Missing Data Methodology: Sensitivity analysis after multiple imputation

Within epidemiological and clinical research, missing data are a common issue which are often inappropriately handled in practice. Multiple imputation (MI) is a popular tool used to `fill in' partially observed data with plausible values drawn from an appropriate imputation distribution. Software generally implements MI under the assumption that data are `missing at random' (MAR) i.e. that the missing mechanism is not dependent on the missing data conditional on the observed data. This is a strong inherently untestable assumption, and if incorrect can result in misleading inferences. The sensitivity of inferences to this assumption needs to be assessed by exploring the alternative assumption that missing data are `missing not at random' (MNAR) i.e. even conditioned on the observed data, the probability of missing observations depends on their unseen, underlying values. Broadly there are two ways to frame, and perform sensitivity analyses (SA) to accomplish this: using a pattern mixture model or a selection model. Motivated by a cancer dataset, we develop a novel pattern mixture approach to collecting and incorporating in the analysis prior information elicited from experts. We demonstrated the inferential validity of our approach by simulation. Our second example is an individual patient meta-analysis of sudden infant death syndrome studies. We extended existing multilevel MI software to perform SA for the risk of bed sharing in these complex data. Inferences were found to be robust. Finally we considered a proposal of Carpenter et al. (2007) for SA after MI by reweighting. We developed a modification, which dramatically improves its performance in small data sets. The routine use of SA in applied research is held back by the lack of practical methodology and examples. This thesis addresses these issues, and so lowers the barrier to the widespread adoption of SA

BASH: badmouthing, attitudes and stigmatisation in healthcare as experienced by medical students.

Aims and method We used an online questionnaire to investigate medical students' perceptions of the apparent hierarchy between specialties, whether they have witnessed disparaging comments ('badmouthing' or 'bashing') against other specialists and whether this has had an effect on their career choice. Results In total, 960 students from 13 medical schools completed the questionnaire; they ranked medical specialties according to the level of badmouthing and answered questions on their experience of specialty bashing. Psychiatry and general practice attracted the greatest number of negative comments, which were made by academic staff, doctors and students. Twenty-seven per cent of students had changed their career choice as a direct result of bashing and a further 25.5% stated they were more likely to change their specialty choice. Although 80.5% of students condemned badmouthing as unprofessional, 71.5% believed that it is a routine part of practising medicine. Clinical implications Bashing of psychiatry represents another form of stigmatisation that needs to be challenged in medical schools. It not only has an impact on recruitment into the specialty, but also has the wider effect of stigmatising people with mental health disorders

The spread of rhizoctoniosis in potato plantings in the conditions of the North-West of the Russian Federation with a heterogeneous content of nutrients in the soil

Rhizoctoniosis is one of the most common and harmful diseases of potatoes in the North-West of Russia. The degree of its manifestation depends on many factors, including the content of basic nutrients in the soil. In the Leningrad region the effect of prolonged application of organic and mineral fertilizers on the degree and nature of the manifestation of rhizoctoniosis was studied in potato variety Meteor in forage and field crop rotations. By the results of the detailed accounting carried out in 2022 including observation of all potato plantings (43406 in total) it was determined that rhizoctoniosis damage had random distribution character in field crop rotation and focal distribution in forage crop rotation. This conclusion was confirmed by respective coefficients of variation (79 and 87 %) and aggregation (1.0 and 1.5). Spatial heterogeneity of plants damaged by rhizoctoniosis was visualized on digital maps compiled with GIS AFI and Surfer 11 while grouping the data into elementary sections. There was sufficient influence of cultivation and fertilization of different levels on rhizoctoniosis spread. The influence of cultivation was weak and statistically significant only in forage crop rotation, where there was an increase of rhizoctoniosis damage of potato plants (by 1.7-2.5 times compared to low cultivated soil). Under mineral fertilizers application there was a decrease of rhizoctoniosis damage of potato plants both in field crop rotation (by 1.1-1.7 times compared to variant without fertilizers application), and in forage crop rotation (by 1.1-1.3 times). Complex influence of soil cultivation and fertilization of potato plantings caused a decrease of rhizoctoniosis damage of potato tubers by 1.9 and 2.0 times in field and forage crop rotations, respectively

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

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

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

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

A cross‐sectional investigation into the role of intersectionality as a moderator of the relation between youth adversity and adolescent depression/anxiety symptoms in the community

Background: Adolescents exposed to adversity show higher levels of depression and anxiety, with the strongest links seen in socially/societally disadvantaged individuals (e.g., females, low socioeconomic status [SES]), as well as neurodivergent individuals. The intersection of these characteristics may be important for the differential distribution of adversity and mental health problems, though limited findings pertain to the extent to which intersectional effects moderate this association. Methods: Combined depression/anxiety symptoms were measured using the emotional problems subscale of the Strengths and Difficulties Questionnaire in 13–14‐year‐olds in Cornwall, United Kingdom in 2017‐2019. In a cross‐sectional design (N = 11,707), multiple group structural equation modeling was used to estimate the effects of youth adversity on depression/anxiety symptoms across eight intersectionality profiles (based on gender [female/male], SES [lower/higher], and traits of hyperactivity/inattention [high/low]). Moderation effects of these characteristics and their intersections were estimated. Results: Youth adversity was associated with higher levels of depression/anxiety (compared to an absence of youth adversity), across intersectional profiles. This effect was moderated by gender (stronger in males; β = 0.22 [0.11, 0.36]), and SES (stronger in higher SES; β = 0.26 [0.14,0.40]); with indications of moderation attributable to the intersection between gender and hyperactivity/inattention (β = 0.21 [−0.02,0.44]). Conclusions: Youth adversity is associated with heightened depression/anxiety across intersectional profiles in 13–14‐year‐olds. The stronger effects observed for males, and for higher SES, may be interpreted in terms of structural privilege. Preliminary findings suggest that vulnerability and resilience to the effects of youth adversity may partially depend on specific intersectional effects. Importantly, the current results invite further investigation in this emerging line of inquiry