Revisiting longitudinal qualitative studies in social work: considerations for design and methodological insights.

This paper undertakes an analysis and discussion of the methodological challenges and insights derived from three longitudinal qualitative studies, all conducted in Chile during the COVID-19 pandemic and subject to comprehensive theoretical-methodological reflection processes centred on their respective designs. This analysis makes a significant contribution to interdisciplinary discussions within social research, with a particular emphasis on longitudinal trajectories. First, we present a comparative analysis of three studies in social work, utilising Saldaña's questions addressing changes and learning in longitudinal studies. The first study explores the labour trajectories of researchers, the second focuses on the educational trajectories of students, and the last examines therapeutic alliance trajectories between social workers and families within the child protection system. Following this, we delve into the methodological decisions made by the research group during the execution of these longitudinal studies. This encompasses an examination of participant involvement, temporal definitions of the adopted designs, and the most suitable methodological tools for analysing change processes over time. The outcomes of this comparative analysis reveal the distinctive characteristics of the three longitudinal studies, providing insights into how the time dimension is explored within them. We highlight key criteria essential for consideration in longitudinal qualitative research, particularly regarding participants and methodology. In conclusion, we advocate for an expanded reflection within the realm of longitudinal qualitative methodology, encompassing aspects such as design choices, approaches to data analysis, integration of technology in information processing, and strategies for maintaining participant engagement.

Role of drug-eluting bead bronchial arterial chemoembolisation in the treatment of non-small cell lung cancer: protocol for a meta-analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) has a poor prognosis. Transvascular intervention is an important approach for treating NSCLC. Drug-eluting bead bronchial artery chemoembolisation (DEB-BACE) is a technique of using DEBs loaded with chemotherapeutic drugs for BACE. This study aims to conduct a meta-analysis to comprehensively assess the effectiveness and safety of DEB-BACE in treating NSCLC and investigate a novel therapeutic strategy for NSCLC. METHODS AND ANALYSIS: Wanfang, China National Knowledge Infrastructure, Medline (via PubMed), Cochrane Library, Scopus and Embase databases will be searched in November 2024. A meta-analysis will be conducted to assess the effectiveness and safety of DEB-BACE in the treatment of NSCLC. The following keywords will be applied: "Carcinoma, Non-Small-Cell Lung", "Non-Small Cell Lung Cancer", "Drug-Eluting Bead Bronchial Arterial Chemoembolization" and "drug-eluting beads". Reports in Chinese or English comparing the efficacy of DEB-BACE with other NSCLC treatment options will be included. Case reports, single-arm studies, conference papers, abstracts without full text and reports published in languages other than English and Chinese will not be considered. The Cochrane Handbook for Systematic Reviews of Interventions will be used to independently assess the risk of bias for each included study. In case of significant heterogeneity between studies, possible sources of heterogeneity will be explored through subgroup and sensitivity analysis. For the statistical analysis of the data, RevMan V.5.3 will be used. ETHICS AND DISSEMINATION: This meta-analysis will seek publication in a peer-reviewed journal on completion. Ethical approval is not required for this study as it is a database-based study. PROSPERO REGISTRATION NUMBER: CRD42023411392.

Integrating evidence and causal mapping of help-seeking behaviour of migrant women with postpartum depression in Shanghai, China: a scoping review protocol.

INTRODUCTION: The estimated prevalence of postpartum depression (PPD) worldwide, in China, and Shanghai is 17.2%, 18.0% and 23.2%, respectively. In 2021, Shanghai housed a population of 3.2 million childbearing-age migrant women, most of whom migrated to the city with their husbands for economic reasons. There is a general lack of help-seeking behaviour for mental disorders in China due to the perceived risk of social stigmatisation. In Shanghai, 70% of women did not seek professional help for perinatal mental health problems. We aim to gather information from multiple perspectives, such as the migrant women with PPD and perinatal depression (PND), their caregivers, health service providers and communities, to understand the help-seeking behaviour of postpartum migrant women with PPD or PND in China. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework for Scoping Reviews will guide this review. A bilingual research librarian developed a comprehensive search strategy to retrieve published and unpublished English and Chinese studies involving factors influencing women's PPD or PND help-seeking behaviour in China. This literature includes perceptions, views, patterns, acceptance and refusal, tendencies, probability, service accessibility and utilisation, and facts. We will search PubMed, Embase, Web of Science and CINAHL for English literature and CINKI for Chinese literature. Backward and forward snowball approaches will be used to identify additional relevant papers from the reference lists of selected papers. Two independent reviewers will screen the title and abstract and review the full text of selected papers to identify eligible articles for data extraction. We will build a Microsoft Access database to record the extracted data. The results will be presented in tables and a causal map to demonstrate the relationships between extracted variables and help-seeking behaviours for PPD and PND. A conceptual simulation model will be formulated based on the information from the literature to validate the logic of the relationships between variables, identify knowledge gaps and gain insights into potential intervention approaches. Experts and stakeholders will be invited to critique and comment on the results during group model building (GMB) workshops in Shanghai. These comments will be essential to validate the findings, receive feedback and obtain additional insights. ETHICS AND DISSEMINATION: The literature review component of our study does not require ethical approval because the information and data collected will be obtained from publicly available sources and will not involve human subjects. Our collaborating research partner, International Peach Maternal Child Hospital, obtained the IRB approval (GKLW-A-2023-020-01) for screening and enrolling participants in GMB workshops. Stanford University received IRB approval under protocol number 67 419. The full review will be presented at a relevant conference and submitted to a peer-reviewed scientific journal for publication to report findings.

Health literacy - study protocol for LiSa cohort study.

BACKGROUND: Health literacy is the degree to which individuals have the ability to find, understand, and use information and services to inform health-related decisions and actions for themselves and others, whether at home, at the workplace, in the community, marketplace, healthcare sector, or the political arena. The main aim of this project is to measure health literacy in the adult population living in the municipality of Leiria over the next 10 years. As secondary objectives it is intended to characterize anxiety and depression, metabolic risk and health behaviors in the same population and over the same period. METHODS: This is a prospective cohort study that collects data on HL, anxiety and depression, health characteristics, health behavior and sociodemographic data. The study population will be composed by adults (≥ 18 years old) who are non-institutionalized and living in private households in Leiria. The random sample is stratified by gender and age groups. A face-to-face interview will be conducted with the Computer Assisted Personal Interview at baseline. Follow-up will be carried out every 2 years via telephone call. The association between independent variables and health literacy is examined by means of variance analysis with measurement repetition, and taking into consideration follow-up. DISCUSSION: The LiSa project is a population-based study, derived from a random sampling technique that will allow the analysis of health outcomes in a representative sample of the population of the municipality of Leiria. The LiSa study will be a valuable resource for epidemiological research, as it will provide fundamental information to improve public health policies regarding health literacy in Portugal. TRIAL REGISTRATION: Clinical trials: NCT05558631 (registered on 26/09/2022).

Sample Size Determination and Study Design Impact on Dose-Scale Pharmacodynamic Bioequivalence: a Case Study Using Orlistat.

Dose-scale pharmacodynamic bioequivalence is recommended for evaluating the consistency of generic and innovator formulations of certain locally acting drugs, such as orlistat. This study aimed to investigate the standard methodology for sample size determination and the impact of study design on dose-scale pharmacodynamic bioequivalence using orlistat as the model drug. A population pharmacodynamic model of orlistat was developed using NONMEM 7.5.1 and utilized for subsequent simulations. Three different study designs were evaluated across various predefined relative bioavailability ratios of test/reference (T/R) formulations. These designs included Study Design 1 (2×1 crossover with T1 60 mg, R1 60 mg, and R2 120 mg), Study Design 2 (2×1 crossover with T2 120 mg, R1 60 mg, and R2 120 mg), and Study Design 3 (2×2 crossover with T1 60 mg, T2 120 mg, R1 60 mg, and R2 120 mg). Sample sizes were determined using a stochastic simulation and estimation approach. Under the same T/R ratio and power, Study Design 3 required the minimum sample size for bioequivalence, followed by Study Design 1, while Study Design 2 performed the worst. For Study Designs 1 and 3, a larger sample size was needed on the T/R ratio < 1.0 side for the same power compared to that on the T/R ratio > 1.0 side. The opposite asymmetry was observed for Study Design 2. We demonstrated that Study Design 3 is most effective for reducing the sample size for orlistat bioequivalence studies, and the impact of T/R ratio on sample size shows asymmetry.

Improving laboratory animal genetic reporting: LAG-R guidelines.

The biomedical research community addresses reproducibility challenges in animal studies through standardized nomenclature, improved experimental design, transparent reporting, data sharing, and centralized repositories. The ARRIVE guidelines outline documentation standards for laboratory animals in experiments, but genetic information is often incomplete. To remedy this, we propose the Laboratory Animal Genetic Reporting (LAG-R) framework. LAG-R aims to document animals' genetic makeup in scientific publications, providing essential details for replication and appropriate model use. While verifying complete genetic compositions may be impractical, better reporting and validation efforts enhance reliability of research. LAG-R standardization will bolster reproducibility, peer review, and overall scientific rigor.

Optimization of the extraction process for Shenshou Taiyi powder based on Box-Behnken experimental design, standard relation, and FAHP-CRITIC methods.

BACKGROUND: Ancient classic prescription play a crucial role in the preservation and advancement of traditional Chinese medicine (TCM) theories. They represent a significant milestone in the ongoing development and transmission of TCM knowledge and practices and are considered one of the breakthroughs in the development of TCM inheritance. In the process of developing ancient classic prescriptions, many problems may still arise in ensuring quality consistency between traditional methods and modern production processes, among which the extraction process poses major challenges. This paper introduces a practical approach extracting an ancient classic prescription using a modern extraction process. The technique is demonstrated through the study of the extraction process of Shenshou Taiyi powder (STP). METHODS: This study focuses on optimising the STP extraction process to ensure consistency in the quality of the product obtained through ancient and modern processes using the standard relation and fuzzy analytic hierarchical process (FAHP) and criteria importance through intercriteria correlation (CRITIC) method integrated weights combined with the Box-Behnken response surface test. Using the contents of rosmarinic acid, isoimperatorin, puerarin, as well as the extract yield and fingerprint similarity as evaluation indexes of STP, the Box-Behnken response surface method was employed to examine the varying extraction parameters, including water addition ratio, extraction duration, and number of extractions. The weighted coefficients for each parameter were calculated by combining the benchmark correlation and FAHP-CRITIC method, deriving a comprehensive score. RESULTS: The optimal extraction process for STP consisted of a two extractions, each using at a tenfold quantity of water, performed for one hour. Process verification across three separate batches yielded a comprehensive score of 94.7, with a relative standard deviation of 0.76%. CONCLUSIONS: The application of the Box-Behnken response surface method combined with standard relation and FAHP-CRITIC approach proved to be stable and feasible for optimising the extraction process of STP.

Statistical characteristics of analytical studies published in Peruvian medical journals from 2021 to 2022: A methodological study.

OBJECTIVE: While statistical analysis plays a crucial role in medical science, some published studies might have utilized suboptimal analysis methods, potentially undermining the credibility of their findings. Critically appraising analytical approaches can help elevate the standard of evidence and ensure clinicians and other stakeholders have trustworthy results on which to base decisions. The aim of the present study was to examine the statistical characteristics of original articles published in Peruvian medical journals in 2021-2022. DESIGN AND SETTING: We performed a methodological study of articles published between 2021 and 2022 from nine medical journals indexed in SciELO-Peru, Scopus, and Medline. We included original articles that conducted analytical analyses (i.e., association between variables). The statistical variables assessed were: statistical software used for analysis, sample size, and statistical methods employed (measures of effect), controlling for confounders, and the method employed for confounder control or epidemiological approaches. RESULTS: We included 313 articles (ranging from 11 to 77 across journals), of which 67.7% were cross-sectional studies. While 90.7% of articles specified the statistical software used, 78.3% omitted details on sample size calculation. Descriptive and bivariate statistics were commonly employed, whereas measures of association were less common. Only 13.4% of articles (ranging from 0% to 39% across journals) presented measures of effect controlling for confounding and explained the criteria for selecting such confounders. CONCLUSION: This study revealed important statistical deficiencies within analytical studies published in Peruvian journals, including inadequate reporting of sample sizes, absence of measures of association and confounding control, and suboptimal explanations regarding the methodologies employed for adjusted analyses. These findings highlight the need for better statistical reporting and researcher-editor collaboration to improve the quality of research production and dissemination in Peruvian journals.

Tutorial on Biostatistics: Sample Size and Power Calculation for Ophthalmic Studies With Correlated Binary Eye Outcomes.

Purpose: To describe and demonstrate sample size and power calculation for ophthalmic studies with a binary outcome from one or both eyes. Methods: We describe sample size and power calculation for four commonly used eye designs: (1) one-eye design or person-design: one eye per subject or outcome is at person-level; (2) paired design: two eyes per subject and two eyes are in different treatment groups; (3) two-eye design: two eyes per subject and both eyes are in the same treatment group; and (4) mixture design: mixture of one eye and two eyes per subject. For each design, we demonstrate sample size and power calculations in real ophthalmic studies. Results: Using formulas and commercial or free statistical packages including SAS, STATA, R, and PS, we calculated sample size and power. We demonstrated that different statistical packages require different parameters and provide similar, yet not identical, results. We emphasize that studies using data from two eyes of a subject need to account for the intereye correlation for appropriate sample size and power calculations. We demonstrate the gain in efficiency in designs that include two eyes of a subject compared to one-eye designs. Conclusions: Ophthalmic studies use different eye designs that include one or both eyes in the same or different treatment groups. Appropriate sample size and power calculations depend on the eye design and should account for intereye correlation when two eyes from some or all subjects are included in a study. Calculations can be executed using formulas and commercial or free statistical packages.

Ngulluk Moort, Ngulluk Boodja, Ngulluk Wirin (our family, our country, our spirit): An Aboriginal Participatory Action Research study protocol.

Globally, Indigenous children have historical and contemporary connections with government child protection services that have caused significant harm to their long-term health and wellbeing. Innovative, culturally secure and recovery focussed service provision is required. This paper describes a research protocol that has been designed by Indigenous researchers led by Indigenous Elders, to explore culturally secure care planning and service delivery in out-of-home care agencies in Australia. Using participatory action research methods, we will collect data using a variety of forums, including focus groups and semi-structured interviews. These data will explore the challenges for out-of-home care agencies in providing culturally secure care-planning, cultural activity and resources, and explore solutions to address factors that influence health and can assist to redress social inequities for Indigenous children. We aim to recruit approximately 100 participants for the qualitative study and 40 participants for the quantitative survey. Study participants will initially be recruited using purposive sampling, and as the study progresses will be recruited using a mixture of purposive and convenience sampling techniques. The rich data that this study is expected to yield, will inform ways to collect cultural information about Indigenous children and ways to provide cultural connections and activities that will have benefit to Indigenous children and families, and a broad range of social services.

Targeted psychological and psychosocial interventions for auditory hallucinations in persons with psychotic disorders: Protocol for a systematic review and meta-analysis.

BACKGROUND: In recent years, a growing body of evidence has demonstrated the efficacy of non-pharmacological interventions for schizophrenia spectrum disorders (SSD) including positive symptoms such as auditory hallucinations (AH). However, clinical trials predominantly examine general treatment effects for positive symptoms. Therefore, previous research is lacking in comprehensive and clear evidence about psychological and psychosocial approaches that are primarily tailored to treat AH. To overcome this knowledge gap in the current literature, we will conduct a systematic review and meta-analysis to assess the efficacy of clearly targeted psychological and psychosocial interventions for AH in persons with SSD. METHODS AND ANALYSIS: This study protocol has been developed according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. We will include all randomized controlled trials analyzing the efficacy of targeted psychological and psychosocial interventions especially aimed at treating AH in SSD. We will include studies on adult patients with SSD experiencing AH. The primary outcome will be the change on a published rating scale measuring AH. Secondary outcomes will be delusions, overall symptoms, negative symptoms, depression, social functioning, quality of life, and acceptability (drop-out). We will search relevant databases and the reference lists of included literature. The study selection process will be conducted by two independent reviewers. We will conduct a random-effect meta-analysis to consider heterogeneity across studies. Analyses will be carried out by software packages in R. The risk of bias in each study will be evaluated using the Cochrane Risk of Bias tool. Assessment of heterogeneity and sensitivity analysis will be conducted. DISCUSSION: The proposed study will augment the existing evidence by providing an overview of effective treatment approaches and their overall efficacy at treating AH in SSD. These findings will complement existing evidence that may impact future treatment implementations in clinical practice by addressing effective strategies to treat AH and therefore improve outcomes for the addressed population. ETHICS AND DISSEMINATION: No ethical issues are foreseen. We will publish the results from this study in peer-reviewed journals and at relevant scientific conferences. TRIAL REGISTRATION: PROSPERO registration number: CRD42023475704.

Health Outcomes around Pregnancy and Exposure to HIV/Antiretrovirals (HOPE) study protocol: a prospective observational cohort study of reproductive-aged women living with HIV.

INTRODUCTION: Over 265 000 women are living with HIV in the USA, but limited research has investigated the physical, mental and behavioural health outcomes among women living with HIV of reproductive age. Health status during the reproductive years before, during and after pregnancy affects pregnancy outcomes and long-term health. Understanding health outcomes among women living with HIV of reproductive age is of substantial public health importance, regardless of whether they experience pregnancy. The Health Outcomes around Pregnancy and Exposure to HIV/Antiretrovirals (HOPE) study is a prospective observational cohort study designed to investigate physical and mental health outcomes of young women living with HIV as they age, including HIV disease course, engagement in care, reproductive health and choices and cardiometabolic health. We describe the HOPE study design, and characteristics of the first 437 participants enrolled as of 1 January 2024. METHODS AND ANALYSIS: The HOPE study seeks to enrol and follow 1630 women living with HIV of reproductive age, including those with perinatally-acquired HIV, at 12 clinical sites across 9 US states and Puerto Rico. HOPE studies multilevel dynamic determinants influencing physical, mental and social well-being and behaviours of women living with HIV across the reproductive life course (preconception, pregnancy, post partum, not or never-pregnant), informed by the socioecological model. Key research areas include the clinical course of HIV, relationship of HIV and antiretroviral medications to reproductive health, pregnancy outcomes and comorbidities and the influence of racism and social determinants of health. HOPE began enrolling in April 2022. ETHICS AND DISSEMINATION: The HOPE study received approval from the Harvard Longwood Campus Institutional Review Board, the single institutional review board of record for all HOPE sites. Results will be disseminated through conference presentations, peer-reviewed journals and lay summaries.

Post-traumatic stress disorder symptoms following exposure to acute psychological trauma in children aged 8-16 years in South Africa: protocol for the Sinethemba longitudinal study.

INTRODUCTION: Children exposed to trauma are vulnerable to developing post-traumatic stress disorder (PTSD) and other adverse mental health outcomes. In low-and middle-income countries (LMICs), children are at increased risk of exposure to severe trauma and co-occurring adversities. However, relative to high-income countries, there is limited evidence of the factors that predict good versus poor psychological recovery following trauma exposure in LMIC children, and the role of caregiver support in these high-adversity communities. METHODS AND ANALYSIS: We will conduct a longitudinal, observational study of 250 children aged 8-16 years and their caregivers in South Africa, following child exposure to acute trauma. Dyads will be recruited from community hospitals following a potentially traumatic event, such as a motor vehicle accident or assault. Potential participants will be identified during their hospital visit, and if they agree, will subsequently be contacted by study researchers. Assessments will take place within 4 weeks of the traumatic event, with 3-month and 6-month follow-up assessments. Participants will provide a narrative description of the traumatic event and complete questionnaires designed to give information about social and psychological risk factors. Child PTSD symptoms will be the primary outcome, and wider trauma-related mental health (depression, anxiety, behavioural problems) will be secondary outcomes. Regression-based methods will be used to examine the association of psychosocial factors in the acute phase following trauma, including caregiver support and responding, with child PTSD and wider mental health outcomes. ETHICS AND DISSEMINATION: Ethical approvals have been granted by Stellenbosch University and the University of Bath, with additional approvals to recruit via hospitals and healthcare clinics being granted by the University of Cape Town, the Department of Health and the City of Cape Town. Study findings will be disseminated via publication in journals, workshops for practitioners and policy-makers, and public engagement events.

Leishmaniases in Ethiopia: a scoping review protocol to determine the scope of research and remaining gaps.

INTRODUCTION: The leishmaniases are among the group of neglected tropical diseases that cause significant morbidity and mortality each year. Currently, the East Africa region has the highest visceral leishmaniasis burden in the world. Ethiopia is one of the East African countries that reports both visceral and cutaneous forms of the disease. As part of the Nairobi Declaration, Ethiopia showed commitment to the elimination of visceral leishmaniasis by 2030. In this endeavour, it is important to understand the scope of research conducted on leishmaniases in the country and identify where the research gaps exist. Determining the research landscape is vital in the plan towards leishmaniases control and elimination. It will help to reference conducted research, determine if systematic reviews are warranted and help prioritise future research directions. METHODS AND ANALYSIS: This protocol was developed with reference to the JBI Scoping Review Methodology Group's guidance on conducting scoping reviews and the PRISMA-ScR reporting guidelines for scoping reviews. The following databases will be searched: PubMed, Embase via Embase.com, Web of Science Core Collection, Cochrane CENTRAL, Global Index Medicus, ClinicalTrials.gov, the Pan African Clinical Trials Registry and PROSPERO. Locally published literature that may not be indexed in the above-mentioned systems will be identified through team members familiar with the setting. Each record will be dually and blindly reviewed in an abstract-title screen and full-text screen using inclusion-exclusion criteria. Included articles must contain an in-depth discussion of leishmaniasis in Ethiopia. Data extracted will consist of study themes, study types, and categories and subcategories each defined in the developed codebook, in addition to type of leishmania, year of publication, funding source and the number of citations. Results will be reported with summary statistics. ETHICS AND DISSEMINATION: Individual consenting and ethical approvals are not applicable. We plan to disseminate our findings to the appropriate stakeholders.

Sample size calculation for comparing two ROC curves.

Biomarkers are key components of personalized medicine. In this paper, we consider biomarkers taking continuous values that are associated with disease status, called case and control. The performance of such a biomarker is evaluated by the area under the curve (AUC) of its receiver operating characteristic curve. Oftentimes, two biomarkers are collected from each subject to test if one has a larger AUC than the other. We propose a simple non-parametric statistical test for comparing the performance of two biomarkers. We also present a simple sample size calculation method for this test statistic. Our sample size formula requires specification of AUC values (or the standardized effect size of each biomarker between cases and controls together with the correlation coefficient between two biomarkers), prevalence of cases in the study population, type I error rate, and power. Through simulations, we show that the testing on two biomarkers controls type I error rate accurately and the proposed sample size closely maintains specified statistical power.

Ginseng supplementation and cardiovascular disease risk factors: a protocol for GRADE-assessed systematic review and dose-response meta-analysis.

INTRODUCTION: Heart diseases constitute a significant global public health concern. Cardiovascular diseases (CVDs) are characterised by disruptions in blood circulation and are notably prevalent among adults exposed to Westernised diets. Ginseng, a medicinal plant, has been recognised for its healing properties and has a history of use spanning thousands of years. This systematic review aims to evaluate the efficacy of ginseng in modifying risk factors for CVD, including lipid profiles, glycaemic control, anthropometric indices, inflammation indicators, blood pressure, oxidative stress, liver function tests, adipokines and heart rate among individuals aged 18 and above, encompassing both genders. METHODS AND ANALYSIS: We will conduct an electronic search for articles published from inception to September 2023 using a predefined search strategy in PubMed, Scopus, Web of Science, CENTRAL and EMBASE. Our search will focus exclusively on randomised controlled clinical trials involving both healthy and unhealthy participants. The process of reviewing articles, extracting pertinent information and assessing the quality of studies using the Cochrane risk of bias tool will be carried out independently by two reviewers. Any discrepancies will be resolved through discussion with a third party. If a sufficient number of eligible studies are identified, a meta-analysis will be conducted using these outcomes. ETHICS AND DISSEMINATION: This study serves as the procedural framework for a comprehensive examination and does not require ethical approval. Additionally, the study adhered to the guidelines outlined in the Declaration of Helsinki. Ethical approval for the study was obtained from the Ethics Committee of Golestan University of Medical Sciences (IR.GOUMS.REC.1402.298). PROSPERO REGISTRATION NUMBER: CRD42023465688.

Protocol for a systematic review with prospective individual patient data meta-analysis in EGFR-mutant NSCLC with brain metastases to assess the effect of SRS+osimertinib compared to osimertinib alone: the STARLET Collaboration.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice. METHODS: Randomised controlled trials will be eligible if they include participants with BM arising from EGFR-mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform's Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups. ETHICS AND DISSEMINATION: Approved by each trial's ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases. PROSPERO REGISTRATION: CRD42022330532.

Understanding the physiological and biological response to ambient heat exposure in pregnancy: protocol for a systematic review and meta-analysis.

INTRODUCTION: Climate change increases not only the frequency, intensity and duration of extreme heat events but also annual temperatures globally, resulting in many negative health effects, including harmful effects on pregnancy and pregnancy outcomes. As temperatures continue to increase precipitously, there is a growing need to understand the underlying biological pathways of this association. This systematic review will focus on maternal, placental and fetal changes that occur in pregnancy due to environmental heat stress exposure, in order to identify the evidence-based pathways that play a role in this association. METHODS AND ANALYSIS: We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search PubMed and Ovid Embase databases from inception using tested and validated search algorithms. Inclusion of any studies that involve pregnant women and have measured environmental heat stress exposure and either maternal, placental or fetal physiological or biochemical changes and are available in English. Modelling studies or those with only animals will be excluded. The risk of bias will be assessed using the Office of Health Assessment and Translation tool. Abstract screening, data extraction and risk of bias assessment will be conducted by two independent reviewers.Environmental parameters will be reported for each study and where possible these will be combined to calculate a heat stress indicator to allow comparison of exposure between studies. A narrative synthesis will be presented following standard guidelines. Where outcome measures have at least two levels of exposure, we will conduct a dose-response meta-analysis should there be at least three studies with the same outcome. A random effects meta-analysis will be conducted where at least three studies give the same outcome. ETHICS AND DISSEMINATION: This systematic review and meta-analysis does not require ethical approval. Dissemination will be through peer-reviewed journal publication and presentation at international conferences/interest groups. PROSPERO REGISTRATION NUMBER: CRD42024511153.

The Cleft Collective: protocol for a longitudinal prospective cohort study.

INTRODUCTION: Cleft lip and/or palate (CL/P) affects 1 in 700 live births globally. Children born with CL/P and their families face various challenges throughout the child's development. Extant research is often limited by small numbers and single-centre data. The Cleft Collective, a national cohort study in the UK, aims to build a resource, available to collaborators across the globe, to understand causes, best treatments and long-term outcomes for those born with CL/P, ultimately seeking to enhance their quality of life through improved understanding and care. METHODS AND ANALYSIS: A longitudinal prospective cohort study of children born with CL/P and their families. Recruitment occurs across the UK and started in November 2013. Recruitment will continue until September 2027 with an estimated final sample of 4822 children born with CL/P (1157 cleft lip including/excluding the alveolus; 2112 cleft palate only; 1042 unilateral cleft lip and palate and 511 bilateral cleft lip and palate). Biological samples are collected from all recruited members of the family. Parental and child questionnaires are collected at key time points throughout the child's development. Surgical data are collected at the time of surgical repair of the child's cleft. Consent is obtained to link to external data sources. Nested substudies can be hosted within the cohort. Regular engagement with participants takes place through birthday cards for the children, social media posts and newsletters. Patient and Public Involvement is conducted through the Cleft Lip And Palate Association and Cleft Collective Patient Consultation Group who provide insightful and essential guidance to the Cleft Collective throughout planning and conducting research. ETHICS AND DISSEMINATION: The Cleft Collective was ethically approved by the National Research Ethics Service committee South West-Central Bristol (REC13/SW/0064). Parental informed consent is required for participation. Findings from the Cleft Collective are disseminated through peer-reviewed publications, conference presentations, newsletters and social media.

Improving health system responses when patients are harmed: a protocol for a multistage mixed-methods study.

INTRODUCTION: At least 10% of hospital admissions in high-income countries, including Australia, are associated with patient safety incidents, which contribute to patient harm ('adverse events'). When a patient is seriously harmed, an investigation or review is undertaken to reduce the risk of further incidents occurring. Despite 20 years of investigations into adverse events in healthcare, few evaluations provide evidence of their quality and effectiveness in reducing preventable harm.This study aims to develop consistent, informed and robust best practice guidance, at state and national levels, that will improve the response, learning and health system improvements arising from adverse events. METHODS AND ANALYSIS: The setting will be healthcare organisations in Australian public health systems in the states of New South Wales, Queensland, Victoria and the Australian Capital Territory. We will apply a multistage mixed-methods research design with evaluation and in-situ feasibility testing. This will include literature reviews (stage 1), an assessment of the quality of 300 adverse event investigation reports from participating hospitals (stage 2), and a policy/procedure document review from participating hospitals (stage 3) as well as focus groups and interviews on perspectives and experiences of investigations with healthcare staff and consumers (stage 4). After triangulating results from stages 1-4, we will then codesign tools and guidance for the conduct of investigations with staff and consumers (stage 5) and conduct feasibility testing on the guidance (stage 6). Participants will include healthcare safety systems policymakers and staff (n=120-255) who commission, undertake or review investigations and consumers (n=20-32) who have been impacted by adverse events. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Northern Sydney Local Health District Human Research Ethics Committee (2023/ETH02007 and 2023/ETH02341).The research findings will be incorporated into best practice guidance, published in international and national journals and disseminated through conferences.