Amiodarone and pulmonary toxicity in atrial fibrillation: a nationwide Israeli study.

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.

Hematological Markers in Children and Adults with Atopic Dermatitis: A Retrospective Cohort Study.

INTRODUCTION: Atopic dermatitis (AD) is a common chronic skin disease with an inflammatory pathophysiology that includes the activation of the innate and adaptive immune systems. We aimed to investigate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-lymphocyte ratio (ELR), and eosinophil-to-neutrophil ratio (ENR) in AD patients, according to age and disease severity. METHODS: This is a retrospective, population-based cohort study conducted between the years 2005 and 2020, comparing hematological markers of AD patients and sex-age-ethnicity-matched controls. AD patients were further divided by age and disease severity (mild, moderate-to-severe AD). We created a decision tree to predict moderate-severe AD. RESULTS: A total of 13,928 patients with AD were included in this study: 6,828 adults and 7,100 children, with 13,548 controls. NLR, PLR, and ELR were lower in children compared to adults (p values <0.001). NLR, PLR, ELR, and ENR were increased in moderate-severe AD patients compared to mild AD patients (p values <0.001). PLR, ELR, and ENR were increased in AD patients versus controls (p values <0.001), with an additional increase in the NLR of moderate-to-severe AD patients. Patients with an ELR <0.21, a PLR >161, and ENR ≤0.016 should be considered high risk for developing severe AD, as well as patients with an ELR >0.21 and age at diagnosis <30 or age >30 years and mean platelet volume ≤9. CONCLUSION: Hematological ratios were significantly higher in moderate-to-severe AD patients, compared to mild AD patients. Hematological markers were lower in children with AD compared to adults, except for ENR, likely reflecting age-related changes in blood count parameters. These markers can assist in the management and follow-up of AD patients.

Differences in Treatment Patterns and Outcomes of Acute Myocardial Infarction for Low- and High-Income Patients in 6 Countries.

Importance: Differences in the organization and financing of health systems may produce more or less equitable outcomes for advantaged vs disadvantaged populations. We compared treatments and outcomes of older high- and low-income patients across 6 countries. Objective: To determine whether treatment patterns and outcomes for patients presenting with acute myocardial infarction differ for low- vs high-income individuals across 6 countries. Design, Setting, and Participants: Serial cross-sectional cohort study of all adults aged 66 years or older hospitalized with acute myocardial infarction from 2013 through 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data. Exposures: Being in the top and bottom quintile of income within and across countries. Main Outcomes and Measures: Thirty-day and 1-year mortality; secondary outcomes included rates of cardiac catheterization and revascularization, length of stay, and readmission rates. Results: We studied 289 376 patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and 843 046 hospitalized with non-STEMI (NSTEMI). Adjusted 30-day mortality generally was 1 to 3 percentage points lower for high-income patients. For instance, 30-day mortality among patients admitted with STEMI in the Netherlands was 10.2% for those with high income vs 13.1% for those with low income (difference, -2.8 percentage points [95% CI, -4.1 to -1.5]). One-year mortality differences for STEMI were even larger than 30-day mortality, with the highest difference in Israel (16.2% vs 25.3%; difference, -9.1 percentage points [95% CI, -16.7 to -1.6]). In all countries, rates of cardiac catheterization and percutaneous coronary intervention were higher among high- vs low-income populations, with absolute differences ranging from 1 to 6 percentage points (eg, 73.6% vs 67.4%; difference, 6.1 percentage points [95% CI, 1.2 to 11.0] for percutaneous intervention in England for STEMI). Rates of coronary artery bypass graft surgery for patients with STEMI in low- vs high-income strata were similar but for NSTEMI were generally 1 to 2 percentage points higher among high-income patients (eg, 12.5% vs 11.0% in the US; difference, 1.5 percentage points [95% CI, 1.3 to 1.8 ]). Thirty-day readmission rates generally also were 1 to 3 percentage points lower and hospital length of stay generally was 0.2 to 0.5 days shorter for high-income patients. Conclusions and Relevance: High-income individuals had substantially better survival and were more likely to receive lifesaving revascularization and had shorter hospital lengths of stay and fewer readmissions across almost all countries. Our results suggest that income-based disparities were present even in countries with universal health insurance and robust social safety net systems.

The variability of diagnosed migraine epidemiology amongst different municipalities in southern Israel.

BACKGROUND: Appropriate and timely diagnosis is one of the most important milestones in effective migraine care and is affected by public awareness, access to medical care, health care systems, and physicians' knowledge. We assessed the variability in migraine diagnosis rates in different communities under universal national health coverage in Israel. METHODS: In this population-based retrospective, observational, cohort study, adult (≥18 years) migraine patients were identified in the computerized database of the southern district of the Clalit Health Services Health Maintenance Organization (HMO) based on recorded diagnosis and/or purchase of specific anti-migraine acute medication (triptans). Migraine prevalence in 2018 was calculated in the entire study population and in different municipalities. We utilized a standardized (age and gender) mortality ratio (SMR) approach for comparison among the municipalities. RESULTS: In 2018, a total of 29,938 migraine patients were identified out of 391,528 adult HMO members, with an overall prevalence (per 10,000) of migraine of 764.64 (7.65%), 1143.34 (11.43%) for women, and 374.97 (3.75%) for men. Among the municipalities, adjusted prevalence (per 10,000) ranged from 386.15 (3.86%) to 1320.60 (13.21%). The female-to-male ratio ranged from 1.8:1 to 5.1:1. Prevalence rates were positively associated with the socioeconomic status of the municipalities (Spearman rho = 0.472, P = 0.031). CONCLUSIONS: High variability in the prevalence of diagnosed migraine suggests underdiagnosis. Resources for awareness and educational programs should be directed to low diagnosed prevalence communities.

Positive selection and heat-response transcriptomes reveal adaptive features of the Brassicaceae desert model, Anastatica hierochuntica.

Plant adaptation to a desert environment and its endemic heat stress is poorly understood at the molecular level. The naturally heat-tolerant Brassicaceae species Anastatica hierochuntica is an ideal extremophyte model to identify genetic adaptations that have evolved to allow plants to tolerate heat stress and thrive in deserts. We generated an A. hierochuntica reference transcriptome and identified extremophyte adaptations by comparing Arabidopsis thaliana and A. hierochuntica transcriptome responses to heat, and detecting positively selected genes in A. hierochuntica. The two species exhibit similar transcriptome adjustment in response to heat and the A. hierochuntica transcriptome does not exist in a constitutive heat 'stress-ready' state. Furthermore, the A. hierochuntica global transcriptome as well as heat-responsive orthologs, display a lower basal and higher heat-induced expression than in A. thaliana. Genes positively selected in multiple extremophytes are associated with stomatal opening, nutrient acquisition, and UV-B induced DNA repair while those unique to A. hierochuntica are consistent with its photoperiod-insensitive, early-flowering phenotype. We suggest that evolution of a flexible transcriptome confers the ability to quickly react to extreme diurnal temperature fluctuations characteristic of a desert environment while positive selection of genes involved in stress tolerance and early flowering could facilitate an opportunistic desert lifestyle.

Migraine epidemiology and comorbidities in Southern Israel: a clinical database study in a universal health coverage setting.

BACKGROUND: Understanding migraine epidemiology and its burden is crucial for planning health policies and interventions at the local level as well as at the global level. National policies in Israel rely on global estimations and not on local data since local epidemiologic studies had not previously been performed. In this study, we evaluated the epidemiology of migraine in the southern district of Israel using the electronic medical records database of the largest Israeli health maintenance organization (HMO). METHODS: In this population-based, retrospective, observational cohort study, adult migraine patients were identified in the computerized database of the southern district of the Clalit Health Services HMO (total population, 0.75 million). Patients were identified based on recorded diagnosis (International Classification of Diseases, Ninth Revision) and/or claims for specific anti-migraine medication (triptans) between 2000 and 2018. A 1:2 age-, gender-, and primary care clinic-matched control group was used for evaluation of comorbidities. RESULTS: In 2018, a total of 29,938 patients with migraine were identified out of 391,528 adult HMO members. Most of the patients were women (75.8%), and the mean ± standard deviation age at diagnosis was 36.94 ± 13.61 years. The overall prevalence of migraine (per 10,000) was 764.64 (7.65%), 1143.34 (11.43%) for women and 374.97 (3.75%) for men. The highest prevalence was observed in patients aged 50 to 60 years and 40 to 50 years (1143.98 [11.44%] and 1019.36 [10.19%], respectively), and the lowest prevalence was among patients aged 18 to 30 years and > 70 years (433.45 [4.33%] and 398.49 [3.98%], respectively). CONCLUSIONS: This is the first large-scale epidemiologic study of migraine prevalence in Israel. Compared to international estimations, migraine appears to be underdiagnosed in the southern district of Israel.

Evolution and dissemination of the Klebsiella pneumoniae clonal group 258 throughout Israeli post-acute care hospitals, 2008-13.

Objectives: The KPC-producing Klebsiella pneumoniae (KPC-KP) clonal group (CG) 258 has disseminated throughout Israeli post-acute care hospitals (PACHs). The objectives of the study were (i) to describe the evolution and (ii) to understand the dissemination modes of CG 258 in the PACH system in Israel. Methods: KPC-KP surveillance cultures isolates were collected in Israeli PACHs in three national point-prevalence surveys: 2008, 2011 and 2013. CG 258 was identified by pilv-l PCR. WGS was performed for CG 258 isolates from 9 of 14 PACHs and data extracted for core-genome MLST (cgMLST) and for capsule polysaccharide gene cluster analysis. Results: The proportional representation of CG 258 among the KPC-KP isolates increased from 72 of 104 isolates (69.2%) in 2008 to 113 of 133 isolates (85%) in 2011 ( P = 0.004 for 2008 versus 2011) and remained high in 2013 [56 of 67 isolates (83.6%)]. All isolates were related to CG 258 clade 2. cgMLST phylogenetic analysis showed relative convergence in the 2008 survey, with increasing diversification in the subsequent surveys. A predominantly institutional dissemination pattern was observed only in centre F from southern Israel. A predominantly regional dissemination pattern was observed in the two PACHs in Jerusalem. The other PACHs were characterized by a combined institutional and generalized pattern, with the majority of isolates clustering within the same PACH and survey. Conclusions: CG 258 clade 2 has retained its predominance despite increased diversification. Although interchanging of CG 258 strains occurred between most PACHs, local spread is the leading cause of its dissemination.

A combination of gene expression ranking and co-expression network analysis increases discovery rate in large-scale mutant screens for novel Arabidopsis thaliana abiotic stress genes.

As challenges to food security increase, the demand for lead genes for improving crop production is growing. However, genetic screens of plant mutants typically yield very low frequencies of desired phenotypes. Here, we present a powerful computational approach for selecting candidate genes for screening insertion mutants. We combined ranking of Arabidopsis thaliana regulatory genes according to their expression in response to multiple abiotic stresses (Multiple Stress [MST] score), with stress-responsive RNA co-expression network analysis to select candidate multiple stress regulatory (MSTR) genes. Screening of 62 T-DNA insertion mutants defective in candidate MSTR genes, for abiotic stress germination phenotypes yielded a remarkable hit rate of up to 62%; this gene discovery rate is 48-fold greater than that of other large-scale insertional mutant screens. Moreover, the MST score of these genes could be used to prioritize them for screening. To evaluate the contribution of the co-expression analysis, we screened 64 additional mutant lines of MST-scored genes that did not appear in the RNA co-expression network. The screening of these MST-scored genes yielded a gene discovery rate of 36%, which is much higher than that of classic mutant screens but not as high as when picking candidate genes from the co-expression network. The MSTR co-expression network that we created, AraSTressRegNet is publicly available at http://netbio.bgu.ac.il/arnet. This systems biology-based screening approach combining gene ranking and network analysis could be generally applicable to enhancing identification of genes regulating additional processes in plants and other organisms provided that suitable transcriptome data are available.

Identification of male-specific amh duplication, sexually differentially expressed genes and microRNAs at early embryonic development of Nile tilapia (Oreochromis niloticus).

BACKGROUND: The probable influence of genes and the environment on sex determination in Nile tilapia suggests that it should be regarded as a complex trait. Detection of sex determination genes in tilapia has both scientific and commercial importance. The main objective was to detect genes and microRNAs that were differentially expressed by gender in early embryonic development. RESULTS: Artificial fertilization of Oreochromis niloticus XX females with either sex-reversed ΔXX males or genetically-modified YY 'supermales' resulted in all-female and all-male embryos, respectively. RNA of pools of all-female and all-male embryos at 2, 5 and 9 dpf were used as template for a custom Agilent eArray hybridization and next generation sequencing. Fifty-nine genes differentially expressed between genders were identified by a false discovery rate of p < 0.05. The most overexpressed genes were amh and tspan8 in males, and cr/20ß-hsd, gpa33, rtn4ipl and zp3 in females (p < 1 × 10-9). Validation of gene expression using qPCR in embryos and gonads indicated copy number variation in tspan8, gpa33, cr/20ß-hsd and amh. Sequencing of amh identified a male-specific duplication of this gene, denoted amhy, differing from the sequence of amh by a 233 bp deletion on exonVII, hence lacking the capability to encode the protein motif that binds to the transforming growth factor beta receptor (TGF-ß domain). amh and amhy segregated in the mapping family in full concordance with SD-linked marker on LG23 signifying the QTL for SD. We discovered 831 microRNAs in tilapia embryos of which nine had sexually dimorphic expression patterns by a false discovery rate of p < 0.05. An up-regulated microRNA in males, pma-mir-4585, was characterized with all six predicted target genes including cr/20ß-hsd, down-regulated in males. CONCLUSIONS: This study reports the first discovery of sexually differentially expressed genes and microRNAs at a very early stage of tilapia embryonic development, i.e. from 2 dpf. Genes with sexually differential expression patterns are enriched for copy number variation. A novel male-specific duplication of amh, denoted amhy, lacking the TGF-ß domain was identified and mapped to the QTL region on LG23 for SD, thus indicating its potential role in SD.

Association of hematological ratios with psoriasis: a nationwide retrospective cohort study.

BACKGROUND: Psoriasis is a common skin disorder linked to systemic inflammation and immune dysregulation. It is believed to involve activated T cells and neutrophils. Recent research has highlighted the potential role of hematological ratios, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-lymphocyte ratio (ELR), eosinophil-to-neutrophil ratio (ENR), and eosinophil-to-monocyte ratio (EMR), as markers for inflammatory skin diseases, including psoriasis. OBJECTIVES: We aimed to investigate hematological ratios between children and adults, patients and controls, and patients with moderate-to-severe and mild psoriasis. MATERIALS AND METHODS: This national retrospective cohort study included over 16,000 psoriasis patients in Israel. Patients with comorbidities influencing blood counts were excluded. Ratios were calculated from blood counts taken within 30 days of diagnosis. Multivariable logistic regression, including age, gender, ethnicity, smoking status, and socioeconomic status, was performed. RESULTS: Findings revealed age-specific variations in blood counts, hematological ratios, and differences between mild and moderate-severe patients and patients versus controls. Moderate-severe psoriasis patients had elevated neutrophil and eosinophil counts (4.57 vs. 4.25, P < 0.001, and 0.24 vs. 0.22, P = 0.047, respectively), as well as increased NLR (2.46 vs. 2.29, P < 0.001). Multivariable logistic regression analysis confirmed the significance of neutrophil and platelet counts as well as NLR and PLR in predicting psoriasis severity. LIMITATIONS: This was a retrospective study without subjective data on disease severity. CONCLUSION: This study highlights hematologic ratios' diagnostic and prognostic potential in psoriasis.

Nonalcoholic Fatty Liver Disease and Ethnicity: Lessons Learned from the Arab Population in Israel.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. We aimed to investigate the potential similarities and differences regarding the disease among Arabs and Jews. Retrospective study included all patients older than 18 years with NAFLD diagnosis according to ICD-10 codes. Data regarding demographics, comorbidities, and outcomes were retrieved using the MdClone platform from "Clalit" in Israel. Data concerning 34,090 Arab patients and 173,500 Jewish patients with NAFLD were included. Arab patients were significantly younger at diagnosis (35.0 ± 13 years vs. 43.6 ± 15 years, p < 0.001) and had higher rates of obesity and diabetes mellitus (69.5% vs. 56.5% and 27.0% vs. 22.7%, p < 0.001, respectively). Arab patients had higher rates of cirrhosis and portal hypertension-related complications (2.5% vs. 2.0%, p < 0.001), esophageal varices (0.9% vs. 0.5%, p < 0.001), spontaneous bacterial peritonitis (0.3% vs. 0.1%, p < 0.001), and hepatorenal syndrome (0.3% vs. 0.1%, p < 0.001). There was no significant difference in the prevalence of hepatocellular carcinoma between study groups (0.4% vs. 0.5%, p = 0.156). Liver transplantation was performed in 0.2% of Arab NAFLD patients compared to 0.07% of Jewish NAFLD patients (p < 0.001). Lower rates of all-cause mortality were found among the Arab NAFLD patients versus Jewish NAFLD patients (7.7% versus 11.5%, p < 0.001). According to the Cox regression model, Arab ethnicity is a risk factor for death with OR of 1.36. Significant differences regarding comorbidities, complications, liver transplantations rates, and all-cause mortality were found among NAFLD patients of different ethnicities, hence specific population need specific consideration in prevention, early diagnosis and follow up.

Sex-Based Disparities in Acute Myocardial Infarction Treatment Patterns and Outcomes in Older Adults Hospitalized Across 6 High-Income Countries: An Analysis From the International Health Systems Research Collaborative.

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.

Air Pollution and Meteorological Conditions Significantly Associated With Vernal Keratoconjunctivitis Exacerbations.

Purpose: Vernal keratoconjunctivitis (VKC) is a severe chronic allergic inflammation of the ocular surface with episodes of acute exacerbations, that primarily affects children and young adults. Although the etiology and pathogenesis of VKC remain unclear, studies have suggested that environmental factors may be involved. This study aims to investigate the association between exposure to meteorological and environmental factors and the incidence of VKC exacerbations. Methods: This study was conducted in southern Israel, which is a semi-arid, hot, and dry climate with frequent dust storms. Patients diagnosed with VKC were recruited for the study. VKC exacerbations were identified as the need for medical intervention. Pollutants measured included nitrogen dioxide (NO2), ozone (O3), particulate matter (PM10 and PM2.5), sulfur dioxide (SO2), relative humidity (RH), temperature, and solar radiation (SR). To assess the association between VKC exacerbations and exposure to different pollutants, a case-crossover analysis was conducted. We also stratified the analysis by sex, age, ethnicity, immigration status, and social state score. Results: Our results demonstrated that the pollutants NO2, O3, and PM10 were associated with VKC exacerbations with odds ratio (OR) = 2.17 (95% confidence interval [CI] =1.40 to 3.04), OR = 2.28 (95% CI = 1.30 to 3.39), and OR = 1.89 (95% CI = 1.06 to 2.74). Other pollutants PM2.5, temperature, and solar radiation were also independently associated with incidence of exacerbations with OR = 1.15 (95% CI = 0.87 to 1.50), OR = 1.75 (95% CI = 1.16 to 2.65), and OR = 1.37 (95% CI = 1.01 to 1.63) and had varying effects in different demographic strata. Conclusions: The environmental parameters, NO2, O3, PM10, PM2.5, temperature, and solar radiation were found to be significantly associated with VKC exacerbations, with NO2, O3, and PM10 showing the strongest associations. Our findings suggest that environmental factors should be considered when developing strategies to prevent and manage VKC exacerbations.

Herpes zoster and long-term vascular risk: a retrospective cohort study.

Herpes zoster (HZ) represents a serious health problem in the general population due to its abundance and complications. Stroke and acute myocardial infarction are well-documented short-term complications of HZ, primarily due to vasculopathy in the cerebral and coronary arteries. However, no major study to date has specifically demonstrated that HZ is a long-term risk factor for all Major Adverse Cardiac and Cerebrovascular Events (MACCE). A retrospective cohort study was conducted analyzing the association between HZ and MACCE. We compared HZ patients diagnosed between 2001 and 2018 and a matched control group. The model was stratified according to matched pairs and adjusted for age, socioeconomic status, history of dyslipidemia, and prior myocardial infarction (MI). Association between HZ exposure and stroke was assessed through a multivariable Cox regression analysis. The study included 41,930 patients, with 20,965 patients in each group. The risk of MACCE was 19% higher among HZ patients in the first year of follow up (P < 0.001). Antiviral treatment did not positively affect long-term survival among HZ patients (P < 0.001). These results suggest that HZ is a marker of long-term vascular risk. Additional studies will be needed to further evaluate this risk, the impact of HZ vaccination on such risk, and potential mitigation strategies.

Comorbidities and Malignancy among NAFLD Patients Compared to the General Population, A Nation-Based Study.

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease. Aims: We aimed to investigate the frequency of comorbidities and malignancies among NAFLD patients compared to the general population. (2) Methods: A retrospective study included adult patients with a NAFLD diagnosis. A control group was matched for age and gender. Demographics, comorbidities, malignancies, and mortality were collected and compared. (3) Results: 211,955 NAFLD patients were analyzed in comparison to 452,012 matched general population controls. Significantly higher rates of diabetes mellitus (23.2% vs. 13.3%), obesity (58.8% vs. 27.8%), hypertension (57.2% vs. 39.9%), chronic ischemic heart disease (24.7% vs. 17.3%), and CVA (3.2% vs. 2.8%) were found among NAFLD patients. Patients with NAFLD had significantly higher rates of the following malignancies: prostate cancer (1.6% vs. 1.2%), breast cancer (2.6% vs. 1.9%), colorectal cancer (1.8% vs. 1.4%), uterine cancer (0.4 vs. 0.2%), kidney cancer (0.8% vs. 0.5%), but a lower rate of lung cancer (0.9% vs. 1.2%) and stomach cancer (0.3% vs. 0.4%). The all-cause mortality rate among NAFLD patients was significantly lower in comparison to the general population (10.8% vs. 14.7%, p < 0.001). (4) Conclusions: Higher rates of comorbidities and malignancies among NAFLD patients were observed, but a lower rate of all-cause mortality was found.

Colorectal cancer among inflammatory bowel disease patients: risk factors and prevalence compared to the general population.

Background: Colorectal cancer (CRC) is a feared complication of inflammatory bowel disease (IBD). We aimed to investigate the prevalence and risk factors of CRC among a large cohort of IBD patients. Methods: Data on IBD patients free of CRC at baseline was extracted using the MDClone platform of the Clalit health maintenance organization in Israel. We investigated the frequency rate of CRC among IBD patients compared to a control group without IBD. Possible risk factors, including comorbidities and IBD-related medications, were investigated in a multivariate analysis. Results: During a follow-up of 139,448 years among Crohn's disease (CD) patients and 139,533 years among ulcerative colitis (UC) patients, a frequency rate of CRC was 1.5% (191) among 12,888 CD patients and 2.1% (261) among 12,381 UC patients compared to 1.2% among 57,334 controls. In a multivariate analysis of UC patients, age at diagnosis (OR 1.030, p < 0.001), primary sclerosing cholangitis (OR 2.487, p = 0.005), diabetes mellitus (OR 2.01, p < 0.001), and glucocorticoids treatment (OR 1.465, p = 0.008) were found to be predictors of CRC. For CD patients, age at diagnosis (OR 1.035, p < 0.001), primary sclerosing cholangitis (OR 2.25, p = 0.029), and glucocorticoids treatment (OR 2.07, p < 0.001) were found to be predictors for CRC, but not diabetes mellitus. Conclusion: Despite the continuously decreasing rates of CRC among IBD patients, these are still higher in IBD patients compared to the general population. IBD patients, particularly those with risk factors, require special consideration in follow-up for CRC.

Variation in care for patients presenting with hip fracture in six high-income countries: A cross-sectional cohort study.

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.

Comorbidities and Outcomes among Females with Non-Alcoholic Fatty Liver Disease Compared to Males.

Sex-based medicine is an important emerging discipline within medicine. We investigated the clinical characteristics, complications, and outcomes of Nonalcoholic Fatty Liver Disease (NAFLD) in females compared to males. Demographics, comorbidities, malignancy, complications, outcomes, and all-cause mortality of NAFLD patients older than 18 years were analyzed. The data were extracted using the MDClone platform from "Clalit" in Israel. A total of 111,993 (52.8%) of the study subjects were females with an average age of 44.4 ± 14.7 years compared to 39.62 ± 14.9 years in males, p < 0.001. Significantly higher rates of hypertension, diabetes mellitus, obesity, dementia, and thyroid cancer and lower rates of ischemic heart disease (22.3% vs. 27.3%, p < 0.001) were found among females. Females had a higher rate of cirrhosis, 2.3% vs. 1.9%, p < 0.001, and a lower rate of hepatocellular carcinoma, 0.4% vs. 0.5%, p < 0.001. In the multivariate analysis, a relationship between age, diabetes mellitus, and cirrhosis development were found among males and females. A lower age-adjusted mortality rate was found among females, 94.5/1000 vs. 116/1000 among males. In conclusion, older age at diagnosis, higher rates of hypertension, diabetes mellitus, obesity, cirrhosis, and a lower age-adjusted all-cause mortality rate were found among females with NAFLD.

Comorbidities and Risk Factors of Patients Diagnosed with CRC after Positive Fecal Test in Real Life.

(1) Background: Fecal occult blood test (FOBT) is the modality of choice in most countries for colorectal cancer (CRC) screening. We aimed to investigate the risk factors for CRC among patients with a positive FOBT in real life. (2) Methods: This was a retrospective study that included patients who tested positive for FOBT. Data regarding the comorbidities and laboratories were collected and compared between CRC and non-CRC groups. (3) Results: Positive FOBT was found among 45,500 (5.36%) subjects and CRC was found in 1502 (3.3%). CRC patients were older, age 62.7 ± 7.15 years compared with 59.33 ± 7.3 years (p < 0.001), and had significantly higher rates of hypertension (48.4% vs. 44.7%, p = 0.002), iron-deficiency anemia (20.6% vs. 16.4, p < 0.001), family history of CRC (7.3% vs. 5.1%, p < 0.001), and previous CRC (6.5% vs. 0.3%, p < 0.001). Lower levels of hemoglobin, iron, and ferritin were found in the CRC group. Age, family history of CRC, and previous CRC were found to be significant risk factors for diagnosis of CRC after positive FOBT with OR of 1.057, 1.4, and 15.9, respectively. (4) Conclusions: Iron-deficiency anemia, family history of CRC, previous colorectal cancer, and low hemoglobin, iron, and ferritin levels should direct physicians to give high priority to colonoscopy scheduling.

Variation in revascularisation use and outcomes of patients in hospital with acute myocardial infarction across six high income countries: cross sectional cohort study.

OBJECTIVES: To compare treatment and outcomes for patients admitted to hospital with a primary diagnosis of ST elevation or non-ST elevation myocardial infarction (STEMI or NSTEMI) in six high income countries with very different healthcare delivery systems. DESIGN: Retrospective cross sectional cohort study. SETTING: Patient level administrative data from the United States, Canada (Ontario and Manitoba), England, the Netherlands, Israel, and Taiwan. PARTICIPANTS: Adults aged 66 years and older admitted to hospital with STEMI or NSTEMI between 1 January 2011 and 31 December 2017. OUTCOMES MEASURES: The three categories of outcomes were coronary revascularisation (percutaneous coronary intervention or coronary artery bypass graft surgery), mortality, and efficiency (hospital length of stay and 30 day readmission). Rates were standardised to the age and sex distribution of the US acute myocardial infarction population in 2017. Outcomes were assessed separately for STEMI and NSTEMI. Performance was evaluated longitudinally (over time) and cross sectionally (between countries). RESULTS: The total number of hospital admissions ranged from 19 043 in Israel to 1 064 099 in the US. Large differences were found between countries for all outcomes. For example, the proportion of patients admitted to hospital with STEMI who received percutaneous coronary intervention in hospital during 2017 ranged from 36.9% (England) to 78.6% (Canada; 71.8% in the US); use of percutaneous coronary intervention for STEMI increased in all countries between 2011 and 2017, with particularly large rises in Israel (48.4-65.9%) and Taiwan (49.4-70.2%). The proportion of patients with NSTEMI who underwent coronary artery bypass graft surgery within 90 days of admission during 2017 was lowest in the Netherlands (3.5%) and highest in the US (11.7%). Death within one year of admission for STEMI in 2017 ranged from 18.9% (Netherlands) to 27.8% (US) and 32.3% (Taiwan). Mean hospital length of stay in 2017 for STEMI was lowest in the Netherlands and the US (5.0 and 5.1 days) and highest in Taiwan (8.5 days); 30 day readmission for STEMI was lowest in Taiwan (11.7%) and the US (12.2%) and highest in England (23.1%). CONCLUSIONS: In an analysis of myocardial infarction in six high income countries, all countries had areas of high performance, but no country excelled in all three domains. Our findings suggest that countries could learn from each other by using international comparisons of patient level nationally representative data.