The US Food and Drug Administration launched Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development, calling for the paradigm shift from finding the maximum tolerated dose to the identification of optimal biological dose (OBD). Motivated by a real-world drug development program, we propose a master-protocol-based platform trial design to simultaneously identify OBDs of a new drug, combined with standards of care or other novel agents, in multiple indications. We propose a Bayesian latent subgroup model to accommodate the treatment heterogeneity across indications, and employ Bayesian hierarchical models to borrow information within subgroups. At each interim analysis, we update the subgroup membership and dose-toxicity and -efficacy estimates, as well as the estimate of the utility for risk-benefit tradeoff, based on the observed data across treatment arms to inform the arm-specific decision of dose escalation and de-escalation and identify the OBD for each arm of a combination partner and an indication. The simulation study shows that the proposed design has desirable operating characteristics, providing a highly flexible and efficient way for dose optimization. The design has great potential to shorten the drug development timeline, save costs by reducing overlapping infrastructure, and speed up regulatory approval.

BACKGROUND: Cancer is the leading cause of death worldwide, with breast cancer being one of the most commonly diagnosed types. Low-income and middle-income countries account for nearly half of all breast cancer cases and related fatalities. In Africa, mortality rates are higher and survival rates are lower compared with developed countries. Timeliness of care is a critical aspect of healthcare, but various studies and healthcare systems use different criteria and methods to measure it. Assessing the breast cancer care pathway and understanding the determinants of delayed care are essential for effective interventions. Therefore, this scoping review aims to evaluate the methods used to measure the timeliness of breast cancer care, identify specific points in the care pathway where delays are most frequently reported, and examine the factors affecting the timeliness of breast cancer care in Africa.
METHODS: We will conduct this scoping review using the Arksey and O\'Malley framework endorsed by the Joanna Briggs Institute. A scoping review of articles written in English concerning the timeliness of breast cancer care in the African context will be undertaken. Six electronic databases (MEDLINE, EMBASE, CINAHL, SCOPUS, WEB Of SCIENCE and PsycINFO) will be searched to identify published literature on timeliness of breast care in Africa. Two reviewers will independently screen the articles at both the abstract and full-text stages, guided by predetermined inclusion and exclusion criteria. The full texts of identified studies will be further examined and charted using a data extraction form guided by the Model of Pathways to Treatment framework. Publications describing the time to diagnosis and its associated factors in the contexts of breast cancer will be considered for inclusion, with no restrictions based on date of publication. Studies that are published in languages other than English and that do not focus on the timeliness of care or time-related aspects within the care pathway will be excluded. Evidence will be narratively synthesised and analysed.
BACKGROUND: Ethical approval is not needed as this scoping review does not involve collecting data from human participants. The results produced from this review will be submitted to a scientific peer-reviewed journal for publication and will be presented at scientific meetings.

UNASSIGNED: Multiple sclerosis (MS) is the most common non-traumatic disabling disease affecting young adults. A definitive curative treatment is currently unavailable. Many randomized controlled trials (RCTs) have reported the efficacy of Chinese herbal medicine (CHM) on MS. Because of the uncertain quality of these RCTs, the recommendations for routine use of CHM for MS remain inconclusive. The comprehensive evaluation of the quality of RCTs of CHM for MS is urgent.
UNASSIGNED: Nine databases, namely, PubMed, Embase, Web of Science, Cochrane Library, EBSCO, Sinomed, Wanfang Database, China National Knowledge Infrastructure, and VIP Database, were searched from inception to September 2023. RCTs comparing CHM with placebo or pharmacological interventions for MS were considered eligible. The Consolidated Standards of Reporting Trials (CONSORT) and its extension for CHM formulas (CONSORT-CHM Formulas) checklists were used to evaluate the reporting quality of RCTs. The risk of bias was assessed using the Cochrane Risk of Bias tool. The selection criteria of high-frequency herbs for MS were those with cumulative frequency over 50% among the top-ranked herbs.
UNASSIGNED: A total of 25 RCTs were included. In the included RCTs, 33% of the CONSORT items and 21% of the CONSORT-CHM Formulas items were reported. Eligibility title, sample size calculation, allocation concealment, randomized implementation, and blinded description in CONSORT core items were reported by less than 5% of trials. For the CONSORT-CHM Formulas, the source and authentication method of each CHM ingredient was particularly poorly reported. Most studies classified the risk of bias as \"unclear\" due to insufficient information. The top five most frequently used herbs were, in order, Radix Rehmanniae Preparata, Radix Rehmanniae Recens, Herba Epimedii, Scorpio, and Poria. No serious adverse effect had been reported.
UNASSIGNED: The low reporting of CONSORT items and the unclear risk of bias indicate the inadequate quality of RCTs in terms of reporting completeness and result validity. The CONSORT-CHM Formulas appropriately consider the unique characteristics of CHM, including principles, formulas, and Chinese medicinal substances. To improve the quality of RCTs on CHM for MS, researchers should adhere more closely to CONSORT-CHM Formulas guidelines and ensure comprehensive disclosure of all study design elements.

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BACKGROUND: The purpose of this protocol is to investigate the risk factors, critical evaluation contents and preventive measures of high-output enterostomy.
METHODS: This scoping review will follow the Joanna Briggs Institute guidelines for scoping reviews. PubMed, EMBASE, CINAHL, the Chinese Biological Literature Database and the Cochrane Library will be searched for relevant literature published from January 2015 to January 2024. The Grading of Recommendations, Assessment, Development and Evaluation and the Risk Of Bias In Non-randomised Studies of Interventions will be used to assess the reliability of the evidence.
BACKGROUND: As this scoping review involves database searches for literature analysis, informed consent and ethical approval from patients will not be required. The findings will provide essential decision-making information for researchers, clinicians and ostomy nursing staff. The results of the review will be presented at a scientific conference and published in a peer-reviewed journal.

BACKGROUND: Osteoporotic vertebral compression fracture (OVCF) is a common complication in elderly patients with osteoporosis. Despite undergoing percutaneous kyphoplasty (PKP) treatment, a significant percentage of OVCF patients (1.8% to 31.9%) continue to experience residual low back pain. While acupuncture has shown promise in relieving this pain, there is currently no systematic review on its efficacy specifically for residual low back pain after PKP in OVCF patients. This project aims to evaluate the effectiveness and safety of acupuncture as a treatment for this condition.
METHODS: A comprehensive search will be conducted, including manual and electronic searches of literature published. Various databases such as MEDLINE, PubMed, EMBASE, Web of Science, Cochrane Library, International Clinical Trial Registration Platform, China National Knowledge Network, China Biomedical Literature Database, China Scientific Journal Database and Wan-fang Database will be explored. Additional sources like bibliographies and meeting minutes will also be searched. All randomised controlled clinical trials related to acupuncture for treating residual low back pain after PKP in OVCF patients will be included. Two researchers will independently perform study selection, data extraction and quality assessment. The primary outcome measure will be pain relief assessed using a visual analogue scale (VAS) or other validated scales. Secondary outcomes include effectiveness, Oswestry dysfunction index (ODI), quality of life questionnaire (QUALEFFO-41), follow-up relapse rate and adverse events. If feasible, a meta-analysis using RevMan V.5.3 software will be conducted. Otherwise, descriptive or subgroup analyses will be performed. Database searches will commence after the publication of this agreement, with an estimated commencement date of 1 August 2024.
BACKGROUND: Ethical approval is not required since this review does not involve individual patient data. The findings will be disseminated through peer-reviewed journals or relevant conferences.
UNASSIGNED: CRD42023478838.

病因学研究在解析疾病发展的复杂机制中具有关键作用。病例对照研究和队列研究作为两种主要的分析性研究方法，广泛应用于揭示暴露因素与疾病之间的关系。然而在实践中这两种方法均面临一系列问题和挑战。本文通过结合具体案例批判性分析，重点阐述这两种方法在病因学研究中面临的问题，并提供相应的解决方法，为未来的病因学研究提供更可靠的科学支持。.

BACKGROUND: Osteoporotic fractures are a leading cause of disability and contribute significantly to medical care costs worldwide. Variations in bone mineral density and the risk of osteoporosis are notably influenced by altitude. This study aims to longitudinally examine individuals with osteoporosis and low bone mass at three different altitudes (low, high and very high) to understand the effects of high-altitude environments on bone density.
METHODS: This multicentre, prospective cohort study will involve 893 participants divided into three groups based on altitude: low (500-1500 m), high (2500-4500 m) and very high (4500-5500 m). Participants will undergo comprehensive diagnostic assessments, including demographic data collection, structured questionnaires, medical examinations and clinical laboratory tests. Follow-up visits will occur annually for a minimum of 5 years. The primary outcome will be changes in bone mineral density values. Secondary outcomes will include the incidence of osteoporosis and osteoporotic fractures. Cox proportional hazard models will be used to calculate the risk associated with osteoporotic events and related fractures.
BACKGROUND: The study has been approved by the Institutional Review Board of the Hospital of Chengdu Office of People\'s Government of Tibetan Autonomous Region (No: 2024-70). The acquired insights will be disseminated via academic forums, scholarly articles and stakeholder engagement sessions.
BACKGROUND: ChiCTR2300078872.

BACKGROUND: Despite the favourable efficacy of antiretroviral therapy (ART), HIV/AIDS continues to impose significant disease burdens worldwide. This study aims to systematically review published prognostic prediction models for survival outcomes of treatment experienced people living with HIV (TE-PLHIV), to describe their characteristics, compare their performance and assess the risk of bias and real-world clinical utility.
METHODS: Studies will be identified through a comprehensive search in PubMed, EMBASE, Scopus, the Cochrane Library, and OpenGrey databases. Two reviewers will independently conduct a selection of eligible studies, data extraction and critical appraisal. Included studies will be systematically summarised using appropriate tools designed for prognostic prediction modelling studies. Where applicable, evidence will be summarised with meta-analyses.
BACKGROUND: Ethical approval is not required because only available published data will be analysed. The results of this work will be published in a peer-reviewed journal.
BACKGROUND: PROSPERO registration number CRD42023412118.

BACKGROUND: Symptom networks offer a theoretical basis for developing personalised and precise symptom management strategies. However, symptom networks in lymphoma patients during chemotherapy have been rarely reported. This study intends to establish contemporaneous symptom networks in lymphoma patients during chemotherapy and explore the centrality indices and density in these symptom networks.
METHODS: This is a single-centre prospective cross-sectional study. A total of 315 lymphoma patients admitted to the Lymphoma Department of Shanxi Bethune Hospital since 1 June 2024 will be selected as the study subjects. The patient-reported outcome measures of General Data Questionnaire and Lymphoma Symptom Assessment Scale will be assessed. R package will be used to construct a contemporaneous symptom network, explore the relationship between core and analysed symptoms and analyse the predictive role of network density on patient prognosis.
BACKGROUND: This study adheres to the principles of the Declaration of Helsinki and relevant ethical guidelines. Ethical approval has been obtained from Shanxi Bethune Hospital Ethics Committee (approval number: YXLL-2023-186). The final outcomes will be published in a peer-reviewed journal and disseminated through a conference.