A significant proportion of individuals suffering from post COVID-19 condition (PCC, also known as long COVID) can present with persistent, disabling fatigue similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-viral fatigue syndromes. There remains no clear pharmacological therapy for patients with this subtype of PCC, which can be referred to as post-COVID fatigue syndrome (PCFS). A low dose of the opioid antagonist naltrexone (ie, low-dose naltrexone (LDN)) has emerged as an off-label treatment for treating fatigue and other symptoms in PCC. However, only small, non-controlled studies have assessed LDN in PCC, so randomised trials are urgently required.

A prospective, randomised, double-blind, parallel arm, placebo-controlled phase II trial will be performed to assess the efficacy of LDN for improving fatigue in PCFS. The trial will be decentralised and open to eligible individuals throughout the Canadian province of British Columbia (BC). Participants will be recruited through the province-wide Post-COVID-19 Interdisciplinary Clinical Care Network (PC-ICCN) and research volunteer platform (REACH BC). Eligible participants will be 19–69 years old, have had a confirmed or physician-suspected SARS-CoV-2 infection at least 3 months prior and meet clinical criteria for PCFS adapted from the Institute of Medicine ME/CFS criteria. Individuals who are taking opioid medications, have a history of ME/CFS prior to COVID-19 or history of significant liver disease will be excluded. Participants will be randomised to an LDN intervention arm (n=80) or placebo arm (n=80). Participants in each arm will be prescribed identical capsules starting at 1 mg daily and follow a prespecified schedule for up-titration to 4.5 mg daily or the maximum tolerated dose. The trial will be conducted over 16 weeks, with assessments at baseline, 6, 12 and 16 weeks. The primary outcome will be fatigue severity at 16 weeks evaluated by the Fatigue Severity Scale. Secondary outcomes will include pain Visual Analogue Scale score, overall symptom severity as measured by the Patient Phenotyping Questionnaire Short Form, 7-day step count and health-related quality of life measured by the EuroQol 5-Dimension questionnaire.

The trial has been authorised by Health Canada and approved by The University of British Columbia/Children’s and Women’s Health Centre of British Columbia Research Ethics Board. On completion, findings will be disseminated to patients, caregivers and clinicians through engagement activities within existing PCC and ME/CFS networks. Results will be published in academic journals and presented at conferences.

NCT05430152.

Tuberculosis (TB) remains a public health concern in Kenya despite the massive global efforts towards ending TB. The impediments to TB prevention and care efforts include poor health systems, resource limitations and other sociopolitical contexts that inform policy and implementation. Notably, TB cases are much higher in men than women. Therefore, the political economy analysis (PEA) study provides in-depth contexts and understanding of the gender gaps to access and successful treatment for TB infection.

PEA adopts a qualitative, in-depth approach through key informant interviews (KII) and documentary analysis.

The KIIs were distributed among government entities, academia, non-state actors and community TB groups from Kenya.

The themes identified were mapped onto the applied PEA analysis framework domains. The contextual and institutional issues included gender concerns related to the disconnect between TB policies and gender inclusion aspects, such as low prioritisation for TB programmes, limited use of evidence to inform decisions and poor health system structures. The broad barriers influencing the social contexts for TB programmes were social stigma and cultural norms such as traditional interventions that negatively impact health-seeking behaviours. The themes around the economic situation were poverty and unemployment, food insecurity and malnutrition. The political context centred around the systemic and governance gaps in the health system from the national and devolved health functions.

Broad contextual factors identified from the PEA widen the disparity in targeted gender efforts toward men. Following the development of effective TB policies and strategies, it is essential to have well-planned gendered responsive interventions with a clear implementation plan and monitoring system to enhance access to TB prevention and care.

Sub-Saharan Africa continues to experience a syndemic of HIV and non-communicable diseases (NCDs). Vertical (stand-alone) HIV programming has provided high-quality care in the region, with almost 80% of people living with HIV in regular care and 90% virally suppressed. While integrated health education and concurrent management of HIV, hypertension and diabetes are being scaled up in clinics, innovative, more efficient and cost-effective interventions that include decentralisation into the community are required to respond to the increased burden of comorbid HIV/NCD disease.

This protocol describes procedures for a process evaluation running concurrently with a pragmatic cluster-randomised trial (INTE-COMM) in Tanzania and Uganda that will compare community-based integrated care (HIV, diabetes and hypertension) with standard facility-based integrated care. The INTE-COMM intervention will manage multiple conditions (HIV, hypertension and diabetes) in the community via health monitoring and adherence/lifestyle advice (medicine, diet and exercise) provided by community nurses and trained lay workers, as well as the devolvement of NCD drug dispensing to the community level. Based on Bronfenbrenner’s ecological systems theory, the process evaluation will use qualitative methods to investigate sociostructural factors shaping care delivery and outcomes in up to 10 standard care facilities and/or intervention community sites with linked healthcare facilities. Multistakeholder interviews (patients, community health workers and volunteers, healthcare providers, policymakers, clinical researchers and international and non-governmental organisations), focus group discussions (community leaders and members) and non-participant observations (community meetings and drug dispensing) will explore implementation from diverse perspectives at three timepoints in the trial implementation. Iterative sampling and analysis, moving between data collection points and data analysis to test emerging theories, will continue until saturation is reached. This process of analytic reflexivity and triangulation across methods and sources will provide findings to explain the main trial findings and offer clear directions for future efforts to sustain and scale up community-integrated care for HIV, diabetes and hypertension.

The protocol has been approved by the University College of London (UK), the London School of Hygiene and Tropical Medicine Ethics Committee (UK), the Uganda National Council for Science and Technology and the Uganda Virus Research Institute Research and Ethics Committee (Uganda) and the Medical Research Coordinating Committee of the National Institute for Medical Research (Tanzania). The University College of London is the trial sponsor. Dissemination of findings will be done through journal publications and stakeholder meetings (with study participants, healthcare providers, policymakers and other stakeholders), local and international conferences, policy briefs, peer-reviewed journal articles and publications.

ISRCTN15319595.

To capture UK medical students’ self-reported knowledge and harm assessment of psychedelics and to explore the factors associated with support for changing the legal status of psychedelics to facilitate further clinical research.

Cross-sectional, anonymous online survey of UK medical students using a non-random sampling method.

UK medical schools recognised by the General Medical Council.

132 medical students who had spent an average of 3.8 years (SD=1.4; range: 1–6) in medical school.

Most students (83%) reported that they were aware of psychedelic research and only four participants (3%) said that they were not interested in learning more about this type of research. Although medical students’ harm assessment of psychedelics closely aligned with that of experts, only 17% of students felt well-educated on psychedelic research. Teachings on psychedelics were only rarely encountered in their curriculum (psilocybin: 14.1 (SD=19.9), scale: 0 (never) to 100 (very often)). Time spent at medical schools was not associated with more knowledge about psychedelics (r=0.12, p=0.129). On average, this sample of medical students showed strong support for changing the legal status of psychedelics to facilitate further research into their potential clinical applications (psilocybin: 80.2 (SD=24.8), scale: 0 (strongly oppose) to 100 (strongly support)). Regression modelling indicated that greater knowledge of psychedelics (p

Our findings reveal a significant interest among UK medical students to learn more about psychedelic research and a strong support for further psychedelic research. Future studies are needed to examine how medical education could be refined to adequately prepare medical students for a changing healthcare landscape in which psychedelic-assisted therapy could soon be implemented in clinical practice.

Iron deficiency is a major public health problem that affects the physical and cognitive development of children under 5 years of age (under-5 children) in sub-Saharan Africa (SSA). However, the factors associated with the limited consumption of iron-rich foods in the region are poorly understood.

This study examined the prevalence and determinants of iron-rich food deficiency among under-5 children in 26 SSA countries.

This nationally representative quantitative study employed pooled data from Demographic and Health Surveys conducted between 2010 and 2019.

Representative samples comprising 296 850 under-5 children from the various countries were used. Bivariate and multivariate logistic regression models were used to determine the associations between the lack of iron-rich food uptake and various sociodemographic factors.

The overall prevalence of iron-rich food deficiency among the children in the entire sample was 56.75%. The prevalence of iron-rich food deficiency varied widely across the 26 countries, ranging from 42.76% in Congo Democratic Republic to 77.50% in Guinea. Maternal education, particularly primary education (OR 0.62, 95% CI 0.57 to 0.68) and higher education (OR 0.58, 95% CI 0.52 to 0.64), demonstrated a reduced likelihood of iron-rich food deficiency in the sample. Likewise, paternal education, with both primary education (OR 0.69, 95% CI 0.63 to 0.75) and higher education (OR 0.66, 95% CI 0.60 to 0.73) showed decreased odds of iron-rich food deficiency. Postnatal visits contributed significantly to reducing the odds of iron-rich food deficiency (OR 0.90, 95% CI 0.83 to 0.95), along with antenatal visits, which also had a positive impact (OR 0.84, 95% CI 0.74 to 0.95). Finally, residents in rural areas showed slightly higher odds of iron-rich food deficiency (OR 1.12, 95% CI 1.10 to 1.28).

Based on the findings, interventions targeting iron-food deficiency in the SSA region should take into strong consideration the key determinants highlighted in this study.

A non-contrast CT head scan (NCCTH) is the most common cross-sectional imaging investigation requested in the emergency department. Advances in computer vision have led to development of several artificial intelligence (AI) tools to detect abnormalities on NCCTH. These tools are intended to provide clinical decision support for clinicians, rather than stand-alone diagnostic devices. However, validation studies mostly compare AI performance against radiologists, and there is relative paucity of evidence on the impact of AI assistance on other healthcare staff who review NCCTH in their daily clinical practice.

A retrospective data set of 150 NCCTH will be compiled, to include 60 control cases and 90 cases with intracranial haemorrhage, hypodensities suggestive of infarct, midline shift, mass effect or skull fracture. The intracranial haemorrhage cases will be subclassified into extradural, subdural, subarachnoid, intraparenchymal and intraventricular. 30 readers will be recruited across four National Health Service (NHS) trusts including 10 general radiologists, 15 emergency medicine clinicians and 5 CT radiographers of varying experience. Readers will interpret each scan first without, then with, the assistance of the qER EU 2.0 AI tool, with an intervening 2-week washout period. Using a panel of neuroradiologists as ground truth, the stand-alone performance of qER will be assessed, and its impact on the readers’ performance will be analysed as change in accuracy (area under the curve), median review time per scan and self-reported diagnostic confidence. Subgroup analyses will be performed by reader professional group, reader seniority, pathological finding, and neuroradiologist-rated difficulty.

The study has been approved by the UK Healthcare Research Authority (IRAS 310995, approved 13 December 2022). The use of anonymised retrospective NCCTH has been authorised by Oxford University Hospitals. The results will be presented at relevant conferences and published in a peer-reviewed journal.

NCT06018545.

Invasive non-typhoidal Salmonella (iNTS) serovars are a major cause of community-acquired bloodstream infections in sub-Saharan Africa (SSA). In this setting, Salmonella enterica serovar Typhimurium accounts for two-thirds of infections and is associated with an estimated case fatality rate of 15%–20%. Several iNTS vaccine candidates are in early-stage assessment which—if found effective—would provide a valuable public health tool to reduce iNTS disease burden. The CHANTS study aims to develop a first-in-human Salmonella Typhimurium controlled human infection model, which can act as a platform for future vaccine evaluation, in addition to providing novel insights into iNTS disease pathogenesis.

This double-blind, safety and dose-escalation study will randomise 40–80 healthy UK participants aged 18–50 to receive oral challenge with one of two strains of S. Typhimurium belonging to the ST19 (strain 4/74) or ST313 (strain D23580) lineages. 4/74 is a global strain often associated with diarrhoeal illness predominantly in high-income settings, while D23580 is an archetypal strain representing invasive disease-causing isolates found in SSA. The primary objective is to determine the minimum infectious dose (colony-forming unit) required for 60%–75% of participants to develop clinical or microbiological features of systemic salmonellosis. Secondary endpoints are to describe and compare the clinical, microbiological and immunological responses following challenge. Dose escalation or de-escalation will be undertaken by continual-reassessment methodology and limited within prespecified safety thresholds. Exploratory objectives are to describe mechanisms of iNTS virulence, identify putative immune correlates of protection and describe host–pathogen interactions in response to infection.

Ethical approval has been obtained from the NHS Health Research Authority (London—Fulham Research Ethics Committee 21/PR/0051; IRAS Project ID 301659). The study findings will be disseminated in international peer-reviewed journals and presented at national/international stakeholder meetings. Study outcome summaries will be provided to both funders and participants.

NCT05870150

Inappropriate use of antibiotics is a major driver of antibiotic resistance. A few studies conducted in Africa have documented that about half of hospitalised patients who receive antibiotics should not have received them. A few hospital-based studies that have been conducted in Sierra Leone have documented a high usage of antibiotics in hospitals. Therefore, we conducted a nationwide point prevalence survey on antibiotic use among hospitalised patients in Sierra Leone.

We conducted a hospital-based, cross-sectional survey on the use of antibiotics using the WHO point prevalence survey methodology.

The study was conducted in 26 public and private hospitals that are providing inpatient healthcare services.

All patients admitted to paediatric and adult inpatient wards before or at 08:00 on the survey date were enrolled.

Prevalence of antibiotic use, antibiotics Access, Watch and Reserve (AWaRe) categorisation, indication for antibiotic use prevalence and proportion of bacteria culture done.

Of the 1198 patient records reviewed, 883 (73.7%, 95% CI 71.1% to 76.2%) were on antibiotics. Antibiotic use was highest in the paediatric wards (306, 85.7%), followed by medical wards (158, 71.2%), surgical wards (146, 69.5%), mixed wards (97, 68.8%) and lowest in the obstetrics and gynaecology wards (176, 65.7%). The most widely prescribed antibiotics were metronidazole (404, 22.2%), ceftriaxone (373, 20.5%), ampicillin (337, 18.5%), gentamicin (221, 12.1%) and amoxicillin (90, 5.0%). Blood culture was only done for one patient and antibiotic treatments were given empirically. The most common indication for antibiotic use was community-acquired infection (484, 51.9%) followed by surgical prophylaxis (222, 23.8%).

There was high usage of antibiotics in hospitals in Sierra Leone as the majority of patients admitted received an antibiotic. This has the potential to increase the burden of antibiotic resistance in the country. We, therefore, recommend the establishment of hospital antimicrobial stewardship programmes according to the WHO core components.

To explore and model factors affecting antibiotic prescribing decision-making early in the pandemic.

Semistructured qualitative interview study.

National Health Service (NHS) trusts/health boards in England and Wales.

Clinicians from NHS trusts/health boards in England and Wales.

Individual semistructured interviews were conducted with clinicians in six NHS trusts/health boards in England and Wales as part of the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients study, a wider study that included statistical analysis of procalcitonin (PCT) use in hospitals during the first wave of the pandemic. Thematic analysis was used to identify key factors influencing antibiotic prescribing decisions for patients with COVID-19 pneumonia during the first wave of the pandemic (March to May 2020), including how much influence PCT test results had on these decisions.

During the first wave of the pandemic, recommendations to prescribe antibiotics for patients with COVID-19 pneumonia were based on concerns about secondary bacterial infections. However, as clinicians gained more experience with COVID-19, they reported increasing confidence in their ability to distinguish between symptoms and signs caused by SARS-CoV-2 viral infection alone, and secondary bacterial infections. Antibiotic prescribing decisions were influenced by factors such as clinician experience, confidence, senior support, situational factors and organisational influences. A decision-making model was developed.

This study provides insight into the decision-making process around antibiotic prescribing for patients with COVID-19 pneumonia during the first wave of the pandemic. The importance of clinician experience and of senior review of decisions as factors in optimising antibiotic stewardship is highlighted. In addition, situational and organisational factors were identified that could be optimised. The model presented in the study can be used as a tool to aid understanding of the complexity of the decision-making process around antibiotic prescribing and planning antimicrobial stewardship support in the context of a pandemic.

ISRCTN66682918.

Frailty is a common syndrome of physiological decline among older adults characterised by vulnerability to adverse outcomes and loss of functional independence after major surgery.1 The study by Goeddel et al2 examined 11 geriatric domains associated with frailty that were collected before surgery using the Edmonton...