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.

Impact of flash glucose monitoring on glucose control and hospitalization in type 1 diabetes: A nationwide cohort study.

BACKGROUND: We evaluated the impact of flash continuous glucose monitoring (FCGM) on glycemic control and healthcare burden in a large real-world cohort of patients with type 1 diabetes (T1D) initiating FCGM technology. METHODS: In this retrospective cohort study, we included adults (age ≥18 years) with T1D from a large Health Maintenance Organization in Israel, who initiated FCGM during 2018. Primary outcomes included change in HbA1c ≥3 months following FCGM commencement and change in rate of internal-medicine hospitalization. Additional outcomes included changes in glucose test strip purchases, diabetes related outpatient health care visits and hospitalization for diabetic ketoacidosis (DKA) and/or severe hypoglycemia. RESULTS: The study included 3490 patients, followed for a median of 14 (inter-quartile range 11-15) months after FCGM commencement. Among 2682 patients with an HbA1c measured both at baseline and ≥3 months after FCGM initiation, average HbA1c declined from 8.1% ± 1.46% to 7.9% ± 1.31% (P < .001) at first measurement and was maintained during follow up. Specifically, in those with HbA1c ≥8%, a mean decline of 0.5% (P < .001) was observed. A clinically significant HbA1c reduction of ≥0.5% was experienced by 25.5% of the patients. The rate of internal medicine hospitalization, visits to primary care, or visits to endocrine/diabetes specialists in the period following FCGM commencement vs the 6 months prior was significantly reduced (P < .001). Hospitalization for DKA and/or hypoglycemia declined as well (P = .004). CONCLUSIONS: FCGM was associated with significant and durable improvement in glycemic control as well as reduced consumption of healthcare services.

Calcium Channel Blockers and the Risk for Lung Cancer: A Population-Based Nested Case-Control Study.

BACKGROUND: It has been suggested that calcium channel blockers (CCBs) may increase the risk of lung cancer; however, current evidence is conflicting and limited. OBJECTIVE: Investigate the associations between CCB use and lung cancer. METHODS: We conducted a population-based nested case-control study. A cohort was formed of patients prescribed their first antihypertensive agent from 2000 to 2014. CCB exposure information was obtained by identification of all prescriptions dispensed during study follow-up. Cases were patients newly diagnosed with lung cancer during follow-up. Each case was matched with 10 controls by age, sex, calendar year of cohort entry, and duration of follow-up. Multivariate conditional logistic regression was used to estimate odds ratios (ORs) with 95% CIs of lung cancer associated with ever use of CCBs. RESULTS: During a median follow-up of 6.2 years, we identified 4174 cases of lung cancer. Ever use of CCBs was associated with an increased risk of lung cancer (adjusted OR = 1.13; 95% CI = 1.06-1.21), when compared with the use of other antihypertensive drugs. A duration-response relation was observed, with the ORs gradually increasing with longer cumulative duration of CCB use (<5 years: OR = 1.12, 95% CI = 1.04-1.20; 5-10 years: OR = 1.22, 95% CI = 1.07-1.40; >10 years: OR = 1.33, 95% CI = 0.90-1.96; P trend < 0.001). Conclusion and Relevance: The results of this large population-based study indicate that the use of CCBs is associated with a modest but significant increase in the risk of lung cancer. This association appeared to increase with longer duration of use.

Risk of serious infections, cutaneous bacterial infections, and granulomatous infections in patients with psoriasis treated with anti-tumor necrosis factor agents versus classic therapies: Prospective meta-analysis of Psonet registries.

BACKGROUND: Anti-tumor necrosis factor (TNF) therapy in psoriasis has been associated with an increased risk of serious infections compared with nonbiologic systemic therapies. OBJECTIVE: We sought to quantify the risk of: (1) serious infections (leading to hospitalization, sequelae, or death); and (2) "any infection," bacterial cutaneous infections, and granulomatous infections among patients receiving anti-TNF therapy compared with nonbiologics (acitretin, methotrexate, cyclosporine). METHODS: We used prospective meta-analysis to combine data from the Psocare registry (Italy), Biobadaderm registry (Spain), and Clalit Health Services database (Israel), including 17,739 patients and 23,357.5 person-years of follow-up. RESULTS: For serious infections, age, gender, and Charlson morbidity index adjusted hazard ratio of exposure to anti-TNFs compared with nonbiologics was 0.98 (95% confidence interval 0.80-1.19), for bacterial cutaneous infections it was 1.00 (95% confidence interval 0.62-1.61), and for granulomatous infections it was 1.23 (95% confidence interval 0.82-1.84). Using methotrexate as comparator and comparing first year of exposure with later exposure did not modify the results. For any infectious episode, risks and relative risks were heterogeneous among registries, probably because of different definitions of outcome. LIMITATIONS: There was lack of power to describe risk of single drugs. CONCLUSION: In current clinical practice, treatment with anti-TNF drugs was not associated with a higher risk of serious infections than treatment with nonbiologic systemic therapy.

Biologic drug survival in Israeli psoriasis patients.

BACKGROUND: Drug survival is defined as the time period of treatment with a certain drug until its cessation. The role of previous exposure to traditional systemic treatments in biologic survival is still unknown. OBJECTIVE: To investigate the drug survival rates of biologic treatments in patients with psoriasis and to identify predictor factors. METHODS: Survival analysis was performed on patients with severe psoriasis who received adalimumab, infliximab, etanercept, and ustekinumab for treatment of psoriasis, drawn from the Clalit Health Services database. Multivariate analysis was performed adjusting for demographic variables; metabolic syndrome and its components; psoriatic arthritis; biologic naivety; coadministration of methotrexate, acitretin, or cyclosporine; and previous standard systemic treatment exposure. RESULTS: Among 907 patients treated with 1575 biologic treatments, ustekinumab had a significantly higher survival rate than tumor necrosis factor inhibitors. Biologic naivety and concomitant methotrexate intake were positive predictors for drug survival, whereas the female sex and the duration of previous systemic treatments were negative predictors. LIMITATIONS: Data regarding disease severity or duration could not be drawn from the Clalit Health Services database. CONCLUSION: Ustekinumab had better retention rates in comparison with other investigated biologics in patients with severe psoriasis, most of whom used it as a third line therapy.

The 'real-life' impact of adding bevacizumab to first-line therapy in metastatic colorectal cancer patients: a large Israeli retrospective cohort study.

BACKGROUND: After a decade of extensive use, the actual contribution of bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC) is still unclear. OBJECTIVE: To evaluate 'real-life' outcomes of patients with mCRC before and after the introduction of bevacizumab to standard mCRC first-line practice. METHODS: Using the computerized administrative database of Clalit Health Services' (CHS), Israel's largest health care provider, we retrospectively compared two cohorts (n = 1739): (A) all CHS' patients diagnosed with mCRC between January 2000 and December 2004 that received first-line irinotecan or oxaliplatin-based combination chemotherapy (before bevacizumab was introduced) (n = 1052), and (B) all patients that started first-line irinotecan or oxaliplatin combination chemotherapy together with bevacizumab between September 2006 and December 2009 (after bevacizumab was fully reimbursed in Israel for mCRC first-line therapy) (n = 687). The primary endpoint was overall survival (OS) and secondary endpoints were first-line progression-free survival (PFS) and metastatectomy rates. RESULTS: Median OS was longer in Cohort B than in Cohort A [23.0 months vs.15.0, adjusted hazard ratio (HR), 0.75]. Secondary outcomes were also better; PFS of 14.0 months vs. 9.8 in the earlier period (HR, 0.75) and metastatectomy rate of 8.1% versus 3.9%. The longer OS in Cohort B was preserved even after controlling for latter-line epidermal growth factor receptor (EGFR) inhibitor use (HR = 0.77). CONCLUSION: In this analysis, OS, PFS and metastatectomy rates of first-line treatment of mCRC were significantly higher in the later period of the study. These results, derived from 'real-life' practice, suggest that the use of bevacizumab, among other alterations in the clinical management of mCRC between the two periods, might have had a significant contribution to these outcomes, and may therefore support the current practice of adding bevacizumab to first-line treatment of mCRC.

Factors associated with drug survival of methotrexate and acitretin in patients with psoriasis.

Drug survival has recently become an important clinical issue in psoriasis. However, there has been little research into factors associated with drug survival of methotrexate and acitretin. The aim of this study was to investigate factors associated with drug survival of methotrexate and acitretin treatment for psoriasis. Survival analysis was performed in patients who received methotrexate or acitretin for the treatment of psoriasis, drawn from the Clalit Health Services database. Investigated factors included demographic variables, obesity, metabolic syndrome, psoriatic arthritis, administration route and folic acid supplementation. Among 6,256 patients, factors associated with treatment drop-out were: younger age (p <0.001) and psoriatic arthritis (acitretin p < 0.001). For methotrexate, metabolic syndrome (p = 0.033), intramuscular administration route of injection (p <0.001) and lack of folic acid supplementation (p <0.001) were associated with treatment drop-out. In patients with psoriasis, some ancillary factors may modify the drug survival of acitretin and methotrexate.

The association between infantile microcytic anemia and attention deficit hyperactivity disorder, a case-control study.

Background: Microcytic anemia due to iron deficiency is the most common type of anemia in children in Israel and many parts of the world, and has been shown to have negative consequences for the cognitive performance. We aimed to examine the association between microcytic anemia at age 9-18 months and ADHD during childhood. Methods: This case-control study included healthy children aged 6-18 years at data collection (April 2020), insured by Clalit-Health-Services, and aged 9-18 months between June 2004 and December 2013, when a blood-count was performed. The study group included children diagnosed with ADHD based on the medical documentation of at least two consecutive stimulant prescriptions. A control group without any stimulant prescriptions was matched in a ratio of 1-3:1, by year of birth, sex and cultural background. Any microcytic anemia was defined as Hb < 10.5 g/dl and MCV 60-75 fl. Moderate microcytic anemia as Hb 7-9.9 g/dl. We performed a conditional-logistic-regression analysis, adjusted by socioeconomic status (SES) and year of birth. Sensitivity analysis examined this association stratified by sex, cultural background, SES and age at data collection quintiles. Results: Any microcytic anemia prevalence was lower in the ADHD group (n = 19,467) as compared to the controls (n = 39,004) (3.4 % and 4.0 %, respectively), adjusted-OR = 0.86 (95%CI: 0.78, 0.98). The prevalence of moderate microcytic anemia was similar (0.9 % vs. 1.0 %). Lower any microcytic anemia prevalence in the ADHD group was found in boys, secular-traditional Jews, and in the 4th quintile of age (12.1-13.5 years). Conclusions: We found a small inverse association between microcytic anemia at 9-18-months and ADHD during childhood, thus rejecting our hypothesis that microcytic anemia at infancy is associated with a higher prevalence of ADHD. Further studies are warranted, to examine the effects of ID and brain iron concentration on the development of ADHD in childhood.

The Risk of Herpes Zoster Events in Patients with Spondyloarthritis and the Effect of BNT162b2 mRNA COVID-19 Vaccine.

The data on the risk of herpes zoster (HZ) in spondyloarthropathy (SpA) patients are sparse, especially regarding its association with the novel mRNA COVID-19 vaccines and immunosuppressants. We aimed to evaluate whether SpA diagnosis and/or immunosuppressant use affect HZ risk and the influence of mRNA COVID-19 vaccination. We assessed the association between SpA (psoriatic arthritis (PsA) and ankylosing spondylitis (AS)) diagnoses and HZ in a large population database with patients matched by age and sex to controls. We also assessed the association between the COVID-19 vaccine and new-onset HZ using two nested case-control studies, identifying all new HZ cases diagnosed from 1 January-31 December 2021 within the SpA and general population cohorts, matched randomly by sex, age and HZ index date to controls without HZ. Exposure to mRNA COVID-19 vaccination was ascertained in the 6 weeks prior to the index date both in cases and controls. In our results, the incidence rate of HZ was higher in PsA patients vs. the general population, at 1.03 vs. 0.64 per 100 person-years, respectively (adjusted HR = 1.55; 95%CI, 1.19-2.02). Within the SpA group, Jak-I treatment was associated with a higher risk of developing new-onset HZ (adjusted OR = 3.79; 1.15-12.5). Multivariable conditional logistic regression models we used showed no association between COVID-19 vaccination and new-onset HZ among the SpA patients (OR = 1.46; 0.68-3.14).

COVID-19 Vaccine Effectiveness among Patients with Psoriatic Disease: A Population-Based Study.

Limited information is available on the effectiveness of COVID-19 vaccination in patients with psoriasis and psoriatic arthritis (psoriatic disease (PsD)). The objective of our research was to assess the effectiveness of mRNA COVID-19 vaccination in preventing SARS-CoV-2 positivity and severe infection in a cohort of patients with PsD and the association of immunosuppressants on SARS-CoV-2 infection-related outcomes from December 2020 to December 2021. Vaccine effectiveness was assessed in a matched nested case control study using conditional logistic regression adjusted for demographics, comorbidities and immunosuppressant use. Study outcomes included SARS-CoV-2 positivity and severe COVID-19 (moderate-to-severe COVID-19-related hospitalizations or death). At least one dose of mRNA COVID-19 vaccine was associated with reduced risk of SARS-CoV-2 positivity and severe COVID-19 (OR = 0.41 (95% CI, 0.38-0.43) and OR = 0.15 (95% CI, 0.11-0.20), respectively). A more significant effect was found among patients who received three vaccines doses compared with those who did not receive any (OR (for positive SARS-CoV-2) = 0.13 (95% CI, 0.12-0.15) and OR (for severe disease) = 0.02 (0.01-0.05)). Etanercept and methotrexate were associated with higher risk of SARS-CoV-2 positivity (1.58 (1.19-2.10), p = 0.001 and 1.25 (1.03-1.51), p = 0.03, respectively). In conclusion, our results show that mRNA COVID-19 vaccines are effective in reducing both infection and severe COVID-19-related outcomes.

The association between BNT162b2 vaccinations and incidence of immune-mediated comorbidities.

BACKGROUND: A large vaccination campaign was initiated worldwide in December 2020 in order to prevent infection with SARS-CoV-2 and severe Covid-19 disease. However, long-term adverse effects of vaccination remain unclear. Therefore, our objective was to examine the association between vaccination and the incidence of autoimmune diagnoses in the first year after vaccine uptake. METHODS: This retrospective cohort study based on Clalit Health Services (CHS) comprehensive database compared the rates of immune-mediated diagnoses among BNT162b2 vaccinated versus unvaccinated individuals. As a reference, a secondary cohort compared individuals infected with Sars-CoV-2 versus uninfected individuals. The minimum follow-up period was 4 months. The cohorts were divided into 4 age groups (12-17, 18-44, 45-64, 65 years or older). Multivariate Cox proportional hazard regression models were applied, followed by a correction for multiple comparisons using the False Discovery Rate (FDR) method, hence accounting for the investigation of multiple clinical outcomes. RESULTS: Increased risk for immune-mediated diagnoses following vaccination with BNT162b2 was observed for psoriasis in all age groups (HR 1.41-1.69), colitis among patients younger than 65 years (HR 1.38-1.93), vitiligo in patients aged 45-64 (HR 2.82, 95 %CI: 1.57-5.08) and for polymyalgia-rheumatica in patients aged 65 years or older (HR 2.12, 95 % CI: 1.3-3.47). In the reference cohort, patients who were infected by Covid-19 were at increased risk for fibromyalgia (HR 1.72, 95 % CI: 1.36-2.19 in individuals aged 18-44; HR 1.71, 95 % CI: 1.31-2.22 in individuals aged 45-64), and hypothyroidism (HR 1.54, 95 % CI: 1.15-2.07 in individuals aged 65 years or older). CONCLUSIONS: The BNT162b2 vaccine was associated with increased risk (though rare) for psoriasis, colitis and polymyalgia rheumatica. These findings should be considered as a part of the risk-benefit assessment when planning future vaccination programs for various population groups.

Epidemiological trends in psoriatic arthritis: a comprehensive population-based study.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic, potentially debilitating inflammatory arthritis often associated with psoriasis. Understanding the epidemiology of PsA across diverse populations can provide valuable insights into its global burden and the role of genetic and environmental factors. This study aimed to estimate PsA's temporal trends, prevalence, and incidence, while assessing variations in age, gender, and ethnicity in Israel from 2016 to 2022. METHODS: Data were sourced from the Clalit Health Services (CHS) database, covering over half of the Israeli population. Algorithm-based definitions for PsA and psoriasis cases were used. Demographic factors, including age, gender, socioeconomic status (SES), ethnicity, urban/rural residence, BMI, and smoking status, were analyzed. Standardized prevalence and incidence rates were calculated. Logistic regression analyses examined associations of sociodemographic variables with PsA. RESULTS: In 2022, the prevalence of PsA was 0.221%, with an incidence rate of 13.54 per 100,000 population. This prevalence has tripled since 2006, reflecting a rising trend in PsA over time. Females exhibited a higher prevalence (1.15; 95%CI 1.09-1.21), and PsA was more common in Jewish individuals (1.58; 95%CI 1.45-1.71) those with higher SES (1.4; 95% CI 1.31, 1.5), and those with obesity (2.17; 95%CI 2.04-2.31). CONCLUSIONS: This comprehensive population-based study pointed to an increase prevalence of PsA, emphasizing the rising healthcare demands and economic burden faced by this patient population. Further research is essential to delve into the factors driving these trends.

The risk factors for uveitis among psoriatic arthritis patients: a population-based cohort study.

OBJECTIVE: To assess the frequency of uveitis in patients with psoriatic arthritis (PsA) in the era of biologics and to identify risk factors associated with uveitis. METHODS: A retrospective matched cohort study was conducted within the database of a large healthcare provider. Newly diagnosed 6147 adult PsA patients between 2005 and 2020 were matched by the index date of PsA diagnosis, age, sex, and ethnicity to 23,999 randomly selected controls. This cohort was used to examine the association between PsA and uveitis. An additional analysis was conducted within the PsA group to identify uveitis risk factors, using two analytic approaches: a retrospective cohort study and a nested case-control study. RESULTS: Uveitis was diagnosed in 107 patients in the PsA group (1.7%) vs 187 (0.8%) patients in the control group (adjusted HR, 2.38, 95% CI 1.80-3.15, p<0.005) and was similar when the analysis was confined to patients without past uveitis. Uveitis was diagnosed more in females (2.1% vs 1.3%, HR 1.61, 95% CI 1.09-2.40, p<0.05), and was acute in all cases. Anterior uveitis was documented in 41.1% of the cases, 64.5% unilateral, and 9.3% bilateral. In the PsA group, using nested case control approach, only past uveitis [adjusted OR 136.4 (95% CI 27.38-679.88), p<0.005] and treatment with etanercept [adjusted OR 2.57 (95% CI 1.45-4.57), p=0.001] were independently associated with uveitis. Only one PsA patient with uveitis (out of 107) required systemic oral treatment with prednisone, while the rest of the patients were treated with topical glucocorticosteroids only. CONCLUSION: PsA is associated with increased risk of uveitis. Past uveitis and treatment with etanercept were associated with higher risk of uveitis. Key Points • Psoriatic arthritis (PsA) is a major risk factor for uveitis with hazard ratio of 2.38 compared to healthy individuals without PsA. • Among PsA patients, the past event of uveitis and treatment with etanercept are risk factors for uveitis. • Uveitis in patients treated with biologics for their PsA requires topical therapy only in most of the cases.

Estimating the economic burden of long-Covid: the additive cost of healthcare utilisation among COVID-19 recoverees in Israel.

INTRODUCTION: Postacute sequelae resulting from SARS-CoV-2 infections (LONG-COVID) have been reported. The resulting added economic burden from the perspective of healthcare organisations is not clear. Therefore, this study aims to evaluate the additive healthcare costs among COVID-19 recoverees, in a large community-dwelling general population, as incurred by an insurer-provider organisation over time. METHODS: In this historical cohort study, cost data from Clalit Health Services (CHS) were analysed. The primary endpoint was the direct cost incurred by CHS per month per person. Costs were measured for COVID-19 recoverees and matched controls, from January 2019 to January 2022. Difference in differences (DiDs) were calculated as the difference in mean monthly costs in cases and controls in the post-COVID-19 individual period, deducing their cost difference in a prepandemic 12 months baseline period. RESULTS: Among N=642 868 community-dwelling COVID-19 recoverees, 268 948 (40.8%) were 0-19 years old and 63 051 (9.6%) were 60 years or older. A total of 16 017 (2.5%) of recoverees had been hospitalised during the acute phase of the COVID-19 disease. Costs in cases and controls converged after 16 months from recovery. The mean monthly cost incurred by CHS per COVID-19 recoverees over up to 15 months (mean: 8.25) of post-COVID-19 follow-up was higher by 8.2% (US$8.2) compared with matched controls. The excess cost attributable to post-COVID-19 effects (DID) was 7.6% of the cost in controls (US$7.7 per patient per month). Both net and relative DIDs were substantially higher in patients who required hospitalisation during the acute phase of COVID-19 and in older adults. Excess in hospitalisations, primary care physicians and medical specialists' visits-related costs were observed. CONCLUSIONS: Long-term effects of SARS-CoV-2 infections translate into excess healthcare costs, months after recovery, hence requiring adjustments of funds allocation. These excess costs gradually diminish after recoveree, returning to baseline differences 16 months after recoveree.

Treatment Persistence of Apremilast Among Patients with Psoriatic Arthritis.

Introduction: Persistence in drug therapy reflects treatment effectiveness and tolerability. We aim to estimate the persistence of apremilast prescribed to patients with psoriatic arthritis (PsA) and to identify characteristics associated with treatment discontinuation in a real-world setting. Methods: Patients with PsA treated with apremilast from January 2016 were identified from a large health database and followed until medication stop date (using 3-months grace period), death or the end of observation period (June 2021). Demographic data, Charlson comorbidity index and concomitant and previous use of conventional and biologic DMARDs were extracted. The reasons for drug discontinuation were manually retrieved from patient charts. Time to discontinuation was estimated using survival analysis using Kaplan-Meier functions. Results: Overall, 568 PsA patients treated with apremilast were identified. The mean age was 55.3±14.0 years, of whom 332 (58.5%) were females, 38.4% were obese (BMI>30), 75.2% had a Charlson comorbidity index>1, 24.1% were on concomitant treatment with methotrexate and 72.4% were biologic naïve. The median persistent period was 6.1,95% CI (5.2-6.9) months in which only 16.9% remained persistent on apremilast. No difference was found with regard to age, sex, socioeconomic status, ethnicity and obesity between patients who were persistent compared to patients who discontinued apremilast. Concomitant treatment with methotrexate and prior history of biologic therapy did not affect drug persistency (log rank P=0.957 and 0.082, respectively). Causes for treatment discontinuation were due to lack of skin efficacy in 19.4%, lack of joint efficacy in 33.3%, combined skin and joint inefficacy at 2.3% and due to side effects in 24.1%. Conclusion: In this large observational retrospective cohort of patients treated with apremilast, a relatively low drug persistence was observed with 6-month and 1-year survival rates of 50.3% and 31.3%, respectively. Treatment discontinuation was mainly due to joint inefficacy, advocating for more studies for proper patient selection to assure treatment effectiveness and persistency.

Factors Associated with Using Telemedicine in the Primary Care Clinics during the COVID-19 Pandemic in Israel.

BACKGROUND: The COVID-19 pandemic generated an extraordinary need for telemedicine. OBJECTIVE: To identify the factors and multi-way interactions associated with telemedicine use in primary healthcare during the COVID-19 pandemic. METHODS: This population-based study included all members (2,722,773) aged ≥18 years of the largest healthcare organization in Israel who used primary care clinic services between 1 March 2020 and 31 December 2021. Individuals were classified as telemedicine users (≥1 phone/video visits or asynchronous encounters) or non-telemedicine users (only in-person encounter/s). RESULTS: Ethnicity was the most discriminative variable associated with telemedicine use, with 85% and 52% users among Jews and Arabs, respectively. Higher odds for telemedicine utilization were observed among women, residents of urban areas, those confined to home, individuals with high level of technology literacy, residents of the central area (in Jews only), young Jews, and older Arabs. Based on decision tree analysis, the segments of the population with the lowest telemedicine use were characterized by lower primary care needs and comorbidities, as well as low technology literacy. The proportion of telemedicine use in these groups was 56% and 27% in Jews and in Arabs, respectively. CONCLUSION: A proactive intervention program should be applied among populations who are less likely to use telemedicine in the primary care clinics, including Arabs, Jews who live in the distant periphery, and individuals with low technology literacy.

The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study.

BACKGROUND: Although the risk of cardiovascular disease has been discussed extensively in both psoriasis (PsO) and psoriatic arthritis (PsA), very few studies have addressed the occurrence of venous thromboembolic (VTE) events among PsO patients, and even fewer in PsA. Thus, our goal was to assess the association between PsA and VTE events using a large population-based database. METHODS: This retrospective cohort study includes all 5,275 patients with newly diagnosed PsA from the largest health care provider in Israel between January 2003 and December 2018. Identified PsA patients were matched by age, sex, ethnicity, and index date with 21,011 controls without PsA from the same database. Both groups were followed through June 30, 2019 for the occurrence of VTE event. Cox proportional hazard regression models were used to assess the association between PsA and VTE. RESULTS: PsA cohort consisted of 53.2% females with mean age of 51.7±15.4 Sixty-two patients (1.2%) were diagnosed with VTE in the PsA group and 176 patients (0.8%) in the control group (p=0.023, HR=1.40, 95% CI 1.05-1.87). However, there was no increased risk of VTE among PsA patients on multivariable analysis (p=0.16, HR=1.27, 95% CI 0.91-1.80). Within the PsA group, patients with VTE were more often of older age and with history of VTE. CONCLUSIONS: This study suggests that the increased risk of VTE in PsA patients appears to be related to the underlying comorbidities and not independently associated with PsA. Age and previous history of VTE were the only risk factors associated with increased risk of VTE in patients with PsA. Addressing VTE risk is recommended especially in the era of Janus kinase inhibitors.

The Association of Psoriatic Arthritis With All-cause Mortality and Leading Causes of Death in Psoriatic Arthritis.

OBJECTIVE: To examine the association between psoriatic arthritis (PsA) and all-cause mortality from a large population-based database. METHODS: Patients with PsA from the Clalit Health Services database were identified between 2003-2018 and matched to 4 controls by age, sex, ethnicity, and index date. Patient demographics, comorbidities, and treatments were extracted. Mortality data were obtained from the Israeli Notification of Death certificate. The proportionate mortality rate (PMR) of the leading causes of death was calculated and compared to that of the general population. Cox proportional hazard regression models were used to estimate the crude and the multivariate adjusted HR for the association between PsA and all-cause mortality and for factors associated with mortality within the PsA group. RESULTS: There were 5275 patients with PsA and 21,011 controls included and followed for 7.2 ± 4.4 years. The mean age was 51.7 ± 15.4 years, and 53% were females. Among patients with PsA, 38.2% were on biologics. Four hundred seventy-one (8.9%) patients died in the PsA group compared to 1668 (7.9%) in the control group. The crude HR for the association of PsA and all-cause mortality was 1.16 (95% CI 1.04-1.29) and 1.02 (95% CI 0.90-1.15) on multivariate analysis. Malignancy was the leading cause of death (26%), followed by ischemic heart disease (15.8%); this is in keeping with the leading causes of death in the general population. Older age, male sex, lower socioeconomic status, increased BMI, increased Charlson comorbidity index scores, and history of psoriasis or hospitalization in 1 year prior to entry were positive predictors for mortality. CONCLUSION: No clinically relevant increase in mortality rate was observed in patients with PsA, and specific PMRs were similar to those of the general population.

Vitamin D deficiency is associated with higher risks for SARS-CoV-2 infection and COVID-19 severity: a retrospective case-control study.

Robust evidence of whether vitamin D deficiency is associated with COVID-19 infection and its severity is still lacking. The aim of the study was to evaluate the association between vitamin D levels and the risks of SARS-CoV-2 infection and severe disease in those infected. A retrospective study was carried out among members of Clalit Health Services (CHS), the largest healthcare organization in Israel, between March 1 and October 31, 2020. We created two matched case-control groups of individuals for which vitamin D levels and body mass index (BMI) were available before the pandemic: group (A), in which 41,757 individuals with positive SARS-CoV-2 PCR tests were matched with 417,570 control individuals without evidence of infection, and group (B), in which 2533 patients hospitalized in severe condition for COVID-19 were matched with 2533 patients who were tested positive for SARS-CoV-2, but were not hospitalized. Conditional logistic models were fitted in each of the groups to assess the association between vitamin D levels and outcome. An inverse correlation was demonstrated between the level of vitamin D and the risks of SARS-CoV-2 infection and of severe disease in those infected. Patients with very low vitamin D levels (< 30 nmol/L) had the highest risks for SARS-CoV-2 infection and also for severe COVID-19 when infected-OR 1.246 [95% CI 1.210-1.304] and 1.513 [95% CI 1.230-1.861], respectively. In this large observational population study, we show a significant association between vitamin D deficiency and the risks of SARS-CoV-2 infection and of severe disease in those infected.

Identification of drugs associated with reduced severity of COVID-19 - a case-control study in a large population.

Background: Until coronavirus disease 2019 (COVID-19) drugs specifically developed to treat COVID-19 become more widely accessible, it is crucial to identify whether existing medications have a protective effect against severe disease. Toward this objective, we conducted a large population study in Clalit Health Services (CHS), the largest healthcare provider in Israel, insuring over 4.7 million members. Methods: Two case-control matched cohorts were assembled to assess which medications, acquired in the last month, decreased the risk of COVID-19 hospitalization. Case patients were adults aged 18 to 95 hospitalized for COVID-19. In the first cohort, five control patients, from the general population, were matched to each case (n=6202); in the second cohort, two non-hospitalized SARS-CoV-2 positive control patients were matched to each case (n=6919). The outcome measures for a medication were: odds ratio (OR) for hospitalization, 95% confidence interval (CI), and the p-value, using Fisher's exact test. False discovery rate was used to adjust for multiple testing. Results: Medications associated with most significantly reduced odds for COVID-19 hospitalization include: ubiquinone (OR=0.185, 95% CI [0.058 to 0.458], p<0.001), ezetimibe (OR=0.488, 95% CI [0.377 to 0.622], p<0.001), rosuvastatin (OR=0.673, 95% CI [0.596 to 0.758], p<0.001), flecainide (OR=0.301, 95% CI [0.118 to 0.641], p<0.001), and vitamin D (OR=0.869, 95% CI [0.792 to 0.954], p<0.003). Remarkably, acquisition of artificial tears, eye care wipes, and several ophthalmological products were also associated with decreased risk for hospitalization. Conclusions: Ubiquinone, ezetimibe, and rosuvastatin, all related to the cholesterol synthesis pathway were associated with reduced hospitalization risk. These findings point to a promising protective effect which should be further investigated in controlled, prospective studies. Funding: This research was supported in part by the Intramural Research Program of the National Institutes of Health, NCI.