Real-world effectiveness and safety of oral azvudine versus Paxlovid in patients with COVID-19 and pre-existing hypertension: a multicentre, retrospective, cohort study in Henan Province, China

Objectives
Azvudine and Paxlovid are the primary antiviral agents for the management of COVID-19. However, there is currently insufficient evidence regarding the effectiveness and safety of these drugs in treating COVID-19 patients with pre-existing hypertension. The objective of this study was to assess their effectiveness and safety among those patients in a real-world context.

Design
Retrospective cohort study.

Setting
Electronic medical record data of COVID-19 patients with pre-existing hypertension were extracted from nine hospitals in Henan Province from 5 December 2022 to 31 January 2023.

Participants
Following 2:1 propensity score matching (PSM), 996 individuals who received treatment with azvudine and 498 individuals who received treatment with Paxlovid were included in the analysis.

Primary and secondary outcome measures
The primary outcome was all-cause death and the secondary outcome was the composite disease progression.

Results
Following adherence to the inclusion and exclusion criteria and 2:1 PSM, 996 individuals were included in the azvudine group and 498 in the Paxlovid group. The Cox regression analysis revealed that the azvudine group had a significantly lower risk of all-cause death compared with the Paxlovid group (HR 0.64, 95% CI 0.455 to 0.911, p=0.013). However, there was no statistically significant difference in composite disease progression between the two groups (HR 0.93, 95% CI 0.711 to 1.229, p=0.629). Subgroup analysis indicated that, compared with Paxlovid, patients with moderate disease receiving azvudine treatment exhibited a significantly reduced risk of composite disease progression (HR 0.46, 95% CI 0.24 to 0.89). The safety analysis showed that the azvudine group had fewer adverse events.

Conclusions
Among COVID-19 patients with pre-existing hypertension, the effectiveness of azvudine is not inferior to Paxlovid in reducing all-cause death and composite disease progression, with fewer adverse events.

Trial registration number
NCT06349655.

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Yoga for older adults with multimorbidity: teaching insights for optimising participant safety and inclusion from the process evaluation of the Gentle Years Yoga trial

Objectives
To develop a teaching exemplar for optimising the safe and accessible delivery of chair-based yoga to multimorbid older adult populations.

Design
A qualitative process evaluation embedded within the multi-site, randomised controlled Gentle Years Yoga trial for older adults (65+ years) with two or more long-term health conditions (trial status: completed).

Setting
Online and face-to-face interviews were conducted with participants and yoga teachers involved in the 12-week chair-based yoga intervention. Interview data were supplemented with observations of in-person and online yoga class delivery.

Participants
All yoga teachers delivering the yoga intervention were invited to take part in the interviews, together with a subsample of participants receiving the yoga intervention. Participants were purposively selected to represent the trial cohort demographics of gender, age, ethnicity, index of multiple deprivation, and number and intensity of chronic health conditions.

Results
25 yoga participants and 11 yoga teachers took part in one (N=19) or two (N=17) interviews. Participants were aged 66–91 years (mean age 74 years), with 2–8 long-term health conditions, most commonly osteoarthritis (N=15, 60%), cardiovascular disease (N=14, 56%), sensory conditions (N=9, 36%) and depression or anxiety (N=8, 32%). Yoga teachers were predominantly female (N=10, 91%), with 4–35 years yoga teaching experience across multiple yoga styles. Feedback from yoga teachers and participants was classified into six categories, generating a 21-item teaching exemplar. These covered aspects of delivery including class size and delivery formats, choosing appropriate physical content, enhancing inclusivity of personal beliefs through non-physical content, proactive teaching styles, communication tips and ways to boost visibility.

Conclusions
This 21-item list adds to the current educational base of yoga for older adults. Addressing both face-to-face and online class formats, this exemplar offers pragmatic guidance for yoga teachers to enhance the safe and accessible delivery of chair-based yoga to older adults and multimorbid populations.

Trial registration number
ISRCTN13567538.

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Predictive accuracy of ophthalmic artery Doppler for pre-eclampsia: a systematic review

Objectives
This systematic review investigated available evidence on the stand-alone and incremental predictive performance of ophthalmic artery Doppler (OAD) for pre-eclampsia.

Design
Systematic review.

Data sources
We conducted a literature search from PubMed (Medline), the Cochrane CENTRAL, EMBASE and Scopus from inception to 8 April 2025.

Eligibility criteria
Studies eligible for inclusion were prospective or retrospective cohort studies, case-control studies or randomised controlled trials that reported on the predictive performance of OAD for pre-eclampsia in singleton pregnancies; and conducted in either high-income country (HIC) or low- and middle-income country (LMIC).

Data extraction and synthesis
Two reviewers independently screened and assessed articles for inclusion. One reviewer then extracted data using a standardised data extraction sheet, and any uncertainties were discussed with a second reviewer. The Prediction model Risk of Bias Assessment Tool was used for quality and risk of bias assessment. Findings were summarised and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement and synthesised qualitatively.

Results
We identified and included 11 observational studies (3 from HIC and 8 from LMICs) with a total of 12 150 singleton pregnancies, of which 517 (4.3%) were complicated by pre-eclampsia at end of follow-up. The included studies were of varied quality, with three at low risk of bias, four at unclear risk and four at high risk. No interventional study was identified. Three studies (27.3%) recruited high-risk pregnancies (defined according to the American College of Obstetricians and Gynecologists (ACOG) criteria as one or more of the following: chronic hypertension, personal or family history of pre-eclampsia, early (≤18 years) or late (≥40 years) first pregnancy, primipaternity, chronic kidney disease, increased body mass index >30 kg/m2, presence of diabetes mellitus prior to pregnancy, autoimmune disease and thrombophilia), while eight studies (72.7%) recruited undetermined risk pregnancies. Stand-alone performance of OAD (interpreted by area under the receiver operating curve at 95% CI) showed that in the first trimester, the peak systolic velocity (PSV) ratio demonstrated very good predictive ability (0.97, 95% CI 0.92 to 1.0) (n=1 study), and the second PSV (PSV2) demonstrated very good predictive ability (0.91, 95% CI 0.82 to 0.99) (n=1 study). Also, PSV2 demonstrated fair predictive ability (0.61, 95% CI 0.42 to 0.79; and 0.53, 95% CI 0.40 to 0.66) for early and late pre-eclampsia, respectively (n=1 study). In the second trimester, the PSV ratio demonstrated very good predictive ability (0.88, 95% CI 0.84 to 0.91) (n=1 study), and PSV2 demonstrated good predictive ability (0.73, 95% CI 0.66 to 0.81; and 0.76, 95% CI 0.71 to 0.81) for pre-eclampsia (n=2 studies). In the third trimester, the PSV ratio demonstrated good predictive ability (0.82, 95% CI 0.73 to 0.89; and 0.77, 95% CI 0.71 to 0.82) for preterm and term pre-eclampsia, respectively (n=1 study). Also, PSV2 demonstrated good predictive ability 0.70 (0.57 to 0.84) (n=1 study).
Subsequently, in the second trimester, PSV ratio demonstrated better incremental predictive performance than uterine artery pulsatility index for preterm pre-eclampsia, when added to maternal factors and mean arterial pressure (MAP) (56.1%–80.2% vs 56.1%–74.8% detection rate (DR) at 10% FPR) (n=1 study). Also in the third trimester, adding PSV ratio to maternal factors and MAP was superior to soluble fms-like tyrosine kinase-1/placental growth factor ratio in predicting pre-eclampsia at

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Cross-sectional study of the rates of military sexual trauma (MST) and associations with adverse mental health outcomes among UK female ex-service personnel: a study protocol

Introduction
This study investigates the rates of military sexual trauma (MST) and its associations with adverse mental health among a sample of UK female ex-service personnel who served during the Iraq/Afghanistan eras.

Methods and analysis
Female ex-service personnel, who participated in the fourth phase (Phase 4) of the King’s Centre for Military Health Research (KCMHR) Health and Well-being Cohort Study (2022–2023) and consented to be recontacted for follow-up studies (n=295), are being invited to participate in an online questionnaire between July 2024 and February 2025. The questionnaire contains surveys and questions related to experiences of sexual harassment and sexual assault during and outside of military service, disordered eating and broader female health issues. While the questionnaire relates to several female health topics, this study focuses on the surveys related to experiences of sexual trauma and eating disorders. Sociodemographic variables and some health variables, including post-traumatic stress disorder (PTSD), complex PTSD, common mental disorders, alcohol misuse, physical somatisation and social support, will be extracted from participants’ pre-existing data collected in Phase 4 of the KCMHR Cohort Study. Analyses will assess rates of MST, and hierarchical multiple logistic regressions will investigate associated health impacts. Rates and ORs, employing 95% CIs, will be reported.

Ethics and dissemination
This study has been granted full ethical approval by the King’s College London Research Ethics Committee (Ref: HR/DP-23/24–39040). Participants provide informed consent before participating and have access to a signposting booklet containing contact details for a range of support services. A risk protocol is in place, which outlines the procedure to be undertaken if a participant contacts the research team in distress. Findings will form part of a PhD thesis and will be further disseminated through peer-reviewed publication and dissemination with veteran mental health services and charities, and relevant government departments.

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Background rates of medical events of interest before and during the COVID-19 pandemic: a longitudinal cohort study using claims data

Importance
Background rates are critical for contextualising safety signals arising from COVID-19-related interventions in investigational or real-world settings.

Objective
To estimate background rates of medical events of interest (MEI) for which COVID-19 infection and/or COVID-19 interventions may be risk factors in two US claims databases.

Design, setting and participants
This retrospective cohort study spans the pre-COVID-19 (2018–2019) and COVID-19 (2020–2021) periods. We constructed three cohorts, in each of Inovalon/HealthVerity (Inovalon/HV) and Optum databases: a COVID-19-positive adult cohort (2020–2021), a paediatric cohort (2018–2021) and a high-risk cohort (2018–2021) comprising patients at increased risk for severe COVID-19. Participants were indexed on the day they first qualified to enter each cohort during the study period. Background rates of 17 MEI were estimated per 1000 person-years (PY) with 95% CIs.

Main outcomes and measures
Annual incidence rates (IRs) of 17 MEI.

Results
Overall, 758 414 (COVID-19-positive adults; 57.8% women), 12 513 664 (high-risk adults; 56.8% women) and 8 510 627 (paediatric patients; 49.1% women) patients were identified in the HV database. IRs of MEI varied substantially by year, data source, study cohort and duration of follow-up. The IRs of MEI were highest among COVID-19-positive adults and lowest among paediatric patients. For example, IR of myocarditis/pericarditis per 1000 PY was 3.0 (95% CI: 2.6 to 3.4) in the COVID-19-positive adult cohort vs 0.36 (95% CI: 0.34 to 0.37) among high-risk adults and 0.05 (95% CI: 0.05 to 0.06) among paediatric patients. In the COVID-19-positive adult cohort, we observed higher IRs during 90-day follow-up (eg, IR of acute myocardial infarction (AMI) 26.5 (95% CI: 25.3 to 27.7)) vs 365-day follow-up (eg, IR of AMI 20.0 (95% CI: 9.2 to 20.8)) and during 2020 compared with 2021. IRs were higher in the high-risk adult and paediatric populations during the pre-COVID-19 period than during the COVID-19 pandemic.

Conclusions
Substantial variability was observed in IRs of MEI by study cohort, year, data source and follow-up duration. When generating background rates for contextualising safety signals from COVID-19 interventions, careful consideration must be given to the indicated subpopulation of interest, COVID-19-related temporal variations and data sources.

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Palliative care communication between patients with intellectual disabilities and hospice staff: a Conversation Analysis pilot study

Introduction
Communication challenges are among the main barriers for people with intellectual disabilities in accessing palliative care. They include inadequate skills among staff and difficulties with confirming understanding and around the presentation and assessment of symptoms. In-depth analysis of interactions between people with an intellectual disability and staff may shed light on these communicative challenges as well as facilitators. However, no studies have closely analysed the interactions between people with an intellectual disability and professionals within palliative care settings.

Methods and analysis
This protocol describes a pilot study assessing the feasibility and acceptability of conducting a Conversation Analysis study involving video-recording palliative care conversations between people with intellectual disabilities and professionals.
Three conversations between patients with an intellectual disability, their companions and palliative care staff will be video recorded in a UK hospice. Recordings will be transcribed and analysed using Conversation Analysis. Communication phenomena of interest and worth further exploration will be identified in collaboration with key stakeholders.

Ethics and dissemination
The study received a favourable opinion by a UK research ethics committee in February 2025. All participants must provide informed consent to take part in the study. It will be carefully assessed that potential participants with an intellectual disability have capacity to consent to take part. Accessible study information materials for participants with an intellectual disability are available (ie, easy-read and video).
Study findings will be disseminated in academic papers and conference presentations. Progress and findings will also be shared via social media and with relevant groups of people with intellectual disabilities, family carers, service providers and academics.

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Exploring evidence gaps in clinical trials in thermal burns care: an umbrella review

Background
Gaps in research evidence lead to research waste. In burns treatment, there is a paucity of reliable evidence or data. This contributes to inconsistent patient care, especially on a global scale, where low-resource countries often lack access to the latest research advancements. This umbrella review was undertaken as part of the James Lind Alliance Priorities in Global Burns Research Prioritisation Setting Partnership (PSP) and aimed to identify and assess the quality of evidence in thermal burns care. The objective was to map which interventions in thermal burns care are supported by a reliable evidence base and for which the evidence is lacking.

Methods
Systematic reviews of randomised controlled trials in thermal burns were identified and assessed using reliability criteria determined a priori. Multiple systematic review databases were searched in June 2023, including the Cochrane Library, KSR Evidence database and NIHR Journals Library. Summary of findings and, where available, Grading of Recommendations Assessment, Development and Evaluation was used to assess certainty of evidence. Reliable reviews were mapped onto clinical categories identified by patients, carers and healthcare professionals as part of the PSP.

Results
232 systematic reviews were identified, of which 83 met reliability criteria and were included. The main reason for not meeting reliability criteria was poorly defined eligibility criteria (n=128). Of the 83 reliable reviews, most were conducted in pain (n=28) or wound management (n=14) and acute care (n=13). Certainty of evidence was mixed. Reviews mapped onto nine of the 17 clinical categories identified by the PSP.

Conclusion
This review summarises the available high-quality evidence in burns care and identifies evidence gaps, indicating that many important clinical questions remain unanswered. There is a discrepancy between the treatments investigated in high-quality research and the clinical areas considered as most important to stakeholders. These findings provide direction for future research to improve global burns care.

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Preventing the transition from acute to chronic low back pain using home-based neuromodulation: protocol for a randomised, controlled study

Introduction
Chronic low back pain (LBP) is among the world’s leading causes of disability and declines in quality of life. Despite considerable financial and research investment, current interventions demonstrate only modest success or are associated with deleterious side effects. Furthermore, most treatment efforts are directed towards LBP that has already become chronic, rather than interventions capable of preventing pain chronicity in the first instance. Transcranial direct current stimulation (tDCS), a portable and cost-effective form of non-invasive brain stimulation, presents a potential means of targeting acute pain and preventing the transition to chronic pain. However, this approach has been limited primarily to experimental settings that require intensive appointments and specialist expertise. Thus, this assessor-blinded, participant-blinded, and therapist-blinded, randomised controlled trial aims to explore the effectiveness of home-based tDCS for improving pain and disability in people with acute LBP. This may provide insight into the potential for tDCS to expedite recovery from acute LBP and prevent pain chronicity.

Methods and analysis
40 individuals with acute LBP (onset

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Evaluation of the outpatient parenteral antimicrobial therapy (OPAT) service in Malaysian public hospitals: a mixed-methods study protocol

Introduction
Outpatient parenteral antimicrobial therapy (OPAT) is an innovative approach to manage infections that require extended courses of intravenous antibiotics by enabling patients to receive treatment in an outpatient setting. In Malaysia, there has yet to be a systematic evaluation of the OPAT service. This study aims to describe the safety, clinical indications and treatment outcomes of the OPAT service in Malaysia, assess patients’ satisfaction and experiences and determine the facilitators and barriers associated with the provision of the OPAT service in Malaysia.

Methods and analysis
A mixed-methods approach combining qualitative and quantitative methods will be employed for a comprehensive understanding of the provision of the OPAT service in Malaysian public hospitals. The study consists of four distinct parts: systematic review, retrospective cohort analysis of clinical outcomes, patients’ satisfaction survey and focus group discussions on providers’ experiences. A longitudinal analysis of the clinical outcomes (treatment success/failure, infection cure, adverse events, readmission and mortality) of the OPAT patients’ cohort will be conducted using descriptive and conclusive statistics, in addition to rates of patients’ satisfaction and evaluation of providers’ experiences.

Ethics and dissemination
This study is registered in the National Medical Research Register (NMRR ID-24-00941-2C8) and approved by the Medical Research and Ethics Committee, Ministry of Health Malaysia (Ref: 24-00941-2C8). Written informed consent will be obtained from all participants. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

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