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.
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.
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.
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.
Psoriatic arthritis (PsA) is a chronic, potentially debilitating inflammatory arthritis often associated with psoriasis. Understanding the epidemiology of PsA across diverse populations can provide ...valuable insights into its global burden and the role of genetic and environmental factors. This study aimed to estimate PsA's temporal trends, prevalence, and incidence, while assessing variations in age, gender, and ethnicity in Israel from 2016 to 2022.
Data were sourced from the Clalit Health Services (CHS) database, covering over half of the Israeli population. Algorithm-based definitions for PsA and psoriasis cases were used. Demographic factors, including age, gender, socioeconomic status (SES), ethnicity, urban/rural residence, BMI, and smoking status, were analyzed. Standardized prevalence and incidence rates were calculated. Logistic regression analyses examined associations of sociodemographic variables with PsA.
In 2022, the prevalence of PsA was 0.221%, with an incidence rate of 13.54 per 100,000 population. This prevalence has tripled since 2006, reflecting a rising trend in PsA over time. Females exhibited a higher prevalence (1.15; 95%CI 1.09-1.21), and PsA was more common in Jewish individuals (1.58; 95%CI 1.45-1.71) those with higher SES (1.4; 95% CI 1.31, 1.5), and those with obesity (2.17; 95%CI 2.04-2.31).
This comprehensive population-based study pointed to an increase prevalence of PsA, emphasizing the rising healthcare demands and economic burden faced by this patient population. Further research is essential to delve into the factors driving these trends.
Limited information is available on the effectiveness of COVID-19 vaccination in patients with psoriasis and psoriatic arthritis (psoriatic disease (PsD)). The objective of our research was to assess ...the effectiveness of mRNA COVID-19 vaccination in preventing SARS-CoV-2 positivity and severe infection in a cohort of patients with PsD and the association of immunosuppressants on SARS-CoV-2 infection-related outcomes from December 2020 to December 2021. Vaccine effectiveness was assessed in a matched nested case control study using conditional logistic regression adjusted for demographics, comorbidities and immunosuppressant use. Study outcomes included SARS-CoV-2 positivity and severe COVID-19 (moderate-to-severe COVID-19-related hospitalizations or death). At least one dose of mRNA COVID-19 vaccine was associated with reduced risk of SARS-CoV-2 positivity and severe COVID-19 (OR = 0.41 (95% CI, 0.38-0.43) and OR = 0.15 (95% CI, 0.11-0.20), respectively). A more significant effect was found among patients who received three vaccines doses compared with those who did not receive any (OR (for positive SARS-CoV-2) = 0.13 (95% CI, 0.12-0.15) and OR (for severe disease) = 0.02 (0.01-0.05)). Etanercept and methotrexate were associated with higher risk of SARS-CoV-2 positivity (1.58 (1.19-2.10),
= 0.001 and 1.25 (1.03-1.51),
= 0.03, respectively). In conclusion, our results show that mRNA COVID-19 vaccines are effective in reducing both infection and severe COVID-19-related outcomes.
The data on the risk of herpes zoster (HZ) in spondyloarthropathy (SpA) patients are sparse, especially regarding its association with the novel mRNA COVID-19 vaccines and immunosuppressants. We ...aimed to evaluate whether SpA diagnosis and/or immunosuppressant use affect HZ risk and the influence of mRNA COVID-19 vaccination. We assessed the association between SpA (psoriatic arthritis (PsA) and ankylosing spondylitis (AS)) diagnoses and HZ in a large population database with patients matched by age and sex to controls. We also assessed the association between the COVID-19 vaccine and new-onset HZ using two nested case-control studies, identifying all new HZ cases diagnosed from 1 January-31 December 2021 within the SpA and general population cohorts, matched randomly by sex, age and HZ index date to controls without HZ. Exposure to mRNA COVID-19 vaccination was ascertained in the 6 weeks prior to the index date both in cases and controls. In our results, the incidence rate of HZ was higher in PsA patients vs. the general population, at 1.03 vs. 0.64 per 100 person-years, respectively (adjusted HR = 1.55; 95%CI, 1.19-2.02). Within the SpA group, Jak-I treatment was associated with a higher risk of developing new-onset HZ (adjusted OR = 3.79; 1.15-12.5). Multivariable conditional logistic regression models we used showed no association between COVID-19 vaccination and new-onset HZ among the SpA patients (OR = 1.46; 0.68-3.14).
Background and Objectives
Previous small studies have proposed a higher incidence of acute mastoiditis in Israeli pediatric patients than in other Western countries. The aim of this study was to ...describe the incidence of acute mastoiditis and its epidemiological features over a decade, in order to identify variables that could possibly affect the incidence.
Methods
All admitted patients aged <18 years diagnosed with acute mastoiditis between 2008 and 2018 at Clalit Healthcare Services were identified and a database was generated.
Results
A total of 1189 and 1115 patients met the inclusion criteria, respectively. Acute mastoiditis diagnosis was confirmed in 95.2% of the patients. The incidence was 7.78 cases per 100,000 children‐years but was significantly higher in children under 2 years of age (average of 38.31 per 100,000 children‐years). No specific pattern was observed in the annualized incidence rate during the study period. Acute mastoiditis was significantly more common in children of Jewish descent than non‐Jewish (10.4 vs. 3.03 per 100,000 children‐years, P < 0.001) and of high socioeconomic status and is more common in the winter. The prevalence of household parental smoking (52%) was more than double that previously reported in the Israeli population.
Conclusions
A higher incidence of acute mastoiditis was observed in the Israeli population than in other reports. The age‐dependent rate was identified along with unique epidemiological features such as seasonality, higher incidence in patients of Jewish descent, or high socioeconomic status. Related parental smoking habits lend further support against the exposure of young children to household smoking.
Level of evidence: Individual retrospective cohort study.
This large‐scale retrospective study from Israel included 1189 cases of pediatric acute mastoiditis in a 10‐year period. Looking deeper into the population, we found a high incidence of 7.78 to 100,000 children which was shown to be much higher in children with specific epidemiologic features, such as age under 2 years and parental smoking.
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Concomitant use of direct oral anticoagulants (DOACs) and medications with inhibition/induction effect on P‐gp/CYP3A might increase risk of bleeding/treatment failure, respectively. We designed a ...nested case‐control study within a Clalit cohort of patients with atrial fibrillation (AF) and a cohort of patients with venous thromboembolism, new users of a DOAC (January 1, 2010 to August 24, 2020). Propensity scores were constructed from demographic/clinical characteristics, and medications at cohort entry. Each case of: (i) serious bleeding event; (ii) stroke/systemic emboli (SE) in patients with AF; (iii) recurrent thromboembolism in patients with thromboembolism, was matched by age, sex, length of follow‐up, year of cohort entry, DOAC type, and DOAC indication, to up to 20 controls. Within 89,284 patients with AF and venous thromboembolism and 126,302 patient‐years of follow‐up, there were 1,587 serious bleeding events. Risk of serious bleeding increased in association with concurrent prescription of P‐gp/CYP3A4 inhibitors. Specifically, higher bleeding risk was associated with dabigatran‐verapamil, rivaroxaban‐verapamil, and rivaroxaban‐amiodarone concurrent prescriptions: adjusted odds ratios (ORs) 2.29 (1.13–4.60), 2.18 (1.07–4.40), and 1.68 (1.14–2.49), respectively. There were 1,116 events of stroke/SE, in 79,302 DOAC‐treated patients with AF and 118,124 patient‐years of follow‐up. Concomitant use of phenytoin, carbamazepine, valproic acid, or levetiracetam was associated with risk for stroke/SE: adjusted OR 2.18 (1.55–3.10). Risk of recurrent venous thromboembolism could not be assessed due to the low number of cases. Concurrent prescriptions of dabigatran or rivaroxaban with verapamil, and of rivaroxaban with amiodarone, are associated with increased risk for serious bleeding. Higher risk for stroke/SE in patients with AF is associated with concurrent prescriptions of DOACs with phenytoin, carbamazepine, valproic acid, or levetiracetam.
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Development of autoantibodies following BNT162b2 mRNA COVID-19 vaccination and their association with disease flares in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and the ...general population: results of 1-year prospective follow-up study. We conducted a prospective study aimed at investigating the incidence of appearance of autoantibodies (antinuclear, antiphospholipid, and rheumatoid factor) in the sera of 463 adult patients with AIIRD compared to 55 controls from the general population prior to, and following the second and third vaccine doses, and at 1-year of follow-up. Pre- and post-vaccination disease activity indices and the association of autoantibodies with rheumatic disease flares and new onset AIIRD were examined. Autoantibody development of any type in AIIRD patients vs. the controls was 4.0% (vs. 6.7%,
= 0.423) following two vaccine doses and 7.6% (vs. 0%,
= 0.152) after three doses. There was no significant difference in sex, age, or disease-type among individuals with and without autoantibody development, regardless of the immunosuppressant use. More patients developed autoantibodies following the third than the second vaccine dose (
= 0.004). Disease flares occurred in 5.8% and 7.2% of AIIRD patients following second and third vaccine doses, respectively, with autoantibody production increasing the risk of flares following the second (
= 0.002) and third (
= 0.004) vaccine doses. BNT162b2 vaccination resulted in the development of autoantibodies in a minority of AIIRD patients and controls. Autoantibody development was associated with disease flares in patients, but no new-onset autoimmunity was observed.
The association of bronchiectasis with chronic rhinosinusitis (CRS) has been reported. However, apart from primary ciliary dyskinesia (PCD) and cystic fibrosis (CF), predisposing conditions have not ...been established. We aimed to define clinical and laboratory features that differentiate patients with bronchiectasis with upper airway symptoms (UASs) and without PCD from patients without UASs. We reviewed charts of adults with bronchiectasis, excluding CF and PCD. UASs were defined as nasal discharge most days of the year, sinusitis or nasal polyps. Laboratory data included IgG, total IgE, blood eosinophils, sputum bacteriology and lung function. A radiologist blinded to UAS presence scored bronchiectasis (Reiff score) and sino-nasal pathology (Lund-Mackay score). Of 197 patients, for the 70 (35%) with UASs, symptoms started earlier (34±25
46±24 years; p=0.001), disease duration was longer (median 24
12 years; p=0.027), exacerbations were more frequent (median 3
2 per year; p=0.14), and peripheral blood eosinophil (median 230
200 μL
; p=0.015) and total IgE (median 100
42 IU·mL
; p=0.085) levels were higher. The sinus computed tomography score was independently associated with exacerbations, with 1 point on the Lund-Mackay score associated with a 1.03-fold increase in the number of exacerbations per year (95% CI 1.0-1.05; p=0.004). These findings may implicate a higher disease burden in patients with UASs. We hypothesise that UASs precede and may in some cases lead to the development of bronchiectasis.
Airway clearance is a fundamental component of bronchiectasis care. Lung clearance index (LCI) is a measurement of ventilation inhomogeneity. Its responsiveness to long-term airway clearance is ...unknown. We aimed to compare two methods of daily airway clearance over 4 weeks: autogenic drainage (AD) and oscillating positive airway pressure (oPEP), and to determine effects of airway clearance on LCI and clinical outcomes.
Adults with bronchiectasis naive to airway clearance were randomised to daily airway clearance with either AD or oPEP. Difference in LCI as primary outcome, spirometry, sputum volume and purulence, and quality of life were at randomisation and after 4 weeks of airway clearance.
51 patients (32 women and 19 men, mean age 66.2±12.8 years) were randomised and 49 completed the study (25 AD and 24 oPEP). The LCI and forced expiratory volume in 1 s did not change between visits between groups (difference between groups 0.02), nor between visits in either group. Sputum quantity decreased in 12 out of 24 (50%) of the oPEP group, and in six out of 25 (24%) of the AD group (p=0.044). The "treatment burden" worsened or was unchanged in 70% of participants randomised to AD and 55% randomised to oPEP (p=0.038).
Sputum quantity decreased in more participants randomised to oPEP group after 1 month of daily airway clearance, with a better treatment burden. The effects of 4 weeks of airway clearance on LCI were not significant in either treatment group.
It has been shown that the population average blood glucose level of diabetes patients shows seasonal variation, with higher levels in the winter than summer. However, seasonality in the population ...averages could be due to a tendency in the individual to seasonal variation, or alternatively due to occasional high winter readings (spiking), with different individuals showing this increase in different winters. A method was developed to rule out spiking as the dominant pattern underlying the seasonal variation in the population averages. Three years of data from three community-serving laboratories in Israel were retrieved. Diabetes patients (N = 3243) with a blood glucose result every winter and summer over the study period were selected. For each individual, the following were calculated: seasonal average glucose for all winters and summers over the period of study (2006-2009), winter-summer difference for each adjacent winter-summer pair, and average of these five differences, an index of the degree of spikiness in the pattern of the six seasonal levels, and number of times out of five that each winter-summer difference was positive. Seasonal population averages were examined. The distribution of the individual's differences between adjacent seasons (winter minus summer) was examined and compared between subgroups. Seasonal population averages were reexamined in groups divided according to the index of the degree of spikiness in the individual's glucose pattern over the series of seasons. Seasonal population averages showed higher winter than summer levels. The overall median winter-summer difference on the individual level was 8 mg dL (0.4 mmol L). In 16.9% (95% confidence interval CI: 15.6-18.2%) of the population, all five winter-summer differences were positive versus 3.6% (95% CI: 3.0-4.2%) where all five winter-summer differences were negative. Seasonal variation in the population averages was not attenuated in the group having the lowest spikiness index; comparison of the distributions of the winter-summer differences in the high-, medium-, and low-spikiness groups showed no significant difference (p = .213). Therefore, seasonality in the population average blood glucose in diabetes patients is not just the result of occasional high measurements in different individuals in different winters, but presumably reflects a general periodic tendency in individuals for winter glucose levels to be higher than summer levels. (Author correspondence: anneke@clalit.org.il)
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