Evolving Improved Sampling Protocols for Dose-Response Modelling Using Genetic Algorithms with a Profile-Likelihood Metric.

Practical limitations of quality and quantity of data can limit the precision of parameter identification in mathematical models. Model-based experimental design approaches have been developed to minimise parameter uncertainty, but the majority of these approaches have relied on first-order approximations of model sensitivity at a local point in parameter space. Practical identifiability approaches such as profile-likelihood have shown potential for quantifying parameter uncertainty beyond linear approximations. This research presents a genetic algorithm approach to optimise sample timing across various parameterisations of a demonstrative PK-PD model with the goal of aiding experimental design. The optimisation relies on a chosen metric of parameter uncertainty that is based on the profile-likelihood method. Additionally, the approach considers cases where multiple parameter scenarios may require simultaneous optimisation. The genetic algorithm approach was able to locate near-optimal sampling protocols for a wide range of sample number (n = 3-20), and it reduced the parameter variance metric by 33-37% on average. The profile-likelihood metric also correlated well with an existing Monte Carlo-based metric (with a worst-case r > 0.89), while reducing computational cost by an order of magnitude. The combination of the new profile-likelihood metric and the genetic algorithm demonstrate the feasibility of considering the nonlinear nature of models in optimal experimental design at a reasonable computational cost. The outputs of such a process could allow for experimenters to either improve parameter certainty given a fixed number of samples, or reduce sample quantity while retaining the same level of parameter certainty.

Co-creation of a toolkit to assist risk communication and clinical decision-making in severe preeclampsia: SPOT-Impact study design.

Globally, the incidence of hypertensive disorders of pregnancy, especially preeclampsia, remains high, particularly in low- and middle-income countries. The burden of adverse maternal and perinatal outcomes is particularly high for women who develop a hypertensive disorder remote from term (<34 weeks). In parallel, many women have a suboptimal experience of care. To improve the quality of care in terms of provision and experience, there is a need to support the communication of risks and making of treatment decision in ways that promote respectful maternity care. Our study objective is to co-create a tool(kit) to support clinical decision-making, communication of risks and shared decision-making in preeclampsia with relevant stakeholders, incorporating respectful maternity care, justice, and equity principles. This qualitative study detailing the exploratory phase of co-creation takes place over 17 months (Nov 2021-March 2024) in the Greater Accra and Eastern Regions of Ghana. Informed by ethnographic observations of care interactions, in-depth interviews and focus group and group discussions, the tool(kit) will be developed with survivors and women with hypertensive disorders of pregnancy and their families, health professionals, policy makers, and researchers. The tool(kit) will consist of three components: quantitative predicted risk (based on external validated risk models or absolute risk of adverse outcomes), risk communication, and shared decision-making support. We expect to co-create a user-friendly tool(kit) to improve the quality of care for women with preeclampsia remote from term which will contribute to better maternal and perinatal health outcomes as well as better maternity care experience for women in Ghana.

Adverse maternal and perinatal outcomes is high for women who develop preeclampsia remote from term (<34 weeks). To improve the quality of provision and experience of care, there is a need to support communication of risks and treatment decisions that promotes respectful maternity care.This article describes the methodology deployed to cocreate a user-friendly tool(kit) to support risk communication and shared decision-making in the context of severe preeclampsia in a low resource setting.

Approaches and experiences implementing remote, electronic consent at the Leeds Clinical Trials Research Unit.

BACKGROUND: Use of electronic methods to support informed consent ('eConsent') is increasingly popular in clinical research. This commentary reports the approach taken to implement electronic consent methods and subsequent experiences from a range of studies at the Leeds Clinical Trials Research Unit (CTRU), a large clinical trials unit in the UK. MAIN TEXT: We implemented a remote eConsent process using the REDCap platform. The process can be used in trials of investigational medicinal products and other intervention types or research designs. Our standard eConsent system focuses on documenting informed consent, with other aspects of consent (e.g. providing information to potential participants and a recruiter discussing the study with each potential participant) occurring outside the system, though trial teams can use electronic methods for these activities where they have ethical approval. Our overall process includes a verbal consent step prior to confidential information being entered onto REDCap and an identity verification step in line with regulator guidance. We considered the regulatory requirements around the system's generation of source documents, how to ensure data protection standards were upheld and how to monitor informed consent within the system. We present four eConsent case studies from the CTRU: two randomised clinical trials and two other health research studies. These illustrate the ways eConsent can be implemented, and lessons learned, including about differences in uptake. CONCLUSIONS: We successfully implemented a remote eConsent process at the CTRU across multiple studies. Our case studies highlight benefits of study participants being able to give consent without having to be present at the study site. This may better align with patient preferences and trial site needs and therefore improve recruitment and resilience against external shocks (such as pandemics). Variation in uptake of eConsent may be influenced more by site-level factors than patient preferences, which may not align well with the aspiration towards patient-centred research. Our current process has some limitations, including the provision of all consent-related text in more than one language, and scalability of implementing more than one consent form version at a time. We consider how enhancements in CTRU processes, or external developments, might affect our approach.

Measuring protective efficacy and quantifying the impact of drug resistance: A novel malaria chemoprevention trial design and methodology.

BACKGROUND: Recently revised WHO guidelines on malaria chemoprevention have opened the door to more tailored implementation. Countries face choices on whether to replace old drugs, target additional age groups, and adapt delivery schedules according to local drug resistance levels and malaria transmission patterns. Regular routine assessment of protective efficacy of chemoprevention is key. Here, we apply a novel modelling approach to aid the design and analysis of chemoprevention trials and generate measures of protection that can be applied across a range of transmission settings. METHODS AND FINDINGS: We developed a model of genotype-specific drug protection, which accounts for underlying risk of infection and circulating genotypes. Using a Bayesian framework, we fitted the model to multiple simulated scenarios to explore variations in study design, setting, and participant characteristics. We find that a placebo or control group with no drug protection is valuable but not always feasible. An alternative approach is a single-arm trial with an extended follow-up (>42 days), which allows measurement of the underlying infection risk after drug protection wanes, as long as transmission is relatively constant. We show that the currently recommended 28-day follow-up in a single-arm trial results in low precision of estimated 30-day chemoprevention efficacy and low power in determining genotype differences of 12 days in the duration of protection (power = 1.4%). Extending follow-up to 42 days increased precision and power (71.5%) in settings with constant transmission over this time period. However, in settings of unstable transmission, protective efficacy in a single-arm trial was overestimated by 24.3% if recruitment occurred during increasing transmission and underestimated by 15.8% when recruitment occurred during declining transmission. Protective efficacy was estimated with greater precision in high transmission settings, and power to detect differences by resistance genotype was lower in scenarios where the resistant genotype was either rare or too common. CONCLUSIONS: These findings have important implications for the current guidelines on chemoprevention efficacy studies and will be valuable for informing where these studies should be optimally placed. The results underscore the need for a comparator group in seasonal settings and provide evidence that the extension of follow-up in single-arm trials improves the accuracy of measures of protective efficacy in settings with more stable transmission. Extension of follow-up may pose logistical challenges to trial feasibility and associated costs. However, these studies may not need to be repeated multiple times, as the estimates of drug protection against different genotypes can be applied to different settings by adjusting for transmission intensity and frequency of resistance.

Standard cardiopulmonary resuscitation versus chest compressions only after out-of-hospital cardiac arrest: a protocol for a systematic review and meta-analysis.

INTRODUCTION: The 2020 American Heart Association guidelines encourage lay rescuers to provide chest compression-only cardiopulmonary resuscitation to simplify the process and encourage cardiopulmonary resuscitation initiation. However, recent clinical trials had contradictory results about chest compression-only cardiopulmonary resuscitation. This study will aim to compare standard and chest compressions-only cardiopulmonary resuscitation after out-of-hospital cardiac arrest. METHODS AND ANALYSIS: This study will retrieve only randomised and quasi-randomised controlled trials from the Cochrane Library, PubMed, Web of Science and Embase databases. Data on study design, participant characteristics, intervention details and outcomes will be extracted by a unified standard form. Primary outcomes to be assessed are hospital admission, discharge, and 30-day survival, and return of spontaneous circulation. The Grading of Recommendations, Assessment, Development and Evaluation framework will evaluate the quality of evidence. Cochrane's tool for assessing the risk of bias will evaluate risk deviation. If the I2 statistic is lower than 40%, the fixed-effects model will be used for meta-analysis. Otherwise, the random-effects model will be used. The search will be performed following the publication of this protocol (estimated to occur on 30 December 2024). DISCUSSION: This study will evaluate the effect of chest compression-only cardiopulmonary resuscitation after out-of-hospital cardiac arrest and provide evidence for cardiopulmonary resuscitation guidelines. ETHICS AND DISSEMINATION: No patient or public entity will be involved in this study. Therefore, the study does not need to be ethically reviewed. The results of the study will be disseminated through peer-reviewed journal publications and committee conferences. PROSPERO REGISTRATION NUMBER: CRD42021295507.

Effectiveness and cost-effectiveness of community-based directly observed treatment (DOT) versus health facility-based DOT of tuberculosis in Africa: protocol for a systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) remains a significant global health challenge, especially prevalent in the WHO African region. The WHO's End TB Strategy emphasises effective treatment approaches such as directly observed therapy (DOT), yet the optimal implementation of DOT, whether through health facility-based (HF DOT) or community-based (CB DOT) approaches, remains uncertain. OBJECTIVE: To conduct a systematic comparison of the effectiveness and cost-effectiveness of Community-Based Directly Observed Treatment (CB DOT) versus Health Facility-Based Directly Observed Treatment (HF DOT) for tuberculosis (TB) treatment in African settings. METHODS: We will conduct a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search PubMed, Embase, Web of Science, Scopus and the Cochrane Library for articles published up to 30 March 2023, without date restrictions. Eligible studies must be full economic evaluations conducted in African countries, comparing CB DOT to HF DOT regarding treatment outcomes and costs. Exclusion criteria include non-English, non-peer-reviewed or studies lacking caregiver involvement in CB DOT, health facility-based DOT comparison, direct comparability between CB DOT and HF DOT, significant selection bias or non-economic evaluations. Data extraction will be performed independently by reviewers, and meta-analyses will use STATA software. To pool the data, a random-effect model will be applied, and quality assessment of the studies will be conducted. ETHICS AND DISSEMINATION: Ethical approval is not required as the study will use previously published articles available publicly. Findings will be presented at international and national conferences and published in open-access, peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023443260.

Personal growth initiative across the life span: a systematic review protocol of quantitative studies using the Personal Growth Initiative Scale-II.

BACKGROUND: Personal Growth Initiative (PGI) a multi-dimensional construct, conceptualised as a skill set that helps individuals to intentionally grow is considered an important construct throughout the life span. Coping with the challenges, transitions, experiences and stressors of life requires an active growth orientation. In previous empirical research, the construct has been measured by either the PGIS-I or PGIS-II, of which only the latter takes account of the theoretically established multi-dimensionality of the construct. This paper describes the protocol for conducting a systematic review of published peer-reviewed empirical research articles on the multi-dimensional construct of PGI. The aim of this review is threefold: (1) to better understand the multi-dimensional construct PGI in different contexts and populations, (2) to improve our understanding of the reliability and validity of the PGIS-II in various research populations and (3) to obtain an overview of its associations with relevant psychosocial factors. METHODS: For the development of this protocol, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) reporting guidelines were used. Four databases and one registry will be searched using a predetermined search strategy for relevant studies. Studies will be screened, by two reviewers independently, against the established inclusion criteria. During the data extraction process, the quality of the included studies will be assessed using the Quality Assessment for Survey Studies in Psychology (Q-SSP). The collected data will then be analysed and reported in both narrative and tabular form according to the PRISMA 2020 statement guidelines and flow diagram. DISCUSSION: The findings of this study will increase our understanding of the dynamics of PGI throughout the lifespan, its associations with other psychosocial factors and the psychometric properties of the PGIS-II. It will also clarify where additional research is needed. The objectives of the proposed review can provide a basis for the development of practical applications and interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022377342.

A systematic review to determine the effect of strategies to sustain chronic disease prevention interventions in clinical and community settings: study protocol.

BACKGROUND: The primary purpose of this review is to synthesise the effect of strategies aiming to sustain the implementation of evidenced-based interventions (EBIs) targeting key health behaviours associated with chronic disease (i.e. physical inactivity, poor diet, harmful alcohol use, and tobacco smoking) in clinical and community settings. The field of implementation science is bereft of an evidence base of effective sustainment strategies, and as such, this review will provide important evidence to advance the field of sustainability research. METHODS: This systematic review protocol is reported in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) checklist. Methods will follow Cochrane gold-standard review methodology. The search will be undertaken across multiple databases, adapting filters previously developed by the research team, data screening and extraction will be performed in duplicate, strategies will be coded using an adapted sustainability-explicit taxonomy, and evidence will be synthesised using appropriate methods (i.e. meta-analytic following Cochrane or non-meta-analytic following SWiM guidelines). We will include any randomised controlled study that targets any staff or volunteers delivering interventions in clinical or community settings. Studies which report on any objective or subjective measure of the sustainment of a health prevention policy, practice, or programme within any of the eligible settings will be included. Article screening, data extraction, risk of bias, and quality assessment will be performed independently by two review authors. Risk of bias will be assessed using Version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2). A random-effect meta-analysis will be conducted to estimate the pooled effect of sustainment strategies separately by setting (i.e. clinical and community). Sub-group analyses will be undertaken to explore possible causes of statistical heterogeneity and may include the following: time period, single or multi-strategy, type of setting, and type of intervention. Differences between sub-groups will be statistically compared. DISCUSSION/CONCLUSION: This will be the first systematic review to determine the effect of strategies designed to support sustainment on sustaining the implementation of EBIs in clinical and community settings. The findings of this review will directly inform the design of future sustainability-focused implementation trials. Further, these findings will inform the development of a sustainability practice guide for public health practitioners. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022352333.

Upstrapping to determine futility: predicting future outcomes nonparametrically from past data.

BACKGROUND: Clinical trials often involve some form of interim monitoring to determine futility before planned trial completion. While many options for interim monitoring exist (e.g., alpha-spending, conditional power), nonparametric based interim monitoring methods are also needed to account for more complex trial designs and analyses. The upstrap is one recently proposed nonparametric method that may be applied for interim monitoring. METHODS: Upstrapping is motivated by the case resampling bootstrap and involves repeatedly sampling with replacement from the interim data to simulate thousands of fully enrolled trials. The p-value is calculated for each upstrapped trial and the proportion of upstrapped trials for which the p-value criteria are met is compared with a pre-specified decision threshold. To evaluate the potential utility for upstrapping as a form of interim futility monitoring, we conducted a simulation study considering different sample sizes with several different proposed calibration strategies for the upstrap. We first compared trial rejection rates across a selection of threshold combinations to validate the upstrapping method. Then, we applied upstrapping methods to simulated clinical trial data, directly comparing their performance with more traditional alpha-spending and conditional power interim monitoring methods for futility. RESULTS: The method validation demonstrated that upstrapping is much more likely to find evidence of futility in the null scenario than the alternative across a variety of simulations settings. Our three proposed approaches for calibration of the upstrap had different strengths depending on the stopping rules used. Compared to O'Brien-Fleming group sequential methods, upstrapped approaches had type I error rates that differed by at most 1.7% and expected sample size was 2-22% lower in the null scenario, while in the alternative scenario power fluctuated between 15.7% lower and 0.2% higher and expected sample size was 0-15% lower. CONCLUSIONS: In this proof-of-concept simulation study, we evaluated the potential for upstrapping as a resampling-based method for futility monitoring in clinical trials. The trade-offs in expected sample size, power, and type I error rate control indicate that the upstrap can be calibrated to implement futility monitoring with varying degrees of aggressiveness and that performance similarities can be identified relative to considered alpha-spending and conditional power futility monitoring methods.

Implementation of a primary-tertiary shared care model to improve the detection of familial hypercholesterolaemia (FH): a mixed methods pre-post implementation study protocol.

INTRODUCTION: Familial hypercholesterolaemia (FH) is an autosomal dominant inherited disorder of lipid metabolism and a preventable cause of premature cardiovascular disease. Current detection rates for this highly treatable condition are low. Early detection and management of FH can significantly reduce cardiac morbidity and mortality. This study aims to implement a primary-tertiary shared care model to improve detection rates for FH. The primary objective is to evaluate the implementation of a shared care model and support package for genetic testing of FH. This protocol describes the design and methods used to evaluate the implementation of the shared care model and support package to improve the detection of FH. METHODS AND ANALYSIS: This mixed methods pre-post implementation study design will be used to evaluate increased detection rates for FH in the tertiary and primary care setting. The primary-tertiary shared care model will be implemented at NSW Health Pathology and Sydney Local Health District in NSW, Australia, over a 12-month period. Implementation of the shared care model will be evaluated using a modification of the implementation outcome taxonomy and will focus on the acceptability, evidence of delivery, appropriateness, feasibility, fidelity, implementation cost and timely initiation of the intervention. Quantitative pre-post and qualitative semistructured interview data will be collected. It is anticipated that data relating to at least 62 index patients will be collected over this period and a similar number obtained for the historical group for the quantitative data. We anticipate conducting approximately 20 interviews for the qualitative data. ETHICS AND DISSEMINATION: Ethical approval has been granted by the ethics review committee (Royal Prince Alfred Hospital Zone) of the Sydney Local Health District (Protocol ID: X23-0239). Findings will be disseminated through peer-reviewed publications, conference presentations and an end-of-study research report to stakeholders.

Cost analysis for initiating an integrated package of essential non-communicable disease interventions (PEN-Plus) in Kondoa District Hospital, Tanzania: a time-driven activity-based costing (TDABC) study protocol.

INTRODUCTION: Non-communicable diseases (NCDs) constitute approximately 74% of global mortality, with 77% of these deaths occurring in low-income and middle-income countries. Tanzania exemplifies this situation, as the percentage of total disability-adjusted life years attributed to NCDs has doubled over the past 30 years, from 18% to 36%. To mitigate the escalating burden of severe NCDs, the Tanzanian government, in collaboration with local and international partners, seeks to extend the integrated package of essential interventions for severe NCDs (PEN-Plus) to district-level facilities, thereby improving accessibility. This study aims to estimate the cost of initiating PEN-Plus for rheumatic heart disease, sickle cell disease and type 1 diabetes at Kondoa district hospital in Tanzania. METHODS AND ANALYSIS: We will employ time-driven activity-based costing (TDABC) to quantify the capacity cost rates (CCR), and capital and recurrent costs associated with the implementation of PEN-Plus. Data on resource consumption will be collected through direct observations and interviews with nurses, the medical officer in charge and the heads of laboratory and pharmacy units/departments. Data on contact times for targeted NCDs will be collected by observing a sample of patients as they move through the care delivery pathway. Data cleaning and analysis will be done using Microsoft Excel. ETHICS AND DISSEMINATION: Ethical approval to conduct the study has been waived by the Norwegian Regional Ethics Committee and was granted by the Tanzanian National Health Research Ethics Committee NIMR/HQ/R.8a/Vol.IX/4475. A written informed consent will be provided to the study participants. This protocol has been disseminated in the Bergen Centre for Ethics and Priority Setting International Symposium, Norway and the 11th Muhimbili University of Health and Allied Sciences Scientific Conference, Tanzania in 2023. The findings will be published in peer-reviewed journals for use by the academic community, researchers and health practitioners.

Prevalence and health effects of post-COVID-19 condition in Africa: a scoping review protocol.

INTRODUCTION: SARS-CoV-2 pandemic has caused global devastations in the social, economic and health systems of every nation, but disproportionately the nations in Africa. Apart from its grave effects on the global systems, is the persistence of post-COVID-19 condition in individuals infected with the virus. Therefore, the aim of this scoping review is to collate and summarise the existing research evidence about the prevalence and health effects of post-COVID-19 infection conditions in Africa. METHODS AND ANALYSIS: Five main databases will be thoroughly searched from 1 September 2023 to 30 April 2024, for eligible articles based on the inclusion and exclusion criteria. These databases include PubMed, Central, Scopus, Dimensions AI and JSTOR. Meanwhile, Arksey and O'Malley guidelines will guide this scoping review using article published between 1 January 2020 and 30 April 2024. This review will provide a useful insight into the prevalence of the post-COVID-19 symptoms and their health effects within the population in Africa. The results and findings of the review will be valuable for health system interventions, including restructuring and reorientation of health systems in the continent. ETHICS AND DISSEMINATION: This scoping review will involve analysis of secondary data, therefore, no ethical approval is needed. Dissemination of the results will be done through international journals and available research conferences.

Exploring type 2 diabetes self-management practices in rural Bangladesh: facilitators, barriers and expectations-a qualitative study protocol.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a global public health crisis impacting low-income and middle-income countries such as Bangladesh. While self-management is encouraged for individuals with T2DM, there is a significant lack of knowledge regarding the factors of facilitators, barriers and expectations associated with T2DM self-management in Bangladesh. This research aims to investigate the potential elements that support, impede and are anticipated in the effective practice of self-management for T2DM in rural areas of Bangladesh. METHODS AND ANALYSIS: This study will use an exploratory qualitative approach. 16 focus group discussions, 13 in-depth interviews and 9 key informant interviews will be conducted among multilevel stakeholders, including people with T2DM, their caregivers, healthcare providers, health managers/administrators and policy planners. Interviews will be audio-recorded, transcribed, translated and analysed using thematic analysis. ETHICS AND DISSEMINATION: This research project has been approved by the Monash University Human Research Ethics Committee (project reference number: 39483) and the Ethical Review Committee of the Centre for Injury Prevention and Research, Bangladesh (Memo: CIPRB/ERC/2023/14). Research findings will be disseminated in peer-reviewed journals and conference presentations. Published reports will include group data. Individual data privacy will be strictly maintained.

Saxon Epidemiological Study in General Practice-6 (SESAM-6): protocol of a cross-sectional study.

INTRODUCTION: General practitioners (GPs) are mostly the first point of contact for patients with health problems in Germany. There is only a limited epidemiological overview data that describe the GP consultation hours based on other than billing data. Therefore, the aim of Saxon Epidemiological Study in General Practice-6 (SESAM-6) is to examine the frequency of reasons for encounter, prevalence of long-term diagnosed diseases and diagnostic and therapeutic decisions in general practice. This knowledge is fundamental to identify the healthcare needs and to develop strategies to improve the GP care. The results of the study will be incorporated into the undergraduate, postgraduate and continuing medical education for GP. METHODS AND ANALYSIS: This cross-sectional study SESAM-6 is conducted in general practices in the state of Saxony, Germany. The study design is based on previous SESAM studies. Participating physicians are assigned to 1 week per quarter (over a survey period of 12 months) in which every fifth doctor-patient contact is recorded for one-half of the day (morning or afternoon). To facilitate valid statements, a minimum of 50 GP is required to document a total of at least 2500 doctor-patient contacts. Univariable, multivariable and subgroup analyses as well as comparisons to the previous SESAM data sets will be conducted. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the Technical University of Dresden in March 2023 (SR-EK-7502023). Participation in the study is voluntary and will not be remunerated. The study results will be published in peer-reviewed scientific journals, preferably with open access. They will also be disseminated at scientific and public symposia, congresses and conferences. A final report will be published to summarise the central results and provided to all study participants and the public.

Optimal approach for ultrasound-guided transversus abdominis plane (TAP) blocks for abdominal surgeries: a protocol for systematic review and meta-analysis.

INTRODUCTION: Transversus abdominis plane (TAP) blocks are commonly used for postoperative analgesia after various abdominal surgeries. There are several different approaches for performing TAP blocks, mainly including posterior, lateral and subcostal approaches. An increasing number of randomised controlled trials (RCTs) have compared the analgesic effects of different TAP block approaches, but the results have not been consistent. This protocol aims to determine the optimal approach of ultrasound-guided TAP blocks for postoperative analgesia after abdominal surgery. METHODS AND ANALYSIS: Four databases, including Web of Science, PubMed, EMBASE and the Cochrane Library will be systematically searched to identify RCTs that compared the analgesic effects of different ultrasound-guided TAP block approaches. The search interval will range from the inception of the databases to 30 July 2024. The postoperative opioid consumption over 24 hours will be defined as the primary outcome. The secondary outcomes will include the analgesia duration, postoperative pain scores at rest and during movement at different timepoints and the incidence of adverse effects. All the statistical analyses will be conducted using RevMan V.5.4. The quality of evidence will be evaluated by the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval will not be needed. The results will be submitted to one peer-reviewed journal when completed. PROSPERO REGISTRATION NUMBER: CRD42024510141.

How does eligibility for GusNIP produce prescriptions relate to fruit and vegetable purchases and what factors shape the relationship? A protocol for a secondary analysis of nationally representative data in the USA.

INTRODUCTION: US Department of Agriculture (USDA) Gus Schumacher Nutrition Incentive Programme (GusNIP) produce prescription programme (PPR) 'prescriptions' provide eligible participants with low income, risk for diet-related chronic disease and food insecurity a healthcare issued incentive to purchase lower to no cost fruits and vegetables (FVs). However, GusNIP requirements specify that PPR prescriptions can only be redeemed for fresh (not frozen, canned or dried) FVs. This requirement may prevent participants from fully engaging in or benefiting from GusNIP PPR, given communities with lower healthy food access may have reduced fresh FV accessibility. METHODS AND ANALYSIS: We will use the nationally representative 2012-2013 National Household Food Acquisition and Purchase Survey (FoodAPS) and complementary FoodAPS Geography Component data in a secondary data analysis to examine how household GusNIP PPR eligibility relates to the quantity and variety of fresh, frozen, canned and dried FV purchases and to what extent individual, household and food environment factors shape the relationship. FoodAPS data include household food purchasing and acquisition information across a 7 day period from 14 317 individuals among 4826 households and was collected between April 2012 and January 2013. The FoodAPS Geography Component provides information about the local community/environment relative to FoodAPS households. This study will examine the correlation or association of selected variables between different quantities and varieties of fresh, frozen, canned and dried FVs, as well as correlations among multilevel predictors. ETHICS AND DISSEMINATION: We are following data integrity standards as outlined by agreements with the USDA Economic Research Service. All results of analyses will undergo a thorough disclosure review to ensure no identifiable data are shared. Results will be disseminated to research, practice and policy communities using an Open Access peer-reviewed manuscript(s), scientific and practice presentations, and a public facing report and infographic.

Impacts on paediatricians testifying in cases of child maltreatment: protocol for a systematic review.

INTRODUCTION: Paediatricians perform medical assessments for children in cases of suspected child maltreatment. Due to their role with statutory child protection agencies and police, paediatricians may be asked to testify in court about child protection and criminal justice matters. To the authors' knowledge, there has been no previous systematic review of the literature synthesising the evidence on the impacts on paediatricians testifying in cases of child maltreatment. METHODS AND ANALYSIS: A search strategy comprising indexed and key terms will be applied to six electronic reference databases from inception to May 2023: Medline, EMBASE, PsycINFO, CINAHL, Criminal Justice Abstracts and Cochrane Library. Two reviewers will independently screen titles and abstracts and full-text articles against predefined eligibility criteria to identify studies of interest. Conflicts will be independently adjudicated by a third reviewer. ETHICS AND DISSEMINATION: Since the systematic review methodology aims at synthesising information from available publications, this study does not require ethical approval. An article reporting the results of the systematic review will be submitted for publication in a scientific journal, presented at relevant conferences and used in subsequent stakeholder consultations.

Factors influencing the outcomes of non-pharmacological interventions for managing fatigue across the lifespan of people living with musculoskeletal (MSK) conditions: a scoping review protocol.

INTRODUCTION: Fatigue is an important and distressing symptom for many people living with chronic musculoskeletal (MSK) conditions. Many non-pharmacological interventions have been investigated in recent years and some have been demonstrated to be effective in reducing fatigue and fatigue impact, however, there is limited guidance for clinicians to follow regarding the most appropriate management options. The objective of this scoping review is to understand and map the extent of evidence in relation to the factors that relate to the outcome of non-pharmacological interventions on MSK condition-related fatigue across the lifespan. METHODS AND ANALYSIS: This scoping review will include evidence relating to people of all ages living with chronic MSK conditions who have been offered a non-pharmacological intervention with either the intention or effect of reducing fatigue and its impact. Databases including AMED, PsycINFO, CINAHLPlus, MEDLINE, EMBASE and Scopus will be searched for peer-reviewed primary research studies published after 1 January 2007 in English language. These findings will be used to identify factors associated with successful interventions and to map gaps in knowledge. ETHICS AND DISSEMINATION: Ethical approval was not required for this review. Findings will be disseminated by journal publications, conference presentations and by communicating with relevant healthcare and charity organisations.

Impact of androgenic anabolic steroid use on cardiovascular and mental health in Danish recreational athletes: protocol for a nationwide cross-sectional cohort study as a part of the Fitness Doping in Denmark (FIDO-DK) study.

INTRODUCTION: The use of androgenic anabolic steroids (AASs) among recreational athletes is steadily increasing. However, knowledge regarding the potentially harmful effects of AAS primarily originates from case reports and small observational studies. This large-scale study aims to investigate the impact of AAS use on vascular plaque formation, preclinical coronary disease, cardiac function, circulating cardiovascular risk markers, quality of life (QoL) and mental health in a broad population of illicit AAS users. METHODS AND ANALYSES: A nationwide cross-sectional cohort study including a diverse population of men and women aged ≥18 years, with current or previous illicit AAS use for at least 3 months. Conducted at Odense University Hospital, Denmark, the study comprises two parts. In part A (the pilot study), 120 recreational athletes with an AAS history will be compared with a sex-matched and age-matched control population of 60 recreational athletes with no previous AAS use. Cardiovascular outcomes include examination of non-calcified coronary plaque volume and calcium score using coronary CT angiography, myocardial structure and function via echocardiography, and assessing carotid and femoral artery plaques using ultrasonography. Retinal microvascular status is evaluated through fundus photography. Cardiovascular risk markers are measured in blood. Mental health outcomes include health-related QoL, interpersonal difficulties, body image concerns, aggression dimensions, anxiety symptoms, depressive severity and cognitive function assessed through validated questionnaires. The findings of our comprehensive study will be used to compose a less intensive investigatory cohort study of cardiovascular and mental health (part B) involving a larger group of recreational athletes with a history of illicit AAS use. ETHICS AND DISSEMINATION: The study received approval from the Regional Committee on Health Research Ethics for Southern Denmark (S-20210078) and the Danish Data Protection Agency (21/28259). All participants will provide signed informed consent. Research outcomes will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT05178537.