Search

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the gradual death of motor neurons in the brain and spinal cord, leading to fatal paralysis. Socioeconomic status (SES) is a measure of an individual's shared economic and social status, which has been shown to have an association with health outcomes. Understanding the impact of SES on health conditions is crucial, as it can influence and be influenced by health-related variables. The role of socioeconomic status in influencing the risk and progression of ALS has not been established, and understanding the various factors that impact ALS is important in developing strategies for treatment and prevention. To investigate this relationship, we recruited 413 participants with definite, probable, or possible ALS according to the El Escorial criteria, from three tertiary centers in London, Sheffield, and Birmingham. Logistic regression was used to examine the association between case-control status, socioeconomic criteria, and ALS risk. Linear regression was used to examine the association between age of onset and socioeconomic variables. Two sensitivity analyses were performed, one using an alternative occupational classifier, and the other using Mendelian Randomization analysis to examine association. There was no significant relationship between any variables and ALS risk. We found an inverse relationship between mean lifetime salary and age of ALS onset (Beta = −0.157, p = 0.011), but no effect of education or occupation on the age of onset. The finding was confirmed in both sensitivity analyses and in Mendelian Randomization. We find that a higher salary is associated with a younger age of ALS onset taking into account sex, occupation, years of education, and clinical presentation. [ABSTRACT FROM AUTHOR]

This study explores the complexities of developing feminist archives with a particular focus on the 'Feminist Approaches to Youth Sexuality (FAYS)' archive, created as part of the Reanimating Data project (RAD, 2018-21). Through this case study, we explore the ethical considerations and practices involved in reanimating a landmark feminist study, the Women, Risk, and AIDS Project (WRAP), and emphasize the ethical dimensions of reanimation processes, considering feminist ethics of care and risk. We also explore the concept of rematriation, which is rooted in indigenous feminist scholarship. This concept has become a guiding principle in our efforts to return WRAP to its geo-political context. As such, the article is structured into the following three sections: data in the attic, on recovery and rematriation; feminist ethics, on care and risk; and feminist archival praxis, on reanimating and language. [ABSTRACT FROM AUTHOR]

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 (NCT 03421743). [ABSTRACT FROM AUTHOR]

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. Rachel M Thomson and colleagues used a policy model to simulate how a Universal Basic Income might influence mental health for working-age adults in the UK. Author summary: Why was this study done?: Universal Basic Income (UBI) is a radical social security policy proposal where everyone in a society would receive a regular, unconditional cash payment. It has been suggested that UBI might be beneficial for mental health. However, there has never been a trial of a true UBI in a high-income country to know what its potential mental health impacts might be. What did the researchers do and find?: We used a policy model to simulate how a UBI might influence mental health for working-age adults in the United Kingdom. We found that the effects of UBI were very sensitive to assumptions we made about how people's employment choices might respond to receiving the money—if people choose to stay in work, UBI may have small benefits for population mental health, but if people are more likely to leave work, population mental health may actually worsen. The groups most likely to experience positive mental health effects of UBI were women and those with the lowest educational qualifications. What do these findings mean?: UBI may have potential to improve population mental health in high-income countries, but only if people do not choose to leave work in response to the policy. More real-world research is needed to know how people are likely to respond to receiving a UBI in reality. The main limitation of our modelling study is that it looks at how UBI would influence mental health only through income and employment, and other pathways might also be important to include in future research. [ABSTRACT FROM AUTHOR]

Policy PointsIncome 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

What do we do with emotion in biographical research: is it an end in itself, a symptom to be explained, a thread to be pulled? This paper presents an experiment in methodology within a field of biographical methods that involved revisiting a single qualitative interview after the elapse of thirty years. The interview with 22 year old Stacey was troubling at the time it was generated (as captured in fieldnotes and interview transcript) and was still troubling when these documents were reprised. Naming sadness as an emotion at play in the material took teamwork and emotionally engaged methods of analysis and interpretation. Working with psychoanalytically informed theories we show how a curiosity about emotion and a willingness to follow feelings can help connect individual stories to collective histories. The paper presents group based analyses and writing methods as a way of tracing the psychic logics of story through scenic material (what we call 'emotional bombshells'). We consider the difference that time might make to an analysis, considering the possibility that more time might produce more perspective through allowing the original context to be rendered (more) visible. We also suggest that clock time can be transcended when considering unconscious processes and experiences that resist narrative. Recontextualising research materials can enrich meaning and further realise the value of qualitative interviews that always contain more to be heard, resituated in new times and relationships. This is not simply an exercise in nostalgia but is offered as a method in its own right, reanimation as a route to the generation of new intergenerational knowledge of a thick present in which past, present and future co-exist. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

What are participants and researchers agreeing to when they consent to having data archived and what do they imagine the future life of their data to be? In this paper, we reflect on a project that deliberately started rather than ended with the archive. The Everyday Childhoods project invited children and their families to take part in the creation of an open access public archive documenting everyday childhoods using a range of multimedia data. Families and researchers were invited into the archive, encouraged to imagine different kinds of secondary use and to speak directly to future user of their data through short films and postcards. This paper raises questions concerning the place of the archive in different disciplinary traditions; the roles of researcher and archivist in safekeeping, gatekeeping and caring for data collections; and the place of qualitative longitudinal research as a site of innovation within a new data landscape. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-g 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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Kirsten rat sarcoma (KRAS) is one of the most frequently mutated oncogenes in solid tumours. It encodes an important signalling pathway that drives cellular proliferation and growth. It is frequently mutated in aggressive advanced solid tumours, particularly colorectal, lung and pancreatic cancer. Since the first mutated KRAS was discovered in the 1980s, decades of research to develop targeted inhibitors of mutant KRAS have fallen short of the task, until recently. Multiple agents are now in clinical trials, including specific mutant KRAS inhibitors, pan-KRAS inhibitors, therapeutic vaccines and other targeted inhibitors. Mutant-specific KRAS G12C inhibitors are the most advanced, with two inhibitors, adagrasib and sotorasib, achieving approval in 2021 for the second-line treatment of patients with KRAS G12C mutant lung cancer. In this review, we summarise the importance of mutant KRAS in solid tumours, prior attempts at inhibiting mutant KRAS, and the current promising targeted agents being investigated in clinical trials, along with future challenges. [ABSTRACT FROM AUTHOR]

Non-tuberculous mycobacteria (NTM) are an emerging group of pulmonary infectious pathogens of increasing importance to the management of patients with cystic fibrosis (CF). NTM include slow-growing mycobacteria such as Mycobacterium avium complex (MAC) and rapidly growing mycobacteria such as Mycobacterium abscessus. The incidence of NTM in the CF population is increasing and infection contributes to significant morbidity to the patient and costs to the health system. Treating M. abscessus requires the combination of multiple costly antibiotics for months, with potentially significant toxicity associated with treatment. Although international guidelines for the treatment of NTM infection in CF are available, there are a lack of robust pharmacokinetic studies in CF patients to inform dosing and drug choice. This paper aims to outline the pharmacokinetic and pharmacodynamic factors informing the optimal treatment of NTM infections in CF. [ABSTRACT FROM AUTHOR]

Background: In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture conversion by month 6 in patients with treatment-refractory Mycobacterium avium complex lung disease (ALIS plus GBT, 29% [65/224] vs GBT alone, 8.9% [10/112]; P < .0001).Research Question: In patients who achieved culture conversion by month 6 in the CONVERT study, was conversion sustained (negative sputum culture results for 12 months with treatment) and durable (negative sputum culture results for 3 months after treatment) and were there any additional safety signals associated with a full treatment course of 12 months after conversion?Study Design and Methods: Adults were randomized 2:1 to receive ALIS plus GBT or GBT alone. Patients achieving culture conversion by month 6 continued therapy for 12 months followed by off-treatment observation.Results: More patients randomized to ALIS plus GBT (intention-to-treat population) achieved conversion that was both sustained and durable 3 months after treatment vs patients randomized to GBT alone (ALIS plus GBT, 16.1% [36/224] vs GBT alone, 0% [0/112]; P < .0001). Of the patients who achieved culture conversion by month 6, 55.4% of converters (36/65) in the ALIS plus GBT treated arm vs no converters (0/10) in the GBT alone arm achieved sustained and durable conversion (P = .0017). Relapse rates through 3 months after treatment were 9.2% (6/65) in the ALIS plus GBT arm and 30.0% (3/10) in the GBT alone arm. Common adverse events among ALIS plus GBT-treated patients (dysphonia, cough, dyspnea, hemoptysis) occurred mainly within the first 8 months of treatment.Interpretation: In a refractory population, conversion was sustained and durable in more patients treated with ALIS plus GBT for 12 months after conversion than in those treated with GBT alone. No new safety signals were associated with 12 months of treatment after conversion.Trial Registry: ClinicalTrials.gov; No.: NCT02344004; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Australia and New Zealand have the highest incidence and mortality rates for melanoma in the world. Local surgery is still the standard treatment of primary cutaneous melanoma, and it is therefore important that surgeons understand the optimal care pathways for patients with melanoma. Accurate staging is critical to ensure a reliable assessment of prognosis and to guide treatment selection. Sentinel node biopsy (SNB) plays an important role in staging and the provision of reliable prognostic estimates for patients with cutaneous melanoma. Patients with stage III melanoma have a substantial risk of disease recurrence following surgery, leading to poor long-term outcomes. Systemic immunotherapies and targeted therapies, known to be effective for stage IV melanoma, have now also been shown to be effective as adjuvant post-surgical treatments for resected stage III melanoma. These patients should be made aware of this and preferably managed in an integrated multidisciplinary model of care, involving the surgeon, medical oncologists and radiation oncologists. This review considers the impact of a recent update to the American Joint Committee on Cancer (AJCC) staging system, the role of SNB for patients with high-risk primary melanoma and recent advances in adjuvant systemic therapies for high-risk patients. [ABSTRACT FROM AUTHOR]

Australia and New Zealand have the highest incidence and mortality rates for melanoma in the world. Local surgery is still the standard treatment of primary cutaneous melanoma, and it is therefore important that surgeons understand the optimal care pathways for patients with melanoma. Accurate staging is critical to ensure a reliable assessment of prognosis and to guide treatment selection. Sentinel node biopsy (SNB) plays an important role in staging and the provision of reliable prognostic estimates for patients with cutaneous melanoma. Patients with stage III melanoma have a substantial risk of disease recurrence following surgery, leading to poor long‐term outcomes. Systemic immunotherapies and targeted therapies, known to be effective for stage IV melanoma, have now also been shown to be effective as adjuvant post‐surgical treatments for resected stage III melanoma. These patients should be made aware of this and preferably managed in an integrated multidisciplinary model of care, involving the surgeon, medical oncologists and radiation oncologists. This review considers the impact of a recent update to the American Joint Committee on Cancer (AJCC) staging system, the role of SNB for patients with high‐risk primary melanoma and recent advances in adjuvant systemic therapies for high‐risk patients. [ABSTRACT FROM AUTHOR]

Adverse events are frequent in nontuberculous mycobacteria pulmonary disease treatment, but evidence to support their management is scarce. An expert panel survey on management of adverse events shows consistent opinions on management of hepatoxicity, ocular toxicity, ototoxicity, tinnitus, and gastrointestinal upset. These opinions can provide assistance in individual patient management decisions. [ABSTRACT FROM AUTHOR]

Rationale: Patients with refractory Mycobacterium avium complex (MAC) lung disease have limited treatment options. In the CONVERT study, amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) increased culture conversion rates versus GBT alone by Month 6. Limited data are available regarding >6-month treatment in a refractory population.Objectives: Evaluate 12-month safety, tolerability, and efficacy of ALIS+GBT.Methods: Adults with refractory MAC lung disease not achieving culture conversion by CONVERT Month 6 could enroll in this open-label extension (INS-312) to receive 590 mg once-daily ALIS+GBT for 12 months. Two cohorts enrolled: the "ALIS-naive" cohort included patients randomized to GBT alone in CONVERT, and the "prior-ALIS" cohort included those randomized to ALIS+GBT in CONVERT. Safety and tolerability of ALIS over 12 months (primary endpoint) and culture conversion by Months 6 and 12 were assessed.Results: In the ALIS-naive cohort, 83.3% of patients (n = 75/90) experienced respiratory treatment-emergent adverse events (TEAEs), and 35.6% (n = 32) had serious TEAEs; 26.7% (n = 24) achieved culture conversion by Month 6 and 33.3% (n = 30) by Month 12. In the prior-ALIS cohort, 46.6% of patients (n = 34/73) experienced respiratory TEAEs, and 27.4% (n = 20) had serious TEAEs; 9.6% (n = 7) achieved culture conversion by Month 6 (≤14 mo ALIS exposure) and 13.7% (n = 10) by Month 12 (≤20 mo ALIS exposure). Nephrotoxicity-related TEAEs and measured hearing decline were infrequent in both cohorts.Conclusions: In up to 20 months of ALIS use, respiratory TEAEs were common, nephrotoxicity and hearing decline were infrequent, and culture conversion continued beyond 6 months of therapy.Clinical trial registered with www.clinicaltrials.gov (NCT02628600). [ABSTRACT FROM AUTHOR]

The treatment options for patients with melanoma have expanded significantly over the past decade. In particular, the use of targeted therapy and immunotherapy has dramatically transformed the outlook for patients with advanced disease. These treatments are now being utilised as adjuvant therapy for patients with earlier stage melanoma after surgical resection. We review the latest updates for melanoma staging, surgical resection, radiotherapy and systemic therapies. [ABSTRACT FROM AUTHOR]

In this article we engage critically with how metaphors have been used in sociological youth studies, including a turn to new metaphors that capture the foreclosure of futures and experiences of waiting, delay and non-institutional temporalities. Drawing on the resources of queer theory we challenge the developmentalism that underpins youth studies, employing notions of the impasse and growing sideways to capture the open-endedness of young adult lives. Working with data from a qualitative longitudinal study of Danish youth, we focus on how 47 young people responded to an invitation to talk about and through an object that represented the last three years of their lives. These rich accounts can be understood as examples of Paul Riceour's 'metaphoric discourse', characterised by the simultaneity of 'is' and 'is not'. The article first offers a schema of the biographical objects (trophies, hobbies, mortal, connective and protest) that captures the work of 'being in time' for young adults, mapping this onto the formal and informal markers of adulthood. We then engage with participants' own metaphorical thinking in greater depth – suggesting that the paradoxical metaphors that emerge from their talk can expand how we understand the struggle for maturity. The metaphor of open-endedness is offered as a hybrid term, allowing us to look in two directions at once: capturing and comparing transitions as part of a project of social justice, while also recognising the limits of such frameworks for understanding the experiences of a new generation. [ABSTRACT FROM AUTHOR]

Emphasizing the need for "second adjuvant" treatment in this setting, a retrospective study found that 43% of patients who recur during or after adjuvant PD-1 inhibitor have locoregional disease only, but 37% of these patients then develop distant disease soon after [[19]]. Patients with melanoma who have regional nodal or in-transit involvement at diagnosis (stage III) are at a high risk for recurrence, with the 5-year survival ranging from 93% for IIIA to 32% for IIID disease [[1]]. Given that the risk of further (distant) recurrence is high and that there is no evidence to suggest that patients become cross-resistant to both targeted and immunotherapies, BRAF mutant patients who recur despite one therapy should be considered for the alternative "second adjuvant" therapy (e.g. initial immunotherapy, subsequent targeted therapy) [[16], [20]]. Treatment selection therefore should be guided by sub-stage, patient co-morbidities (e.g. autoimmune conditions), patient preference regarding potential toxicities, and access to available treatments. [Extracted from the article]

Inhibition of myostatin- and activin-mediated SMAD2/3 signaling using ligand traps, such as soluble receptors, ligand-targeting propeptides and antibodies, or follistatin can increase skeletal muscle mass in healthy mice and ameliorate wasting in models of cancer cachexia and muscular dystrophy. However, clinical translation of these extracellular approaches targeting myostatin and activin has been hindered by the challenges of achieving efficacy without potential effects in other tissues. Toward the goal of developing tissue-specific myostatin/activin interventions, we explored the ability of transmembrane prostate androgen-induced (TMEPAI), an inhibitor of transforming growth factor-β (TGF-β1)-mediated SMAD2/3 signaling, to promote growth, and counter atrophy, in skeletal muscle. In this study, we show that TMEPAI can block activin A, activin B, myostatin and GDF-11 activity in vitro. To determine the physiological significance of TMEPAI, we employed Adeno-associated viral vector (AAV) delivery of a TMEPAI expression cassette to the muscles of healthy mice, which increased mass by as much as 30%, due to hypertrophy of muscle fibers. To demonstrate that TMEPAI mediates its effects via inhibition of the SMAD2/3 pathway, tibialis anterior (TA) muscles of mice were co-injected with AAV vectors expressing activin A and TMEPAI. In this setting, TMEPAI blocked skeletal muscle wasting driven by activin-induced phosphorylation of SMAD3. In a model of cancer cachexia associated with elevated circulating activin A, delivery of AAV:TMEPAI into TA muscles of mice bearing C26 colon tumors ameliorated the muscle atrophy normally associated with cancer progression. Collectively, the findings indicate that muscle-directed TMEPAI gene delivery can inactivate the activin/myostatin-SMAD3 pathway to positively regulate muscle mass in healthy settings and models of disease. [ABSTRACT FROM AUTHOR]

The optimal duration of immunotherapy treatment for cancer patients is unknown. As the survival data from early immunotherapy trials mature we are beginning to appreciate how durable responses can be post‐discontinuation. The purpose of this brief communication is to comment on treatment duration of immunotherapy in patients with melanoma and non‐small cell lung cancer and to provide practice guidance in support of discontinuation. [ABSTRACT FROM AUTHOR]

Keywords: Narrative; boundary object; longitudinal research; future; prospective social action EN Narrative boundary object longitudinal research future prospective social action 367 375 9 04/20/20 20200701 NES 200701 Introduction I can only answer the question "What am I to do?" Methodologically, this orientation privileges ethnographic approaches that thrust the narrative researcher into "the scenes of storytelling" (Gubrium & Holstein, [16], p. 250) to investigate how stories are produced and used in local contexts (Polletta et al, 2011). Contemporary narrative research continues to advance our understanding of narrative identities (e.g. Mattingly, [31]; MacAdams [34]) as well as practices of storytelling (e.g. De Fina, [13]; Tutenges, [60]). Theoretically, narrative criminology also takes inspiration from the philosophy of Ricoeur, especially his idea that narrative shapes experience in a constitutive sense as experience is always understood and acted upon in storied ways (Presser & Sandberg 2015, 4). [Extracted from the article]

Mixed methods longitudinal studies continue to be rare, yet have potential for transcending the limits of qualitative and quantitative paradigms. This article compares the life stories of 47 young people generated from a cohort study of 6000 children born in 1995. The cases were sampled through an association between two variables – drug use and leaving school early – generating a four-field table. Comparing the cases within and across each table cells, we question the 'black box' logic that underpins the assumption that cannabis smoking is consequential for educational success. Moving into a qualitative paradigm we reconceptualise the cases as butterflies captured in a net and work deductively to understand the species captured. Culminating with an analysis of a single case over time, we argue that narrative approaches are the starting point for understanding subsequent social action, providing a basis for larger scale quantitative modeling. [ABSTRACT FROM AUTHOR]

Despite the increasing incidence of metastatic melanoma in the older population, there is relatively limited specific data surrounding the use of immunotherapy for the treatment of advanced melanoma for patients above the age of 65 years. To date, there has not been a prospective trial done to evaluate the safety and efficacy of using immunotherapy to treat older patients with advanced melanoma. Older patients are often under-represented in clinical trials. In addition, older patients in clinical trials may have lower Eastern Cooperative Oncology Group (ECOG) performance score and fewer co-morbidities, and thus trial data may not truly reflect the experience of treating older patients. The purpose of this descriptive review is to examine the efficacy and safety data of the three currently approved immune checkpoint inhibitors for advanced melanoma treatment in older patients. Our review of available data established that the efficacy and tolerability of immunotherapy in older patients are comparable to results seen in younger patients. However, a dedicated, prospective, randomised trial to assess the safety, tolerability, and quality-of-life parameters of immunotherapy in the older population would provide further insight on the value of these treatments. [ABSTRACT FROM AUTHOR]

Across national contexts, research shows that young people who live in child protection facilities often have negative experiences of power relations. In this article we look for a suitable method which takes account of power relations while investigating young people's perspectives on their everyday lives. We first present the results of an international methodological literature review concerned with the study of everyday life of young people, including ethical discussions arising among researchers. Drawing on this, our own research devised a shortitudinal, qualitative and cross-national approach which was designed to empower young participants during the research process. Sixteen young people living in care in France and in England participated in this project. Here we discuss the ways in which this approach functioned to give participants control--over the use they made of the research tools, over the topics that were discussed, and over the spaces in which research data were generated. Some of the data show how young people's choices reflect the areas where they feel powerful. We argue that using this method enabled insights into the ways in which young people were able to create or protect agentic spaces within the constrained everyday lives of child protection. [ABSTRACT FROM AUTHOR]

Purpose: Australian data regarding the management of patients with bronchiectasis is scarce. We sought to compare the management of adults with bronchiectasis attending tertiary Australian centres with recent national and international guidelines. Methods: The Australian Bronchiectasis Registry is a centralised database of patients with radiologically confirmed bronchiectasis unrelated to cystic fibrosis recruited from 14 tertiary Australian hospitals. We excluded children (<18 years) and those with incomplete data, leaving 589 adults for cross-sectional analyses. We compared the proportion of patients receiving certain therapies, as compared to the proportion eligible for those treatments according to the current guidelines and baseline clinical information available from the registry. Results: Pulmonary rehabilitation was attended by 22%, although it was indicated in 67% of the cohort. Airway clearance was undertaken in 52% of patients, although 71% reported chronic productive cough. Sputum bacterial culture results were available for 59%, and mycobacterial culture results were available for 29% of the cohort. Inhaled antibiotics were used in half of potentially eligible patients. Despite guideline recommendations against routine use, inhaled corticosteroids were used in 48% of patients. Long-term macrolides were used in 28% of participants. Conclusions: Discrepancies exist between guideline recommendations and real-world treatment of bronchiectasis in Australia, even in tertiary centres. These findings suggest the need for increased patient referral to pulmonary rehabilitation, increased attention to airway clearance, increased collection of sputum samples (especially for mycobacterial culture) and rationalisation of inhaled corticosteroid use. These findings encourage a review of treatment access and will inform ongoing education to promote evidence-based care for people living with bronchiectasis. [ABSTRACT FROM AUTHOR]

Background and objective: Aerosol transmission of Pseudomonas aeruginosa has been suggested as a possible mode of respiratory infection spread in patients with cystic fibrosis (CF); however, whether this occurs in other suppurative lung diseases is unknown. Therefore, we aimed to determine if (i) patients with bronchiectasis (unrelated to CF) or chronic obstructive pulmonary disease (COPD) can aerosolize P. aeruginosa during coughing and (ii) if genetically indistinguishable (shared) P. aeruginosa strains are present in these disease cohorts. Methods: People with bronchiectasis or COPD and P. aeruginosa respiratory infection were recruited for two studies. Aerosol study: Participants (n = 20) underwent cough testing using validated cough rigs to determine the survival of P. aeruginosa aerosols in the air over distance and duration. Genotyping study:P. aeruginosa sputum isolates (n = 95) were genotyped using the iPLEX20SNP platform, with a subset subjected to the enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC‐PCR) assay to ascertain their genetic relatedness. Results: Aerosol study: Overall, 7 of 20 (35%) participants released P. aeruginosa cough aerosols during at least one of the cough aerosol tests. These cough aerosols remained viable for 4 m from the source and for 15 min after coughing. The mean total aerosol count of P. aeruginosa at 2 m was two colony‐forming units. Typing study: No shared P. aeruginosa strains were identified. Conclusion: Low viable count of P. aeruginosa cough aerosols and a lack of shared P. aeruginosa strains observed suggest that aerosol transmission of P. aeruginosa is an unlikely mode of respiratory infection spread in patients with bronchiectasis and COPD. Our study shows that patients with bronchiectasis and chronic obstructive pulmonary disease (COPD) can release potentially infectious aerosols during coughing; however, no shared stains of Pseudomonas aeruginosa were identified in our study. The results suggest that aerosol transmission is an unlikely mode of cross‐infection in patients with bronchiectasis and COPD. Watch the video abstract See related Editorial [ABSTRACT FROM AUTHOR]

Background: Brain radiotherapy is used in the management of melanoma brain metastases (MBM) and can result in radionecrosis. Anti‐PD‐1 is active in the brain and may increase the risk of radionecrosis when combined with radiotherapy. We studied the incidence, associated factors and management of radionecrosis in longer‐term survivors with MBM treated with this combination. Methods: Patients with MBM treated with radiotherapy and anti‐PD‐1 who survived >1 year were identified to determine radionecrosis incidence (Cohort A, n = 135). Cohort A plus additional radionecrosis cases were examined for factors associated with radionecrosis and management (Cohort B, n = 148). Results: From Cohort A, 17% developed radionecrosis, with a cumulative incidence at 2 years of 18%. Using Cohort B, multivariable analysis confirmed an association between radionecrosis and elevated lactate dehydrogenase (p = 0.0496) and prior treatment with ipilimumab (p = 0.0319). Radionecrosis was diagnosed based on MRI (100%), symptoms (69%) and pathology (56%). Treatment included corticosteroids, bevacizumab and neurosurgery. Conclusions: Radionecrosis is a significant toxicity in longer‐term melanoma survivors with MBM treated with anti‐PD‐1 and radiotherapy. Identification of those at risk of radionecrosis who may avoid radiotherapy is required. [ABSTRACT FROM AUTHOR]

Background: The inter‐jurisdictional National Mutual Acceptance (NMA) scheme for Human Research Ethics Committee (HREC) approvals of human research is designed to reduce the reported delays and costs of ethical review. Introduction of the NMA set forth an uncoupling of the ethics and governance review processes, permitting a single ethical review for multiple sites, while continuing separate governance review for each centre covering financial and operational aspects of the research project. Aim: To compare the time required to gain ethics and governance approvals in Australia for a non‐interventional investigator‐led study from December 2015 to approval times for an earlier pre‐NMA study utilising a similar study design and study sites and evaluate the effect that the NMA has had on total approval time for non‐interventional multi‐centre projects. Methods: We recorded the time taken to obtain ethics and governance approval at 16 sites for our nationwide low‐risk non‐interventional study looking at the prevalence and aetiology of non‐tuberculous mycobacterial infection in people with cystic fibrosis in Australia. Results: Applications were submitted to three hospitals and one university HREC to conduct our study at 16 hospital sites, HREC approval took from 16 to 79 days (median 28). Subsequent site‐specific governance approval at 15 hospital sites took 23–225 days (median 83). The entire process of gaining ethical and governance approval to conduct the study at 16 sites took 24 months at an estimated cost of AU$56000 (US$ 42 000). Conclusion: Lengthy governance approval processes negate benefits gained from centralised ethics review under the NMA. [ABSTRACT FROM AUTHOR]

Rationale: Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives: To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods: Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite at least 6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS + GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as three consecutive monthly MAC-negative sputum cultures by Month 6. Measurements and Main Results: Enrolled patients (ALIS + GBT, n = 224; GBT-alone, n = 112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS + GBT and 10 of 112 (8.9%) with GBT alone (odds ratio, 4.22; 95% confidence interval, 2.08-8.57; P < 0.001). Patients in the ALIS + GBT arm versus GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% confidence interval, 2.00-7.60). Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS + GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions: Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by Month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT02344004). [ABSTRACT FROM AUTHOR]

Objective It is known that mental health deteriorated following the 2008 global financial crisis, and that subsequent UK austerity policies post-2010 disproportionately impacted women and those in deprived areas. We aimed to assess whether gender and socioeconomic inequalities in poor mental health have changed since the onset of austerity policies. Design Repeat cross-sectional analysis of survey data. Setting England. Participants Nationally and regionally representative samples of the working-age population (25-64 years) from the Health Survey for England (1991-2014). Outcome measures Population-level poor mental health was measured by General Health Questionnaire-12 (GHQ) caseness, stratified by gender and socioeconomic position (area-level deprivation and highest educational attainment). Results The prevalence of age-adjusted male GHQ caseness increased by 5.9% (95% CI 3.2% to 8.5%, p<0.001) from 2008 to 2009 in the immediate postrecession period, but recovered to prerecession levels after 2010. In women, there was little change in 2009 or 2010, but an increase of 3.0% (95% CI 1.0% to 5.1%, p=0.004) in 2012 compared with 2008 following the onset of austerity. Estimates were largely unchanged after further adjustment for socioeconomic position, employment status and household income as potential mediators. Relative socioeconomic inequalities in GHQ caseness narrowed from 2008 to 2010 immediately following the recession, with Relative Index of Inequality falling from 2.28 (95% CI 1.89 to 2.76, p<0.001) to 1.85 (95% CI 1.43 to 2.38, p<0.001), but returned to prerecession levels during austerity. Conclusions Gender inequalities in poor mental health narrowed following the Great Recession but widened during austerity, creating the widest gender gap since 1994. Socioeconomic inequalities in poor mental health narrowed immediately postrecession, but this trend may now be reversing. Austerity policies could contribute to widening mental health inequalities. [ABSTRACT FROM AUTHOR]