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All-cause and cause-specific mortality differences between migrant workers and local workers: a population-based cohort study in Denmark.
Get PDFMigrants are prone to poor working conditions in high-risk industries, yet little is known about their mortality risk compared to local-born workers. This study compares all-cause and cause-specific mortality between foreign-born and local-born workers, and identifies at-risk foreign-born workers. A nationwide register-based cohort study was performed using data on migrant workers obtaining residence permits in Denmark during 2015-22. Comparison group comprised Danish-born workers matched by age and sex. Survival analysis using extended Cox model was used to estimate all-cause and cause-specific mortality. Subgroup analysis was conducted by region of birth, economic sector, and occupation. Male migrant workers from Central Europe, Eastern Europe, and Central Asia had higher risk of all-cause mortality than Danish-born workers (HR = 1.30 [95% CI: 1.09-1.54]), attributed to accident deaths (HR = 1.64 [1.06-2.53]), whereas migrants from other regions had lower risk. Migrant workers from these regions were more likely to work in high-risk economic sectors and occupations, such as agriculture and construction. When stratified by economic sector and by occupation, among the elementary occupations, migrant workers from these regions still had a higher risk of all-cause mortality (HR = 1.70 [1.10-2.64]) and accident mortality (HR = 1.51 [1.22-1.85]) than Danish-born workers. Migrant workers from Central Europe, Eastern Europe, and Central Asia are more likely to die from accidents than Danish-born workers. This increased risk was partially explained by their higher representation in at-risk sectors and occupations. There is a need to better understand the structural determinants of health faced by these migrants, particularly in elementary occupations, to prevent avoidable deaths
Occupational health in the era of climate change and the green transition: a call for research.
Get PDFWork and working conditions are fundamental social determinants of health. Climate change poses an urgent and growing threat to workers' health, through both direct exposure to environmental hazards and indirect exacerbation of social and health inequalities. Occupational health, which focusses on the promotion of mental and physical health and well-being of workers, is a key but often overlooked area in this context. Research at the intersection of climate change and occupational health remains limited. At the same time, climate change mitigation and adaptation efforts are driving rapid transformations in the workplace, including shifts towards sustainability and circular economy models. These transitions are creating new occupational hazards, including in renewable energy and circular economy sectors. We argue for increased investment in occupational health research and surveillance to address the evolving impacts of both climate change and the green transition, to better promote and protect workers' health and rights
Modelling Population Genetic Screening in Rare Neurodegenerative Diseases
Get PDFImportance: Genomic sequencing enables the rapid identification of a breadth of genetic variants. For clinical purposes, sequencing for small genetic variations is considered a solved problem, while challenges remain for structural variants, given the lower sensitivity and specificity. Interest has recently risen among governing bodies in developing protocols for population-wide genetic screening. However, usefulness is constrained when the probability of being affected by a rare disease remains low, despite a positive genetic test. This is a common scenario in neurodegenerative disorders. The problem is recognised among statisticians and statistical geneticists but is less well-understood by clinicians and researchers who will act on these results, and by the general public who might access screening services directly without the appropriate support for interpretation.
Observations: We explore the probability of subsequent disease following genetic screening of several variants, both single nucleotide variants (SNVs) and larger repeat expansions, for two neurological conditions, Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS), comparing these results with screening for phenylketonuria, which is well-established. The risk following a positive screening test was 0.5% for C9orf72 in ALS and 0.4% for HTT in HD when testing repeat expansions, for which the test had sub-optimal performance (sensitivity = 99% and specificity = 90%), and 12.7% for phenylketonuria and 10.9% for ALS SOD1 when testing pathogenic SNVs (sensitivity = 99.96% and specificity = 99.95%). Subsequent screening confirmation via PCR for C9orf72 led to a 2% risk of developing ALS as a result of the reduced penetrance (44%).
Conclusions and Relevance: We show that risk following a positive screening test result can be strikingly low for rare neurological diseases, even for fully penetrant variants such as HTT, if the test has sub-optimal performance. Accordingly, to maximise the utility of screening, it is vital to prioritise protocols with very high sensitivity and specificity, and a careful selection of markers for screening, giving regard to clinical interpretability, actionability, high penetrance, and secondary testing to confirm positive findings
Exploring interrelationships between structural, social, and biological determinants of vaccine impact in Kenya and Uganda: VAnguard community mixed methods study protocol
Get PDFBackground The key principle underlying the UN Sustainable Development Goals is to “leave no one behind”. However, following the COVID-19 pandemic, sub-optimal vaccine coverage is a continuing concern in low-and middle-income countries (LMICs) and there is increasing evidence of impaired vaccine immunogenicity and efficacy in LMICs, compared to high-income countries (HICS) and in rural, compared to urban settings. It is documented that countries with the lowest vaccination coverage suffer the highest health inequalities. For vaccines to achieve their full health benefit, structural, social and biological determinants that impair vaccine impact must be concurrently addressed. This study aims to explore how structural, social and biological determinants interact to influence vaccine impact in vulnerable communities across Kenya and Uganda. By understanding these interactions, we can develop strategies to improve vaccine impact in vulnerable populations. Methods The study will utilise a cross-sectional mixed-methods design. It will be conducted in three counties in Kenya (Kilifi, Kwale and Kisumu) and three districts in Uganda (Kampala, Kikuube and Namayingo). We will conduct (i) in-depth interviews, (ii) focus group discussions (FGDs) with key community stakeholders, and (iii) a household-based quantitative survey where blood and stool samples of 1032 participants (172 in each community) will be collected. Samples will be used to measure proxy markers of reduced vaccine coverage and impaired vaccine immunogenicity. Conclusions The results of this study will identify potential determinants of vaccine impact that are modifiable. This evidence will be used in the development of a modelling framework to assess the likely impact of interventions targeting specific determinants of impact, both solely and concertedly, and how these might be tailored to different communities.</ns7:p
Ashwagandha (Withania somnifera (L.) Dunal) for promoting recovery in long covid: protocol for a randomised placebo-controlled clinical trial (APRIL Trial).
Get PDFBACKGROUND: Long covid describes a syndrome of persistent symptoms following COVID-19 and is responsible for substantial healthcare and economic burden. Currently, no effective treatments have been established. Ashwagandha (Withania somnifera (L.) Dunal) is a medicinal herb traditionally used in India for its immune-strengthening and anti-inflammatory properties. Withanolides, a family of steroid-derived molecules unique to Ashwagandha, have been shown to modulate inflammatory pathways in animal models, and several small randomised trials in humans support its effectiveness for reducing symptoms that are also associated with long covid. Therefore, this study aims to assess whether Ashwagandha is effective and safe for improving functional status and reducing symptom burden in adults living with long covid. METHODS: A randomised double-blind placebo-controlled trial will be performed at participating general practice (GP) surgeries and long covid clinics across the UK. Individuals diagnosed with long covid will be screened for eligibility and then randomised 1:1 to take 1000 mg daily of Ashwagandha root extract tablets (standardised to <0.9% withanolides) or matching placebo tablets for 3 months (target, n = 2500). Monthly online surveys will be performed to collect patient-reported outcomes, and monthly safety monitoring, including liver function tests, will be conducted by clinical site teams. The primary outcome of the Post-COVID Functional Status Scale score at 3 months will be assessed by baseline-adjusted ordinal logistic regression, according to a pre-published statistical analysis plan. The secondary outcomes included validated quality of life and long covid symptom scales, work status and productivity and adverse events. The trial has been approved as a Clinical Trial of an Investigational Medicinal Produce by the Medicines and Healthcare Regulatory Authority and by the NHS Research Ethics Committee and Health Research Authority. DISCUSSION: Treatments for long covid are urgently needed. This trial will robustly evaluate the safety and efficacy of a candidate treatment with a promising efficacy and safety profile. If found to be effective, the findings will likely influence treatment guidelines and improve health outcomes in those living with long covid. TRIAL REGISTRATION NUMBER: This trial was pre-registered on 15/08/2022: ISRCTN12368131
Changes in food quality and habits in urban Ghana: evidence from a mixed-methods study.
Get PDFBACKGROUND: Globally, diets are changing from good quality to limited nutrition. However, an in-depth analysis of the nature of the changes is under-researched. This study examined past and current food consumption, acquisition, and preparation habits of urban poor residents in Accra, Ghana. METHODS: Data from the Contextual Awareness Response and Evaluation: Diabetes in Ghana project was used. The Food Group Diversity Score, NCD-Risk and NCD-Protect scores were calculated using the Diet Quality Questionnaire and analysed using means and crosstabulations with the estimation of the 95% confidence intervals (n = 854). Focus group discussions were held to discuss current and past food habits, and data were analysed thematically (n = 30). The qualitative and quantitative data were integrated during the analysis. RESULTS: From the early 1950s to the 1980s, the community consumed more traditional homemade meals made from cassava, corn and plantains (such as fufu, kenkey, kokonte and ampesi). Currently, the community consume these traditional meals in addition to foods considered modern, such as instant noodles (6%), milk (19%), rice (67%), sugar-sweetened beverages (21%), and Milo (21%). Respondents, on average, ate four food groups (x̄=3.8 ± 1.5) and about half were food insecure (47%). The most frequently consumed NCD-protect foods were whole grains (63%) and other vegetables (69%). The NCD-risk items commonly consumed were deep-fried foods (23%), unprocessed red meat (22%) and sugar-sweetened beverages (21%). CONCLUSION: Respondents reported a shift from home cooking and communal meals toward eating out-of-home meals. The current dietary habits reflect a hybrid of modern foods with traditional foods. Food insecurity is high, and their diets provide little protection against chronic non-communicable diseases. This limits opportunities to move towards healthy diets and improved health outcomes as envisioned in the Agenda 2030
Effect of a pay-it-forward strategy on reducing HPV vaccine delay and increasing uptake among 15- to 18-year-old girls in China: A randomized controlled trial.
Get PDFBACKGROUND: Catch-up human papillomavirus (HPV) vaccination is challenging in many low- and middle-income countries (LMICs). Pay-it-forward offers an individual a subsidized vaccine, then an opportunity to donate to help others access vaccinations. Our randomized control trial assessed the effectiveness of pay-it-forward in improving HPV vaccination among girls aged 15-18 years in China. METHODS AND FINDINGS: This study was conducted from July 6, 2022, to June 9, 2023, in four community health centers (CHCs) in Chengdu, western China. Eligible participants were unvaccinated girls living in the service areas of CHCs. Participants were initially recruited via telephone and, after providing verbal consent, attended in-person visit where they were randomly assigned using the sealed envelope method to either the pay-it-forward arm (received a community subsidy of 47.7 USD covering the first vaccine and an opportunity to support others) or control arm (self-paid vaccination at the market price). Participants were unblinded only after the envelope was opened, while the CHC staff coordinators, physicians prescribing the vaccine, outcome assessors, and data analysts were blinded to the intervention allocation. The primary outcome was the first-dose HPV vaccination rate, verified against clinical records. Data were analyzed using the intention-to-treat approach. We identified 662 participants per phone invitation. A total of 321 participants showed up in the health centers and randomly assigned to the pay-it-forward arm (n = 161) or control arm (n = 160). Most caregivers were female (80.1%, 257/321). In the pay-it-forward arm, 55 of 161 (34.2%) girls received the HPV vaccine, compared with 28 of 160 (17.5%) girls in the control arm (adjusted proportion difference = 17.9%, (95% CI [8.7%, 27.0%]; P < 0.001). Among 55 girls in the pay-it-forward arm who received the vaccination, 37 (67.3%) wrote a postcard message, and 39 (70.9%) of their caregivers donated to support future girls. The financial cost per person vaccinated was 230 in the pay-it-forward arm. The trial had several limitations, including a 54% clinic attendance rate (360 of 662 consented participants attended) and its conduct in a single western province of China. CONCLUSIONS: The pro-social pay-it-forward strategy was effective to increase catch-up HPV vaccination among teenage girls. This approach also enhanced vaccine confidence among participants. Pay-it-forward demonstrates promise as an effective intervention to improve vaccine uptake through community engagement. TRIAL REGISTRATION: Chinese clinical trial registry ChiCTR2200055542 (https://www.chictr.org.cn/hvshowproject.html?id=183292&v=1.3)
Prevalence of asymptomatic malaria in high- and low-transmission areas of Tanzania: The role of asymptomatic carriers in malaria persistence and the need for targeted surveillance and control efforts.
Get PDFAs many countries implement different programs aimed at eliminating malaria, attention should be given to asymptomatic carriers that may interrupt the progress. This was a community-based cross-sectional study conducted in Tanzania from December 2022 to July 2023 within 4 villages from each of the 3 regions, Geita and Kigoma, which are high malaria transmission, and Arusha, which is low transmission. Malaria was diagnosed in asymptomatic individuals aged 1 year and older using the malaria rapid diagnostic test and light microscope. A total of 2,365 of 3,489 (67.9%) participants were enrolled from high-transmission villages. The overall prevalence was 25.5% and 15.8% by malaria rapid diagnostic test and light microscope, respectively. Using the respective tools, the prevalence was significantly higher at 35.6% (confidence interval (CI)=23.6-49.9) and 23.1% (CI=16.2-35.1) in the high-transmission regions (Geita and Kigoma) compared with 2.9% (CI=1.1-3.5) and 1.1% (CI=0.7-1.8) in the low-transmission region (Arusha). Children younger than 15 years and males accounted for the greatest proportion of infections. In the study area, the prevalence of asymptomatic cases was higher than that of reported symptomatic cases in health facilities. We hypothesize that these parasite reservoirs may contribute to the persistence of malaria in the country. Therefore, to achieve comprehensive malaria control in the country, the surveillance and screening of asymptomatic malaria cases are vital
Is health technology assessment value for money? Estimating the return on investment of health technology assessment in India (HTAIn).
Get PDFAn increasing investment in health technology assessment (HTA) in low-income and middle-income countries has generated greater interest from policy-makers about the value and return on investment (ROI) of HTA. Few studies have, however, quantified the benefits of HTA in terms of its value to the health system. This evaluation aims to quantify the impact and ROI achieved by the HTA agency in India (HTAIn).A framework developed by the University of Glasgow was used to review three 'hta's commissioned by HTAIn between 2018 and 2020, taking into account the opportunity cost of investing in these processes. Costs included fixed costs for HTAIn and costs for undertaking each 'hta'. Attributable benefits are calculated by subtracting the counterfactual (benefits that might have been realised without an HTA) from realised benefits.HTAIn sits under the Department of Health Research, Ministry of Health and Family Welfare, Government of India. It was set up to facilitate the process of transparent and evidence-informed decision-making in healthcare in India.HTA helps decision-makers to understand the consequences of alternative courses of action and to select the options that produce the best outcomes at the lowest cost. Institutionalisation of HTA is seen as pivotal to supporting universal health coverage as a means of supporting a better allocation of finite resources, cost containment and the maximisation of health.Net health benefits are our measure of value. The ROI of HTAIn is calculated by aggregating attributable benefits and offsetting them against the costs of investment.Our findings show that investing in HTAIn yields a return of 9:1, with potential to increase to 71:1 with full implementation of HTA recommendations. Variability of ROI ranged from 5:1 to 40:1 between the different interventions and diseases.While HTAIn requires financial investment, it is an efficient use of resources. The potential for greater impact and the variability of the ROI between interventions underline the importance of planning for implementation and good topic selection in HTA
Adapting COVID-19 research infrastructure to capture influenza and respiratory syncytial virus alongside SARS-CoV-2 in UK healthcare workers winter 2022/23: Results of a pilot study in the SIREN cohort.
Get PDFINTRODUCTION: The combination of patient illness and staff absence driven by seasonal viruses culminates in annual "winter pressures" on UK healthcare systems and has been exacerbated by COVID-19. In winter 2022/23 we introduce multiplex testing aiming to determine the incidence of SARS-CoV-2, influenza and respiratory syncytial virus (RSV) in our cohort of UK healthcare workers (HCWs). METHODS: The pilot study was conducted from 28/11/2022-31/03/2023 within the SIREN prospective cohort study. Participants completed fortnightly questionnaires, capturing symptoms and sick leave, and multiplex PCR testing for SARS-CoV-2, influenza and RSV, regardless of symptoms. PCR-positivity rates by virus were calculated over time, and viruses were compared by symptoms and severity. Self-reported symptoms and associated sick leave were described. Sick leave rates were compared by vaccination status and demographics. RESULTS: 5,863 participants were included, 84.6% female, 70.3% ≥ 45-years, 91.4% of White ethnicity and 82.6% in a patient facing role. PCR-positivity peaked in early December for all three viruses (4.6 positives per 100 tests (95%CI 3.5, 5.7) SARS-CoV-2, 3.9 (95%CI 2.2, 5.6) influenza, 1.4 (95%CI 0.4, 2.4) RSV), declining to <0.3/100 tests after January for influenza/RSV, and around 2.5/100 tests for SARS-CoV-2. Over one-third of all infections were asymptomatic, and symptoms were similar for all viruses. 1,368 (23.3%) participants reported taking sick leave, median 4 days (range 1-59). Rates of sick leave were higher in participants with co-morbidities, working in clinical settings, and who had not been vaccinated (COVID-19 booster or seasonal influenza vaccine) versus those who had received neither vaccine (2.04 vs 1.41 sick days/100 days, adjusted Incidence Rate Ratio 1.47 (95%CI 1.38, 1.56). CONCLUSION: This pilot demonstrated the use of multiplex testing allowed better understanding of the impact of seasonal respiratory viruses and respective vaccines on the HCW workforce. This highlights the important information on asymptomatic infection and persisting levels of SARS-CoV-2 infection