Effectiveness of the BioFire FilmArray for the rapid detection of bloodstream infection in haematological patients with febrile neutropenia (the ONFIRE study): study protocol of a prospective, multicentre observational study at three reference university hospitals in Spain

Introduction
Bloodstream infection (BSI) due to multidrug-resistant Gram-negative bacilli is a serious global health problem that has a profound impact on severely immunosuppressed neutropenic haematological patients. Prompt institution of appropriate antimicrobial therapy is crucial for improving outcomes in these patients, and in an era of multidrug resistance, antimicrobial stewardship programmes are mandatory. Blood cultures, the current gold standard for the diagnosis of BSI, present two main drawbacks: the prolonged time to results and their low sensitivity, especially if the patient has received antimicrobial treatment before blood extraction. The aim of this study is to determine whether a molecular technique, the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel, achieves higher sensitivity and specificity than conventional blood cultures for the microbiological diagnosis of BSI in haematological patients with febrile neutropenia.

Methods and analysis
This multicentre, prospective, observational study will be conducted at three reference university hospitals in Spain. The population will comprise haematological patients scheduled to undergo diagnostic blood cultures as standard care for the microbiological diagnosis of the febrile neutropenia episode. The BioFire FilmArray panel will be performed in patients with positive blood cultures at the time of blood culture positivity and in patients with negative blood cultures at 48 hours of incubation. The primary endpoint will be the sensitivity and specificity of the BioFire FilmArray BCID2 panel compared with conventional blood cultures. The secondary endpoints will be this same comparison in the subgroup of patients with recent (

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Development of a large Danish single-centre retro- and prospective transgender cohort using a web-based platform: a study protocol of a transgender cohort study

Introduction
Referrals for gender-affirming healthcare services have surged in recent decades, presumably driven by increased visibility, acceptance and reduced barriers to care. Despite these advances, transgender and gender-diverse individuals continue to face significant mental health challenges, including elevated rates of anxiety, depression as well as high prevalence of autistic traits. Gender-affirming hormonal treatment (GAHT) has been suggested to improve mental health and quality of life (QoL) among transgender individuals; however, the short- and long-term treatment effects of GAHT are not yet fully understood. Therefore, this study aims to establish a comprehensive cohort of transgender individuals at the Centre for Gender Identity (CGI), Aalborg University Hospital, Denmark, to enhance understanding and treatment outcomes.

Methods and analysis
The Transgender Cohort (TraCK) will recruit participants from February 14, 2024, with recruitment occurring continuously alongside yearly follow-up. This single-centre cohort study will include both retrospective and prospective data collection. Transgender individuals referred to CGI will be invited to participate in the study via the Danish digital mail system called e-Boks. Participants must provide informed consent and complete a baseline questionnaire. Data will be collected from self-reported questionnaires and medical records across multiple specialists. Self-reported questionnaires include WHO-Quality of Life BREF, Eating Disorders Examination Questionnaire, Autism Spectrum Quotient, Transgender Congruence Scale, and Gender Minority Stress and Resilience Measure. Medical records will provide information on demographics, mental health, physical health, and gender-affirming treatment details. Data will be managed using REDCap, ensuring compliance with GDPR and the National Data Protection Act.

Ethics and dissemination
While recognising the potential privacy risks associated with data collection, the study considers these outweighed by the benefits of advancing knowledge on gender diversity and the impacts of gender-affirming care. The North Jutland Region Ethics Committee reviewed the project, determining no formal approval was needed, but it was registered and approved (no. F2024-012) by the North Jutland Region. Findings will be disseminated through peer-reviewed journals, conferences, and accessible reports for participants.

Registration details
This study is registered with the North Jutland Region (no. F2024-012). Recruitment and data collection began on February 14, 2024, and will continue alongside yearly follow-up. Keywords Transgender individuals, transgender and gender-diverse, transgender cohort, transgender health, transgender research, cohort study, gender-affirming care.

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Strategic multimodal intervention in at-risk elderly Indians for prevention of dementia (SMRUTHI INDIA): a cohort multiple randomised controlled trial (cmRCT) protocol

Introduction
Treating modifiable risk factors of dementia may prevent or delay dementia cases by up to 40%. The ‘Strategic Multimodal Intervention in at-risk Elderly Indians for Prevention of Dementia (SMRUTHI INDIA)’ study will be conducted to establish a trial-ready cohort of elderly Indians who are at high risk of developing dementia.

Methods and analysis
The main aim of the study is to create and study a cohort of individuals at high risk of dementia in rural India, where we can do multiple intervention trials. The study uses the ‘Cohort Multiple Randomised Controlled Trial’ (cmRCT) design, which combines a cohort study with in-built provisions to do multiple randomised controlled trials. A large rural cohort of size 10 000 (four zones of India, through established Indian Council of Medical Research – Model Rural Health Research Units) will be followed systematically with yearly neuropsychological evaluation for 5 years (the current funding supports first 3000 participants). The study also proposes to design a multimodal ‘care bundle’ for the prevention of dementia, which is culturally tailored and context-specific to the Indian population. This intervention will undergo testing for feasibility in the hospital setting at the central coordinating site through a pilot randomised controlled trial (6 months, 30 participants). In parallel, the care bundle will be culturally and linguistically adapted and pilot-tested in 20 participants in each zone. The final curated care bundle (first intervention that is planned) will then be tested for efficacy in phase 2 of the SMRUTHI INDIA cmRCT cohort.

Ethics and dissemination
The study has received ethical clearance at the central coordinating site and at each of the four clinical sites by the Institute Research Committee of each site. The outcomes of the study will be disseminated to various target audiences, including research participants, general public, scientific community and policy makers through national and international conferences and events, social media, various community engagement activities and publication in peer-reviewed journals.

Trial registration number
The study protocol is registered in the Clinical Trial Registry of India (CTRI/2024/01/061172).

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Factors Associated With Early Reocclusion in Recanalized Intracranial Atherosclerotic Occlusion: ANGEL-REBOOT Insights

Stroke, Ahead of Print. BACKGROUND:Early reocclusion following successful recanalization through mechanical thrombectomy is linked to poor clinical outcomes in patients with stroke with intracranial atherosclerotic occlusion (ICAS-O). However, the factors influencing early reocclusion remain inadequately understood. This study is a post hoc analysis of 24-hour reocclusion in patients with successfully recanalized ICAS-O from a multicenter trial.METHODS:Patients with successfully recanalized ICAS-O were selected from the ANGEL-REBOOT trial (Randomized Study of Bailout Intracranial Angioplasty Following Thrombectomy for Acute Large Vessel Occlusion). Reocclusion was defined as a 24-hour arterial occlusive lesion score of 0 to 1, determined by magnetic resonance or computed tomography angiography. Possible factors associated with early reocclusion were screened through univariable analysis, and then, multivariable logistic regression was used to identify independent factors associated with early reocclusion.RESULTS:Among the 348 patients in the ANGEL-REBOOT trial, 21 could not be diagnosed with ICAS-O, 14 failed recanalization by the end of the procedure, and 14 had no follow-up angiography data. Finally, a total of 299 subjects were included, with a median age of 63 (interquartile range, 55–69) years, and 77 of 299 (25.75%) were females. The 24-hour reocclusion rate was 9.7% (29/299). Through backward elimination, 3 independent factors remained in the final multivariable logistic regression model. Specifically, puncture-to-recanalization time (per hour increase: odds ratio, 1.80 [95% CI, 1.31–2.47]) was positively associated with reocclusion, while general anesthesia (odds ratio, 0.25 [95% CI, 0.10–0.65]) and a postprocedural expanded Thrombolysis in Cerebral Infarction score of 2c-3 (odds ratio, 0.35 [95% CI, 0.14–0.85]) were negatively associated with reocclusion. Compared with patients without reocclusion, those with reocclusion had significantly greater 90-day modified Rankin Scale scores (median 4 versus 1, Mann-WhitneyUtest;P

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Economic burden of hypertension in Iran: a prevalence-based cost of illness study

Objectives
Hypertension is one of the silent diseases and is the major cause of many chronic conditions. The treatment services for hypertension and its cardiovascular complications impose high costs on society and the health system. However, in LMCs, there is not enough evidence-based information about the costs of high blood pressure. This study aims to assess the economic burden of hypertension in Iran in 2020.

Design
A prevalence-based cost of illness study.

Setting
Data on hypertension and selected diseases, including their prevalence, incidence, mortality risk and death counts, were sourced from literature reviews, the Global Burden of Disease (GDP) and the Non-Communicable Diseases Research Centre. Cost estimates were derived from health insurance data, surveys, research studies and treatment protocols. Additional data, such as population, employment rates, household activity rates, wage rates and GDP per capita, were obtained from the Statistical Centre of Iran and the World Bank.

Participants and methods
A prevalence-based cost of illness study was used to estimate the economic burden of hypertension. The focus was on the most significant diseases associated with high blood pressure, including coronary heart disease, ischaemic stroke, haemorrhagic stroke and the direct costs of hypertension. Subsequently, the total number of patients was multiplied by the average cost per patient for each disease. To calculate the average cost, inpatient and outpatient, direct non-medical and indirect costs of diseases were estimated and multiplied by a population-attributed fraction of high blood pressure. Direct costs (hospitalisation and outpatient costs and direct non-medical costs) of hypertension were calculated using the bottom-up approach, and the human capital approach was used to calculate indirect costs.

Results
According to the results of the study, the total economic burden of hypertension was $ purchasing power parity (PPP) 12 848.22 million, of which the share of direct medical, non-medical and indirect costs of hypertension were $ PPP 7245.13 million (56.4%), $ PPP 1173.42 million (9.1%) and $ PPP 4429.68 million (34.5%), respectively. The total economic burden of high blood pressure was equal to 23% of the total economic burden of four chronic diseases.

Conclusion
The economic burden of high blood pressure in the country is very high and significant, and it was equivalent to about 1% of the country’s gross domestic product in 2020, which shows the necessity of preventive interventions.

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Peer support enhanced behavioural crisis response teams in the emergency department: protocol for a stepped-wedge cluster-randomised controlled trial

Introduction
Despite expert recommendations to prioritise non-invasive and patient-centred approaches for behavioural crisis management, physical restraints are commonly used in the emergency department (ED). Patients describe the restraint process as coercive and dehumanising. The use of peer support workers, who are individuals with lived experience of mental illness and behavioural conditions, has shown positive patient outcomes when assisting individuals experiencing behavioural crises. However, there is limited evidence of the implementation of such an approach in the ED setting. The goal of this study is to evaluate if the implementation of a Peer support enhanced Agitation Crisis response Team (PACT) for behavioural crisis management in the ED is more effective than usual care to reduce restraint use and improve outcomes among patients presenting to the ED with behavioural crises.

Methods and analysis
We will first conduct a stakeholder-informed needs assessment to codesign the protocol and then train staff and peers in PACT intervention readiness. Next, a stepped-wedge, cluster-randomised controlled trial will be conducted over 3 years at five ED sites across a healthcare system in the Northeast USA. The PACT intervention will integrate peer delivery of trauma-informed care within a structured, interprofessional, team-based response protocol for behavioural crisis management. The primary outcome is the rate of physical restraint and/or sedation use. The secondary outcome is the level of patient agitation during the ED visit. Analyses of primary and secondary outcomes will be conducted using generalised linear mixed models.

Ethics and dissemination
This protocol has been approved by the Yale University Human Investigation Committee (protocol number 2000037554). The study is deemed minimal risk and has been granted a waiver of consent for trial participants. However, verbal consent will be obtained for a subset of patients receiving follow-up data collection. Results will be disseminated through publications in open-access, peer-reviewed journals, via scientific presentations, or through direct mail notifications.

Trial registration number
Clinicaltrials.gov: NCT06556069.

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[Articles] Association between physical activity and risk of anxiety: a dose-response meta-analysis of 11 international cohorts

Our research confirmed a dose-response relationship between physical activity and anxiety risk, and increasing physical activity within the range recommended by the World Health Organization (WHO) (10–20 MET-h/week) can significantly reduce anxiety risk. Subgroup analysis showed that this protective effect was most significant during the 5-year follow-up period, with a maximum anxiety risk reduction of 49%. Exceeding the recommended dose, there may be additional smaller benefits between doses 20–30 MET-h/week, and exceeding 50 MET-h/week may become a risk factor.

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A Nationwide Factorial Randomized Trial of Electronic Nudges to Patients with Chronic Kidney Disease and Their General Practices for Increasing Guideline-Directed Medical Therapy: The NUDGE-CKD Trial

Circulation, Ahead of Print. Background: Many individuals with chronic kidney disease (CKD) face considerable but modifiable risk of cardiovascular and renal outcomes due to suboptimal implementation of guideline-directed medical therapy (GDMT). We investigated whether electronic letter-based nudges delivered to individuals with CKD and their general practices could increase GDMT uptake.Methods: This was a nationwide 2×2 factorial implementation trial, with randomization at the patient and general-practice level, and analyzed at the patient level. All Danish adults with a hospital-diagnosis of CKD and access to the official Danish electronic letter system were individually randomized in a 1:1 ratio to usual care (no letter) or to receive an electronic letter-based nudge on GDMT in CKD; general practices of individuals with CKD were independently randomized (1:1) to receive no letter or an electronic informational letter on GDMT. Intervention letters were delivered on August 19, 2024. Data were collected through the Danish administrative health registries. Primary endpoint was a filled prescription of a renin-angiotensin system inhibitor (RASi) or a sodium-glucose cotransporter-2 inhibitor (SGLT2i) within 6 months of intervention delivery.Results: A total of 22,617 patients with CKD were randomized to the patient-level intervention, with 11,223 allocated to receive the electronic nudge letter and 11,394 to usual care. Separately, 1,540 general practices caring for 28,069 patients with CKD were randomized to the provider-level intervention, with 774 practices (13,959 patients) allocated to the intervention and 766 practices (14,110 patients) to usual care. During follow-up, 7,303 (65.1%) allocated to the patient-directed nudge had filled a prescription of RASi or SGLT2i compared with 7,505 (65.9%) in usual care (difference, 0.79 percentage points; 95% confidence interval (CI), -2.03 to 0.45; P=0.21). Among patients of practices receiving the provider-directed letter, 8,921 (63.9%) filled a prescription for RASi or SGLT2i compared with 9,086 (64.4%) in the usual care group (difference, -0.49 percentage points; 95%CI, -1.64 to 0.66; P=0.41). No interaction was observed between the two interventions (pinteraction=0.85).Conclusions: In this nationwide pragmatic, 2×2 factorial implementation trial, electronic letter-based nudges on GDMT delivered to patients with CKD or their general practice did not increase the uptake of RASi or SGLT2i as compared with usual care.

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British Society of Gastroenterology practice guidance on the management of acute and chronic gastrointestinal symptoms and complications as a result of treatment for cancer

Background
Survival rates after a diagnosis of cancer are improving. Poorly managed gastrointestinal (GI) side effects can interfere with delivery of curative cancer treatment. Long-term physical side effects of cancer therapy impinge on quality of life in up to 25% of those treated for cancer, and GI side effects are the most common and troublesome.

Aim
To provide comprehensive, practical guidance on the management of acute and chronic luminal gastrointestinal symptoms arising during and after treatment for cancer

Methods
A multidisciplinary expert group including patients treated for cancer, divided into working parties to identify, and synthesise recommendations for the optimal assessment, diagnosis and appropriate interventions for luminal GI side effects of systemic and local cancer therapies. Recommendations were developed using the principles of the BMJ AGREE II reporting.

Results
103 recommendations were agreed. The importance of the patient perspective and what can be done to support patients are emphasised. Key physiological principles underlying the development of GI toxicity arising from cancer therapy are outlined. Individual symptoms or symptom clusters are poor at distinguishing the underlying cause(s), and investigations are required if empirical therapy does not lead rapidly to significant benefits. Patients frequently have multiple GI causes for symptoms; all need to be diagnosed and optimally treated to achieve resolution. Investigations and management approaches now known to be ineffective or of questionable benefit are highlighted.

Conclusions
The physical, emotional and financial costs to individuals, their families and society from cancer therapy can be considerable. Identifying and signposting affected patients who require specialist services is the role of all clinicians. Progress in the treatment of cancer increasingly means that patients require expert, multidisciplinary supportive care providing effective and safe treatment at every stage of the cancer journey. Development of such expertise should be prioritised as should the education of health professionals and the public in what, when and how acute and chronic gastrointestinal symptoms and complications should be managed.

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External validation of risk prediction models for post-stroke mortality in Berlin

Objectives
Prediction models for post-stroke mortality can support medical decision-making. Although numerous models have been developed, external validation studies determining the models’ transportability beyond the original settings are lacking. We aimed to assess the performance of two prediction models for post-stroke mortality in Berlin, Germany.

Design
We used data from the Berlin-SPecific Acute Treatment in Ischaemic or hAemorrhagic stroke with Long-term follow-up (B-SPATIAL) registry.

Setting
Multicentre stroke registry in Berlin, Germany.

Participants
Adult patients admitted within 6 hours after symptom onset and with a 10th revision of the International Classification of Diseases discharge diagnosis of ischaemic stroke, haemorrhagic stroke or transient ischaemic attack at one of 15 hospitals with stroke units between 1 January 2016 and 31 January 2021.

Primary outcome measures
We evaluated calibration (calibration-in-the-large, intercept, slope and plot) and discrimination performance (c-statistic) of Bray et al’s 30-day mortality and Smith et al’s in-hospital mortality prediction models. Information on mortality was supplemented by Berlin city registration office records.

Results
For the validation of Bray et al’s model, we included 7879 patients (mean age 75; 55.0% men). We observed 763 (9.7%) deaths within 30 days of stroke compared with 680 (8.6%) predicted. The model’s c-statistic was 0.865 (95% CI: 0.851 to 0.879). For Smith et al’s model, we performed the validation among 1931 patients (mean age 75; 56.2% men), observing 105 (5.4%) in-hospital deaths compared with the 92 (4.8%) predicted. The c-statistic was 0.891 (95% CI: 0.864 to 0.918). The calibration plots of both models revealed an underestimation of the mortality risk for high-risk patients.

Conclusions
Among Berlin stroke patients, both models showed good calibration performance for low and medium-risk patients and high discrimination while underestimating risk among high-risk patients. The acceptable performance of Bray et al’s model in Berlin illustrates how a small number of routinely collected variables can be sufficient for valid prediction of post-stroke mortality.

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Spatial and spatio-temporal analysis for malaria hotspot identification: a scoping review protocol

Introduction
Malaria hotspots have been the focus of public health managers during the last two decades because of the potential elimination gains that can be obtained by targeting them. Advances in spatial technologies in the 20th century such as geographic information systems, remotely sensed satellite data on climate and ecology, and statistical methods for spatial cluster detection have enhanced our ability to map fine-scale patterns of malaria transmission. This led to the diversification of analytical approaches and a lack of consensus on methods and standardised indicators for malaria hotspot detection, raising challenges for comparing and synthesising findings across different studies. This review aims to fill this gap by identifying and summarising all publicly available peer-reviewed articles on spatial and spatio-temporal analytical approaches used to detect malaria hotspots while highlighting research gaps.

Methods
This scoping review will follow the Joanna Briggs Institute Framework. A comprehensive search will be conducted in PubMed, Medline, Web of Science, Scopus and Embase using keywords related to malaria, hotspots and detection. Retrieved articles published between 1 January 2000 and 31 December 2024 in English or French will be uploaded to Covidence for screening. Empirical studies that apply spatial or spatio-temporal analytical methods to detect malaria hotspots will be included. Studies will be excluded if they rely solely on geographical visualisation without formal spatial analysis. Data extraction will be performed by two independent reviewers, with disagreements resolved by discussion. Data will be summarised using descriptive statistics and thematic analysis.

Ethics and dissemination
This scoping review will involve the secondary analysis of published literature on malaria hotspot analysis; therefore, ethics approval is not required. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews checklist will be used to ensure transparency and methodological rigour in reporting. The findings will be disseminated through publication in a peer-reviewed journal and presented at scientific conferences via abstracts, oral or poster presentations.

Trial egistration number
This review has been registered on the Open Science Framework under the DOI: https://doi.org/10.17605/OSF.IO/C8KUN.

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Studies on cognitive performance among older people living with HIV in eastern Europe and central Asia: a scoping review

Background
Despite the growth of the population of older people living with HIV (PLWH), data on cognitive disorders among older PLWH, particularly in low- and middle-income countries, are scarce. These data are especially underrepresented in the literature from eastern Europe and central Asia (EECA).

Objectives
This scoping review aimed to describe the peer-reviewed literature on cognitive health among PLWH in the EECA region.

Eligibility criteria
We selected articles from peer-reviewed journals that reported on cognitive assessments or the prevalence and characteristics of cognitive disorders among adult (≥18 years) PLWH in EECA countries (Armenia, Azerbaijan, Belarus, Estonia, Georgia, Kazakhstan, Kyrgyzstan, Latvia, Lithuania, Moldova, Russia, Tajikistan, Turkmenistan, Ukraine and Uzbekistan). Studies assessing cognition among PLWH related to traumatic brain injury, brain tumours, COVID-19, meningitis, neurosyphilis and/or other central nervous system infections were excluded.

Source of evidence
We searched for relevant data published up to March 2025 using four online databases (PubMed, CINAHL, Web of Science and PsycINFO).

Charting methods
Covidence, a web-based collaborative software platform, was used for data screening and extraction. Two independent reviewers screened abstracts and full texts, resolving disagreements through consensus. The data were extracted based on the predefined data extraction criteria.

Results
A total of 1388 peer-reviewed articles were identified; 295 articles were removed due to duplication; and 1053 and 25 articles were excluded based on the abstract/title and full-text screenings, respectively. Finally, 15 articles met the inclusion criteria. All 15 studies used different neuropsychological assessments to measure cognitive performance by domain and/or cognitive disorders among various subgroups of PLWH. One cross-sectional study focused on older populations (≥40 years old), using standardised cognitive performance assessment tests. However, it neither provided information about the prevalence estimate of cognitive disorders nor identified risk factors.

Conclusion
Existing literature on cognitive disorders among older PLWH in the EECA region is limited and insufficient to estimate prevalence, or identify risk factors, and ultimately develop appropriate policy addressing the needs of older PLWH in this region. This scoping review underscores the urgent need for large-scale, longitudinal studies employing standardised, culturally adapted neuropsychological batteries and adherence to rigorous reporting standards.

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