Women in Health and their Economic, Equity and Livelihood statuses during Emergency Preparedness and Response (WHEELER) protocol: a mixed methods study in Kenya

Introduction
Kenya reported its first COVID-19 case on 13 March 2020. Pandemic-driven health system changes followed and unforeseen societal, economic and health effects reported. This protocol aims to describe the methods used to identify the gender equality and health equity gaps and possible disproportional health and socioeconomic impacts experienced by paid and unpaid (community health volunteer) female healthcare providers in Kilifi and Mombasa Counties, Kenya during the COVID-19 pandemic.

Methods and analysis
Participatory mixed methods framed by gender analysis and human-centred design will be used. Research implementation will follow four of the five phases of the human-centred design approach. Community research advisory groups and local advisory boards will be established to ensure integration and the sustainability of participatory research design.

Ethics and dissemination
Ethical approval was obtained from the Institutional Scientific and Ethics Review Committee at the Aga Khan University and the University of Manitoba.
This study will generate evidence on root cultural, structural, socioeconomic and political factors that perpetuate gender inequities and female disadvantage in the paid and unpaid health sectors. It will also identify evidence-based policy options for future safeguarding of the unpaid and paid female health workforce during emergency preparedness, response and recovery periods.

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Investigating the efficacy and safety of olanzapine prophylaxis for opioid-induced nausea and vomiting (JORTC-PAL20): a study protocol for an open-label, single-arm exploratory study

Introduction
In opioid therapy for cancer pain, opioid-induced nausea and vomiting (OINV) occur in 20%–40% of patients during initial opioid treatment or increasing opioid doses. OINV result in failure to achieve pain relief due to poor opioid adherence. Therefore, antiemetics are used to prevent OINV, but their efficacy and safety in this context have not yet been fully elucidated. Olanzapine is a promising antiemetic for the prophylaxis of chemotherapy-induced nausea and vomiting.

Methods and analysis
This single-arm, single-centre exploratory study will evaluate the prophylactic antiemetic efficacy and safety of 5 mg olanzapine in patients with cancer pain who are withholding initial regular opioid therapy. Thirty-five patients will be enrolled. The primary endpoint is the proportion of patients achieving complete control (CC) of OINV during 5 days of opioid treatment. CC was defined as the absence of emetic episodes, no need for rescue medication to treat nausea, and minimal or no nausea (3 or less on an 11-point categorical scale). Secondary endpoints include the complete response, defined as no emetic episodes and no use of rescue medication during the overall assessment period, the time from opioid initiation to first emetic episode, the time from opioid initiation to first rescue antiemetic administration, and adverse events graded by Patient-Reported Outcome (PRO) Common Terminology Criteria for Adverse Events (CTCAE) version 1.0 and CTCAE version 5.0.

Ethics and dissemination
This study protocol was approved by National Cancer Center Hospital Certified Review Board. The results will be used as preliminary data to conduct a validation study.

Trial registration number
Japan Registry of Clinical Trials (jRCT) jRCTs031220008.

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Health economic evaluations of preventative care for perinatal anxiety and associated disorders: a rapid review

Objectives
Perinatal mental health problems affect one in five women and cost the UK £8.1 billion for every year of births, with 72% of this cost due to the long-term impact on the child. We conducted a rapid review of health economic evaluations of preventative care for perinatal anxiety and associated disorders.

Design
This study adopted a rapid review approach, using principles of the standard systematic review process to generate quality evidence. This methodology features a systematic database search, Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram, screening of evidence, data extraction, critical appraisal and narrative synthesis.

Data sources
PubMed, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Applied Social Sciences Index and Abstracts, PsycINFO and MEDLINE.

Eligibility criteria for selecting studies
Studies that evaluated the costs and cost-effectiveness of preventative care for perinatal anxiety and associated disorders carried out within the National Health Service and similar healthcare systems.

Data extraction and synthesis
A minimum of two independent reviewers used standardised methods to search, screen, critically appraise and synthesise included studies.

Results
The results indicate a lack of economic evaluation specifically for perinatal anxiety, with most studies focusing on postnatal depression (PND). Interventions to prevent postnatal mental health problems are cost-effective. Modelling studies have also been conducted, which suggest that treating PND with counselling would be cost-effective.

Conclusion
The costs of not intervening in maternal mental health outweigh the costs of preventative interventions. Preventative measures such as screening and counselling for maternal mental health are shown to be cost-effective interventions to improve outcomes for women and children.

PROSPERO registration number
CRD42022347859.

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Prevalence of alcohol use and associated factors since COVID-19 among school-going adolescents within the Southern African Development Community: a systematic review protocol

Introduction
The COVID-19 pandemic has significantly shaped the global landscape and impacted various aspects of individuals’ lives, especially the behaviour of school-going adolescents regarding substance use. Among these substances, alcohol is the most predominant substance, particularly among school-going adolescents, who also are highly susceptible to harmful alcohol use, such as poor academic performance, psychiatric disorders and disrupted social lives. This review will synthesise the known prevalence estimates and associated factors of alcohol use among school-going adolescents in the Southern African Development Community (SADC) since the COVID-19 pandemic.

Methods and analysis
We will perform a systematic review in line with the Cochrane Handbook for Systematic Reviews. We will systematically search for selected global databases (ScienceDirect, EbscoHost, PsycINFO and PubMed) and regional electronic databases (African Index Medicus, Sabinet and African Journals OnLine). Peer-reviewed literature published between 11 March 2020 and 10 March 2024 will be considered for eligibility without language restriction. All 16 countries of the SADC region will be included in the review. The Mixed-Methods Appraisal Tool checklist for quality appraisal will be used to appraise the methodological quality of the included studies. Depending on the level of heterogeneity, prevalence estimates will be pooled in a meta-analysis; narrative synthesis will be applied to describe the reported associated factors of alcohol use.

Ethics and dissemination
We will not seek ethical approval from an institutional review board since the study will not involve gathering data directly from individual school-going adolescents, nor will it violate their privacy. When completed, the full report of this review will be submitted to a journal for peer-reviewed publication; the key findings will be presented at local and international conferences with a partial or full focus on (adolescent) alcohol (mis)use.

PROSPERO registration number
CRD42023452765.

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Assessing caregiver burden in advanced kidney disease: protocol for a systematic review of the measurement properties of instruments and tools

Introduction
Caregiver burden is a significant issue in the care of patients with advanced kidney disease. Its assessment is crucial for evaluating the needs of caregivers and for the development of interventions to support them. Several instruments have been developed to measure caregiver burden in these patients. However, the measurement properties of these instruments have not been systematically reviewed.

Methods and analysis
This systematic review will include a comprehensive search of databases including PubMed, CINAHL, Embase, Cochrane Library, SCOPUS and Web of Science by using keywords and MeSH terms to identify relevant studies starting from each database inception to 1 January 2024 and covering papers in English. The search strategy will combine relevant keywords and database-specific subject headings related to the following concepts: (1) caregivers, (2) burden, stress, distress, (3) chronic kidney disease, end-stage kidney disease, dialysis. Reference lists of eligible articles will also be hand searched. We will include quantitative and qualitative studies evaluating measurement properties of instruments assessing caregiver burden in caregivers of adult patients (aged ≥18 years). Data will be extracted from the selected studies and analysed using the COnsensus-based Standards for the selection of health Measurement INstruments checklist as the study quality assessment tool. Subsequently, the van der Vleuten utility index will be used to critique and categorise the instruments. A narrative that synthesises the utility of all instruments will be presented along with recommendations for the selection of instruments depending on specific clinical contexts. This systematic review will provide an overview of the measurement properties of available instruments, including discussion on reliability, validity and responsiveness. Results from the review may give rise to the subsequent development of most appropriate instrument that could be applied to the assessment of caregiver burden in advanced kidney disease.

Ethics and dissemination
Ethics approval is not required as this study will merely synthesise data from published studies. The results will be disseminated through peer-reviewed publications as well as conference presentations.

PROSPERO registration number
CRD42023433906.

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Effectiveness, barriers and facilitating factors of strategies for active delabelling of patients with penicillin allergy labels: a systematic review protocol

Introduction
Up to 15% of adult patients in the clinical setting report to be allergic to penicillin. However, in most cases, penicillin allergy is not confirmed. Due to the negative aspects associated with erroneous penicillin allergy, the implementation of active delabelling processes for penicillin allergy is an important part of antibiotic stewardship programmes. Depending on the clinical setting, different factors need to be considered during implementation. This review examines the effectiveness of different delabelling interventions and summarises components and structures that facilitate, support or constrain structured penicillin allergy delabelling.

Methods and analysis
This review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The databases MEDLINE (via PubMed), EMBASE and Cochrane Library were searched for studies reporting on any intervention to identify, assess or rule out uncertain penicillin allergy. To improve completeness, two further databases are also searched for grey literature. Study design, intervention type, professional groups involved, effectiveness, limitations, barriers, facilitating factors, clinical setting and associated regulatory factors will be extracted and analysed. In addition, exclusion criteria for participation in the delabelling intervention and criteria for not delabelling penicillin allergy will be summarised. In case of failed protocols, these are highlighted and quantitatively analysed if possible. Two independent reviewers will perform the screening process and data extraction. Discordant decisions will be resolved through review by a third reviewer. Bias assessment of the individual studies will be performed using the Newcastle Ottawa Scale.

Ethics and dissemination
Because individual patient-related data are not analysed, an ethical approval is not required. The review will be published in a peer-reviewed scientific journal.

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Tobacco use and behaviour among South African adolescents and young adults: systematic review and meta-analysis

Objective
Tobacco use, particularly the initiation of smoking during adolescence and young adulthood, represents a significant public health concern in South Africa. This study aims to conduct a comprehensive review of published literature about tobacco use and behaviour among adolescents and young adults and to determine an aggregated prevalence estimate of tobacco use within this demographic.

Design
Systematic review and meta-analysis.

Data sources
PubMed/MEDLINE, EMBASE, Cochrane Library, Scopus and Google Scholar were searched from 1 January 2000 through 31 October 2023.

Eligibility criteria
Studies were eligible for inclusion if they were cross-sectional studies conducted in South Africa and measured the prevalence and determinants of tobacco use among adolescents and young adults aged 12–24 years.

Data extraction and synthesis
Two reviewers independently extracted information for each article and saved it into an Excel spreadsheet. Risk of bias analysis was conducted using the Risk of Bias Assessment Tool for non-randomised studies. The methodology quality of each selected study was evaluated using the Joanna Briggs Institute checklist. The heterogeneity of prevalence estimates was assessed using I2 statistic (random-effects DerSimonian-Laid approach).

Results
Out of 73 articles identified, 12 articles were included in the analysis. The pooled prevalence of current tobacco use among South African adolescents and young adults was estimated to be 22%. The pooled prevalence of tobacco use among school dropouts, university students and secondary school learners was 51%, 20% and 16%, respectively. Stratifying using gender, boys (26%) were two times more likely to use tobacco than girls (13%).

Conclusion
The elevated occurrence of tobacco usage among South African adolescents and young adults is a relevant public health concern. There is a need for more population-based prevalence studies at a national level to estimate the burden of tobacco use in South Africa.

PROSPERO registration number
CRD42023428369.

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Improving safety and preventing falls using an evidence-based, front-line staff huddling practice: protocol for a pragmatic trial to increase quality of care in State Veterans Homes

Introduction
Falls in nursing homes are a major cause for decreases in residents’ quality of life and overall health. This study aims to reduce resident falls by implementing the LOCK Falls Programme, an evidence-based quality improvement intervention. The LOCK Falls Programme involves the entire front-line care team in (1) focusing on evidence of positive change, (2) collecting data through systematic observation and (3) facilitating communication and coordination of care through the practice of front-line staff huddles.

Methods and analysis
The study protocol describes a mixed-methods, 4-year hybrid (type 2) effectiveness-implementation study in State Veterans Homes in the USA. The study uses a pragmatic stepped-wedge randomised trial design and employs relational coordination theory and the Reach, Effectiveness, Adoption, Implementation and Maintenance framework to guide implementation and evaluation. A total of eight State Veterans Homes will participate and data will be collected over an 18-month period. Administrative data inclusive of all clinical assessments and Minimum Data Set assessments for Veterans with a State Veterans Home admission or stay during the study period will be collected (8480 residents total). The primary outcome is a resident having any fall. The primary analysis will be a partial intention-to-treat analysis using the rate of participants experiencing any fall. A staff survey (n=1200) and qualitative interviews with residents (n=80) and staff (n=400) will also be conducted. This research seeks to systematically address known barriers to nursing home quality improvement efforts associated with reducing falls.

Ethics and dissemination
This study is approved by the Central Institutional Review Board (#167059-11). All participants will be recruited voluntarily and will sign informed consent as required. Collection, assessment and managing of solicited and spontaneously reported adverse events, including required protocol alterations, will be communicated and approved directly with the Central Institutional Review Board, the data safety monitoring board and the Office of Research and Development. Study results will be disseminated through peer-reviewed publications and conference presentations at the Academy Health Annual Research Meeting, the Gerontological Society of America Annual Scientific Meeting and the American Geriatrics Society Annual Meeting. Key stakeholders will also help disseminate lessons learnt.

Trial registration number
NCT05906095.

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Review of Evaluation and Treatment of Knee Pain—Reply

In Reply We appreciate Dr Misseri and colleagues’ interest in our Review article. They raise a relevant point about RFA as a potential treatment option for managing knee osteoarthritis pain. Research on this topic has mostly been published in anesthesiology and pain medicine journals, likely because specialist pain management physicians usually perform this procedure. Few studies about RFA have been published in rheumatology, orthopedic, and osteoarthritis journals, at least until very recently.

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RNA Therapeutics for the Cardiovascular System

Circulation, Volume 149, Issue 9, Page 707-716, February 27, 2024. RNA therapeutics hold significant promise in the treatment of cardiovascular diseases. RNAs are biologically diverse and functionally specific and can be used for gain- or loss-of-function purposes. The effectiveness of mRNA-based vaccines in the recent COVID-19 pandemic has undoubtedly proven the benefits of an RNA-based approach. RNA-based therapies are becoming more common as a treatment modality for cardiovascular disease. This is most evident in hypertension where several small interfering RNA–based drugs have proven to be effective in managing high blood pressure in several clinical trials. As befits a rapidly burgeoning field, there is significant interest in other classes of RNA. Revascularization of the infarcted heart through an mRNA drug is under clinical investigation. mRNA technology may provide the platform for the expression of paracrine factors for myocardial protection and regeneration. Emergent technologies on the basis of microRNAs and gene editing are tackling complex diseases in a novel fashion. RNA-based gene editing offers hope of permanent cures for monogenic cardiovascular diseases, and long-term control of complex diseases such as essential hypertension, as well. Likewise, microRNAs are proving effective in regenerating cardiac muscle. The aim of this review is to provide an overview of the current landscape of RNA-based therapies for the treatment of cardiovascular disease. The review describes the large number of RNA molecules that exist with a discussion of the clinical development of each RNA type. In addition, the review also presents a number of avenues for future development.

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Pragmatic phase II clinical trial to improve depression care in a real-world diverse MS cohort from an academic MS centre in Northern California: MS CATCH study protocol

Introduction
Depression occurs in over 50% of individuals living with multiple sclerosis (MS) and can be treated using many modalities. Yet, it remains: under-reported by patients, under-ascertained by clinicians and under-treated. To enhance these three behaviours likely to promote evidence-based depression care, we engaged multiple stakeholders to iteratively design a first-in-kind digital health tool. The tool, MS CATCH (Care technology to Ascertain, Treat, and engage the Community to Heal depression in patients with MS), closes the communication loop between patients and clinicians. Between clinical visits, the tool queries patients monthly about mood symptoms, supports patient self-management and alerts clinicians to worsening mood via their electronic health record in-basket. Clinicians can also access an MS CATCH dashboard displaying patients’ mood scores over the course of their disease, and providing comprehensive management tools (contributing factors, antidepressant pathway, resources in patient’s neighbourhood). The goal of the current trial is to evaluate the clinical effect and usability of MS CATCH in a real-world clinical setting.

Methods and analysis
MS CATCH is a single-site, phase II randomised, delayed start, trial enrolling 125 adults with MS and mild to moderately severe depression. Arm 1 will receive MS CATCH for 12 months, and arm 2 will receive usual care for 6 months, then MS CATCH for 6 months. Clinicians will be randomised to avoid practice effects. The effectiveness analysis is superiority intent-to-treat comparing MS CATCH to usual care over 6 months (primary outcome: evidence of screening and treatment; secondary outcome: Hospital Anxiety Depression Scale-Depression scores). The usability of the intervention will also be evaluated (primary outcome: adoption; secondary outcomes: adherence, engagement, satisfaction).

Ethics and dissemination
University of California, San Francisco Institutional Review Board (22-36620). The findings of the study are planned to be shared through conferences and publishments in a peer-reviewed journal. The deidentified dataset will be shared with qualified collaborators on request, provision of CITI and other certifications, and data sharing agreement. We will share the results, once the data are complete and analysed, with the scientific community and patient/clinician participants through abstracts, presentations and manuscripts.

Trial registration number
NCT05865405.

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Can we develop consensus on long-term follow-up and surveillance of primary shoulder arthroplasty? A study protocol using a real-time Delphi technique among expert clinicians in the UK

Background
Shoulder arthroplasty incidence is projected to continue its exponential growth and the resultant burden of monitoring patients with shoulder arthroplasty implants creates significant pressure on orthopaedic services. Surveillance offers the opportunity to study implant longevity, detect failing implants and potentially perform revision at lower morbidity and cost. There is a paucity of evidence to support recommendations on long-term follow-up in shoulder arthroplasty. Prospective studies comparing long-term follow-up and structure are impractical from time, resource and cost perspectives. A real-time Delphi technique represents a mechanism by which experts involved in long-term follow-up of primary shoulder arthroplasty can formulate recommendations via a transparent, reproducible and efficient process. We outline the protocol for a real-time Delphi study seeking consensus on long-term follow-up and surveillance of primary shoulder arthroplasty .

Methods
A real-time Delphi technique will be used. A planning committee will design the Delphi statements. A steering committee will supervise and monitor the real-time Delphi process. Participants will be asked to rate their agreement with statements using a 5-point Likert scale. The Delphi statements will be derived from review of published literature, and the strength of evidence available for each statement will be provided. We will offer participation to all surgeons and extended-scope practitioners who are current members of the British Elbow & Shoulder Society (BESS) and have clinical practice involving shoulder arthroplasty follow-up. The questionnaire will be active for 4 weeks and requires a minimum of 20 participants. Consensus agreement is defined as 70% of participants selecting at least a 4-point on a 5-point Likert scale.

Discussion
We anticipate the outlined study will achieve consensus on long-term follow-up and surveillance of primary shoulder arthroplasty. We intend to use the expert consensus recommendations achieved, in addition to the limited applicable published evidence available, to produce BESS-affiliated guidelines on long-term follow-up and surveillance of primary shoulder arthroplasty.
Ethics
Ethical approval is not required for the real-time Delphi study.
We expect the results of this initiative will be published in a peer-reviewed, high-impact journal.

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Voice disorder recognition using machine learning: a scoping review protocol

Introduction
Over the past decade, several machine learning (ML) algorithms have been investigated to assess their efficacy in detecting voice disorders. Literature indicates that ML algorithms can detect voice disorders with high accuracy. This suggests that ML has the potential to assist clinicians in the analysis and treatment outcome evaluation of voice disorders. However, despite numerous research studies, none of the algorithms have been sufficiently reliable to be used in clinical settings. Through this review, we aim to identify critical issues that have inhibited the use of ML algorithms in clinical settings by identifying standard audio tasks, acoustic features, processing algorithms and environmental factors that affect the efficacy of those algorithms.

Methods
We will search the following databases: Web of Science, Scopus, Compendex, CINAHL, Medline, IEEE Explore and Embase. Our search strategy has been developed with the assistance of the university library staff to accommodate the different syntactical requirements. The literature search will include the period between 2013 and 2023, and will be confined to articles published in English. We will exclude editorials, ongoing studies and working papers. The selection, extraction and analysis of the search data will be conducted using the ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews’ system. The same system will also be used for the synthesis of the results.

Ethics and dissemination
This scoping review does not require ethics approval as the review solely consists of peer-reviewed publications. The findings will be presented in peer-reviewed publications related to voice pathology.

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