This systematic review aims to synthesise current evidence on gut microbiome profiles among children with sickle cell disease (SCD), assess the influence of analgesic and antibiotic use, and explore the contributions of environmental factors on their gut microbiota diversity. Through identification of consistent microbial patterns and gaps in the existing literature, this review will provide vital insight into potential microbiome-targeted strategies for improving health outcomes in paediatric SCD care.

Studies describing the gut microbiota among paediatric SCD human subjects (

Ethical approval will not be required as this is a systematic review of published data. The findings will be disseminated through publications in peer-reviewed journals and presentations at relevant scientific conferences.

CRD420251102736.

Depression and sub-diagnostic depressive syndromes are prevalent and associated with suffering and reduced life expectancy. Access to care is limited even in countries with developed healthcare systems. In this context, it is important to strengthen the self-management expertise of people suffering from depressive symptoms. Smartphones offer the possibilities for improved self-management based on long-term monitoring of symptoms.

The present multicentre randomised controlled trial (the Protecting mental health in times of change (MENTINA) trial) aims to evaluate whether (1) daily smartphone-based monitoring and automatic rule-based feedback+smartphone-based outcome evaluations versus (2) smartphone-based outcome evaluations alone will improve depressive symptoms and other clinically relevant outcomes in participants with current depressive symptoms and/or one or more prior depressive episodes during a 12-month trial period.

The MENTINA trial is a multicentre randomised controlled parallel-group trial conducted in Denmark, Germany and Spain. Participants with current depressive symptoms and/or one or more previous depressive episodes are invited to participate. The included participants will be randomised to (1) daily smartphone-based monitoring and automatic rule-based feedback+outcome evaluations via smartphone (intervention group) or (2) outcome evaluations via smartphone alone (control group). All participants can continue with ongoing treatment in case they receive it. The trial started in May 2025 and has currently included 115 participants. The outcomes are differences between the intervention group and the control group in (1) Patient Health Questionnaire 9-items (PHQ-9) measured every 14th day during the 12-month trial period (primary), (2) WHO Quality of Life-BREF, Generalised Anxiety Disorder-7, monthly change in PHQ-9, proportion of participants with ≥50% reduction in PHQ-9, remission rate defined as PHQ-9≤9 and ≥5-point improvement, PHQ-9 scores after 6 months, area under the curve for PHQ-9 over the 12 months trial period, subgroup analyses in PHQ-9 in participants with or without lifetime depression, Perceived Stress Scale, user-reported healthcare contacts, usability of the app and negative effects, number of depressive episodes+duration and depressive-free days based on PHQ-9. A total of 660 participants will be included in the MENTINA trial.

The MENTINA trial is funded by the European Union under Grant Agreement No. 101 080 651. Ethical approval and approval from Medical Agencies have been obtained from Denmark (CIV-25-02-051094), Germany (CIV-25-02-05109) and Spain (CIV-25-02-051094). The results will be published in peer-reviewed academic journals, presented at scientific meetings and disseminated to patients’ organisations and media outlets.

NCT06919133.

Version 6, January 2026.

Long-term brain health profiles following exposure to repetitive head impacts and/or concussions in contact sports are a public health focus and the subject of a national debate. The true prevalence rates of mild cognitive impairment (MCI) or neurobehavioural dysregulation are unknown in the nearly 20 000 current/living former professional football players. Here, we describe the procedures and methodology of the prevalence study of cognitive function in former professional football players from the Brain Health Initiative at the University of Pittsburgh. The objective is to define the prevalence of normal cognitive function versus neurodegeneration in former professional football players through clinical, neuroimaging and biomarker assessments.

Participants include former professional football players aged 29–59 years at study onset who played a minimum of three professional football games in three professional seasons and non-exposed controls. Participants are recruited by two mechanisms, a random and non-random sample. The full study protocol includes a 3–4-day, multidomain assessment (eg, neurological, neurocognitive, psychiatric, sleep, vestibular, orthopaedic and cardiovascular) for neurodegenerative disease and overall health and function, including MRI, positron emission tomography scans, analysis of blood plasma and cerebrospinal fluid, neurocognitive assessments, applanation tonometry, overnight sleep study and informant interview. A multidisciplinary clinical panel conducts a blinded diagnostic consensus conference to adjudicate the presence of MCI and/or traumatic encephalopathy syndrome, which serve as the study’s primary and secondary outcomes, respectively. Point prevalence of these for both the exposed and unexposed cohorts will be calculated as the primary statistical analysis.

The University of Pittsburgh Institutional Review Board approved the study prior to recruiting human subjects (protocol numbers STUDY19010008: sIRB - Brain Health Initiative (Part 1) and STUDY19030211: sIRB - Brain Health Initiative (Part 2)). The results will be disseminated in peer-reviewed journals and as presentations at national and international scientific conferences.

To assess the association between the maternal continuum of healthcare and child immunisation in East Africa using propensity score matching (PSM).

Cross-sectional study using Demographic and Health Survey data.

This study was conducted in East African countries.

This study included a weighted sample of 13 488 women with children aged 12–23 months.

Child immunisation was the outcome variable of this study.

The PSM estimates indicate that the average treatment effect on the treated for complete child immunisation was 0.0583, meaning that children of mothers who received a complete maternal continuum of care had a 5.83% higher probability of being fully immunised compared with children of mothers with incomplete care. Expressed relative to the treated group’s mean, this corresponds to a 7.48% increase. Additionally, our results indicated that the population average treatment effect was 0.0629. This means that, on average, a complete continuum of maternal healthcare increases the probability of full child immunisation by approximately 6.29% across the entire population.

The study highlights that children whose mothers receive comprehensive maternal healthcare are more likely to complete their childhood immunisations. This finding underscores the need to integrate immunisation services into maternal healthcare programmes to enhance vaccination coverage and promote better child health. To maximise this connection, improving access to maternal healthcare, especially in underserved regions, is crucial, along with ensuring that immunisation is a regular part of maternal care.

Current pharmacological treatment options for painful diabetic neuropathy (PDN) often fail to provide adequate pain relief. However, in the recent SENZA-PDN study, high-frequency 10 kHz spinal cord stimulation (SCS) demonstrated significant long-term improvements in lower limb pain and health-related quality of life (HRQoL) in a PDN population. Furthermore, more than half of 10 kHz SCS recipients showed improved sensory function based on non-blinded clinical assessments in post hoc analysis. We report the design of the PDN-Sensory study, which aims to evaluate changes in pain and neurological function with 10 kHz SCS in the treatment of PDN. The study will include objective measures of neurological function, including the modified Toronto Clinical Neuropathy Score (mTCNS) and intraepidermal nerve fibre density (IENFD).

This multicentre, prospective, randomised controlled trial will compare conventional medical management (CMM) with 10 kHz SCS+CMM in individuals with diabetes and chronic, intractable lower limb pain due to PDN. Participants will be randomised 1:1 to CMM alone or 10 kHz SCS+CMM, with optional crossover at 6 months. The primary outcome is the proportion of participants at 6 months achieving ≥50% pain relief from baseline. The key secondary endpoint is the proportion of participants at 6 months with a reduction in mTCNS of ≥3 points from baseline (excluding changes in foot pain). Additional endpoints at 6 and 12 months include changes from baseline in mTCNS, IENFD, 7-day averaged pain score, pain-related interference, HRQoL, sleep, psychological outcomes, functional status and metabolic parameters.

The study protocol received central approval from the Western Institutional Review Board (IRB #20230954). Local IRB approval will be required before initiation of the study at each participating clinical site. The study complies with Good Clinical Practice guidelines (ISO 14155), the Declaration of Helsinki, and all applicable national, federal and local regulatory requirements. Dissemination plans include presentations at national and international conferences and publication in a peer-reviewed journal with open access.

NCT05777317.

This study aims to assess the burden and predictors of age-related macular degeneration (AMD) among older age patients with diabetes attending comprehensive specialised hospitals in Northwest Ethiopia.

A multicentre cross-sectional study was conducted among older patients with diabetes using a systematic random sampling technique.

The study was conducted at five comprehensive specialised hospitals in Northwest Ethiopia from 8 May to 8 June 2023.

The study included 832 diabetic individuals aged 40 years and above.

Data were collected using a pretested structured questionnaire and physical examinations.

In this study, a total of 832 participants were involved, with a response rate of 96.85%. The burden of AMD was 15.4% (95% CI 13.0% to 18.0%). Male sex (adjusted OR (AOR) 2.04, 95% CI 1.17 to 3.56), older age (AOR 6.91, 95% CI 3.17 to 15.08), diabetes duration of 10 and more years (AOR 3.00, 95% CI 1.91 to 4.69), higher body mass index (AOR 2.56, 95% CI 1.15 to 5.71), presence of hypertension (AOR 2.45, 95% CI 1.56 to 3.85) and family history of diabetes mellitus (DM) (AOR 2.29, 95% CI 1.40 to 3.76) were positively associated with AMD.

This study found that the prevalence of AMD among patients with diabetes was 15.4%. Older age, male sex, longer DM duration, higher body mass index, presence of hypertension and family history of DM were significantly associated with AMD. Targeted screening of at-risk individuals for AMD, public health awareness campaigns focusing on these factors and further research to understand the burden and underlying mechanisms of these associations with AMD are recommended.

Our objective was to examine the barriers and facilitators encountered by primary and secondary healthcare professionals when collaborating at the care continuum between primary and secondary care. We aimed to identify specific challenges, observed benefits and proposed changes. By analysing these experiences and identifying opportunities for redesign, we aimed to define specific domains that could improve collaboration, thereby supporting sustainable access to and quality of care in the face of rising demand and constrained resources.

A qualitative exploratory study using semi-structured interview data guided by two domains of the Consolidated Framework for Implementation Research (CFIR), including Inner Setting—Tension for Change and Individual Characteristics, as well as selected implementation outcomes defined by Proctor et al, all viewed through a service (re)design lens.

Consultation and communication between primary and secondary healthcare professionals in a Dutch urbanised area.

37 users of collaboration services (eg, telephone, correspondence) were interviewed between August 2021 and October 2022, including 14 general practitioners (GPs) (10 females, 4 males) and 23 specialists (10 females, 13 males).

Four key domains with subthemes, subdivided per operation and CFIR domain, were identified as central to optimising the collaboration of professionals within the primary-secondary care continuum: (1) software and record integration; (2) seamless personal interaction; (3) eliminating a sense of ‘us vs them’ and (4) gaps in continuity of care.

This study reveals that healthcare professionals in both primary and secondary care face similar collaboration challenges due to system-level issues and inadequate collaboration tools, leading to increased workload, miscommunication and reduced quality of care. Improving collaboration between GPs and specialists requires not only adjustments to individual services, but a comprehensive overhaul of the referral and back-referral process. A more integrated approach, addressing key domains, is crucial for enhancing care quality, streamlining workflows and improving health outcomes.

Acute hypoxaemic respiratory failure is a common reason for intensive care unit (ICU) admission. Non-invasive respiratory support strategies such as high-flow nasal oxygen (HFNO) and helmet non-invasive ventilation may reduce the need for invasive mechanical ventilation and death. The High-flow nasal Oxygen with or without alternating helmet Non-invasive ventilation for Oxygenation sUpport in acute Respiratory failure pilot trial is designed to compare helmet non-invasive ventilation combined with HFNO vs HFNO alone in patients with acute hypoxaemic respiratory failure and to determine the feasibility of a larger randomised controlled trial.

This is a pragmatic, open-label, multicentre randomised controlled pilot trial enrolling 200 critically ill adults with acute hypoxaemic respiratory failure across 12 Canadian ICUs. Participants are randomised 1 to 1 to receive either helmet non-invasive ventilation plus HFNO or HFNO alone for at least 48 hours. The primary aim is to assess feasibility metrics including recruitment rate, protocol adherence and fidelity to pre-specified intubation criteria. Secondary outcomes include rates of intubation, all-cause mortality, ventilator-free days, ICU length of stay and quality of life at 6 months. Primary and secondary outcomes will be analysed using Bayesian methods.

Ethics approval has been obtained at all participating centres. Findings will inform the feasibility and design of a future full-scale trial and be disseminated through peer review publications and conference presentations.

ClinicalTrials.gov Identifier: NCT05078034.

Early-life exposures, such as nutritional deficiencies, stress, smoking, toxins, medications, diseases, infections and inflammation may affect multiple physiological and metabolic systems in the offspring, including hormonal regulation, bone metabolism and mineralisation, and body composition. Moreover, the effect of these early-life exposures on later health may potentially be mediated through adverse neonatal epigenetic reprogramming of bone-related genes affecting health later in life, especially skeletal development and bone density. Thus, to advance this research further, the overall aim of the project is to investigate if (a) neonatal epigenetic and genetic signature; (b) maternal risk factors during preconception and pregnancy, such as medicine use, diseases, socioeconomic status, major life events, weight, growth and lifestyle; (c) risk factors at birth, such as instrumental delivery, mode of delivery, medicine use, injuries, diseases, weight, size for gestational age, ponderal index, gestational age; and (d) childhood risk factors, such as diseases, medicine use, major life events, weight, growth and lifestyle are associated with hormonal status, lipids, bone turnover markers, bone mineral density, fat mass and lean body mass at age 18–19 years.

Population-based, nationwide, cross-sectional clinical study with potential for longitudinal reassessment. Danish women and men aged 18–19 years old will be selected at random from the Danish National Population Registry and invited if they have available neonatal dried blood spot cards. A total of 2000 individuals will be enrolled. The study combines register data, and neonatal epigenetic and genetic analyses from stored blood with clinical and survey data. Body composition will be measured using dual-energy X-ray absorptiometry. Adult blood and hair samples will be obtained to assess hormonal status, lipids and bone turnover markers. Height, weight, waist and hip circumference, and blood pressure will be measured. Questionnaires on well-being, sleep patterns, dietary and exercise habits, onset of puberty, use of cannabis, nicotine, alcohol and pain medication will be included. Information on medicine use, diseases, socioeconomic status, major life events, weight, growth and lifestyle will be obtained from the national administrative and health registers at the time of conception and during pregnancy for the parents, as well as from the participants throughout their lifetime. Health registries include the Danish Medical Birth Register, the National Patient Register, the Danish National Prescription Register, the National Child Health Register and Statistics Denmark. Multivariate regression analyses will be performed.

This nationwide study has been approved by the Regional Committees on Health Research Ethics for Southern Denmark (S-20230105). The study participants will be enrolled in the study following their informed written consent. Results will be submitted for publication. The Strengthening the Reporting of Observational Studies in Epidemiology Statement guidelines will be used for reporting.

NCT06509776.

To determine the association between rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection following home, community and work-related exposures, to assess real-world relative vaccine effectiveness, and to determine whether anti-receptor-binding domain (RBD) IgG levels were associated with the rates of subsequent infection.

Prospective cohort of 34 months’ duration (February 2021 to December 2023).

Teachers and education workers working ≥8 hours per week in the Canadian province of Ontario.

3155 education workers were eligible for the risk factor analysis; 2977 for the serological analysis.

Rate of SARS-CoV-2 infection.

1909 SARS-CoV-2 infections were reported (0.93 per 1000 participant-days); the highest incidence occurred during the period dominated by the Omicron BA.2 variant (2.01 per 1000 participant-days). Rates of infection were significantly higher following the repeal of the mask mandate. Compared with participants without known contact with an infected person, those in close contact with infected adult or child household members (adjusted HR (aHR) 1.43; 95% CI 1.24 to 1.65 and 1.39; 95% CI 1.17 to 1.65, respectively), coworkers (aHR 1.28; 95% CI 1.10 to 1.50), or individuals from more than one setting (aHR 1.44; 95% CI 1.27 to 1.64) had higher rates of infection. Participants with three or more doses of vaccine were 79%–87% less likely to develop SARS-CoV-2 than participants who had two or fewer vaccine doses. Blood samples with anti-RBD antibody levels in the highest quintile (≥5850 binding antibody unit/mL) were associated with a lower rate of subsequent infection (aHR 0.40; 95% CI 0.23 to 0.72) compared with samples with RBD levels below the threshold of detection.

Risk of SARS-CoV-2 infection in education workers occurred at home as well as the workplace, indicating the need to practise multiple intervention strategies whenever the potential for transmission of respiratory diseases is high. COVID-19 vaccines provided protection through December 2023.

To evaluate the patterns of abnormal estimated glomerular filtration rate (eGFR) and urine albumin–creatinine ratio (UACR) follow-up testing for the detection of chronic kidney disease (CKD) in Australian general practices.

Retrospective, population-based observational study.

2 717 966 adults who visited a MedicineInsight participating general practice between 1 January 2012 and 31 December 2020, had ≥1 serum creatinine measurement (with or without a UACR measurement) and did not have CKD at baseline.

‘Guideline-concordant follow-up’ was defined as having a record of a repeat eGFR or UACR testing (assessed separately) within 6 months following the abnormal (eGFR2; UACR≥2.5 mg/mmol in males, ≥3.5 mg/mmol in females) incident result. Multivariable logistic regression was used to identify patient factors associated with receiving appropriate follow-up testing.

A total of 220 841 and 114 889 patients with an abnormal incident eGFR and UACR result, respectively, were identified. Nearly half (45.0%) of the patients with an abnormal eGFR result and over two-thirds (69.7%) of the patients with an abnormal UACR result did not have a follow-up test within 6 months. Patient factors associated with a higher likelihood of follow-up eGFR testing included indicators of poorer baseline health and greater CKD risk, such as comorbid diabetes (adjusted OR 1.36, 95% CI 1.32 to 1.40) or more severe incident eGFR (adjusted ORs for eGFR categories 30–44, 15–29 and

In this large, population-based study, we observed substantial gaps in the follow-up of abnormal eGFR and UACR for the detection of CKD in primary care settings. Effective strategies to optimise follow-up testing for CKD detection are needed.

Total diet replacements (TDRs) and weight loss medications (WLMs) have proven effective in producing substantial weight loss for individuals with obesity. Evidence is lacking on whether combining these treatments is effective and cost-effective in primary care for adults with obesity class I (body mass index (BMI) 30–34.9) or uncomplicated obesity class II or higher (BMI≥35 without obesity-related disease).

LightCARE is a 2-year 1:1 randomised, parallel-group, clinical superiority trial with blinded outcome assessment evaluating the benefits and harms of an intensive weight loss (IWL) intervention compared with usual care for adults with obesity in Denmark and the UK. The trial will include 400 participants aged 18–60 years with obesity class I or uncomplicated obesity class II or higher. The IWL programme aims to achieve and maintain a weight loss of ≥20% through a flexible and individualised combination of TDR, behavioural support, including physical activity and sleep guidance, and WLM if needed and will continue for 2 years. The control group will receive usual care offered in each country, typically consisting of brief behavioural support for weight loss. The primary outcome is body weight 2 years after randomisation. Secondary outcomes will include the proportion of participants achieving ≥20% weight loss, Short-Form-36 Mental Component Score, 4-m gait speed and Metabolic Syndrome Severity-Z score. Serious adverse events, the incidence of eating disorders and bone mineral density will be evaluated as safety outcomes. We will also examine the cost-effectiveness of the intervention, within the trial and in the longer term through modelling. We will conduct a process evaluation to inform any future implementation.

Ethical approval was granted in Denmark (December 2023, H-23051332) and the UK (August 2024, 24/SC/0210). Findings from the trial will be disseminated through peer-reviewed journals and scientific conferences.

NCT06321432.

Little research has been done on post-COVID symptoms at 24 months postinfection and on the association these may have on health-related quality of life (HRQOL).

We assessed the prevalence and severity of post-COVID symptoms and quantified EuroQol 5 Dimension 5 Level (EQ-5D-5L), self-perceived health question (EuroQol Visual Analogue Scale (EQ-VAS)) and health utility scores (HUS) up to 24 months follow-up.

The longitudinal multiple cohort CORona Follow-Up (CORFU) study combines seven COVID-19 patient cohorts and a survey among the general public. The participants received questionnaires on several time points. Participants were stratified by: without a known SARS-CoV-2 infection (control group), proven SARS-CoV-2 infection but non-hospitalised, proven SARS-CoV-2 infection hospitalised to the ward, and proven SARS-CoV-2 infection hospitalised to the intensive care unit (ICU).

In this study, data of seven COVID-19 patient cohorts and a survey among the general public are included.

Former COVID-19 patients and controls participated in this cohort study.

Former COVID-19 patients and non-COVID-19 controls were sent questionnaires on symptoms associated with post-COVID condition. The CORFU questionnaire included 14 symptom questions on post-COVID condition using a five-level Likert-scale format. Furthermore, HRQOL was quantified using the EuroQol EQ-5D-5L questionnaire: EQ-VAS and the EQ-5D-5L utility score. The EQ-5D-5L questionnaire includes five domains that are scored on a five-point Likert scale: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

A total of 901 participants (and 434 controls) responded at 24 months follow-up. In all former COVID-19 patients, the presence of post-COVID condition at 24 months was observed in 62 (42.5%, 95% CI 34.3% to 50.9%) of the non-hospitalised patients, 333 (65.0%, 95% CI 60.7% to 69.2%) of the hospitalised ward patients and 156 (63.2%, 95% CI 56.8% to 69.2%) of the ICU patients, respectively (p

Many former COVID-19 patients experience post-COVID symptoms at 24 months follow-up, with the highest prevalence in hospitalised participants. Also, former patients reported a lower HRQOL.

The CORFU study was registered at clinicaltrials.gov (registration number NCT05240742).

Guideline-based strategies to prevent chronic kidney disease (CKD) progression and complications are available, yet their implementation in clinical practice is uncertain. We aimed to synthesise the available evidence on the concordance of CKD care with clinical guidelines to identify gaps and inform future CKD care.

Systematic review and meta-analysis.

We systematically searched MEDLINE (OVID), EMBASE (OVID) and CINAHL (EBSCOhost) (to 18 July 2025) for observational studies of adults with CKD reporting data on the quality of CKD care. We assessed data on quality indicators of CKD care across domains that related to patient monitoring (glomerular filtration rate and albuminuria), medications use (ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), statins) and treatment targets (blood pressure (BP) and HbA1c). Pooled estimates (95% CI) of the percentage of patients who met the quality indicators for CKD care were estimated using random effects model.

59 studies across 24 countries, including a total of 3 003 641 patients with CKD, were included. Across studies, 81.3% (95% CI: 75% to 87.6%) of patients received eGFR monitoring, 47.4% (95% CI: 40.0% to 54.7%) had albuminuria testing, and 90% (95% CI: 84.3% to 95.9%) had BP measured. ACEIs/ARBs were prescribed among 56.7% (95% CI: 51.5% to 62%), and statins among 56.6% (95% CI: 48.9% to 64.3%) of patients. BP (systolic BP ≤140/90 mm Hg) and HbA1c (

Current evidence shows substantial variation in CKD care quality globally. Guideline-concordant care varied according to quality measures and across patient groups, with gaps in indicators like albuminuria testing. These findings underscore the need for effective quality improvement strategies to address gaps in CKD care, including increased albuminuria testing for risk stratification, together with systematic measures for monitoring care quality.

CRD42023391749.

Loneliness and adverse childhood experiences (ACEs) constitute significant risk factors for mental disorders, with loneliness emerging as a serious global public health concern. Recent research highlights the role of loneliness as a potential link between early life adversities and current psychopathology. However, most studies have been conducted in high-income, highly individualistic countries. This cross-sectional study explores the interplay between loneliness, social network size, recalled ACEs and depressive symptoms in Ethiopia—a low-income and collectivistic cultural context.

The study included 125 psychiatric outpatients at Jimma University Medical Center in Southwest Ethiopia diagnosed with major depressive disorder, bipolar disorder or psychotic disorders, as well as 131 non-clinical participants. Trained interviewers administered the University of California, Los Angeles (UCLA) Loneliness Scale, the Childhood Trauma Questionnaire, the Social Network Index and the WHO-5 Well-Being Index. We used Mann-Whitney U tests, partial correlation and mediation analysis for data analysis.

We found mild-to-moderate correlations between loneliness and ACEs (clinical group: rho=0.29, p1b₁=0.07, 95% CI (0.02 to 0.13); non-clinical group: indirect effect a₁b₁=0.03, 95% CI (0.01 to 0.07)). In contrast, social network size was neither correlated with ACEs nor did it mediate the association between ACEs and depressive symptoms in either group.

This study replicates previous findings that loneliness—rather than social network size—is associated with ACEs and mediates their impact on depressive symptoms. These results support the transcultural and transdiagnostic relevance of loneliness as a universal psychological mechanism, independent of societal structure.

Sepsis is a major cause of death both globally and in the United States. Early identification and treatment of sepsis are crucial for improving patient outcomes. International guidelines recommend hospital sepsis screening programmes, which are commonly implemented in the electronic health record (EHR) as an interruptive sepsis screening alert based on systemic inflammatory response syndrome (SIRS) criteria. Despite widespread use, it is unknown whether these sepsis screening and alert tools improve the delivery of high-quality sepsis care.

The Sepsis Electronic Prompting for Timely Intervention and Care (SEPTIC) master protocol will study two distinct populations in separate trials: emergency department (ED) patients (SEPTIC-ED) and inpatients (SEPTIC-IP). The SEPTIC trials are pragmatic, multicentre, blinded, randomised controlled trials, with equal allocation to compare four SIRS-based sepsis screening alert groups: no alerts (control), nurse alerts only, prescribing clinician alerts only, or nurse and prescribing clinician alerts. Randomisation will be at the patient level. SEPTIC will be performed at eight acute-care hospitals in the greater New York City area and enrol patients at least 18 years old. The primary outcome is the percentage of patients with completion of a modified Surviving Sepsis Campaign (SSC) hour-1 bundle within 3 hours of the first SIRS alert. Secondary outcomes include time from first alert to completion of a modified SSC hour-1 bundle, time from first alert to individual bundle component order and completion, intensive care unit (ICU) transfer, hospital discharge disposition, inpatient mortality at 90 days, positive blood cultures (bacteraemia), adverse antibiotic events, sepsis diagnoses and septic shock diagnoses.

Ethics approval was obtained from the Columbia University Institutional Review Board (IRB) serving as a single IRB. Results will be disseminated in peer-reviewed journal(s), scientific meeting(s) and via social media.

ClinicalTrials.gov: NCT06117605 and NCT06117618.