BMJ Open最新文献

Objective: To examine longitudinal trends in infertility management in women attending general practice.

Design: Cohort study using the national general practice dataset, MedicineInsight.

Setting: Australian general practice.

Interventions: Not applicable.

Participants: The cohort included 2 552 339 women aged 18-49 years with one or more general practice clinical encounters between January 2011 and December 2021.

Primary and secondary outcome measuress: The primary outcome assessed was the proportion of women who had a clinical encounter related to infertility, stratified by year and age group. Second, the proportions of women receiving relevant clinical management actions, including selected pathology tests, imaging ordered and selected medications, were calculated. Univariable logistic regression analyses compared the likelihood of women having a documented clinical encounter related to infertility and receiving selected management actions based on individual characteristics. We also examined practice-level variation in the proportion receiving selected management for infertility by stratifying proportions based on practice site.

Results: A total of 2 552 339 women had one or more clinical encounters with their general practitioner (GP) between January 2011 and December 2021, of which 27 671 (1.1%) had a clinical encounter related to infertility management. The rate of infertility encounters increased from 3.4 per 1000 in 2011 to 5.7 per 1000 in 2021. Over episodes of care, half (50.9%) of women presenting for an infertility encounter had at least one specified pathology test, and almost a quarter (23.1%) had a specified imaging test. A relatively small proportion of infertility encounters (5.4%) resulted in prescribing of a selected infertility medication by the GP.Large variation in clinical management (pathology, imaging and medication prescribing) was evident according to both individual characteristics and also at the clinical-practice level. Factors associated with increased likelihood of being provided infertility medications included younger age, holding a Commonwealth concession card (indicating low income), lower socioeconomic status and living outside a major city.

Conclusions: Clinical encounters related to infertility are increasing in primary care, with large variation evident in corresponding clinical management. These findings support the development of clinical practice guidelines to enhance standardised and equitable approaches towards the management of infertility in primary care.

Introduction: Stroke is a major cause of acquired disability globally, yet the neural mechanisms driving motor recovery post-stroke remain elusive. Recent research has underscored the growing significance of subcortical pathways in neural plasticity and motor control. Among these, the cortico-reticulospinal tract (CRST) has gained attention in rehabilitation due to its unique ascending and descending structural features as well as its cellular properties which position it as an excellent candidate to compensate for inadequate motor control post-stroke. However, the optimal strategies to harness the CRST for motor recovery remain unknown. Non-invasive modulation of the CRST presents a promising though challenging, therapeutic opportunity. Acoustic startle priming (ASP) training and intermittent theta burst stimulation (iTBS) are emerging as potential methods to regulate CRST function. This study aims to investigate the feasibility of segmentally modulating the cortico-reticular and reticulospinal tracts through ASP and iTBS while evaluating the resulting therapeutic effects.

Methods and analysis: This is a randomised, blinded interventional trial with three parallel groups. A total of 36 eligible participants will be randomly assigned to one of three groups: (1) iTBS+ASP group, (2) iTBS+non-ASP group, (3) sham iTBS+ASP group. The trial comprises four phases: baseline assessment, post-first intervention assessment, assessment after 3 weeks of intervention and a 4-week follow-up. The primary outcomes are the changes in the Fugl-Meyer Assessment-Upper Extremity and Modified Ashworth Scale after the 3-week intervention. Secondary outcomes include neurophysiological metrics and neuroimaging results from diffusion tensor imaging and resting-state functional MRI.

Ethics and dissemination: The trial is registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR2400085220) and Medical Ethics Committee of Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology (Registration No.TJ-IRB20231109). It will be conducted in the Departments of Rehabilitation Medicine and Radiology at Tongji Hospital in Wuhan, China. The findings will be disseminated through peer-reviewed journal publications and presentations at scientific conferences.

Trial registration number: ChiCTR2400085220.

Introduction: Pre-eclampsia is a condition associated with significant maternal and neonatal morbidity and mortality. The prediction of pre-eclampsia in high-risk populations using angiogenic markers, such as serum placental growth factor (PlGF) assessment, has been shown to improve maternal outcomes and is recommended by the National Institute for Health and Care Excellence (NICE). However, such tests are not yet available at the point of care (POC). Glycosylated fibronectin (GlyFn) level for the prediction of pre-eclampsia development is available as a POC test (Lumella) and has the potential to aid rapid clinical decision making. This study aimed to test the hypothesis that the sensitivity of the GlyFn test is not inferior to that of the current gold standard of soluble fms-like tyrosine kinase (sFlt)/PlGF-based laboratory testing for pre-eclampsia.

Methods and analysis: This is a multicentre prospective study. Women at risk for pre-eclampsia based on predefined clinical and/or obstetric risk factors will be invited to participate in the study. The recruitment target is 400 participants. Consenting participants will have paired samples for sFlt/PlGF together with POC GlyFn testing. Two follow-up visits are planned at 2 and 4 weeks after the initial recruitment where repeat testing with both tests will be performed. The clinical team will be blinded to the results of the GlyFn test but not that of the sFlt/PlGF test. Clinical care will be based on established protocols incorporating maternal/fetal evaluation and the results of sFlt/PlGF levels. Maternal and neonatal outcome data will be collected to compare the sensitivity and specificity of the tests, with the primary outcome being delivery for pre-eclampsia within 4 weeks.

Ethics and dissemination: Ethical approval has been obtained from the Health Research Authority and Health and Care Research Wales Ethics Committee. The results of this study will be published in peer-reviewed journals and presented at scientific conferences.

Trial registration number: ISRCTN13430018.

Background: The COVID-19 pandemic has widened inequities, affecting migrant and refugee populations in vulnerable situations, who may face elevated risks of infection, constrained healthcare access and discrimination. Inclusive vaccination campaigns are recommended, but barriers persist. This study aimed to identify barriers and facilitators and estimate vaccination coverage among refugees and migrants in low- and middle-income countries, emphasising inclusive policies for effective rollout.

Methods: A mixed-method study was conducted in two phases in Ecuador, Nepal, Pakistan, the Philippines and Rwanda. Phase 1 (March-May 2022) included policy analysis, in-depth interviews and focus-group discussions with 52 key informants analysed with thematic and grounded theory approaches using hybrid coding. Phase 2 (June-August 2022) included a cross-sectional study among refugees and migrants in regular (MIRS) and irregular situations (MIIS) and used descriptive analysis and a COVID-19 Vaccine Equity Index (CVEI).

Results: A total of 1378 individuals responded to the survey (43.8% MIRS, 31.2% MIIS and 25% refugees). 87% reported receiving at least one dose of the COVID-19 vaccine. The CVEI at the global level (0.824) suggested differences in complete vaccination between migrants and other residents in most of the study countries (refugees reported more access to vaccines than MIRS and MIIS). However, the qualitative phase reported delays and inequities in the early stage of the vaccination process in all countries. Overall, 64.2% of respondents perceived that government' campaigns were successful. Both the qualitative and quantitative phases identified several barriers and facilitators. The main barriers included a lack of trust in authorities, extended waiting times and distance to vaccination centres, discrimination and xenophobia, lack of identity documentation, and adverse reaction concerns. On the other hand, the primary facilitators were the widespread distribution of vaccination centres, sources and provision of information, specific campaigns for refugees and migrants, free vaccination and the motivation to protect others' health.

Conclusions: Despite the high coverage of COVID-19 vaccines among refugees and migrants in the study countries, the process had significant barriers. Simple vaccination registration procedures, targeted campaigns, mobile vaccination teams for hard-to-reach and vulnerable groups, and building trust in the host country authorities are pivotal for future and inclusive vaccine deployments.

Introduction: The PRIME-UK randomised controlled trial (RCT) aims to establish whether a model of care that seeks to be proactive, integrated and empower participants, caregivers and healthcare professionals can improve outcomes in people with parkinsonism. Given that this intervention is novel and complex, understanding whether and how the intervention will be acceptable, implementable, cost-effective and scalable across contexts are key questions beyond that of whether 'it works'. We describe an embedded process evaluation to answer these questions, which aims to support interpretation of the trial results, refinement of the intervention and support future scaling of the PRIME-Parkinson model of care.

Methods and analysis: A mixed-methods approach will be used to collect data across four process evaluation domains: implementation, mechanism of change, acceptability and context. Quantitative data will be collected prospectively from all participants and analysed descriptively with exploratory tests of relationships as power allows. Qualitative data will be collected through semistructured interviews with a purposively sampled subpopulation of participants, caregivers and staff members as well as case studies where relevant. Interview transcripts will be analysed thematically using interpretive qualitative analysis. Synthesis of quantitative and qualitative data will also be performed to draw conclusions.

Ethics and dissemination: The quantitative data will be collected as part of the main PRIME-UK RCT which was been granted NHS REC approval (21/LO/0387) on 27 July 2021. The qualitative data will be collected as part of a substudy, 'PRIME-Qual', which was granted NHS REC approval (21/LO/0388) on 14 July 2021. The mixed-methods process evaluation will be published after the conclusion of the trial in addition to the main trial findings.

Trial registration number: NCT05127057.

Introduction: Only 30%-50% of people referred to clinics during community-based eye screening are able to access care in Botswana, India, Kenya and Nepal. The access rate is even lower for certain population groups. This platform trial aims to test multiple, iterative, low-risk public health interventions and simple service modifications with a series of individual randomised controlled trials (RCT) conducted in each country, with the aim of increasing the proportion of people attending.

Methods and analysis: We will set up a platform trial in each country to govern the running of a series of pragmatic, adaptive, embedded, parallel, multiarm, superiority RCTs to test a series of service modifications suggested by intended service users. The aim is to identify serial marginal gains that cumulatively result in large improvements to equity and access. The primary outcome will be the probability of accessing treatment among the population group with the worst access at baseline. We will calculate Bayesian posterior probabilities of clinic attendance in each arm every 72 hours. Each RCT will continually recruit participants until the following default stopping rules have been met: >95% probability that one arm is best; >95% probability that the difference between the best arm and the arms remaining in the trial is <1%; or 10 000 people have been recruited. Lower thresholds may be used for RCTs testing interventions with very low risks and costs. The specific design of cluster RCTs will be determined by our research team once the intervention is known, but the population and outcome will be the same across all trials.This adaptive platform trial will be used to identify effective service modifications, driving continuous improvements in access.

Ethics and dissemination: This trial has been approved by the research ethics committee at the London School of Hygiene & Tropical Medicine (ref: 29549). Approvals for individual interventions will be sought from UK and local ethics committees. Results will be shared via local workshops, social media and peer-reviewed publications.

Trial registration number: ISRCTN53970958.

Background: The traditional neoadjuvant chemoradiotherapy (nCRT) combined with total mesorectal excision has been widely accepted as the standard treatment for patients with locally advanced rectal cancer (LARC). New strategies such as total neoadjuvant therapy (TNT) and neoadjuvant immunotherapy have shown great promise in certain patient populations. Currently, there is an urgent need to stratify patients before treatment to adopt the appropriate neoadjuvant strategies. Our previous study has shown that circulating tumour DNA (ctDNA) effectively reflects tumour burden and genetic characteristics and has significant predictive value for tumour recurrence, demonstrating great potential in guiding the choice of neoadjuvant strategies.

Methods and analysis: The CINTS-R trial is a multicentre, open-label, randomised controlled trial designed to evaluate the efficacy and safety of a ctDNA-guided neoadjuvant treatment strategy compared with conventional neoadjuvant therapy regime in patients with LARC. The trial will enrol 470 patients diagnosed with LARC (staged cT3-4N0 or cTanyN1-2) with tumours located ≤12 cm from the anal verge across seven centres in China. Patients will be randomly assigned in a 2:1 ratio to the experimental group or the control group. Patients in the experimental group will receive different intensities of neoadjuvant chemoradiotherapy (TNT or modified nCRT) or neoadjuvant immunotherapy based on the molecular features of the tumour, baseline ctDNA concentration and changes in ctDNA status early in treatment. Patients in the control group will receive modified nCRT. The primary endpoint is the 2-year disease-related treatment failure rate. The secondary endpoints include time to recurrence, 2-year overall survival, 2-year disease-free survival, clinical complete response (cCR) rate, near cCR rate and pathologically complete response rate, pathological tumour regression grade and quality of life.

Ethics and dissemination: This protocol has been approved by the ethics committee of Peking Union Medical College Hospital, with approval number I-23PJ157, and by the institutional review boards of all the participating centres. All data will be collected and stored in a specially designed database. The results of our trial will be disseminated through peer-reviewed publications and presented at national and international academic conferences.

Trial registration number: This trial is registered on ClinicalTrials.gov and the registration ID is NCT05601505.

Introduction: Postpartum haemorrhage (PPH) negatively impacts women's health. Preventing and managing PPH is important, and nurse-led interventions are needed. However, no systematic review has evaluated the effectiveness of non-invasive uterine massage for PPH prevention. Therefore, this systematic review aims to assess the efficacy of midwife/nurse-led intervention in managing PPH, serving as the best available evidence to develop further guidelines and recommendations in practice and policy-making.

Methods and analysis: This systematic review will follow the JBI methodology for systematic reviews of effectiveness. The search will be conducted in the MEDLINE (PubMed), CINAHL (EBSCO), BENTHUM Science, JBI, Cochrane, ThaiJo and Google Scholar databases. Studies will be included in English and Thai and published between 2015 and 2024. Two independent reviewers will conduct the review, with data extraction and quality evaluation. Studies will be pooled in a statistical meta-analysis using JBI System for the Unified Management, Assessment and Review of Information or other software where possible.

Ethics and dissemination: This systematic review does not require formal ethical approval because all data will be analysed anonymously. The results will provide an overall review and evidence of midwife/nurse-led non-invasive uterine massage intervention in preventing PPH. These findings will be disseminated through peer-reviewed publications.

Prospero registration number: CRD42024566382.

Objectives: To provide insights into the perspectives of clinical specialists (CSs) regarding the efficacy of existing legal interventions (health laws, policies, guidelines, etc) in addressing and managing perinatal depression (PND) in women in India, in the background of the existing policy gap.

Study design and methods: After adopting the consultative participatory approach, a qualitative study involving online, semi-structured, in-depth interviews was conducted. Purposive, and snowball sampling techniques were used to identify and invite the participants. Thematic content analysis was performed. The findings were reported in alignment with the Standards of Reporting Qualitative Research checklist.

Setting: India.

Participants: 12 out of 38 invited CSs participated in the study. All invited participants either had a background in perinatal psychiatry or were experienced in working with the perinatal population and had undertaken evidence-based research regarding perinatal mental health (PMH), in the Indian setting.

Results: Five themes emerged from the collected data including (1) the epidemiology of PND in the Indian context, (2) the management of PND in India and the efficacy of the existing legal frameworks, (3) the need for legal interventions for addressing and managing PND in India, (4) role of legislative instruments, globally, in managing maternal PND and (5) advocacy for PMH by lawyers, and advocates in India.

Conclusions: The existing policy gap is associated with the violation of women's rights. The Mental Health Care Act (MHCA), 2017 should be amended to recognise perinatal women as a vulnerable group and to prioritise their PMH needs. A nationwide policy should be introduced to ensure integrated PMH services.

Introduction: Malaria is still a major health problem in sub-Saharan Africa, where 98% of global malaria mortality occurs. In addition, the spread of Plasmodium falciparum with partial artemisinin resistance in East Africa and beyond is a great concern. The establishment of more effective vector control, in addition to the current long-lasting insecticide-treated net distribution programme, is an urgent task in these areas. One novel vector control candidate is the pyrethroid-PBO ceiling nets (OlysetPlus ceiling nets) which can overcome the problems of variations in net use behaviours and metabolic resistance to insecticide in vectors. Our preliminary study suggests the protective efficacy and high acceptability of this tool. With this proposed second trial, we aim to evaluate the impact of this tool in a different eco-epidemiological setting in the lake endemic region of Kenya.

Methods: A cluster-randomised controlled trial is designed to evaluate the impact of pyrethroid-PBO ceiling nets in Ndhiwa Sub-County, Homa Bay County, Kenya. A total of 44 clusters will be randomly assigned in a 1:1 ratio to the intervention group (pyrethroid-PBO ceiling nets) and the control group. The assignment will be accomplished through covariate-constrained randomisation of clusters. For the primary outcome of clinical malaria incidence, 38 children from each cluster will be enrolled in a cohort and followed for 18 months. We will also evaluate the effects of the intervention on entomological indicators as well as its acceptance by communities and cost-effectiveness.

Ethics and dissemination: Ethics approvals were provided by the Mount Kenya University Institutional Scientific Ethics Review Committee and the Ethics Committee Osaka Metropolitan University. Study results will be shared with study participants and communities, the Homa Bay County government and the Kenya National Malaria Control Programme. Results will also be disseminated through publications, conferences and workshops to help the development of novel malaria control strategies in other malaria-endemic countries.

Trial registration number: UMIN000053873.