Real-World Coverage With Influenza, Pneumococcal, and Herpes Zoster Vaccines Among Patients With Rheumatic Diseases in a Nationwide Healthcare Plan.

OBJECTIVE: Vaccination against preventable infections is important for the management of rheumatic diseases (RDs). This study assessed the vaccination coverage and predictors among patients with RDs using real-world data from Israel. METHODS: This retrospective cross-sectional study, based on a Maccabi Healthcare Services database, included adult patients diagnosed with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and systemic lupus erythematosus (SLE), as of April 30, 2019. Age-specific vaccination coverage for influenza (past year), pneumococcal (23-valent pneumococcal polysaccharide vaccine [PPSV23] and/or 13-valent pneumococcal conjugate vaccine [PCV13]), and live-attenuated herpes zoster (HZ) vaccines (past 5 years) was reported. Logistic regression was used to investigate predictors of vaccination. RESULTS: The study included 14,528 patients (RA: n = 6932; PsA: n = 4395; SLE: n = 1951; > 1 condition: n = 1250). Influenza vaccine coverage among patients with RA, PsA, and SLE was 45.1%, 36.2%, and 33.7%, respectively. For PPSV23, corresponding rates were 19.6%, 16.2%, and 12.6%, respectively. In the elderly population (≥ 65 years), 63.2% had influenza vaccine in the past year and 83.4% had a PPSV23 vaccine in the past 5 years or at age ≥ 65. For PCV13 and HZ, coverage in the overall study population was low at 4.8% and 3.6%, respectively. Central residence and treatment with corticosteroids and biologic or targeted synthetic disease-modifying antirheumatic drugs within the past 5 years were significant predictors of vaccination coverage across all vaccines (P < 0.05). Other predictors varied by vaccine, including female sex (influenza, PPSV23, PCV13), age (influenza, PPSV23), chronic comorbidities (influenza, PPSV23, PCV13), shorter disease duration (PCV13), and high socioeconomic status (PCV13, HZ). CONCLUSION: This study demonstrated suboptimal coverage of influenza, pneumococcal, and HZ vaccination in patients with RA, PsA, and SLE, in particular among younger adults in Israel.

Trends of Diagnosis, Disease Course, and Treatment of Atopic Dermatitis 2012-2021: Real-World Data from a Large Healthcare Provider.

In the last decade, new treatments for atopic dermatitis (AD) have emerged. We aimed to describe trends of the diagnosis, disease course, and treatment of AD over a decade (2012-2021) using data from Maccabi Healthcare Services (a 2.7-million-member healthcare provider in Israel). The AD prevalence was stable (4.0% on 31 December 2021 vs. 4.3% on 31 December 2012). The annual AD incidence was also stable (5.8/1000 in 2012 and 5.7/1000 in 2021). AD-related treatment use was highest in the first year post-diagnosis, and it included, among children (n = 87,414) vs. adults (n = 36,865), low-potency topical corticosteroids (TCS) (41.8% vs. 27.1%), mid-potency TCS (30.1% vs. 28.1%), high-potency TCS (34.9% vs. 60.3%), topical calcineurin inhibitor (10.8% vs. 10.1%), phosphodiesterase-4-inhibitor (0.3% vs. 0.7% overall; approved in 2019), phototherapy (0.1% vs. 2.3%), and systemic/biologic treatments (13.0% vs. 13.3%). Among children diagnosed in 2012 and followed through to 2021 (n = 5248), 21.5% had ≥1 AD diagnosis/treatment 10 years later (among 3223 adults: 38.3%). We conclude that the incidence and prevalence rates of AD were comparable to those in similar database studies and remained relatively stable over the past decade. The results underscore the burden of medication use among children and adults, particularly in the first year after AD diagnosis, and the low rate of AD diagnosis among patients originally diagnosed as children 10 years earlier.

Pre-morbid Laboratory Tests, Diseases, and Medications in Amyotrophic Lateral Sclerosis in Israel.

BACKGROUND: There is an unmet need for real-world data regarding laboratory results, co-morbidities, and medication use prior to the first symptoms of amyotrophic lateral sclerosis (ALS). Researchers must identify specific subpopulations at risk for developing ALS and understand pathogenic mechanisms preceding the clinical presentation of ALS as well as possible subclinical disease manifestations. OBJECTIVES: To valuate the role of laboratory results, co-morbidities, and medication use prior to the first symptoms of patients with ALS in Israel so that specific subpopulations at risk for developing ALS can be identified and for possible subclinical disease manifestations. To understand pathogenic mechanisms preceding the clinical presentation of ALS. METHODS: At the ALS clinic at Tel Aviv Sourasky Medical Center, 259 ALS patients insured by Maccabi Healthcare Services and seen between January 1998 and December 2017 were included. Comparisons of demographics, co-morbidities, medications taken, history of trauma, and laboratory tests prior to disease onset were performed between patients and 1295 matched controls. RESULTS: Prior to disease presentation, ALS patients had a higher frequency of hypertension and cardiovascular disease; presented more frequently with trauma and viral infections; more frequently used analgesics, non-steroidal anti-inflammatory drugs, narcotics, antibiotics, and antiviral medications; and had higher creatine kinase levels. CONCLUSIONS: ALS patients showed higher frequency of cardiovascular disease prior to diagnosis, as well as higher frequency of trauma, infections, and pain medication usage.

Real-World Utilization of Molnupiravir during the COVID-19 Omicron Surge in Israel.

Molnupiravir (MOV) was introduced in Israel in January 2022 during the SARS-CoV-2 Omicron surge for high-risk patients contraindicated for nirmatrelvir/ritonavir. This retrospective cohort study aimed to describe characteristics of patients offered COVID-19 antiviral treatment in Maccabi Healthcare Services (antiviral treatment-eligible cohort; n = 5596) between 12 January and 28 February 2022, and the subset of these who were dispensed MOV (MOV-treated cohort; n = 1147), as well as outcomes following MOV dispensation. Median (interquartile range) age in the antiviral treatment-eligible and MOV-treated cohorts were 70.5 (61.1, 77.3) and 74.1 (64.3, 81.7) years, respectively. The MOV-treated cohort (male: 53.2%) had high rates of COVID-19 vaccination (91.4%) and comorbidities, including immunosuppression (40.0%) and chronic kidney disease (67.0%; eGFR < 30 mL/min/1.73 m2: 28.8%), and most used comedications either contraindicated or with major potential for drug-drug interactions with nirmatrelvir/ritonavir (87.3%). At 28 days post-MOV dispensation, the cumulative incidence (95% CI) of COVID-19-related hospitalization and/or all-cause mortality was 3.6% (2.5%, 4.6%), with similar rates across sexes and age groups (18-64 vs. ≥65 years), and lower rates among recently vaccinated and/or recently SARS-CoV-2-infected patients. These data describe the characteristics and outcomes for MOV-treated patients in Israel, whose clinical characteristics may preclude the use of nirmatrelvir/ritonavir to treat their COVID-19 infection.

Management and outcome of 500 multiple myeloma patients treated for first relapse outside clinical studies.

Treatment options for multiple myeloma (MM) at 1st relapse are expanding. The current study compared common 2nd line regimens administered in a real-world setting. MM patients registered in Maccabi health care services and treated with second line therapy during 2014-2020 were evaluated, analyzing factors affecting time to third line therapy (TT3T). The study included 500 MM patients, previously treated with proteasome inhibitor (PI)-based induction. Median age at second line treatment was 68.5 years (IQR: 61.6-76.4). Most patients received a triplet based induction composed of PI (n = 471, 94.2%), with (n = 71) or without IMID (n = 400), followed by second line treatment composed of lenalidomide-dexamethasone (RD) (n = 225, 45%) or lenalidomide-dexamethasone-daratumumab (RD-Dara (n = 104, 20.8%)). Multivariable analysis confirmed treatment type (RD-Dara vs. IMID) to be associated with a lower risk to progress to third line therapy; (HR = 0.5, 95% CI 0.3-0.86, p = 0.012). Within a median follow-up period of 22.5 months (intraquartile range 11.1-39.4 m), median TT3T was not reached in patients receiving RD-Dara vs. 32.4 months (95% CI 18.0-46.8 m) with IMID, 18 months (95% CI 10.4-25.6 m) with IMID-PI and 12.1 months (95% CI 5.6-18.7 m) with PI-based regimen. In contrast, PI vs. IMID-based therapy and increased body weight were associated with a higher likelihood of progression (HR = 2.56 (95% CI 1.49-4.42); HR = 1.43, (95% CI 0.96-2.14), p = 0.08). To conclude, second line therapy with RD-Dara was associated with a significantly longer TT3T compared with IMID-based regimen, longer than obtained with PI-IMID and PI-based regimens, in patients treated outside clinical studies and previously exposed to bortezomib.

Implementing electronic patient reported outcomes in inflammatory bowel disease: patient participation, score reliability and validity.

BACKGROUND: Patient-reported outcome measures (PROMs) are recommended for assessing patient-centered outcomes in inflammatory bowel disease (IBD). The main aims were to assess the level of participation in an electronic PROM (ePROM) data collection system among patients with IBD, and evaluate reliability and validity of the resulting scores. METHODS: Patients included in the IBD registry of Maccabi Healthcare Services, a state-mandated healthcare provider for over 2.6 million people in Israel, were invited to complete the IBD-Control measure and a general health item, with follow-up ePROMs at 3 and 6 months including a global rating of change item. Descriptive statistics were used to compare patient characteristics by participation rate, and assess survey completion time. Initial scores were assessed for internal consistency reliability using Cronbach's alpha. Test-retest reliability was assessed using the intraclass correlation coefficient from paired scores of patients identified as unchanged between the initial and first follow-up. Construct validity was assessed by the ability of IBD-control scores to discriminate between patient sub-groups in expected ways. Empirical validity was assessed using ePROM score correlations with laboratory markers of disease activity. Score coverage was also assessed. RESULTS: A total of 13,588 patients were invited to participate [Mean age = 49 years (SD = 17); females = 51%]. Participation rate was 31.5%. Participants compared to non-participants were slightly older, were more likely to be female, to have a history of biologic treatment, to have higher socio-economic status, and to be more experienced in the usage of the digital patient portal. Median survey completion time was approximately 1:30 min. Internal consistency and test-retest reliability were 0.86 and 0.98, respectively. Scores discriminated between patient sub-groups in clinically expected ways, with expected correlations to laboratory markers of disease activity. A notable ceiling effect was observed (> 15%) for IBD-Control scores. CONCLUSIONS: Feasibility, reliability, and validity of the ePROM system was supported for measuring the level of perceived disease control in patients diagnosed with IBD in Israel. Additional research is needed to identify ways to increase patient participation, assess clinical implications of the identified measurement ceiling of the IBD-control, and evaluate the added value of the derived scores in support of clinical decision making.

Characteristics of Atopic Dermatitis Patients Treated with Crisaborole: Real-World Data from a Large Healthcare Provider Database in Israel.

Background: In recent years, new treatments dedicated to atopic dermatitis (AD) have become available in Israel, including crisaborole, a small molecule with unique benzoxaborole chemistry. Objective: To describe baseline characteristics, history of AD therapies, and use of health-care services of early crisaborole users in real-world settings. Methods: A retrospective cohort study was performed using the data of a large health provider in Israel. AD patients treated with crisaborole since it became commercially available in Israel in July 2019 through end of Sep 2020, were included. Baseline demographics and clinical characteristics, prior AD-related treatments and healthcare resource utilization were collected. Results: A total of 441 patients were included (57.8% females, median age = 21.1y; interquartile range = 10.5-40.8). In 62.1%, a dermatologist prescribed the first dispensed crisaborole. Median time from AD diagnosis to crisaborole treatment was 6.6 years. Up to 12 months prior to crisaborole treatment, low-, mid- and high-potency TCS were used by 30.8%, 31.1% and 55.8% of patients, respectively. Treatments related to moderate-to-severe AD were dispensed to 38.5% of patients in the prior 5 years. Asthma and allergic rhinitis were documented among 22.2% and 37.2%, respectively. In the past year, patients had a median of 9 visits to primary care physicians, 84.6% visited a dermatologist (≥5 visits: 12.9%). Conclusion: While crisaborole is indicated for mild-to-moderate disease, results suggest that a significant proportion of patients had history of advanced AD therapies suggestive of moderate-to-severe AD.

Safety and Effectiveness Using 8 Weeks of Glecaprevir/Pibrentasvir in HCV-Infected Treatment-Naïve Patients with Compensated Cirrhosis: The CREST Study.

INTRODUCTION: In clinical trials with hepatitis C virus-infected treatment-naïve (TN) patients with compensated cirrhosis (CC), glecaprevir/pibrentasvir (G/P), a fixed-dose, once-daily, pangenotypic regimen, has demonstrated sustained virologic response at posttreatment Week 12 (SVR12) > 95%. We evaluated the real-world safety and effectiveness of 8-week G/P therapy in TN patients with CC, including certain subgroups of interest. METHODS: The CREST study is a real-world, noninterventional, multicenter study retrospectively assessing data from Canada, Germany, Israel, Italy, and Spain. The full analysis set (FAS) designated all patients in the study; the modified analysis set (MAS) excluded patients who discontinued G/P for nonvirologic failure or who had missing SVR12 data. The primary endpoint was SVR12; safety endpoints were also assessed. RESULTS: A total of 386 patients were included in the FAS, 375 patients completed the study, and 325 patients were included in the MAS; 51 patients had missing SVR12 data. Overall, in the MAS and FAS, SVR12 was achieved in 99.1% and 84.2% of patients, respectively. In subgroups of interest, the percentage of patients achieving SVR12 in the MAS (and FAS) was: genotype (GT)3: 97.5% (80.6%); FibroScan® ≥ 12.5 kPa: 98.9% (89.3%); platelet count < 100 × 109/l: 100% (88.2%); both platelets < 150 × 109/l and FibroScan® > 20 kPa: 100% (88.9%); aspartate aminotransferase-to-platelet ratio index > 1.09: 98.7% (83.1%); fibrosis-4 index > 3.25: 98.6% (84.0%); albumin < 3 g/dl: 100% (91.7%); people who use drugs: 97.7% (84.3%); psychiatric disorders: 96.6% (84.8%); and human immunodeficiency virus coinfection: 100% (95.0%). Overall, 26.9% (104/386) of patients experienced an adverse event, none of which were classed as serious. CONCLUSION: In this real-world cohort, 8 weeks of G/P therapy was well tolerated in TN patients with CC. SVR12 rates were similar to clinical trials, supporting 8-week treatment in TN patients with CC, including those with signs of advanced liver disease and GT3 infection.

Epidemiology and Economic Burden of Atopic Dermatitis: Real-World Retrospective Data from a Large Nationwide Israeli Healthcare Provider Database.

INTRODUCTION: Real-world data on the epidemiology and economic burden of atopic dermatitis (AD) are limited. Here we describe the epidemiology and economic burden of AD using electronic healthcare data from Israel. METHODS: A retrospective study was performed using the Maccabi Healthcare Services database. AD incidence in 2008-2017 and point prevalence (ADprev) on 31 December 2017 were described using diagnosis codes for overall patients, and sex and age subgroups. For ADprev, severity was defined using recently dispensed treatments for AD. Annual healthcare resource utilization in AD prevalent patients was compared with non-AD matched controls using generalized linear modelling. Direct annual costs were estimated also. RESULTS: AD incidence was 7.0/1000 person-years; overall prevalence was 4.4% (female patients 4.5%, male patients 4.3%; age 0 to less than 6 months, 0.9%; 6 months to less than 12 years, 11.0%; 12 to less than 18 years, 5.8%; 18 years or older, 2.2%). Among ADprev (n = 94,483), mild, moderate, and severe AD comprised 57.7%, 36.2%, and 6.1% (adults 43.8%, 46.3%, 9.9%), respectively. Dermatologist and allergist visits and hospitalization rates (at least one) were 40.7%, 6.6%, and 3.8% in 2017. Compared with controls, overall and moderate-to-severe AD were associated with 36% and 52% increases in annual per-person costs (incremental costs $126 and $190). CONCLUSIONS: AD epidemiology in Israel is comparable with other real-world database studies. AD imposes an economic burden that increases with disease severity.

Occurrence and costs of atopic dermatitis in IsraelAtopic dermatitis is a disease that causes the skin to be inflamed and itchy. Atopic dermatitis is most common in children but can also occur in adolescents and adults. Using data from a large healthcare provider in Israel, this study aimed to describe how common atopic dermatitis is within the population. Costs related to the use of healthcare services (such as visits to dermatologists and creams to treat atopic dermatitis) in the year 2017 were compared between persons with versus without atopic dermatitis. For the years 2008 to 2017, approximately 7 out of 1000 people were newly diagnosed with atopic dermatitis each year (incidence). Among people alive on 31 December 2017, 4.4% had atopic dermatitis (prevalence), with 42.3% suggestive of moderate to severe disease. Patients with atopic dermatitis, particularly those with more severe disease, used healthcare services more frequently. Compared with people without atopic dermatitis, medical costs among patients with atopic dermatitis were 36% higher (corresponding to added costs of $126 per person per year). This study helps to better understand how many people have atopic dermatitis, and what healthcare resources are needed to manage this disease.

Burden of Endometriosis: Infertility, Comorbidities, and Healthcare Resource Utilization.

The goal of our study was to evaluate the burden of endometriosis in the community by comparing healthcare resource utilization, total direct medical costs, infertility, and comorbidity rates of women with and without a diagnosis of endometriosis. A retrospective case-control study was performed using the databases of a 2.1 million-member nationwide healthcare plan. The study population included women aged 15-55 years enrolled in the healthcare plan. Women with a diagnosis (ICD-9) of endometriosis were compared to controls without diagnosed endometriosis. Women were individually matched (1:4) on age and residence area. Patient characteristics were described, including infertility, comorbidities, and annual healthcare resource utilization. Total direct medical costs were analyzed in a generalized linear model adjusting for age. Women with endometriosis (n = 6146, mean age ± SD: 40.4 ± 8.0 y) were significantly more likely than controls (n = 24,572) to have a lower BMI and a higher socioeconomic status. After adjusting for BMI and socioeconomic status, endometriosis was significantly associated with infertility (OR = 3.3; 95% CI 3.1-3.5), chronic comorbidities, higher utilization of healthcare services (hospitalization: OR = 2.3; 95% CI 2.1-2.5), pain medications, and antidepressants. Women aged 15-19 y with endometriosis had substantially higher utilization of primary care visits (57.7% vs. 14.4%) and oral contraceptive use (76.9% vs. 9.6%). Direct medical costs associated with endometriosis were higher than those for controls (OR = 1.75; 95% CI 1.69-1.85). Endometriosis is associated with a high burden of comorbidities, increased healthcare resource utilization, and excess costs, particularly for younger patients whose healthcare needs may differ widely from the older population.

Treatment patterns, persistence with therapy, and outcomes of ustekinumab in Crohn's disease: Real-world data analysis.

BACKGROUND AND AIM: In 2017, ustekinumab (UST) was included in Israel's National Basket of Health Services for treatment of biologic-experienced Crohn's disease (CD) patients with moderately to severely active disease. This study aims to provide real-world evidence on persistence and clinical outcomes among early users of UST. METHODS: This retrospective cohort study was conducted using data from Maccabi Healthcare Services (MHS; 2.5-million-member state-mandated health provider, Israel). Adult patients with a CD diagnosis code who had ≥1 dispensed UST prescription in 2017-2018 and at least 12 months of prior continuous health plan enrollment were included. Outcomes, including treatment discontinuation, dose-escalation (based on shortened intervals between purchases), CD-related surgery, CD-related hospitalization, corticosteroid (CS) discontinuation, and use of opioids were evaluated from the date of first dispensed UST through the end of 2019 using Kaplan-Meier analysis. RESULTS: A total of 162 eligible patients (81 [49.4%] female; median age 34.4 years [IQR 23.2-46.3]; median years since CD diagnosis 8.6 [IQR 4·8-16.0]) were enrolled in the study. Discontinuation rate after 365 and 540 days of follow-up was 27.8% and 35.6%. Dose escalation was estimated at 15.4% and 28.6%, respectively. The first-year cumulative rate of CD-related surgery and CD-related hospitalization were estimated at 4.7% and 9.8%, respectively. CONCLUSION: In this real-world CD cohort of UST users, results suggest persistence is relatively high as compared to other biologics for CD. Comparative effectiveness of different biologic treatments for CD in this population should be further explored.

Health Care Resource Utilization and Economic Burden Associated With Congenital Cytomegalovirus Infection: A Longitudinal Analysis of Data From Clinical Practice at a Large Health Care Provider in Israel.

PURPOSE: Congenital cytomegalovirus infection (cCMVi) is the leading cause of nonhereditary sensorineural hearing loss and can cause other long-term neurodevelopmental disabilities; however, data on the economic burden of cCMVi during early childhood are scarce. The primary objective of the study was to describe longitudinal patterns of health care resource utilization (HCRU) and direct medical costs among infants with cCMVi compared to infants unexposed to cCMVi. METHODS: A retrospective cohort study was performed using data on infants born between 2013 and 2017, as captured in the database of Maccabi Healthcare Services, a 2.5 million-member health care organization in Israel. cCMVi cases were identified by physician diagnosis and/or dispensed valganciclovir within 90 days after birth. Infants born to mothers CMV-seronegative throughout pregnancy were selected for comparison (unexposed controls). Infants were retrospectively followed up through December 31, 2018, or 4 years of age (Y4). HCRU included physician visits, hospital admissions, audiology tests/procedures, imaging, and valganciclovir treatment. Direct medical costs, in US dollars per person per year (USD PPPY) were calculated from the health-system perspective. To compare costs of cCMVi cases and controls, direct medical costs were estimated using a generalized linear model with a log link function and γ distribution after adjustment for patient characteristics. FINDINGS: A total of 351 cCMVi cases and 11,733 control infants with continuous follow-up during their first year of life (Y1) were included in the study. In Y1, cases were more likely to have a hospital admission (8.5% cases vs 4.5% control; P < 0.001) and higher numbers of pediatrician visits (median, 18 vs 15), audiology visits and tests, and cranial ultrasounds (all, P < 0.05). Longitudinally, incremental costs associated with cases were highest in Y1 (1686.7 USD PPPY; cost ratio = 2.6; P < 0.001) and remained elevated through Y4. IMPLICATIONS: cCMVi was associated with substantial increases in HCRU and economic burden during early childhood, and particularly during the first year of life.

Cutaneous Comorbidities Associated With Atopic Dermatitis in Israel: A Retrospective Real-World Data Analysis.

BACKGROUND: Patients with atopic dermatitis (AD) are susceptible to infectious and inflammatory cutaneous comorbidities. OBJECTIVE: The aim of the study was to describe the prevalence of cutaneous comorbidities associated with AD, including their relationship with AD severity. METHODS: A retrospective cross-sectional analysis was performed using the Israeli Maccabi Healthcare Services database. Prevalent AD cases on December 31, 2017, were diagnosed with AD at any time since 1998 and had 1 or more recent (2013-2017) AD diagnoses. Dispensed AD treatments within 5 or fewer years served as a surrogate for AD severity. Cutaneous comorbidities in AD cases were compared with non-AD controls matched 1:1 on age, sex, and residential area. Among adults, comorbidities were compared across AD severity using multinomial logistic regression. RESULTS: The eligible population included 94,483 patients with mild (57.7%), moderate (36.2%), or severe (6.1%) AD, and 94,483 matched non-AD controls. Skin infections, inflammatory skin conditions, cutaneous manifestations of AD, and sweat gland disorders were more prevalent ( P < 0.001) in patients with AD than in controls. Most cutaneous comorbidities that were more prevalent in adult patients with AD were also significantly ( P < 0.001) associated with AD severity. CONCLUSIONS: This study suggests that AD is associated with many infectious and inflammatory cutaneous comorbidities and highlights the relationship between AD severity and comorbidity prevalence.

The Effectiveness of the Two-Dose BNT162b2 Vaccine: Analysis of Real-World Data.

BACKGROUND: Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were shown to be highly efficacious in preventing the disease in randomized controlled trials; nonetheless, evidence on the real-world effectiveness of this vaccine is limited. Study objective was to evaluate the effectiveness of BNT162b2 vaccine in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and mortality. METHODS: This historical cohort study included members of a large health provider in Israel that were vaccinated with at least 1 dose of BNT162b2. The primary outcome was incidence rate of a SARS-CoV-2 infection confirmed with real-time polymerase chain reaction (rt-PCR), between 7 and 27 days after second dose (protection-period), as compared to days 1-7 after the first dose, where no protection by the vaccine is assumed (reference-period). RESULTS: Data of 1 178 597 individuals vaccinated with BNT162b2 were analyzed (mean age 47.7 years [SD = 18.1], 48.4% males) of whom 872 454 (74.0%) reached the protection period. Overall, 4514 infections occurred during the reference period compared to 728 during the protection period, yielding a weighted mean daily incidence of 54.8 per 100 000 (95% confidence interval [CI]: 26.1-115.0 per 100 000) and 5.4 per 100 000 (95% CI: 3.5-8.4 per 100 000), respectively. The vaccine effectiveness in preventing infection was 90% (95% CI: 79%-95%) and 94% (95% CI: 88%-97%) against COVID-19. Among immunosuppressed patients, vaccine effectiveness against infection was 71% (95% CI: 37%-87%). The adjusted hazard ratios for hospitalization in those infected were 0.82 (95% CI: .36-1.88), 0.45 (95% CI: .23-.90), and 0.56 (95% CI: .36-.89) in the age groups 16-44, 45-64. and ≥75 years, respectively. CONCLUSIONS: The effectiveness of the BNT162b2 vaccine is comparable to the one reported in the phase III clinical trial.

Epidemiology of cytomegalovirus infection in pregnancy in Israel: Real-world data from a large healthcare organization.

Congenital cytomegalovirus infection (cCMVi) is the leading cause of nonhereditary sensorineural hearing loss among newborns. Women newly acquiring cytomegalovirus infection (CMVi) during pregnancy have the highest risk of vertical transmission. This study aimed to describe the epidemiology of CMVi in pregnancy in a large healthcare database. A retrospective cohort study was performed using the Maccabi Healthcare Services database (Israel). Women aged 18-44 years old on July 1, 2013 with no record of pregnancy in the prior 6 months were followed through December 31, 2017 for first pregnancy occurrence. Pregnancy outcomes (live birth, spontaneous/therapeutic abortions, stillbirth, and uncertain outcomes) were captured. CMV test results were obtained to assess serostatus at the start of pregnancy (SoP) and primary CMV infection (CMVi) during pregnancy. Associations of demographic and reproductive factors with pCMVi were investigated (multivariable logistic regression). The study included 84 699 pregnant women (median age = 31 years; interquartile range = 28-35). Live birth, fetal loss, and uncertain pregnancy outcomes accounted for 76.8%, 18.2%, and 5.0%, respectively. The seroprevalence of CMV at the start of pregnancy in this cohort was 63.4% (95% confidence interval [CI]: 63.1-63.7). Among seronegative women with available test results (n = 10 657), CMVi incidence was 14.5 per 1000 (95% CI = 12.2-16.7). In multivariate logistic regression models adjusting for maternal age, CMVi was significantly associated with having one or more prior live births (odds ratio [OR]: 3.8 [95% CI: 2.6-5.4]) and having a child less than 6 years of age (OR: 4.3 [95%CI: 3.0-6.1]). One in three pregnant women in Israel is at risk for primary CMVi. This study demonstrates that real-world electronic healthcare data can be leveraged to support clinical management and development of interventions for congenital CMV by identifying women at high risk for CMVi during pregnancy.

HIV Pre-Exposure Prophylaxis (PrEP) purchase patterns and STI occurrence among Israeli men: A cohort analysis.

BACKGROUND: HIV Pre-exposure prophylaxis (PrEP) is the regular use of antiretroviral medication by people who are not infected with HIV to prevent seroconversion. Israel approved PrEP for continuous use in 2017, and Israeli Health Maintenance Organizations (HMO) offered PrEP with a copayment to eligible members. METHODOLOGY: This retrospective cohort study included all people who were dispensed PrEP between September 2017 to June 2019 in the second largest HMO in Israel. Statistical analysis, including Kaplan Meier, was conducted to evaluate user PrEP purchase, adherence to medical follow-up, and clinical outcomes. RESULTS: In total, a cohort of 757 PrEP users were followed for 657.8 person-years. All but one user were male; median age was 35 years. At baseline, 0.8% had gonorrhea and 1.5% had chlamydia infections and 4.4% had recent syphilis infection. Continuous use of PrEP (without interruption/discontinuation) was observed in 29.9%, while 39.9% interrupted and 30.3% discontinued use. Median time to first interruption/discontinuation was 4.0 months. At 6-12 months after initiation, 79.8% of users had a documented HIV test, 77.3% a Chlamydia-Gonorrhea panel, and 78.9% a creatinine test. There was one new case of HIV among the cohort, five months after PrEP discontinuation. Estimated first-year infection rates were 5.0%, 8.6% and 6.8% for gonorrhea, chlamydia and first-time syphilis, respectively. CONCLUSIONS: This study shows heterogeneous PrEP purchase patterns and required medical follow-up, and an increase in STIs among consistent PrEP users. Improving adherence to recommended medical follow-up during PrEP use is essential in PrEP's integration into Israel's national HIV prevention strategy.

Diabetes, but not pre-diabetes, is associated with shorter time to second-line therapy and worse outcomes in patients with multiple myeloma.

About 20% of MM patients have T2DM. We assessed the impact of T2DM/pre-T2DM on MM progression and OS. We collected retrospective data of newly diagnosed MM patients in Maccabi health services, Israel, between 2012 and 2016. The study included 503 MM patients, median age 67.2 years (IQR: 33.5-91.2). Median follow-up was 32 months (IQR 19.4-47). T2DM and pre-T2DM were recorded in 24.1% and 51% patients, respectively. Median TT2T and OS in the cohort were 17.5 months (95% confidence interval (CI) 15-20) and unreached, respectively. T2DM patients had shorter TT2T (HR = 1.31, 95%CI 1.0-1.72, p=.047), particularly transplanted patients; 20.2 vs. 40 months (HR = 2.09, 95%CI 1.18-3.71, p=.012). In a multivariable model, T2DM had a borderline significant risk of all-cause mortality, adjusted HR 1.38 (p=.09). Pre-diabetes had no impact on TT2T or OS. T2DM predicted a shorter TT2T, particularly in transplanted patients, and tended to be associated with shorter survival.

Epidemiology, longitudinal treatment patterns and outcomes of chronic lymphocytic leukemia in Israel.

This study aims to describe chronic lymphocytic leukemia (CLL) epidemiology, treatment patterns and outcomes in a 2.3-million-member healthcare provider database (Maccabi Healthcare Services, Israel). Newly-diagnosed CLL patients (1999-2017) were followed through 31/3/2018. A total of 1857 newly-diagnosed CLL patients were included. Annual incidence was 5.82 per 100,000 population. Median overall survival (OS) was 12.7 (95%CI: 11.8-13.5) years since diagnosis. Approximately 1/3 initiated treatment within 5 y. A statistical trend (p = 0.066) for improved OS over time was observed among younger patients (age <70 y) treated in 2009-2017 vs. 1999-2008). Among patients treated since 2009 (n = 411; median age = 68y), fludarabine-cyclophosphamide-rituximab (FCR), bendamustine-rituximab and obinutuzumab ± chlorambucil accounted for 19.5%, 12.2% and 11.4% of first line, respectively. Median (95%CI) time to next treatment and OS were 3.1(2.6-3.6) and 7.0(6.3-7.7) years, respectively. CLL incidence in Israel is comparable to developed countries. Real-world data suggest a trend of improved survival over the last decade among patients treated before age 70.

Real-world epidemiology, treatment patterns and survival of multiple myeloma patients in a large nationwide health plan.

BACKGROUND: Survival of patients with multiple myeloma (MM) has improved significantly with access to autologous stem cell transplant (SCT) and new treatments. This study aims to describe epidemiology, treatment patterns, and outcomes of MM in Israel. METHODS: A retrospective observational study was conducted in Maccabi Healthcare Services, a 2-million-member nationwide health plan in Israel. MM was defined by cross-linking data on MM diagnoses, dispensed treatments, and serum free light-chain assays. Point prevalence (31/12/2016) and incidence (2012-2016) rates were age-standardized. Newly diagnosed and treated patients (2009-2015) were followed through 31/12/2016 for progression to second-line (L2), with death as a competing risk. RESULTS: MM prevalence and incidence rates were 26.2 and 4.6 per 100,000 population, respectively. In the treatment cohort (N = 552), mean ±â€¯SD) age was 65.6 ±â€¯11.3) years (60.1% male) and median (95% CI) OS in years was 5.2 (4.3-6.1) overall and 6.5 (4.9-8.1) for first-line (L1) bortezomib (N = 421). In a multivariable analysis, OS was significantly higher among patients starting L1 in 2012-2015 vs. 2009-2011. Within a year, 38.4% underwent SCT. Cumulative incidence of L2 was 38.2% and 51.4% within 1 and 2 years, respectively, and was associated with older age (≥65y; P < 0.001). CONCLUSION: These results from a large heterogeneous population demonstrate MM incidence and survival rates that are in line with the literature, together with a significant improvement in overall survival over time. Approximately half of newly treated patients progressed to L2 within two years. These results will serve as a baseline for further research to evaluate the clinical impact of new interventions.