Ran D. Balicer

Is Childhood Vaccination Associated With Asthma? A Meta-analysis of Observational Studies

BACKGROUND. The possible link between immunization and atopic diseases has been under intense debate in the last decade. OBJECTIVE. The aim of this study was to systematically review the available evidence on the association of whole-cell pertussis and BCG vaccination with the risk of asthma in childhood and adolescence. METHODS. The major medical electronic databases (Medline, National Library of Medicine Gateway, and Cochrane Library) were searched, and reference lists of the relevant publications were reviewed for relevant birth-cohort studies and randomized, controlled trials from 1966 to March 2006. Only studies that directly compared vaccinated and unvaccinated children, validated vaccination status by medical charts, and used preset criteria to define asthma were included. Data were abstracted by using a standardized protocol and computerized report form. Results were analyzed by applying a fixed-effect or random-effect model, according to the heterogeneity of the studies. Sensitivity analyses by scoring criteria were performed. RESULTS. Seven studies of pertussis vaccination (with a total of 186663 patients) and 5 studies of BCG vaccination (with a total of 41479 patients) met our inclusion criteria. No statistically significant association was detected between either whole-cell pertussis or BCG vaccination and incidence rates of asthma during childhood and adolescence. This lack of a significant association proved to be robust on sensitivity analyses for BCG but not for pertussis vaccine. CONCLUSIONS. Currently available data, based on observational studies, do not support an association, provocative or protective, between receipt of the BCG or whole-cell pertussis vaccine and risk of asthma in childhood and adolescence.

Microarray analysis identifies altered regulation of nuclear receptor family members in the pre-disease state of multiple sclerosis

Molecular mechanisms that influence susceptibility to multiple sclerosis are poorly understood. We analyzed peripheral blood gene expression profiles in nine healthy subjects up to nine years before the onset of multiple sclerosis in comparison with 11 age-, gender-, and origin-matched healthy subjects who remained multiple sclerosis-free, and 31 subjects during the first clinical episode of multiple sclerosis. Within the 1051 highly variable genes that differentiated between multiple sclerosis-to-be and multiple sclerosis-free subjects, we identified activation of TCR signaling that triggered the Cbl and MAPK cascade in concert with downstream synergic over-expression of NFAT and MEF2B, but failed to augment the expression of the nuclear receptor gene family members NR4A1, NR2F1, VDR and MEF2B, that further resulted in impaired apoptotic machinery. Comparison between multiple sclerosis-to-be and first clinical onset of multiple sclerosis operating module networks demonstrated the evolution of altered regulation of nuclear receptor-dependent apoptosis. Our findings demonstrating a silent multiple sclerosis trait that is associated with suppressed expression of the nuclear receptor network and inhibited apoptosis of activated T-cells support the role of these transcription signals in the evolution of the autoimmune processes that operate in the pre-disease stage of multiple sclerosis.

Prospective National Study of the Prevalence, Incidence, Management and Outcome of a Large Contemporary Cohort of Patients With Incident Non‐Valvular Atrial Fibrillation

Background There are few studies of atrial fibrillation (AF) outside of North America or Europe. The aim of the present study was to assess the prevalence, incidence, management and outcomes of patients with new atrial fibrillation, in a large contemporary cohort (2004–2012) of adult patients. Methods and Results The Clalit Health Services (CHS) computerized database of 2 420 000 adults, includes data of community clinic visits, hospital discharge records, medical diagnoses, medications, medical interventions, and laboratory test results. The prevalence of AF on January 1, 2004 was 71 644 (3%). Prevalence and incidence of AF increased with age and was higher in men versus women. During the study period (2004–2012) 98 811 patients developed new non‐valvular AF (mean age −72, 50% women, 46% with cardiovascular disease, 6% with prior stroke). The rate of persistent warfarin use (dispensed for >3 months in a calendar year) was low (25.7%) and it increased with increasing stroke risk score. Individual Time in Therapeutic Range (TTR) among warfarin users was 42%. The incidence rate of ischemic stroke and death increased with age. The rate of stroke increased from 2 per 1000 person years in patients with CHA2DS2_VASC SCORE of 0, to 58 per 1000 person years in those with a score of 9. Conclusions In the present study the prevalence and incidence of AF, stroke, and death were comparable to those reported in Europe and North America. The low use of anticoagulation calls for measures to increase adherence to current treatment recommendations in order to improve outcomes.

Priority Setting for Pandemic Influenza: An Analysis of National Preparedness Plans

The authors provide a targeted review of national pandemic influenza plans from the developed and developing world, describing national variations in prioritization of vaccines and antiviral medications.

Predicting 30-day readmissions with preadmission electronic health record data.

Background:Readmission prevention should begin as early as possible during the index admission. Early identification may help target patients for within-hospital readmission prevention interventions. Objectives:To develop and validate a 30-day readmission prediction model using data from electronic health records available before the index admission. Research Design:Retrospective cohort study of admissions between January 1 and March 31, 2010. Subjects:Adult enrollees of Clalit Health Services, an integrated delivery system, admitted to an internal medicine ward in any hospital in Israel. Measures:All-cause 30-day emergency readmissions. A prediction score based on before admission electronic health record and administrative data (the Preadmission Readmission Detection Model—PREADM) was developed using a preprocessing variable selection step with decision trees and neural network algorithms. Admissions with a recent prior hospitalization were excluded and automatically flagged as “high-risk.” Selected variables were entered into multivariable logistic regression, with a derivation (two-thirds) and a validation cohort (one-third). Results:The derivation dataset comprised 17,334 admissions, of which 2913 (16.8%) resulted in a 30-day readmission. The PREADM includes 11 variables: chronic conditions, prior health services use, body mass index, and geographical location. The c-statistic was 0.70 in the derivation set and of 0.69 in the validation set. Adding length of stay did not change the discriminatory power of the model. Conclusions:The PREADM is designed for use by health plans for early high-risk case identification, presenting discriminatory power better than or similar to that of previously reported models, most of which include data available only upon discharge.

An Outbreak of Norovirus Gastroenteritis on an Israeli Military Base

Background:Noroviruses (NVs) are a predominant cause of viral gastroenteritis outbreaks, but they are difficult to identify because they cannot be cultivated in cell culture. Therefore, reverse-transcriptase polymerase chain reaction (RT-PCR) assays are widely used in the testing of clinical stool specimens for NV. However, testing of perianal swabs in the context of an outbreak is considered to be an insensitive method for identification of NV using the RT-PCR technique. An outbreak of acute gastroenteritis involving 159 soldiers on a training base of the Israel Defense Force in December 1999 allowed us to evaluate this identification method.Patients and Methods:An epidemiologic investigation, a sanitation survey and a case-control study of exposure to different food items served up to 48 h preceding the outbreak were conducted. Stool samples in the form of post-defecation perianal swabs were collected from 24 ill personnel and three non-ill food handlers. Swabs were tested for the presence of NV by RT-PCR assay.Results:Epidemiologic data were consistent with a pointsource food-borne outbreak which was associated with consumption of fresh vegetable salad in the base mess hall (OR = 4.38, 95% CI 1.51–13.35). Both epidemiologic and clinical features were suggestive of gastroenteritis caused by NV, and upon laboratory analysis perianal swabs from four of 24 cases were positive for NV.Conclusion:The combination of practical specimen collection with perianal post-defecation swabs, and the utilization of a molecular epidemiology approach, can simplify the rapid identification of outbreaks caused by NVs.

Inverse Association Between Helicobacter pylori and Pediatric Asthma in a High‐Prevalence Population

Background:  Helicobacter pylori‐associated disease has led to aggressive diagnostic and eradication protocols that are partially responsible for the decrease in prevalence of H. pylori carriage. Recent evidence indicates that in low‐prevalence populations, H. pylori may have protective effects on allergic diseases. The aim of this study was to explore the relationship between pediatric asthma and H. pylori infection in a population with high prevalence of H. pylori infection.

A systematic analytic approach to pandemic influenza preparedness planning.

The World Health Organization warns that a flu pandemic is inevitable, and possibly imminent. Barnett and colleagues discuss a tool called the Haddon Matrix that could help in pandemic influenza planning.

Applying risk perception theory to public health workforce preparedness training.

Since 9/11, public health has seen a progressive culture change toward a 24/7 emergency response organizational model. This transition entails new expectations for public health workers, including (1) a readiness and willingness to report to duty in emergencies and (2) an ability to effectively communicate risk to an anxious public about terrorism or naturally occurring disasters. To date, however, research on readiness education for health department workers has focused little attention upon the risk perceptions that may influence their willingness to report to duty during disasters, as well as their ability to provide effective emergency risk communication to the public. Here, we apply risk perception factors to explore the potential barriers and remedies to effective public health workforce emergency response.

Time-Dependent Risk of Cancer After a Diabetes Diagnosis in a Cohort of 2.3 Million Adults

Using a time-dependent approach, we investigated all-site and site-specific cancer incidence in a large population stratified by diabetes status. The study analyzed a closed cohort comprised of Israelis aged 21-89 years, enrolled in a health fund, and followed from 2002 to 2012. Adjusting for age, ethnicity, and socioeconomic status, we calculated hazard ratios for cancer incidence using Cox regression separately for participants with prevalent and incident diabetes; the latter was further divided by time since diabetes diagnosis. Of the 2,186,196 individuals included in the analysis, 159,104 were classified as having prevalent diabetes, 408,243 as having incident diabetes, and 1,618,849 as free of diabetes. In both men and women, diabetes posed an increased risk of cancers of the liver, pancreas, gallbladder, endometrium, stomach, kidney, brain (benign), brain (malignant), colon/rectum, lung (all, adenocarcinoma, and squamous cell carcinoma), ovary, and bladder, as well as leukemia, multiple myeloma, non-Hodgkin lymphoma, and breast cancer in postmenopausal women. No excess risk was observed for breast cancer in premenopausal women or for thyroid cancer. Diabetes was associated with a reduced risk of prostate cancer. Hazard ratios for all-site and site-specific cancers were particularly elevated during the first year following diabetes diagnosis. The findings of this large study with a time-dependent approach are consistent with those of previous studies that have observed associations between diabetes and cancer incidence.