Lena Novack

Iatrogenic Gastric Acid Suppression and the Risk of Nosocomial Clostridium difficile Infection

BACKGROUND The incidence and severity of Clostridium difficile infections are increasing. Acid-suppressive therapy has been suggested as a risk factor for C difficile, but this remains controversial. METHODS We conducted a pharmacoepidemiologic cohort study, performing a secondary analysis of data collected prospectively on 101 796 discharges from a tertiary care medical center during a 5-year period. The primary exposure of interest was acid suppression therapy, classified by the most intense acid suppression therapy received (no acid suppression, histamine(2)-receptor antagonist [H(2)RA] therapy, daily proton pump inhibitor [PPI], and PPI more frequently than daily). RESULTS As the level of acid suppression increased, the risk of nosocomial C difficile infection increased, from 0.3% (95% confidence interval [CI], 0.21%-0.31%) in patients not receiving acid suppressive therapy to 0.6% (95% CI, 0.49%-0.79%) in those receiving H(2)RA therapy, to 0.9% (95% CI, 0.80%-0.98%) in those receiving daily PPI treatment, and to 1.4% (1.15%-1.71%) in those receiving more frequent PPI therapy. After adjustment for comorbid conditions, age, antibiotics, and propensity score-based likelihood of receipt of acid-suppression therapy, the association persisted, increasing from an odds ratio of 1 (no acid suppression [reference]) to 1.53 (95% CI, 1.12-2.10) (H(2)RA), to 1.74 (95% CI, 1.39-2.18) (daily PPI), and to 2.36 (95% CI, 1.79-3.11) (more frequent PPI). Similar estimates were found with a matched cohort analysis and with nested case-control techniques. CONCLUSIONS Increasing levels of pharmacologic acid suppression are associated with increased risks of nosocomial C difficile infection. This evidence of a dose-response effect provides further support for the potentially causal nature of iatrogenic acid suppression in the development of nosocomial C difficile infection.

The effect of statin therapy on infection-related mortality in patients with atherosclerotic diseases*

Objective:Statins have pleiotropic effects that are independent of their lipid-lowering ability. We have previously shown that prior statin therapy is associated with a decreased risk of severe sepsis in patients admitted with acute bacterial infection. The aim of this study was to determine whether statin therapy is associated with a decreased risk of infection-related mortality. Design:A prospective, observational, population-based study. Setting:Tertiary university medical center. Patients:Using a computerized database, 11,490 patients with atherosclerotic diseases were identified and followed for up to 3 yrs. Two groups of patients were compared: those receiving statins in the final month before follow-up termination and those who were not. Interventions:None. Measurements and Main Results:The primary outcome was infection-related mortality. Of the 11,362 patients included in the final analysis, 5,698 (50.1%) belonged to the statin group. Median follow-up was 19.8 months (interquartile range, 14.3–33.3). The risk of infection-related mortality was significantly lower in the statin compared with the no-statin group (0.9% vs. 4.1%), reflecting a relative risk of 0.22 (95% confidence interval, 0.17–0.28). Stepwise Cox proportional hazard survival analysis including a propensity score for receiving statins revealed that the protective effect of statins adjusted for all known potential confounders remained highly significant (hazard ratio, 0.37; 95% confidence interval, 0.27–0.52). Conclusions:Therapy with statins may be associated with a reduced risk of infection-related mortality. This protective effect is independent of all known comorbidities and dissipates when the medication is discontinued. If this finding is supported by prospective controlled trials, statins may play an important role in the primary prevention of infection-related mortality.

Association of lipid levels during gestation with preeclampsia and gestational diabetes mellitus: a population-based study

OBJECTIVE The study evaluates lipids profile changes during gestation in pregnancies with and without preeclampsia and/or gestational diabetes. STUDY DESIGN Lipid profiles were assessed between year prior and after pregnancy in 9911 women without cardiovascular comorbidities. RESULTS Lipid levels during gestation varied substantially with a nadir following conception and a peak at delivery. Compared to preconception levels total cholesterol levels increased from 164.4 mg/dL to 238.6 mg/dL and triglycerides (TGs) from 92.6 mg/dL to 238.4 mg/dL. The composite endpoint (gestational diabetes mellitus or preeclampsia) occurred in 1209 women (12.2%). Its prevalence increased with levels of TG-from 7.2% in the group with low TGs (<25th percentile adjusted for the gestational month) to 19.8% in the group with high TGs (>75th percentile), but was not associated with high-density lipoprotein levels. In multivariate analysis higher TGs levels, but not low high-density lipoprotein, were associated with the primary endpoint. CONCLUSION Lipid levels change substantially during gestation. Abnormal levels of TGs are associated with pregnancy complications.

Evidence-based medicine: assessment of knowledge of basic epidemiological and research methods among medical doctors

Background: An understanding of statistical methods and basic epidemiology are crucial for the practice of modern medicine. Aims: To assess (1) the knowledge of basic methods of conducting research and data analysis among residents and practicing doctors and (2) the effect of country of medical school graduation, professional status, medical article reading and writing experience on the level of this knowledge. Methods: Data were collected by means of a supervised self-administered questionnaire, which was distributed among doctors at Soroka Medical Center, Beer-Sheva, Israel. The questionnaire included 10 multiple-choice questions on basic epidemiology and statistics, and respondent demographical data. Results: Of the 260 eligible doctors, 219 (84.2%) returned completed questionnaires. Of the 219 doctors, 50% graduated more than 8.5 years ago, 39.7% were specialists and the remaining were residents. The most frequent specialty was internal medicine (37.4%). Israel was the most frequent country of graduation (45.7%), followed by the former Soviet Union (Eastern medical education; 38.4%). The median total score of knowledge was 4 of 10 questions (interquartile range 2–6). A higher score was associated with a Western medical education, being a specialist, shorter elapsed time since graduation, higher number of publications and self-reported reading of “methods” and “discussion” sections in scientific articles. Conclusion: This study found a low level of knowledge of basic principles of research methods and data analysis among doctors, and this knowledge considerably differed by country of medical school graduation.

Urinary concentrations of organophosphate pesticide metabolites in adults in Israel: demographic and dietary predictors.

Exposure to organophosphate pesticides (OPs) in agricultural and urban populations has been associated with a range of adverse health effects. The purpose of the current study was to estimate exposure to OPs in the general adult population in Israel and to determine dietary and demographic predictors of exposure. We measured six non-specific organophosphate pesticide metabolites (dialkyl phosphates) in urine samples collected from 247 Israeli adults from the general population. We collected detailed demographic and dietary data from these individuals, and explored associations between demographic and dietary characteristics and urinary dialkyl phosphate concentrations. OP metabolites were detectable in all urine samples. Concentrations of several dialkyl phosphate metabolites (dimethylphosphate, dimethylthiophosphate, diethylphosphate) were high in our study population relative to the general populations in the US and Canada and were comparable to those reported in 2010 in France. Total dialkyl phosphates were higher in individuals with fruit consumption above the 75th percentile. In a multivariate analysis, total molar dialkyl phosphate concentration increased with age and was higher in individuals with high income compared to individuals with the lowest income. Total diethyl metabolite concentrations were higher in females and in study participants whose fruit consumption was above the 75th percentile. In conclusion, we found that levels of exposure to OP pesticides were high in our study population compared to the general population in the US and Canada and that intake of fruits is an important source of exposure.

Impact of target lesion and nontarget lesion cardiac events on 5-year clinical outcomes after sirolimus-eluting or bare-metal stenting.

OBJECTIVES We sought to compare patient-oriented outcomes related to target vessel or nontarget vessel events for sirolimus-eluting stents (SES) versus bare-metal stents. BACKGROUND SES significantly reduce restenosis but the influence of reduced restenosis on overall patient-oriented outcome has not been reported. METHODS The study population included 1,057 patients randomized in the SIRIUS (Sirolimus-Eluting Stent in De Novo Native Coronary Lesions) study and followed clinically for 5 years. The primary end point was a composite of all-cause mortality, any myocardial infarction, or any repeat revascularization. In secondary analyses, myocardial infarction and repeat revascularization events attributed to the target vessel or a nontarget vessel were compared by stent type. RESULTS Patients with an SES were more likely to be free from the primary composite end point at 5 years (60.4% vs. 47.8%, p < 0.001) chiefly due to a sustained reduction in target lesion revascularization for SES (cumulative incidence: 12.5% vs. 28.8%, p < 0.001). There was no difference in the cumulative incidence of myocardial infarction or revascularization attributed to remote segments of the target vessel. Events attributed to the nontarget vessel were frequent and not different for SES versus bare-metal stents (25.7% vs. 25.8%). CONCLUSIONS The benefit of SES over bare-metal stents for reduced target lesion revascularization is maintained for 5 years. Remote coronary segments of the target vessel and nontarget vessel remain an important cause of future adverse events despite sustained restenosis benefit.

The percentage of patients achieving PASI 75 after 1 month and remission time after climatotherapy at the Dead Sea

Background  Dead Sea climatotherapy (DSC) is a highly effective treatment for psoriasis; however, there are scanty data concerning the duration of post‐therapy remission.

Urinary concentrations of environmental contaminants and phytoestrogens in adults in Israel

BACKGROUND The Ministry of Health Biomonitoring Study estimated exposure of individuals in the Israeli population to bisphenol A (BPA), organophosphate (OP) pesticides, phthalates, cotinine, polycyclic aromatic hydrocarbons (PAHs), and the phytoestrogenic compounds genistein and daidzein. METHODS In 2011, 250 individuals (ages 20-74) were recruited from five different regions in Israel. Urine samples were collected and questionnaire data were obtained, including detailed dietary data (food frequency questionnaire and 24hour recall). Urinary samples were analyzed for BPA, OP metabolites (dialkyl phosphates), phthalate metabolites, cotinine, PAH metabolites, genistein, and daidzein. RESULTS AND DISCUSSION BPA urinary concentrations were above the limit of quantification (LOQ) in 89% of the samples whereas urinary concentrations of phthalate metabolites were above the LOQ in 92-100% of the samples. PAH metabolites were above the LOQ in 63-99% of the samples whereas OP metabolites were above the LOQ in 44-100% of the samples. All non-smoking participants had detectable levels of cotinine in their urine; 63% had levels above the LOQ, and the rate of quantification was high compared to the general non-smoking population in Canada. Median creatinine adjusted concentrations of several OP metabolites (dimethyl phosphate, dimethyl thiophosphate) were high in our study population compared to the general US and Canadian populations. Median creatinine adjusted urinary BPA concentrations in the study population were comparable to those in Belgium and Korea; higher than those reported for the general US, German, and Canadian populations; and very low compared to health-based threshold values. Phthalate concentrations were higher in our study population compared to the general US population but values were very low compared to health-based threshold values. Median creatinine adjusted PAH concentrations were generally comparable to those reported for the general US population; median creatinine adjusted daidzein concentrations were high in our population compared to the general US population whereas genistein concentrations were comparable. CONCLUSIONS We interpreted observed urinary contaminant levels observed in our study by comparing values with health-based threshold values and/or values from international human biomonitoring studies. Using this data interpretation scheme, we identified two contaminants as being of potential public health concern and high priority for public health policy intervention: environmental tobacco smoke (ETS) and OP pesticides. We used the data collected in this study to support public health policy interventions. We plan to conduct a follow-up biomonitoring study in 2015 to measure ETS and OP exposure in the general population in Israel, to evaluate the effectiveness of relevant policy interventions.

DIC Score in Pregnant Women – A Population Based Modification of the International Society on Thrombosis and Hemostasis Score

Objectives The objectives of this study were: 1) To determine the component needed to generate a validated DIC score during pregnancy. 2) To validate such scoring system in the identification of patients with clinical diagnosis of DIC. Material and Methods This is a population based retrospective study, including all women who gave birth at the ‘Soroka University Medical Center’ during the study period, and have had blood coagulation tests including complete blood cell count, prothrombin time (PT)(seconds), partial thromboplastin time (aPTT), fibrinogen, and D-dimers. Nomograms for pregnancy were established, and DIC score was constructed based on ROC curve analyses. Results 1) maternal plasma fibrinogen concentrations increased during pregnancy; 2) maternal platelet count decreased gradually during gestation; 3) the PT and PTT values did not change with advancing gestation; 4) PT difference had an area under the curve (AUC) of 0.96 (p<0.001), and a PT difference ≥1.55 had an 87% sensitivity and 90% specificity for the diagnosis of DIC; 5) the platelet count had an AUC of 0.87 (p<0.001), an 86% sensitivity and 71% specificity for the diagnosis of DIC; 6) fibrinogen concentrations had an AUC of 0.95 (p<0.001) and a cutoff point ≤3.9 g/L had a sensitivity of 87% and a specificity of 92% for the development of DIC; and 7) The pregnancy adjusted DIC score had an AUC of 0.975 (p<0.001) and at a cutoff point of ≥26 had a sensitivity of 88%, a specificity of 96%, a LR(+) of 22 and a LR(−) of 0.125 for the diagnosis of DIC. Conclusion We could establish a sensitive and specific pregnancy adjusted DIC score. The positive likelihood ratio of this score suggests that a patient with a score of ≥26 has a high probability to have DIC.

Acid suppression therapy does not predispose to Clostridium difficile infection: the case of the potential bias.

Objective An adverse effect of acid-suppression medications on the occurrence of Clostridium difficile infection (CDI) has been a common finding of many, but not all studies. We hypothesized that association between acid-suppression medications and CDI is due to the residual confounding in comparison between patients with infection to those without, predominantly from non-tested and less sick subjects. We aimed to evaluate the effect of acid suppression therapy on incidence of CDI by comparing patients with CDI to two control groups: not tested patients and patients suspected of having CDI, but with a negative test. Methods We conducted a case-control study of adult patients hospitalized in internal medicine department of tertiary teaching hospital between 2005–2010 for at least three days. Controls from each of two groups (negative for CDI and non-tested) were individually matched (1∶1) to cases by primary diagnosis, Charlson comorbidity index, year of hospitalization and gender. Primary outcomes were diagnoses of International Classification of Diseases (ICD-9)–coded CDI occurring 72 hours or more after admission. Results Patients with CDI were similar to controls with a negative test, while controls without CDI testing had lower clinical severity. In multivariable analysis, treatment by acid suppression medications was associated with CDI compared to those who were not tested (OR = 1.88, p-value = 0.032). Conversely, use of acid suppression medications in those who tested negative for the infection was not associated with CDI risk as compared to the cases (OR = 0.66; p = 0.059). Conclusions These findings suggest that the reported epidemiologic associations between use of acid suppression medications and CDI risk may be spurious. The control group choice has an important impact on the results. Clinical differences between the patients with CDI and those not tested and not suspected of having the infection may explain the different conclusions regarding the acid suppression effect on CDI risk.