Dapagliflozin versus sacubitril-valsartan for heart failure with mildly reduced or preserved ejection fraction.

Background and aim: Heart failure with preserved ejection fraction (HFpEF) is associated with an increased risk of heart failure (HF) hospitalizations and cardiovascular death (CVD). Both dapagliflozin and sacubitril-valsartan have recently shown convincing reductions in the combined risk of CVD and HF hospitalizations in patients with HF and mildly reduced ejection fraction (HFmrEF) or HFpEF. We aimed to investigate the cost-per-outcome implications of dapagliflozin vs sacubitril-valsartan in the treatment of HFmrEF or HFpEF patients. Methods: We compared the annualized cost needed to treat (CNT) to prevent the composite outcome of total HF hospitalizations and CVD with dapagliflozin or sacubitril-valsartan. The CNT was estimated by multiplying the annualized number needed to treat (aNNT) by the annual cost of therapy. The aNNT was calculated based on data collected from the DELIVER trial for dapagliflozin and a pooled analysis of the PARAGLIDE-HF and PARAGON-HF trials for sacubitril-valsartan. Costs were based on 2022 US prices. Scenario analyses were performed to attenuate the differences in the studies' populations. Results: The aNNT with dapagliflozin in DELIVER was 30 (95% confidence interval [CI]: 21-62) versus 44 (95% CI: 25-311) with sacubitril-valsartan in a pooled analysis of PARAGLIDE-HF and PARAGON-HF, with an annual cost of $4,951 and $5,576, respectively. The corresponding CNTs were $148,547.13 (95% CI: $103,982.99-$306,997.39) for dapagliflozin and $245,346.77 (95% CI: $139,401.58-1,734,155.60) for sacubitril-valsartan for preventing the composite outcome of CVD and HF hospitalizations. The CNT for preventing all-cause mortality was lower for dapagliflozin than sacubitril-valsartan $1,128,958.15 [CI: $401,077.24-∞] vs $2,185,816.71 [CI: $607,790.87-∞]. Conclusion: Dapagliflozin provides a better monetary value than sacubitril-valsartan in preventing the composite outcome of total HF hospitalizations and CVD among patients with HFmrEF or HFpEF.

Risk calculator for incident atrial fibrillation across a range of prediction horizons.

BACKGROUND: The increasing burden of atrial fibrillation (AF) emphasizes the need to identify high-risk individuals for enrolment in clinical trials of AF screening and primary prevention. We aimed to develop prediction models to identify individuals at high-risk of AF across prediction horizons from 6-months to 10-years. METHODS: We used secondary-care linked primary care electronic health record data from individuals aged ≥30 years without known AF in the UK Clinical Practice Research Datalink-GOLD dataset between January 2, 1998 and November 30, 2018; randomly divided into derivation (80%) and validation (20%) datasets. Models were derived using logistic regression from known AF risk factors for incident AF in prediction periods of 6 months, 1-year, 2-years, 5-years, and 10-years. Performance was evaluated using in the validation dataset with bootstrap validation with 200 samples, and compared against the CHA2DS2-VASc and C2HEST scores. RESULTS: Of 2,081,139 individuals in the cohort (1,664,911 in the development dataset, 416,228 in the validation dataset), the mean age was 49.9 (SD 15.4), 50.7% were women, and 86.7% were white. New cases of AF were 7,386 (0.4%) within 6 months, 15,349 (0.7%) in 1 year, 38,487 (1.8%) in 5 years, and 79,997 (3.8%) by 10 years. Valvular heart disease and heart failure were the strongest predictors, and association of hypertension with AF increased at longer prediction horizons. The optimal risk models incorporated age, sex, ethnicity, and 8 comorbidities. The models demonstrated good-to-excellent discrimination and strong calibration across prediction horizons (AUROC, 95%CI, calibration slope: 6-months, 0.803, 0.789-0.821, 0.952; 1-year, 0.807, 0.794-0.819, 0.962; 2-years, 0.815, 0.807-0.823, 0.973; 5-years, 0.807, 0.803-0.812, 1.000; 10-years 0.780, 0.777-0.784, 1.010), and superior to the CHA2DS2-VASc and C2HEST scores. The models are available as a web-based FIND-AF calculator. CONCLUSIONS: The FIND-AF models demonstrate high discrimination and calibration across short- and long-term prediction horizons in 2 million individuals. Their utility to inform trial enrolment and clinical decisions for AF screening and primary prevention requires further study.

Risk of atrial fibrillation and association with other diseases: protocol of the derivation and international external validation of a prediction model using nationwide population-based electronic health records.

INTRODUCTION: Atrial fibrillation (AF) is a major public health issue and there is rationale for the early diagnosis of AF before the first complication occurs. Previous AF screening research is limited by low yields of new cases and strokes prevented in the screened populations. For AF screening to be clinically and cost-effective, the efficiency of identification of newly diagnosed AF needs to be improved and the intervention offered may have to extend beyond oral anticoagulation for stroke prophylaxis. Previous prediction models for incident AF have been limited by their data sources and methodologies. METHODS AND ANALYSIS: We will investigate the application of random forest and multivariable logistic regression to predict incident AF within a 6-month prediction horizon, that is, a time-window consistent with conducting investigation for AF. The Clinical Practice Research Datalink (CPRD)-GOLD dataset will be used for derivation, and the Clalit Health Services (CHS) dataset will be used for international external geographical validation. Analyses will include metrics of prediction performance and clinical utility. We will create Kaplan-Meier plots for individuals identified as higher and lower predicted risk of AF and derive the cumulative incidence rate for non-AF cardio-renal-metabolic diseases and death over the longer term to establish how predicted AF risk is associated with a range of new non-AF disease states. ETHICS AND DISSEMINATION: Permission for CPRD-GOLD was obtained from CPRD (ref no: 19_076). The CPRD ethical approval committee approved the study. CHS Helsinki committee approval 21-0169 and data usage committee approval 901. The results will be submitted as a research paper for publication to a peer-reviewed journal and presented at peer-reviewed conferences. TRIAL REGISTRATION NUMBER: A systematic review to guide the overall project was registered on PROSPERO (registration number CRD42021245093). The study was registered on ClinicalTrials.gov (NCT05837364).

Dapagliflozin versus empagliflozin in patients with chronic kidney disease.

Background and Aim: Dapagliflozin and empagliflozin have demonstrated favorable clinical outcomes among patients with chronic kidney disease (CKD). However, their comparative monetary value for improving outcomes in CKD patients is unestablished. We examined the cost-per-outcome implications of utilizing dapagliflozin as compared to empagliflozin for prevention of renal and cardiovascular events in CKD patients. Methods: For calculation of preventable events we divided the allocated budget by the cost needed to treat (CNT) for preventing a single renal or cardiovascular event. CNT was derived by multiplying the annualized number needed to treat (aNNT) by the annual therapy cost. The aNNTs were determined based on data from the DAPA-CKD and EMPEROR-KIDNEY trials. The budget limit was defined based on the threshold recommended by the United States' Institute for Clinical and Economic Review. Results: The aNNT was 42 both dapagliflozin (95% confidence interval [CI]: 34-59) and empagliflozin (CI: 33-66). The CNT estimates for the prevention of one primary event for dapagliflozin and empagliflozin were comparable at $201,911 (CI: $163,452-$283,636) and $209,664 (CI: $164,736-$329,472), respectively. However, diabetic patients had a higher CNT with dapagliflozin ($201,911 [CI: $153,837-$346,133]) than empagliflozin ($134,784 [CI: $109,824-$214,656]), whereas non-diabetic patients had lower CNT for dapagliflozin ($197,103 [CI: $149,029-$346,133]) than empagliflozin ($394,368 [CI: $219,648-$7,093,632]). The CNT for preventing CKD progression was higher for dapagliflozin ($427,858 [CI: $307,673-$855,717]) than empagliflozin ($224,640 [CI: $169,728-$344,448]). For preventing cardiovascular death (CVD), the CNT was lower for dapagliflozin ($1,634,515 [CI: $740,339-∞]) than empagliflozin ($2,990,208 [CI: $1,193,088-∞]). Conclusion: Among patients with CKD, empagliflozin provides a better monetary value for preventing the composite renal and cardiovascular events in diabetic patients while dapagliflozin has a better value for non-diabetic patients. Dapagliflozin provides a better monetary value for the prevention of CVD, whereas empagliflozin has a better value for the prevention of CKD progression.

Incident cardiovascular, renal, metabolic diseases and death in individuals identified for risk-guided atrial fibrillation screening: a nationwide cohort study.

OBJECTIVE: Risk-guided atrial fibrillation (AF) screening may be an opportunity to prevent adverse events in addition to stroke. We compared events rates for new diagnoses of cardio-renal-metabolic diseases and death in individuals identified at higher versus lower-predicted AF risk. METHODS: From the UK Clinical Practice Research Datalink-GOLD dataset, 2 January 1998-30 November 2018, we identified individuals aged ≥30 years without known AF. The risk of AF was estimated using the FIND-AF (Future Innovations in Novel Detection of Atrial Fibrillation) risk score. We calculated cumulative incidence rates and fit Fine and Gray's models at 1, 5 and 10 years for nine diseases and death adjusting for competing risks. RESULTS: Of 416 228 individuals in the cohort, 82 942 were identified as higher risk for AF. Higher-predicted risk, compared with lower-predicted risk, was associated with incident chronic kidney disease (cumulative incidence per 1000 persons at 10 years 245.2; HR 6.85, 95% CI 6.70 to 7.00; median time to event 5.44 years), heart failure (124.7; 12.54, 12.08 to 13.01; 4.06), diabetes mellitus (123.3; 2.05, 2.00 to 2.10; 3.45), stroke/transient ischaemic attack (118.9; 8.07, 7.80 to 8.34; 4.27), myocardial infarction (69.6; 5.02, 4.82 to 5.22; 4.32), peripheral vascular disease (44.6; 6.62, 6.28 to 6.98; 4.28), valvular heart disease (37.8; 6.49, 6.14 to 6.85; 4.54), aortic stenosis (18.7; 9.98, 9.16 to 10.87; 4.41) and death from any cause (273.9; 10.45, 10.23 to 10.68; 4.75). The higher-risk group constituted 74% of deaths from cardiovascular or cerebrovascular causes (8582 of 11 676). CONCLUSIONS: Individuals identified for risk-guided AF screening are at risk of new diseases across the cardio-renal-metabolic spectrum and death, and may benefit from interventions beyond ECG monitoring.

Prediction models for heart failure in the community: A systematic review and meta-analysis.

AIMS: Multivariable prediction models can be used to estimate risk of incident heart failure (HF) in the general population. A systematic review and meta-analysis was performed to determine the performance of models. METHODS AND RESULTS: From inception to 3 November 2022 MEDLINE and EMBASE databases were searched for studies of multivariable models derived, validated and/or augmented for HF prediction in community-based cohorts. Discrimination measures for models with c-statistic data from ≥3 cohorts were pooled by Bayesian meta-analysis, with heterogeneity assessed through a 95% prediction interval (PI). Risk of bias was assessed using PROBAST. We included 36 studies with 59 prediction models. In meta-analysis, the Atherosclerosis Risk in Communities (ARIC) risk score (summary c-statistic 0.802, 95% confidence interval [CI] 0.707-0.883), GRaph-based Attention Model (GRAM; 0.791, 95% CI 0.677-0.885), Pooled Cohort equations to Prevent Heart Failure (PCP-HF) white men model (0.820, 95% CI 0.792-0.843), PCP-HF white women model (0.852, 95% CI 0.804-0.895), and REverse Time AttentIoN model (RETAIN; 0.839, 95% CI 0.748-0.916) had a statistically significant 95% PI and excellent discrimination performance. The ARIC risk score and PCP-HF models had significant summary discrimination among cohorts with a uniform prediction window. 77% of model results were at high risk of bias, certainty of evidence was low, and no model had a clinical impact study. CONCLUSIONS: Prediction models for estimating risk of incident HF in the community demonstrate excellent discrimination performance. Their usefulness remains uncertain due to high risk of bias, low certainty of evidence, and absence of clinical effectiveness research.

Safety of monovalent and bivalent BNT162b2 mRNA COVID-19 vaccine boosters in at-risk populations in Israel: a large-scale, retrospective, self-controlled case series study.

BACKGROUND: COVID-19 continues to be a major health threat, particularly among at-risk groups, including individuals aged 60 years or older and people with particular medical conditions. Nevertheless, the absence of sufficient vaccine safety information is one of the key contributors to vaccine refusal. We aimed to assess the short-term safety profile of the BNT162b2 mRNA COVID-19 vaccine booster doses. METHODS: In this self-controlled case series study, we used a database of members of the largest health-care organisation in Israel. We analysed the medical records of individuals at risk of COVID-19 complications who had received two doses of the monovalent BNT162b2 mRNA COVID-19 vaccine (tozinameran, Pfizer-BioNTech) as their primary course of vaccination and then also received BNT162b2 mRNA COVID-19 vaccine boosters between July 30, 2021, and Nov 28, 2022, as a monovalent first or second booster, or as a bivalent first, second, or third booster, or a combination of these. We included individuals who had active membership of the health-care organisation and who were alive (excluding COVID-19 deaths) throughout the entire study period. We excluded individuals who, during the study period, were either not active Clalit Health Services members or died of non-COVID-19 causes, and those who were infected with COVID-19 during the 7-day period after vaccination. Individuals' at-risk status was assessed on the day before the baseline period started. The primary outcome was non-COVID-19 hospitalisation for 29 adverse events that might be associated with vaccination. For each adverse event, we compared the risk difference of hospitalisation during a 28-day pre-vaccination baseline period versus during a 28-day post-vaccination period, using a non-parametric percentile bootstrap method. FINDINGS: Of the 3 574 243 members of the health-care organisation, 1 073 110 received a first monovalent booster, 394 251 received a second monovalent booster, and 123 084 received a bivalent first, second, or third booster. Overall, we found no indication of an elevated risk of non-COVID-19 hospitalisation following administration of any of the booster vaccines (risk difference in events per 100 000 individuals: first monovalent booster -37·1 [95% CI -49·8 to -24·2]; second monovalent booster -37·8 [-62·2 to -13·2]; and bivalent booster -18·7 [-53·6 to 15·4]). Except for extremely rare elevated risks after the first monovalent booster-of myocarditis (risk difference 0·7 events per 100 000 individuals [95% CI 0·3-1·3]), seizures (2·2 [0·4-4·1]), and thrombocytopenia (2·6 [0·7-4·7])-we found no safety signals in other adverse events, including ischaemic stroke. INTERPRETATION: This study provides the necessary vaccine safety assurances for at-risk populations to receive timed roll-out booster vaccinations. These assurances could reduce vaccine hesitancy and increase the number of at-risk individuals who opt to become vaccinated, and thereby prevent the severe outcomes associated with COVID-19. FUNDING: Israel Science Foundation and Israel Precision Medicine Partnership programme.

Examining the Patterns of Mpox Vaccine Uptake in a Vulnerable Population.

BACKGROUND: The current Mpox outbreak presents unique vaccination challenges in vulnerable populations. Understanding factors associated with vaccine uptake in vulnerable populations is required for a successful vaccination campaign. METHODS: This population-based cohort study was conducted in Clalit Health Services and included all individuals eligible for the Modified Vaccinia Ankara vaccine. Cox proportional hazards models were used to assess the characteristics associated with uptake of the first vaccine dose. RESULTS: Attendance to a primary healthcare clinic in the Tel Aviv district, repeated sexually transmitted infection screening, and the recent purchase of HIV-PrEP or PDE5 inhibitors were associated with higher vaccine adherence, whereas previous nonadherence with recommended vaccines, low sociodemographic status, and history of HIV were associated with lower adherence. CONCLUSIONS: These findings highlight the need for proactive patient and healthcare provider-oriented educational campaigns to curb vaccine hesitancy, and may help direct resources toward underserved populations, hence increasing equality in vaccine enrollment.

Liraglutide versus semaglutide for weight reduction-a cost needed to treat analysis.

OBJECTIVE: Higher doses of the glucagon-like peptide-1 agonists liraglutide and, more recently, semaglutide have demonstrated a significant reduction in body weight. However, their comparative value for money for this indication is unclear. METHODS: The cost needed to treat to achieve a 1% reduction in body weight using semaglutide or liraglutide was calculated. The body weight reductions were extracted from the published STEP 1 trial and the SCALE trial results, respectively. A scenario analysis was performed to mitigate the primary differences between the two studies' populations. Drug costs were based on US GoodRx prices as of October 2022. RESULTS: Liraglutide in STEP 1 resulted in a weight loss of 5.4% (95% CI: 5%-5.8%). Semaglutide in SCALE resulted in a weight loss of 12.4% (95% CI: 11.5%-13.4%). The total cost of therapy with liraglutide during the trial was estimated at $17,585 compared with $22,878 with semaglutide. Accordingly, the cost needed to treat per 1% of body weight reduction with liraglutide is estimated at $3256 (95% CI: $3032-$3517) compared with $1845 (95% CI: $1707-$1989) with semaglutide. CONCLUSIONS: Semaglutide provides significantly better value for money than liraglutide for weight reduction.

Risk assessment of human mpox infections: retrospective cohort study.

OBJECTIVES: The global supply of vaccines against mpox (previously called monkeypox virus infection) was significantly lower than the demand. Therefore, evidence-based vaccine prioritization criteria, based on risk assessment were needed. Our objective was therefore to identify the characteristics of individuals at the highest risk for mpox. METHODS: This population-based cohort study included all Clalit Health Services (CHS) subjects assumed to be at risk for mpox. The eligibility criteria for inclusion were determined based on known characteristics of people with infection worldwide and insights of lesbian, gay, bisexual, transgender, queer+ (LGBTQ+) -specialized CHS clinicians. Cox hazards models were used to identify the risk factors for mpox within the study cohort. The study commenced on 6 June 2022, the date of the first known mpox in CHS members, until 31 July 2022, when the mpox vaccination campaign started. RESULTS: A total of 8088 individuals of 4.7 million CHS members (0.18%) were identified according to the study inclusion criteria. Of those, 69 (0.85%) developed infection during the study period. Risk factors for mpox were birth in 1980 or later (hazard ratio, 5.04; 95% CI, 2.11-12.02), history of syphilis (2.62; 1.58-4.35), registration to primary healthcare clinics in the Tel Aviv district (2.82; 1.44-5.54), HIV-pre-exposure prophylaxis medication use (3.96; 2.14-7.31), PDE5 inhibitors use (2.92; 1.77-4.84), and recent sexually transmitted infections (STIs) within the last 18 months (2.27; 1.35-3.82). No infections were observed in individuals with none of the factors. Individuals with three or more risk factors had a 20.30-fold (10.39-39.69) higher risk for mpox compared with those with 0-2, with 85.5% (75.0-92.8%) sensitivity and 77.8% (76.9-78.7%) specificity. DISCUSSION: Weighting individuals' risk levels based on validated risk factors against vaccine availability can assist health systems in the equitable prioritization of vaccine allocation in various future outbreaks, given supply-demand gaps.

Effect of Dapagliflozin Versus Empagliflozin on Cardiovascular Death in Patients with Heart Failure Across the Spectrum of Ejection Fraction: Cost per Outcome Analysis.

BACKGROUND: Dapagliflozin and empagliflozin have shown clinical benefits in patients with heart failure (HF). Their comparative monetary value remains undetermined, and we therefore sought to compare the cost-per-outcome implications of utilizing dapagliflozin versus empagliflozin to prevent cardiovascular death (CVD) in patients with HF across the spectrum of ejection fraction. METHODS: We estimated the cost needed to treat (CNT) to prevent one CVD with either dapagliflozin or empagliflozin. CNT was estimated by multiplying the annualized number needed to treat (aNNT) by the annual cost of therapy. The aNNTs were calculated based on data from the DAPA-HF and DELIVER trials for dapagliflozin, and the EMPEROR-Reduced and EMPEROR-Preserved trials for empagliflozin. Drug costs were calculated as 75% of the 2022 US National Average Drug Acquisition Cost. RESULTS: The aNNT to prevent one event of CVD was 110 (95% confidence interval [CI] 58-∞) for dapagliflozin in a pooled analysis of DAPA-HF and DELIVER versus 204 (95% CI 71-∞) for empagliflozin in a pooled analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials. The annual costs of therapy were $4807 and $4992, respectively. The corresponding CNTs were $528,770 (95% CI $278,806-∞) for dapagliflozin and $1,018,368 (95% CI $354,432-∞) for empagliflozin. This remained consistent in Europe, using the price estimates in Germany, with CNT (€77,490 for dapagliflozin and €143,708 for empagliflozin). CONCLUSION: In incorporating data from all four outcomes trials of sodium-glucose cotransporter 2 inhibitors, dapagliflozin provides better monetary value for preventing CVD events in patients with HF across the spectrum of ejection fraction.

Effectiveness of a bivalent mRNA vaccine booster dose to prevent severe COVID-19 outcomes: a retrospective cohort study.

BACKGROUND: In late 2022, the SARS-CoV-2 omicron (B.1.1.529) BA.5 sublineage accounted for most of the sequenced viral genomes worldwide. Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the omicron BA.4 and BA.5 sublineages. Since September, 2022, a single bivalent mRNA vaccine booster dose has been recommended for adults who have completed a primary SARS-CoV-2 vaccination series and are at high risk of severe COVID-19. We aimed to evaluate the effectiveness of a bivalent mRNA vaccine booster dose to reduce hospitalisations and deaths due to COVID-19. METHODS: We did a retrospective, population-based, cohort study in Israel, using data from electronic medical records in Clalit Health Services (CHS). We included all members of CHS who were aged 65 years or older and eligible for a bivalent mRNA COVID-19 booster vaccination. We used hospital records to identify COVID-19-related hospitalisations and deaths. The primary endpoint was hospitalisation due to COVID-19, which we compared between participants who received a bivalent mRNA booster vaccination and those who did not. A Cox proportional hazards regression model with time-dependent covariates was used to estimate the association between the bivalent vaccine and hospitalisation due to COVID-19 while adjusting for demographic factors and coexisting illnesses. FINDINGS: Between Sept 27, 2022, and Jan 25, 2023, 569 519 eligible participants were identified. Of those, 134 215 (24%) participants received a bivalent mRNA booster vaccination during the study period. Hospitalisation due to COVID-19 occurred in 32 participants who received a bivalent mRNA booster vaccination and 541 who did not receive a bivalent booster vaccination (adjusted hazard ratio 0·28, 95% CI 0·19-0·40). The absolute risk reduction for hospitalisations due to COVID-19 in bivalent mRNA booster recipients versus non-recipients was 0·089% (95% CI 0·075-0·101), and the number needed to vaccinate to prevent one hospitalisation due to COVID-19 was 1118 people (95% CI 993-1341). INTERPRETATION: Participants who received a bivalent mRNA booster vaccine dose had lower rates of hospitalisation due to COVID-19 than participants who did not receive a bivalent booster vaccination, for up to 120 days after vaccination. These findings highlight the importance of bivalent mRNA booster vaccination in populations at high risk of severe COVID-19. Further studies with longer observation times are warranted. FUNDING: None.

Prediction of short-term atrial fibrillation risk using primary care electronic health records.

OBJECTIVE: Atrial fibrillation (AF) screening by age achieves a low yield and misses younger individuals. We aimed to develop an algorithm in nationwide routinely collected primary care data to predict the risk of incident AF within 6 months (Future Innovations in Novel Detection of Atrial Fibrillation (FIND-AF)). METHODS: We used primary care electronic health record data from individuals aged ≥30 years without known AF in the UK Clinical Practice Research Datalink-GOLD dataset between 2 January 1998 and 30 November 2018, randomly divided into training (80%) and testing (20%) datasets. We trained a random forest classifier using age, sex, ethnicity and comorbidities. Prediction performance was evaluated in the testing dataset with internal bootstrap validation with 200 samples, and compared against the CHA2DS2-VASc (Congestive heart failure, Hypertension, Age >75 (2 points), Stroke/transient ischaemic attack/thromboembolism (2 points), Vascular disease, Age 65-74, Sex category) and C2HEST (Coronary artery disease/Chronic obstructive pulmonary disease (1 point each), Hypertension, Elderly (age ≥75, 2 points), Systolic heart failure, Thyroid disease (hyperthyroidism)) scores. Cox proportional hazard models with competing risk of death were fit for incident longer-term AF between higher and lower FIND-AF-predicted risk. RESULTS: Of 2 081 139 individuals in the cohort, 7386 developed AF within 6 months. FIND-AF could be applied to all records. In the testing dataset (n=416 228), discrimination performance was strongest for FIND-AF (area under the receiver operating characteristic curve 0.824, 95% CI 0.814 to 0.834) compared with CHA2DS2-VASc (0.784, 0.773 to 0.794) and C2HEST (0.757, 0.744 to 0.770), and robust by sex and ethnic group. The higher predicted risk cohort, compared with lower predicted risk, had a 20-fold higher 6-month incidence rate for AF and higher long-term hazard for AF (HR 8.75, 95% CI 8.44 to 9.06). CONCLUSIONS: FIND-AF, a machine learning algorithm applicable at scale in routinely collected primary care data, identifies people at higher risk of short-term AF.

Real-world effectiveness of a single dose of mpox vaccine in males.

The recent global outbreak of the monkeypox (mpox) virus in humans was declared a public health emergency by the World Health Organization in July 2022. The smallpox and mpox vaccine (JYNNEOS; Modified Vaccinia Ankara-Bavarian Nordic; MVA-BN), provided as a two-dose regimen, is currently the primary vaccine utilized against mpox. However, the efficacy of MVA-BN against mpox has never been demonstrated in clinical trials to date. Due to the limited supply of vaccines, the World Health Organization has recommended prioritizing the vaccination of high-risk groups. We evaluated the real-world effectiveness of a single, subcutaneous dose of MVA-BN in this observational, retrospective cohort study, which included the analysis of electronic health records of all members of Clalit Health Services eligible for the vaccine on 31 July 2022. We used a Cox proportional hazards regression model with time-dependent covariates to estimate the association between vaccination and mpox while adjusting for sociodemographic and clinical risk factors. In an analysis of 2,054 male individuals who met vaccine eligibility criteria, 1,037 (50%) were vaccinated during the study recruitment period and completed at least 90 d of follow-up. During the study period, 5 and 16 infections were confirmed in vaccinated and unvaccinated individuals, respectively. The adjusted vaccine effectiveness was estimated at 86% (95% confidence interval, 59-95%). Our results suggest that a single dose of subcutaneous MVA-BN in this high-risk cohort is associated with a significantly lower risk of MPXV infection.

Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis.

AIMS: Higher doses of the glucagon-like peptide-1 agonist semaglutide and, more recently, tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 agonist showed a significant reduction in body weight in patients with type 2 diabetes mellitus. However, their comparative value for money for this indication is unclear. Therefore, we aimed to establish which provides better value for money. MATERIALS AND METHODS: We calculated the cost needed to treat to achieve a 1% reduction in body weight using high-dose tirzepatide (15 mg) versus semaglutide (2.4 mg). The body weight reductions were extracted from published results of SURMOUNT-1 and STEP 1 trials, respectively. In addition, we performed a scenario analysis to mitigate the primary differences between the two study populations. Drug costs were based on US GoodRx prices as of October 2022. RESULTS: Using tirzepatide resulted in a weight loss of 17.8% (95% CI: 16.3%-19.3%) compared with 12.4% (95% CI: 11.5%-13.4%) for semaglutide. The total cost of 72 weeks of tirzepatide was estimated at $17 527 compared with $22 878 for 68 weeks of semaglutide. Accordingly, the cost needed to treat per 1% of body weight reduction with tirzepatide is estimated at $985 (95% CI: $908-$1075) compared with $1845 (95% CI: $1707-$1989) with semaglutide. Scenario analysis confirmed these findings. CONCLUSIONS: Tirzepatide provides better value for money than semaglutide for weight reduction.