Youth adversity and trajectories of depression/anxiety symptoms in adolescence in the context of intersectionality in the United Kingdom.

BACKGROUND: Youth adversity is associated with persistence of depression and anxiety symptoms. This association may be greater for disadvantaged societal groups (such as females) compared with advantaged groups (e.g. males). Given that persistent symptoms are observed across a range of disadvantaged, minoritized, and neurodivergent groups (e.g. low compared with high socio-economic status [SES]), the intersection of individual characteristics may be an important moderator of inequality. METHODS: Data from HeadStart Cornwall (N = 4441) was used to assess the effect of youth adversity on combined symptoms of depression and anxiety (Strengths and Difficulties Questionnaire emotional problems subscale) measured at three time-points in 11-14-year-olds. Latent trajectories and regressions were estimated for eight intersectionality profiles (based on gender, SES, and hyperactivity/inattention), and moderating effects of the individual characteristics and their intersections were estimated. RESULTS: Youth adversity was associated with higher average depression/anxiety symptoms at baseline (11-12-years) across all intersectionality profiles. The magnitude of effects differed across profiles, with suggestive evidence for a moderating effect of youth adversity on change over time in depression/anxiety symptoms attributable to the intersection between (i) gender and SES; and (ii) gender, SES, and hyperactivity/inattention. CONCLUSIONS: The detrimental effects of youth adversity pervade across intersectionality profiles. The extent to which these effects are moderated by intersectionality is discussed in terms of operational factors. The current results provide a platform for further research, which is needed to determine the importance of intersectionality as a moderator of youth adversity on the development of depression and anxiety symptoms in adolescence.

Evaluation of platelet indices as markers of tuberculosis among children in India.

Children with tuberculosis have increased platelet count and platelet/lymphocyte ratio along with decreased mean platelet volume, suggesting that these indices may be useful as adjunct tools in diagnosis of paediatric tuberculosis https://bit.ly/3Ga4AWT.

Inflammation and epithelial repair predict mortality, hospital readmission, and growth recovery in complicated severe acute malnutrition.

Severe acute malnutrition (SAM) is the most high-risk form of undernutrition, particularly when children require hospitalization for complications. Complicated SAM is a multisystem disease with high inpatient and postdischarge mortality, especially in children with comorbidities such as HIV; however, the underlying pathogenesis of complicated SAM is poorly understood. Targeted multiplex biomarker analysis in children hospitalized with SAM (n = 264) was conducted on plasma samples, and inflammatory markers were assessed on stool samples taken at recruitment, discharge, and 12 to 24 and 48 weeks after discharge from three hospitals in Zimbabwe and Zambia. Compared with adequately nourished controls (n = 173), we found that at baseline, complicated SAM was characterized by systemic, endothelial, and intestinal inflammation, which was exacerbated by HIV infection. This persisted over 48 weeks despite nutritional recovery and was associated with children's outcomes. Baseline plasma concentrations of vascular endothelial growth factor, glucagon-like peptide-2, and intestinal fatty acid-binding protein were independently associated with lower mortality or hospital readmission over the following 48 weeks. Following principal components analysis of baseline biomarkers, higher scores of a component representing growth factors was associated with greater weight-for-height z score recovery and lower mortality or hospital readmission over the 48 weeks. Conversely, components representing higher gut and systemic inflammation were associated with higher mortality or hospital readmission. These findings highlight the interplay between inflammation, which damages tissues, and growth factors, which mediate endothelial and epithelial regeneration, and support further studies investigating interventions to reduce inflammation and promote epithelial repair as an approach to reducing mortality and improving nutritional recovery.

Estimating the impact of alternative programmatic cotrimoxazole strategies on mortality among children born to mothers with HIV: A modelling study.

BACKGROUND: World Health Organization (WHO) guidelines recommend cotrimoxazole prophylaxis for children who are HIV-exposed until infection is excluded and vertical transmission risk has ended. While cotrimoxazole has benefits for children with HIV, there is no mortality benefit for children who are HIV-exposed but uninfected, prompting a review of global guidelines. Here, we model the potential impact of alternative cotrimoxazole strategies on mortality in children who are HIV-exposed. METHODS AND FINDINGS: Using a deterministic compartmental model, we estimated mortality in children who are HIV-exposed from 6 weeks to 2 years of age in 4 high-burden countries: Côte d'Ivoire, Mozambique, Uganda, and Zimbabwe. Vertical transmission rates, testing rates, and antiretroviral therapy (ART) uptake were derived from UNAIDS data, trial evidence, and meta-analyses. We explored 6 programmatic strategies: maintaining current recommendations; shorter cotrimoxazole provision for 3, 6, 9, or 12 months; and starting cotrimoxazole only for children diagnosed with HIV. Modelled alternatives to the current strategy increased mortality to varying degrees; countries with high vertical transmission had the greatest mortality. Compared to current recommendations, starting cotrimoxazole only after a positive HIV test had the greatest predicted increase in mortality: Mozambique (961 excess annual deaths; excess mortality 339 per 100,000 HIV-exposed children; risk ratio (RR) 1.06), Uganda (491; 221; RR 1.04), Zimbabwe (352; 260; RR 1.05), and Côte d'Ivoire (125; 322; RR 1.06). Similar effects were observed for 3-, 6-, 9-, and 12-month strategies. Increased mortality persisted but was attenuated when modelling lower cotrimoxazole uptake, smaller mortality benefits, higher testing coverage, and lower vertical transmission rates. The study is limited by uncertain estimates of cotrimoxazole coverage in programmatic settings; an inability to model increases in mortality arising from antimicrobial resistance due to limited surveillance data in sub-Saharan Africa; and lack of a formal health economic analysis. CONCLUSIONS: Changing current guidelines from universal cotrimoxazole provision for children who are HIV-exposed increased predicted mortality across the 4 modelled high-burden countries, depending on test-to-treat cascade coverage and vertical transmission rates. These findings can help inform policymaker deliberations on cotrimoxazole strategies, recognising that the risks and benefits differ across settings.

Effectiveness and cost-effectiveness of online recorded recovery narratives in improving quality of life for people with non-psychotic mental health problems: a pragmatic randomized controlled trial.

Narratives describing first-hand experiences of recovery from mental health problems are widely available. Emerging evidence suggests that engaging with mental health recovery narratives can benefit people experiencing mental health problems, but no randomized controlled trial has been conducted as yet. We developed the Narrative Experiences Online (NEON) Intervention, a web application providing self-guided and recommender systems access to a collection of recorded mental health recovery narratives (n=659). We investigated whether NEON Intervention access benefited adults experiencing non-psychotic mental health problems by conducting a pragmatic parallel-group randomized trial, with usual care as control condition. The primary endpoint was quality of life at week 52 assessed by the Manchester Short Assessment (MANSA). Secondary outcomes were psychological distress, hope, self-efficacy, and meaning in life at week 52. Between March 9, 2020 and March 26, 2021, we recruited 1,023 participants from across England (the target based on power analysis was 994), of whom 827 (80.8%) identified as White British, 811 (79.3%) were female, 586 (57.3%) were employed, and 272 (26.6%) were unemployed. Their mean age was 38.4±13.6 years. Mood and/or anxiety disorders (N=626, 61.2%) and stress-related disorders (N=152, 14.9%) were the most common mental health problems. At week 52, our intention-to-treat analysis found a significant baseline-adjusted difference of 0.13 (95% CI: 0.01-0.26, p=0.041) in the MANSA score between the intervention and control groups, corresponding to a mean change of 1.56 scale points per participant, which indicates that the intervention increased quality of life. We also detected a significant baseline-adjusted difference of 0.22 (95% CI: 0.05-0.40, p=0.014) between the groups in the score on the "presence of meaning" subscale of the Meaning in Life Questionnaire, corresponding to a mean change of 1.1 scale points per participant. We found an incremental gain of 0.0142 quality-adjusted life years (QALYs) (95% credible interval: 0.0059 to 0.0226) and a £178 incremental increase in cost (95% credible interval: -£154 to £455) per participant, generating an incremental cost-effectiveness ratio of £12,526 per QALY compared with usual care. This was lower than the £20,000 per QALY threshold used by the National Health Service in England, indicating that the intervention would be a cost-effective use of health service resources. In the subgroup analysis including participants who had used specialist mental health services at baseline, the intervention both reduced cost (-£98, 95% credible interval: -£606 to £309) and improved QALYs (0.0165, 95% credible interval: 0.0057 to 0.0273) per participant as compared to usual care. We conclude that the NEON Intervention is an effective and cost-effective new intervention for people experiencing non-psychotic mental health problems.

A tailored psychological intervention for anxiety and depression management in people with chronic obstructive pulmonary disease: TANDEM RCT and process evaluation.

Background: People with chronic obstructive pulmonary disease have high levels of anxiety and depression, which is associated with increased morbidity and poor uptake of effective treatments, such as pulmonary rehabilitation. Cognitive-behavioural therapy improves mental health of people with long-term conditions and could potentially increase uptake of pulmonary rehabilitation, enabling synergies that could enhance the mental health of people with chronic obstructive pulmonary disease. Aim: Our aim was to develop and evaluate the clinical effectiveness and cost effectiveness of a tailored cognitive-behavioural approach intervention, which links into, and optimises the benefits of, routine pulmonary rehabilitation. Design: We carried out a pragmatic multicentre randomised controlled trial using a 1.25 : 1 ratio (intervention : control) with a parallel process evaluation, including assessment of fidelity. Setting: Twelve NHS trusts and five Clinical Commissioning Groups in England were recruited into the study. The intervention was delivered in participant's own home or at a local NHS facility, and by telephone. Participants: Between July 2017 and March 2020 we recruited adults with moderate/very severe chronic obstructive pulmonary disease and mild/moderate anxiety and/or depression, meeting eligibility criteria for assessment for pulmonary rehabilitation. Carers of participants were invited to participate. Intervention: The cognitive-behavioural approach intervention (i.e. six to eight 40- to 60-minute sessions plus telephone support throughout pulmonary rehabilitation) was delivered by 31 trained respiratory healthcare professionals to participants prior to commencing pulmonary rehabilitation. Usual care included routine pulmonary rehabilitation referral. Main outcome measures: Co-primary outcomes were Hospital Anxiety and Depression Scale - anxiety and Hospital Anxiety and Depression Scale - depression at 6 months post randomisation. Secondary outcomes at 6 and 12 months included health-related quality of life, smoking status, uptake of pulmonary rehabilitation and healthcare use. Results: We analysed results from 423 randomised participants (intervention, n = 242; control, n = 181). Forty-three carers participated. Follow-up at 6 and 12 months was 93% and 82%, respectively. Despite good fidelity for intervention delivery, mean between-group differences in Hospital Anxiety and Depression Scale at 6 months ruled out clinically important effects (Hospital Anxiety and Depression Scale - anxiety mean difference -0.60, 95% confidence interval -1.40 to 0.21; Hospital Anxiety and Depression Scale - depression mean difference -0.66, 95% confidence interval -1.39 to 0.07), with similar results at 12 months. There were no between-group differences in any of the secondary outcomes. Sensitivity analyses did not alter these conclusions. More adverse events were reported for intervention participants than for control participants, but none related to the trial. The intervention did not generate quality-of-life improvements to justify the additional cost (adjusted mean difference £770.24, 95% confidence interval -£27.91 to £1568.39) to the NHS. The intervention was well received and many participants described positive affects on their quality of life. Facilitators highlighted the complexity of participants' lives and considered the intervention to be of potential valuable; however, the intervention would be difficult to integrate within routine clinical services. Our well-powered trial delivered a theoretically designed intervention with good fidelity. The respiratory-experienced facilitators were trained to deliver a low-intensity cognitive-behavioural approach intervention, but high-intensity cognitive-behavioural therapy might have been more effective. Our broad inclusion criteria specified objectively assessed anxiety and/or depression, but participants were likely to favour talking therapies. Randomisation was concealed and blinding of outcome assessment was breached in only 15 participants. Conclusions: The tailored cognitive-behavioural approach intervention delivered with fidelity by trained respiratory healthcare professionals to people with chronic obstructive pulmonary disease was neither clinically effective nor cost-effective. Alternative approaches that are integrated with routine long-term condition care are needed to address the unmet, complex clinical and psychosocial needs of this group of patients. Trial registration: This trial is registered as ISRCTN59537391. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/146/02) and is published in full in Health Technology Assessment; Vol. 28, No. 1. See the NIHR Funding and Awards website for further award information.

People with long-standing lung problems, such as chronic obstructive pulmonary disease, often also have anxiety and depression, which further reduces their quality of life. Two existing treatments could help. Pulmonary rehabilitation (a programme of exercise and education) improves both the physical and mental health of people with chronic obstructive pulmonary disease. Cognitive­behavioural therapy (a talking therapy) may reduce anxiety and depression. The TANDEM [Tailored intervention for Anxiety and Depression Management in chronic obstructive pulmonary disease (COPD)] intervention linked these two treatments by providing talking therapy based on cognitive­behavioural therapy during the waiting time following referral for pulmonary rehabilitation. The TANDEM treatment was delivered by respiratory healthcare professionals (e.g. nurses or physiotherapists) trained to deliver the talking therapy in six to eight weekly sessions. The sessions were conducted in the participant's home (or another convenient location), with brief telephone support during the pulmonary rehabilitation. Of 423 participants recruited to the study, 242 participants received TANDEM talking therapy and 181 participants received usual care (including a referral to pulmonary rehabilitation). We measured mental health, quality of life, social life, attendance at pulmonary rehabilitation and healthcare use in both groups at 6 and 12 months. Forty-three carers joined the study and we assessed their mental well-being. We interviewed patients, carers and health professionals to find out their views and experience of the TANDEM treatment. We also examined whether or not the TANDEM treatment was good value for money. The TANDEM treatment did not improve the mental or the physical health of people with chronic obstructive pulmonary disease. In addition, the TANDEM treatment cost the NHS an extra £770 per patient, which was not good value for money. The TANDEM treatment was well received, and many participants told us how it had helped them. Heath-care professionals noted how participants did not just have chronic obstructive pulmonary disease, but were coping with many physical, mental and social problems. The TANDEM intervention was not effective and, therefore, other strategies will be needed to help people with chronic obstructive pulmonary disease and mental health problems live with their condition.

Cross-sectional survey of sexual health professionals' experiences and perceptions of the 2022 mpox outbreak in the UK.

OBJECTIVE: To understand the experiences and perceptions of sexual health professionals responding to the May 2022 mpox outbreak in the UK. DESIGN: Cross-sectional, anonymous, online survey collecting quantitative and qualitative data. Convenience sample recruited via an international network of sexual health and HIV clinicians responding to mpox and promoted through clinical associations and social media. Survey domains included: clinical workload; preparedness, support, and training; safety at work; vaccination; and well-being. Qualitative descriptive analysis of open-text responses was conducted to support interpretation of the quantitative data. PARTICIPANTS: Participants who were employed as sexual health professionals in the UK and had direct clinical experience of mpox were included in the analysis. The survey was completed between 11 August and 31 October 2022 by 139 respondents, the majority of whom were doctors (72.7%), cis-female (70.5%) and White (78.4%). RESULTS: 70.3% reported that they were required to respond to mpox in addition to their existing clinical responsibilities, with 46.8% working longer hours as a result. In the open-text data, respondents highlighted that workload pressures were exacerbated by a lack of additional funding for mpox, pre-existing pressures on sexual health services, and unrealistic expectations around capacity. 67.6% of respondents reported experiencing negative emotional impact due to their mpox work, with stress (59.0%), fatigue (43.2%) and anxiety (36.0%) being the most common symptoms. 35.8% stated that they were less likely to remain in their profession because of their experiences during the mpox outbreak. In the open-text data, these feelings were ascribed to post-COVID exhaustion, understaffing and frustration among some participants at the handling of the mpox response. CONCLUSIONS: These findings indicate that sexual health services require increased funding and resources, along with evidence-based well-being interventions, to support sexual health professionals' outbreak preparedness and recovery.

Severe acute malnutrition promotes bacterial binding over proinflammatory cytokine secretion by circulating innate immune cells.

Children with severe acute malnutrition (SAM) have high infectious mortality and morbidity, implicating defects in their immune defenses. We hypothesized that circulating innate immune cells from children (0 to 59 months) hospitalized with SAM in Zambia and Zimbabwe (n = 141) have distinct capacity to respond to bacteria relative to adequately nourished healthy controls (n = 92). SAM inpatients had higher neutrophil and monocyte Escherichia coli binding capacity but lower monocyte activation and proinflammatory mediator secretion in response to lipopolysaccharide or heat-killed Salmonella typhimurium than controls. Among SAM cases, wasting severity was negatively associated with cytokine secretion, children with HIV had lower monocyte activation, and the youngest children released the least myeloperoxidase upon stimulation. Inpatient bacterial binding capacity and monocyte activation were associated with higher odds of persistent SAM at discharge, a risk factor for subsequent mortality. Thus, SAM shifts innate immune cell function, favoring bacterial containment over proinflammatory activation, which may contribute to health deficits after discharge.

The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial: Protocol for school-age follow-up.

Background: There is a need for follow-up of early-life stunting intervention trials into childhood to determine their long-term impact. A holistic school-age assessment of health, growth, physical and cognitive function will help to comprehensively characterise the sustained effects of early-life interventions. Methods: The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe assessed the effects of improved infant and young child feeding (IYCF) and/or improved water, sanitation and hygiene (WASH) on stunting and anaemia at 18 months. Among children enrolled to SHINE, 1,275 have been followed up at 7-8 years of age (1,000 children who have not been exposed to HIV, 268 exposed to HIV antenatally who remain HIV negative and 7 HIV positive children). Children were assessed using the School-Age Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox, to measure their growth, body composition, cognitive and physical function. In parallel, a caregiver questionnaire assessed household demographics, socioeconomic status, adversity, nurturing, caregiver support, food and water insecurity. A monthly morbidity questionnaire is currently being administered by community health workers to evaluate school-age rates of infection and healthcare-seeking. The impact of the SHINE IYCF and WASH interventions, the early-life 'exposome', maternal HIV, and contemporary exposures on each school-age outcome will be assessed. We will also undertake an exploratory factor analysis to generate new, simpler metrics for assessment of cognition (COG-SAHARAN), growth (GROW-SAHARAN) and combined growth, cognitive and physical function (SUB-SAHARAN). The SUB-SAHARAN toolbox will be used to conduct annual assessments within the SHINE cohort from ages 8-12 years. Ethics and dissemination: Approval was obtained from Medical Research Council of Zimbabwe (08/02/21) and registered with Pan-African Clinical Trials Registry (PACTR202201828512110, 24/01/22). Primary caregivers provided written informed consent and children written assent. Findings will be disseminated through community sensitisation, peer-reviewed journals and stakeholders including the Zimbabwean Ministry of Health and Child Care.

Protocol for secondary data analysis of 4 UK cohorts examining youth adversity and mental health in the context of intersectionality.

BACKGROUND: Youth adversity (e.g., abuse and bullying victimisation) is robust risk factor for later mental health problems (e.g., depression and anxiety). Research shows the prevalence of youth adversity and rates of mental health problems vary by individual characteristics, identity or social groups (e.g., gender and ethnicity). However, little is known about whether the impact of youth adversity on mental health problems differ across the intersections of these characteristics (e.g., white females). This paper reports on a component of the ATTUNE research programme (work package 2) which aims to investigate the impact and mechanisms of youth adversity on depressive and anxiety symptoms in young people by intersectionality profiles. METHODS: The data are from 4 UK adolescent cohorts: HeadStart Cornwall, Oxwell, REACH, and DASH. These cohorts were assembled for adolescents living in distinct geographical locations representing coastal, suburban and urban places in the UK. Youth adversity was assessed using a series of self-report questionnaires and official records. Validated self-report instruments measured depressive and anxiety symptoms. A range of different variables were classified as possible social and cognitive mechanisms. RESULTS AND ANALYSIS: Structural equation modelling (e.g., multiple group models, latent growth models) and multilevel modelling will be used, with adaptation of methods to suit the specific available data, in accord with statistical and epidemiological conventions. DISCUSSION: The results from this research programme will broaden our understanding of the association between youth adversity and mental health, including new information about intersectionality and related mechanisms in young people in the UK. The findings will inform future research, clinical guidance, and policy to protect and promote the mental health of those most vulnerable to the negative consequences of youth adversity.

Tailored psychological intervention for anxiety or depression in COPD (TANDEM): a randomised controlled trial.

BACKGROUND: The TANDEM multicentre, pragmatic, randomised controlled trial evaluated whether a tailored psychological intervention based on a cognitive behavioural approach for people with COPD and symptoms of anxiety and/or depression improved anxiety or depression compared with usual care (control). METHODS: People with COPD and moderate to very severe airways obstruction and Hospital Anxiety and Depression Scale subscale scores indicating mild to moderate anxiety (HADS-A) and/or depression (HADS-D) were randomised 1.25:1 (242 intervention and 181 control). Respiratory health professionals delivered the intervention face-to-face over 6-8 weeks. Co-primary outcomes were HADS-A and HADS-D measured 6 months post-randomisation. Secondary outcomes at 6 and 12 months included: HADS-A and HADS-D (12 months), Beck Depression Inventory II, Beck Anxiety Inventory, St George's Respiratory Questionnaire, social engagement, the EuroQol instrument five-level version (EQ-5D-5L), smoking status, completion of pulmonary rehabilitation, and health and social care resource use. RESULTS: The intervention did not improve anxiety (HADS-A mean difference -0.60, 95% CI -1.40-0.21) or depression (HADS-D mean difference -0.66, 95% CI -1.39-0.07) at 6 months. The intervention did not improve any secondary outcomes at either time-point, nor did it influence completion of pulmonary rehabilitation or healthcare resource use. Deaths in the intervention arm (13/242; 5%) exceeded those in the control arm (3/181; 2%), but none were associated with the intervention. Health economic analysis found the intervention highly unlikely to be cost-effective. CONCLUSION: This trial has shown, beyond reasonable doubt, that this cognitive behavioural intervention delivered by trained and supervised respiratory health professionals does not improve psychological comorbidity in people with advanced COPD and depression or anxiety.

Public understanding and awareness of and response to monkeypox virus outbreak: A cross-sectional survey of the most affected communities in the United Kingdom during the 2022 public health emergency.

OBJECTIVES: Our objective was to examine the public response to public health and media messaging during the human monkeypox virus (MPXV) outbreak in the UK, focusing on at-risk communities. METHODS: A co-produced, cross-sectional survey was administered in June and July 2022 using community social media channels and the Grindr dating app. Basic descriptive statistics, logistic regression, and odds ratio p values are presented. RESULTS: Of 1932 survey respondents, 1750 identified as men, 88 as women, and 64 as gender non-conforming. Sexual identity was described as gay/lesbian/queer (80%), bisexual (12%), heterosexual (4%), and pansexual (2%); 39% were aged <40 years; 71% self-identified as White, 3% as Black, 8% as Asian, 2%as LatinX, and 11% as 'Mixed or Other' heritage groups. In total, 85% were employed and 79% had completed higher education. A total of 7% of respondents identified themselves as living with HIV. Overall, 34% reported limited understanding of public health information, 52% considered themselves at risk, 61% agreed that people with MPXV should isolate for 21 days, 49% reported they would first attend a sexual health clinic if symptomatic, 86% reported they would accept a vaccine, and 59% believed that MPXV originated from animals. The most trusted sources of information were healthcare professionals (37%), official health agencies (29%), and mainstream media (12%). CONCLUSIONS: Vaccine acceptability was very high, yet the understanding and acceptance of public health information varied. Social determinants of health inequalities already shaping the UK landscape risk were compounded in this new emergency. Engagement with structurally disadvantaged members of affected communities and better dissemination of public health messaging by trusted healthcare professionals are essential for the public health response.

Comparison of two mycobacterial strains in performance of the whole blood mycobacterial growth inhibition assay in Indian children.

A major challenge in tuberculosis is identifying correlates of a protective immune response. The Mycobacterial Growth Inhibition Assay (MGIA) is a functional assay providing an integrated measure of the host immune response to mycobacteria. However, its feasibility is limited by reliance on biosafety level 3 facilities, and its performance has not been widely evaluated in TB-endemic settings. Here, we compared two mycobacterial strains (M. tuberculosis H37Rv versus attenuated M. bovis BCG) in the performance of whole-blood MGIA in 30 TB-exposed children (median age 2 years) in Chennai, India. The time-to-positivity in both assays was similar (5.7 days vs 6 days) and the mycobacterial growth of M. tuberculosis H37Rv and M. bovis BCG were correlated (r = 0.64, p<0.0001). In Bland-Altman analysis, the bias was -0.54 days (95% limit of agreement -2.08, 0.99). Collectively, our results indicate that M. tuberculosis H37Rv can be substituted with the less virulent M. bovis BCG strain to improve feasibility of the MGIA assay, particularly in low-income settings.

Death after surgery among patients with chronic disease: prospective study of routinely collected data in the English NHS.

BACKGROUND: Five million surgeries take place in the NHS each year. Little is known about the prevalence of chronic diseases among these patients, and the association with postoperative outcomes. METHODS: Analysis of routine data from all NHS hospitals in England including patients aged ≥18 yr undergoing non-obstetric surgery between January 1, 2010 and December 31, 2015. The primary outcome was death within 90 days after surgery. For each chronic disease, we adjusted for age, sex, presence of other diseases, emergency surgery, and year using logistic regression models. We defined high-risk diseases as those with an adjusted odds ratio (OR) for death ≥2 and report associated 2-yr survival. RESULTS: We included 8 624 611 patients (median age, 53 [36-68] yr), of whom 6 913 451 (80.2%) underwent elective surgery and 1 711 160 (19.8%) emergency surgery. Overall, 2 311 600 (26.8%) patients had a chronic disease, of whom 109 686 (4.7%) died within 90 days compared with 24 136 (0.4%) of 6 313 011 without chronic disease. Respiratory disease (1 002 281 [11.6%]), diabetes mellitus (662 706 [7.7%]), and cancer (310 363; 3.6%) were the most common. Four chronic diseases accounted for 7.7% of patients but 59.0% of deaths: cancer (37 693 deaths [12.1%]; OR=8.3 [8.2-8.5]), liver disease (8638 deaths [10.3%]; OR=4.5 [4.4-4.7]), cardiac failure (26 604 deaths [12.6%]; OR=2.4 [2.4-2.5]), and dementia (19 912 deaths [17.9%]; OR=2.0 [1.9-2.0]). Two-year survival was 67.7% among patients with high-risk chronic disease, compared with 97.1% without. CONCLUSION: One in four surgical patients has a chronic disease with an associated 10-fold increase in risk of postoperative death. Two-thirds of all deaths after surgery occur among patients with high-risk diseases (cancer, cardiac failure, liver disease, dementia).

Which resources help young people to prevent and overcome mental distress in deprived urban areas in Latin America? A protocol for a prospective cohort study.

INTRODUCTION: Improving the mental health of young people is a global public health priority. In Latin America, young people living in deprived urban areas face various risk factors for mental distress. However, most either do not develop mental distress in the form of depression and anxiety, or recover within a year without treatment from mental health services. This research programme seeks to identify the personal and social resources that help young people to prevent and recover from mental distress. METHODS AND ANALYSIS: A cross-sectional study will compare personal and social resources used by 1020 young people (aged 15-16 and 20-24 years) with symptoms of depression and/or anxiety and 1020 without. A longitudinal cohort study will follow-up young people with mental distress after 6 months and 1 year and compare resource use in those who do and do not recover. An experience sampling method study will intensively assess activities, experiences and mental distress in subgroups over short time periods. Finally, we will develop case studies highlighting existing initiatives that effectively support young people to prevent and recover from mental distress. The analysis will assess differences between young people with and without distress at baseline using t-tests and χ2 tests. Within the groups with mental distress, multivariate logistic regression analyses using a random effects model will assess the relationship between predictor variables and recovery. ETHICS AND DISSEMINATION: Ethics approvals are received from Ethics Committee in Biomedical Research, Faculty of Medicine, University of Buenos Aires; Faculty of Medicine-Research and Ethics Committee of the Pontificia Universidad Javeriana, Bogotá; Institutional Ethics Committee of Research of the Universidad Peruana Cayetano Heredia and Queen Mary Ethics of Research Committee. Dissemination will include arts-based methods and target different audiences such as national stakeholders, researchers from different disciplines and the general public. TRIAL REGISTRATION NUMBER: ISRCTN72241383.

Adolescent mental health difficulties and educational attainment: findings from the UK household longitudinal study.

OBJECTIVE: This study examines whether there is an independent association between mental difficulties in adolescence and educational attainment at age 16. DESIGN: Longitudinal study. SETTING: Nationally representative data from the UK Household Longitudinal Study (UKHLS) were linked to the National Pupil Database for England. PARTICIPANTS: Respondents (N=1100) to the UKHLS between 2009 and 2012 were linked to the National Pupil Database to investigate longitudinal associations between mental difficulties at ages 11-14 and educational attainment at age 16 (General Certificate of Secondary Education (GCSE)). PRIMARY OUTCOME MEASURE: Not gaining five or more GCSE qualifications at age 16, including English and maths at grade A*-C. RESULTS: An atypical total mental health difficulty score measured using the Strengths and Difficulties Questionnaire at ages 11-14 predicted low levels of educational attainment at age 16 (OR: 3.11 (95% CI: (2.11 to 4.57)). Controlling for prior attainment and family sociodemographic factors, happiness with school (/work) and parental health, school engagement and relationship with the child partially attenuated the association, which was significant in the fully adjusted model (2.05, 95% CI (1.15 to 3.68)). The association was maintained in the fully adjusted model for males only (OR: 2.77 (95% CI (1.24 to 6.16)) but not for females. Hyperactivity disorder strongly predicted lower attainment for males (OR: 2.17 (95% CI: (1.11 to 4.23)) and females (OR: 2.85 (95% CI (1.30 to 6.23)). CONCLUSION: Mental difficulties at ages 11-14 were independently linked to educational success at age 16, highlighting an important pathway through which health in adolescence can determine young people's life chances.

Recorded Mental Health Recovery Narratives as a Resource for People Affected by Mental Health Problems: Development of the Narrative Experiences Online (NEON) Intervention.

BACKGROUND: The internet enables sharing of narratives about health concerns on a substantial scale, and some digital health narratives have been integrated into digital health interventions. Narratives describing recovery from health problems are a focus of research, including those presented in recorded (eg, invariant) form. No clinical trial has been conducted on a web-based intervention providing access to a collection of Recorded Recovery Narratives (RRNs). OBJECTIVE: This study presents knowledge produced through the development of the Narrative Experiences Online (NEON) Intervention, a web-based intervention incorporating the algorithmic recommendation of RRNs. METHODS: Knowledge was gathered through knowledge integration (KI) activities. KI1 synthesized previous studies to produce the NEON Impact Model describing how accessing RRNs produces health-related outcomes. KI2 developed curation principles for the NEON Collection of RRNs through consultation with the NEON Lived Experience Advisory Panel and the curation of a preliminary collection. KI3 identified harm minimization strategies for the NEON Intervention through consultation with the NEON International Advisory Board and Lived Experience Advisory Panel. The NEON Intervention was finalized through 2 research studies (RS). In RS1, mental health service users (N=40) rated the immediate impact of randomly presented narratives to validate narrative feedback questions used to inform the recommendation algorithm. In RS2, mental health service users (n=25) were interviewed about their immediate response to a prototype of the NEON Intervention and trial procedures and then were interviewed again after 1 month of use. The usability and acceptability of the prototype and trial procedures were evaluated and refinements were made. RESULTS: KI1 produced the NEON Impact Model, which identifies moderators (recipient and context), mechanisms of connection (reflection, comparison, learning, and empathy), processes (identification of change from narrative structure or content and internalization of observed change), and outcomes (helpful and unhelpful). KI2 identified 22 curation principles, including a mission to build a large, heterogeneous collection to maximize opportunities for connection. KI3 identified seven harm minimization strategies, including content warnings, proactive and reactive blocking of narratives, and providing resources for the self-management of emotional distress. RS1 found variation in the impact of narratives on different participants, indicating that participant-level feedback on individual narratives is needed to inform a recommender system. The order of presentation did not predict narrative feedback. RS2 identified amendments to web-based trial procedures and the NEON Intervention. Participants accessed some narratives multiple times, use reduced over the 4-week period, and narrative feedback was provided for 31.8% (105/330) of narrative accesses. CONCLUSIONS: RRNs can be integrated into web-based interventions. Evaluating the NEON Intervention in a clinical trial is feasible. The mixed methods design for developing the NEON Intervention can guide its extension to other clinical populations, the design of other web-based mental health interventions, and the development of narrative-based interventions in mental health.

Road traffic noise, noise sensitivity, noise annoyance, psychological and physical health and mortality.

BACKGROUND: Both physical and psychological health outcomes have been associated with exposure to environmental noise. Noise sensitivity could have the same moderating effect on physical and psychological health outcomes related to environmental noise exposure as on annoyance but this has been little tested. METHODS: A cohort of 2398 men between 45 and 59 years, the longitudinal Caerphilly Collaborative Heart Disease study, was established in 1984/88 and followed into the mid-1990s. Road traffic noise maps were assessed at baseline. Psychological ill-health was measured in phase 2 in 1984/88, phase 3 (1989/93) and phase 4 (1993/7). Ischaemic heart disease was measured in clinic at baseline and through hospital records and records of deaths during follow up. We examined the longitudinal associations between road traffic noise and ischaemic heart disease morbidity and mortality using Cox Proportional Hazard Models and psychological ill-health using Logistic Regression; we also examined whether noise sensitivity and noise annoyance might moderate these associations. We also tested if noise sensitivity and noise annoyance were longitudinal predictors of ischaemic heart disease morbidity and mortality and psychological ill-health. RESULTS: Road traffic noise was not associated with ischaemic heart disease morbidity or mortality. Neither noise sensitivity nor noise annoyance moderated the effects of road traffic noise on ischaemic heart disease morbidity or mortality. High noise sensitivity was associated with lower ischaemic heart disease mortality risk (HR = 0.74, 95%CI 0.57, 0.97). Road traffic noise was associated with Phase 4 psychological ill-health but only among those exposed to 56-60dBA (fully adjusted OR = 1.82 95%CI 1.07, 3.07). Noise sensitivity moderated the association of road traffic noise exposure with psychological ill-health. High noise sensitivity was associated longitudinally with psychological ill-health at phase 3 (OR = 1.85 95%CI 1.23, 2.78) and phase 4 (OR = 1.65 95%CI 1.09, 2.50). Noise annoyance predicted psychological ill-health at phase 4 (OR = 2.47 95%CI 1.00, 6.13). CONCLUSIONS: Noise sensitivity is a specific predictor of psychological ill-health and may be part of a wider construct of environmental susceptibility. Noise sensitivity may increase the risk of psychological ill-health when exposed to road traffic noise. Noise annoyance may be a mediator of the effects of road traffic noise on psychological ill-health.

Missing data: A statistical framework for practice.

Missing data are ubiquitous in medical research, yet there is still uncertainty over when restricting to the complete records is likely to be acceptable, when more complex methods (e.g. maximum likelihood, multiple imputation and Bayesian methods) should be used, how they relate to each other and the role of sensitivity analysis. This article seeks to address both applied practitioners and researchers interested in a more formal explanation of some of the results. For practitioners, the framework, illustrative examples and code should equip them with a practical approach to address the issues raised by missing data (particularly using multiple imputation), alongside an overview of how the various approaches in the literature relate. In particular, we describe how multiple imputation can be readily used for sensitivity analyses, which are still infrequently performed. For those interested in more formal derivations, we give outline arguments for key results, use simple examples to show how methods relate, and references for full details. The ideas are illustrated with a cohort study, a multi-centre case control study and a randomised clinical trial.