Association between under-dose of enzyme replacement therapy and quality of life in adults with late-onset Pompe disease in China: A retrospective matched cohort study.

BACKGROUND: Due to the high cost of enzyme replacement therapy (ERT), most of adults with late-onset Pompe disease (LOPD) who received ERT used the medication with insufficient dosefs in China. OBJECTIVE: To compare the change in quality of life (QoL) between adults with LOPD receiving under-dose ERT and no ERT, and identify factors associated with the change of QoL. METHODS: A retrospective matched cohort study was conducted among adult patients with LOPD in a nationwide Pompe registry in China. Eligible participants were those who completed two investigations, and didn't expose to ERT at baseline or before. The treated group were those who used ERT during follow-up; the untreated group received general care. The treated and untreated group were matched with a ratio of 1:2. QoL was assessed by the SF-12 and EQ-5D-5L. The dose of ERT was evaluated by the ratio of actual vials patients used divided by the indicated vials patients should use. The treated patients were further classified into mild and severe under-dose users by the median ratio. Multivariate linear regression analyses were performed to estimate the average treatment effect in the treated groups and identify factors associated with the changes of QoL scores. RESULTS: The study sample included 5 mild under-dose users, 6 severe under-dose users, and 22 untreated participants. Compared with the untreated group, mild under-dose ERT had no significant effect on the changes of QoL scores. In contrast, severe under-dose ERT was associated with a decline of physical QoL (ß = -6.19, p = 0.001), but an increase of overall health state (ß = 19.69, p = 0.032). A higher score of physical QoL (ß = -0.74, p = 0.001) and overall health state (ß = -0.69, p<0.001) at baseline was associated with decline in corresponding scores at follow-up. Being female was a contributor to the worsening of the overall health state (ß = -22.79, p = 0.002), while being employed or at school was a predictor of improvement in mental QoL (ß = 5.83, p = 0.002). CONCLUSIONS: A Pompe-disease specific instrument based on patient experiences is warranted to closely monitor changes in QoL on a routine basis. It is desirable for patients with severe under-dose ERT to discuss with physicians whether to adjust treatment strategies.

Integrating machine learning and artificial intelligence in life-course epidemiology: pathways to innovative public health solutions.

The integration of machine learning (ML) and artificial intelligence (AI) techniques in life-course epidemiology offers remarkable opportunities to advance our understanding of the complex interplay between biological, social, and environmental factors that shape health trajectories across the lifespan. This perspective summarizes the current applications, discusses future potential and challenges, and provides recommendations for harnessing ML and AI technologies to develop innovative public health solutions. ML and AI have been increasingly applied in epidemiological studies, demonstrating their ability to handle large, complex datasets, identify intricate patterns and associations, integrate multiple and multimodal data types, improve predictive accuracy, and enhance causal inference methods. In life-course epidemiology, these techniques can help identify sensitive periods and critical windows for intervention, model complex interactions between risk factors, predict individual and population-level disease risk trajectories, and strengthen causal inference in observational studies. By leveraging the five principles of life-course research proposed by Elder and Shanahan-lifespan development, agency, time and place, timing, and linked lives-we discuss a framework for applying ML and AI to uncover novel insights and inform targeted interventions. However, the successful integration of these technologies faces challenges related to data quality, model interpretability, bias, privacy, and equity. To fully realize the potential of ML and AI in life-course epidemiology, fostering interdisciplinary collaborations, developing standardized guidelines, advocating for their integration in public health decision-making, prioritizing fairness, and investing in training and capacity building are essential. By responsibly harnessing the power of ML and AI, we can take significant steps towards creating healthier and more equitable futures across the life course.

Patterns of the Health and Economic Burden of 33 Rare Diseases in China: Nationwide Web-Based Study.

BACKGROUND: Rare diseases (RDs) affect millions of individuals collectively worldwide, contributing to significant burdens on patients and families in various aspects. However, there is a lack of evidence on the underlying patterns of burdens among diverse RDs for informing targeted social and health policies to address the unmet needs of this vulnerable population. OBJECTIVE: This study aimed to examine the underlying patterns of the health and economic burden of 33 different RDs in China and identify the potential determinants. METHODS: A nationwide internet-based cross-sectional survey was conducted in China between 2019 and 2020. Physical and mental health burden was measured by health-related quality of life. Economic burden was evaluated based on the proportions of direct medical, direct nonmedical, and indirect costs relative to household income. We used cluster analysis to identify patterns of health and economic burdens and conducted multinomial logistic regression to explore potential predictors of cluster membership. RESULTS: The study included 8454 adults and 8491 children affected by 33 RDs. The following 3 clusters were identified: "extremely high burden" (representing 92/8454, 1.1% and 19/8491, 0.2% of adult and pediatric patients, respectively), "overall high burden" (5933/8454, 70.2% and 4864/8491, 57.3%, respectively), and "overall low burden" (2429/8454, 28.7% and 3608/8491, 42.5%, respectively). Wilson disease, Marfan syndrome, and Langerhans cell histiocytosis more likely resulted in an "extremely high burden" than others. Poverty was significantly associated with being in this extremely high burden group. Diseases causing neuromuscular symptoms and requiring long-term treatment (eg, amyotrophic lateral sclerosis, spinocerebellar ataxia, and Dravet syndrome) were prevalent in the "overall high burden" group. Key predictors of this group included older age, lower socioeconomic status, diagnostic delay, and comorbidity. CONCLUSIONS: This study provides novel and valuable evidence on the burden of RDs in developing regions like China. The findings reveal significant disparities in the impact of RDs, emphasizing the need for targeted health care interventions and policies.

Fluorometric determination of mecA gene in MRSA with a graphene-oxide based bioassay using flap endonuclease 1-assisted target recycling and Klenow fragment-triggered signal amplification.

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant bacterium that causes a wide range of illnesses, necessitating the development of new technologies for its detection. Herein, we propose a graphene oxide (GO)-based sensing platform for the detection of mecA gene in MRSA using flap endonuclease 1 (FEN1)-assisted target recycling and Klenow fragment (KF)-triggered signal amplification. Without the target, all the DNA probes were adsorbed onto GO, resulting in fluorescence quenching of the dye. Upon the addition of the target, a triple complex was formed that triggered FEN1-assisted target recycling and initiated two polymerization reactions with the assistance of KF polymerase, generating numerous dsDNA that were repelled by GO. These dsDNAs triggered fluorescence enhancement when SYBR Green I was added. Therefore, the target DNA was quantified by measuring the fluorescence at excitation and emission wavelengths of 480/526 nm. This mecA gene assay showed a good linear range from 1 to 50 nM with a lower limit of detection of 0.26 nM, and displayed good applicability to the analysis of real samples. Thus, a new method for monitoring MRSA has been developed that has great potential for early clinical diagnosis and treatment.

Corrigendum to "Do children with disabilities have the same opportunities to play as children without disabilities? Evidence from the multiple indicator cluster surveys in 38 low and middle-income countries" [ECLINM 67 (2023) 102361].

[This corrects the article DOI: 10.1016/j.eclinm.2023.102361.].

Are children with disabilities more likely to be malnourished than children without disabilities? Evidence from the Multiple Indicator Cluster Surveys in 30 countries.

Introduction: A key Sustainable Development Goal target is to eliminate all forms of malnutrition. Existing evidence suggests children with disabilities are at greater risks of malnutrition, exclusion from nutrition programmes and mortality from severe acute malnutrition than children without disabilities. However, there is limited evidence on the nutritional outcomes of children with disabilities in large-scale global health surveys. Methods: We analysed Multiple Indicator Cluster Survey data from 30 low and middle-income countries to compare nutritional outcomes for children aged 2-4 years with and without disabilities. We estimated the adjusted prevalence ratios for stunting, wasting and underweight comparing children with and without disabilities by country and sex, using quasi-Poisson models with robust SEs. We accounted for the complex survey design, wealth quintile, location and age in the analyses. We meta-analysed these results to create an overall estimate for each of these outcomes. Results: Our analyses included 229 621 children aged 2-4 across 30 countries, including 15 071 children with disabilities (6.6%). Overall, children with disabilities were more likely to be stunted (adjusted risk ratio (aRR) 1.16, 95% CI 1.11 to 1.20), wasted (aRR 1.28, 95% CI 1.18 to 1.39) and underweight (aRR 1.33, 95% CI 1.17, 1.51) than children without disabilities. These patterns were observed in both girls and boys with disabilities, compared with those without. Conclusion: Children with disabilities are significantly more likely to experience all forms of malnutrition, making it critical to accelerate efforts to improve disability inclusion within nutrition programmes. Ending all forms of malnutrition will not be achievable without a focus on disability.

Temporal trends in population attributable fractions of modifiable risk factors for dementia: a time-series study of the English Longitudinal Study of Ageing (2004-2019).

BACKGROUND: Interest in modifiable risk factors (MRFs) for dementia is high, given the personal, social, and economic impact of the disorder, especially in ageing societies such as the United Kingdom. Exploring the population attributable fraction (PAF) of dementia attributable to MRFs and how this may have changed over time remains unclear. Unravelling the temporal dynamics of MRFs is crucial for informing the development of evidence-based and effective public health policies. This investigation examined the temporal trajectories of MRFs for dementia in England. METHODS: We used data from the English Longitudinal Study of Ageing, a panel study over eight waves collected between 2004 and 2019 (76,904 interviews in total). We calculated the PAFs for twelve MRFs (including six early- to mid-life factors and six late-life factors), as recommended by the Lancet Commission, and the individual weighted PAFs (IW-PAFs) for each risk factor. Temporal trends were analysed to understand the changes in the overall PAF and IW-PAF over the study period. Subgroup analyses were conducted by sex and socioeconomic status (SES). RESULTS: The overall PAF for dementia MRFs changed from 46.73% in 2004/2005 to 36.79% in 2018/2019, though this trend was not statistically significant. During 2004-2019, hypertension, with an average IW-PAF of 8.21%, was the primary modifiable determinant of dementia, followed by obesity (6.16%), social isolation (5.61%), hearing loss (4.81%), depression (4.72%), low education (4.63%), physical inactivity (3.26%), diabetes mellitus (2.49%), smoking (2.0%), excessive alcohol consumption (1.16%), air pollution (0.42%), and traumatic brain injury (TBI) (0.26%). During 2004-2019, only IW-PAFs of low education, social isolation, and smoking showed significant decreasing trends, while IW-PAFs of other factors either did not change significantly or increased (including TBI, diabetes mellitus, and air pollution). Upon sex-specific disaggregation, a higher overall PAF for MRFs was found among women, predominantly associated with later-life risk factors, most notably social isolation, depression, and physical inactivity. Additionally, hearing loss, classified as an early- to mid-life factor, played a supplementary role in the identified sex disparity. A comparable discrepancy was evident upon PAF evaluation by SES, with lower income groups experiencing a higher dementia risk, largely tied to later-life factors such as social isolation, physical inactivity, depression, and smoking. Early- to mid-life factors, in particular, low education and obesity, were also observed to contribute to the SES-associated divergence in dementia risk. Temporal PAF and IW-PAF trends, stratified by sex and SES, revealed that MRF PAF gaps across sex or SES categories have persisted or increased. CONCLUSIONS: In England, there was little change over time in the proportion of dementia attributable to known modifiable risk factors. The observed trends underscore the continuing relevance of these risk factors and the need for targeted public health strategies to address them.

Association between the hearing aid and mental health outcomes in people with hearing impairment: A case-control study among 28 European countries.

BACKGROUND: Hearing loss affects over 1.5 billion individuals globally, with significant implications for mental health. This study investigates the association between hearing aid use and mental health outcomes, by particularly focusing on depression and unmet mental health needs (UMHN), across a diverse international sample. METHODS: Utilizing data from the third wave of the European Health Interview Survey (EHIS), this study involved 17,660 participants with hearing impairment from 28 countries. The study examined the association between hearing aid use and mental health outcomes, including the likelihood of moderate and severe depression and UMHN due to lack of contact with general practitioners (GPs) and mental health specialists. Logistic regression models, adjusted for socio-demographic characteristics, health risk behaviours, and other relevant variables, were employed. Inverse probability weights were used to mitigate potential selection bias. RESULTS: Hearing aid usage was associated with significantly lower likelihoods of moderate depression (Odds Ratio [OR] = 0.58, 95%CI = [0.54, 0.63]) and severe depression (OR = 0.61, 95%CI = [0.55, 0.69]), compared to non-usage. Hearing aid usage was also associated with reduced UMHN due to lack of GP contact for moderate (OR = 0.82, 95%CI = [0.75, 0.89]) and severe depression (OR = 0.75, 95%CI = [0.59, 0.95]). The depression risk reductions were greater among females and higher-educated subgroups but lower in individuals aged ≥65 years. Income level and rurality also impacted UMHN due to the lack of GP contact. No associations were found between hearing aids and UMHN due to the lack of mental health specialist contact. CONCLUSIONS: Hearing aid adoption showed protective associations against mood disorders and lowered unmet primary mental healthcare needs. Tailoring intervention strategies to vulnerable sociodemographic profiles could optimize mental health benefits among those with hearing loss. Integrating hearing health services within mental healthcare delivery frameworks is vital amidst the rising global burden.

Temporal trends and disparities of population attributable fractions of modifiable risk factors for dementia in China: a time-series study of the China health and retirement longitudinal study (2011-2018).

Background: In China, dementia poses a significant public health challenge, exacerbated by an ageing population and lifestyle changes. This study assesses the temporal trends and disparities in the population-attributable fractions (PAFs) of modifiable risk factors (MRFs) for new-onset dementia from 2011 to 2018. Methods: We used data from the China Health and Retirement Longitudinal Study (CHARLS), covering 75,214 person-waves. We calculated PAFs for 12 MRFs identified by the Lancet Commission (including six early-to mid-life factors and six late-life factors). We also determined the individual weighted PAFs (IW-PAFs) for each risk factor. Subgroup analyses were conducted by sex, socio-economic status (SES), and geographic location. Findings: The overall PAF for dementia MRFs had a slight increase from 45.36% in 2011 to 52.46% in 2018, yet this change wasn't statistically significant. During 2011-2018, the most contributing modifiable risk was low education (average IW-PAF 11.3%), followed by depression, hypertension, smoking, and physical inactivity. Over the eight-year period, IW-PAFs for risk factors like low education, hypertension, hearing loss, smoking, and air pollution showed decreasing trends, while others increased, but none of these changes were statistically significant. Sex-specific analysis revealed higher IW-PAFs for traumatic brain injury (TBI), social isolation, and depression in women, and for alcohol and smoking in men. The decline in IW-PAF for men's hearing loss were significant. Lower-income individuals had higher overall MRF PAFs, largely due to later-life factors like depression. Early-life factors, such as TBI and low education, also contributed to SES disparities. Rural areas reported higher overall MRF PAFs, driven by factors like depression, low education, and hearing loss. The study also found that the gap in MRF PAFs across different SES groups or regions either remained constant or increased over the study period. Interpretation: The study reveals a slight but non-significant increase in dementia's MRF PAF in China, underscoring the persistent relevance of these risk factors. The findings highlight the need for targeted public health strategies, considering the demographic and regional differences, to effectively tackle and reduce dementia risk in China's diverse population. Funding: This work was supported by the PKU Young Scholarship in Global Health and Development.

Sex-Specific Differences in the Progression of Huntington's Disease Symptoms - A National Study in China.

INTRODUCTION: Huntington's disease (HD) is a rare, inherited neurodegenerative disorder. Despite extensive research on symptom progression and sex differences in Western populations, little is known about these aspects within the Chinese context. The objective of this study was to investigate the temporal trends of symptoms in individuals with HD in China. METHODS: A nationwide cross-sectional study was conducted in Chinese individuals diagnosed with HD. Symptom progression over time, encompassing physical, psychiatric, and cognitive symptoms, was self-reported. We calculated the proportions of individuals who currently had each symptom by disease duration, and tested corresponding temporal trends by linear regression analyses. RESULTS: A total of 269 individuals diagnosed with HD were included. Specific symptoms were found to progress more significantly in males compared to females over time, including psychotic symptoms (p = 0.007), urinary incontinence (p = 0.013), reduced concentration (p = 0.005), font alteration (p = 0.029), atypical facial expression (p = 0.037), and suicidal ideation (p = 0.047). In terms of cognitive and psychiatric symptoms, no significant temporal trends were identified in females, while males demonstrated significant increasing trends, with reduced concentration (p = 0.005) and psychotic symptoms (p = 0.007) standing out. CONCLUSIONS: This study emphasizes the existence of sex-specific symptom progression in HD within the Chinese population, underscoring the importance of considering sex in clinical practice. Further research should investigate the mechanisms behind these differences and explore tailored treatment options.

Global antimicrobial resistance and antibiotic use in COVID-19 patients within health facilities: A systematic review and meta-analysis of aggregated participant data.

OBJECTIVES: The COVID-19 pandemic has posed a significant threat to the global healthcare system, presenting a major challenge to antimicrobial stewardship worldwide. This study aimed to provide a comprehensive and up-to-date picture of global antimicrobial resistance (AMR) and antibiotic use in COVID-19 patients. METHODS: We conducted a systematic review to determine the prevalence of AMR and antibiotic usage among COVID-19 patients receiving treatment in healthcare facilities. Our search encompassed the PubMed, Web of Science, Embase, and Scopus databases, spanning studies published from December 2019 to May 2023. We utilized random-effects meta-analysis to assess the prevalence of multidrug-resistant organisms (MDROs) and antibiotic use in COVID-19 patients, aligning with both the WHO's priority list of MDROs and the AWaRe list of antibiotic products. Estimates were stratified by region, country, and country income. Meta-regression models were established to identify predictors of MDRO prevalence and antibiotic use in COVID-19 patients. The study protocol was registered with PROSPERO (CRD 42023449396). RESULTS: Among the 11,050 studies screened, 173 were included in the review, encompassing a total of 892,312 COVID-19 patients. MDROs were observed in 42.9% (95% CI 31.1-54.5%, I2 = 99.90%) of COVID-19 patients: 41.0% (95% CI 35.5-46.6%) for carbapenem-resistant organisms (CRO), 19.9% (95% CI 13.4-27.2%) for methicillin-resistant Staphylococcus aureus (MRSA), 24.9% (95% CI 16.7-34.1%) for extended-spectrum beta-lactamase-producing organisms (ESBL), and 22.9% (95% CI 13.0-34.5%) for vancomycin-resistant Enterococcus species (VRE), respectively. Overall, 76.2% (95% CI 69.5-82.9%, I2 = 99.99%) of COVID-19 patients were treated with antibiotics: 29.6% (95% CI 26.0-33.4%) with "Watch" antibiotics, 22.4% (95% CI 18.0-26.7%) with "Reserve" antibiotics, and 16.5% (95% CI 13.3-19.7%) with "Access" antibiotics. The MDRO prevalence and antibiotic use were significantly higher in low- and middle-income countries than in high-income countries, with the lowest proportion of antibiotic use (60.1% (95% CI 52.1-68.0%)) and MDRO prevalence (29.1% (95% CI 21.8-36.4%)) in North America, the highest MDRO prevalence in the Middle East and North Africa (63.9% (95% CI 46.6-81.2%)), and the highest proportion of antibiotic use in South Asia (92.7% (95% CI 90.4-95.0%)). The meta-regression identified antibiotic use and ICU admission as a significant predictor of higher prevalence of MDROs in COVID-19 patients. CONCLUSIONS: This systematic review offers a comprehensive and current assessment of MDRO prevalence and antibiotic use among COVID-19 patients in healthcare facilities. It underscores the formidable challenge facing global efforts to prevent and control AMR amidst the backdrop of the COVID-19 pandemic. These findings serve as a crucial warning to policymakers, highlighting the urgent need to enhance antimicrobial stewardship strategies to mitigate the risks associated with future pandemics.

Social Environment, Lifestyle, and Genetic Predisposition With Dementia Risk: A Long-Term Longitudinal Study Among Older Adults.

BACKGROUND: The role of social environment, that is, the aggregate effect of social determinants of health (SDOHs), in determining dementia is unclear. METHODS: We developed a novel polysocial risk score for dementia based on 19 SDOH among 5 199 participants in the Health and Retirement Study, United States, to measure the social environmental risk. We used a survival analysis approach to assess the association between social environment and dementia risk in 2006-2020. We further studied the interaction between social environment and lifestyles, and explored racial disparities. RESULTS: The study participants (mean age = 73.4 years, SD = 8.3; 58.0% female; 11.6% African American) were followed up for an average of 6.2 years, and 1 089 participants developed dementia. Every 1-point increase in the polysocial risk score (ranging from 0 to 10) was associated with a 21.6% higher risk (adjusted hazard ratio [aHR] = 1.21, 95% confidence intervals [95% CI] = 1.15-1.26) of developing dementia, other things being equal. Among participants with high social environmental risk, regular exercise and moderate drinking were associated with a 43%-60% lower risk of developing dementia (p < .001). In addition, African Americans were 1.3 times (aHR = 2.28, 95% CI = 1.96-2.66) more likely to develop dementia than European Americans, other things being equal. CONCLUSION: An adverse social environment is linked to higher dementia risk, but healthy lifestyles can partially offset the increased social environmental risk. The polysocial risk score can complement the existing risk tools to identify high-risk older populations, and guide the design of targeted social environmental interventions, particularly focusing on improving the companionship of the older people, to prevent dementia.

Dose-Dependent Association Between Body Mass Index and Mental Health and Changes Over Time.

Importance: Overweight and obesity affect 340 million adolescents worldwide and constitute a risk factor for poor mental health. Understanding the association between body mass index (BMI) and mental health in adolescents may help to address rising mental health issues; however, existing studies lack comprehensive evaluations spanning diverse countries and periods. Objective: To estimate the association between BMI and mental health and examine changes over time from 2002 to 2018. Design, Setting, and Participants: This was a repeated multicountry cross-sectional study conducted between 2002 and 2018 and utilizing data from the Health Behaviour in School-aged Children (HBSC) survey in Europe and North America. The study population consisted of more than 1 million adolescents aged 11 to 15 years, with all surveyed children included in the analysis. Data were analyzed from October 2022 to March 2023. Main Outcomes and Measures: Mental health difficulties were measured by an 8-item scale for psychological concerns, scoring from 0 to 32, where a higher score reflects greater psychosomatic issues. BMI was calculated using weight divided by height squared and adjusted for age and sex. Data were fitted by multilevel generalized additive model. Confounders included sex, living with parents, sibling presence, academic pressure, the experience of being bullied, family affluence, screen time, and physical activity. Results: Our analysis of 1 036 869 adolescents surveyed from 2002 to 2018, with a mean (SD) age of 13.55 (1.64) years and comprising 527 585 girls (50.9%), revealed a consistent U-shaped association between BMI and mental health. After accounting for confounders, adolescents with low body mass and overweight or obesity had increased psychosomatic symptoms compared to those with healthy weight (unstandardized ß, 0.14; 95% CI, 0.08 to 0.19; unstandardized ß, 0.27; 95% CI, 0.24 to 0.30; and unstandardized ß, 0.62; 95% CI, 0.56 to 0.67, respectively), while adolescents with underweight had fewer symptoms (unstandardized ß, -0.18; 95% CI, -0.22 to -0.15). This association was observed across different years, sex, and grade, indicating a broad relevance to adolescent mental health. Compared to 2002, psychosomatic concerns increased significantly in 2006 (unstandardized ß, 0.19; 95% CI, 0.11 to 0.26), 2010 (unstandardized ß, 0.14; 95% CI, 0.07 to 0.22), 2014 (unstandardized ß, 0.48; 95% CI, 0.40 to 0.56), and 2018 (unstandardized ß, 0.82; 95% CI, 0.74 to 0.89). Girls reported significantly higher psychosomatic concerns than boys (unstandardized ß, 2.27; 95% CI, 2.25 to 2.30). Compared to primary school, psychosomatic concerns rose significantly in middle school (unstandardized ß, 1.15; 95% CI, 1.12 to 1.18) and in high school (unstandardized ß, 2.12; 95% CI, 2.09 to 2.15). Conclusions and Relevance: Our study revealed a U-shaped association between adolescent BMI and mental health, which was consistent across sex and grades and became stronger over time. These insights emphasize the need for targeted interventions addressing body image and mental health, and call for further research into underlying mechanisms.

Impact evaluation of a cash-plus programme for children with disabilities in the Xiengkhouang Province in Lao PDR: study protocol for a non-randomised controlled trial.

INTRODUCTION: More than 170 countries have implemented disability-targeted social protection programmes, although few have been rigorously evaluated. Consequently, a non-randomised controlled trial is being conducted of a pilot 'cash-plus' programme implemented by UNICEF Laos and the Laos government for children with disabilities in the Xiengkhouang Province in Laos. The intervention combines a regular cash transfer with provision of assistive devices and access for caregivers to a family support programme. METHODS AND ANALYSIS: The non-randomised controlled trial will involve 350 children with disabilities across 3 districts identified by programme implementers as eligible for the programme (intervention arm). Implementers have also identified approximately 180 children with disabilities in neighbouring districts, who would otherwise meet eligibility criteria but do not live in the project areas (control arm). The trial will assess the impact of the programme on child well-being (primary outcome), as well as household poverty, caregiver quality of life and time use (secondary outcomes). Baseline data are being collected May-October 2023, with endline 24 months later. Analysis will be intention to treat. A complementary process evaluation will explore the implementation, acceptability of the programme, challenges and enablers to its delivery and mechanisms of impact. ETHICS AND DISSEMINATION: The study has received ethical approval from the London School of Hygiene and Tropical Medicine and the National Ethics Committee for Health Research in Laos. Informed consent and assent will be taken by trained data collectors. Data will be collected and stored on a secure, encrypted server and its use will follow a detailed data management plan. Findings will be disseminated in academic journals and in short briefs for policy and programmatic actors, and in online and in-person events. TRIAL REGISTRATION NUMBER: ISRCTN80603476.

Predicting patients with dementia most at risk of needing psychiatric in-patient or enhanced community care using routinely collected clinical data: retrospective multi-site cohort study.

BACKGROUND: Dementia is a common and progressive condition whose prevalence is growing worldwide. It is challenging for healthcare systems to provide continuity in clinical services for all patients from diagnosis to death. AIMS: To test whether individuals who are most likely to need enhanced care later in the disease course can be identified at the point of diagnosis, thus allowing the targeted intervention. METHOD: We used clinical information collected routinely in de-identified electronic patient records from two UK National Health Service (NHS) trusts to identify at diagnosis which individuals were at increased risk of needing enhanced care (psychiatric in-patient or intensive (crisis) community care). RESULTS: We examined the records of a total of 25 326 patients with dementia. A minority (16% in the Cambridgeshire trust and 2.4% in the London trust) needed enhanced care. Patients who needed enhanced care differed from those who did not in age, cognitive test scores and Health of the Nation Outcome Scale scores. Logistic regression discriminated risk, with an area under the receiver operating characteristic curve (AUROC) of up to 0.78 after 1 year and 0.74 after 4 years. We were able to confirm the validity of the approach in two trusts that differed widely in the populations they serve. CONCLUSIONS: It is possible to identify, at the time of diagnosis of dementia, individuals most likely to need enhanced care later in the disease course. This permits the development of targeted clinical interventions for this high-risk group.

HIV knowledge and access to testing for people with and without disabilities in low- and middle-income countries: evidence from 37 Multiple Indicator Cluster Surveys.

INTRODUCTION: Disability and HIV are intricately linked, as people with disabilities are at higher risk of contracting HIV, and living with HIV can lead to impairments and disability. Despite this well-established relationship, there remains limited internationally comparable evidence on HIV knowledge and access to testing for people with disabilities. METHODS: We used cross-sectional data from 37 Multiple Indicator Cluster Surveys. Surveys were from six UNICEF regions, including East Asia and Pacific (n = 6), East and Central Asia (n = 7), Latin America and the Caribbean (n = 6), Middle East and North Africa (n = 4), South Asia (n = 2) and sub-Saharan Africa (n = 12). A total of 513,252 people were eligible for inclusion, including 24,695 (4.8%) people with disabilities. We examined risk ratios and 95% confidence intervals for key indicators on HIV knowledge and access to testing for people with disabilities by sex and country. We also conducted a meta-analysis to get a pooled estimate for each sex and indicator. RESULTS: Men and women with disabilities were less likely to have comprehensive knowledge about HIV prevention (aRR: 0.74 [0.67, 0.81] and 0.75 [0.69, 0.83], respectively) and to know of a place to be tested for HIV (aRR: 0.95 [0.92, 0.99] and 0.94 [0.92, 0.97], respectively) compared to men and women without disabilities. Women with disabilities were also less likely to know how to prevent mother-to-child transmission (aRR: 0.87 [0.81, 0.93]) and ever have been tested for HIV (aRR: 0.90 [0.85, 0.94]). CONCLUSIONS: Men and women with disabilities have lower overall HIV knowledge and in particular women with disabilities also indicate lower testing rates. Governments must include people with disabilities in HIV programmes by improving disability-inclusion and accessibility to HIV-related information, education and healthcare services.

The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study.

BACKGROUND: A significant proportion of people with clozapine-treated schizophrenia develop 'checking' compulsions, a phenomenon yet to be understood. AIMS: To use habit formation models developed in cognitive neuroscience to investigate the dynamic interplay between psychosis, clozapine dose and obsessive-compulsive symptoms (OCS). METHOD: Using the anonymised electronic records of a cohort of clozapine-treated patients, including longitudinal assessments of OCS and psychosis, we performed longitudinal multi-level mediation and multi-level moderation analyses to explore associations of psychosis with obsessiveness and excessive checking. Classic bivariate correlation tests were used to assess clozapine load and checking compulsions. The influence of specific genetic variants was tested in a subsample. RESULTS: A total of 196 clozapine-treated individuals and 459 face-to-face assessments were included. We found significant OCS to be common (37.9%), with checking being the most prevalent symptom. In mediation models, psychosis severity mediated checking behaviour indirectly by inducing obsessions (r = 0.07, 95% CI 0.04-0.09; P < 0.001). No direct effect of psychosis on checking was identified (r = -0.28, 95% CI -0.09 to 0.03; P = 0.340). After psychosis remission (n = 65), checking compulsions correlated with both clozapine plasma levels (r = 0.35; P = 0.004) and dose (r = 0.38; P = 0.002). None of the glutamatergic and serotonergic genetic variants were found to moderate the effect of psychosis on obsession and compulsion (SLC6A4, SLC1A1 and HTR2C) survived the multiple comparisons correction. CONCLUSIONS: We elucidated different phases of the complex interplay of psychosis and compulsions, which may inform clinicians' therapeutic decisions.

Association of Socioeconomic Status and a Broad Combination of Lifestyle Factors With Adult-Onset Asthma: A Cohort Study.

BACKGROUND: The prevalence of asthma is gradually increasing worldwide, and there are socioeconomic inequalities in the risk of developing asthma. OBJECTIVE: To evaluate whether the lifestyle is associated with asthma in adults, as well as whether and to what extent healthy lifestyles may modify socioeconomic status (SES) inequities in asthma. METHODS: This study included a total of 223,951 participants from the UK Biobank. Smoking, physical activity, alcohol consumption, healthy diet patterns, sedentary time, and sleep duration items were used to construct the lifestyle score. Income, education, and occupation were used to assess SES. Cases of adult-onset asthma were identified on the basis of electronic health records. The Cox proportional hazards regression was used to explore the association of socioeconomic inequality and lifestyle factors with asthma. RESULTS: Compared with the most healthy lifestyle category, the hazard ratios (95% CIs) of the moderately healthy lifestyle and least healthy lifestyle categories for asthma were 1.08 (1.01-1.15) and 1.29 (1.20-1.39), respectively. A significant interaction (Pinteraction < .05) was found between lifestyle categories and SES, and the association between them was more pronounced in participants with low SES (hazard ratioleast healthy vs most healthy, 1.58; 95% CI, 1.40-1.80). The joint analysis revealed that the risk of asthma was highest among participants with the lowest SES and the least healthy lifestyles (hazard ratio, 2.02; 95% CI, 1.74-2.33). CONCLUSIONS: Unhealthy lifestyle factors are associated with an increased risk of asthma in adults, and socioeconomically disadvantaged groups are more negatively affected by unhealthy lifestyles. Public health strategies for asthma prevention may need to be tailored according to SES, and social policies to reduce poverty are needed alongside lifestyle interventions in areas of deprivation.

Social support and medication adherence among adult myasthenia gravis patients in China: the mediating role of mental health and self-efficacy.

BACKGROUND: Myasthenia gravis (MG), a rare chronic neuromuscular disorder, is characterized by progressive physical decline and requires long-term pharmacological treatment. Due to the decline of physical and social abilities, MG patients are in great need of social support, including tangible and emotional support. This study aims to examine the association between social support and medication adherence and the possible mediating effects of mental health and self-efficacy among MG patients. METHODS: A cross-sectional analysis of a nationwide MG registry was conducted on 865 patients under oral medication treatment in China between June and July 2022. Validated scales were used to measure the respondent's mental distress (Four-item Patient Health Questionnaire), social support (Modified Medical Outcomes Study Social Support Scale), self-efficacy for medication use (Self-efficacy for Appropriate Medication Use Scale), and medication adherence (Morisky Medication Adherence Scale, MMAS). RESULTS: The association between social support and medication adherence and possible mediating effects of mental distress and self-efficacy were tested by structural equation model, with significant demographic and disease-related factors adjusted. The respondents showed a very low level of medication adherence (71.2% poor adherence; 1.4% high adherence; mean MMAS = 4.65). The level of social support was positively associated with medication adherence, and such association was fully mediated by two indirect pathways: through self-efficacy (ß = 0.07, proportion mediated = 63.8%); and through mental distress and then self-efficacy (ß = 0.01, proportion mediated = 6.7%). CONCLUSION: Provision of social support and interventions on mental health with emphasis on improving self-efficacy for medication use may effectively improve medication adherence among MG patients.

Evaluation of a disability-inclusive ultra-poor graduation programme in Uganda: study protocol for a cluster-randomised controlled trial with process evaluation.

BACKGROUND: There is little evidence on how to support ultra-poor people with disabilities to adopt sustainable livelihoods. The Disability-Inclusive Graduation (DIG) programme targets ultra-poor people with disabilities and/or women living in rural Uganda. The programme is an adaptation of an ultra-poor graduation model that has been shown to be effective in many contexts but not evaluated for people with disabilities. METHODS: The DIG programme works with project participants over a period of 18 months. Participants receive unconditional cash transfers for 6 months, training, access to savings-and-loans groups, and a capital asset that forms the basis of their new livelihood. The programme is also adapted to address specific barriers that people with disabilities face. Eligible households are clustered by geographical proximity in order to deliver the intervention. Eligibility is based on household screening to identify the 'ultra-poor' based on proxy means testing-both households with and without people with disabilities are included in the programme. Clusters are randomly selected prior to implementation, resulting in 96 intervention and 89 control clusters. The primary outcome of the trial is per-capita household consumption. Before the start of the intervention, a baseline household survey is conducted (November 2020) among project participants and those not offered the programme, a similar endline survey is conducted with participants with disabilities at the end of programme implementation in July 2022, and a second endline survey for all participants in October 2023. These activities are complemented by a process evaluation to understand DIG programme implementation, mechanisms, and context using complementary qualitative and quantitative methods. Ethical approval for the research has been received from Mildmay Uganda Research Ethics Committee and London School of Hygiene and Tropical Medicine. DISCUSSION: DIG is a promising intervention to evaluate for people with disabilities, adapted to be disability inclusive across programme components through extensive consultations and collaboration, and has proven efficacy at reducing poverty in other marginalised groups. However, evaluating a well-evidenced intervention among a new target group poses ethical considerations. TRIAL REGISTRATION: Registry for International Development Impact Evaluations, RIDIE-STUDY-ID-626008898983a (20/04/22). ISRCTN registry, ISRCTN78592382 . Retrospectively registered on 17/08/2023.