This study aims to explore the ability to identify high-grade intracranial arterial stenosis (ICAS) by an artificial intelligence (AI) designed to detect large vessel occlusions (LVO) and the clinical relevance of these ‘false positive’ findings.

We are presenting a retrospective cohort study.

The study was conducted at a supraregional stroke centre of an urban tertiary care provider.

Consecutive stroke cases treated between January 2023 and December 2023 of patients >18 years of both sexes and any ethnicity were eligible for inclusion. 934 patients (52.7% male) with a mean age of 71.7±13.6 years (25–101 years) were included.

CT angiographies were analysed by a deep learning algorithm for LVO detection of the anterior circulation. AI results were compared with radiology reports and secondary focused evaluation.

Diagnostic accuracies for ICAS detection by the AI were calculated.

Primary reports identified 30 ICAS and nine additional ICAS were detected during secondary evaluation (incidence 4.2%). The sensitivity of radiology reports was 77% (95% CI 0.61 to 0.89), the specificity 99% (95% CI 0.98 to 1.00), negative predictive value (NPV) 99% (95% CI 0.98 to 0.99) and positive predictive value (PPV) 79% (95% CI 0.65 to 0.88). The AI identified 13 of 39 ICAS correctly. 18 false positive cases (neither LVO nor ICAS) were flagged by the AI. The sensitivity of the algorithm was 33% (95% CI 0.19 to 0.50), the specificity 98% (95% CI 0.97 to 0.99), the NPV 97% (95% CI 0.96 to 0.98) and PPV 42% (95% CI 0.28 to 0.58).

Detection of high-grade ICAS by an algorithm trained to identify LVO is per se a false positive finding but occurred in 13 of 39 cases. Dedicated training for ICAS might lead to a beneficial tool during the diagnostic work-up for ischaemic stroke.

German Register for Clinical Trials (DRKS: DRKS00034019 https://drks.de/search/de/trial/DRKS00034019).

The dynamic physiological and hormonal changes through the menopause transition predispose women to an increased risk of chronic diseases including cardiovascular disease, metabolic disease, depression and dementia. The underlying mechanisms remain unclear, yet it is thought that chronic systemic inflammation and changes to lifestyle behaviours play important roles. The LIfestyle risk Factors for chronic disease across the stagEs of reproductive ageing (LIFE study) is a cross-sectional study aimed to characterise how hormonal and lifestyle (physical activity, diet and sleep) differences across pre, peri and postmenopause influence chronic systemic inflammation, visceral adiposity, cognitive function and sleep health.

Women aged between 40 and 65 years were recruited and classified into pre, peri or postmenopausal groups. Body composition measures and blood samples were collected. Sleep and physical activity were objectively measured using activPAL4 and ActiGraph GT9X link accelerometer over 7 days. Participants were also provided with a sleep diary. Physical function was assessed using the Short Physical Performance Battery. Cognitive function was evaluated using Addenbrooke’s Cognitive Examination-III and Cambridge Neuropsychological Test Automated Battery. Participants completed a series of questionnaires: Depression, Anxiety and Stress Scale-21, RuSATED, Berlin Questionnaire, Insomnia Severity Index, Activities-specific Balance Confidence Scale and the Australian Eating Survey.

Ethical approval was received from the relevant University Human Research Ethics Committee (ethics approval number #S221718) prior to the commencement of the research project. Data collection is ongoing and expected to be completed by April 2026. Results are expected to be available from July 2026. Findings will be disseminated in national and international conferences and in peer-reviewed journals and expected to inform how differences in lifestyle behaviours across menopause influence chronic systemic inflammation, visceral adiposity and cognitive function. Understanding and characterising the links between lifestyle behaviours and menopausal symptoms will inform targeted strategies to improve long-term well-being, heart, brain and metabolic health.

Adult-onset type 1 diabetes (T1D) is often misclassified as type 2 diabetes (T2D), resulting in delayed treatment, missed opportunities for referrals to specialists and increased risk of complications including diabetic ketoacidosis. An electronic medical record (EMR)-based algorithm—originally trained on a large national EMR dataset to identify likely misclassified adult-onset T1D cases—was tested and retrained on a health information exchange (HIE) dataset from HealthShare Exchange (HSX). Promising results were achieved on historical data, particularly when using the retrained algorithm. However, its prospective validation is essential to more reliably assess its clinical utility and real-world precision in flagging high-risk patients for clinician review.

This is a prospective, multicentre, non-interventional cohort study in two HSX-member healthcare organisations (HCOs) in southeastern Pennsylvania. At the onset of the study, all adult T2D patients are scored by the algorithm analysing HIE data on relevant predictors found in the 24-month lookback period. Patients meeting a prespecified score threshold estimated in retrospective testing to yield 10% recall will be presented to designated endocrinology or primary care providers for structured chart review, attribution confirmation and guideline-concordant follow-up (including autoantibody testing where appropriate). The primary endpoint is positive predictive value for confirmed adult-onset T1D among flagged patients. Secondary endpoints characterise operational cascade metrics (attribution, provider recommendation, test ordering/results and diagnosis updates) along with 95% CIs. Exploratory endpoints will assess provider adoption, interpretability and workflow integration via structured provider interviews.

This study was reviewed and approved by Advarra Institutional Review Board (protocol Pro00075945). The Institutional Review Board waived patient informed consent and granted a full waiver of HIPAA authorisation for patient records, while providers were required to provide written informed consent. HSX data were accessed and shared under its member-defined use cases. Findings will be disseminated via peer-reviewed publications and conference presentations. Reporting will follow Strengthening the Reporting of Observational Studies in Epidemiology guidance for cohort studies.

This study aimed to analyse temporal trends in fertility and birth rates, examine maternal characteristics and forecast future demographic changes in Georgia.

This was a retrospective observational study using population-level data from the National Statistics Office of Georgia (Geostat) and the Georgian Birth Registry (GBR). Temporal trends were analysed using Prais-Winsten regression models and annual percentage changes (APCs) and future projections were generated using autoregressive integrated moving average (ARIMA) models.

The study included data on 543 662 live births retrieved from the Geostat for the period 2014–2024. Additionally, maternal characteristics were analysed for 366 684 births recorded in the GBR for the period 2017–2024. Selection criteria included all live births during the study period, with no specific exclusion criteria applied.

Primary outcome measures were trends in the total fertility rate (TFR) and crude birth rate (CBR) over the study period (2014–2024) and their projections for 2025–2034. Secondary outcome measures were concurrent changes in maternal characteristics, including maternal age, nationality, place of residence, region of residence and parity.

Between 2014 and 2024, Georgia’s TFR declined from 2.30 to 1.68 children per woman (APC=3.12%, 95% CI –3.65 to –2.59), and the CBR dropped from 16.3 to 10.7 births per 1000 population per year (APC=4.39%, 95% CI –4.63 to –4.15). Fertility rates decreased most significantly among women aged

Georgia is undergoing a demographic transition characterised by declining fertility rates and delayed childbearing. Assuming the mechanisms underlying 2014–2024 data remain unchanged, projections indicate a continued decline in fertility and birth rates by 2034, which may pose significant social and economic challenges for the country. Further research is needed to explore the underlying factors driving these trends and to develop strategies to address the potential implications of this demographic shift.

To determine the prevalence and clinical characteristics associated with polyneuropathy in kidney transplant recipients (KTRs).

Cross-sectional study.

SENS study at the University Medical Center Groningen, the Netherlands, December 2021–May 2023.

KTR, participating in the ongoing TransplantLines Biobank and Cohort Study, ≥12 months post-transplantation.

Participants underwent a structured neurological assessment including history taking, neurological examination, quantitative sensory testing and nerve conduction studies. An expert panel classified participants into no/possible, probable/definite large fibre polyneuropathy or small fibre neuropathy. Large-fibre subtypes included axonal or demyelinating, pure sensory, pure motor and sensorimotor. To assess potential associations with clinical characteristics, logistic regression analysis was conducted.

We included 160 KTRs with a mean age of 59.8±11.6 years at a median of 6.1 (95% CI 3.9 to 13.1) years post-transplantation, with 16 KTRs (10%) diagnosed with polyneuropathy before study inclusion. In total, 84 KTRs (53%) were identified with large fibre polyneuropathy and 7 KTRs (4%) with small fibre neuropathy. KTRs with large fibre polyneuropathy presented with either sensor-predominant polyneuropathy (40 KTR (48%)) or sensorimotor polyneuropathy (44 KTR (52%)). We found no neurophysiological characteristics of demyelination. Overall, 18% (95% CI 11% to 27%) of KTRs with large fibre polyneuropathy were asymptomatic. Higher age (OR=1.04 (1.01 to 1.08), p=0.01), male sex (OR=2.55 (1.19 to 5.60), p=0.02), diabetes (OR=5.58 (1.36 to 38.14), p=0.03) and elevated urea levels (OR=1.12 (1.04 to 1.23), p=0.01) were significantly associated with polyneuropathy in KTR.

In contrast with previous studies, axonal sensory or sensorimotor polyneuropathy is highly prevalent and often underdiagnosed in KTR. Next to higher age and male sex, it was independently associated with diabetes and higher urea levels. Further research is needed to reveal the aetiology and course of polyneuropathy in KTRs.

NCT04664426.

The BioCaPPE (Biomarkers of Prostate Cancer/Prevention and Environment) study is a multicentre prospective observational cohort designed to identify biomarkers associated with prostate cancer (PCa) risk that may be modifiable through lifestyle factors. This paper describes the cohort, along with the data and bio-samples available for future studies in PCa risk assessment.

Canadian men at risk of PCa were enrolled based on one of two criteria (1) negative first prostate biopsy within 6 months from enrolment (Group 1); or (2) a prostate-specific antigen (PSA) blood level between 2.5 and 10 ng/mL without prior prostate biopsy (Group 2). At baseline, blood samples and comprehensive data were collected. PCa incidence and lifestyle factors were updated for all participants over 2 years, with extended follow-up for those who provided additional consent.

Recruitment was conducted across four health centres in Quebec, Canada. A total of 2053 men were enrolled—1499 in Group 1 and 554 in Group 2. All participants completed the initial visit, which included collection of medical and family history, anthropometric measurements, demographic information, dietary and alcohol intake, physical activity, tobacco use, medication use, and quality of life assessments, and candidate biomarker measurements. At the 2-year mark, 7.2% of participants had developed PCa; this figure has since increased to 15.3% (median follow-up: 6.1 years). Additionally, 84% (n=1718) consented to ongoing annual follow-up.

This large, prospective cohort of men at risk of PCa offers valuable resources for risk stratification and primary prevention. The BioCaPPE biosamples and data are available to support the identification of lifestyle-related biomarkers associated with PCa risk in this population.

ClinicalTrials.gov Identifier: NCT03383016.

Despite growing evidence and specific guidelines, people with knee and hip osteoarthritis often do not receive appropriate care. This review aims to identify healthcare utilisation and its predictors to optimise existing services and identify unmet needs across different healthcare systems using Andersen’s Healthcare Utilisation Model as a reference.

We conducted a scoping review and included studies published between 2010 and 2023 that assessed the healthcare utilisation in people with osteoarthritis. We examined general practitioner and orthopaedist consultations, physiotherapy, medication, hospitalisation and emergency department visits.

PubMed, Livivo, Cochrane Library, CINAHL Complete and Web of Science were searched from January 2010 until November 2023. An updated literature search was conducted in December 2025.

We analysed the included studies by means of thematic analysis and descriptive representation of quantitative data.

The literature search identified 4228 articles, of which 2380 articles were included in the title/abstract screening after excluding duplicates. After the full-text screening of 97 articles, we included 39 (n=4 233 566) publications for data extraction and data synthesis. Most studies were conducted in the USA, Australia, Germany and the UK—few from Asia, Middle and South America and other European countries. Utilised healthcare services are general practitioner consultations (mean use: 43% of participants, n=6), opioid (36%, n=8) and non-steroidal anti-inflammatory drug use (42%, n=7), emergency department visits (27%, n=3), orthopaedic surgeon consultations (26%, n=4), total joint replacement surgery (26%, n=3), physiotherapy (14%, n=8), hospitalisation (11%, n=7) and psychotherapy (6%, n=2). Among predisposing characteristics, older age, female gender, ethnicity, high socioeconomic status, social support and fear of certain treatment options were related to higher healthcare utilisation. In those, gender (n=8 studies) and age (n=6 studies) were primarily discussed. Regarding enabling and need factors, increased healthcare utilisation is associated with urban residence and being insured as well as having pain and comorbidities.

Results vary between countries. Against the background of existing guidelines, there is a need for promoting the utilisation of non-surgical and non-pharmacological treatments, such as physiotherapy, which have proven to be effective. Special attention should be given to predictors when promoting appropriate healthcare utilisation. Addressing the identified predictors associated with healthcare utilisation may lead to more appropriate osteoarthritis care. Further research is needed to address healthcare stakeholders’ (physiotherapists, insurers, patients and practitioners) needs and roles in the process.

Protocol registration on PROSPERO (CRD42023475803).

Gambling encompasses all activities that involve betting or wagering money. It is highly prevalent both in Canada and worldwide. While most individuals gamble without experiencing harm, some develop problem gambling, which is associated with serious psychological, relational and financial outcomes. Sexual and gender diversity (SGD) populations experience disproportionately high rates of mental health disorders, although little is known about their gambling trajectories. Knowledge in this regard is mainly based on cross-sectional studies, with no longitudinal evidence being available internationally. This gap in the literature restricts understanding of how problematic gambling emerges and evolves among SGD populations. It also limits the development of prevention and harm reduction strategies tailored to their realities.

This five-year longitudinal study will use a mixed-methods explanatory and sequential design in two phases. The first phase is a prospective cohort study. A self-report questionnaire will be administered online via a web panel to Canadian residents who are 18 years of age or older, self-identify as SGD and have gambled at least once in the previous 12 months (n=2500). This survey will be repeated annually over the course of three years to describe respondents’ gambling habits, model their trajectories and identify factors associated with problematic gambling. The second phase is a descriptive qualitative study. Semi-structured interviews will be conducted with respondents from phase 1 who present problematic gambling (n=40) to explore their experiences and lived realities.

This research project has been ethically and scientifically approved by the Research Ethics Committee and by the CIUSSS de l’Estrie—CHUS scientific evaluation committee on November 3, 2025 (reference number: 2026-6060 Trajectoires-JHA-LGBTQ). For all phases of the study, written or verbal consent will be obtained from each participant. A copy of the consent form and contact information will be sent to each participant.

Spinal cord injury (SCI) impairs autonomic functions, which are ranked among the highest priorities for recovery. The loss of autonomic control, including bowel, bladder, sexual and cardiovascular functions, interferes with rehabilitation and decreases health-related quality of life (HRQoL). Preliminary evidence indicates that non-invasive transcutaneous spinal cord stimulation (TCSCS) has the potential to improve autonomic stability in people with SCI. However, the optimal stimulation site for improving autonomic responses remains to be determined. This pilot randomised clinical trial aims to explore the efficacy of non-invasive mid-thoracic and lumbosacral TCSCS (proof-of-concept) for blood pressure stability (orthostatic hypotension and autonomic dysreflexia burden) alongside end-organ autonomic functions (lower urinary tract, bowel and sexual function) and HRQoL.

30 participants with chronic (>1 year) motor-complete SCI (American Spinal Injuries Association Impairment Scale A and B) at or above T6 will be enrolled in this open-label, two-arm randomised pilot clinical trial. Participants will be block randomised into either the mid-thoracic or lumbosacral TCSCS group. Participants will then undergo 8 weeks of TCSCS (3 times per week for 60 min; 24 sessions total) while in a seated position. Post-treatment effects will be recorded following the 8-week intervention and follow-up effects will be recorded 8 weeks after the end of the intervention. Primary and secondary outcomes will assess resting blood pressure, autonomic dysreflexia, orthostatic hypotension and lower urinary tract, bowel and sexual functions as well as HRQoL.

This study is approved by The University of British Columbia’s Clinical Research Ethics Board (UBC CREB H22-00365), and by Health Canada for Investigational Testing Authorisations (ITA) for Class II medical devices used in this trial (ITA#346875 TESCoN; ITA#381 154 SCONE). The findings will be disseminated through peer-reviewed publications, conferences, seminars and SCI community outreach.

NCT05369520.

The overall aim of the present project is to increase healthcare professionals’ ability to ask about exposure and to identify individuals exposed to intimate partner violence (IPV). The project will evaluate the effects of three different interventions that can be assumed to increase healthcare professionals’ ability to ask and identify individuals who have been or are exposed to IPV.

This project has a quasi-experimental design. After a 2-month baseline period, participating care units (primary health centres, maternal health clinics and youth guidance clinics) will be assigned to one of three interventions to potentially increase the ability to enquire and identify patient exposure to IPV: (1) healthcare professionals’ use of a standardised questionnaire about exposure to IPV in patient meetings, (2) training through the use of a virtual patient case tailored to health professionals and (3) a combination of (1) and (2) earlier. Preintervention (baseline) and postintervention measurements of the health professionals’ enquiry and identification of patients exposed to IPV will be used to explore the effect of the interventions. Focus group interviews with the participating health professionals will be used as a qualitative method, applying thematic analysis, to explore which intervention they perceive as most effective in increasing their ability to identify victims of IPV.

Data analysis will focus on a comparison of pre- and post-measurements regarding the number of patients asked about and identified patients in each intervention arm that have been or are exposed to IPV. Measurements will be carried out per care unit at the group level. Qualitative data from focus group interviews will be analysed using thematic analysis.

All participants will sign a written consent form and the study has been approved by the Swedish Ethical Review Authority (Dnr 2023-03399-01). The study will be conducted according to good clinical practice and the Declaration of Helsinki. The results of this study will increase knowledge about how identification of violence in close relationships can be improved in the clinical setting through publications in peer-reviewed journals and presentations at national and international scientific conferences.

Recruiting since May 2024. Expected trial termination December 2026.

NCT06322251.

The literature on sustainability performance frameworks for healthcare organisations varies in its applicability to different types of organisations and settings, functions and activities, and definitions and dimensions of sustainability. This fragmentation creates implementation barriers which may be overcome by consolidating existing evidence in a format that can be linked directly to organisations’ business models. This protocol proposes a scoping review to assess the extent of the literature on frameworks for monitoring and evaluating the multidimensional sustainability performance of healthcare organisations and to assemble a consolidated framework in an operationally relevant format to support progress towards sustainable healthcare organisations.

The search strategy will be applied across Semantic Scholar, Google Scholar, Web of Science, MEDLINE, Embase, Academic Search Premier, CINAHL and Business Source Premier databases. Search results from 2009, coinciding with the publication of the WHO’s ‘Healthy Hospitals, Healthy Planet, Healthy People’ report, will be considered. The scoping review will include studies reporting on multidimensional sustainability monitoring or evaluation frameworks applied or developed for use at the level of healthcare delivery organisations. Studies relating to operational units within organisations or to healthcare systems will be excluded. The review’s context will be restricted to operational sustainability and will not consider the literature on sustainable design planning and construction of new facilities. No specific exclusion criteria will be applied to the types of healthcare delivery organisations nor participants implicated in the frameworks. Title and abstract screening against the inclusion and exclusion criteria, followed by full-text assessment of remaining articles, will be performed by two reviewers. Data from included studies will be extracted using a custom-designed extraction tool, analysed using topic or thematic analysis to consolidate themes and presented within the triple-layered business model canvas.

Only publicly available sources will be used; research ethics approval is not required. Findings will be submitted to a peer-reviewed journal and presented at scientific meetings.

One-third of patients operated for degenerative conditions in the lumbar spine do not report substantial improvement after 12 months. Most previous outcome prediction models are classifiers. This constrains nuances in prediction and use for decision support.

To develop and test models for the prediction of continuous outcome scores and retrieval of similar patients’ outcomes, and to evaluate the models’ fairness.

Norwegian public and private specialist healthcare.

All cases recorded with an elective operation for lumbar disc herniation (LDH, n=18 377) or lumbar spinal stenosis (LSS, n=24 540) in the Norwegian Registry for Spine Surgery from 1 January 2007 to 23 May 2023.

All outcomes were patient-reported 12 months after the operation. The primary outcome was the Oswestry disability index (ODI), modelled on a scale ranging from 0 to 100. Numeric Rating Scale scores (range 0–10) for back and leg pain were secondary outcomes.

We selected 22 predictors recorded preoperatively by patients and clinicians based on Shapley Additive Explanations values. Data were split into 80%/20% training/test samples for LDH and LSS. Six machine learning methods for regression, that is, with a continuous outcome (extreme gradient boosting (XGBoost), Gaussian process regression, gradient boosting regression, artificial neural networks and linear regression), were trained for both conditions using fivefold cross-validation. We report the magnitude and distribution of errors as mean absolute error (MAE) with 95% CIs, and explanatory power as the coefficient of determination (R²). Fairness and calibration were assessed with violin and calibration plots of error. We developed a patient-similarity function that uses a K-nearest neighbour model to retrieve the individual outcomes of the 50 most similar patients and evaluated it by calculating L1 distances (Manhattan distances) across subgroups.

XGBoost regression performed best for both conditions. The models showed good calibration and predicted ODI with MAE 11.32 (95% CI 11.00 to 11.63) and R² 0.27 (95% CI 0.24 to 0.29) for LDH and MAE 12.05 (95% CI 11.76 to 12.32) and R² 0.31 (95% CI 0.28 to 0.34) for LSS. The MAEs for back and leg pain were 2.09 (95% CI 2.04 to 2.15) and 1.95 (95% CI 1.90 to 2.00) for LDH and 2.33 (95% CI 2.28 to 2.38) and 2.13 (95% CI 2.08 to 2.16) for LSS. All models were fair with differences in error between subgroups for sex, age, education level and native language. In the patient-similarity function, distances at baseline were evenly distributed across subgroups.

Our machine learning models predicted continuous outcomes with MAEs close to the SEs of measurements. The models were fair across sociodemographic subgroups. We succeeded in developing a patient-similarity function which supplements the predictions.

Excessive gestational weight gain increases the risk of complications in pregnancy, childbirth and later in life among pregnant women living with overweight and their offspring. Therefore, this study aimed to develop and examine the feasibility of a digital intervention supporting recommended gestational weight gain and the recommended level of physical activity, targeting pregnant women with a body mass index (BMI) of 27 or above.

Intervention development was guided by the Medical Research Council guideline on the development and evaluation of complex interventions, and subsequent feasibility testing was conducted in a non-randomised design.

The obstetric department at Copenhagen University Hospital—North Zealand, Denmark.

98 pregnant women living with overweight participated in feasibility testing.

The intervention developed in this study was a mobile phone application with a digital care guide containing text and video information supporting recommended gestational weight gain and physical activity levels. The video material featured multiple healthcare professionals and a pregnant woman from the target group.

The main feasibility measures were participant recruitment and engagement with the digital care guide throughout pregnancy.

Recruitment rates were satisfactory, with 69% of eligible pregnant women consenting to participation. The participants used the application and engaged with the digital care guide; however, use of the care guide diminished as pregnancy progressed.

We developed a digital care guide supporting recommended gestational weight gain and physical activity levels for pregnant women with a BMI of 27 or higher. Feasibility testing indicated that there is sufficient interest in participating in a study promoting recommended weight gain and physical activity to warrant a larger effectiveness trial.

To estimate the relative effectiveness of vaccination (0, 1, 2, ≥3 doses) and prior infection, in combination, on risk of SARS-CoV-2 infection/reinfection.

Prospective cohort study.

We recruited participants for the Aegis Study from nine clinics across five US states. Participants must have been 18 years or older, had a history of a positive PCR for SARS-CoV-2, SARS-CoV-2 antigen or antibody test for SARS-CoV-2 with documentation or had no suspected or documented prior SARS-CoV-2 infection, intended to remain in study area for the next 12 months, and had elevated risk of future SARS-CoV-2 exposure. Exclusion criteria included acute illness, contraindication to phlebotomy, use of immunosuppressants or receipt of systemic immunoglobulins.

We used extended Cox regression with robust standard errors to estimate the association between time-varying number of vaccine doses and baseline prior infection on risk of infection/reinfection among a prospective cohort of US adults between February 2021 and January 2023, accounting for censoring using inverse probability of censoring weights. Additionally, to quantify possible exposure misclassification of prior infection by comparing prior infection operationalised as (1) documented/self-reported prior infection and (2) documented/self-reported prior infection plus nucleocapsid antibody indication of prior infection.

Of n=2178 who completed enrolment, n=1887 adults (63% female; 65% non-Latino White) contributed 366 905 days of observation. Participants contributed an average of 7.2 months of follow-up between February 2021 and January 2023. 28% (n=533) of individuals were infected or reinfected during the study period. Similar relative effectiveness was observed between the two different operationalisations of prior infection. After correction for prior infection status in the nearly 16% of those without study documentation of prior infection who had nucleocapsid antibody levels comparable to documented cases, relative to the unvaccinated with no prior infection, estimated effectiveness generally increased with increasing vaccine doses and prior infection (without prior infection: one (17%, 95% CI –31% to 47%), two (49%, 95% CI 31% to 63%), ≥three (71%, 95% CI 58% to 80%) vaccine doses; with prior infection: none (56%, 95% CI 30% to 72%), one (71%, 95% CI 42% to 86%), two (65%, 95% CI 49% to 76%), ≥three (80%, 95% CI 68% to 88%) vaccine doses). Pairwise comparisons at each vaccine dose (ref: no prior infection) revealed that prior infection provided additional protection, with stronger relationships for no and one dose (none: 56% (95% CI 30% to 72%), one: 66% (95% CI 28% to 84%), two: 31% (95% CI 7% to 49%), ≥three 31% (95% CI 0% to 53%)). There was a marked decrease in the protection offered by vaccination, prior infection, or both in the Omicron period versus pre-Omicron period.

In our real-world observational sample, vaccination (with two and ≥three vaccine doses of any Food and Drug Administration Emergency Use Authorization approved vaccine) and prior infection conferred benefits for protection against infection/reinfection. Re-classification of prior infection status based on antibody levels had little effect on results.