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.

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. 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. 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 non-users 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). This study suggests that use of PDE5 inhibitors is not associated with decreased risk of dementia.

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.

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 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.

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.

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.

Association between Vaccination with the BNT162b2 mRNA Coronavirus Disease 2019 Vaccine and Noninfectious Uveitis: A Population-Based Study.

PURPOSE: To assess the association between BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine and the risk of active noninfectious uveitis (NIU). DESIGN: Retrospective, population-based study. PARTICIPANTS: Two million six hundred two thousand five hundred fifty-seven people who received the first vaccine dose between December 20, 2020, and April 30, 2021, and 2 441 719 people who received the second vaccine dose between January 10, 2021, and April 30, 2021. METHODS: Events of active NIU were included if they occurred within 21 days after either vaccine dose. Active NIU was defined as newly active or worsening ocular inflammation requiring initiation or increase in local or systemic corticosteroids. Observed cases were compared with the expected number, based on the experience of the population in 2019. MAIN OUTCOME MEASURES: Age- and sex-adjusted standardized incidence ratios (SIRs) and attributable risks after BNT126b2 vaccination. RESULTS: Overall, 100 and 88 events of active NIU were recorded within 21 days after the first and second vaccine doses, respectively. Using the experience of the population in 2019 as a reference, after the first dose, the estimated age- and sex-adjusted SIR was 1.41 (95% confidence interval [CI], 1.15-1.71) along with a 21-day attributable risk of 1.12 cases per 100 000 vaccinees. After the second dose, the SIR was 1.31 (95% CI, 1.05-1.62), with an estimated attributable risk of 0.86 cases per 100 000 vaccinees. Anterior uveitis was the most common site of inflammation, occurring in 90.96% of eyes, and idiopathic uveitis was the most common cause (56.38%). CONCLUSIONS: This study suggests that the BNT162b2 mRNA COVID-19 vaccine may be associated with an increased risk of active NIU. However, considering the small effect size and study limitations, this study does not provide proof for a cause-and-effect relationship. The small estimated attributable risks suggest that the impact on public health is relatively minor.

Outcomes of atrial fibrillation ablation in patients with or without silent pulmonary veins from prior ablation procedure.

INTRODUCTION: Pulmonary venous (PV) electrical recovery underlies most arrhythmia recurrences after atrial fibrillation (AF) ablation. Little is known about procedural profiles and outcomes of patients with electrically silent PVs upon redo ablation for AF. METHODS: In a prospectively maintained registry, we enrolled 838 consecutive patients (2013-2016) undergoing redo ablation procedures. Ablation procedures targeted the PVs, the PV antra, and non-PV sites at operators' discretion. Procedural profiles and clinical outcomes were assessed. The primary outcome was freedom from AF after a 3-month blanking period. The secondary outcome was improvement in quality of life. RESULTS: Most patients undergoing redo AF ablation (n = 684, 82%) had PV reconnection while the remaining 154 (18%) had electrically silent PVs. Patients with recurrent AF and electrically silent PVs were older (66 vs. 64 years, p = .02), had more prior ablation procedures (median 2 IQR 1-3 vs 1 IQR 1-2 p = .001), were more likely to have non-paroxysmal AF (62% vs. 49%, p = .004) and atrial flutter (48% vs. 29%, p = .001) and had significantly larger left atrial volumes (89 vs. 81 ml, p = .003). Patients with silent PVs underwent a more extensive non-PV ablation strategies with antral extension of prior ablation sets in addition to ablation of the roof, appendage, inferior to the right PVs, peri-mitral flutter lines, cavotricuspid isthmus lines and ablation in the coronary sinus. Upon one year of follow-up, patients with electrically silent PVs were less likely to remain free from recurrent atrial arrhythmias (64% vs. 76%, p = .008). Regardless of PV reconnection status, redo ablation resulted in improvement in quality of life. CONCLUSION: Rhythm control with extensive ablation allowed maintenance of sinus rhythm in about two thirds of patients with silent PVs during redo AF ablation procedures. Regardless of PV reconnection status, redo ablation resulted in improvement in quality of life. This remains a challenging group of patients, highlighting the need to better understand non-PV mediated AF.

Bayesian network meta-analysis comparing cryoablation, radiofrequency ablation, and antiarrhythmic drugs as initial therapies for atrial fibrillation.

BACKGROUND: Antiarrhythmic drugs (AADs) and catheter ablation are first line treatments of paroxysmal atrial fibrillation (PAF), however, there exists a paucity of data regarding the potential benefit of different catheter ablation technologies versus AADs as an early rhythm strategy. OBJECTIVE: To assess the safety and efficacy of cryoablation versus radiofrequency ablation (RFA) versus AADs as a first line therapy of PAF. METHODS: MEDLINE, Embase, Scopus and CENTRAL were searched to retrieve randomized clinical trials (RCTs) comparing cryoablation, RFA or AADs to one another as first line therapies for atrial fibrillation (AF). The primary outcome was overall freedom from arrhythmia recurrence (AF, atrial flutter [AFL], atrial tachycardia). Secondary outcomes included freedom from symptomatic arrhythmia recurrence, hospitalization, and serious adverse events. A random-effects Bayesian network meta-analysis was used to calculate odds ratios (OR) and 95% credible intervals (CrI). RESULTS: Six RCTs (N = 1212) met the inclusion criteria (605 AADs, 365 Cryoablation, and 245 RFA). Compared with AADs, overall recurrence was reduced with RFA (OR: 0.31; 95% CrI: 0.10-0.71) and cryoablation (OR: 0.39; 95% CrI: 0.16-1.00). Comparing ablation (cryoablation and RFA) with AADs in respect to freedom from symptomatic AF recurrence, neither cryoablation (OR: 0.35; 95% CrI: 0.06-1.96) nor RFA (OR: 0.34; 95% CrI: 0.07-1.27) resulted in statistically significant reductions individually compared to AADs, though pooled ablation with both technologies showed lower odds of arrhythmia recurrence (OR: 0.35; 95% CrI: 0.13-0.79). In terms of serious adverse events rates, neither cryoablation (OR: 0.77; 95% CrI: 0.44-1.39) nor RFA (OR: 1.45; 95% CrI: 0.67-3.23) were significantly different to AADs. RFA resulted in a statistically significant reduction in hospitalizations compared to AAD (OR: 0.08; 95% CrI: 0.01-0.99), whereas cryoablation did not (OR: 0.77; 95% CrI: 0.44-1.39). The surface under the cumulative ranking curve showed RFA to be the most effective treatment at reducing overall rates of recurrence, symptomatic recurrence and hospitalizations; whereas cryoablation was most likely to reduce serious adverse events. CONCLUSION: Cryoablation and RFA are both effective and safe first line therapies for AF compared to AADs, with RFA being the most effective at reducing recurrences.

Efficacy and Safety of Catheter Ablation vs Antiarrhythmic Drugs as Initial Therapy for Management of Symptomatic Paroxysmal Atrial Fibrillation: A Meta-Analysis.

BACKGROUND: Catheter ablation is an effective treatment for atrial fibrillation (AF), primarily performed in patients who fail antiarrhythmic drugs. Whether early catheter ablation, as first-line therapy, is associated with improved clinical outcomes remains unclear. METHODS: Electronic databases (PubMed, Scopus, Embase) were searched until March 28th, 2021. Randomized controlled trials (RCTs) compared catheter ablation vs antiarrhythmic drug therapy as first-line therapy were included. The primary outcome of interest was the first documented recurrence of any atrial tachyarrhythmia (symptomatic or asymptomatic; AF, atrial flutter, and atrial tachycardia). Secondary outcomes included symptomatic atrial tachyarrhythmia (AF, atrial flutter, and atrial tachycardia) and serious adverse events. Unadjusted risk ratios (RR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance considered if the confidence interval (CI) excludes one and p < 0.05. RESULTS: A total of six RCTs with 1212 patients (Ablation n = 609; Antiarrhythmic n = 603) were included. Follow- up period ranged from 1-2 years. Patients who underwent ablation were less likely to experience any recurrent atrial tachyarrhythmia when compared to patients receiving antiarrhythmic drugs (RR 0.63; 95% CI 0.55-0.73; p < 0.00001). Symptomatic atrial tachyarrhythmia was also lower in the ablation arm (RR 0.53; 95% CI 0.32-0.87; p = 0.01). No statistically significant differences were noted for overall any type of adverse events (RR 0.93; 95% CI 0.68-1.27; p = 0.64) and cardiovascular adverse events (RR 0.90; 95% CI 0.56-1.44; p = 0.65) respectively. CONCLUSIONS: Catheter ablation, as first-line therapy, was associated with a significantly lower rate of tachyarrhythmia recurrence compared to conventional antiarrhythmic drugs, with a similar adverse effect risk profile. These findings support a catheter ablation strategy as first-line therapy among patients with symptomatic paroxysmal atrial fibrillation.

Exploring the effectiveness of a patient-tailored integrative oncology program on emotional distress during chemotherapy for localized cancer.

STUDY OBJECTIVE: There is a need to explore how patient-tailored integrative oncology (IO) programs reduce emotional distress. This study set out to bridge the IO research gap between non-specific, quality of life-related and specific emotional-related concerns in chemotherapy-treated patients. METHODS: This pragmatic, prospective and preference-controlled study examined patients attending an integrative-physician consultation and weekly IO treatments during adjuvant/neo-adjuvant chemotherapy for localized cancer. Patients choosing to attend ≥4 IO sessions (highly adherent to integrative care, AIC) were compared to low AIC patients using the ESAS (Edmonton Symptom Assessment Scale) anxiety, depression and sleep; and the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) emotional functioning scale, at baseline, 6 and 12 weeks. Emotional distress was assessed by ESAS anxiety and depression, considered as the primary study outcomes. RESULTS: Of 439 participants, 260 (59%) were high-AIC and 179 low-AIC, both with similar baseline demographic and cancer-related characteristics. At 6 weeks, high-AIC patients reported greater improvement on ESAS sleep (p = 0.044); within-group improvement on ESAS anxiety and; and EORTC emotional functioning. Compared with low-AIC, high-AIC patients showed greater improvement on ESAS depression (p = 0.022) and sleep (p = 0.015) in those with high baseline ESAS anxiety scores (≥7); and ESAS anxiety (p = 0.049) for patients moderately anxious (4-6) at baseline. CONCLUSIONS: High-AIC was associated with significantly reduced anxiety, depression and sleep severity at 6 weeks, especially those with high-to-moderate baseline anxiety levels. These findings reduce the research gap, suggesting specific emotional-related effects of IO.