A historical cohort study with 27,754 individuals on the association between meat consumption and gastrointestinal tract and colorectal cancer incidence.

In order to explore the association between meat consumption and gastrointestinal/colorectal cancer (CRC) risk and to estimate the Israeli population attributable fraction (PAF), we conducted a collaborative historical cohort study using the individual participant data of seven nutritional studies from the past 6 decades. We included healthy adult men and women who underwent a nutritional interview. Dietary assessment data, using food-frequency or 24-h recall questionnaires, were harmonized. The study file was linked to the National Cancer and death registries. Among 27,754 participants, 1216 (4.4%) were diagnosed with gastrointestinal cancers and 839 (3.0%) with CRC by the end of 2016. Using meta-analysis methods applied to Cox proportional hazard models (adjusted for daily energy intake, sex, age, ethnic origin, education and smoking),100 g/day increments in beef, red meat and poultry consumption, and 50 g/day increment in processed meat consumption were associated with hazard ratios (HRs) and 95% confidence intervals of 1.46 (1.06-2.02), 1.15 (0.87-1.52), 1.06 (0.89-1.26), and 0.93 (0.76-1.12), respectively, for CRC. Similar results were obtained for gastrointestinal cancer, although red meat consumption reached statistical significance (HR = 1.27; 95%CI: 1.02-1.58). The PAFs associated with a reduction to a maximum of 50 g/day in the consumption of red meat were 2.7% (95%CI: -1.9 to 12.0) and 5.2% (0.3-13.9) for CRC and gastrointestinal cancers, respectively. Reduction of beef consumption to a maximum of 50 g/day will result in a CRC PAF reduction of 7.5% (0.7%-24.3%). While beef consumption was associated with gastrointestinal/CRC excess risk, poultry consumption was not. A substantial part of processed meat consumption in Israel is processed poultry, perhaps explaining the lack of association with CRC.

Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel.

BACKGROUND: Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance. METHODS: We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition. We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons. RESULTS: Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal. The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46). As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20). The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637. CONCLUSIONS: The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.

Phosphodiesterase-5 Inhibitors and Dementia Risk: A Real-World Study.

INTRODUCTION: Biological and scarce epidemiological evidence suggested that phosphodiesterase-5 inhibitors (PDE5i) might reduce dementia risk. We aimed to examine the association between PDE5i and dementia using real-world data. METHODS: Two retrospective cohorts within the database of Clalit, the largest healthcare provider in Israel (2005-2023), were studied. The first cohort included new daily users, older than 50 years of age, of low-dose tadalafil, prescribed for benign prostatic hypertrophy (BPH), propensity-score matched to new-users of alpha-1 blockers, and analyzed using 2-year lag time. The second cohort included patients with erectile dysfunction, with/without any PDE5i treatment, using time-dependent analysis. Individuals in the cohorts were followed through May 2023 for the occurrence of dementia. RESULTS: The first cohort included 5,204 tadalafil initiators propensity-score matched to 18,565 alpha-1 blockers initiators. There was no association between tadalafil use and dementia risk, HR = 0.99 (95% CI: 0.88-1.12), p = 0.927. Similar results were obtained in a competing risk analysis, and in a sensitivity analysis in which we restricted the cohort to patients older than 60 years at cohort entry. The second cohort of 133,336 patients with erectile dysfunction included new users and nonusers of any PDE5i. In a mean follow-up of 7.9 years, 8,631 patients were newly diagnosed with dementia. In a time-dependent multivariable analysis, PDE5i use was not associated with reduced dementia risk, HR = 0.95 (95% CI: 0.86-1.04). Results were not changed in sensitivity analyses (patients older than 60 years or stratification by PDE5i type). CONCLUSION: This study suggests that the use of PDE5 inhibitors is not associated with decreased risk of dementia.

Efficacy, adherence and persistence of various glucagon-like peptide-1 agonists: nationwide real-life data.

AIM: The management of type 2 diabetes mellitus has advanced in the last two decades since the introduction of glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, multiple factors may interfere with achieving better glycaemic control. This study evaluated the differences between various GLP-1RAs in efficacy, adherence and persistence. MATERIALS AND METHODS: We conducted a retrospective cohort study using the electronic medical database from Clalit Health Services. Adults with type 2 diabetes mellitus who purchased any GLP-1RA between 2009 and 2021 were included. The Index Date was defined as the date of the first purchase of any GLP-1RA. We evaluated the adherence, persistence and glycaemic control after GLP-1RAs initiation. Baseline glycaemic and post-treatment glycaemic controls were analysed. RESULTS: In total, 70 654 patients were included. The mean age was 11.7 ± 60.4, and 51% were females. A significant reduction in glycated haemoglobin (HbA1c) was observed in all patients who received GLP-1RAs. However, the percentage of changes in the HbA1c was higher among weekly GLP-1RA than daily initiators (14.6% vs. 10.2%, p < 0.001). The proportion of subjects with any decrease in HbA1c was higher among the once-weekly compared with the daily dose (82.4% vs. 74.7%) and mainly patients initiated semaglutide or dulaglutide, with 16.0% and 14.7% reduction. The frequency of good adherence (the proportion of days covered ≥80%) was significantly higher among the weekly group odds ratio = 1.25 (95% confidence interval 1.21-1.28). Good adherence was reported in older age, female gender, Jewish ethnicity and high socio-economic status (p < 0.001). CONCLUSIONS: Weekly GLP-1RAs initiators were more adherent, persistent to therapy and achieved better glycaemic control. Epidemiological variables might play a role in achieving this goal.

Acute post-procedural inducibility is a poor predictor of clinical outcomes in high-risk patients (PAINESD > 17) undergoing scar-related ventricular tachycardia ablation.

AIMS: Ventricular tachycardia (VT) non-inducibility in response to programmed ventricular stimulation (PVS) is a widely used procedural endpoint for VT ablation despite inconclusive evidence with respect to clinical outcomes in high-risk patients. The aim is to determine the utility of acute post-ablation VT inducibility as a predictor of VT recurrence, mortality, or mortality equivalent in high-risk patients. METHODS AND RESULTS: We conducted a retrospective analysis of high-risk patients (defined as PAINESD > 17) who underwent scar-related VT ablation at our institution between July 2010 and July 2022. Patients' response to PVS (post-procedure) was categorized into three groups: Group A, no clinical VT or VT with cycle length > 240 ms inducible; Group B, only non-clinical VT with cycle length > 240 ms induced; and Group C, all other outcomes (including cases where no PVS was performed). The combined primary endpoint included death, durable left ventricular assist device placement, and cardiac transplant (Cox analysis). Ventricular tachycardia recurrence was considered a secondary endpoint (competing risk analysis). Of the 1677 VT ablation cases, 123 cases met the inclusion criteria for analysis. During a 19-month median follow-up time (interquartile range 4-43 months), 82 (66.7%) patients experienced the composite primary endpoint. There was no difference between Groups A and C with respect to the primary [hazard ratio (HR) = 1.21 (0.94-1.57), P = 0.145] or secondary [HR = 1.18 (0.91-1.54), P = 0.210] outcomes. These findings persisted after multivariate adjustments. The size of Group B (n = 13) did not permit meaningful statistical analysis. CONCLUSION: The results of post-ablation PVS do not significantly correlate with long-term outcomes in high-risk (PAINESD > 17) VT ablation patients.

Cryoballoon pulmonary vein isolation versus radiofrequency ablation of the pulmonary veins and left atrial posterior wall: Patient-reported outcomes.

BACKGROUND: Data are lacking on patient-reported outcomes (PRO) following cryoballoon ablation (CBA) versus radiofrequency ablation (RFA). We sought to evaluate QoL and clinical outcomes of cryoballoon pulmonary vein isolation only (CRYO-PVI-ONLY) versus RFA with PVI and posterior wall isolation (RF-PVI+PWI) in a large prospective PRO registry. METHODS: Patients who underwent AF ablation (2013-2016) at our institution were enrolled in an automated, prospectively maintained PRO registry. CRYO-PVI-ONLY patients were matched (1:1) with RF-PVI+PWI patients based on age, gender, and type of AF (paroxysmal vs. persistent). QoL and clinical outcomes were assessed using PRO surveys at baseline and at 1-year. The atrial fibrillation symptom severity scale (AFSSS) was the measure for QoL. Additionally, we assessed patient-reported clinical improvement, arrhythmia recurrence, and AF burden (as indicated by AF frequency and duration scores). RESULTS: A total of 296 patients were included (148 in each group, 72% paroxysmal). By PRO, a significant improvement in QoL was observed in the overall study population and was comparable between CRYO-PVI-ONLY and RF-PVI+PWI (baseline median AFSSS of 11.5 and 11; reduced to 2 and 4 at 1 year, respectively; p = 0.44). Similarly, the proportion of patients who reported improvement in their overall QoL and AF related symptoms was high and similar between the study groups [92% (CRYO-PVI-ONLY) vs. 92.8% (RF-PVI+PWI); p = 0.88]. Arrhythmia recurrence was significantly more common in the CRYO-PVI-ONLY group (39.7%) compared to RF-PVI+PWI (27.7 %); p = 0.03. Comparable results were observed in paroxysmal and persistent AF. CONCLUSION: CRYO-PVI-ONLY and RF-PVI+PWI resulted in comparable improvements in patient reported outcomes including QoL and AF burden; with RF-PVI+PWI being more effective at reducing recurrences.

Methodology and challenges for harmonization of nutritional data from seven historical studies.

BACKGROUND: Collection of detailed dietary data is labor intensive and expensive, harmonization of existing data sets has been proposed as an effective tool for research questions in which individual studies are underpowered. METHODS: In this paper, we describe the methodology used to retrospectively harmonize nutritional data from multiple sources, based on the individual participant data of all available studies, which collected nutritional data in Israel between 1963 and 2014. This collaboration was established in order to study the association of red and processed meat with colorectal cancer. Two types of nutritional questionnaires, the Food Frequency Questionnaires (FFQ) and the 24-h dietary recall (24HR recall), and different food composition tables, were used by the participating studies. The main exposure of interest included type of meat (total meat, red meat, and poultry) and level of processing. RESULTS: A total of 29,560 Israeli men and women were enrolled. In studies using FFQ,the weighted mean intakes of total, red, processed meat, and poultry were 95, 27, 37 and 58 gr/day and 92, 25, 10, and 66 gr/day in studies using 24HR recall, respectively.. Despite several methodological challenges, we successfully harmonized nutritional data from the different studies. CONCLUSIONS: This paper emphasizes the significance and feasibility of harmonization of previously collected nutritional data, offering an opportunity to examine associations between a range of dietary exposures and the outcome of interest, while minimizing costs and time in epidemiological studies.

Subacute Thyroiditis Following COVID-19 and COVID-19 Vaccination.

OBJECTIVE: COVID-19 infection and immunizations have been implicated in developing a range of thyroid diseases, including subacute thyroiditis (SAT). This study aimed to evaluate the association between COVID-19 infection and/or COVID-19 vaccination with SAT. METHODS: A population of 3 million adults insured by Clalit Health Services was evaluated from March 2020 to September 2022. Patients with a new diagnosis of SAT were identified and matched in a 1:10 ratio to a control group. Each control was assigned an index date that was identical to that of their matched case, defined as the date of SAT diagnosis. Multivariate conditional logistic regression models were used to evaluate the association between COVID-19 infection, vaccine, and thyroiditis. RESULTS: A total of 3221 patients with SAT were matched with 32 210 controls. Rates of COVID-19 vaccination (first, second, or third dose) and COVID-19 infection were evaluated prior to the date of SAT diagnosis (disease group) or index date (control group) to detect a possible association. No difference was detected between the groups in relation to vaccinations at the 30 days, 60 days, and 90 days of time points (P = .880/0.335/0.174, respectively). No difference was found between groups in relation to COVID-19 infection at these time points (P = .735/0.362/0.956, respectively). There was higher use of medications for the treatment of thyroiditis, including nonsteroidal anti-inflammatory drugs (28.6% vs 7.9%, P < .01), steroids (10.3% vs 1.8%, P < .01), and beta-blockers (18.3% vs 5.4%, P < .01). CONCLUSION: Based on this large population study, no association was found between COVID-19 infection and/or the COVID-19 vaccine and SAT.

Risk factors for recurrent acute mastoiditis in pediatric patients: a registry-based cohort study.

OBJECTIVE: To describe characteristics of pediatric patients with recurrent acute mastoiditis, and to identify risk factors for this condition. STUDY DESIGN: A retrospective cohort study. SETTING: Data based on electronic medical records of the largest Health Maintenance Organization in Israel. METHODS: Children hospitalized due to acute mastoiditis during the years 2008-2018 were identified, and their diagnosis was verified. Patients with recurrent acute mastoiditis were identified and grouped, and their characteristics were outlined and compared to those of the original group to identify risk factors for recurrence. RESULTS: During the 11-year period, a total of 1115 cases of children hospitalized due to acute mastoiditis were identified with a weighted incidence rate of 7.8/100,000. Of this group, 57 patients were diagnosed with recurrence following a full clinical recovery. The incidence proportion of recurrent acute mastoiditis was 5.1% (57/1115), male-to-female ratio was 27:30, 73.4% were younger than 24 months, the median period from the first episode was 3.4 months (IQR 2.0;10.0), and 82.5% of the patients (n = 47) had a single recurrence, whereas 18.5% (n = 10) had two recurrences or more. Mastoidectomy and swelling over the mastoid area during the first episode were identified as the main risk factors for recurrent mastoiditis HR = 4.7 [(2.7-8.2), p < 0.001] and HR = 2.55 [(1.4-4.8), p = 0.003], respectively. Mastoidectomy was the only independent significant risk factor for recurrence in a multivariate analysis. CONCLUSIONS: Mastoidectomy and swelling over the mastoid area during the first episode of acute mastoiditis were found strongly related independent risk factor for future recurrent episodes of acute mastoiditis.

CHA2DS2-VASc Score as a Predictor of Adverse Outcomes after Ischemic Stroke in Patients without Atrial Fibrillation.

BACKGROUND: Ischemic stroke is associated with increased risk of morbidity and mortality in future vascular events. OBJECTIVES: To investigate whether CHA2DS2-VASc scores aid in risk stratification of middle-aged patients without atrial fibrillation (AF) experiencing ischemic stroke. METHODS: We analyzed data of 2628 patients, aged 40-65 years with no known AF who presented with acute ischemic stroke between January 2020 and February 2022. We explored the association between CHA2DS2-VASc scores categorized by subgroups (score 2-3, 4-5, or 6-7) with major adverse cardiac and cerebrovascular events (MACCE) including recurrent stroke, myocardial infarction, coronary revascularization, or all-cause death during a median follow-up of 19.9 months. RESULTS: Mean age was 57 years (30% women); half were defined as low socioeconomic status. Co-morbidities included hypertension, diabetes, obesity, and smoking in 40-60% of the patients. The incidence rate of MACCE per 100 person-years was 6.7, 12.2, and 21.2 in those with score 2-3, 4-5, and 6-7, respectively. In a multivariate cox regression model, compared to patients with score 2-3 (reference group), those with score 4-5 and 6-7 had an adjusted hazard ratio (95% confidence interval [95%CI]) for MACCE of 1.74 (95%CI 1.41-2.14) and 2.87 (95%CI 2.10-3.93), respectively. The discriminative capacity of CHA2DS2-VASc score for overall MACCE was modest (area under curve 0.63; 95%CI 0.60-0.66), although better for myocardial infarction 0.69 (95% CI 0.61-0.77). CONCLUSIONS: CHA2DS2-VASc score may predict future MACCE in middle-aged patients with ischemic stroke and no history of AF.

Effectiveness of Evusheld in Immunocompromised Patients: Propensity Score-Matched Analysis.

BACKGROUND: Tixagevimab and cilgavimab, a combined monoclonal antibody (Evusheld), was granted emergency use authorization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preexposure prophylaxis in individuals with immunocompromising conditions. In this study we used population-based real-world data to evaluate the effectiveness of Evusheld in immunocompromised patients. METHODS: Using the computerized database of the largest healthcare provider in Israel, we identified all adult immunocompromised patients who were eligible to receive Evusheld (150 mg tixagevimab and 150 mg cilgavimab) on 15 February 2022. Patients with a documentation of a prior SARS-CoV-2 infection were excluded. A total of 703 patients who received Evusheld were propensity score matched, using a ratio of 1:4, with 2812 patients who had not received Evusheld (control group). Patients were followed through 30 June 2022 for up to 90 days for the first documentation of SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19)-related hospitalization. RESULTS: Overall, 72 patients in the Evusheld group and 377 patients in the control group had SARS-CoV-2 infection, reflecting an incidence rate of 4.18 and 5.64 per 100 person-months, respectively. The hazard ratios were 0.75 (95% confidence interval [CI]: .58-.96) for SARS-CoV-2 infection and 0.41 (95% CI: .19-.89) for COVID-19-related hospitalization in the Evusheld group compared to the control group. The magnitude of relative risk reduction of each outcome was greater in nonobese patients (P for interaction = .020 and .045, respectively). CONCLUSIONS: This study suggests that Evusheld is effective in reducing the risk of SARS-CoV-2 infection and COVID-19 hospitalization in immunocompromised patients. The effectiveness of this dose appears to be greater in nonobese patients.

Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients.

BACKGROUND: Paxlovid was granted an Emergency Use Authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19), based on the interim analysis of the Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial. Paxlovid effectiveness needs to be assessed in a noncontrolled setting. In this study we used population-based real-world data to evaluate the effectiveness of Paxlovid. METHODS: The database of the largest healthcare provider in Israel was used to identify all adults aged 18 years or older with first-ever positive test for severe acute respiratory syndrome coronavirus 2 between January and February 2022, who were at high risk for severe COVID-19 and had no contraindications for Paxlovid use. Patients were included irrespective of their COVID-19 vaccination status. Cox hazard regression was used to estimate the 28-day hazard ratio (HR) for severe COVID-19 or mortality with Paxlovid examined as time-dependent variable. RESULTS: Overall, 180 351 eligible patients were included; of these, only 4737 (2.6%) were treated with Paxlovid, and 135 482 (75.1%) had adequate COVID-19 vaccination status. Both Paxlovid and adequate COVID-19 vaccination status were associated with significant decrease in the rate of severe COVID-19 or mortality with adjusted HRs of 0.54 (95% confidence interval [CI], .39-.75) and 0.20 (95% CI, .17-.22), respectively. Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease (interaction P < .05 for all). No significant interaction was detected between Paxlovid treatment and COVID-19 vaccination status. CONCLUSIONS: This study suggests that in the era of Omicron and in real-life settings, Paxlovid is highly effective in reducing the risk of severe COVID-19 or mortality.

Effectiveness of Molnupiravir in High-Risk Patients: A Propensity Score Matched Analysis.

BACKGROUND: Molnupiravir was granted emergency use authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19). In this study, we used population-based real-world data to evaluate the effectiveness of molnupiravir. METHODS: The database of the largest healthcare provider in Israel was used to identify all adults with first-ever positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) performed in the community during January-February 2022, who were at high risk for severe COVID-19, and had no contraindications for molnupiravir use. Patients were included regardless of SARS-CoV-2 vaccination status. A total of 2661 patients who received molnupiravir were propensity score matched with 2661 patients who have not received molnupiravir (control group). Patients were followed through 10 March 2022 for up to 28 days for the first occurrence of the composite severe COVID-19 or COVID-19-specific mortality. RESULTS: The composite outcome occurred in 50 patients in the molnupiravir group and 60 patients in the control group. Molnupiravir was associated with a nonsignificant reduced risk of the composite outcome: hazard ratio, 0.83 (95% confidence interval, .57-1.21). However, subgroup analyses showed that molnupiravir was associated with a significant decrease in the risk of the composite outcome in older patients 0.54 (0.34-0.86), in females 0.41 (0.22-0.77), and in patients with inadequate COVID-19 vaccination 0.45 (0.25-0.82). The results were similar when each component of the composite outcome was examined separately. CONCLUSIONS: This study suggests that in the era of Omicron and in real-life setting, molnupiravir might be effective in reducing the risk of severe COVID-19 and COVID-19-related mortality, particularly in specific subgroups.

Rationale and design of a randomized study comparing the Watchman FLX device to DOACs in patients with atrial fibrillation.

BACKGROUND: Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a nonpharmacologic alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacologic strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy. STUDY DESIGN: A total of 3,000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months postimplant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary end points will be evaluated at 3 years: (1) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for noninferiority, and (2) nonprocedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant nonmajor bleeding) tested for superiority in the device arm against DOACs. The third primary noninferiority end point is the composite of ischemic stroke and systemic embolism at 5 years. Secondary end points include 3- and 5-year rates of (1) ISTH-defined major bleeding and (2) the composite of cardiovascular death, all stroke, systemic embolism, and nonprocedural ISTH bleeding. CONCLUSIONS: This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF. CLINICAL TRIAL REGISTRATION: NCT04394546.

Anticoagulation after pulmonary vein isolation for atrial fibrillation: Associations with CHA2DS2-VASc score, sex, and rhythm.

Guidelines recommend using the CHA2DS2-VASc score to determine anticoagulation decisions in atrial fibrillation (AF) patients, including those who undergo pulmonary vein isolation (PVI), however this may not consistently occur in the real-world setting because of other clinical factors. We sought to evaluate the anticoagulation prescription rates patterns in AF patients 1 year PVI at our institution. Consecutive AF patients undergoing PVI in our prospective registry during 2014-2018 who were alive at 1-year post-PVI were studied. Anticoagulation prescription rates at this time-point were adjudicated, and correlated to CHA2DS2-VASc score, sex, and heart rhythm status at 1 year. Amongst 4596 patients undergoing PVI, mean age was 64.2 ± 10.0 years, 1328 (28.9%) were female, and based on CHA2DS2-VASc score anticoagulation was not indicated, can be considered and indicated in 872 (19.0%), 1183 (25.7%), and 2541 (55.3%) patients, respectively. At 1-year after PVI, 3504 (76.2%) patients were on anticoagulation, and 792 (17.2%) had recurrence of AF. Anticoagulation was continued in over half of AF patients without classic CHA2DS2-VASc indication particularly in those with AF recurrence and women, while they were mildly under-prescribed in those with indication, especially for those without AF recurrence and men. In a large real world cohort of patients after PVI, anticoagulation prescription is not solely depending on the CHA2DS2-VASc score and sex, but also heart rhythm status and other clinical or imaging factors.

Impact of obesity on catheter ablation of atrial fibrillation: Patient characteristics, procedural complications, outcomes, and quality of life.

INTRODUCTION: Obesity is a well-known risk factor for atrial fibrillation (AF). We aim to evaluate the effect of baseline obesity on procedural complications, AF recurrence, and symptoms following catheter ablation (CA). METHODS: All consecutive patients undergoing AF ablation (2013-2021) at our center were enrolled in a prospective registry. The study included all consecutive patients with available data on body mass index (BMI). Primary endpoint was AF recurrence based on electrocardiographic documentation. Patients were categorized into five groups according to their baseline BMI. Patients survey at baseline and at follow-up were used to calculate AF symptom severity score (AFSS) as well as AF burden (mean of AF duration score and AF frequency score; scale 0: no AF to 10: continuous and 9 frequencies/durations in between). Patients were scheduled for follow-up visits with 12-lead electrocardiogram at 3, 6, and 12 months after ablation, and every 6 months thereafter. RESULTS: A total of 5841 patients were included (17% normal weight, 34% overweight, 27% Class I, 13% Class II, and 9% Class III obesity). Major procedural complications were low (1.5%) among all BMI subgroups. At 3 years AF recurrence was the highest in Class III obesity patients (48%) followed by Class II (43%), whereas Class I, normal, and overweight had similar results with lower recurrence (35%). In multivariable analyses, Class III obesity (BMI ≥ 40) was independently associated with increased risk for AF recurrence (hazard ratio, 1.30; confidence interval, 1.06-1.60; p = .01), whereas other groups had similar risk in comparison to normal weight. Baseline AFSS was lowest in normal weight, and highest in Obesity-III, median (interquartile range) 10 (5-16) versus 15 (10-21). In all groups, CA resulted in a significant improvement in their AFSS with a similar magnitude among the groups. At follow-up, AF burden was minimal and did not differ significantly between the groups. CONCLUSION: AF ablation is safe with a low complication rate across all BMI groups. Morbid obesity (BMI ≥ 40) was significantly associated with reduced AF ablation success. However, ablation resulted in improvement in QoL including reduction of the AFSS, and AF burden regardless of BMI.

Impact of redo ablation for atrial fibrillation on patient-reported outcomes and quality of life.

INTRODUCTION: Catheter ablation for atrial fibrillation (AF) is frequently used for the purpose of rhythm control and improved quality of life (QoL). Although success rates are high, a significant proportion of patients require redo ablation. Data are scarce on patient-centered outcomes and QoL in patients undergoing redo AF ablation. We aimed to assess QoL and clinical outcomes using a large prospectively maintained patient-reported outcomes (PRO) registry. METHODS: All patients undergoing redo AF ablation (2013-2016) at our center were enrolled in a prospective registry for outcomes and assessed for QoL using automated PRO surveys (baseline, 3 and 6 months after ablation, every 6 months thereafter). Data were collected over 3 years of follow-up. The atrial fibrillation symptom severity scale (AFSSS) was used as the main measure for QoL. Additional variables included patient-reported improvement, AF burden, and AF-related healthcare utilization including emergency room (ER) visits and hospitalizations. RESULTS: A total of 848 patients were included (28% females, mean age 63.8, 51% persistent AF). By automated PRO, significant improvement in QoL was noted (baseline median AFSSS of 12 [5-18] and ranged between 2 and 4 on subsequent assessments; p < .0001), with ≥70%of patients reported remarkable improvement in their AF-related symptoms. The proportion of patients in AF at the time of baseline survey was 36%, and this decreased to <8% across all time points during follow-up (p < .0001). AF burden was significantly reduced (including frequency and duration of episodes; p < .0001), with an associated decrease in healthcare utilization after 6 months from the time of ablation (including ER visits and hospitalizations; p < .0001). The proportion of patients on anticoagulants or antiarrhythmics decreased on follow-up across all time points (p < .0001 for all variables). CONCLUSION: Most patients derive significant QoL benefit from redo AF ablation; with reduction of both AF burden and healthcare utilization.

Long-Term Efficacy and Safety of Left Atrial Appendage Occlusion (LAAO) vs Direct Oral Anticoagulation (DOAC) in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Prevention of stroke by anticoagulation is essential in patients with Atrial fibrillation (AF); with direct oral anticoagulants (DOACs) being preferred over warfarin in most patients. The Long-term efficacy and safety of DOACs vs. Left Atrial Appendage Occlusion (LAAO) remain unknown. Methods: Electronic databases (PubMed, Embase, Scopus) were searched from inception to February 10th, 2021. The primary endpoint was cardiovascular mortality. Secondary outcomes included incidence of ischemic stroke/transient ischemic attack (TIA) and systemicembolism. The safety endpoint was clinically relevant bleeding (a composite of major or minor clinically relevant bleeding). Results: A total of three studies with 3039 participants (LAAO = 1465; DOACs = 1574) were included. Mean age was 74.2 and 75.3 years in the LAAO and DOAC group respectively. Average follow-up period was 2 years. There was no difference in terms of cardiac mortality (RR 0.90, 95% CI 0.40-2.03; p = 0.81), ischemic stroke/TIA (RR 1.15, 95% CI 0.80-1.65; p = 0.46; I 2 = 0) and clinically significant bleeding (RR 0.77, 95% CI 0.50-1.17; p = 0.22; I 2 = 69) between the groups. Conclusions: Among patients with AF, LAAO was comparable to DOACs with similar efficacy and safety profiles.

The relationship between patients' kidney stone type and demographics in Israel: analysis of 10 K patients.

PURPOSE: To analyze urinary stone composition in Israel and assess the effects of key demographic parameters (gender, age, socioeconomic status, ethnicity, medical history and geographic region) on stone composition. METHODS: A retrospective review was conducted of stone analysis of 10,633 patients from an HMO Israeli database analyzed by a central laboratory from 2014 to 2019 and subjected to Fourier-transform infrared spectroscopy. Associations between stone composition and different demographic parameters were determined using the Chi-square test. RESULTS: Calcium oxalate (CaOx) monohydrate accounted for 51.9% of the stones. Of the total sample, 5776 stones had one single component (54%), whereas 4857 (46%) had mixed components. Men had a higher frequency of CaOx stones (89.6% vs. 85.6%), whereas women had a higher frequency of calcium phosphate, infection, and cystine stones (27.2%, 17.7%, and 0.9% vs. 17.2%, 7.5%, and 0.5%, respectively). Cystine stones were more abundant in Arabs (1.2% vs. 0.5% in the Jewish population). Lower socioeconomic status was associated with a higher prevalence of calcium phosphate, uric acid, and infection stones and a lower prevalence of CaOx stones. Uric acid stones were associated with medical conditions such as diabetes, hypertension, ischemic heart disease, and obesity (28.3%, 24.9%, 25.7%, and 22.6% vs. 9.6%, 8.4%, 12.3%, and 10.3%, respectively). CONCLUSIONS: Stone types were highly influenced by patients' demographics. COM was the most common stone component in either pure or complex form. UA stone prevalence was found to increase with age and was associated with medical conditions such as diabetes, hypertension, ischemic heart disease, and obesity.

Association between COVID-19 vaccination and myasthenia gravis: A population-based, nested case-control study.

BACKGROUND: Existing data regarding the link between COVID-19 vaccine and myasthenia gravis (MG) are scarce. We aimed to assess the association between Pfizer-BioNTech vaccine with both new-onset MG and MG exacerbation. METHODS: For the first aim, we conducted a nested case-control study in a cohort of 3,052,467 adults, without a diagnosis of MG, from the largest healthcare provider in Israel. Subjects were followed from January 1, 2021 until June 30, 2022 for the occurrence of MG. Ten randomly selected controls were matched to each case of new-onset MG on age and sex. For the second aim, a nested case-control study was conducted in a cohort of 1446 MG patients. Four randomly selected MG patients (controls) were matched to each case of MG exacerbation. Exposure to COVID-19 vaccine in the prior 4 weeks was assessed in cases and controls. RESULTS: Overall, 332 patients had new-onset MG and were matched with 3320 controls. Multivariable conditional logistic regression models showed that the odds ratio (OR) for new-onset MG, associated with COVID-19 vaccine, was 1.14 (95% CI 0.73-1.78). The results were consistent in sensitivity analysis that used more stringent criteria to define MG. Overall, 62 patients with MG exacerbation were matched to 248 MG controls. The multivariable OR for MG exacerbation, associated with COVID-19 vaccine, was 1.35 (95% CI 0.37-4.89). All results were similar when the prior exposure to COVID-19 vaccine was extended to 8 weeks. CONCLUSION: This study suggests that Pfizer-BioNTech vaccine is not associated with increased risk of new-onset nor exacerbation of MG.