[IMPACT OF CLINICAL PHARMACIST CONSULTATIONS ON RATE OF COMPLICATIONS, RE-HOSPITALIZATIONS AND MORTALITY IN PATIENTS UNDERGOING BARIATRIC SURGERY].

BACKGROUND: Patients undergoing bariatric surgery are prone to changes in absorption, improvement in their chronic diseases and other pharmacokinetic/pharmacodynamic alteration which can affect continuation and the required doses of their chronic medications. OBJECTIVES: To examine the effect of a clinical pharmacist's consultation on the rate of complications, re-hospitalizations and mortality among patients who underwent bariatric surgery. METHODS: In this retrospective cohort study, results of bariatric patients who were consulted by a clinical pharmacist between the years 2013-2019 were compared with the results of a wider group of bariatric patients with chronic diseases who were recorded in the Israeli General Bariatric Registry during the same years. The intervention cohort included bariatric patients members of Clalit Health Services, who were treated at the Herzliya Medical Center and who were identified by the treating staff as complex cases requiring drug counseling. The primary outcomes measured in the study included: rates of surgical complications, re-hospitalizations, and death up to one year after surgery. RESULTS: The intervention group included 165 patients; the 12 month rate of re-hospitalization in the intervention group was 10.9% vs. 19.5% in the comparison group (p=0.005). The rate of documented postoperative complications was 2.7% vs. 3.9% (p=0.462) and mortality was null vs. 0.16%. CONCLUSIONS: Although the intervention population was identified in advance as more complex in terms of age and background morbidity, the rate of re-hospitalization and mortality was significantly lower in the intervention group than in the general bariatric surgery population in Israel. These results demonstrate the importance of referring to a specialized clinical pharmacist around bariatric surgery for improving patient safety, especially in complex patients.

Can Consultation by a Clinical Pharmacist Prevent Morbidity and Mortality in Patients Undergoing Bariatric Surgery?

The purpose of this work was to investigate the effect of clinical pharmacist consultation on the long-term morbidity and mortality outcomes among patients undergoing bariatric surgery. In this retrospective cohort study, 165 bariatric patients at Herzliya Medical Center who were identified as complex cases and were consulted by a clinical pharmacist (2013-2019) were compared with a wider group of bariatric patients with chronic diseases who were recorded in the Israeli General Bariatric Registry during the same years. The primary outcomes were rates of surgical complications, re-hospitalizations, and death up to one year after surgery. The secondary outcome was the rate of re-hospitalizations in different time periods. The twelve (12)-month rate of re-hospitalization in the intervention group was 10.9% vs. 19.5% in the comparison group (p = 0.005); the rate of documented postoperative complications was 2.7% vs. 3.9% (p = 0.462), and mortality was null vs. 0.16%, respectively. As for the secondary outcomes, the rates of re-hospitalizations in the periods of 0-30, 31-90, 91-180, and 181-365 days after surgery were 1.8% vs. 5.3% (p = 0.046), 2.4% vs. 4.1% (p = 0.278), 3.6% vs. 4.8% (p = 0.476), and 7.3% vs. 9.9% (p = 0.256) in the intervention vs. comparison cohorts, respectively. In conclusion, this study demonstrates the importance and benefit of referring to a specialized clinical pharmacist around bariatric surgery for improving patient safety, especially in complex patients. This is the first study to look at the long-term effects of clinical pharmacist consultation on re-hospitalization and mortality among bariatric patients, and our encouraging outcomes should hopefully stimulate more studies to show the invaluable role of specialized clinical pharmacists.

Publicly Funded Cancer Care: Are Adjuvant Therapies Prioritized Over Treatment of Metastatic Cancer? The Israeli Experience.

PURPOSE: In Israel, a public committee advises which new medications should be reimbursed subject to an annual budget allocation. The committee considers clinical trial outcomes, professional societies' preferences, projected budget impacts, and other social and ethical aspects. The Israeli oncologists' society places a strong emphasis on prioritizing adjuvant therapies because of their potential to advance cure. In 2023, several novel adjuvant therapies were suggested for national funding. Our objective was to ascertain whether Israeli decision makers have embraced the practice of prioritizing budgets for therapies with curative intent over late-disease therapy. METHODS: We collected data on all proposed cancer therapies for the 2023 update: indications, treatment settings, European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) score, and whether accepted for reimbursement. The rates of acceptance were compared between drugs in curative and noncurative settings. Data were extracted from the official Israeli Ministry of Health publications and ESMO-MCBS website. RESULTS: Seven of the eight proposed therapies with curative intent received reimbursement approval (88%), in contrast to 11 of the 55 therapies for advanced/metastatic stages (20%). Among all advanced disease therapies with a high ESMO-MCBS score of 4, only four of 16 (25%) secured reimbursement approval. CONCLUSION: Our analysis revealed that during the 2023 reimbursement deliberations, Israeli policymakers embraced the prioritization of potentially curative therapies over treatments for incurable cancers, including several interventions that have demonstrated significant improvements in overall survival and/or quality of life. Introducing objective cost-effectiveness measures as a guiding framework for comparing competing medications may offer some resolution to this complex challenge.

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.

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.

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.

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.

Arterial and Venous Thromboembolism in ALK-Rearrangement-Positive Non-small Cell Lung Cancer: A Population-Based Cohort Study.

INTRODUCTION: There is scarce data regarding the incidence of venous thromboembolism (VTE) and arterial thromboembolism (ATE) in the molecular subtypes of non-small cell lung cancer (NSCLC). We aimed to investigate the association between Anaplastic Lymphoma Kinase (ALK)-positive NSCLC and thromboembolic events. METHODS: A retrospective population-based cohort study of the Clalit Health Services database, included patients with NSCLC diagnosed between 2012 and 2019. Patients exposed to ALK-tyrosine-kinase inhibitors (TKIs) were defined as ALK-positive. The outcome was VTE (at any site) or ATE (stroke or myocardial infarction) 6 months prior to the diagnosis of cancer, until 5 years post-diagnosis. The cumulative incidence of VTE and ATE and hazard-ratios (HR) with 95% CIs were calculated (at 6- 12- 24 and 60-months), using death as a competing risk. Cox proportional hazards multivariate regression was performed, with the Fine and Gray correction for competing risks. RESULTS: The study included 4762 patients, of which 155 (3.2%) were ALK-positive. The overall 5-year VTE incidence was 15.7% (95% CI, 14.7-16.6%). ALK-positive patients had a higher VTE risk compared to ALK-negative patients (HR 1.87 [95% CI, 1.31-2.68]) and a 12-month VTE incidence of 17.7% (13.9-22.7%) compared to 9.9% (9.1-10.9%) in ALK-negative patients. The overall 5-year ATE incidence was 7.6% [6.8-8.6%]. ALK positivity was not associated with ATE incidence (HR 1.24 [0.62-2.47]). CONCLUSIONS: In this study, we observed a higher VTE risk, but not ATE risk, in patients with ALK-rearranged NSCLC relative to those without ALK rearrangement. Prospective studies are warranted to evaluate thromboprophylaxis in ALK-positive NSCLC.

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.

Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge.

BACKGROUND: The oral protease inhibitor nirmatrelvir has shown substantial efficacy in high-risk, unvaccinated patients infected with the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data regarding the effectiveness of nirmatrelvir in preventing severe coronavirus disease 2019 (Covid-19) outcomes from the B.1.1.529 (omicron) variant are limited. METHODS: We obtained data for all members of Clalit Health Services who were 40 years of age or older at the start of the study period and were assessed as being eligible to receive nirmatrelvir therapy during the omicron surge. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association of nirmatrelvir treatment with hospitalization and death due to Covid-19, with adjustment for sociodemographic factors, coexisting conditions, and previous SARS-CoV-2 immunity status. RESULTS: A total of 109,254 patients met the eligibility criteria, of whom 3902 (4%) received nirmatrelvir during the study period. Among patients 65 years of age or older, the rate of hospitalization due to Covid-19 was 14.7 cases per 100,000 person-days among treated patients as compared with 58.9 cases per 100,000 person-days among untreated patients (adjusted hazard ratio, 0.27; 95% confidence interval [CI], 0.15 to 0.49). The adjusted hazard ratio for death due to Covid-19 was 0.21 (95% CI, 0.05 to 0.82). Among patients 40 to 64 years of age, the rate of hospitalization due to Covid-19 was 15.2 cases per 100,000 person-days among treated patients and 15.8 cases per 100,000 person-days among untreated patients (adjusted hazard ratio, 0.74; 95% CI, 0.35 to 1.58). The adjusted hazard ratio for death due to Covid-19 was 1.32 (95% CI, 0.16 to 10.75). CONCLUSIONS: Among patients 65 years of age or older, the rates of hospitalization and death due to Covid-19 were significantly lower among those who received nirmatrelvir than among those who did not. No evidence of benefit was found in younger adults.

Aspirin with Low-Dose Ticagrelor or with Low-Dose Rivaroxaban for Secondary Prevention: A Cost per Outcome Analysis.

INTRODUCTION: Secondary prevention of cardiovascular events among patients with diagnosed cardiovascular disease and high ischemic risk poses a significant challenge in clinical practice. The combinations of aspirin with low-dose (LD) ticagrelor or LD rivaroxaban have shown superiority in preventing major adverse cardiovascular events (MACE) compared with aspirin treatment alone. The comparative value for money of these two regimens remains unexplored. METHODS: We analyzed each regimen's annual cost needed to treat (CNT) by multiplying the annualized number needed to treat (aNNT) by the annual cost of each drug. The aNNTs were based on outcome data from PEGASUS TIMI-54 and COMPASS trials. Scenario analyses were performed to overcome variances in terms of population risk. Costs were calculated as 75% of US National Average Drug Acquisition Cost (NADAC), extracted in January 2022. The primary outcome was defined as CNT to prevent one MACE across the two regimens. Secondary value analysis was performed for myocardial infarction (MI), stroke, and cardiovascular death as separate outcomes. RESULTS: The aNNTs to prevent MACE with LD ticagrelor and with LD rivaroxaban were 229 [95% confidence interval (CI) 141-734] and 147 (95% CI 104-252), respectively. At an annual cost of US$3726 versus US$4533, the corresponding CNTs were US$853,254 (95% CI 525,366-2,734,884) with LD ticagrelor and US$666,351 (95% CI 471,432-1,142,316) with LD rivaroxaban. CONCLUSION: Combining aspirin with LD rivaroxaban provides better value for money than with LD ticagrelor for secondary prevention of MACE.

Oral versus subcutaneous semaglutide for prevention of major adverse cardiovascular events: cost per outcome analysis of SUSTAIN-6 and PIONEER-6.

BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP1a), reduces the risk of major adverse cardiovascular events (MACE) in patients with Type 2 diabetes mellitus (T2DM). An oral version of semaglutide is now available, and patients may prefer it over the subcutaneous form. Our objective was to compare the value for money of the two modalities by assessing the cost needed to treat (CNT) to prevent MACE. METHODS: The CNT to prevent MACE was figured by multiplying the one-year number needed to treat (NNT) with either oral or subcutaneous semaglutide by the annual cost of therapy. Efficacy estimates and the resulting NNT figures were extracted from the published results of the SUSTAIN-6 and the PIONEER-6 trials for the injectable and oral versions of semaglutide, respectively. Drug costs were estimated as 75% of the United States national average drug acquisition cost listing in June 2021. We performed a scenario analysis to mitigate the primary differences between the populations in the two trials. Sensitivity analysis was performed to evaluate the effect of price changes of the interventions. RESULTS: The CNT to prevent one MACE with subcutaneous semaglutide in SUSTAIN-6 was $966,693 ($594,888-$5,035,302) compared to $948,689 ($463,465-∞) with oral semaglutide in PIONEER-6. The scenario analysis demonstrated a 17% lower CNT for oral semaglutide. The difference between CNTs was sensitive to price fluctuations of the two interventions. CONCLUSIONS: Oral and subcutaneous semaglutide prescribed to prevent MACE in patients with T2DM provide similar value for money. The choice between both therapies should be guided mainly by patient preferences.

Effectiveness of a second BNT162b2 booster vaccine against hospitalization and death from COVID-19 in adults aged over 60 years.

The rapid emergence of the B.1.1.529 (Omicron) variant of SARS-CoV-2 led to a global resurgence of coronavirus disease 2019 (COVID-19). Israeli authorities approved a fourth COVID-19 vaccine dose (second booster) for individuals aged 60 years and over who had received a first booster dose 4 or more months earlier. Evidence for the effectiveness of a second booster dose in reducing hospitalizations and mortality due to COVID-19 is warranted. This retrospective cohort study included all members of Clalit Health Services who were aged 60-100 years and who were eligible for the second booster on 3 January 2022. Hospitalizations and mortality due to COVID-19 in participants who received the second booster were compared with those for participants who received one booster dose. Cox proportional hazards regression models with time-dependent covariates were used to estimate the association between the second booster and hospitalization and death due to COVID-19 while adjusting for demographic factors and coexisting illnesses. A total of 563,465 participants met the eligibility criteria. Of those, 328,597 (58%) received a second booster dose during the 40 day study period. Hospitalization due to COVID-19 occurred in 270 of the second-booster recipients and in 550 participants who received one booster dose (adjusted hazard ratio, 0.36; 95% confidence interval (CI): 0.31-0.43). Death due to COVID-19 occurred in 92 second-booster recipients and in 232 participants who received one booster dose (adjusted hazard ratio, 0.22; 95% CI: 0.17-0.28). This study demonstrates a substantial reduction in hospitalizations and deaths due to COVID-19 conferred by a second booster in Israeli adults aged 60 years and over.

Rate of breast biopsy referrals in female BRCA mutation carriers aged 50 years or more: a retrospective comparative study and matched analysis.

PURPOSE: To evaluate the total biopsy and positive biopsy rates in women at high risk of breast cancer compared to the general population. METHODS: The study group consisted of 330 women with pathogenic variants (PVs) in BRCA1/2 attending the dedicated multidisciplinary breast cancer clinic of a tertiary medical center in Israel. Clinical, genetic, and biopsy data were retrieved from the central healthcare database and the medical files. Patients aged 50 years or older during follow-up were matched 1:10 to women in the general population referred for routine breast cancer screening at the same age, as recommended by international guidelines. The groups were compared for rate of biopsy studies performed and percentage of positive biopsy results. Matched analysis was performed to correct for confounders. RESULTS: The total biopsy rate per 1000 follow-up years was 61.7 in the study group and 22.7 in the control group (p < 0.001). The corresponding positive biopsy rates per 1000 follow-up years were 26.4 and 2.0 (p < 0.001), and the positive biopsy percentages, 42.9% and 8.7% (p < 0.0001). CONCLUSION: Women aged 50 + years with PVs in BRCA1/2 attending a dedicated clinic have a 2.7 times higher biopsy rate per 1000 follow-up years, a 13.2 times higher positive biopsy rate per 1000 follow-up years, and a 4.9 times higher positive biopsy percentage than same-aged women in the general population.