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Objective: To compare the Respiratory Syncytial Virus (RSV) hospitalization burden among 29-34 weeks gestational age (wGA) preterm infants between seasons with and without routine palivizumab prophylaxis, by utilizing the 2021 off-season RSV surge., Methods: This multi-center retrospective study was conducted in 11 medical centers across Israel. We included infants > 1 year-old, with wGA data, hospitalized with RSV infection from November 2017-August 2021. National palivizumab compliance data were collected separately. We compared two periods: in-season (November-March) with routine palivizumab prophylaxis as the reference, and off-season (April-October) without prophylaxis as the primary risk factor. The primary outcome was the proportion of RSV hospitalizations in 29-34 wGA infants relative to total RSV admissions, calculated separately for each period. Secondary outcomes included clinical severity parameters., Results: A total of 3296 infants were admitted during the RSV in-season, and 1044 during the off-season. National palivizumab compliance among eligible infants during the in-season study years was 91%-95%. The proportion of 29-34 wGA infants was significantly higher during the off-season compared to the in-season period (7% vs. 2.1%, p < 0.001). In a multivariable logistic regression model, the odds of hospitalization for 29-34 wGA preemies were 2.6 times higher during the off-season compared to the in-season (95% CI: 1.8-3.9, p < 0.001), independent of demographic covariates. Clinical severity was similar between the two periods., Conclusions: Our results revealed a significantly higher proportion of 29-34 wGA infants hospitalized during seasons without palivizumab prophylaxis compared to seasons with palivizumab prophylaxis. These findings highlight the importance of including 29-34 wGA infants into future RSV immunoprophylaxis recommendations., (© 2025 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: The best first-line monotherapy for hypertension remains uncertain, as current guidelines suggest that thiazides, angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs) are appropriate in the absence of specific comorbidities. We aimed to compare the outcomes of first-line antihypertensive classes in a real-life setting with a long follow-up period., Methods: This nationwide retrospective new-user cohort study included patients insured by the largest health maintenance organization in Israel. We included patients with a new diagnosis of hypertension between 2008 and 2021 who initiated treatment with a single first-line drug for hypertension. Outcomes were assessed with and without propensity score matching for confounding factors. The primary composite outcome was the first occurrence of myocardial infarction (MI), acute coronary syndrome (ACS), stroke, or heart failure (HF)., Results: A total of 97,639 patients initiated antihypertensive treatment with a single drug as first-line therapy. The most commonly prescribed class was ACEis/ARBs (66,717, 68.3%), followed by CCBs (15,922, 16.3%), beta-blockers (BBs, 12,869, 13.2%), and thiazides (2,131, 2.2%). For the primary outcome, the hazard ratios (HRs) for BBs, CCBs, and ACEis/ARBs were 1.44 (95% CI 1.25-1.66), 1.10 (95% CI 0.96-1.27), and 1.13 (95% CI 0.99-1.29), respectively, when compared to thiazides., Conclusion: When initiating pharmacotherapy for hypertension with a single drug, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers were associated with similar risk of MI, ACS, stroke, or HF when compared to thiazides, while beta-blockers were associated with increased risk., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To understand whether parental smoking influences adeno/tonsillectomy rates in their offspring. A population-based case-control study using data from Clalit Health Services. Israeli children aged 0-18 years who underwent adeno/tonsillectomy between 2003 and 2022 were 1:3 matched with same-age, sex, and ethnicity controls. Parental smoking habits were linked to their children's files. Conditional logistic regression models estimated odds ratios (ORs) for adeno/tonsillectomy associated with parental smoking, adjusting for socioeconomic status. We identified 11,184 children who underwent surgery and 33,552 controls (mean age ± SD 4.10 ± 2.50 years). The likelihood of undergoing adeno/tonsillectomy was significantly higher for children with either one smoking parent (OR 1.14; 95%CI 1.09-1.19) or both (OR 1.53; 95%CI 1.39-1.68) compared to children of non-smokers. The association was more evident for tonsillectomy alone, with an OR of 3.20 (95%CI 2.06-4.97) when both parents were smokers. These associations remained consistent even after adjusting for socioeconomic status. Parental smoking rates were higher in the surgical group across all categories. Maternal smoking prevalence was 10% versus 7.5%, and paternal smoking prevalence was 36% versus 32%, in the surgical group vs. the control group, accordingly. The proportion of children with only one smoking parent was 34% compared to 31%, and for cases with both parents smoking, the rate was 6.3% versus 4.3%., Conclusion: Parental smoking is associated with higher rates of pediatric adenoidectomy, tonsillectomy, and adenotonsillectomy, especially if both parents smoke. Counseling parents on the negative effects of smoking on their children is crucial in reducing the incidence of these surgeries., What Is Known: • Parental smoking can cause multiple pediatirc diseases., What Is New: • Parental smoking is associated with higher rate of adenotonsillar surgery., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: There is a perception that income-based disparities are present in most countries but may differ in magnitude. However, there are few international comparisons that describe income-based disparities across countries and none that focus on hip fractures., Objective: To compare treatment patterns and outcomes of high- and low-income older adults hospitalized with hip fracture across six high-income countries., Design: Retrospective serial cross-sectional cohort study., Participants: Adults aged ≥ 66 years hospitalized with hip fracture from 2013 to 2019 in Canada, England, Israel, the Netherlands, Taiwan, and the USA using population-representative patient-level administrative data., Main Measures: Older adults in the top and bottom income quintiles within countries were compared on 30-day and 1-year mortality, treatment approaches, hospital length of stay (LOS), 30-day readmission rates, time to surgery, and discharge disposition., Key Results: Annual age- and sex-standardized incidence rates of hip fracture were higher for low- than for high-income populations in all countries except in the USA. In all countries, adjusted 1-year mortality was lower for high-income than low-income patients, with the largest difference in Israel (- 10.0 percentage points [95% confidence interval [CI], - 15.2 to - 4.8 percentage points]). Across countries, utilization of total hip arthroplasty was 0.1 (95% CI, 0.0-0.2 percentage points) to 6.9 percentage points (95% CI, 4.6-9.2 percentage points) higher among high- vs. low-income populations. With few exceptions, LOS, adjusted 30-day readmission rate, and time to surgery were shorter and lower for high-income patients., Conclusions: Income-based disparities in treatments and outcomes for older adults hospitalized for hip fractures differed in magnitude, but were present in all six high-income countries. Defying our expectations, the USA did not have consistently larger disparities than other countries suggesting that the impacts of poverty exist in vastly different healthcare systems and transcend geopolitical borders., Competing Interests: Declarations:. Conflict of Interest:: The authors declare that they do not have a conflict of interest., (© 2024. The Author(s).)

Background: Respiratory syncytial virus (RSV) is a significant cause of illness in adults, especially older adults and those with underlying conditions. This study aimed to assess the incidence of RSV hospitalizations in adults and identify risk factors for hospitalization and poor outcomes., Methods: A retrospective cohort study was conducted using data from two hospitals in southern Israel from 2016-2022. We calculated incidence rates of RSV and influenza hospitalizations. Risk factors for hospitalization were analyzed using Poisson regression. We evaluated poor outcomes (death, ICU admission, or mechanical ventilation) among RSV-hospitalized patients., Results: The median annual incidence of RSV hospitalization was 28.2/100,000 population, increasing with age to 199/100,000 in those ≥75 years. Significant risk factors for RSV hospitalization included pulmonary diseases (RR 4.2, 95% CI 3.4-5.2), cardiovascular diseases (RR 3.3, 95% CI 2.6-4.2), and chronic renal failure (RR 2.9, 95% CI 2.3-3.7). Among hospitalized RSV patients, 13.9% had poor outcomes. Renal failure (RR 1.81, 95% CI 1.23-2.66), neutropenia (RR 2.53, 95% CI 1.19-5.35), neutrophilia (RR 1.66, 95% CI 1.81-2.34), and lymphopenia (RR 2.03, 95% CI 1.37-3.0) were associated with poor outcomes., Conclusions: RSV causes a substantial burden of hospitalizations in adults, particularly among older adults and those with comorbidities. Identifying high-risk groups can help target prevention and treatment strategies, including vaccination.

Acute bronchiolitis is among the most common causes of hospitalizations in infants worldwide. Associations between weight and severity of respiratory syncytial virus (RSV) bronchiolitis remain unclear. The aim of this study was to evaluate this association. A single-center, retrospective cohort study of infants aged under 24 months, who were hospitalized between 2018 and 2022 for RSV bronchiolitis. Data from computerized medical records were extracted using the MDclone platform. Participants were divided into three groups according to weight percentiles: underweight (below 5th percentile), normal-weight, and overweight (above 85th percentile). A total of 1936 infants (mean age 6.3 months, 55% males) were included, comprising 274 infants who were underweight, 1470 with normal weight, and 192 with overweight. Underweight infants had a higher rate of admission to the pediatric intensive care unit (PICU) (9.1% vs. 3.5%, P < 0.005) and prolonged length of stay (LOS) in the hospital (3.13 vs. 2.79 days P < 0.001) compared to those with normal weight. Hyponatremia was also more common in the underweight group (23% vs. 15%, P < 0.001). A multivariable model accounting for prematurity and birthweight predicted a relative risk of 2.01 (95% CI 1.13-3.48, P = 0.015) for PICU admission and 1.42 (95% CI 1.17-1.7, P < 0.001) for a prolonged LOS. Being overweight was not associated with a more severe disease.  Conclusion: Underweight infants, hospitalized for RSV bronchiolitis, had a more severe disease course with a higher complication rate, including PICU admission and prolonged LOS. Thus, careful attention and supervision should be given to this subgroup of infants. What is Known: • Established risk factors for severe bronchiolitis include prematurity, BPD, CHD, and compromised immunity. • Abnormal weight status has been associated with an increased risk for morbidity and mortality from infectious diseases, proposedly due to the effects on endocrine and immunologic systems. What is New: • Underweight infants hospitalized with RSV bronchiolitis face an independent risk of PICU admission and prolonged hospital stay. • Conversely, overweight infants did not display associations with severity measures in our study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Schizophrenia symptomatology includes negative symptoms and cognitive impairment. Several studies have linked schizophrenia with the PDE4 family of enzymes due to their genetic association and function in cognitive processes such as long-term potentiation. We conducted a systematic gene expression meta-analysis of four PDE4 genes (PDE4A-D) in 10 brain sample datasets (437 samples) and three blood sample datasets (300 samples). Subsequently, we measured mRNA levels in iPSC-derived hippocampal dentate gyrus neurons generated from fibroblasts of three groups: healthy controls, healthy monozygotic twins (MZ), and their MZ siblings with schizophrenia. We found downregulation of PDE4B in brain tissues, further validated by independent data of the CommonMind consortium (515 samples). Interestingly, the downregulation signal was present in a subgroup of the patients, while the others showed no differential expression or even upregulation. Notably, PDE4A, PDE4B, and PDE4D exhibited upregulation in iPSC-derived neurons compared to healthy controls, whereas in blood samples, PDE4B was found to be upregulated while PDE4A was downregulated. While the precise mechanism and direction of altered PDE4 expression necessitate further investigation, the observed multilevel differential expression across the brain, blood, and iPSC-derived neurons compellingly suggests the involvement of PDE4 genes in the pathophysiology of schizophrenia.

Chronic spontaneous urticaria (CSU) is a disturbing skin condition often severely detrimental to quality of life. Haematological markers of inflammation such as neutrophil-to-lymphocyte and platelet-to-lymphocyte may be used in the assessment of inflammatory skin diseases. Their usefulness in urticaria is unknown. Neutrophil- to-lymphocyte, platelet-to-lymphocyte, and total serum IgE were investigated in urticaria patients: acute spontaneous urticaria (ASU) versus CSU, children versus adults with CSU, and patients with mild-to-moderate versus severe CSU. This retrospective cohort study included patients of all ages diagnosed with urticaria between 2005 and 2020 and blood counts within 30 days of diagnosis. Patients with comorbidities influencing blood cells (infection, surgery, malignancy) were excluded. Neutrophil-to-lymphocyte and platelet-to-lymphocyte were evaluated in patients with ASU vs CSU and mild-to-moderate CSU vs severe CSU (defined by the use of systemic medications or hospitalizations). A total of 13,541 urticaria patients were included in the study. CSU patients (n = 5,021) had higher neutrophil-to-lymphocyte and platelet-to-lymphocyte, as well as serum IgE levels compared with ASU patients (n = 8,520). Adults had higher neutrophil-to-lymphocyte and platelet-to-lymphocyte than children. Severely affected patients (n = 53) had higher neutrophil-to-lymphocyte and platelet-to-lymphocyte compared with mild-to-moderately affected patients (n = 4,968). Patients with higher neutrophil-to-lymphocyte and platelet-to-lymphocyte had higher odds of having CSU rather than ASU and severe urticaria rather mild-to-moderate. In conclusion, neutrophil-to-lymphocyte and platelet-to-lymphocyte are simple and available markers that can be used to predict and assess severe and chronic urticaria.

Background: Sex differences in acute myocardial infarction treatment and outcomes are well documented, but it is unclear whether differences are consistent across countries. The objective of this study was to investigate the epidemiology, use of interventional procedures, and outcomes for older females and males hospitalized with ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI) in 6 diverse countries., Methods: We conducted a serial cross-sectional cohort study of 1 508 205 adults aged ≥66 years hospitalized with STEMI and NSTEMI between 2011 and 2018 in the United States, Canada, England, the Netherlands, Taiwan, and Israel using administrative data. We compared females and males within each country with respect to age-standardized hospitalization rates, rates of cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery within 90 days of hospitalization, and 30-day age- and comorbidity-adjusted mortality., Results: Hospitalization rates for STEMI and NSTEMI decreased between 2011 and 2018 in all countries, although the hospitalization rate ratio (rate in males/rate in females) increased in virtually all countries (eg, US STEMI ratio, 1.58:1 in 2011 and 1.73:1 in 2018; Israel NSTEMI ratio, 1.71:1 in 2011 and 2.11:1 in 2018). Rates of cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery were lower for females than males for STEMI in all countries and years (eg, US cardiac catheterization in 2018, 88.6% for females versus 91.5% for males; Israel percutaneous coronary intervention in 2018, 76.7% for females versus 84.8% for males) with similar findings for NSTEMI. Adjusted mortality for STEMI in 2018 was higher for females than males in 5 countries (the United States, Canada, the Netherlands, Israel, and Taiwan) but lower for females than males in 5 countries for NSTEMI., Conclusions: We observed a larger decline in acute myocardial infarction hospitalizations for females than males between 2011 and 2018. Females were less likely to receive cardiac interventions and had higher mortality after STEMI. Sex disparities seem to transcend borders, raising questions about the underlying causes and remedies., Competing Interests: Disclosures None.

Background: Hematological markers such as eosinophil-to-lymphocyte (ELR), eosinophil-to-neutrophil (ENR), and eosinophil-to-monocyte (EMR) ratios may be used in the assessment of skin diseases. However, the relationship with vitiligo remains unclear., Objectives: We investigated ELR, ENR, and EMR in vitiligo patients and the association with severe vitiligo., Methods: This study included patients of all ages diagnosed with vitiligo between 2005-2020. ELR, EMR, and ENR were calculated from complete blood counts within 30 days of the first recorded vitiligo diagnosis and 12-18 months before the vitiligo diagnosis. We evaluated the associations between ELR, ENR, and EMR and vitiligo., Results: 9,826 vitiligo patients (8,398 adults and 1,428 children) and 8,951 age and sex-matched controls were included in this study. We found that ELR, EMR, and ENR were higher in children than in adults. Patients with vitiligo had higher ENR and EMR than their matched controls. Patients with severe vitiligo had higher ELR, ENR, and EMR compared to patients with mild vitiligo. Patients with increased ENR and EMR 12-18 months before the vitiligo diagnosis had a higher chance of having severe vitiligo (ENR: OR = 7.40, p<0.001, EMR: OR = 3.17, p<0.001)., Conclusion: ELR, ENR, and EMR may be used in the assessment and prognosis of vitiligo, especially in severe cases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Weissmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aims: Amiodarone-related interstitial lung disease (ILD) is the most severe adverse effect of amiodarone treatment. Most data on amiodarone-related ILD are derived from periods when amiodarone was given at higher doses than currently used., Methods: A nationwide population-based study was conducted among patients with incident atrial fibrillation (AF) between 1 December 1999 and 31 December 31 2021. Amiodarone-exposed patients were matched 1:1 with controls unexposed to amiodarone based on age, sex, ethnicity, and AF diagnosis duration. The final patient cohort included only matched pairs where amiodarone therapy was consistent throughout follow-up. Directed acyclic graphs and inverse probability treatment weighting (IPTW) modelling were used. Patients with either prior ILD or primary lung cancer (PLC) were excluded. The primary outcome was the incidence of any ILD. Secondary endpoints were death and PLC., Results: The final cohort included 6039 amiodarone-exposed patients who were matched with unexposed controls. The median age was 73.3 years, and 51.6% were women. After a mean follow-up of 4.2 years, ILD occurred in 242 (2.0%) patients. After IPTW, amiodarone exposure was not significantly associated with ILD [hazard ratio (HR): 1.45, 95% confidence interval (CI): 0.97, 2.44, P = 0.09]. There was a trivial higher relative risk of ILD among amiodarone-exposed patients between Years 2 and 8 of follow-up [maximal risk ratio (RR): 1.019]. Primary lung cancer occurred in 97 (0.8%) patients. After IPTW, amiodarone was not associated with PLC (HR: 1.18, 95% CI: 0.76, 2.08, P = 0.53). All-cause death occurred in 2185 (18.1%) patients. After IPTW, amiodarone was associated with reduced mortality risk (HR: 0.65, 95% CI: 0.60, 0.72, P < 0.001). The results were consistent across a variety of sensitivity analyses., Conclusion: In a contemporary AF population, low-dose amiodarone was associated with a trend towards increased risk of ILD (15%-45%) but a clinically negligible change in absolute risk (maximum of 1.8%), no increased risk of PLC, and a lower risk of all-cause mortality., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hip fractures are costly and common in older adults, but there is limited understanding of how treatment patterns and outcomes might differ between countries., Methods: We performed a retrospective serial cross-sectional cohort study of adults aged ≥66 years hospitalized with hip fracture between 2011 and 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data. We examined mortality, hip fracture treatment approaches (total hip arthroplasty [THA], hemiarthroplasty [HA], internal fixation [IF], and nonoperative), and health system performance measures, including hospital length of stay (LOS), 30-day readmission rates, and time-to-surgery., Results: The total number of hip fracture admissions between 2011 and 2018 ranged from 23,941 in Israel to 1,219,696 in the US. In 2018, 30-day mortality varied from 3% (16% at 1 year) in Taiwan to 10% (27%) in the Netherlands. With regards to processes of care, the proportion of hip fractures treated with HA (range 23%-45%) and THA (0.2%-10%) differed widely across countries. For example, in 2018, THA was used to treat approximately 9% of patients in England and Israel but less than 1% in Taiwan. Overall, IF was the most common surgery performed in all countries (40%-60% of patients). IF was used in approximately 60% of patients in the US and Israel, but only 40% in England. In 2018, rates of nonoperative management ranged from 5% of patients in Taiwan to nearly 10% in England. Mean hospital LOS in 2018 ranged from 6.4 days (US) to 18.7 days (England). The 30-day readmission rate in 2018 ranged from 8% (in Canada and the Netherlands) to nearly 18% in England. The mean days to surgery in 2018 ranged from 0.5 days (Israel) to 1.6 days (Canada)., Conclusions: We observed substantial between-country variation in mortality, surgical approaches, and health system performance measures. These findings underscore the need for further research to inform evidence-based surgical approaches., (© 2023 The American Geriatrics Society.)

Objective: Acute bronchiolitis is the most common cause of hospitalization in young children. Data on monocyte-to-lymphocyte-ratio (MLR) and neutrophil-to-lymphocyte-ratio (NLR) as biomarkers are limited. We aim to evaluate these ratios in children hospitalized with respiratory syncytial virus (RSV) bronchiolitis and their value as biomarkers for severe clinical outcomes., Study Design: A single-center retrospective cohort study of children aged <2 years hospitalized due to RSV bronchiolitis, between January 2018 and March 2022, with a complete blood count upon admission. We divided the cohort into quartiles based on MLR and NLR values. We examined associations between quartiles and four clinical severity outcomes., Results: A total of 2038 children (median age: 4.4 months, IQR: 1.9-9.8) were included in the study. The median MLR and NLR values for quartiles 1-4 were 0.14, 0.22, 0.30, 0.47, and 0.37, 0.70, 1.16, 2.29, respectively. Children with higher MLR had higher hospitalization rates to the pediatric intensive care unit (PICU) (Q1 2.4%, Q4 9.4%, p < .001), extended hospital stays (Q1 19.4%, Q4 32%, p < .001), and lower minimal oxygen saturation (Q1 90%, Q4 87%, p < .001). Cut-off values of 0.34 for MLR and 0.67 for NLR optimally identified PICU admissions. In a model accounting for age and sex, the fourth MLR quartile had an RR of 3.4 (95% CI: 1.76-7.22) and successfully predicted PICU admissions (area under the curve = 0.73; 95% CI: 0.681-0.789)., Conclusions: MLR and NLR are potential biomarkers for identifying children with RSV bronchiolitis at a higher risk for severe outcomes, specifically PICU admission., (© 2023 Wiley Periodicals LLC.)