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We lead multidisciplinary applied research and training to rethink the way health care is delivered in general practice and across the community.
Implementing the NIHR Oxford Health BRC's Equality, Diversity and Inclusion Strategy
The National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre (BRC) published its first equality, diversity and inclusion (EDI) strategy in 2023. This 5-year strategy aims to establish and enhance the evidence base for EDI, including data collection processes to enhance the diversity of research participants and the workforce. The NIHR has started to collect protected characteristics from applicants for research funding. Although the collection of the data is optional, it could become mandatory in the future. At the Public Mental Health Implementation Centre (PMHIC), of the Royal College of Psychiatry, we undertook a mapping and scoping project to provide Oxford Health BRC partners with insights into data collection for EDI purposes at the local level and identify any challenges and opportunities. This report also proposes solutions to overcoming possible ethical dilemmas, as well as enablers and barriers to implementing the BRC’s EDI strategy.
Recommendation to update the British Society for Cutaneous Allergy corticosteroid series
Background Patch testing is an important investigation when dermatitis is unresponsive to, or worsened by, topical corticosteroid treatment. There is a balance to be struck between testing too many allergens, which is expensive, time consuming and risks causing sensitization, and testing too few, which risks missing the diagnosis. The current British Society for Cutaneous Allergy (BSCA) corticosteroid series comprises eight allergens and was last updated in February 2007. Aim To review and update the BSCA corticosteroid series. Methods We retrospectively analysed data from 16 patch test centres in the UK and Ireland for all patients who were patch tested to a corticosteroid series between August 2017 and July 2019. We recorded the allergens tested, the number and percentage tested to a corticosteroid series and the number of positive results for each allergen. We identified the allergens that test positive in≥0.1% of selectively tested patients. Results Overall, 3531 patients were tested to a corticosteroid series in the 16 centres. The number of allergens tested ranged from 7 to 18 (mean 10). The proportion of patch test patients who were tested to a corticosteroid series ranged from 1% to 99%. Six allergens in the 2017 BSCA series tested positive in≥0.1% of patients. Nine allergens not in the BSCA corticosteroid series tested positive in≥0.1% of patients. Conclusion This audit demonstrates the importance of regular review of recommended series and the significant variations in practice. The new BSCA corticosteroid series that we recommend contains 13 haptens, with the addition of the patient’s own steroid creams as appropriate.
Total hip replacement and surface replacement for the treatment of pain and disability resulting from end-stage arthritis of the hip (review of technology appraisal guidance 2 and 44): systematic review and economic evaluation
BACKGROUND: Total hip replacement (THR) involves the replacement of a damaged hip joint with an artificial hip prosthesis. Resurfacing arthroplasty (RS) involves replacement of the joint surface of the femoral head with a metal surface covering.
Aspirin in primary prevention of cardiovascular disease and cancer: A systematic review of the balance of evidence from reviews of randomized trials
Background: Aspirin has been recommended for primary prevention of cardiovascular disease (CVD) and cancer, but overall benefits are unclear. We aimed to use novel methods to re-evaluate the balance of benefits and harms of aspirin using evidence from randomised controlled trials, systematic reviews and meta-analyses. Methods and Findings: Data sources included ten electronic bibliographic databases, contact with experts, and scrutiny of reference lists of included studies. Searches were undertaken in September 2012 and restricted to publications since 2008. Of 2,572 potentially relevant papers 27 met the inclusion criteria. Meta-analysis of control arms to estimate event rates, modelling of all-cause mortality and L'Abbé plots to estimate heterogeneity were undertaken. Absolute benefits and harms were low: 60-84 major CVD events and 34-36 colorectal cancer deaths per 100,000 person-years were averted, whereas 46-49 major bleeds and 68-117 gastrointestinal bleeds were incurred. Reductions in all-cause mortality were minor and uncertain (Hazard Ratio 0.96; 95% CI: 0.90-1.02 at 20 years, Relative Risk [RR] 0.94, 95% CI: 0.88-1.00 at 8 years); there was a non-significant change in total CVD (RR 0.85, 95% CI: 0.69-1.06) and change in total cancer mortality ranged from 0.76 (95% CI: 0.66-0.88) to 0.93 (95% CI: 0.84-1.03) depending on follow-up time and studies included. Risks were increased by 37% for gastrointestinal bleeds (RR 1.37, 95% CI: 1.15-1.62), 54%-66% for major bleeds (Rate Ratio from IPD analysis 1.54, 95% CI: 1.30-1.82, and RR 1.62, 95% CI: 1.31-2.00), and 32%-38% for haemorrhagic stroke (Rate Ratio from IPD analysis 1.32; 95% CI: 1.00-1.74; RR 1.38; 95% CI: 1.01-1.82). Conclusions: Findings indicate small absolute effects of aspirin relative to the burden of these diseases. When aspirin is used for primary prevention of CVD the absolute harms exceed the benefits. Estimates of cancer benefit rely on selective retrospective re-analysis of RCTs and more information is needed. Copyright © 2013 Sutcliffe et al.
Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer: A systematic review and overview of reviews
Background: Prophylactic aspirin has been considered to be beneficial in reducing the risks of heart disease and cancer. However, potential benefits must be balanced against the possible harm from side effects, such as bleeding and gastrointestinal (GI) symptoms. It is particularly important to know the risk of side effects when aspirin is used as primary prevention - that is when used by people as yet free of, but at risk of developing, cardiovascular disease (CVD) or cancer. In this report we aim to identify and re-analyse randomised controlled trials (RCTs), systematic reviews and meta-analyses to summarise the current scientific evidence with a focus on possible harms of prophylactic aspirin in primary prevention of CVD and cancer. Objectives: To identify RCTs, systematic reviews and meta-analyses of RCTs of the prophylactic use of aspirin in primary prevention of CVD or cancer. To undertake a quality assessment of identified systematic reviews and meta-analyses using meta-analysis to investigate study-level effects on estimates of benefits and risks of adverse events; cumulative meta-analysis; exploratory multivariable meta-regression; and to quantify relative and absolute risks and benefits. Methods: We identified RCTs, meta-analyses and systematic reviews, and searched electronic bibliographic databases (from 2008 September 2012) including MEDLINE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, NHS Centre for Reviews and Dissemination, and Science Citation Index. We limited searches to publications since 2008, based on timing of the most recent comprehensive systematic reviews. Results: In total, 2572 potentially relevant papers were identified and 27 met the inclusion criteria. Benefits of aspirin ranged from 6% reduction in relative risk (RR) for all-cause mortality [RR 0.94, 95% confidence interval (CI) 0.88 to 1.00] and 10% reduction in major cardiovascular events (MCEs) (RR 0.90, 95% CI 0.85 to 0.96) to a reduction in total coronary heart disease (CHD) of 15% (RR 0.85, 95% CI 0.69 to 1.06). Reported pooled odds ratios (ORs) for total cancer mortality ranged between 0.76 (95% CI 0.66 to 0.88) and 0.93 (95% CI 0.84 to 1.03). Inclusion of the Women's Health Study changed the estimated OR to 0.82 (95% CI 0.69 to 0.97). Aspirin reduced reported colorectal cancer (CRC) incidence (OR 0.66, 95% CI 0.90 to 1.02). However, including studies in which aspirin was given every other day raised the OR to 0.91 (95% CI 0.74 to 1.11). Reported cancer benefits appeared approximately 5 years from start of treatment. Calculation of absolute effects per 100,000 patient-years of follow-up showed reductions ranging from 33 to 46 deaths (all-cause mortality), 60-84 MCEs and 47-64 incidents of CHD and a possible avoidance of 34 deaths from CRC. Reported increased RRs of adverse events from aspirin use were 37% for GI bleeding (RR 1.37, 95% CI 1.15 to 1.62), between 54% (RR 1.54, 95% CI 1.30 to 1.82) and 62% (RR 1.62, 95% CI 1.31 to 2.00) for major bleeds, and between 32% (RR 1.32, 95% CI 1.00 to 1.74) and 38% (RR 1.38, 95% CI 1.01 to 1.82) for haemorrhagic stroke. Pooled estimates of increased RR for bleeding remained stable across trials conducted over several decades. Estimates of absolute rates of harm from aspirin use, per 100,000 patient-years of follow-up, were 99-178 for non-trivial bleeds, 46-49 for major bleeds, 68-117 for GI bleeds and 8-10 for haemorrhagic stroke. Meta-analyses aimed at judging risk of bleed according to sex and in individuals with diabetes were insufficiently powered for firm conclusions to be drawn. Limitations: Searches were date limited to 2008 because of the intense interest that this subject has generated and the cataloguing of all primary research in so many previous systematic reviews. A further limitation was our potential over-reliance on study-level systematic reviews in which the person-years of follow-up were not accurately ascertainable. However, estimates of number of events averted or incurred through aspirin use calculated from data in study-level meta-analyses did not differ substantially from estimates based on individual patient data-level meta-analyses, for which person-years of follow-up were more accurate (although based on less-than-complete assemblies of currently available primary studies). Conclusions: We have found that there is a fine balance between benefits and risks from regular aspirin use in primary prevention of CVD. Effects on cancer prevention have a long lead time and are at present reliant on post hoc analyses. All absolute effects are relatively small compared with the burden of these diseases. Several potentially relevant ongoing trials will be completed between 2013 and 2019, which may clarify the extent of benefit of aspirin in reducing cancer incidence and mortality. Future research considerations include expanding the use of IPD meta-analysis of RCTs by pooling data from available studies and investigating the impact of different dose regimens on cardiovascular and cancer outcomes. Funding: The National Institute for Health Research Health Technology Assessment programme. © Queen's Printer and Controller of HMSO 2013.
Protocol: A metabolomic analysis of convalescent inflammatory conditions
Background ‘The term ‘long covid’ describes persistent symptoms following infection with SARS-CoV-2 that are not explained by an alternative diagnosis. It embraces a number of globally used terms and reported prevalence is highly variable. In the United Kingdom (UK) in 2023, approximately 2.9% of the population were thought to be affected. The condition manifests in a constellation of fluctuant symptoms, which persist beyond the acute infection and frequently profoundly impact an individual’s functional and relational capacity. The underlying mechanisms remain imperfectly understood and there is great demand for diagnostic tools that distinguish long covid from other chronic conditions. This study aims to utilise metabolomics to develop such a test and identify potential pathophysiological mechanisms. Methods Blood and urine samples will be collected at two timepoints at least 9 months apart from non-hospitalised individuals with a previous confirmed COVID-19 infection. This population will be divided into those who recovered completely within six weeks and those who continue to experience persistent symptoms. Samples will be analysed using 1H NMR spectroscopy and the resultant metabolomic profiles will be subject to multivariate pattern recognition techniques. This will produce mathematical models capable of distinguishing these long covid and control groups. Symptoms, potential confounders, and qualitative narrative data will be collected alongside this process to add deeper richness to the subsequent analysis. Primary Outcome The creation of a diagnostic test for long covid using 1H NMR metabolomics. Secondary Outcomes The development of algorithms that predict the severity and chronicity of long covid, identification of subgroup differences in metabolomic and immune profiles, and triangulation with symptom and narrative data to produce a deeper understanding of the patient experience. Conclusion This study seeks to advance the understanding of long covid using advanced multi-omic and narrative techniques, which may offer potential diagnostic and therapeutic avenues.
Study protocol: Comparison of different risk prediction modelling approaches for COVID-19 related death using the OpenSAFELY platform.
On March 11th 2020, the World Health Organization characterised COVID-19 as a pandemic. Responses to containing the spread of the virus have relied heavily on policies involving restricting contact between people. Evolving policies regarding shielding and individual choices about restricting social contact will rely heavily on perceived risk of poor outcomes from COVID-19. In order to make informed decisions, both individual and collective, good predictive models are required. For outcomes related to an infectious disease, the performance of any risk prediction model will depend heavily on the underlying prevalence of infection in the population of interest. Incorporating measures of how this changes over time may result in important improvements in prediction model performance. This protocol reports details of a planned study to explore the extent to which incorporating time-varying measures of infection burden over time improves the quality of risk prediction models for COVID-19 death in a large population of adult patients in England. To achieve this aim, we will compare the performance of different modelling approaches to risk prediction, including static cohort approaches typically used in chronic disease settings and landmarking approaches incorporating time-varying measures of infection prevalence and policy change, using COVID-19 related deaths data linked to longitudinal primary care electronic health records data within the OpenSAFELY secure analytics platform.
Prevalence of orthostatic intolerance in long covid clinic patients and healthy volunteers: A multicenter study
Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.
What is quality in long covid care? Lessons from a national quality improvement collaborative and multi-site ethnography
Background: Long covid (post covid-19 condition) is a complex condition with diverse manifestations, uncertain prognosis and wide variation in current approaches to management. There have been calls for formal quality standards to reduce a so-called “postcode lottery” of care. The original aim of this study—to examine the nature of quality in long covid care and reduce unwarranted variation in services—evolved to focus on examining the reasons why standardizing care was so challenging in this condition. Methods: In 2021–2023, we ran a quality improvement collaborative across 10 UK sites. The dataset reported here was mostly but not entirely qualitative. It included data on the origins and current context of each clinic, interviews with staff and patients, and ethnographic observations at 13 clinics (50 consultations) and 45 multidisciplinary team (MDT) meetings (244 patient cases). Data collection and analysis were informed by relevant lenses from clinical care (e.g. evidence-based guidelines), improvement science (e.g. quality improvement cycles) and philosophy of knowledge. Results: Participating clinics made progress towards standardizing assessment and management in some topics; some variation remained but this could usually be explained. Clinics had different histories and path dependencies, occupied a different place in their healthcare ecosystem and served a varied caseload including a high proportion of patients with comorbidities. A key mechanism for achieving high-quality long covid care was when local MDTs deliberated on unusual, complex or challenging cases for which evidence-based guidelines provided no easy answers. In such cases, collective learning occurred through idiographic (case-based) reasoning, in which practitioners build lessons from the particular to the general. This contrasts with the nomothetic reasoning implicit in evidence-based guidelines, in which reasoning is assumed to go from the general (e.g. findings of clinical trials) to the particular (management of individual patients). Conclusion: Not all variation in long covid services is unwarranted. Largely because long covid’s manifestations are so varied and comorbidities common, generic “evidence-based” standards require much individual adaptation. In this complex condition, quality improvement resources may be productively spent supporting MDTs to optimise their case-based learning through interdisciplinary discussion. Quality assessment of a long covid service should include review of a sample of individual cases to assess how guidelines have been interpreted and personalized to meet patients’ unique needs. Study registration: NCT05057260, ISRCTN15022307.
Mobilisation in the EveNing to prevent and TreAt deLirium (MENTAL): a mixed-methods, randomised controlled feasibility trial
Background: Delirium is common in critically ill patients and associated with longer hospital stays, increased morbidity and higher healthcare costs. Non-pharmacological interventions have been advocated for delirium management, however there is little evidence evaluating feasibility and acceptability of physical interventions administered in the evening. The aim of this study was to conduct a feasibility trial of evening mobilisation to prevent and treat delirium in patients admitted to intensive care. Methods: In this mixed-methods, randomised controlled feasibility trial we recruited participants from intensive care units at two university hospitals in the United Kingdom. Eligible participants who were able to respond to verbal stimulus (Richmond agitation and sedation scale ≥3) and expected to stay in intensive care for at least 24 h were randomly assigned (1:1) to receive usual care or usual care plus evening mobilisation. The evening mobilisation was delivered between 19:00 and 21:00, for up to seven consecutive evenings or ICU discharge, whichever was sooner. All outcome assessments were completed by a team member blinded to randomisation and group allocation. Primary objective was to assess feasibility and acceptability of evening mobilisation. Primary feasibility outcomes were recruitment, consent and retention rates, and intervention fidelity. Intervention acceptability was evaluated through semi-structured interviews of participants and staff. Secondary outcomes included prevalence in incidence and duration of delirium, measured using the Confusion Assessment Method for ICU. This trial is registered at ClinicalTrials.gov, NCT05401461. Findings: Between July 16th, 2022, and October 31st, 2022, 58 eligible patients (29 usual care; 29 usual care plus evening mobilisation) were enrolled. We demonstrated the feasibility and acceptability of both the trial design and evening mobilisation intervention. Consent and retention rates over three months were 88% (58/66) and 90% (52/58) respectively, with qualitative analysis demonstrating good acceptability reported by both participants and staff. Secondary outcomes for the evening intervention group compared with the control group were: delirium incidence 5/26 (19%; 95% CI: 6–39%) vs 8/28 (29%; 95% CI: 13–49%) and mean delirium duration 2 days (SD 0.7) vs 4.25 days (SD 2.0). Interpretation: Results of this trial will inform the development of a definitive full-scale randomised controlled trial investigating the effects of evening mobilisation to treat delirium and improve health-related outcomes. Funding: None.
Mobilisation in the EveNing to TreAt deLirium (MENTAL): Protocol for a mixed-methods feasibility randomised controlled trial
Introduction Delirium is common in critically ill patients and is associated with longer hospital stays, increased mortality and higher healthcare costs. A number of risk factors have been identified for the development of delirium in intensive care, two of which are sleep disturbance and immobilisation. Non-pharmacological interventions for the management of intensive care unit (ICU) delirium have been advocated, including sleep protocols and early mobilisation. However, there is a little published evidence evaluating the feasibility and acceptability of evening mobilisation. Methods and analysis Mobilisation in the EveNing to TreAt deLirium (MENTAL) is a two-centre, mixed-methods feasibility randomised controlled trial (RCT). Sixty patients will be recruited from ICUs at two acute NHS trusts and randomised on a 1:1 basis to receive additional evening mobilisation, delivered between 19:00 and 21:00, or standard care. The underpinning hypothesis is that the physical exertion associated with evening mobilisation will promote better sleep, subsequently having the potential to reduce delirium incidence. The primary objective is to assess the feasibility and acceptability of a future, multicentre RCT. The primary outcome measures, which will determine feasibility, are recruitment and retention rates, and intervention fidelity. Acceptability of the intervention will be evaluated through semi-structured interviews of participants and staff. Secondary outcome measures include collecting baseline, clinical and outcome data to inform the power calculations of a future definitive trial. Ethics and dissemination Ethical approval has been obtained through the Wales Research and Ethics Committee 6 (22/WA/0106). Participants are required to provide written informed consent. We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media. Trial registration number NCT05401461.
Cognitive dysfunction after covid-19
As of March 2023, when the Office for National Statistics stopped collecting data on this condition, 1.879 million individuals had self-assessed as having long covid - symptoms lasting more than 12 weeks following acute covid-19 infection. Of these, the proportion of individuals with symptoms lasting two years or more is around 42%, suggesting a decline in new cases of long covid but a persistence of those with ongoing symptoms.1 Some systematic reviews and meta-analyses have reported that up to a third of such individuals have persistent symptoms of cognitive impairment,23 but estimates vary widely and are complicated by methodological heterogeneity - eg, study size, assessment approach, follow-up duration, and different sampling frames (from self-reported surveys4 to large retrospective matched cohort studies of health records5), as discussed in a recent meta-analysis.6
Hypertension and Atrial Fibrillation: A Frontier Review From the AF-SCREEN International Collaboration.
Hypertension is the leading modifiable risk factor for atrial fibrillation (AF) and is estimated to be present in >70% of AF patients. This Frontiers Review was prepared by 29 expert members of the AF-SCREEN International Collaboration to summarize existing evidence and knowledge gaps on links between hypertension, AF, and their cardiovascular sequelae; simultaneous screening for hypertension and AF; and the prevention of AF through antihypertensive therapy. Hypertension and AF are inextricably connected. Both are easily diagnosed, often silent, and frequently treated inadequately. Together, they additively increase the risk of ischemic stroke, heart failure, and many types of dementia, resulting in greater all-cause mortality, considerable disease burden, and increased health care expenditures. Automated upper arm cuff blood pressure devices with implemented technology can be used to simultaneously detect both hypertension and AF. However, positive screening for AF with an oscillometric blood pressure monitor still requires ECG confirmation. The current evidence suggests that high-risk individuals aged ≥65 years or with treatment-resistant hypertension could benefit from AF screening. Since antihypertensive therapy effectively lowers AF risk, particularly in individuals with left ventricular dysfunction, hypertension should be the key target for AF prediction and prevention rather than merely a comorbidity of AF. Nevertheless, several important gaps in knowledge need to be filled over the next years, including the ideal method and selection of patients for simultaneous screening of hypertension and AF and the optimal antihypertensive drug class and blood pressure targets for AF prevention.
The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis
Background: Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date. Methods: We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. Findings: We estimated 541 000 deaths (95% UI 370 000–763 000) associated with bacterial AMR and 133 000 deaths (90 100–188 000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195 000 deaths (104 000–333 000) associated with resistance, followed by intra-abdominal infections (127 000 deaths [81 900–185 000]) and respiratory infections (120 000 deaths [94 500–154 000]). Seven leading pathogens were responsible for about 457 000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen–drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR. Interpretation: The high levels of resistance for several important bacterial pathogens and pathogen–drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen–drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours. Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.
Fatal journeys: causes of death in international travellers in South America
BACKGROUND: Understanding mortality among travellers is essential for mitigating risks and enhancing travel safety. However, limited evidence exists on severe illnesses and injuries leading to death among travellers, particularly in low- and middle-income countries and remote regions. METHODS: We conducted a retrospective census study using country-level observational data from death certificates of travellers of seven South American countries (Argentina, Brazil, Chile, Colombia, Ecuador, Peru and Uruguay) from 2017 to 2021. Causes of death were evaluated using ICD-10 codes, categorized into non-communicable diseases (NCDs), communicable diseases and injuries. We quantified causes of death by demographic characteristics (e.g. age, sex) and geographical variables. Chi-square tests were used to assess differences between categories. We calculated crude mortality rates and incidence rate ratios (IRRs) per country's subregions. RESULTS: A total of 17 245 deaths were reported. NCDs (55%) were the most common cause of death, followed by communicable diseases (23.4%) and injuries (18.1%). NCD-associated deaths increased after age 55 years and were highest among ≥85 years. Communicable diseases were more common at younger age (<20 years). Injury-associated deaths were more common in men (79.9%) and 25-29-year-olds (17.1%). Most deaths (68.2%) could have been avoided by prevention or treatment. Mortality risk was higher among travellers in bordering regions between countries. In Roraima (Brazil) and Norte de Santander (Colombia), locations bordering Venezuela, the death IRR was 863 and 60, respectively. These countries' reference mortality rates in those regions were much lower. More than 80% of the deaths in these border regions of Brazil and Colombia involved Venezuelan citizens. CONCLUSION: The study identified risk factors and high-risk locations for deaths among travellers in seven countries of South America. Our findings underscore the need for specific health interventions tailored to traveller demographics and destination to optimize prevention of avoidable deaths in South America.
Contamination effects in cluster randomised trials of TB interventions
BACKGROUNDCluster randomised trials (CRTs) of TB interventions have achieved mixed results, with many lacking significant reductions in outcomes. Contamination in CRTs, resulting from short and long-term movement between clusters and the general population, may dilute the impact of measured intervention.METHODSWe systematically reviewed the literature to identify CRTs that aimed to capture the population-level effects of the intervention on TB. Details of trial designs, interventions, outcomes, populations, cluster configurations, and geographic data were extracted to produce text summaries, descriptive statistics, and spatial analyses.RESULTSWe screened 1,039 abstracts and included 20 reports from seven CRTs. The median number of clusters was 32 (IQR 23-61), with populations ranging from 400-50,000 individuals per cluster. Four trials reported spatial data, from which the mean distance between clusters was 12.3 km (range 3.71-35.9). Several trials acknowledged design limitations, such as small cluster sizes and population mobility, which could have led to underestimations of intervention impact. Trials used various geographic, social, and pre-existing TB measures to select and allocate study clusters. Data on the potential for contamination are inconsistent.CONCLUSIONGaps remain in the reporting of methods and results, suggesting necessary improvements to standardised reporting tools. These insights can inform recommendations for improved CRT design and reporting practices..
Cost-effectiveness of integrated maternal HIV, syphilis, and hepatitis B screening opt-out strategies in Nepal: a modelling study
Background: The World Health Organisation (WHO) developed a comprehensive framework encouraging an integrated approach to achieve triple elimination of vertical transmission of HIV, syphilis, and hepatitis B in Asia. Current screening practices in Nepal show significantly lower coverage for syphilis and hepatitis B compared to HIV suggesting potential for integration. In this study, we aimed to model the cost-effectiveness of triple screening during antenatal care in Nepal. Methods: We modelled maternal HIV, hepatitis B, and syphilis cascade of care and their corresponding disease states using disease-specific Markov models over a 20-year horizon with a cycle length of one year. We compared dual integrated screening for HIV and syphilis and triple integrated screening for HIV, syphilis, and hepatitis B with HIV screening only. Costs were estimated from a provider's perspective. Results were presented as incremental cost-effectiveness ratios (ICERs). Univariable and probabilistic sensitivity analyses were conducted. Findings: Our modelling analysis showed that dual-integrated screening for HIV and syphilis was highly cost-effective when compared to current strategy of screening for HIV only (ICERs of US$18). Triple-integrated antenatal screening for HIV, syphilis, and hepatitis B was highly cost-effective compared with dual-integrated strategy with an ICER of US$114. Moreover, 100% and 98% of the probabilistic sensitivity analysis estimates for dual- and triple-integrated screening were proven cost-effective, compared to HIV-only screening. Interpretation: Our results support WHO recommendations for implementing integrated triple antenatal screening in Nepal and Asia more broadly, aiming to reduce maternal and neonatal morbidity through early detection and intervention. Funding: No funding was reported.