London School of Hygiene and Tropical Medicine

We synthesise perinatal mental health (PMH) evidence and provide recommendations for future research and practices in Pakistan. The burden is significantly higher relative to many other countries, with adverse effects on women and children. Few locally developed interventions involving non-specialists have shown promise, but integrating these into maternal and child health services (MCH) at scale remains a challenge. We recommend broadening the scope of PMH research in accordance with the World Health Organization's stepped care model, and advancing the use of implementation science, digital technology and exploring low-cost models. Programmes and policies should prioritise incorporating PMH into MCH services in health planning and budgeting.

Background The lives of adolescents and young people living with HIV (LHIV) are dominated by complex psychological and social stressors. These may be more pronounced among those perinatally infected. This longitudinal mixed-methods study describes the clinical and psychosocial challenges faced by HIV perinatally infected young mothers in Harare, Zimbabwe to inform tailored support. Methods HIV perinatally infected young mothers were recruited in 2013 and followed up in 2019. In 2013, they completed a structured interview, clinical examination, psychological screening and had viral load and drug resistance testing. A subset completed in-depth interviews (n = 10). In 2019, they were re-interviewed and had viral load testing. Data were analyzed using STATA 15.0. and thematic analysis. Results Nineteen mothers aged 17–24 years were recruited in 2013. Eleven (57.9%) were successfully recontacted in 2019; 3 had died, 2 had relocated and 3 were untraceable. In 2013, all 19 mothers were taking antiretroviral therapy (median duration 8 years, range 2–11 years) and median CD4 count was 524 (IQR 272). In 2013, eight mothers (42.1%) had virological failure (≥1000 copies/ml) (3 of whom subsequently died) and 7 (36.8%) had evidence of drug resistance. In 2019, the proportion with virological failure was 2/11 (18.1%). Six of 11 (54.5%) had switched to second line therapy. In 2013, 64.3% were at risk of common mental disorder and this risk was higher at follow-up (72.7%). Qualitative data highlighted three pertinent themes: HIV status disclosure, adherence experiences and, social and emotional support. Conclusions Findings from this study underscore the significant clinical, social and psychological challenges faced by perinatally infected young mothers. The high rates of virological failure, drug resistant mutations, mental health issues and mortality observed in this population indicate the need for tailored and comprehensive health and support services to assist these young mothers.

Background Effective treatments are now available, which have demonstrated reductions in amyloid plaque burden while slowing cognitive decline in early symptomatic Alzheimer’s disease (AD). Intervening before onset of cognitive impairment could provide greater benefit, particularly for individuals who carry an autosomal dominant mutation known to cause AD. To better guide the design of upcoming prevention trials, reliable sample size estimates for detecting relevant reductions in pathology are needed. Method Longitudinal PIB PET and CSF biomarker data were obtained from the Dominantly Inherited Alzheimer Network Observation study (datafreeze 14, see Table). Participants were included in the analysis based on eligibility criteria from DIAN‐TU‐001: estimated years to expected onset (EYO) between ‐15 to +10 and global Clinical Dementia Rating (CDR) score between 0 and 1, inclusive. Sample size estimates were also obtained for trials with individuals having CDR = 0 only. Linear mixed‐effects models were used to estimate baseline values and rates of change in outcome measures for mutation carriers and non‐carriers. Outcomes included CSF biomarkers of amyloid and p‐tau 181 using three assays (INNOTEST, XMAP and Lumipulse) and Standardized Uptake Value Ratio (SUVR, cerebellar grey matter reference region) of PIB PET from six regions. We then used these estimates to compute sample size estimates to detect a 25% reduction in pathology by four years, assuming 5% significance, 80% power, and 40% dropout. Uncertainty in sample size estimates was quantified through bootstrapping. Result There were large differences between carriers and non‐carriers at baseline and the end of a four‐year study (Figure 1). Sample size estimates were consistently higher in scenarios involving only CDR = 0 carriers (Figure 2). For PIB PET cortical mean, 40[95%CI: 26,66] pariticpants per arm would be needed to detect a 25% reduction and (63[40,115] for the CDR = 0 subsample. Similar estimates were observed for individual brain regions. XMAP Aβ42 (CDR 0‐1: 21, [11,65], CDR 0: 51 [21,333]) and Lumipulse Aβ42‐40 ratio (CDR 0‐1: 22 [13,46], CDR 0: 47[25,104]) were the most promising CSF outcome measures. Conclusion Sample size estimates needed to detect a 25% reduction in pathology levels in prevention studies are in the range of 30‐40 participants per arm.

Background Some infections may be associated with poor brain health, but evidence from low and middle‐income countries (LMICs) is limited. Therefore, we aimed to investigate associations between nine infections and cognitive function, depression, and frailty in India. Methods We conducted a cross‐sectional study using data from Wave 1 (2017‐2019) of the Longitudinal Aging Study in India (LASI) survey of adults (≥45years) from 35 of India’s 36 states and union territories. Survey data were collected via face‐to‐face interviews and direct health measurements. We investigated the association between nine infections either self‐reported ever (periodontal disease) or in the two years before interview (jaundice/hepatitis, malaria, tuberculosis, typhoid, chikungunya, diarrhoea/gastroenteritis, dengue, urinary tract infection [UTI]), and global cognitive function, depression and frailty. We used survey‐weighted logistic regression to estimate odds ratios comparing impaired cognition, depression, or frailty in people with at least one infection (and each individual infection) to those without infection. Results We included 64,682 respondents; median age 59 years (IQR:50‐67), 53.5% female. Accounting for survey weighting, thirty‐five percent (n = 23,783) of respondents reported at least one infection. After adjusting for demographic, social/environmental, lifestyle, and chronic health conditions, we saw evidence of association between having at least one infection and both depression (OR: 1.30 [95%CI: 1.23‐1.36]) and frailty (OR: 1.78 [95%CI: 1.69‐1.87]) (Figure 1). We saw strong associations between jaundice/hepatitis and frailty (OR: 2.20 [95%CI: 1.90‐2.54]), and UTIs and both frailty (OR: 3.08 [95%CI: 2.65‐3.59]) and depression (OR: 1.38 [95%CI:1.19, 1.61]). In contrast, having at least one infection was associated with reduced odds of impaired cognition (OR: 0.81 [95%CI: 0.76‐0.87]). Conclusions Our results suggest that infections are associated with increased depression and frailty in adults ≥45 years in India. However, reported infections were associated with better cognition, which may be explained by preferential recall of infections in those with better cognition. Longitudinal studies are needed to investigate a causal link between infections and adverse brain health, and to guide interventions to reduce the burden of impaired cognition, depression, and frailty in India and LMICs more widely.

Background In elite athletes, participation in sports associated with repetitive head injury exposure has been linked to an increased risk of neurodegeneration later in life. However, there has been limited study in more general populations. We aimed to investigate whether participation in such sports impacted outcomes relevant to brain health in a cohort of British‐born older adults. Methods 441 participants from Insight 46 (a sub‐study of the 1946 British Birth Cohort) were asked whether they participated in rugby, soccer, or boxing, consistently for at least a year (yes/no) at various epochs of life (<20, 20‐49 and 50+ years). Individuals underwent baseline florbetapir‐PET, serial brain MRI and cognitive assessments (mean age at baseline assessment 70.6 years, mean interval between visits = 2.4 years). A range of life course data were included in analyses, including attitudes to sports, education, engagement in physical activity and self‐reported symptomatic head injury. Result As only one female identified as participating in rugby, soccer, or boxing, only males were included in analyses: 101/232 males (43.5%) stated they participated in at least one of these sports, 46 of whom participated for more than one epoch. Univariate analyses revealed participation was associated with a range of demographic factors including: a preference “to play rough sports” aged 13 (p<0.001); a higher level of education (p = 0.007); engagement in physical activity aged 36 (p<0.001); and 43 (p = 0.017); and greater risk of self‐reported symptomatic head injury (35.3% vs 14.7%, p<0.001). There were no significant associations between participation in these sports and baseline cognitive function or decline, beta‐amyloid deposition, white matter hypertintensity volume, or baseline/longitudinal change in total brain or hippocampal volume (table 1). Longer duration of participation (≥ two epochs vs one) was associated with lower hippocampal volume at baseline (p = 0.006) but did not predict subsequent atrophy or any other outcome examined (table 2). Conclusion Previous exposure to sports associated with repetitive head injuries is common amongst British‐born older adults and associated with a range of demographic factors relevant to brain health. Longer duration of exposure predicted lower hippocampal volume age 70 years, but there was no evidence of significantly accelerated atrophy or cognitive decline beyond this.

Background Substantial evidence suggests association between increased inflammatory markers and Alzheimer’s disease. However, evidence for association between the inflammatory skin disease psoriasis and dementia is limited and conflicting. Additionally, few studies investigate how psoriasis severity influences risk. Method We used primary care electronic health records from the UK’s Clinical Practice Research Datalink Aurum and linked hospital admissions data for a matched cohort study (1997‐2022) of individuals ≥40years. We matched (age, sex, primary care practice) individuals with psoriasis, without replacement, with up to five comparators without psoriasis in calendar date order. People with psoriasis were followed from latest of: first psoriasis diagnosis, practice registration +1year, study start, age 40, date practice met quality‐control standards. Comparators were followed from the same date as their psoriasis match. We used Cox regression, stratified by matched set, to estimate hazard ratios (HR) comparing dementia risk in those with and without psoriasis. Result In preliminary analyses, we identified 360,014 individuals with psoriasis matched to 1,799,617 without. After implicitly adjusting for age, sex, practice and calendar period (through underlying timescale and matching), and adjusting for lifestyle factors (smoking, harmful alcohol, obesity) and comorbidities (cardiovascular, cerebrovascular, chronic liver and chronic lung diseases, diabetes mellitus, depression, hyperlipidaemia, hypertension), we found evidence of association between psoriasis and all‐cause dementia (HR 1.04, 95%CI 1.01‐1.06), although absolute rate differences were small (approximately 4 per 10,000 person years). We found evidence of association between psoriasis and vascular dementia (HR 1.09, 95%CI 1.04‐1.15), but no evidence of association with Alzheimer’s (HR 1.02, 95%CI 0.98‐1.05). Compared to those without psoriasis, the association with all cause dementia was stronger in moderate‐to‐severe psoriasis (HR 1.17, 95%CI 1.07, 1.27) than in mild psoriasis (HR 1.02, 95%CI 1.00, 1.04). We plan to: further adjust for additional potential confounders (including deprivation, ethnicity, chronic kidney disease) using more nuanced sequential modelling; and assess how robust our findings are in sensitivity analyses. Conclusion Our findings suggest that risk of all‐cause dementia, but not Alzheimer’s, is slightly higher in people with psoriasis, and risk is greater in more severe psoriasis. However, relative risk and absolute risk differences were small.

Background Associations of common infections with Alzheimer’s disease have been reported, but potential mechanisms underlying these relationships are unclear. A hypothesised mechanism is amyloid‐beta (Aβ) aggregation as a defense mechanism in response to infection, with subsequent tau accumulation. However, no studies have assessed associations of infections with cerebral Aβ and tau pathology in vivo. We investigated relationships between serum antibodies to common infections and Aβ pathology quantified using PET in the Insight 46 neuroimaging cohort. Method Circulating antibody levels against 14 pathogens, measured at age 60‐64, were modelled as pathogen serostatus, cumulative pathogen burden, and seroreactivity tertiles. Their associations with Aβ‐PET positivity, assessed 7.3(±1.3) years after serology measurement, were modelled using multivariable logistic regression. Model 1 adjusted for sex and ages at serology and PET scan, models 2‐4 additionally adjusted for APOE ε4 carriage, education, and inflammatory markers respectively. We tested for interactions in associations by APOE ε4 carriage and education, and interactions between herpes simplex virus 1 and both cytomegalovirus and varicella‐zoster virus. Analyses were repeated using Aβ‐PET deposition as a continuous variable. Result 424 individuals had serology and Aβ‐PET data (Tables 1 and 2). Individuals seropositive to Epstein‐Barr virus (EBV) had higher odds of Aβ‐PET positivity in all models, with a large point estimate but wide confidence intervals including null (Model 2: OR 3.11; 95% CI: 0.96,10.09; Figure 1). Similar patterns were observed when analysing Aβ‐PET continuously (Model 2: 22% higher burden; 95% CI: ‐4, 47%). Individuals seropositive to Toxoplasma gondii (T.gondii) had a higher likelihood of Aβ‐PET positivity with large confidence intervals including null (Model 2: OR 1.60; 95% CI: 0.87, 2.94; Figure 1). There was modest evidence for an interaction between human herpesvirus 7 (HHV7) and education in relation to Aβ‐PET positivity (lower Aβ risk among HHV7 seropositives with higher education). No other pronounced findings were observed. Conclusion Results suggest potentially strong associations of EBV and T.gondii seropositivity with Aβ burden, however, the large CIs including null suggest the study lacked power to generate precise estimates. Findings warrant replication in other larger cohorts and with other neurobiomarkers. We plan to expand our analyses to plasma p‐tau217 as another outcome (N≤1454).

Background Accelerated epigenetic ageing has been associated with various age‐related health outcomes, but its relevance for dementia risk prediction is unclear. We investigated whether accelerated midlife epigenetic age associates with poor later‐life brain health. Methods Participants were 230 individuals from Insight 46, drawn from the 1946 British Birth Cohort, a population‐based study of individuals born in the first week of March 1946. DNA methylation was measured at 53 years using Infinium MethylationEPIC BeadChip and GrimAge and PhenoAge were calculated. ‘Age acceleration’ was derived for each clock (AgeAccelGrim and AgeAccelPheno), as previously. At 69‐71 years, we measured MRI whole brain and white matter hyperintensity volume, amyloid‐PET burden, plasma neurofilament light, and MRI Brain Age (with chronological age subtracted to produce the Brain‐Predicted Age Difference/Brain‐PAD). For n=176 with follow‐up MRI aged 72‐75 (n=176), whole brain atrophy was calculated using the boundary shift integral. CSF p‐tau181 was measured in n=64. Results Despite participants’ highly similar chronological age (mean=53.4 years, SD=0.2), there was considerable variation in AgeAccelGrim (SD=4.8yr) and AgeAccelPheno (SD=5.6yr). Linear regression revealed that accelerated GrimAge was associated with smaller later‐life whole brain volume, (b=‐1.9ml, p=0.010), whilst accelerated PhenoAge was associated with greater whole brain atrophy (b=0.403, p=0.001). Neither GrimAge nor PhenoAge acceleration was associated with amyloid‐PET burden. Accelerated PhenoAge was associated with higher white matter hyperintensity burden (b=0.03, p=0.04). Acceleration in both GrimAge (b=0.4pg/ml, p=0.001) and PhenoAge (b=0.4pg/ml, p=0.001) was linked to higher plasma neurofilament light, and both AgeAccelGrim (r=0.32, p=0.010) and AgeAccelPheno (r=0.35, p=0.005) were positively correlated with CSF p‐Tau181. MRI brain age (Brain‐PAD) was significantly correlated with AgeAccelGrim (r=0.15, p=0.02) but not AgeAccelPheno (r=0.08, p=0.2). Conclusion Acceleration of midlife epigenetic age was associated with a wide range of features of poor brain health ∼20 years later, in a population‐based sample. Epigenetic clocks may hold promise as tools for future brain health prediction.

Background Indonesia has implemented a series of healthcare reforms including its national health insurance scheme (Jaminan Kesehatan Nasional, JKN) to achieve universal health coverage. However, there is evidence of inequitable healthcare utilization in Indonesia, raising concerns that the poor might not be benefiting fully from government subsidies. This study aims to identify factors affecting healthcare utilization in Indonesia. Methods This study analysed cross-sectional survey data collected by the “Equity and Health Care Financing in Indonesia” (ENHANCE) Study. Andersen’s behavioural model of health services use was adopted as a framework for understanding healthcare utilization in Indonesia. Sociodemographic variables were categorized into predisposing, enabling and need factors. Outcome measures included the utilization of primary and secondary health services. Multi-level logistic regression models were run to examine factors associated with each type of health service utilization. Results Of the 31,864 individuals included in the ENHANCE survey, around 14% had used outpatient services in the past month. Fewer than 5% of the study population had visited hospitals for inpatient care and about 23% used maternal and child health services in the past 12 months. Age, gender and self-rated health were key determinants of health services utilization. No significant differences in primary care utilization were found among people with different insurance status, but people who received subsidised premiums under the JKN were more likely to receive primary care from public health facilities and less likely from private health facilities. Compared to people who pay JKN insurance premiums themselves, the uninsured and those whose premiums were subsidised by the government were less likely to visit public and private hospitals when other factors were controlled. Conclusion This study demonstrates that the distribution of healthcare utilization in Indonesia is largely equitable as predisposing factors (age and gender) and health need were found to greatly influence the utilization of different types of health services. However, enabling factors such as health insurance status were also found to be associated with inequity in utilization of hospital services. Further policy actions regarding resource allocation and health service planning are warranted to achieve a more equitable pattern of health service use in Indonesia.

Background People with disabilities due to neglected tropical diseases (NTDs), such as leprosy and lymphatic filariasis (LF), often encounter situations of stigma and discrimination that significantly impact their mental wellbeing. Mental wellbeing services are often not available at the peripheral level in NTD-endemic countries, and there is a need for such services. Basic psychological support for persons with NTDs (BPS-N) from peers is an important potential solution for addressing mental wellbeing problems. As there was no written document advising delivery of such support, NLR India brought experts together to develop a new guide. This paper describes the process used in developing the guide and provides information about its content. Methods As a qualitative and participatory methodology, more than 10 meetings and workshops were held to consider the suitability of existing guides for chronic stress in NTDs and develop a new guide through consensus and adaptations; attendees included both technical experts and affected persons. The first meeting was a 3-day virtual workshop held on 9–11 June 2020, followed by other online meetings. The BPS-N guide development happened during the COVID-19 lockdowns. The Psychological First Aid (PFA) package of WHO was selected as a suitable basic model for adaptation. Aspects of the Rights-Based Counselling intervention were also integrated into the new guide. Two teams were formed for drafting and reviewing the guide. Results All suggested changes were discussed, and a consensus reached for developing the document. The affected persons contextualized the content for ensuring its relevance and practicality. The new BPS-N guide was simple, professionally sound, ethical, adequate, and appropriate. The guide promotes knowledge, skills, compassion, and action among peer supporters. Conclusion The new guide, through regular trainings, behavior change, and action principles will likely provide much-needed services. It is important that the new guide be now tested, and modifications made if needed.

Chicken meat (broiler) production is a rapidly growing livestock sector in India, and one dominated by contract farming. Studies have reported high levels of antibiotic use in Indian broiler farms which is concerning given this is one of the driving forces for the development of antibiotic resistance. This study used the economic lens of agency theory to examine strategic decisions which occur during contract broiler production and their potential impact on antibiotic use, using West Bengal as a case study. Agency theory focuses on the informational asymmetry and opportunism between service providers and seekers and the subsequent agency cost needed to avoid aberrant outcomes. Interviews were conducted with key informants (n = 6) and stakeholders (n = 20) associated with broiler production, and broiler farmers (17 contract and four non-contract), using online and face-to-face interviews. Data were analysed descriptively using manifest content analysis and interpretatively using reflexive thematic analysis. Contract farming in West Bengal exists within a series of inter-dependent relationships, many of which contain information asymmetry and can be subject to opportunism. Positioning contract companies as principals seeking labour from agents, we see how out-sourcing of production to distal farms led to antibiotics being used as a risk mitigation strategy. This was further compounded by concerns about the Mycoplasma status of breeding stock, and a perception that broiler day old chicks were infected, resulting in use of antibiotics belonging to classes deemed critically important for human health. While antibiotic use decisions were predominately made by contract companies, they were dependent on the decisions farmers and breeding companies made concerning biosecurity and production practices. In turn, farmers’ decisions were shaped by factors such as access to financial and social capital. Thus, efforts to reduce antibiotic use in West Bengal’s broilers must not just focus on changing the prescribing behavior of individuals but more broadly consider the environment within which contracting exists.

During the COVID-19 pandemic, heterologous vaccination strategies were employed to alleviate the strain on vaccine supplies. The Thailand Ministry of Health adopted these strategies using vector, inactivated, and mRNA vaccines. However, this approach has introduced challenges for SARS-CoV-2 sero-epidemiology studies. Our study analysed 647 samples from healthcare workers who received CoronaVac, ChAdOx1 nCoV-19, and BNT162b2 vaccines. The serological profile encompassed responses to various SARS-CoV-2 variants and vectors, measuring IgG, IgM, and IgA isotypes, alongside IgG avidity assays. The results demonstrated that heterologous CoronaVac/ChAdOx1 nCoV-19 schedules elicited significantly stronger antibody responses compared to homologous schedules (IgG: 1.2-fold, IgM: 10.9-fold, IgA: 3.1-fold increase). Additionally, a heterologous BNT162b2 boost at 4-weeks post-initial vaccination showed greater antibody levels than a ChAdOx1 nCoV-19 boost (IgG: 1.1-fold, IgM: slight decrease, IgA: 1.5-fold increase). Using a combination of three analytes, IgG against wild-type Spike trimer, nucleoprotein and Omicron receptor binding domains, enabled the clustering of responses within a statistical Gaussian mixture model that successfully discriminates between breakthrough infections and vaccination types (F-score = 0.82). The development of statistical models to predict breakthrough infections can improve serological surveillance. Overall, our study underscores the necessity for vaccine (re-)development and the creation of serological tools to monitor vaccine performance.

Mental health service use by individuals of South Asian origin living outside of South Asia is influenced by cultural factors such as endorsing psycho-social-spiritual over biological explanations, somatisation, and stigma. The aim of this review is to synthesise the evidence about (a) explanatory models of common mental disorders (CMDs) among people of South Asian origin residing in high-income countries, and (b) their help-seeking for CMDs, including formal and informal care. The systematic review protocol was registered a priori on Prospero (registration number CRD42021287583). We ran extensive searches on explanatory models and help-seeking of people of South Asian origin across five databases (MEDLINE, Embase, Cumulated Index to Nursing and Allied Health (CINAHL), PsycINFO, and Global Health). We extracted the data and conducted a narrative synthesis. We included 33 reports and 29 studies (9,030 participants). The participants in the included studies viewed CMDs through a psychosocial rather than a biological lens (e.g., resulting from family issues vs. neurotransmitters). Causal attributions included life stressors and attitudinal and religious/spiritual factors. Commonly used help-seeking strategies included private coping (i.e., crying or praying), speaking to friends and family, and visiting their General Practitioner. We can conclude that cultural factors play an important role in how South Asian individuals experience and understand CMDs. To cope, they use pluralistic help-seeking strategies. Implications for clinical practice and policy include increasing research on the explanatory models of CMDs, involving family in services, and developing community-based interventions for individuals who do not engage with formal care.

Objectives COVID-19 vaccine was rolled out for the public in August 2021 in Zamfara state, Northen Nigeria. We determined the factors influencing COVID-19 vaccine acceptance. Settings We executed a community-based analytical cross-sectional study during the first 4 months of the second phase of the COVID-19 (Oxford/AstraZeneca) mass vaccination campaign in Zamfara state. Participants We used multistage sampling to select 910 household heads. Outcome measures We used a semistructured electronic questionnaire to collect data on sociodemographic characteristics, uptake and acceptance of COVID-19 vaccine between 12 October and 20 December 2021. We calculated frequencies, proportions, adjusted ORs and 95% CIs for factors influencing COVID-19 vaccine acceptance using logistic regression. Results Our respondents had a median age of 48 years (IQR: 37–55), 78.1% (711) were men, a majority more than 30 years, and only 8.9% (81) had received COVID-19 vaccine. Of the 829 unvaccinated respondents, 10.1% (84) accepted to take the vaccine, the current week of the interview while 12.2% (101) rejected the vaccine. Individuals aged 30 years and older (adjusted OR (aOR)=2.39, 95% CI 1.16 to 4.94, p=0.018), who owned a mobile phone (aOR=25.35, 95% CI 11.23 to 57.23, p<0.001) and a television (aOR=3.72, 95% CI 1.09 to 12.69, p=0.036), with medium–high levels of trust (aOR=7.41, 95% CI 3.10 to 17.74, p<0.001), and those with a medium–high (positive) levels of attitude (aOR=1.82, 95% CI 1.06 to 3.11, p=0.029) were more likely to accept the COVID-19 vaccine. Also, those who had been vaccinated with other vaccines (aOR=2.2, 95% CI 1.09 to 4.43, p=0.027) and those previously tested for COVID-19 (aOR=2.0, 95% CI 1.10 to 3.66, p=0.023) were also more likely to accept it. Conclusion COVID-19 vaccine had a poor uptake and acceptance. Factors such as age, awareness, trust and previous vaccination experience played a significant role in COVID-19 vaccine acceptance. We recommended targeted public health campaigns, improving community engagement and building trust in community leaders, healthcare providers and public health institutions.

Background The primary endpoint in diabetes-related foot ulcer (DFU) trials is often time to healing, defined as complete re-epithelialisation with absence of drainage, requiring clinical expert assessment as the gold standard. Central blinded photograph review for confirmation of healing is increasingly being undertaken for internal validity. The Diabetic Foot Ulcer Photography study aims to determine the agreement between blinded independent review panel members for assessing ulcer healing status in patients with DFUs. Methods and analysis Photographs of ulcers clinically assessed as healed or not healed across 300 participants recruited to one of two randomised controlled trials (MIDFUT and CODIFI2), will be independently reviewed by a central blinded panel consisting of four clinicians with expertise in ulcer healing assessment. Staff at recruiting sites will take photographs using a standardised camera and protocol. Photographs will be reviewed at three levels of magnification: raw image, image standardised to a measurement scale included in the photograph and standardised image with magnification permitted. Reviewers will assess the healing status and their confidence level in making a healing judgement, with reasons reported for a low confidence rating. Analysis at each level of magnification will estimate inter- and intra-rater reliability on the assessments of healing of photographs with the clinical assessment (primary) and confidence rating using multivariable logistic mixed models. Analysis of the learning curve for the assessment of healing and confidence rating will use exponential and two-phase models. Ethics and dissemination Ethics approval has been granted by the National Research Ethics Service Committees (MIDFUT 17/YH/0055; CODIFI2 18-WS-0235). All participants will provide a written informed consent for photography before recruited onto the respective study. Photographs will be transferred to the trials’ coordinating centre via a secure file transfer service and saved in a restricted access folder on a secure server. Results will be disseminated via publications in scientific journals and conference presentations. Trial registration number MIDFUT ( ISRCTN64926597 ) and CODIFI2 ( ISRCTN74929588 ).

This article explores the multiplicity of publics that are enacted in relation to infrastructures. We take the case of street lighting infrastructure in the UK in 2013/4, at a point when innovations in light emitting diode (LED) and smart technologies were making the infrastructuring of street lighting newly visible. Multifarious, emergent and recursive publics were variously enacted by lighting professionals, researchers, and publics themselves as part of this infrastructuring. We argue that these publics were constituted vis-à-vis other actors and entities and coalesced around configurations and attributions of knowledge, uncertainty and ignorance. “Supra-publics” indexed long-standing local knowledge gained by lighting professionals. “Occasioned publics” vis-à-vis technocratic expertise emerged when infrastructures became newly visible as lighting professionals (or researchers) consulted publics. “Citizen publics”, mobilized vis-à-vis governance, carefully marshalled experiential knowledge alongside newly acquired technical knowledge. These categories are neither comprehensive nor mutually exclusive, and their contours have shifted since our fieldwork as domains of knowledge and ignorance have changed. However, they are indicative of the multiplicity of publics that are part of lighting infrastructure in liberal states, and suggestive of ways in which publics are not stable entities, but rather in constant flux, as infrastructuring makes light work.

As part of the formative work of the SUCCEED Africa consortium, we followed a participatory process to identify existing gaps and resources needed for the development and implementation of a rights-based intervention for people with lived experience of psychosis in Malawi, Nigeria, Sierra Leone and Zimbabwe. In 2021, we conducted a desk review of published and grey literature on psychosis in the four SUCCEED countries. Using an adapted version of the PRIME situation analysis template, data were extracted across the five domains of the WHO Community-Based Rehabilitation (CBR) Matrix: health, education, livelihoods, social and empowerment. This was supplemented with insights from personal communications with key stakeholders and the lived and professional experiences of team members. Findings indicate that people with lived experience of psychosis have limited access to services and opportunities across the five CBR domains. Participation in social, religious, empowerment and political activities is restricted due to stigma and a lack of advocacy. People with lived experience of psychosis in SUCCEED countries are not generally able to access support in line with essential components of CBR. There is a need for their greater inclusion in policy and advocacy activities.

Background Domestic violence and abuse (DVA) is a violation of human rights that damages the health and well-being of—gay, bisexual and other men who have sex with men (gbMSM). Sexual health services provide a unique opportunity to assess for DVA and provide support. This study explores the feasibility and acceptability of Healthcare Responding to Men for Safety (HERMES), a pilot intervention aimed to improve the identification and referral of gbMSM experiencing DVA in a London NHS Trust. Methods The before and after mixed method evaluation of the intervention included semi-structured interviews with 21 sexual health practitioners, 20 matched pre-post questionnaires, and an audit of 533 patient records to assess identification and referral of gbMSM experiencing DVA. Results HERMES increased practitioners’ self-reported preparedness and confidence in enquiring, identifying and responding to gbMSM experiencing DVA. HERMES increased staff awareness of DVA among these patients, which led to higher identification practices in their work. There was a significant increase in the identification and reporting practices of trained staff (0% to 30%), with 6 (5%) DVA cases identified. However, as far as we could determine, none of these patients contacted the support agency. Conclusions HERMES proved successful in raising staff awareness, provided tools that increased identification and a referral pathway to an external specialist DVA service for the LGBT community. However, the poor uptake of the referral service indicates a need for further exploration of the help-seeking behaviour of gbMSM experiencing DVA and whether they would prefer to receive support within a sexual health service. Reinforcement training and clinical supervision is needed to sustain positive changes in practice over time and address potential challenges posed by staff turnover. Initial training should be conducted through face-to-face sessions with a combination of in-person and e-learning materials and followed by in-person and online reinforcement activities.

nKlebsiella pneumoniae is a common pathogen of healthcare-associated infections expressing a plethora of antimicrobial resistance loci, including ADP-ribosyltransferase coding genes (arr), able to mediate rifampicin resistance. The latter has activity against a broad range of microorganisms by inhibiting DNA-dependent RNA polymerases. This study aims to characterise the arr distribution and genetic context in 138 clinical isolates of K. pneumoniae and correlate these with rifampicin resistance. All isolates were subjected to whole-genome sequencing for species identification, typing and AMR genes identification, along with the determination of the minimum inhibitory concentration (MIC) of rifampicin. Molecular detection of arr genes and class 1 integrons was performed for rifampicin-resistant isolates. Efflux activity was investigated as a possible determinant of rifampicin resistance in isolates devoid of known genetic determinants. Twelve isolates exhibited high rifampicin MICs (≥ 64 mg/L), 124 showed intermediate MICs (16–32 mg/L) and two displayed low (8 mg/L) MICs. Two arr allelic variants, arr-2 and arr-3, were found across one and nine K. pneumoniae isolates, respectively, all within class 1 integrons, including a newly described integron, and all associated with high rifampicin MICs (≥ 64 mg/L). Elevated resistance levels were additionally linked to increased arr-2/3 expression and closer proximity to the promoter. No arr gene or rpoB mutations were found across the remaining two isolates and no correlation between efflux activity and high-level rifampicin resistance was found for both isolates. In conclusion, this study demonstrates that arr genes confer high levels of rifampicin resistance in K. pneumoniae highlighting its widespread dissemination within class 1 integrons.