The Quadrivalent human papillomavirus (HPV) Vaccine Evaluation Study with Addition of the Nonavalent Vaccine Study (QUEST-ADVANCE) aims to provide insight into the long-term immunogenicity and effectiveness of one, two and three HPV vaccine doses. Here, we describe the protocol for QUEST-ADVANCE.
QUEST-ADVANCE is an observational cohort study including males and females who are unvaccinated or vaccinated with the quadrivalent or nonavalent HPV vaccine in British Columbia, Canada. Female participants who are unvaccinated or vaccinated with 1–3 doses of the quadrivalent or nonavalent HPV vaccine at 9–14 years of age will be recruited approximately 5 or 12 years postvaccination eligibility. Male participants who are unvaccinated or vaccinated with 1 or 2 doses of the nonavalent HPV vaccine at 9–14 years of age will be recruited at approximately 5 years postvaccination eligibility. The study involves a maximum of four visits over a period of 4–5 years for female participants, and two visits over a 12-month period for male participants. At each visit, self-collected swabs (cervico-vaginal or penile) and questionnaire data will be collected. In each study group, a subset of participants will be invited to participate in a substudy evaluating the long-term humoral immunogenicity of the HPV vaccine. Additional blood samples will be collected from participants who are part of the immunogenicity substudy. The total required sample size is 7180 individuals. The primary objectives are (1) to examine vaccine effectiveness in males and females against prevalent genital HPV infections for one, two and three doses of the HPV vaccine compared with unvaccinated participants and (2) to evaluate if there is non-inferior immunogenicity as indicated by type-specific antibody response of one dose of the HPV vaccine in 20–27-year-old females vaccinated at 9–14 years of age compared with historical data of three doses of the HPV vaccine females vaccinated at 16–26 years of age up to 12 years postvaccination.
QUEST-ADVANCE was approved by the Research Ethics Board of the University of British Columbia/Children’s and Women’s Health Centre of British Columbia (H20-02111). Individual electronic informed consent or assent will be obtained from each participant before any study-specific procedures are undertaken. Results will be published in an international peer-reviewed journal and on the study website.
Paediatric hospitalisation, encompassing the period from admission to discharge, often involves feelings of pain, fear and anxiety, primarily due to clinical diagnoses and, more significantly, discomfort and stress-inducing procedures. Numerous methodologies and interventions have been investigated and implemented to alleviate these phenomena during paediatric hospitalisation. Virtual reality (VR), for example, has demonstrated efficacy in pain relief for hospitalised children in recent studies. This systematic review, therefore, aims to identify and evaluate the effectiveness of VR in alleviating pain, fear and anxiety in hospitalised children undergoing painful procedures.
This systematic review and meta-analysis will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guidelines. A systematic search will be conducted in March and April 2025 across the following databases, with no restrictions on language or publication year: PubMed, Embase, Scopus, Web of Science, Cumulated Index in Nursing and Allied Health Literature, ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials. Eligible studies will include randomised and quasi-randomised clinical trials involving children (aged 2–10 years) and adolescents (aged 10–18 years) who received VR interventions during painful procedures. Data will be managed and analysed using Review Manager software (RevMan 5.2.3). In cases of significant heterogeneity (I² > 50%), a random-effects model will be employed to combine studies and calculate the OR with a 95% CI. The methodological quality of the included studies will be assessed using the Cochrane Risk of Bias 2.0 tool, and the certainty of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluations framework.
This study will solely review published data; thus, ethical approval is not required. This systematic review is expected to provide subsidies, evidence and insights into the use of VR. It is also anticipated that the results will directly impact the improvement of care for these patients and the qualification of professional care.
CRD42024568297.
Acute pain in the postoperative period of cardiac surgery is mostly treated with opioid analgesics. However, with the risk of adverse reactions and complications, strategies which do not involve opioid analgesics can be considered, such as aromatherapy. This systematic review aims to analyse the effectiveness of aromatherapy in relieving pain in post-cardiac surgery patients.
Two researchers will independently and simultaneously conduct searches and select studies from the following databases: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Literature on Health Sciences, Scopus, Web of Science, Cochrane (Library) and clinical trial registries (clinicaltrials.com), with no language or publication date restrictions. Randomised and quasi-randomised clinical trials on the use of aromatherapy for pain relief in postcardiac surgery patients will be included. Then, two researchers will independently examine the studies based on inclusion criteria, extract data from the included studies and assess the risk of bias using the Risk of Bias 2 tool and the Risk of Bias in Non-randomized Studies of Interventions tool from Cochrane. Data will be synthesised using Review Manager software. The strength of the evidence will be evaluated using the Grading of Recommendation Assessment, Development and Evaluation approach. The literature search, study selection, review and meta-analysis stages will be conducted from early October 2025 to April 2026.
This study is based on secondary data, and therefore ethical approval from a research ethics committee was not required. The results will be disseminated through publication in a peer-reviewed scientific journal.
CRD42024568532.
To explore the use, parameters, safety and outcomes of physical rehabilitation for adults with sepsis.
We conducted a scoping review following the Joanna Briggs Institute framework.
Studies were eligible for inclusion in the study if they included: (1) adults 18 and older, (2) with a previous diagnosis of sepsis, (3) using a physical rehabilitation intervention at any point of sepsis management, (4) published in English or French.
We searched seven databases and screened titles and abstracts, reviewed full texts and performed data extraction independently and in duplicate. We summarised findings narratively using the "population, context, concept" framework and used descriptive statistics where appropriate. End-users reviewed and commented on study findings.
We included 58 studies, representing 77 434 participants, with the majority (79%) being published in the last decade. A large proportion (36%) of physical rehabilitation interventions included exercise and were overseen by a physical therapist (41%). The parameters of the interventions varied widely. However, all interventions (100%) were hospital based and the interventions implemented appeared safe. Of the 28 studies evaluating effectiveness of the intervention, function improved in most studies (78%) following physical rehabilitation.
Research addressing physical rehabilitation for patients with sepsis is increasing. Physical rehabilitation appears safe and may improve functional outcomes in those with sepsis. Future research should report details of intervention parameters and evaluate rehabilitation post-hospital discharge to maximise impact on function and quality of life for sepsis survivors.
The protocol was registered on Open Science Framework Registries (Registration DOI: https://doi.org/10.17605/OSF.IO/2EPJ6).
Acute low back pain (LBP) is a prevalent condition with various non-surgical treatment options, yet no comprehensive network meta-analysis has systematically compared their relative efficacy for pain and disability. This study aims to fill that gap by synthesising available evidence on the efficacy of different types of non-surgical interventions for acute LBP, such as various medications, manual therapies and education-based therapies. Our coprimary objectives are to (1) compare each active treatment to an inert reference for measures of LBP and related disability and (2) rank the efficacy of treatments.
We will conduct a systematic search across multiple databases, including grey literature, to identify randomised controlled trials evaluating non-surgical treatments for acute LBP. Eligible studies must report on pain and/or disability outcomes in adults. The risk of bias will be assessed using the Risk of Bias tool, and the certainty of evidence will be graded using CINeMA (Confidence in Network Meta-Analysis). We will use a frequentist network meta-analysis to pool standardised mean differences in pain and disability, employing random-effects models to account for heterogeneity. A qualitative analysis will assess study characteristics and transitivity, while a quantitative analysis will evaluate efficacy and inconsistency. Results will be presented using network geometry, p-scores, forest plots, funnel plots, Egger’s test, Q-statistics and league tables to visualise both direct and indirect evidence and to identify potential biases.
This review protocol does not involve any primary research with human participants, animal subjects or medical record review. Consequently, this work did not require approval from an institutional review board or ethics committee. Results will be submitted to a peer-reviewed journal and presented at conference(s). De-identified data will be made available in a public repository.
It is unclear how mis- and disinformation regarding healthcare policy changes propagate throughout Latino communities via social media. This may lead to chilling effects that dissuade eligible individuals from enrolling in critical safety net programmes such as Medicaid. This study will examine pathways and mechanisms by which sentiment in response to mis- and disinformation regarding healthcare policies on social media differentially impact health disparity populations, thus supporting the design of tailored social media interventions to mitigate this.
We will search social media from X/Twitter, Facebook/Instagram and Reddit for keywords relating to health benefit programmes. Demographic, geographical location and other characteristics of users will be used to stratify social media data. Posts will be classified as fake-news-related or fact-related based on curated lists of fake-news-related websites. The number, temporal dissemination and positive or negative sentiment in reacting to posts and threads will be examined using the Python-based Valence Aware Dictionary and sEntiment Reasoner (VADER). Using a crowd-sourcing methodology, a novel Spanish-language VADER (S-VADER) will be created to rate sentiment to social media among Spanish-speaking Latinos. With the proposed approach, we will explore reactions to the dissemination of fake-news- or fact-related social media tweets and posts and their sources. Analyses of social media posts in response to healthcare-related policies will provide insights into fears faced by Latinos and Spanish speakers, as well as positive or negative perceptions relating to the policy over time among social media users.
Our study protocol was approved by the University of California, Los Angeles IRB (IRB#23–0 01 123). Results from this study will be disseminated in peer-reviewed journals and conference presentations, and S-VADER will be disseminated to public repositories such as GitHub.
Congenital cytomegalovirus (cCMV) is an important cause of long-term childhood disability. In Australia, the identification and treatment practices and the long-term clinical and neurodevelopmental outcomes of children with cCMV are unknown. The Australasian cCMV Register (ACMVR) is a longitudinal register and resource for research that aims to describe and explore, in Australian children with cCMV: (1) their clinical characteristics over time, (2) antiviral therapy use/prescribing up to 1 year of age and (3) risk factors and potential avenues for prevention of adverse sequelae of the virus.
Children
Ethics and governance approvals, study database and a steering group have been established. Data collection is active in five sites across Australia.
The ACMVR will inform our understanding of the long-term outcomes for children with cCMV in Australia and provide a sampling frame and resource for recruitment in future clinical and epidemiological research to inform practice and policy. New opportunities for the establishment of additional study sites and collaborations with Australian maternity and fetal medicine researchers and with cCMV registries in other countries are currently being explored.
For every 100 women having a vaginal birth, approximately four will experience a severe (third-degree or fourth-degree) perineal tear. Severe perineal tears are associated with significant short-term and long-term consequences if not recognised and repaired. There are global efforts to reduce incidence of severe perineal tears including initiatives to strengthen education and training of clinicians in perineal anatomy and perineal tear assessment and classification. This systematic review aimed to describe and evaluate the effectiveness of these initiatives.
Systematic review, reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Medline (Ovid), CINAHL Complete (EBSCO), MIDIRS and EMBASE (Ovid) were searched through 15 February 2024.
Studies reporting simple or complex interventions aimed at improving the skills and knowledge of clinicians in perineal anatomy and/or the clinical assessment and classification of perineal tears were eligible.
Two reviewers independently screened studies for eligibility and appraised the quality of individual studies using the Cochrane Risk of Bias (RoB) 2.0 tool or Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool.
In total, 7645 citations were screened and 39 studies included. We identified nine unique interventions including training programmes, short workshops and senior obstetrician supervision. Many studies were from high-income countries, in primary care settings and at high risk of bias.
Effective education included practical components, such as hands-on skills and training in perineal anatomy, assessment and classification, rather than senior supervision alone. Ongoing review of practice appears to be crucial for maintaining knowledge and skills. Future research should focus on interventions tailored to limited-resource settings, and the optimal length and intensity of training programmes to assess and classify perineal tears.
CRD42020185431.
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.
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.
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.
Due to numerous comorbidities, complicated medical regimens and age-related difficulties, older adults frequently confront substantial treatment burdens and poor medication adherence, which could result in poor health outcomes. This study assessed the treatment burden and medication adherence among older adults in comprehensive specialised hospitals in the Amhara Region in Ethiopia.
A multicentre hospital-based cross-sectional study was conducted from 30 March to 30 July 2024.
The study was conducted at four comprehensive specialised hospitals in Northwest Ethiopia.
Patients were ≥65 years old, diagnosed with two chronic illnesses and were receiving medical attention for the relevant issue.
This study employed the Multimorbidity Treatment Burden Questionnaire to assess treatment burden and the General Medication Adherence Scale to assess medication adherence. Data analysis was conducted using STATA version 17. Linear and binary logistic regressions were used to analyse the dependent variables of treatment burden and medication adherence to the determining factors, respectively.
422 patients took part in this study. Regarding treatment burden, 75% report a high burden. Of the patients, 32.20% adhered well, whereas 67.80% did not. The medication regimen complexity index (MRCI; β=0.029, 95% CI 0.001 to 0.058; p=0.047), age (β=0.027, 95% CI 0.009 to 0.044; p=0.004) and number of medications (β=0.168, 95% CI 0.045 to 0.291; p=0.007) were associated with higher treatment burden. Variables associated with medication non-adherence included rural residence (adjusted OR 2.249, 95% CI, 1.356 to 3.732; p=0.002), care provided by relatives (1.744, 1.055 to 2.883; p=0.030), moderate Charlson comorbidity index (CCI; 2.241, 1.220 to 4.117; p=0.009), severe CCI (6.953, 3.526 to 13.715; p=0.000), polypharmacy (1.615, 1.055 to 3.230; p=0.044) and treatment burden (1.501, 1.023 to 3.090; p=0.015).
Of the older adult patients enrolled in this study, three-quarters had a high treatment burden, and more than two-thirds had poor adherence. A high treatment burden was associated with age, medication use and MRCI, whereas non-adherence was associated with self-management, residency, CCI, medication use, MRCI and treatment burden.
Musculoskeletal injury (MSKI) is the leading cause of medical downgrading and discharge within the UK military, with lower limb MSKI having the greatest incidence, negatively impacting operational readiness. Pain is a primary limiting factor to rehabilitation progress following MSKI. Heavy-load resistance training (RT; ie, loads >70% 1-repetition maximum) is traditionally used but may be contraindicated due to pain, potentially prolonging recovery and leading to failure of essential physical employment standards for UK military personnel. Low-load RT with blood flow restriction (BFR) can promote favourable morphological and physiological adaption, as well as elicit hypoalgesia in healthy and clinical populations (eg, post-operative), and has proven a viable option in military rehabilitation settings. The acceptability and tolerance of higher relative BFR pressures in persistent pain populations are unknown due to the complexity of presentation and the perception of discomfort experienced during BFR exercise. Greater relative pressures (ie, 80% limb occlusion pressure (LOP)) elicit a greater hypoalgesic response in pain-free individuals, but greater perceived discomfort which may not be tolerated in persistent pain populations. However, lower relative pressure (ie, 40% LOP) has elicited hypoalgesia in pain-free individuals, which therefore may be more clinically acceptable and tolerated in persistent pain populations. The primary aim of both randomised controlled trials (RCT) is to investigate the efficacy and acceptability of using high-frequency, low-load BFR-RT in UK military personnel with lower limb MSKI where persistent pain is the primary limiting factor for progression.
The presented protocol is a two-phase RCT based within a military rehabilitation setting. Phase One is a 1-week RCT to determine the most efficacious and acceptable BFR-RT protocol (7x BFR-RT sessions over 5 days at 40% or 80% LOP; n=28). Phase Two is a 3-week RCT comparing the most clinically acceptable BFR pressure, determined by Phase One (21x BFR-RT sessions over 15 days; n=26) to usual care within UK Defence Rehabilitation residential rehabilitation practices. Outcomes will be recorded at baseline, daily and following completion of the intervention. The primary outcome will be the brief pain inventory. Secondary outcomes include blood biomarkers for inflammation and pain (Phase Two only), injury-specific outcome measures, lower extremity function scale, objective measures of muscle strength and neuromuscular performance, and pressure pain threshold testing.
The study is approved by the Ministry of Defence Research Ethics Committee (2318/MODREC/24) and Northumbria University. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.
Registered with Clinical Trials. The registration numbers are as follows: NCT06621914 (Phase One) and
To estimate the prevalence of urinary incontinence (UI) and its subtypes among nulliparous Chinese women with associated risk factors. The prevalence of UI among those living in urban or rural communities was also analysed with potential risk factors.
This is a secondary analysis of epidemiological survey data on UI in Chinese women. The original study was designed as a nationwide cross-sectional study involving 56 460 adult women conducted from October 2019 to December 2021.
Seven geographic regions of China.
Nulliparous women who were aged ≥20 years old and were permanent residents were included in this secondary analysis. Participants who had severe mental or physical disorders or were pregnant were excluded. Data on demographic characteristics, health status and medical history were collected.
The primary outcome was the prevalence of UI, whereas secondary outcome measures were adjusted odds ratios (aOR) for risk factor analysis.
A total of 6244 nulliparous women were included in the analysis. The prevalence of UI was 1.9% for nulliparous Chinese women, with stress, urgency and mixed UI being prevalent at 0.9%, 0.3% and 0.7%, respectively. The prevalence of UI was 2.1% and 1.6% for urban and rural subgroups. Abnormal body mass index was significantly associated with UI in the nulliparous group (underweight, aOR: 1.88, 95% CI: 1.03 to 3.45, p=0.041; overweight, aOR: 2.26, 95% CI: 1.37 to 3.73, p=0.001; and obesity, aOR: 3.64, 95% CI: 1.86 to 7.15, p
UI among nulliparous women deserves greater public attention. Abnormal body mass index, including underweight status, was found to be a risk factor for UI among Chinese nulliparous women. Further research is required to investigate the mechanism underlying the association between underweight status and UI.
The study was approved by Peking Union Medical College Ethics Committee (No. S-K970) and conducted according to the Declaration of Helsinki. All participants signed consent forms before data collection. A completed STROBE checklist detailing compliance with all 22 items is provided.
This study aims to synthesise evidence on the pooled level of exit knowledge among outpatients served in public hospital pharmacies and private pharmacies in Ethiopia and to identify the associated factors associated with medication knowledge by conducting a systematic review and meta-analysis of primary articles focused on this area.
This systematic review and meta-analysis study employed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
Three electronic databases—MEDLINE, Scopus and Google Scholar—were searched for all English-language articles published from 2010 until 18 December 2024.
The review exclusively included studies that reported original data, were freely accessible in full text and were written in English, as well as those investigating the level of knowledge among outpatients and associated factors, irrespective of study design. Studies lacking abstracts and full texts, reports, qualitative research, and conference summaries were excluded from the analysis.
Data from selected studies were extracted by three independent reviewers using a standardised data extraction format created using Microsoft Excel. Their results were cross-checked by two additional reviewers for consistency.
Of the 521 identified studies, 9 met the inclusion criteria. The overall pooled knowledge level was 45%. Factors associated with knowledge included residence (OR=0.67, 95% CI: 0.27 to 0.71), adequacy of information provided (OR=0.87, 95% CI: 0.24 to 0.90), education level (OR=0.70 CI: 0.39 to 0.89), clarity of instructions (OR=0.80 CI: 0.14 to 0.99) and pharmacist politeness (OR=0.72 CI: 0.46 to 0.77).
The systematic review and meta-analysis showed that pooled patient knowledge regarding their dispensed medications in Ethiopia is about 45%. Key determinant factors of knowledge included education level, quality of pharmacist communication, urban versus rural residence and pharmacist politeness. Recommendations for improvement include enhancing pharmacist training, developing educational materials in local languages, outreach programmes for rural areas and implementing patient-centred care policies.
PROSPERO number: CRD42024560816
Chronic health conditions are the leading causes of morbidity and mortality worldwide, with a disproportionately high burden in low-income and middle-income countries. The burden arising from these conditions presents immense challenges to countries with dysfunctional public healthcare systems, such as South Africa. This necessitates patients to have a good understanding of the conditions and optimal self-management approaches. We explored patients’ understanding of chronic health conditions and self-management practices, including self-monitoring, in the rural South African community of Agincourt in the subdistrict of Bushbuckridge, Mpumalanga Province.
We randomly selected patients receiving routine care for chronic health conditions in primary healthcare facilities who were linked to the Agincourt Health and Demographic Surveillance System to participate in focus group discussions. Six focus groups (three with men and three with women) were conducted, with 17 male and 19 female participants (n=35) living with different chronic health conditions. Data were collected using body mapping exercises and semistructured focus group discussions facilitated by two experienced qualitative research assistants. An inclusive thematic approach was used for analysis.
Participants identified most chronic health conditions and their progression. Participants expressed that some consequences of chronic health conditions were unavoidable and some were attributed to medications. Three themes emerged on the management of chronic health conditions: (1) individual-level management, where participants actively changed or managed lifestyle factors associated with the conditions; (2) clinic-level management and support, where participants believed that following instructions from healthcare providers facilitates better management of their condition(s); and (3) prevention and screening, to prevent disease progression and development of complications. Participants also highlighted the role of religion in the control of chronic disease risk factors and traditional treatments for uncommon conditions such as epilepsy. Costs associated with lifestyle changes and equipment to manage and monitor health were highlighted as barriers to self-management of chronic health conditions.
Our findings contribute to emerging research on chronic health conditions and self-management approaches. Participants in our study demonstrated a good understanding of various chronic health conditions but lacked knowledge of self-management practices and faced barriers to self-management. There is a need for further studies on self-management of chronic health conditions, including self-monitoring among patients in rural sub-Saharan settings.