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).

Extended water stagnation in buildings during the COVID-19 pandemic increases the risks posed by opportunistic pathogens.

The regrowth and subsequent exposure of opportunistic pathogens (OPs) whilst reopening buildings that have been locked down due to the stay-at-home restrictions to limit the spread of COVID-19, is a public health concern. To better understand such microbiological risks due to lowered occupancy and water demand in buildings, first and post-flush water samples (n = 48) were sampled from 24 drinking water outlets from eight university buildings in two campuses (urban and rural), with various end-user occupancies. Both campuses were served with chlorinated water originating from a single drinking water distribution system in South-East Queensland, situated 14 km apart, where the rural campus had lower chlorine residuals. Culture-dependent and culture-independent methods (such as flow cytometry, qPCR and 16S rRNA gene amplicon sequencing) were used concurrently to comprehensively characterise the OPs of interest (Legionella spp., Pseudomonas aeruginosa, and nontuberculous mycobacteria (NTM)) and the premise plumbing microbiome. Results showed that buildings with extended levels of stagnation had higher and diverse levels of microbial growth, as observed in taxonomic structure and composition of the microbial communities. NTM were ubiquitous in all the outlets sampled, regardless of campus or end-user occupancy of the buildings. qPCR and culture demonstrated prevalent and higher concentrations of NTM in buildings (averaging 3.25 log10[estimated genomic copies/mL]) with extended stagnation in the urban campus. Furthermore, flushing the outlets for 30 minutes restored residual and total chlorine, and subsequently decreased the levels of Legionella by a reduction of 1 log. However, this approach was insufficient to restore total and residual chlorine levels for the outlets in the rural campus, where both Legionella and NTM levels detected by qPCR remained unchanged, regardless of building occupancy. Our findings highlight that regular monitoring of operational parameters such as residual chlorine levels, and the implementation of water risk management plans are important for non-healthcare public buildings, as the levels of OPs in these environments are typically not assessed.

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.

In vitro susceptibility testing of imipenem-relebactam and tedizolid against 102 Mycobacterium abscessus isolates.

OBJECTIVES: Mycobacterium abscessus is an emerging infection in people living with lung diseases, including cystic fibrosis (CF) and bronchiectasis, and it has limited treatment options and low cure rates. The off-label use of novel antibiotics developed for other bacterial pathogens offers potential new therapeutic options. We aimed to describe the in vitro activity of imipenem, imipenem-relebactam and tedizolid against comparator antibiotics in M. abscessus isolates from Australian patients with and without CF. METHODS: We performed susceptibility testing for imipenem-relebactam, tedizolid and comparator antibiotics by Clinical and Laboratory Standards Institute (CLSI) criteria against 102 clinical M. abscessus isolates, including 46 from people with CF. RESULTS: In this study, the minimum inhibitory concentration (MICs) of imipenem-relebactam was one-fold dilution less than of imipenem alone. The MIC50 and MIC90 of imipenem-relebactam were 8 and 16 mg/L, respectively, whereas for imipenem they were 16 and 32 mg/L. Tedizolid had an MIC50 and MIC90 of 2 and 4 mg/L, respectively. Forty non-CF isolates had linezolid susceptibility performed, with MIC50 and MIC90 values of 16 and 32 mg/L, respectively, measured. CONCLUSIONS: This study shows lower MICs for imipenem-relebactam and tedizolid compared to other more commonly used antibiotics and supports their consideration in clinical trials for M. abscessus treatment.

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.

The public health implications of the cost-of-living crisis: outlining mechanisms and modelling consequences.

The UK, and other high-income countries, are experiencing substantial increases in living costs. Several overlapping and intersecting economic crises threaten physical and mental health in the immediate and longer term. Policy responses may buffer against the worst effects (e.g. welfare support) or further undermine health (e.g. austerity). We explore fundamental causes underpinning the cost-of-living crisis, examine potential pathways by which the crisis could impact population health and use a case study to model potential impacts of one aspect of the crisis on a specific health outcome. Our modelling illustrates how policy approaches can substantially protect health and avoid exacerbating health inequalities. Targeting support at vulnerable households is likely to protect health most effectively. The current crisis is likely to be the first of many in era of political and climate uncertainty. More refined integrated economic and health modelling has the potential to inform policy integration, or 'health in all policies'.

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.

Environmental risk of nontuberculous mycobacterial infection: Strategies for advancing methodology.

The National Institute of Allergy and Infectious Diseases organized a symposium in June 2022, to facilitate discussion of the environmental risks for nontuberculous mycobacteria exposure and disease. The expert researchers presented recent studies and identified numerous research gaps. This report summarizes the discussion and identifies six major areas of future research related to culture-based and culture independent laboratory methods, alternate culture media and culturing conditions, frameworks for standardized laboratory methods, improved environmental sampling strategies, validation of exposure measures, and availability of high-quality spatiotemporal data.

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.

'Teach me how to look after myself': What people with bronchiectasis want from education in a pulmonary rehabilitation setting.

INTRODUCTION: Pulmonary rehabilitation is recommended for people with bronchiectasis. Various education topics are included in these programmes, but the content is largely guided by the needs of people with other respiratory conditions. OBJECTIVES: With the education topics applicable to people with bronchiectasis unclear, we aimed to explore the perspective of adults with this condition on relevant educational topics in a pulmonary rehabilitation context. METHODS: Participants from the Australian Bronchiectasis Registry were invited to undertake a semi-structured interview. Interview transcripts were coded independently, with themes established by consensus (two researchers). RESULTS: Twenty-one people participated. The major themes were greater clarity on the underlying cause of bronchiectasis and prognosis. Most sought knowledge about self-management strategies and treatments to address extra-pulmonary symptoms. Participants requested more information on physiotherapy options and the role of exercise and physical activity outside of pulmonary rehabilitation. Preferences were mixed for the education delivery model. CONCLUSIONS: We have identified unmet educational topics of interest for people with bronchiectasis. Our study provides a framework for education topics desired by adults with bronchiectasis within a pulmonary rehabilitation setting. The topics identified will guide development of an education curriculum for pulmonary rehabilitation that is more fit-for-purpose for people with bronchiectasis.

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.

Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma.

BACKGROUND: Acral melanoma is a rare melanoma subtype with poor prognosis. Importantly, these patients were not identified as a specific subgroup in the landmark melanoma trials involving ipilimumab and the anti-programmed cell death protein-1 (PD-1) agents nivolumab and pembrolizumab. There is therefore an absence of prospective clinical trial evidence regarding the efficacy of checkpoint inhibitors (CPIs) in this population. Acral melanoma has lower tumor mutation burden (TMB) than other cutaneous sites, and primary site is associated with differences in TMB. However the impact of this on the effectiveness of immune CPIs is unknown. We examined the efficacy of CPIs in acral melanoma, including by primary site. METHODS: Patients with unresectable stage III/IV acral melanoma treated with CPI (anti-PD-1 and/or ipilimumab) were studied. Multivariable logistic and Cox regression analyses were conducted. Primary outcome was objective response rate (ORR); secondary outcomes were progression-free survival (PFS) and overall survival (OS). RESULTS: In total, 325 patients were included: 234 (72%) plantar, 69 (21%) subungual and 22 (7%) palmar primary sites. First CPI included: 184 (57%) anti-PD-1, 59 (18%) anti-PD-1/ipilimumab combination and 82 (25%) ipilimumab. ORR was significantly higher with initial anti-PD-1/ipilimumab compared with anti-PD-1 (43% vs 26%, HR 2.14, p=0.0004) and significantly lower with ipilimumab (15% vs 26%, HR 0.49, p=0.0016). Landmark PFS at 1 year was highest for anti-PD-1/ipilimumab at 34% (95% CI 24% to 49%), compared with 26% (95% CI 20% to 33%) with anti-PD-1 and 10% (95% CI 5% to 19%) with ipilimumab. Despite a trend for increased PFS, anti-PD-1/ipilimumab combination did not significantly improve PFS (HR 0.85, p=0.35) or OS over anti-PD-1 (HR 1.30, p=0.16), potentially due to subsequent therapies and high rates of acquired resistance. No outcome differences were found between primary sites. CONCLUSION: While the ORR to anti-PD-1/ipilimumab was significantly higher than anti-PD-1 and PFS numerically higher, in this retrospective cohort this benefit did not translate to improved OS. Future trials should specifically include patients with acral melanoma, to help determine the optimal management of this important melanoma subtype.

Talimogene laherparepvec resulting in near-complete response in a patient with treatment-refractory Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous tumour of neuroendocrine cell origin, which can grow rapidly and metastasise early. Localised disease is treated with surgery and radiotherapy. Disease that reaches a more advanced stage can be treated with a variety of different treatment modalities including surgery, radiotherapy, chemotherapy, radionuclide therapy, immunotherapy, and intralesional therapy. We report a case of a patient who had exhausted all local and systemic treatment options and who subsequently had an exceptional response to intralesional injection of Talimogene laherparepvec (TVEC).

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.