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.

Effectiveness of Bariatric Metabolic Surgery versus Glucagon-Like Peptide-1 Receptor Agonists for prevention of Congestive Heart Failure.

Comparative evidence for the effects of bariatric metabolic surgery (BMS) and glucagon-like peptide-1 receptor agonists (GLP1-RA) on cardiovascular outcomes is limited. Here, in an observational, retrospective cohort study, we compared the incidence of Congestive Heart Failure (CHF) in adults living with obesity and diabetes without history of CHF (primary CHF) treated with BMS versus GLP-1RA. The population cohort comprised members of Clalit Health Services with no prior history of ischemic heart disease, ischemic stroke, or CHF. During the time period of 2008 - 2021, patients who underwent their first BMS were matched 1:1 with patients who initiated treatment with GLP-1RA, based on clinical characteristics. The study included 2,205 matched pairs of patients (64.5% female), followed for a median of 6.6 years and up to 12 years. Primary incidence of CHF occurred in 26 (1.2%) BMS patients and in 90 GLP1-RA patients (4.1%), adjusted HR: 0.43, 95% CI: 0.27-0.68. Further adjustment for weight reduction did not significantly diminish this association, HR adjusted for weight reduction: 0.48, 95% CI 0.28-0.82, indicating that the differential effect was not mediated through the relative advantage of BMS in maximal weight reduction. In this study, BMS was associated with a stronger reduction in primary incidence of CHF compared to treatment with GLP1-RA. With the increasing use of highly potent next-generation GLP1-RAs, further comparative long-term studies are warranted.

Evaluation of Telephone Visits in Primary Care: Satisfaction of Pediatricians and Family Physicians and Their Perceptions of Quality of Care and Safety.

Telehealth has accelerated since the outbreak of the COVID-19 virus. As telephone visits become more common, it is important to examine the challenges involved in using this modality of care. In this study, we examined family physicians' and pediatricians' perceptions regarding three aspects of the use of telephone visits: quality of care, safety of care, and physicians' satisfaction. A total of 342 family physicians and pediatricians responded to an online survey. Respondents were asked to rate their degree of agreement with 17 statements inquiring about quality, safety, and satisfaction with telephone visits on a Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). This was followed by in-depth interviews between January and April 2023 with 26 physicians. Participants expressed satisfaction (3.66 ± 0.80) with the use of telephone visits and lower assessments of safety (3.03 ± 0.76) and quality (2.27 ± 0.76) of care using the telephone modality. Eighty percent of the respondents think combining a face-to-face visit with a telephone visit is recommended, and 51% noted that the inability to examine patients closely affects and impedes a physician's decision making. Most interviewees indicated that telephone visits are safe only with former patients they had already seen in the clinic. The findings shed light on the perceptions of family physicians and pediatricians regarding telephone visits. The lower assessments of quality and safety compared to the assessment of satisfaction underscore the need for careful use of telephone visits in healthcare. A proper and balanced selection of patients, implementing technological upgrades to the modality, and performing patient education practices are recommended.

Trends in the Incidence of Cardiovascular Diagnoses and Procedures over the Years 2012-2021 in Israel: The Impact of the COVID-19 Pandemic.

Prior studies found reduced incidences of cardiovascular diagnoses and treatments in the initial phase of the COVID-19 pandemic. However, these studies included a limited number of outcomes and did not consider pre-pandemic trends. This study aimed to describe trends in the incidence of cardiovascular diagnoses and treatments over the years 2012-2021 in Israel and to compare the two years of the COVID-19 period with the preceding 8 years. In this retrospective, population-based study, carried out within Clalit Health Services, the incidence rates of cardiovascular outcomes were calculated for individuals aged ≥ 25 (~2.7 million adults per year) during the first (Y1, 3/2020-2/2021) and second (Y2, 3/2021-2/2022) years of COVID-19 and the 8 years prior (3/2012-2/2020). Declines were observed in Y1 compared to 2019 in all diagnoses and treatments: STEMI (-16.3%; 95% CI: -16.6, -16.1), non-STEMI (-16.4%; -16.6, -16.2), AF (-14.1%; -14.2, -14.0), CHF (-7.8%; -7.9, -7.7), CVA (-5.0%; -5.0, -4.9), catheterization (-64.7%; -65.2, -64.2), CABG (-77.7%; -79.2, -76.2), ablation (-21.2%; -22.0, -20.4), pacemaker implantation (-39.3%; -40.7, -37.9), and defibrillator insertion (-12.5%; -13.1, -12.0). Compared with expected rates based on pre-pandemic trends, observed rates were within expected ranges (CHF, CVA, and ablation), less than expected (STEMI, non-STEMI, AF, catheterization, CABG, and pacemaker insertion), or more than expected (defibrillator insertion). In Y2, STEMI, catheterization, and CABG returned to expected rates; non-STEMI and AF were lower than expected; and CHF, CVA, ablation, and pacemaker and defibrillator implantations were higher than expected. Several cardiovascular diagnoses and treatment trends were interrupted by COVID-19. The long-term consequences of these changes should be considered by health policymakers.

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.

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.

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.

Time-varying association of acute and post-acute COVID-19 with new-onset diabetes mellitus among hospitalized and non-hospitalized patients.

INTRODUCTION: Previous studies have shown disruption of glycometabolic control and new diabetes mellitus (DM) diagnosis among patients with COVID-19. It is still unclear how the association of COVID-19 and new-onset DM may be modified by disease severity or vary over time, during acute and post-acute phases. RESEARCH DESIGN AND METHODS: In this retrospective matched cohort study, 157 936 patients with COVID-19 (aged ≥25 years, diagnosis date between March 01, 2020 and August 31, 2021) were compared with individuals without COVID-19, separately for non-hospitalized, hospitalized, and severe hospitalized patients. Stratified Cox proportional hazards models, with changing baseline time (starting at the date of COVID-19 diagnosis, and at 1, 2, 3, and 4 months afterwards), were used to evaluate the occurrence of new DM in relation to COVID-19 infection in different time frames-from each landmark date until end of study. RESULTS: During mean follow-up time of 10.9 months, there were 1145 (0.72%) new diagnoses of DM compared with 1013 (0.64%) in the individuals without COVID-19 (p=0.004). Non-hospitalized patients with COVID-19 were not at higher risk of new DM neither during the acute phase nor afterward. Hospitalized patients with COVID-19 had a higher risk of developing DM, with the highest risk among severe hospitalized patients. This risk among hospitalized patients was highest in the acute phase (HR 2.47 (95% CI 1.86 to 3.29)), attenuated over time, but remained significant at 4-month landmark analysis (HR 1.60 (95% CI 1.12 to 2.29)). CONCLUSIONS: Acute and post-acute COVID-19 were associated with new DM only among hospitalized patients, with the highest risk among those hospitalized with severe disease. Those patients should be followed and monitored post-discharge for new DM. Patients who were not hospitalized did not have higher risk of new-onset DM.

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.

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.

Trends in the Volume and Types of Primary Care Visits during the Two Years of the COVID-19 Pandemic in Israel.

BACKGROUND: The outbreak of the COVID-19 pandemic led to a decrease in primary health care in-person visits and a simultaneous increase in virtual encounters. OBJECTIVE: To quantify the change in the total volume of primary care visits and mix of visit types during the two years of the pandemic in Israel. DESIGN: Cross-sectional study. PARTICIPANTS: All primary care visits by members of the largest healthcare organization in Israel, during three one-year periods: the pre-COVID-19 year (March 2019-February 2020), the first year of COVID-19 (March 2020-February 2021), and the second year of COVID-19 (March 2021-February 2022). MAIN MEASURES: Total volume of primary care visits and mix of visit types. RESULTS: More than 112 million primary care visits were included in the study. The total visit rate per 1000 members did not change significantly between the pre-COVID year (19) and the first COVID year (19.8), but was 21% higher in the second COVID-19 year (23). The rate of in-person visits per 1000 members decreased from 12.0 in the pre-COVID year to 7.7 in the first COVID year and then increased to 9.6 in the second. The rate of phone visits and asynchronous communication increased from 0.7 and 6.3, respectively, in the pre-COVID year, to 4.1 and 8, respectively, in the first COVID year, and remained unchanged in the second. There was substantial variation across age groups and sectors in the adoption of virtual platforms. CONCLUSIONS: The rapid introduction of virtual encounters in primary care tended to displace in-person visits in the first year of the pandemic, but they appear to have been additive in the second. This transition should be monitored, with the goal of ensuring appropriate planning efforts and resource allocation to deal with the potential added burden on medical staff. Efforts should be invested in encouraging the use of virtual platforms in patient groups that currently underutilize it, such as minorities.

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.

The impact of COVID-19 pandemic on emergency department visits and associated mortality during 14 months of the pandemic in Israel.

BACKGROUND: A substantial drop in emergency department (ED) visit volume was previously demonstrated at the onset of the COVID-19 pandemic. OBJECTIVE: To examine changes in the number of non-COVID adult ED visits and their associated 30-day mortality during 14 months of the pandemic in Israel. METHODS: This is a retrospective cohort study including 1,285,270 adult ED visits between 1st March, 2018 and 30th April, 2021 to the internal and surgical EDS in eight general hospitals of the largest healthcare organization in Israel. The 14 months of the pandemic period (March 2020-April 2021) were divided into seven periods according to dates of the three lockdowns. Exposure to each of these periods was compared to the parallel period during the two previous years. March 2020-April 2021 was compared to the parallel periods in 2018 and 2019. RESULTS: During the pandemic period, the largest decline in ED visits (44.6% and 50.9% for internal and surgical EDs, respectively) and the highest excess 30-day mortality following an ED visit (internal EDs Adjusted OR (ORadj), 1.49; 95% CI, 1.34-1.66 and surgical EDs: ORadj 1.50; CI, 1.16-1.94) were 95%, observed during the first lockdown. Both gradually levelled-off subsequently until near-normalization was reached in March-April 2021 for both parameters. CONCLUSIONS: A substantial decline in non-COVID ED visits and excess mortality at the beginning of the pandemic, are probably the results of social distancing restrictions alongside patients' fear of exposure to COVID-19, which gradually moderated thereafter, until near normalization was reached after 14 months. Gradual return to pre-pandemic ED utilization patterns were noticed as the population and the healthcare system acclimatize to life alongside COVID.

Continuous Decline in Myocardial Infarction and Heart Failure Hospitalizations during the First 12 Months of the COVID-19 Pandemic in Israel.

BACKGROUND: A decline in cardiovascular hospitalizations was observed during the initial phases of the COVID-19 pandemic. We examine the continuous effect of the COVID-19 pandemic in reducing cardiovascular hospitalization and associated mortality rates during the first year of the pandemic in Israel. METHODS: We conduct a retrospective cohort study using the data of Clalit Health Services, the largest healthcare organization in Israel. We divide the Corona year into six periods (three lockdowns and three post-lockdowns) and compare the incidence rates of cardiovascular hospitalizations and 30-day all-cause mortality during each period to the previous three years. RESULTS: The number of non-STEMI hospitalizations during the first year of the pandemic was 13.7% lower than the average of the previous three years (95% CI 11-17%); STEMI hospitalizations were 15.7% lower (95% CI 13-19%); CHF (Congestive heart failure) hospitalizations were 23.9% lower (95%, CI 21-27%). No significant differences in 30-day all-cause mortality rates were observed among AMI (acute myocardial infarction) patients during most of the periods, whereas the annual 30-day all-cause mortality rate among CHF patients was 23% higher. CONCLUSIONS: AMI and CHF hospitalizations were significantly lower during the first year of the pandemic relative to 2017-9. Mortality rates were higher in the case of CHF patients but not in the case of AMI patients, possibly due to a change in the clinical acuity of patients arriving at the hospitals. We conclude that targeted public health messaging should be implemented together with proactive monitoring, in order to identify residual disability in patients who may have received non-optimal treatment during the pandemic.

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.

Change in Hospitalizations and 30-Day Mortality of Patients With Acute Myocardial Infarction During the First COVID-19 Lockdown - A Pure Social Isolation Effect?

BACKGROUND: The COVID-19 pandemic has had diverse effects on population health and psychology in relation to non-COVID-19 diseases, as well as on COVID-19 infection. Fewer patients with acute myocardial infarction (AMI) sought medical attention during the first lockdown of the pandemic. METHODS AND RESULTS: We conducted a retrospective cohort study of Clalit Health Services patients treated in multiple hospitals for AMI. We examined the numbers and characteristics of the patients and 30-day mortality during three 5-week phases of the first wave of the COVID-19 pandemic in Israel: pre-lockdown (N = 702), lockdown (N = 584), and lockdown-lift (N = 669). We compared data for the same period in 2018 and 2019. We stratified the data by ST-elevation myocardial infarction (STEMI) and non-STEMI. AMI hospitalizations during the lockdown were 17% lower than in the pre-lockdown period (rate ratio-0.83, 95% CI 0.74-0.93), and 22% and 31% lower than in the corresponding periods in 2018 and 2019, respectively. The reduction was mainly attributed to non-STEMI hospitalizations (26% lower than the pre-lockdown period in 2020). Hospitalizations due to both STEMI and non-STEMI were moderately reduced during the post-lockdown period compared to the corresponding periods in 2018 and 2019. Thirty-day mortality rate was similar for all the periods assessed. CONCLUSIONS: The number of hospitalized patients with AMI during the first COVID-19 lockdown and post-lockdown periods was significantly reduced, without significant changes in 30-day mortality rates.

Adapting to change: Clalit's response to the COVID-19 pandemic.

The COVID-19 pandemic is the most significant global health event of the past century. The profound and unexpected changes that it brought about have forced healthcare organizations to make far-reaching adjustments to accommodate the new reality. With the outbreak of the pandemic in Israel and the understanding of its consequences, Clalit Health Services (Clalit), the largest healthcare organization in Israel, rapidly mobilized in order to provide the best response possible from the perspective of both its patients and its employees. In the short term, four designated workgroups were established just days into the pandemic. Their task was to prepare operational work plans to achieve the following goals: providing the best possible treatment for COVID patients; maintaining the level of care for non-COVID patients; protecting healthcare personnel without compromising their competence and level of functioning; and beginning the process of post-crisis planning. In the context of the long term, and with the understanding that the changes in healthcare brought about by the COVID-19 pandemic would be long-lasting and irreversible, and would act as a catalyst in Clalit's preparations for the future, Clalit has carried out the called-for modifications in its organizational strategy. This was based on the need to shift service and treatment foci from the hospitals to the community and the patient's home and his cellular device, by means of strengthening Clalit's strategic abilities to become more proactive, more digital and more home-based. In this article, we present a survey of Clalit's preparations for the new reality in the short and medium terms, as well as the leveraging of insights gained during the first wave of the pandemic, with goal of revising Clalit's long-term strategic plan. We conclude and point out the organizational abilities required for optimal response to future large-scale emergencies: The ability to quickly identify the need for change, respond quickly while harnessing the various parts of the organization in order to provide an agile and adaptive response, and facilitate long-term planning activity in parallel to providing an operational response in the short and medium terms.

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.

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

BACKGROUND: Until 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. Towards 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 18-95 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.

Statin Therapy for Primary Prevention in the Elderly and Its Association with New-Onset Diabetes, Cardiovascular Events, and All-Cause Mortality.

PURPOSE: This study assessed associations of the use of statins for primary prevention with cardiovascular outcomes among adults ages ≥70 years. METHODS: In a retrospective population-based cohort study, new users of statins without cardiovascular disease or diabetes mellitus were stratified by ages ≥70 years and <70 years. Using a time-dependent approach, adherence to statins was evaluated according to the proportion of days covered: <25%, 25%-50%, 50%-75%, and ≥75%. We assessed associations of statin therapy with increased risk of new-onset diabetes mellitus and with decreased risks of major adverse cardiovascular events and all-cause mortality. RESULTS: Of 42,767 new users of statins, 5970 (14%) were ages ≥70 years. The incident rates of major adverse cardiovascular events, all-cause mortality, and new-onset diabetes mellitus in the highest to lowest proportion of days covered categories were 16.9%, 16.7%, and 9.4% and 6.3%, 1.7%, and 9.4%, respectively. For the older group, the adjusted hazard ratios of major adverse cardiovascular events and mortality were significantly decreased for the highest adherence group (proportion of days covered ≥75%): 0.71 (0.57-0.88) and 0.68 (0.54-0.84), respectively. The respective hazard ratios were less favorable for the younger group: 0.80 (0.68-0.93) and 0.74 (0.58-1.03). The risk of new-onset diabetes mellitus was increased for the younger but not the older group. CONCLUSIONS: Statin use for primary prevention was associated with cardiovascular benefit in adults ages ≥70 years without a significant risk for the development of diabetes. These data may support the use of statin therapy for primary prevention in the elderly.