When confronted with complexity, non-linearity, feedback loops and adaptation processes, systems methods allow a deeper understanding and forecasting of the interactions and spill-over effects common with real-world interventions and policies. CONCLUSIONS: Systems science methods provide a rich methodological toolbox that complements our traditional public health methods. This toolbox may be particularly useful in early stages of the current cost-of-living crisis: for understanding the situation, developing solutions and sandboxing potential responses to improve population health.

Nontuberculous Mycobacteria in Cystic Fibrosis in the Era of Cystic Fibrosis Transmembrane Regulator Modulators.

Nontuberculous mycobacteria (NTM) are a group of mycobacteria which represent opportunistic pathogens that are of increasing concern in people with cystic fibrosis (pwCF). The acquisition has been traditionally though to be from environmental sources, though recent work has suggested clustered clonal infections do occur and transmission potential demonstrated among pwCF attending CF specialist centers. Guidelines for the screening, diagnosis, and identification of NTM and management of pwCF have been published. The emergence of CF-specific therapies, in particular cystic fibrosis transmembrane regulator (CFTR) modulator drugs, have led to significant improvement in the health and well-being of pwCF and may lead to challenges in sampling the lower respiratory tract including to screen for NTM. This review highlights the epidemiology, modes of acquisition, screening and diagnosis, therapeutic approaches in the context of improved clinical status for pwCF, and the clinical application of CFTR modulator therapies.

Effects of poverty on mental health in the UK working-age population: causal analyses of the UK Household Longitudinal Study.

BACKGROUND: Addressing poverty through taxation or welfare policies is likely important for public mental health; however, few studies assess poverty's effects using causal epidemiology. We estimated the effect of poverty on mental health. METHODS: We used data on working-age adults (25-64 years) from nine waves of the UK Household Longitudinal Survey (2009-19; n = 45 497/observations = 202 207 following multiple imputation). We defined poverty as a household equivalized income <60% median, and the outcome likely common mental disorder (CMD) as a General Health Questionnaire-12 score ≥4. We used double-robust marginal structural modelling with inverse probability of treatment weights to generate absolute and relative effects. Supplementary analyses separated transitions into/out of poverty, and stratified by gender, education, and age. We quantified potential impact through population attributable fractions (PAFs) with bootstrapped standard errors. RESULTS: Good balance of confounders was achieved between exposure groups, with 45 830 observations (22.65%) reporting poverty. The absolute effect of poverty on CMD prevalence was 2.15% [%-point change; 95% confidence interval (CI) 1.45, 2.84]; prevalence in those unexposed was 20.59% (95% CI 20.29%, 20.88%), and the odds ratio was 1.17 (95% CI 1.12, 1.24). There was a larger absolute effect for transitions into poverty [2.46% (95% CI 1.56, 3.36)] than transitions out of poverty [-1.49% (95% CI -2.46, -0.53)]. Effects were also slightly larger in women than men [2.34% (95% CI 1.41, 3.26) versus 1.73% (95% CI 0.72, 2.74)]. The PAF for moving into poverty was 6.34% (95% CI 4.23, 8.45). CONCLUSIONS: PAFs derived from our causal estimates suggest moves into poverty account for just over 6% of the burden of CMD in the UK working-age population, with larger effects in women.

To what extent does income explain the effect of unemployment on mental health? Mediation analysis in the UK Household Longitudinal Study.

BACKGROUND: Employment and income are important determinants of mental health (MH), but the extent that unemployment effects are mediated by reduced income is unclear. We estimated the total effect (TE) of unemployment on MH and the controlled direct effect (CDE) not acting via income. METHODS: We included adults 25-64 years from nine waves of the UK Household Longitudinal Study (n = 45 497/obs = 202 297). Unemployment was defined as not being in paid employment; common mental disorder (CMD) was defined as General Health Questionnaire-12 score ≥4. We conducted causal mediation analysis using double-robust marginal structural modelling, estimating odds ratios (OR) and absolute differences for effects of unemployment on CMD in the same year, before (TE) and after (CDE) blocking the income pathway. We calculated percentage mediation by income, with bootstrapped standard errors. RESULTS: The TE of unemployment on CMD risk was OR 1.66 (95% CI 1.57-1.76), with 7.09% (6.21-7.97) absolute difference in prevalence; equivalent CDEs were OR 1.55 (1.46-1.66) and 6.08% (5.13-7.03). Income mediated 14.22% (8.04-20.40) of the TE. Percentage mediation was higher for job losses [15.10% (6.81-23.39)] than gains [8.77% (0.36-17.19)]; it was lowest for those 25-40 years [7.99% (-2.57 to 18.51)] and in poverty [2.63% (-2.22 to 7.49)]. CONCLUSIONS: A high proportion of the short-term effect of unemployment on MH is not explained by income, particularly for younger people and those in poverty. Population attributable fractions suggested 16.49% of CMD burden was due to unemployment, with 13.90% directly attributable to job loss rather than resultant income changes. Similar analytical approaches could explore how this differs across contexts, by other factors, and consider longer-term effects.

Characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic, progressive, and growing worldwide health burden associated with mounting morbidity, mortality, and economic costs. Improvements in NTM-PD management are urgently needed, which requires a better understanding of fundamental immunopathology. Here, we examine temporal dynamics of the immune compartment during NTM-PD caused by Mycobacterium avium complex (MAC) and Mycobactereoides abscessus complex (MABS). We show that active MAC infection is characterized by elevated T cell immunoglobulin and mucin-domain containing-3 expression across multiple T cell subsets. In contrast, active MABS infection was characterized by increased expression of cytotoxic T-lymphocyte-associated protein 4. Patients who failed therapy closely mirrored the healthy individual immune phenotype, with circulating immune network appearing to 'ignore' infection in the lung. Interestingly, immune biosignatures were identified that could inform disease stage and infecting species with high accuracy. Additionally, programmed cell death protein 1 blockade rescued antigen-specific IFN-γ secretion in all disease stages except persistent infection, suggesting the potential to redeploy checkpoint blockade inhibitors for NTM-PD. Collectively, our results provide new insight into species-specific 'immune chatter' occurring during NTM-PD and provide new targets, processes and pathways for diagnostics, prognostics, and treatments needed for this emerging and difficult to treat disease.

Does persistent precarious employment affect health outcomes among working age adults? A systematic review and meta-analysis.

OBJECTIVE: To evaluate the impact of persistent precarious employment (lasting 12+ months) on the health of working age adults, compared with more stable employment. Persistent precarity reflects a shift towards less secure forms of employment and may be particularly important for health. METHODS: Nine databases were systematically searched to identify quantitative studies that assessed the relationship between persistent precarious employment and health outcomes. Risk of bias (RoB) was assessed using an adaptation of the Effective Public Health Practice Project tool. Narrative synthesis and random effects meta-analysis were conducted. Certainty of evidence was assessed using the Grades of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Of 12 940 records screened, 50 studies met the inclusion criteria and 29 were included in meta-analyses. RoB was generally high (n=18). The most reported outcome domain was mental health; with evidence also reported relating to general health, physical health,and health behaviours. Of GRADE assessed outcomes, persistent precarious employment was associated with increased risk of poor self-rated health (OR 1.53, 95% CI 1.09 to 2.14, I2=80%) and mental health symptoms (OR 1.44, 95% CI 1.23 to 1.70, I2=65%). The association with all-cause mortality was imprecisely estimated (OR 1.10, 5% CI 0.91 to 1.33, I2=73%). There was very low GRADE certainty across all outcomes. CONCLUSIONS: Persistent precarious employment is associated with poorer health, particularly for outcomes with short time lags, though associations are small and causality is highly uncertain. Further research using more robust methods is needed but given potential health harms of persistent precarious employment, exploration of precautionary labour regulations and employment policies is warranted.

How do income changes impact on mental health and wellbeing for working-age adults? A systematic review and meta-analysis.

BACKGROUND: Lower incomes are associated with poorer mental health and wellbeing, but the extent to which income has a causal effect is debated. We aimed to synthesise evidence from studies measuring the impact of changes in individual and household income on mental health and wellbeing outcomes in working-age adults (aged 16-64 years). METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, PsycINFO, ASSIA, EconLit, and RePEc on Feb 5, 2020, for randomised controlled trials (RCTs) and quantitative non-randomised studies. We had no date limits for our search. We included English-language studies measuring effects of individual or household income change on any mental health or wellbeing outcome. We used Cochrane risk of bias (RoB) tools. We conducted three-level random-effects meta-analyses, and explored heterogeneity using meta-regression and stratified analyses. Synthesis without meta-analysis was based on effect direction. Critical RoB studies were excluded from primary analyses. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). This study is registered with PROSPERO, CRD42020168379. FINDINGS: Of 16 521 citations screened, 136 were narratively synthesised (12·5% RCTs) and 86 meta-analysed. RoB was high: 30·1% were rated critical and 47·1% serious or high. A binary income increase lifting individuals out of poverty was associated with 0·13 SD improvement in mental health measures (95% CI 0·07 to 0·20; n=42 128; 18 studies), considerably larger than other income increases (0·01 SD improvement, 0·002 to 0·019; n=216 509, 14 studies). For wellbeing, increases out of poverty were associated with 0·38 SD improvement (0·09 to 0·66; n=101 350, 8 studies) versus 0·16 for other income increases (0·07 to 0·25; n=62 619, 11 studies). Income decreases from any source were associated with 0·21 SD worsening of mental health measures (-0·30 to -0·13; n=227 804, 11 studies). Effect sizes were larger in low-income and middle-income settings and in higher RoB studies. Heterogeneity was high (I2=79-87%). GRADE certainty was low or very low. INTERPRETATION: Income changes probably impact mental health, particularly where they move individuals out of poverty, although effect sizes are modest and certainty low. Effects are larger for wellbeing outcomes, and potentially for income losses. To best support population mental health, welfare policies need to reach the most socioeconomically disadvantaged. FUNDING: Wellcome Trust, Medical Research Council, Chief Scientist Office, and European Research Council.

Comparing population-level mental health of UK workers before and during the COVID-19 pandemic: a longitudinal study using Understanding Society.

OBJECTIVES: The COVID-19 pandemic has substantially affected workers' mental health. We investigated changes in UK workers' mental health by industry, socioeconomic class and occupation and differential effects by UK country of residence, gender and age. METHODS: We used representative Understanding Society data from 6474 adults (41 207 observations) in paid employment who participated in pre-pandemic (2017-2020) and at least one COVID-19 survey. The outcome was General Health Questionnaire-12 (GHQ-12) caseness (score: ≥4). Exposures were industry, socioeconomic class and occupation and are examined separately. Mixed-effects logistic regression was used to estimate relative (OR) and absolute (%) increases in distress before and during pandemic. Differential effects were investigated for UK countries of residence (non-England/England), gender (male/female) and age (younger/older) using three-way interaction effects. RESULTS: GHQ-12 caseness increased in relative terms most for 'professional, scientific and technical' (OR: 3.15, 95% CI 2.17 to 4.59) industry in the pandemic versus pre-pandemic period. Absolute risk increased most in 'hospitality' (+11.4%). For socioeconomic class, 'small employers/self-employed' were most affected in relative and absolute terms (OR: 3.24, 95% CI 2.28 to 4.63; +10.3%). Across occupations, 'sales and customer service' (OR: 3.01, 95% CI 1.61 to 5.62; +10.7%) had the greatest increase. Analysis with three-way interactions showed considerable gender differences, while for UK country of residence and age results are mixed. CONCLUSIONS: GHQ-12 caseness increases during the pandemic were concentrated among 'professional and technical' and 'hospitality' industries and 'small employers/self-employed' and 'sales and customers service' workers. Female workers often exhibited greater differences in risk by industry and occupation. Policies supporting these industries and groups are needed.

CD161 expression defines new human γδ T cell subsets.

γδ T cells are a highly versatile immune lineage involved in host defense and homeostasis, but questions remain around their heterogeneity, precise function and role during health and disease. We used multi-parametric flow cytometry, dimensionality reduction, unsupervised clustering, and self-organizing maps (SOM) to identify novel γδ T cell naïve/memory subsets chiefly defined by CD161 expression levels, a surface membrane receptor that can be activating or suppressive. We used middle-to-old age individuals given immune blockade is commonly used in this population. Whilst most Vδ1+subset cells exhibited a terminal differentiation phenotype, Vδ1- subset cells showed an early memory phenotype. Dimensionality reduction revealed eight γδ T cell clusters chiefly diverging through CD161 expression with CD4 and CD8 expression limited to specific subpopulations. Comparison of matched healthy elderly individuals to bronchiectasis patients revealed elevated Vδ1+ terminally differentiated effector memory cells in patients potentially linking this population with chronic proinflammatory disease.

Carriage and Transmission of Macrolide Resistance Genes in Patients With Chronic Respiratory Conditions and Their Close Contacts.

BACKGROUND: Long-term macrolide therapy has been shown to provide benefit to those with a range of chronic respiratory conditions. However, concerns remain about the impact of macrolide exposure on the carriage and abundance of antibiotic resistance genes within the oropharynx. The potential for onward transmission of resistance from macrolide recipients to their close contacts also is poorly understood. RESEARCH QUESTION: Does long-term macrolide use impact carriage of resistance within the oropharyngeal microbiota in people with chronic respiratory conditions and risk of onward transmission to their close contacts? STUDY DESIGN AND METHODS: Oropharyngeal swabs were collected from 93 individuals with chronic respiratory conditions, 53 of whom were receiving long-term macrolide therapy. An oropharyngeal swab also was collected from a close cohabiting contact of each patient. Detection and abundance of 10 macrolide-associated resistance genes with the potential to disseminate via horizontal gene transfer were assessed by quantitative polymerase chain reaction analysis. RESULTS: Detection of resistance genes in macrolide recipients was comparable with that in nonrecipients. However, the normalized gene abundance of erm(B) was significantly higher in the macrolide recipient group (P = .045). Among the close contacts, no between-group differences in resistance gene detection or abundance were identified. Within-group analysis showed that the detection of erm(F) and mef in macrolide recipients, but not nonrecipients, was associated significantly with detection in close contacts (P = .003 and P = .004, respectively). However, between-group analysis showed that treatment group did not predict cocarriage between patients and their close contacts (P > .05 for each gene). INTERPRETATION: Although levels of erm(B) were higher in those receiving long-term macrolide therapy and evidence of gene cocarriage with close contacts was found, no evidence was found that macrolide use increased the onward transmission risk to their close contacts. This study therefore addresses concerns that long-term macrolide therapy could promote the dissemination of transmissible macrolide resistance.

Which is most important for mental health: Money, poverty, or paid work? A fixed-effects analysis of the UK Household Longitudinal Study.

BACKGROUND: The relative importance of income, poverty and unemployment status for mental health is unclear, and understanding this has implications for income and welfare policy design. We aimed to assess the association between changes in these exposures and mental health. METHODS: We measured effects of three transition exposures between waves of the UK Household Longitudinal Study from 2010/11-2019/20 (n=38,697, obs=173,859): income decreases/increases, moving in/out of poverty, and job losses/gains. The outcome was General Health Questionnaire (GHQ), which measures likelihood of common mental disorder (CMD) as a continuous (GHQ-36) and binary measure (score ≥4 = case). We used fixed-effects linear and linear probability models to adjust for time invariant and time-varying confounders. To investigate effect modification, we stratified analyses by age, sex and highest education. RESULTS: A 10% income decrease/increase was associated with a 0.02% increase (95% CI 0.00, 0.04) and 0.01% reduction (95% CI -0.03, 0.02) in likelihood of CMD respectively. Effect sizes were larger for moving into poverty (+1.8% [0.2, 3.5]), out of poverty (-1.8%, [-3.2, -0.3]), job loss (+15.8%, [13.6, 18.0]) and job gain (-11.4%, [-14.4, -8.4]). The effect of new poverty was greater for women (+2.3% [0.8, 3.9] versus +1.2% [-1.1, 3.5] for men) but the opposite was true for job loss (+17.8% [14.4, 21.2] for men versus +13.5% [9.8, 17.2] for women). There were no clear differences by age, but those with least education experienced the largest effects from poverty transitions, especially moving out of poverty (-2.9%, [-5.7, -0.0]). CONCLUSIONS: Moving into unemployment was most strongly associated with CMD, with poverty also important but income effects generally much smaller. Men appear most sensitive to employment transitions, but poverty may have larger impacts on women and those with least education. As the COVID-19 pandemic recedes, minimising unemployment as well as poverty is crucial for population mental health.

Health of people experiencing co-occurring homelessness, imprisonment, substance use, sex work and/or severe mental illness in high-income countries: a systematic review and meta-analysis.

BACKGROUND: People affected by homelessness, imprisonment, substance use, sex work or severe mental illness experience substantial excess ill health and premature death. Though these experiences often co-occur, health outcomes associated with their overlap have not previously been reviewed. We synthesised existing evidence on mortality, morbidity, self-rated health and quality of life among people affected by more than one of these experiences. METHODS: In this systematic review and meta-analysis, we searched Medline, Embase, and PsycINFO for peer-reviewed English-language observational studies from high-income countries published between 1 January 1998 and 11 June 2018. Two authors undertook independent screening, with risk of bias assessed using a modified Newcastle-Ottawa Scale. Findings were summarised by narrative synthesis and random-effect meta-analysis. RESULTS: From 15 976 citations, 2517 studies underwent full-text screening, and 444 were included. The most common exposure combinations were imprisonment/substance use (31% of data points) and severe mental illness/substance use (27%); only 1% reported outcomes associated with more than two exposures. Infections were the most common outcomes studied, with blood-borne viruses accounting for 31% of all data points. Multiple exposures were associated with poorer outcomes in 80% of data points included (sign test for effect direction, p<0.001). Meta-analysis suggested increased all-cause mortality among people with multiple versus fewer exposures (HR: 1.57 and 95% CI: 1.38 to 1.77), though heterogeneity was high. CONCLUSION: People affected by multiple exclusionary processes experience profound health inequalities, though there are important gaps in the research landscape. Addressing the health needs of these populations is likely to require co-ordinated action across multiple sectors, such as healthcare, criminal justice, drug treatment, housing and social security. PROSPERO REGISTRATION NUMBER: CRD42018097189.

Influence of climate variables on the rising incidence of nontuberculous mycobacterial (NTM) infections in Queensland, Australia 2001-2016.

International reports indicate a rising incidence of nontuberculous mycobacterial (NTM) disease. Many infectious diseases have seasonal variation in incidence, and major weather events and climate change have been implicated. The aim of this study was to explore the relationship between climate variables and NTM incident cases in Queensland, Australia. METHODS: NTM data were obtained from the Queensland notifiable conditions database for the period 2001-2016. Rainfall and temperature data were obtained from the Australian Bureau of Meteorology. Poisson regression models were used to assess notification rates (incidence cases per 100,000 population) over time and to estimate incidence rate ratios (IRR). Cross correlation coefficients were used to examine the relationship between rainfall and temperature data and NTM incidence over time in each Hospital and Health Service (HHS). RESULTS: 12,219 NTM cases were reported. The most common species was M. intracellulare (39.1%), followed by M. avium (9.8%), M abscessus (8.5%), M. fortuitum (8.3%), M. chelonae (3.3%), and M. kansasii (2.4%). The estimated incidence rate increased from 11.10 (95% CI 8.10-15.22) in 2001 to 25.88 (95%CI 21.78-30.73) per 100,000 in 2016. The estimated IRR increased for all common species, except M. kansasii. Although increased IRRs were observed for most NTM species, geospatial heterogeneity was observed. The effect of rainfall and temperature on NTM incidence differed between species and geographic regions. CONCLUSIONS: The incidence of NTM infections increased between 2001 and 2016. Variations in temperature and rainfall may play a role in environmental exposure to some species of NTM. Spatial variation in IRR suggests that there may also be other environmental factors that influence transmission.

The Rise of Non-Tuberculosis Mycobacterial Lung Disease.

The incidence and number of deaths from non-tuberculous mycobacterial (NTM) disease have been steadily increasing globally. These lesser known "cousins" of Mycobacterium tuberculosis (TB) were once thought to be harmless environmental saprophytics and only dangerous to individuals with defective lung structure or the immunosuppressed. However, NTM are now commonly infecting seemingly immune competent children and adults at increasing rates through pulmonary infection. This is of concern as the pathology of NTM is difficult to treat. Indeed, NTM have become extremely antibiotic resistant, and now have been found to be internationally dispersed through person-to-person contact. The reasons behind this NTM increase are only beginning to be elucidated. Solutions to the problem are needed given NTM disease is more common in the tropics. Importantly, 40% of the world's population live in the tropics and due to climate change, the Tropics are expanding which will increase NTM infection regions. This review catalogs the global and economic disease burden, at risk populations, treatment options, host-bacterial interaction, immune dynamics, recent developments and research priorities for NTM disease.