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Arboviral infections in southeast Europe: ongoing challenges for diagnosis, outbreak investigation, and preparedness.
Get PDFHealthcare use in individuals with rheumatoid arthritis during the COVID-19 pandemic and beyond: A cohort study in three nations of the UK
No full textObjectives : We aimed to estimate how rheumatology outpatient hospital attendances have changed since the COVID-19 pandemic and determine demographic characteristics associated with observed changes.
Methods : Using three primary and secondary care electronic health record datasets in England (with the approval of NHS England), Scotland, and Wales, we identified people with a diagnosis of rheumatoid arthritis (RA) before 01/04/2019. We determined the proportion of people with rheumatology hospital outpatient appointments each month (April 2019-December 2022 (Wales and Scotland), November 2023 (England)) and quantified changes using interrupted time-series analysis. We used logistic regression to determine characteristics associated with having fewer appointments compared to 2019.
Results : We identified 145,065, 3,813 and 13,637 people coded with RA in England, Scotland, and Wales, respectively. At the start of the COVID-19 pandemic the number of rheumatology outpatient appointments dropped sharply across all nations. In England and Scotland, the percentage of monthly appointments has continued to decline. In Wales, while there was a gradual recovery, rheumatology services have not returned to pre-pandemic levels. In contrast, the number of appointments for other specialties has recovered in all nations. People with no rheumatology outpatient appointments were more often aged over 80, male, and living in rural areas. Ethnic minorities, those living in more deprived, and urban areas had fewer appointments after the start of the pandemic compared to 2019.
Conclusion: For the first time, we compared healthcare use across three UK nations and found rheumatology outpatient appointments had not recovered to pre-COVID-19 pandemic levels, particularly in Scotland and England
DECOVID: A UK Two-Center Harmonized Database of Acute Care Electronic Health Records for COVID-19 Research
Get PDFThe DECOVID database contains harmonized pseudonymized electronic health record (EHR) data on all adult (≥18 years old) patients presenting to two large, digitally mature centers in the United Kingdom between 1 January 2020 and 28 February 2021, with follow-up until at least 28 March 2021. The database was originally developed to support the COVID-19 response but is now available via the PIONEER data hub for researchers to explore a wide range of research questions, including exploratory analyses, risk factor assessment, prediction modeling, and comparative effectiveness studies. Raw data were extracted from local EHRs and transformed into a standardized form (Observational Health Data Sciences and Informatics-Common Data Model version 5.3.1). The database includes 165,420 patients across 256,804 hospital presentations. For these patients, highly granular data are available, including patient demographics, longitudinal vital signs, physiology, treatments, laboratory findings, clinical diagnoses, and outcomes. There are 10,030 patients with COVID-19, of whom 1472 died in hospital
Modelling the health and cost implications of expanded access to HIV, HCV and sexually transmitted infection testing in Switzerland.
Get PDFBACKGROUND: This study was conducted as part of the Swiss National Programme to Stop HIV, Hepatitis B Virus, Hepatitis C Virus and Sexually Transmitted Infections (NAPS), which aims to reduce the spread of sexually transmitted infections in Switzerland. The goal was to identify the most effective and cost-efficient screening strategies to lower the incidence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), syphilis, Neisseria gonorrhoeae and Chlamydia trachomatis by improving access to screening.
METHODS: A Markov model was developed to assess the impact of various screening strategies among key populations over two years, including men who have sex with men (MSM), female sex workers (FSW) and people who inject drugs (PWID). The model further stratifies individuals based on partner number (MSM) and injection-equipment sharing (PWID). Comprehensive cost estimates for screening and treatment were derived from insurance data, literature and expert opinions. The effectiveness of screening interventions was evaluated by measuring reductions in disease incidence and cost savings, comparing the costs of screening to those of acute and chronic care for prevented infections.
RESULTS: Increased screening frequency among key populations led to a reduction in incidence for all five infections studied. The largest effect was seen in people who inject drugs who share injecting equipment, where HCV incidence fell by up to 76% with four annual screens. However, only screening for HIV, HCV and syphilis proved to be cost-saving. Screening for Chlamydia trachomatis and Neisseria gonorrhoeae consistently incurred net costs due to the high screening costs and relatively low treatment costs.
CONCLUSION: Targeted expansion of screening among key populations can reduce the incidence of HIV, HCV and syphilis in Switzerland, with regular screening offering potential cost savings to insurers under specific coverage and treatment scenarios
Co-occurrence of native and invasive malaria vectors in anthropogenic habitats in Metehara, Ethiopia: Opportunities for urban malaria control
Get PDFLocal data are essential to understand the threat posed by invasive Anopheles stephensi and native malaria vectors on urban malaria transmission. This study investigated key bioecological features of invasive and native malaria vectors in Metehara town, Ethiopia. In parallel with a case-control study assessing the impact of An. stephensi on urban malaria transmission, a bioecological assessment was conducted between November 2023 and October 2024. All potential larval breeding habitats were mapped, followed by bimonthly collections of immature and adult mosquitoes from randomly selected locations. Immatures were collected using standard dippers, and adults with CDC light traps, BG Pro traps, and Prokopack aspirators. Adult Anopheles were identified morphologically, while species identification of immatures, adult blood-meal analysis, and sporozoite detection were performed via PCR. Of 767 potential larval breeding habitats, 98.3% (n = 754) were anthropogenic, with the majority (95.2%, n = 730) accessible for oviposition, either fully (73.1%, n = 551) or partially (23.7%, n = 179). More than half were water storage containers for human consumption (37.3%, n = 281) or associated with construction (20.8%, n = 157), while abandoned containers, including discarded tyres, accounted for 22.3% (n = 168). Among anthropogenic habitats positive for Anopheles immatures (55.3%, n = 417), one-third contained both An. stephensi and An. arabiensis. Habitat positivity for An. arabiensis showed significant seasonal variation (likelihood ratio, LR = 46.96, P < 0.01), whereas An. stephensi remained stable (LR = 13.06, P = 0.11). Of 2078 adult catches, An. arabiensis was the most abundant species (63.7%, n = 1323), followed by An. pharoensis (26.4%, n = 549). The human blood index was highest in An. arabiensis (21.8%), compared with An. pharoensis (8.3%) and An. stephensi (1.9%). Sporozoite rate was highest in An. pharoensis (4.2%, 23/548), followed by An. arabiensis (0.4%, 5/1321), while no An. stephensi tested positive (0/173). In conclusion, most breeding habitats were anthropogenic, supporting both native and invasive vectors. Anopheles arabiensis exhibited seasonal variation, whereas An. stephensi remained stable. Integrated vector control targeting anthropogenic larval habitats is recommended. Identification of An. pharoensis from larval pools, given its high sporozoite rate, is critical to guide urban malaria control
Composite endpoints in health technology assessment: Part 1 - an illustration of best modeling practice.
Get PDFComposite endpoints amalgamate multiple clinical outcomes into a single measure, offering efficiency gains in clinical trials through increased event rates and reduced sample sizes, thus accelerating clinical development and regulatory approval. However, employing composite endpoints introduces complexities into health technology assessments (HTAs), particularly in economic modeling, due to the varying clinical significance and cost implications of the components. In this paper, we explore best modeling practice for HTAs that are based on clinical trials that employ composite endpoints. We examine regulatory guidance and discuss statistical solutions for differential component impacts, before presenting a case study based on a recent dapagliflozin submission for reimbursement in heart failure. Our investigation reveals that while composite endpoints can streamline trial analyses and hasten regulatory approval, they also pose a risk of bias in HTA if treatment effects for the components are inappropriately pooled. The paper discusses HTA principles in the context of composite endpoint trials and proposes strategies to develop modeling scenarios and interpret results, especially concerning whether to combine or split out estimates of component treatment effects. A particular focus is the accurate capture of uncertainty, both in terms of the parameter inputs to the model and over the ultimate decision to reimburse. This paper serves as a potential resource for researchers, practitioners and decision-makers, offering insights into best modeling practices that can unlock the full potential of composite endpoints in the pursuit of evidence-based healthcare decision-making
Defining Lifetime Risk Thresholds for Breast Cancer Surgical Prevention.
Get PDFIMPORTANCE: Expanding access to genetic testing and availability of validated breast cancer (BC) risk prediction models are increasingly identifying women at elevated BC risk who do not carry high-penetrance BRCA1/BRCA2/PALB2 pathogenic variants. The precise BC risk threshold for offering risk-reducing mastectomy (RRM) for BC prevention is unknown. OBJECTIVE: To define the lifetime BC risk thresholds for RRM to be cost-effective compared with nonsurgical alternatives for BC prevention. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation used a decision-analytic Markov model to compare the cost-effectiveness of RRM with BC screening and medical prevention in a simulated cohort. Extensive sensitivity analyses were performed. The study setting was from a UK payer perspective over a lifetime horizon until age 80 years. The simulated cohort included women aged 30 to 60 years at varying lifetime BC risks from 17% to 50%. The study was conducted between September 2022 and September 2024. EXPOSURES: Undergoing RRM or receiving risk-stratified BC screening with medical prevention (tamoxifen or anastrozole). MAIN OUTCOMES AND MEASURES: The incremental cost-effectiveness ratio was calculated as incremental cost per quality-adjusted life-year (QALY) gained and compared with the UK willingness-to-pay (WTP) threshold of £20 000 (US 40 555) per QALY. BC cases prevented were estimated at the population level. RESULTS: In the simulated cohort of 100 000 thirty-year-old women in the UK, undergoing RRM became cost-effective at a 34% lifetime BC risk using the £30 000 (US 27 037) per QALY WTP threshold. The identified lifetime BC risk thresholds for RRM to be cost-effective among women aged 35, 40, 45, 50, 55, and 60 years were 31%, 29%, 29%, 32%, 36%, and 42%, respectively, using the £30 000 (US $40 555) per QALY WTP threshold. Overall, undergoing RRM was deemed cost-effective for women aged 30 to 55 years with a lifetime BC risk of at least 35%, with more than 50% of simulations being cost-effective in probabilistic sensitivity analysis. Offering RRM for women with a lifetime BC risk of 35% or higher could potentially prevent approximately 6538 (95% CI, 4454-7041), or approximately 11% (95% CI, 8%-12%), of the 58 756 BC cases occurring annually in women in the UK. In the probabilistic sensitivity analysis, 20.71% to 59.96%, 44.04% to 81.29%, and 97.26% to 99.35% of simulations were cost-effective for women with 35%, 40%, and 50% lifetime BC-risk undergoing RRM at age 30 under the £20 000 to £30 000 per QALY WTP threshold, respectively. CONCLUSIONS AND RELEVANCE: In this economic evaluation, undergoing RRM appears cost-effective for women aged 30 to 55 years with a lifetime BC risk of 35% or higher. These results could have significant clinical implications to expand access to RRM beyond BRCA1/BRCA2/PALB2 pathogenic variant carriers. Future studies evaluating the acceptability, uptake, and long-term outcomes of RRM among these women are warranted
Estimands for Clinical Effectiveness of Risk-Reducing Early Salpingectomy in Women With High Risk of Ovarian Cancer.
Get PDFIMPORTANCE: Risk-reducing early-salpingectomy (RRES) and delayed oophorectomy (DO) is a novel 2-stage alternative prevention strategy to risk-reducing salpingo-oophorectomy (RRSO) that avoids detrimental consequences of premature menopause. However, direct data on the clinical effectiveness for ovarian cancer (OC) risk reduction are lacking.
OBJECTIVE: To explore how to define clinical effectiveness from prospective cohort studies using the estimand framework and sample size requirements. DESIGN,
SETTING, AND PARTICIPANTS: In this comparative effectiveness research study, estimand and analysis options were considered to evaluate the clinical effectiveness of RRES with DO by extending the UK PROTECTOR cohort study, a multicenter, prospective, observational, national cohort study (N = 1250 recruited from January 1, 2019, to December 31, 2024) evaluating RRES and DO for OC surgical prevention. Participants were premenopausal women 30 years or older at increased OC risk due to BRCA1/BRCA2 pathogenic variants. Participants could choose RRES, RRSO, or no surgery at entry. Sample size requirements used initial data (eg, age and BRCA1/2 distribution) from PROTECTOR (analysis undertaken from January 1, 2024, to December 31, 2025).
MAIN OUTCOMES AND MEASURES: Incidence of OC after (not at) RRES and before or at DO in women with normal histologic analysis findings at surgery. The proportion of cancers prevented was estimated as the completement of the observed (O) to expected (E; assuming no preventive effect of surgery) number of cancers detected (1 - O/E).
RESULTS: Initial data were obtained from 889 women in PROTECTOR (overall mean [SD] age, 39 [5] years), with 255 (28.7%) choosing RRSO (mean [SD] age, 42 [4] years), 405 (45.5%) choosing RRES (mean [SD] age, 38 [4] years), and 229 (25.7%) choosing no surgery (mean [SD], 38 [5] years). The preferred estimand outcome was OC incidence after surgery (RRES or RRSO) with a "while on intervention" strategy to account for intercurrent events. The primary target measure was the proportion of cancers prevented for RRES vs no surgery with superiority testing. The secondary target measure was noninferiority of RRES vs RRSO. An estimated 1150 RRES participants with 8 to 10 years of follow-up would provide approximately 92% power to show that 20% or more of cancers are prevented using a 1-sample binomial test of the O:E risk (external reference) at the 5% level under a range of assumptions and at least the same power for a noninferiority margin for the proportion of cancers prevented by RRES of those prevented by RRSO. Estimands based on incidence ratios had an infeasible sample size.
CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of UK BRCA carriers, the estimand differed from other ongoing clinical effectiveness studies of RRES and DO. Advantages include direct use of expected risk at baseline (unknown at design stage), easier interpretation across cohorts than absolute risk differences, and providing a feasible recruitment target for PROTECTOR to evaluate clinical effectiveness
Evaluating the role of community-based multi-disciplinary teams in England's Pioneer integrated health and social care programme: Setting the scene.
Get PDFThis paper introduces an evaluation of community-based, integrated health and social care multi-disciplinary teams (MDTs), primarily serving older people with long-term conditions, undertaken as part of the wider evaluation (2015-2022) of the Integrated Care and Support Pioneer Programme in England (2013-2018). To explain the context within which the MDT evaluation was undertaken, we first outline a brief history of health and social care integration policy in England, describe the Pioneer Programme and the requirements of the national 'longer-term' evaluation of the Pioneers. We then explain our rationale for focusing on MDTs, describe our conceptual framework of MDT functioning and provide a brief description of the evaluation design and methods, highlighting four overarching challenges we faced in undertaking it. We then briefly describe the individual papers that constitute the current supplement