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.
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.
(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.
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.
Graphical Abstract
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.
(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%,
< 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.
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.
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/20β-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/20β-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-β 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/20β-hsd, down-regulated in males.
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-β domain was identified and mapped to the QTL region on LG23 for SD, thus indicating its potential role in SD.
It has been proposed that clustering clinical markers, such as blood test results, can be used to stratify patients. However, the robustness of clusters formed with this approach to data ...pre-processing and clustering algorithm choices has not been evaluated, nor has clustering reproducibility. Here, we made use of the NHANES survey to compare clusters generated with various combinations of pre-processing and clustering algorithms, and tested their reproducibility in two separate samples.
Values of 44 biomarkers and 19 health/life style traits were extracted from the National Health and Nutrition Examination Survey (NHANES). The 1999-2002 survey was used for training, while data from the 2003-2006 survey was tested as a validation set. Twelve combinations of pre-processing and clustering algorithms were applied to the training set. The quality of the resulting clusters was evaluated both by considering their properties and by comparative enrichment analysis. Cluster assignments were projected to the validation set (using an artificial neural network) and enrichment in health/life style traits in the resulting clusters was compared to the clusters generated from the original training set.
The clusters obtained with different pre-processing and clustering combinations differed both in terms of cluster quality measures and in terms of reproducibility of enrichment with health/life style properties. Z-score normalization, for example, dramatically improved cluster quality and enrichments, as compared to unprocessed data, regardless of the clustering algorithm used. Clustering diabetes patients revealed a group of patients enriched with retinopathies. This could indicate that routine laboratory tests can be used to detect patients suffering from complications of diabetes, although other explanations for this observation should also be considered.
Clustering according to classical clinical biomarkers is a robust process, which may help in patient stratification. However, optimization of the pre-processing and clustering process may be still required.
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.
Summary
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.
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