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Addressing the Environmental Impact of Pharmaceuticals: A Call to Action.
The contribution of health care to environmental and climate crises is significant, under-addressed, and with consequences for human health. This editorial is a call to action. Focusing on pharmaceuticals as a major environmental threat, we examine pharmaceutical impacts across their lifecycle, summarising greenhouse gas emissions, pollution, and biodiversity loss, and outlining challenges and opportunities to reduce this impact. We urge health care decision-makers and providers to urgently consider environmental factors in their decision-making relating to both policy, and practice, promoting actions such as rational prescribing, non-pharmaceutical interventions, and research and advocacy for sustainable production, procurement, and use.
Experiential caring and the mobilisation of peerhood in group clinics.
The concept of 'peer support' has generated much interest in mainstream health services. In policy discourse, peer-based initiatives are often described as 'empowering' and seen as contributing to more 'democratic' and 'holistic' forms of care. Focusing on group clinics as one such example, this article challenges the assumption that peer-based initiatives represent a straightforward and unequivocal 'good' when embedded in clinical care. We draw on qualitative data from three studies (2016-2025), including 118 interviews and ethnographic observation in 59 in-person, remote, and hybrid group clinics for diabetes and menopause at 5 primary and secondary care sites in England. Adopting a sociomaterial lens, we uncover how different forms and practices of peerhood emerge (or not) in the circumstances through which these clinics are materialised. We show how biomedical artefacts (e.g. diabetes test results, menopause symptom lists) used as part of consulting play a key role in constituting forms of affiliation and differentiation between patients, in turn determining whether and what forms of peer 'support' (e.g. disciplinary, affirmative) are accomplished. We go on to explore how being presented as a peer as part of clinical consulting brings about new roles and responsibilities for patients, and introduce the term 'experiential caring' to denote a new mode of consulting that mobilises roles, practices, and subjectivities associated with peerhood.
Digitally Enabled Care in Diverse Environments (DECIDE): protocol for a programme of rapid evaluation of technology-enabled remote monitoring in health and social care
Background There is considerable interest in technology-enabled remote monitoring in the UK. The aim is to respond to system pressures and improve access, experience and quality of care. There is an urgent need for process, outcome and impact evaluations of interventions at various stages of development and implementation to address evidence gaps around adoption, spread, sustainability and inequalities. Aim DECIDE (Digitally Enabled Care in Diverse Environments) is a centre for rapid evaluation of technology-enabled remote monitoring funded by the National Institute for Health and Care Research (2023 to 2026). It aims to support service users, service commissioners and providers of remote monitoring services, to enable high quality care. Example questions include: Is the technology-enabled remote monitoring innovation needed and, if so, for whom? How are technology-enabled care pathways implemented, and what are associated outcomes and impacts? What are the opportunities and challenges for sustainability, scale-up and spread? Methods A range of qualitative, quantitative and economic methods will be used. Exact methods and questions will be dependent on the focus, scope and scale of each evaluation. Evaluations will be informed by relevant theory, including the Non-Adoption, Abandonment and the challenges to Spread, Scale-up and Sustainability of technological innovation in health and care (NASSS) framework. A User Advisory Group and External Steering Committee, both with diverse voices, will help shape evaluation design, implementation and dissemination. Project-led dissemination will ensure timely sharing of insights and support impact. Conclusion Evaluations will advance understanding of when and for whom technology-enabled remote monitoring innovation is needed; how it works and how factors related to the intervention, implementation process and wider context influence adoption; associated outcomes and impacts, whether and how these tackle inequalities; and potential challenges to scale and spread. We aim to inform decision-making by policymakers, commissioners, providers, patients/service users and researchers.
After the disruptive innovation: How remote and digital services were embedded, blended and abandoned in UK general practice - longitudinal study.
BACKGROUND: United Kingdom general practices transitioned rapidly to remote-by-default services in 2020 and subsequently considered whether and how to continue these practices. Their diverse responses provided a unique opportunity to study the longer-term embedding, adaptation and abandonment of digital innovations. Research questions: What was the range of responses to the expansion of remote and digital triage and consultations among United Kingdom general practices in the period following the acute phase of the coronavirus disease discovered in 2019 (COVID-19) pandemic? What can we learn from this example about the long-term impacts of crisis-driven sociotechnical change in healthcare settings? METHODS: We collected longitudinal data from 12 general practices from 2021 to 2023, comprising 500 hours of ethnographic observation, 163 interviews in participating practices and linked organisations (132 staff, 31 patients), 39 stakeholder interviews and 4 multi-stakeholder workshops (210 participants), with additional patient and public involvement input. Data were de-identified, uploaded to NVivo (QSR International, Warrington, UK) and synthesised into case studies, drawing on theories of organisational innovation. RESULTS: General practices' longitudinal progress varied, from a near-total return to traditional in-person services to extensive continuing use of novel digital technologies and pathways. Their efforts to find the right balance were shaped and constrained by numerous contextual factors. Large size, slack resources, high absorptive capacity, strong leadership and good intrapractice relationships favoured innovation. Readiness for remote and digital modalities varied depending on local tension for change, practice values and patient characteristics. Technologies' uptake and use were influenced by their material properties and functionality. Embedding and sustaining technologies required ongoing work to adapt and refine tasks and processes and adjust (or, where appropriate, selectively abandon) technologies. Adoption and embedding of technologies were affected by various staff and patient factors. When technologies fitted poorly with tasks and routines or when embedding efforts were unsuccessful, inefficiencies and 'techno-stress' resulted, with compromises to patient access and quality of care. LIMITATIONS: Sampling frame was limited to United Kingdom and patient interviews were relatively sparse. CONCLUSION: There is wide variation in digital maturity among United Kingdom general practices. Low use of remote and digital technologies and processes may be warranted and reflect local strategic choices, but it may also indicate lack of awareness and a reactive rather than strategic approach to digital innovation. We offer an updated typology of digital maturity in general practice with suggestions for tailored support. FUTURE WORK: The typology of digital maturity could be applied further to identify in more detail the kind of support needed for practices that are at different stages of maturity and are serving different populations. The need for strategically traditional practices in deprived settings should also be explored. FUNDING: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR132807.
Migrant women's experience of antenatal care in an urban and rural setting in north and North-West Thailand: A cross sectional survey.
BACKGROUND: Nearly 50 % of women in low- and middle-income countries fail to obtain adequate antenatal care due to barriers in reaching the health facility. A key element of the quality of care is women's perception of treatment they receive. This study aims to compare the perspectives of urban and rural migrant women from Myanmar in Thailand and the obstacles they face when trying to access care. METHODS: From October-2023 to May-2024, a survey was conducted among migrant women, 74 at Sarapee hospital in Chang Mai Province, and 148 at the clinics of Shoklo Malaria Research Unit (SMRU), Tak Province. Questions based on REPRO-Q were used for scoring satisfaction in several domains using a Likert scale ranging from dissatisfied to satisfied. RESULTS: The majority of women in Sarapee and SMRU reported pleasant visits, 86.5 % (64/74), 99.3 % (144/145) respectively. Disrespectful behaviour against migrant women was low and mentioned by 14.9 % (11/74) in Sarapee and 1.4 % (2/148) at SMRU. The women attending care at Sarapee reported significantly lower satisfaction 60.8 % (45/74) on being able to refuse examination or treatment compared to women attending care in SMRU 83.0 % (122/147) P < 0.001. CONCLUSION: Both urban and rural settings had high rates of perceived pleasant visits and recommending the service to friends, although this could result from hesitancy to give negative feedback. At this critical stage of the life course both institutions can improve, to eliminate experiences of perceived disrespectful behavior.
Placental and Cord Blood DNA Methylation Changes Associated With Gestational Diabetes Mellitus in a Marginalized Population: The Untold Role of Saturated Fats.
The role of DNA methylation (DNAm) and its modulation by dietary factors in gestational diabetes mellitus (GDM) remains underexplored, particularly in marginalized populations. This study investigates DNAm alterations in GDM-exposed cord blood and placenta and their association with maternal dietary quality and single nutrient intake in a low-income population from the Myanmar-Thailand border. A matched case-control design (GDM: n = 38, controls: n = 34) was selected from a Myanmar-Thailand pregnancy cohort. Dietary intake was assessed via 24-h recalls and analyzed using Nutritionist Pro, with dietary quality evaluated by the healthy eating index (HEI). DNAm was profiled in 72 cord blood and 72 placental samples using the Infinium MethylationEPIC array. Significant differences in dietary vitamin D, total folate, and saturated fat intake were observed between the groups. RnBeads analyses revealed hypomethylation as the predominant DNAm pattern in GDM, particularly at ADORA2B (placenta) and ZFP57 (cord blood) promoters. The excessive intake of saturated fats was associated with GDM hypomethylation profiles and negatively correlated with ZFP57 methylation levels. This study highlights the influence of saturated fat intake on epigenetic changes in pregnancy, revealing potential biomarkers for GDM and emphasizing the need for tailored, population-specific nutritional interventions to mitigate transgenerational health impacts.
Global, regional, and national prevalence of adult overweight and obesity, 1990-2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021.
BACKGROUND: Overweight and obesity is a global epidemic. Forecasting future trajectories of the epidemic is crucial for providing an evidence base for policy change. In this study, we examine the historical trends of the global, regional, and national prevalence of adult overweight and obesity from 1990 to 2021 and forecast the future trajectories to 2050. METHODS: Leveraging established methodology from the Global Burden of Diseases, Injuries, and Risk Factors Study, we estimated the prevalence of overweight and obesity among individuals aged 25 years and older by age and sex for 204 countries and territories from 1990 to 2050. Retrospective and current prevalence trends were derived based on both self-reported and measured anthropometric data extracted from 1350 unique sources, which include survey microdata and reports, as well as published literature. Specific adjustment was applied to correct for self-report bias. Spatiotemporal Gaussian process regression models were used to synthesise data, leveraging both spatial and temporal correlation in epidemiological trends, to optimise the comparability of results across time and geographies. To generate forecast estimates, we used forecasts of the Socio-demographic Index and temporal correlation patterns presented as annualised rate of change to inform future trajectories. We considered a reference scenario assuming the continuation of historical trends. FINDINGS: Rates of overweight and obesity increased at the global and regional levels, and in all nations, between 1990 and 2021. In 2021, an estimated 1·00 billion (95% uncertainty interval [UI] 0·989-1·01) adult males and 1·11 billion (1·10-1·12) adult females had overweight and obesity. China had the largest population of adults with overweight and obesity (402 million [397-407] individuals), followed by India (180 million [167-194]) and the USA (172 million [169-174]). The highest age-standardised prevalence of overweight and obesity was observed in countries in Oceania and north Africa and the Middle East, with many of these countries reporting prevalence of more than 80% in adults. Compared with 1990, the global prevalence of obesity had increased by 155·1% (149·8-160·3) in males and 104·9% (95% UI 100·9-108·8) in females. The most rapid rise in obesity prevalence was observed in the north Africa and the Middle East super-region, where age-standardised prevalence rates in males more than tripled and in females more than doubled. Assuming the continuation of historical trends, by 2050, we forecast that the total number of adults living with overweight and obesity will reach 3·80 billion (95% UI 3·39-4·04), over half of the likely global adult population at that time. While China, India, and the USA will continue to constitute a large proportion of the global population with overweight and obesity, the number in the sub-Saharan Africa super-region is forecasted to increase by 254·8% (234·4-269·5). In Nigeria specifically, the number of adults with overweight and obesity is forecasted to rise to 141 million (121-162) by 2050, making it the country with the fourth-largest population with overweight and obesity. INTERPRETATION: No country to date has successfully curbed the rising rates of adult overweight and obesity. Without immediate and effective intervention, overweight and obesity will continue to increase globally. Particularly in Asia and Africa, driven by growing populations, the number of individuals with overweight and obesity is forecast to rise substantially. These regions will face a considerable increase in obesity-related disease burden. Merely acknowledging obesity as a global health issue would be negligent on the part of global health and public health practitioners; more aggressive and targeted measures are required to address this crisis, as obesity is one of the foremost avertible risks to health now and in the future and poses an unparalleled threat of premature disease and death at local, national, and global levels. FUNDING: Bill & Melinda Gates Foundation.
Global, regional, and national prevalence of child and adolescent overweight and obesity, 1990-2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021.
BACKGROUND: Despite the well documented consequences of obesity during childhood and adolescence and future risks of excess body mass on non-communicable diseases in adulthood, coordinated global action on excess body mass in early life is still insufficient. Inconsistent measurement and reporting are a barrier to specific targets, resource allocation, and interventions. In this Article we report current estimates of overweight and obesity across childhood and adolescence, progress over time, and forecasts to inform specific actions. METHODS: Using established methodology from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021, we modelled overweight and obesity across childhood and adolescence from 1990 to 2021, and then forecasted to 2050. Primary data for our models included 1321 unique measured and self-reported anthropometric data sources from 180 countries and territories from survey microdata, reports, and published literature. These data were used to estimate age-standardised global, regional, and national overweight prevalence and obesity prevalence (separately) for children and young adolescents (aged 5-14 years, typically in school and cared for by child health services) and older adolescents (aged 15-24 years, increasingly out of school and cared for by adult services) by sex for 204 countries and territories from 1990 to 2021. Prevalence estimates from 1990 to 2021 were generated using spatiotemporal Gaussian process regression models, which leveraged temporal and spatial correlation in epidemiological trends to ensure comparability of results across time and geography. Prevalence forecasts from 2022 to 2050 were generated using a generalised ensemble modelling approach assuming continuation of current trends. For every age-sex-location population across time (1990-2050), we estimated obesity (vs overweight) predominance using the log ratio of obesity percentage to overweight percentage. FINDINGS: Between 1990 and 2021, the combined prevalence of overweight and obesity in children and adolescents doubled, and that of obesity alone tripled. By 2021, 93·1 million (95% uncertainty interval 89·6-96·6) individuals aged 5-14 years and 80·6 million (78·2-83·3) aged 15-24 years had obesity. At the super-region level in 2021, the prevalence of overweight and of obesity was highest in north Africa and the Middle East (eg, United Arab Emirates and Kuwait), and the greatest increase from 1990 to 2021 was seen in southeast Asia, east Asia, and Oceania (eg, Taiwan [province of China], Maldives, and China). By 2021, for females in both age groups, many countries in Australasia (eg, Australia) and in high-income North America (eg, Canada) had already transitioned to obesity predominance, as had males and females in a number of countries in north Africa and the Middle East (eg, United Arab Emirates and Qatar) and Oceania (eg, Cook Islands and American Samoa). From 2022 to 2050, global increases in overweight (not obesity) prevalence are forecasted to stabilise, yet the increase in the absolute proportion of the global population with obesity is forecasted to be greater than between 1990 and 2021, with substantial increases forecast between 2022 and 2030, which continue between 2031 and 2050. By 2050, super-region obesity prevalence is forecasted to remain highest in north Africa and the Middle East (eg, United Arab Emirates and Kuwait), and forecasted increases in obesity are still expected to be largest across southeast Asia, east Asia, and Oceania (eg, Timor-Leste and North Korea), but also in south Asia (eg, Nepal and Bangladesh). Compared with those aged 15-24 years, in most super-regions (except Latin America and the Caribbean and the high-income super-region) a greater proportion of those aged 5-14 years are forecasted to have obesity than overweight by 2050. Globally, 15·6% (12·7-17·2) of those aged 5-14 years are forecasted to have obesity by 2050 (186 million [141-221]), compared with 14·2% (11·4-15·7) of those aged 15-24 years (175 million [136-203]). We forecasted that by 2050, there will be more young males (aged 5-14 years) living with obesity (16·5% [13·3-18·3]) than overweight (12·9% [12·2-13·6]); while for females (aged 5-24 years) and older males (aged 15-24 years), overweight will remain more prevalent than obesity. At a regional level, the following populations are forecast to have transitioned to obesity (vs overweight) predominance before 2041-50: children and adolescents (males and females aged 5-24 years) in north Africa and the Middle East and Tropical Latin America; males aged 5-14 years in east Asia, central and southern sub-Saharan Africa, and central Latin America; females aged 5-14 years in Australasia; females aged 15-24 years in Australasia, high-income North America, and southern sub-Saharan Africa; and males aged 15-24 years in high-income North America. INTERPRETATION: Both overweight and obesity increased substantially in every world region between 1990 and 2021, suggesting that current approaches to curbing increases in overweight and obesity have failed a generation of children and adolescents. Beyond 2021, overweight during childhood and adolescence is forecast to stabilise due to further increases in the population who have obesity. Increases in obesity are expected to continue for all populations in all world regions. Because substantial change is forecasted to occur between 2022 and 2030, immediate actions are needed to address this public health crisis. FUNDING: Bill & Melinda Gates Foundation and Australian National Health and Medical Research Council.
Vaginal microbiota and cytokine levels predict preterm delivery in Asian women
Abstract Background: Preterm birth (PTB) is the most common cause of neonatal morbidity and mortality worldwide. Approximately half of PTBs are linked with microbial etiologies, including pathologic changes to the vaginal microbiota, which vary according to ethnicity. Globally more than 50% of PTBs occur in Asia, but studies of the vaginal microbiome and its association with pregnancy outcomes in Asian women are lacking. This study aimed to characterize the vaginal microbiome and cytokine environment of 18 Karen and Burman pregnant women who delivered preterm and 36 matched controls delivering at full term. Results: Using 16S ribosomal RNA gene sequencing we identified a predictive vaginal microbiota signature for PTB that was detectable as early as the first trimester of pregnancy, characterized by higher levels of Prevotella buccalis , and lower levels of Lactobacillus crispatus and Finegoldia , accompanied by decreased levels of cytokines including IFNγ, IL-4 and TNFα. Conclusion: Our findings highlight new opportunities to predict PTB in Asian women in low-resource settings who are at highest risk of adverse outcomes from unexpected PTB, as well as in Burman/Karen ethnic minority groups in high-resource regions.
Early mucosal responses following a randomised controlled human inhaled infection with attenuated Mycobacterium bovis BCG.
The development of an effective vaccine against Mycobacterium tuberculosis is hampered by an incomplete understanding of immunoprotective mechanisms. We utilise an aerosol human challenge model using attenuated Mycobacterium bovis BCG, in BCG-naïve UK adults. The primary endpoint of this study (NCT03912207) was to characterise the early immune responses induced by aerosol BCG infection, the secondary endpoint was to identify immune markers associated with in-vitro protection. Blinded volunteers were randomised to inhale 1 × 107 CFU aerosolised BCG or 0.9% saline (20:6); and sequentially allocated to bronchoscopy at day 2 or 7 post-inhalation (10 BCG, 3 saline each timepoint). In the bronchoalveolar lavage post-aerosol BCG infection, there was an increase in frequency of eosinophils, neutrophils, NK cells and Donor-Unrestricted T cells at day 7, and the frequency of antigen presenting cells decreased at day 7 compared with day 2. The frequency of interferon-gamma+ BCG-specific CD4+ T cells increased in the BAL and peaked in the blood at day 7 post-BCG infection compared to day 2. BAL cells at day 2 and day 7 upregulated gene pathways related to phagocytosis, MHC-II antigen loading, T cell activation and proliferation. BCG's lack of key virulence factors and its failure to induce granulomas, may mean the observed immune responses do not fully recapitulate Mycobacterium tuberculosis infection. However, human infection models can provide unique insights into early immune mechanisms, informing vaccine design for complex pathogens.
Characterizing Uncertainty in Deep Convection Triggering Using Explainable Machine Learning
Realistically representing deep atmospheric convection is important for accurate numerical weather and climate simulations. However, parameterizing where and when deep convection occurs (“triggering”) is a well-known source of model uncertainty. Most triggers parameterize convection deterministically, without considering the uncertainty in the convective state as a stochastic process. In this study, we develop a machine learning model, a random forest, that predicts the probability of deep convection, and then apply clustering of Shapley additive explanations (SHAP) values, an explainable machine learning method, to characterize the uncertainty of convective events. The model uses observed large-scale atmospheric variables from the Atmospheric Radiation Measurement constrained variational analysis dataset over the Southern Great Plains, United States. The analysis of feature importance shows which mechanisms driving convection are most important, with large-scale vertical velocity providing the highest predictive power for more certain, or easier to predict, convective events, followed by the dynamic generation rate of dilute convective available potential energy. Predictions of uncertain, or harder to predict, convective events instead rely more on other features such as precipitable water or low-level temperature. The model outperforms conventional convective triggers. This suggests that probabilistic machine learning models can be used as stochastic parameterizations to improve the occurrence of convection in weather and climate models in the future.
Adaptive Design for Phase II/III Platform Trial of Lassa Fever Therapeutics.
The current recommendation for treating Lassa fever with ribavirin is supported only by weak evidence. Given the persistent effects in areas with endemic transmission and epidemic potential, there is an urgent need to reassess ribavirin and investigate other potential therapeutic candidates; however, a robust clinical trial method adapted to Lassa fever epidemiology has not yet been established. We propose an adaptive phase II/III multicenter randomized controlled platform trial that uses a superiority framework with an equal allocation ratio and accounts for challenges selecting the primary end point and estimating the target sample size by using an interim analysis.
Invertible Neural Networks for Probabilistic Aerosol Optical Depth Retrieval
Satellite remote sensing is the primary source of global aerosol observations, providing essential data for understanding aerosol-climate interactions and constraining global climate models. To solve the inverse problem at the heart of the retrieval process, traditional algorithms must make simplifications and often cannot quantify uncertainty. In this study, we explore the use of invertible neural networks (INNs) for retrieving aerosol optical depth (AOD) from spectral top-of-atmosphere (TOA) reflectance. INNs can handle the inherent uncertainty of underdetermined inverse problems. They model the forward and inverse processes simultaneously while learning additional random latent variables used to recover full nonparametric posterior distributions for the inverse predictions. We develop location-specific INNs for MODIS sensor data, training on synthetic datasets generated by combining atmospheric reflectance from MODIS dark target (DT) lookup tables (LUTs) and surface reflectance from a MODIS bidirectional reflectance product. The INNs successfully emulate the forward problem and achieve accurate AOD inversion results on synthetic test sets (RMSE 0.05 ). The posterior distributions obtained are reliable (mean absolute calibration error (MACE) 2.5 %), efficiently providing informative predictive uncertainty estimates. In addition, the INNs' invertible architecture is found to promote physically consistent predictions and uncertainties. To further validate them in a real-world context, the INNs are applied to MODIS L1B reflectance observations to produce full-resolution AOD estimates with pixel-level uncertainties. The retrievals are compared to collocated ground measurements from the Aeronet network. The INNs obtain good accuracy in all tested locations in line with the operational DT AOD product (RMSE 0.1 , 74% within DT expected error (EE) bounds). The INNs are also able to retrieve AOD over bright surfaces where DT cannot be applied. Despite uncovered limitations out-of-distribution, the INNs show consistent skill in target domains across diverse land surfaces. The INNs' unique modeling and uncertainty quantification features have the potential to enhance aerosol and climate studies in various real-world contexts.
Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV).
BACKGROUND: The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine were repurposed for the treatment of early COVID-19 based on their antiviral activity in vitro, and observational and clinical trial evidence suggesting they prevented progression to severe disease. However, these SSRIs have not been recommended in therapeutic guidelines and their antiviral activity in vivo has not been characterised. METHODS: PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform trial running in Thailand, Brazil, Pakistan, and Laos. We recruited low-risk adult outpatients aged 18-50 with early symptomatic COVID-19 (symptoms <4 days) between 5 April 2022 and 8 May 2023. Patients were assigned using block randomisation to one of eleven treatment arms including oral fluoxetine (40 mg/day for 7 days), or no study drug. Uniform randomisation ratios were applied across the active treatment groups while the no study drug group comprised ≥20% of patients at all times. The primary endpoint was the rate of oropharyngeal viral clearance assessed until day 7. Measurements were taken daily between days 0 and 7 and analysed in a modified intention-to-treat population (>2 days follow-up).The viral clearance rate was estimated under a Bayesian hierarchical linear model fitted to the log10 viral densities measured in standardised duplicate oropharyngeal swab eluates taken daily over one week (18 measurements per patient). Secondary endpoints were all-cause hospital admission at 28 days, and time to resolution of fever and symptoms. This ongoing trial is registered at ClinicalTrials.gov (NCT05041907). FINDINGS: 271 patients were concurrently randomised to either fluoxetine (n = 120) or no study drug (n = 151). All patients had received at least one COVID-19 vaccine dose and 67% were female (182/271). In the primary analysis, viral clearance rates following fluoxetine were compatible with a small or no increase relative to the no study drug arm (15% increase; 95% credible interval (CrI): -2 to 34%). There were no deaths or hospitalisations in either arm. There were no significant differences in times to symptom resolution or fever clearance between the fluoxetine and the no study drug arms (although only a quarter of patients were febrile at baseline). Fluoxetine was well tolerated, there were no serious adverse events and only one grade 3 adverse event in the intervention arm. INTERPRETATION: Overall, the evidence from this study is compatible with fluoxetine having a weak in vivo antiviral activity against SARS-CoV-2, although the primary endpoint is also compatible with no effect. This level of antiviral efficacy is substantially less than with other currently available antiviral drugs. FUNDING: Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator.
Coming to terms with climate change: a glossary for climate change impacts on mental health and well-being.
Climate change is a major threat to global health. Its effects on physical health are increasingly recognised, but mental health impacts have received less attention. The mental health effects of climate change can be direct (resulting from personal exposure to acute and chronic climatic changes), indirect (via the impact on various socioeconomic, political and environmental determinants of mental health) and overarching (via knowledge, education and awareness of climate change). These impacts are unequally distributed according to long-standing structural inequities which are exacerbated by climate change. We outline key concepts and pathways through which climate change may affect mental health and explore the responses to climate change at different levels, from emotions to politics, to highlight the need for multilevel action. We provide a broad reference to help guide researchers, practitioners and policy-makers in the use and understanding of different terms in this rapidly growing interdisciplinary field.
Self-monitoring of blood pressure following a stroke or transient ischaemic attack (TASMIN5S): a randomised controlled trial.
BACKGROUND: Blood pressure (BP) control following stroke is important but currently sub-optimal. This trial aimed to determine whether self-monitoring of hypertension with telemonitoring and a treatment escalation protocol, results in lower BP than usual care in people with previous stroke or transient ischaemic attack (TIA). METHODS: Unblinded randomised controlled trial, comparing a BP telemonitoring-based intervention with control (usual care) for hypertension management in 12 primary care practices in England. People with previous stroke or TIA with clinic systolic BP 130-180 mmHg, taking ≤ 3 antihypertensive medications and on stable treatment for at least four weeks were randomised 1:1 using secure online system to intervention or control. The BP:Together intervention comprised self-monitoring of blood pressure with a digital behavioural intervention which supported telemonitoring of self-monitored BP with feedback to clinicians and patients regarding medication titration. The planned primary outcome was difference in clinic measured systolic BP 12 months from randomisation but was not available following early study termination due to withdrawal of funding during the COVID-19 pandemic. Instead, in addition to pre-randomised data, routinely recorded BP was extracted from electronic patient records both pre- and post-randomisation and presented descriptively only. An intention to treat approach was taken. RESULTS: From 650 postal invitations, 129 (20%) responded, of whom 95 people had been screened for eligibility prior to the pandemic (November 2019-March 2020) and 55 (58%) were randomised. Pre-randomisation routinely recorded mean BP was 145/78 mmHg in the control (n = 26) and 145/79 mmHg in the self-monitoring (n = 21) groups. Post-randomisation mean BP was 134/73 mmHg in the control (n = 19) and 130/75 mmHg in the self-monitoring (n = 25) groups. Participants randomised to self-monitoring used the intervention for ≥ 7 months in 25/27 (93%) of cases. CONCLUSIONS: Recruitment of people with stroke/TIA to a trial comparing a BP self-monitoring and digital behavioural intervention to usual care was feasible prior to the COVID-19 pandemic and the vast majority of those randomised to intervention used it while the trial was running. Routinely recorded blood pressure control improved in both groups. Digital interventions including self-monitoring are feasible for people with stroke/TIA and should be definitively evaluated in future trials. TRIAL REGISTRATION: ISRCTN57946500 06/09/2019 Prospective.
‘The UNIVERSITY will be for the people’: arts, humanities and the founding of the civic universities
The paper addresses the current crisis in the Arts and Humanities by a foray into history, looking at the ideals and expectations that lay behind the founding of the civic universities in the late-19th and early-20th centuries. Focusing particularly on the case of the University of Sheffield, it explores what founding a university ‘for’ the people meant at that time, and the support from all sides for an education that was not only open to all, but encompassed Literature, Music Education (following the Hadow Reports) and Philosophy as well as the Sciences and more technical instruction. Public engagement, in multiple forms, lay at the heart of these conceptions of a civic university. Considering our current situation, the paper suggests it is time to overturn misplaced conceptions of a ‘useful’ education, and to return to earlier ideals of a university that was truly for the people. (This article is published in the thematic collection ‘The arts and humanities: rethinking value for today—views from Fellows of the British Academy’, edited by Isobel Armstrong.).