[Articles] Efficacy and safety of narlumosbart, an anti-RANKL monoclonal antibody, in postmenopausal women with osteoporosis: a multi-center, randomized, double-blind, placebo- and active-controlled, phased II study

In this phase II trial of postmenopausal women with osteoporosis, narlumosbart demonstrated superiority over placebo in increasing BMD at 12 months following administration at 6-month intervals, with a tolerable safety profile in the short term, consistent with that of anti-RANKL monoclonal antibodies.

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Effect of zinc supplementation on diarrhoea in HIV infection: a protocol for systematic review and meta-analysis of controlled clinical trials

Introduction
Diarrhoea is a common problem in people living with HIV. Some trials have demonstrated the effectiveness of zinc supplementation in the prevention and treatment of diarrhoea; however, several studies employing the effectiveness of zinc supplementation for reducing diarrhoea in HIV infection have reported heterogeneous outcomes, necessitating a systematic review to provide an exhaustive summary of current evidence. This review aims to pool the available evidence on the effectiveness of zinc supplementation on diarrhoea in HIV infection.

Methods and analysis
This systematic review protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. A systematic literature search will be conducted in Chinese and English databases, including PubMed, Scopus, Google Scholar, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure, Chinese Scientific Journal Database, SinoMed and Wanfang, as part of our search strategy from inception to 17 May 2025. Two reviewers will independently identify eligible studies and extract data. The risk of bias in included studies will be assessed using version 2 of the Cochrane risk-of-bias tool for randomised trials. The risk ratio and 95% CIs will be used to estimate the efficacy of treatment and evaluation approach to rate the certainty of evidence. Cochran’s Q and the I2 will be used to evaluate statistical heterogeneity. Data will be analysed using Stata version 13.0.

Ethics and dissemination
Because no patients were involved, ethical approval was not required. The final results of this research will be submitted to a peer-reviewed journal or presented at relevant conferences, and any deviations from this protocol will be recorded and explained in the final report.

PROSPERO registration number
CRD42022328098.

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Mis- and disinformation and perceptions of healthcare policy among Latinos in the USA: protocol for a multi-method social media sentiment analysis study

Introduction
It is unclear how mis- and disinformation regarding healthcare policy changes propagate throughout Latino communities via social media. This may lead to chilling effects that dissuade eligible individuals from enrolling in critical safety net programmes such as Medicaid. This study will examine pathways and mechanisms by which sentiment in response to mis- and disinformation regarding healthcare policies on social media differentially impact health disparity populations, thus supporting the design of tailored social media interventions to mitigate this.

Methods and analysis
We will search social media from X/Twitter, Facebook/Instagram and Reddit for keywords relating to health benefit programmes. Demographic, geographical location and other characteristics of users will be used to stratify social media data. Posts will be classified as fake-news-related or fact-related based on curated lists of fake-news-related websites. The number, temporal dissemination and positive or negative sentiment in reacting to posts and threads will be examined using the Python-based Valence Aware Dictionary and sEntiment Reasoner (VADER). Using a crowd-sourcing methodology, a novel Spanish-language VADER (S-VADER) will be created to rate sentiment to social media among Spanish-speaking Latinos. With the proposed approach, we will explore reactions to the dissemination of fake-news- or fact-related social media tweets and posts and their sources. Analyses of social media posts in response to healthcare-related policies will provide insights into fears faced by Latinos and Spanish speakers, as well as positive or negative perceptions relating to the policy over time among social media users.

Ethics and dissemination
Our study protocol was approved by the University of California, Los Angeles IRB (IRB#23–0 01 123). Results from this study will be disseminated in peer-reviewed journals and conference presentations, and S-VADER will be disseminated to public repositories such as GitHub.

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Scoping review of guidance on safe non-consultant medical staffing recommendations for UK acute hospitals

Objectives
Modern healthcare is delivered by an increasingly multidisciplinary team, complicating workforce management. Patient safety inquiries have led to reports such as the Francis and Berwick reports (2013), which consistently emphasise the need for proper staffing to ensure patient safety. While nursing has seen progress with safe staffing guidelines, there remains a significant gap in guidance for medical staff. In the UK, consultants are the senior members of the medical profession who have achieved a Certification of Completion of Training (CCT) and are able to practice independently. The number of required consultants is based on population needs, and future consultant numbers are used to determine the number of doctor training positions. However, this approach often overlooks the specific staffing needs of individual hospitals, particularly regarding patient safety. Although a named consultant is responsible for patient care, the medical workforce that handles day-to-day operations in acute hospitals consists of a diverse group of staff who require varying degrees of supervision based on their competency and seniority. This group includes medical associates, such as physician associates, and resident doctors (formerly known as junior doctors) who themselves are a heterogeneous group needing different levels of oversight. As a result, the previous focus solely on consultant staffing requirements must be broadened to address the realities of patient care. At present, no single resource provides a comprehensive summary of staffing recommendations that includes all groups within the non-consultant medical workforce. This research aims to identify existing guidance for this part of the medical workforce to support healthcare management. The objectives of this study are, therefore, to identify guidance and recommendations for safe staffing levels from a patient safety perspective for non-consultant medical staff in UK acute hospitals.

Design
A scoping literature review was conducted and is reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.

Data sources
This used five search strategies: internal website searches, Google Scholar searches, general Google searches, medical database searches via Ovid and a snowballing strategy.

Eligibility criteria
English-language resources published from 2015 to 2024 that provide specific guidance on safe medical staffing levels for National Health Service acute hospitals in the UK.

Data extraction and synthesis
Thematic analysis was employed to identify patterns in the diverse guidance discovered, using a hybrid approach that combined human and AI methods. The benefits and limitations of this method are discussed.

Results
The review yielded 10 703 resources, of which 10 met all eligibility criteria for analysis. Identified themes include staffing requirements, staffing recommendations and a tiered system approach.

Conclusions
Medical staffing is complex due to the varying roles and competencies involved. While some guidance exists, there is a clear need for more comprehensive recommendations that go beyond specific specialities. Future research should focus on developing a medical safe staffing tool and addressing the barriers to comprehensive guidance, both of which would enhance patient care.

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[Articles] Antibiotic use for common illnesses in children living with disability: a multi-country study across 42 low- and middle-income countries

Children with disabilities are at a higher risk of developing common illnesses but are not necessarily more or less likely to use antibiotics for these conditions compared to children without disabilities. However, gender, country and impairment type disparities persist. Targeted efforts are needed to address these health inequities and ensure equitable access to care.

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Insurance type and risk of dementia diagnosis after traumatic brain injury: a study of 267 473 US civilians from 2000 to 2022

Objectives
To evaluate how insurance influences the risk of a dementia diagnosis among a large, diverse cohort of US civilian adults with traumatic brain injury (TBI) over a 22-year period.

Design
This is a retrospective cohort study involving individuals diagnosed with TBI.

Setting
The study used the Merative MarketScan Research Database, specifically drawing from the Commercial Claims and Encounters, Medicare Supplemental and Medicaid databases, from 2000 to 2022 in the USA. These databases provide comprehensive insights into healthcare services received by enrollees, including inpatient and outpatient services, outpatient prescription claims, clinical utilisation records and healthcare expenditures.

Participants
267 473 adults aged 55 and older who were diagnosed with a TBI between 1 January 2000 and 31 December 2022. Individuals with unknown TBI severity and dementia claims 2 years preceding TBI were excluded. TBI and dementia diagnoses were identified using International Classification of Disease 9th and 10th editions codes from inpatient and outpatient admission records.

Interventions
None.

Primary and secondary outcome measures
We compared the incidence of all-cause dementia across different insurance types to assess potential disparities in diagnosis following TBI. Cox proportional hazards models, with age as the time scale, were used to study the association between insurance type and dementia diagnosis following a TBI. Models were adjusted for key demographic variables, medical comorbidities and psychiatric conditions to account for potential confounding.

Results
Of the 267 473 individuals with TBI, 12.7% were diagnosed with dementia over a mean follow-up period of 40 months (SD of 42 months). Dementia incidence differed significantly by insurance type, with 18.2% for Medicaid recipients, 17.3% for Medicare beneficiaries and only 2.3% among individuals with commercial insurance. The adjusted HR for dementia was notably higher among individuals enrolled on Medicaid (HR 2.9, 95% CI: 2.8 to 3.1) and Medicare (HR 2.1, 95% CI: 2.0 to 2.2), when compared with those with commercial insurance.

Conclusions
Individuals with TBI covered by Medicaid and Medicare are significantly more likely to be diagnosed with dementia, with a 2.9-fold and 2.1-fold increase risk, respectively, compared with those with commercial insurance. Addressing insurance-related disparities in dementia diagnosis is crucial for building a more equitable healthcare system. It is essential that individuals with TBI cases, regardless of their insurance type, have access to comprehensive care and preventive interventions to achieve the best possible long-term outcomes.

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Disparities in Trends of Gastroenteropancreatic Neuroendocrine Tumor Incidence—Reply

In Reply We read with great interest the letter by Dr Yu et al shedding light on sex and age disparities of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). While we agree with the authors that comparing the incidence rates and trends based on sex and age is of value, the aim of our prior study was not to conduct a head-to-head comparison between different populations. In light of the increasing recognition and familiarity of GEP-NETs by clinicians in the US, our recent epidemiologic analysis aimed to evaluate the national burden of GEP-NETs and to statistically demonstrate the significant increase in GEP-NETs across most gastrointestinal organs while highlighting variations between organs and populations. Our goal was to provide an updated and comprehensive epidemiological understanding of the burden of GEP-NETs using a nationally representative database that covers around 98% of the US population.

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Concerns About Crisis Pregnancy Center Analysis—Reply

In Reply We thank Swartzendruber and Lambert for their interest in our Research Letter on crisis pregnancy centers (CPCs); however, we stand by our findings. The correspondents claim that our definition of CPCs is incorrect. Yet, our definition aligns with common understanding and is remarkably similar to the one used by Swartzendruber and Lambert themselves: “nonprofit organizations with a primary aim of keeping women from having an abortion.” Additionally, we crowdsourced CPCs from lists vetted by experts, including the Fake Clinic Database (Reproaction) and Expose Fake Clinics (Access Front).

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Risk of myocardial infarction and stroke following microbiologically confirmed urinary tract infection: a self-controlled case series study using linked electronic health data

Objectives
The inflammatory response from acute infection may trigger cardiovascular events. We aimed to estimate associations between microbiologically confirmed urinary tract infections (UTIs) and first acute myocardial infarction (MI) and stroke.

Design
We used a self-controlled case series, with risk periods 1–7, 8–14, 15–28 and 29–90 days after UTI. Included individuals experienced the outcome and exposure of interest and acted as their own controls.

Setting
We used individually linked general practice, hospital admission and microbiology data for the population of Wales held by the Secure Anonymised Information Linkage databank.

Participants
Included individuals were Welsh residents aged over 30 years with a record of a hospital admission for MI or stroke (outcomes) and evidence of a microbiologically confirmed UTI (exposure) during the study period of 1 January 2010 to 31 December 2020.

Main outcome measures
The primary outcome was acute MI or stroke identified using the International Classification of Disease V.10 codes from inpatient diagnoses recorded in the Patient Episode Database for Wales. We used Poisson regression to estimate incidence rate ratios (IRRs) and 95% CIs for MI and stroke during predefined risk periods, compared with baseline periods.

Results
During the study period, 51 660 individuals had a hospital admission for MI, of whom 2320 (4.5%) had 3900 microbiologically confirmed UTIs, and 58 150 had a hospital admission for stroke, of whom 2840 (4.9%) had 4600 microbiologically confirmed UTIs. There were 120 MIs during risk periods and 2190 during baseline periods, with an increased risk of MI for 1–7 days following UTI (IRR 2.49, 95% CI (1.65 to 3.77)). There were 200 strokes during risk periods and 2640 during baseline periods, with an increased risk of stroke for 1–7 days following UTI (IRR 2.34, 95% CI (1.61 to 3.40)).

Conclusions
UTI may be a trigger for MI or stroke. Further work is needed to understand mechanisms and test interventions to reduce the risk of cardiovascular events among people with UTIs in primary care.

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Protocol for a multicentre, open-label, dose-escalation phase I/II study evaluating the tolerability, safety, efficacy and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with aggressive natural killer cell leukaemia

Introduction
Aggressive natural killer cell leukaemia (ANKL) is a rare form of NK cell lymphoma with a very low incidence and poor prognosis. While multi-agent chemotherapy including L-asparaginase has been used to treat ANKL patients, they often cannot receive adequate chemotherapy at diagnosis due to liver dysfunction. PPMX-T003, a fully human monoclonal antibody targeting the transferrin receptor 1, shows promise in treating ANKL by helping patients recover from fulminant clinical conditions, potentially enabling a transition to chemotherapy. This study aimed to evaluate the tolerability, safety, efficacy, and pharmacokinetics of repeated continuous intravenous PPMX-T003 in patients with ANKL.

Methods and analysis
This multicentre, open-label, dose-escalation phase I/II study will be conducted at nine hospitals in Japan. Patients diagnosed with ANKL (whether as a primary or recurrent disease) and exhibiting abnormal liver function or hepatomegaly due to the primary disease will be included. The primary endpoint is the tolerability and safety of repeated continuous intravenous administration of PPMX-T003 in the first course, based on adverse events and dose-limiting toxicities. PPMX-T003 will be administered as a continuous intravenous infusion every 24 hours for five consecutive days, followed by a 2-day break. Pretreatment will be provided to minimise the risk of infusion-related reactions. Initial doses of PPMX-T003 will be 0.5, 1.0 or 2.0 mg/kg, with subsequent dose increases determined by the Data and Safety Monitoring Committee. The sample size is set at seven participants, with enrolment increased to up to 12 participants if dose-limiting toxicities occur, based on feasibility due to the rarity of ANKL. Descriptive statistics will summarise data according to initial dose, and pharmacokinetic analysis will be conducted based on administered dose.

Ethics and dissemination
This study was approved by the institutional review boards at participating hospitals. The results will be disseminated in peer-reviewed journals.

Trial registration number
jRCT2061230008 (jRCT); NCT05863234 (ClinicalTrials.gov).

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