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Among 843,208 participants in Israel who were 50 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, those who received a booster had 90% lower mortality due to Covid-19 than those who did not receive a booster. The study period was 54 days; adverse effects were not recorded.

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. A retrospective analysis of data from a large healthcare insurance provider in Israel shows that a second booster shot (fourth dose) of BNT162b2 in people aged 60 years and over results in a substantial reduction in hospitalizations and deaths due to COVID-19.

In a retrospective cohort study from Israel, 149,032 patients who had recovered from SARS-CoV-2 infection were followed over a 270-day period to assess the rate of reinfection according to whether they had subsequently received a Covid-19 vaccine or had remained unvaccinated. The reinfection rate was 10.21 cases per 100,000 persons per day among unvaccinated patients and 2.46 cases among vaccinated patients.

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. Effectiveness of one subcutaneous dose of MVA-BN, the smallpox and mpox vaccine, was estimated to be 86% in a cohort of vaccine-eligible males in Israel, supporting its use to curtail the outbreak of mpox virus.

Background: Demand for elective oocyte cryopreservation (OC) among healthy women delaying childbearing is rising worldwide. Yet, clinicians and patients often rely on limited or indirect evidence to predict age-specific mature oocyte yield. Robust, real-world benchmarks are needed to guide expectations, estimate live birth potential, and optimize treatment planning. Methods: We retrospectively analyzed 400 healthy women aged 30–41 undergoing their first elective OC cycle between 2019 and 2023 at a large, university-affiliated fertility center. Exclusion criteria included infertility, polycystic ovary syndrome, prior ovarian surgery, and other medical indications for OC. All cycles used a standardized GnRH antagonist protocol with an initial gonadotropin dose of 300 IU/day. Only mature (metaphase II) oocytes were cryopreserved. Age-specific percentiles for total and mature oocyte yield were modeled using the General Additive Model for Location, Scale, and Shape (GAMLSS), and nomograms were developed. Results: Mean age was 35.7 years (SD 2.3). Median total and mature oocytes retrieved were 13 (IQR 9–19) and 10 (IQR 7–15), respectively. At the 50th percentile, women aged 30, 35, and 40 yielded 20, 14, and 9 total oocytes, with 15, 11, and 6 mature oocytes cryopreserved. Nomograms across percentiles illustrated a consistent, progressive decline in yield with advancing age. Conclusions: Age-based nomograms derived from real-world data can offer a clinically relevant tool to estimate the likely oocyte yield per cycle. They can help set realistic expectations, guide the number of cycles needed to meet fertility goals, and support evidence-based, shared decision-making in elective OC.

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.

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.

Despite recent therapeutic advances in chronic lymphocytic leukemia (CLL), access to innovative treatments may still be uneven outside Western Europe. This study aimed to explore reimbursement policy and access to novel targeted CLL therapies across selected countries and to analyze factors associated with differences in treatment availability and reimbursement timelines. Reimbursement frameworks, timelines, and accessibility of six novel CLL therapies were assessed across 15 countries in Central and Eastern Europe, the Balkans, Armenia, and Israel. Data were collected via expert surveys in late 2024, based on publicly available national and regional sources. The survey covered reimbursement extent, timelines, policy restrictions, coverage pathways, and health technology assessment (HTA) evaluations. Comparative analyses examined regional differences in reimbursement and their potential drivers. Spearman's rank correlation was used to explore associations between the number of reimbursed therapies, reimbursement delays, and demographic, macroeconomic, and epidemiological variables. The number of reimbursed therapies ranged from zero (Ukraine, Armenia) to five (Czech Republic), with a regional mean of 2.7 (SD = 1.38) and overall mean time to reimbursement of 29.3 months (SD = 21.4). Ibrutinib, reimbursed in 13 countries, had the longest mean reimbursement delay (35.6 months), while venetoclax (11 countries, 26.5 months), acalabrutinib (9 countries, 16.4 months), and zanubrutinib (6 countries, 15.2 months) had shorter delays. Gross domestic product (GPD) showed a moderate positive correlation with the number of reimbursed therapies (ρ = 0.673, p = 0.006). Borderline significant associations were noted for CLL incidence and mortality (p = 0.050). Reimbursement indications were often restricted, particularly for patients without deletion 17p or TP53 mutations who experienced late relapses. Data on HTA outcomes and the number of treated patients were limited in several countries, and common challenges included funding constraints, administrative barriers, and the lack of centralized rare disease policies. Significant disparities in access to targeted CLL therapies persist across the analyzed countries, with the number of reimbursed therapies positively correlated with GDP .

Direct acting antivirals for hepatitis C virus have shown dramatic results in clinical trials. However, their effectiveness has yet to be demonstrated within observational cohorts which lack exclusion criteria found in randomized control trials. To determine the effectiveness of dasabuvir/ombitasvir/paritaprevir/ritonavir in achieving sustained virological response. Retrospective observational cohort study of all Clalit Health Services members with hepatitis C virus genotype 1 who were dispensed dasabuvir/ombitasvir/paritaprevir/ritonavir from January 1, 2015 to-November 31, 2015. There were 564 participants during the study period. The average age was 61.9 years, 52.0% were male, and 61.5% were born Eastern/Central Europe or Central Asia. The prevalence of diabetes was 31.7% and 70.3% were overweight/obese. Cirrhosis was present in 41.0% of participants, of whom 52.8% had stage 4 fibrosis. Of the cohort, 416 (74.8%) had follow-up viral load testing at 10 or more weeks after the end of treatment. We report a sustained virological response of 98.8% among those tested. Treatment with dasabuvir/ombitasvir/paritaprevir/ritonavir demonstrated a near universal effectiveness in achieving a sustained virological response among HCV patients in a large cohort.

The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice. All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services' (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log-rank) method and Cox proportional hazards model. 64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5-16.5) vs. 31.0 for TBP (95% CI: 20.6-41.4), P<0.001. On multivariate analysis, longer OS was preserved for TBP, after controlling for differences in age, adjuvant trastuzumab, duration of first-line trastuzumab therapy, brain metastases, visceral metastases and hormonal treatment [Hazard Ratio (HR) = 0.63, 95% CI: 0.40-0.99, P = 0.045]. In this comparative cohort study, OS of HER2-positive MBC patients treated with TBP was significantly longer than with lapatinib. These results might be especially relevant in settings where ado-trastuzumab-emtansine (TDM-1), the current preferred agent in this setting, is not available yet for patients.