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

Perceived Stress, Resilience, and Wellbeing in Seasoned Isha Yoga Practitioners Compared to Matched Controls During the COVID-19 Pandemic

Background: Yoga practices, including breathing, meditation, and posture protocols (asanas), have been shown to facilitate physical and mental wellbeing. Methods: Seasoned yoga practitioners were recruited from the Isha Foundation. Recruitment of the comparison group was achieved using snowball sampling and were not yoga practitioners. Participants in the non-yoga group were randomized to a 3-min Isha practice or a comparator group asked to perform 15-min of daily reading. Participants completed a series of web-based surveys (REDCap) at baseline, 6, and 12 weeks. These surveys include validated scales and objective questions on COVID-19 infection and medical history. The validated questionnaires assess for: perceived stress (PSS), mood states [anxiety and depression (PHQ-4), joy (DPES-Joy subscale)], mindfulness attention and awareness (MAAS), resilience (BRS), mental wellbeing (WEMWBS) and recovery from traumatic event (PTGI). Weekly activity diaries were employed as a tool for collecting compliance information from study participants. Perceived stress scale scores were identified as primary outcome for this study. Findings: The median Perceived Stress Scale (PSS) score for the yoga practitioners compared to the active and placebo comparators was significantly lower at all time-points: baseline: 11 [IQR 7–15] vs. 16 [IQR 12–21] in both the active and placebo comparators (p \u3c 0.0001); 6 weeks: 9 [IQR 6–13] vs. 12 [IQR 8–17] in the active comparator and 14 [IQR 9–18] in the placebo comparator (p \u3c 0.0001); and 12 weeks: 9 [IQR 5–13] vs. 11.5 [IQR 8–16] in the active comparators and 13 [IQR 8–17] in the placebo comparator (p \u3c 0.0001). Among the randomized participants that were compliant for the full 12 weeks, the active comparators had significantly lower median PSS scores than the placebo comparators 12 weeks [10 (IQR 5–14) vs. 13 (IQR 8–17), p = 0.017]. Further, yoga practitioners had significantly lower anxiety at all three-time points (p \u3c 0.0001), lower depression at baseline and 6 weeks (p \u3c 0.0003), and significantly higher wellbeing (p \u3c 0.0001) and joy (p \u3c 0.0001) at all three-time points, compared to the active and placebo comparator groups. Interpretation: The lower levels of stress, anxiety, depression, and higher level of wellbeing and joy seen in the yoga practitioners compared to the active and placebo comparators illustrate the impact of regular yoga practices on mental health even during the pandemic

Exposure to tobacco smoke based on urinary cotinine levels among Israeli smoking and nonsmoking adults: a cross-sectional analysis of the first Israeli human biomonitoring study

Background Cotinine levels provide a valid measure of exposure to environmental tobacco smoke (ETS). The goal of this study was to examine exposure to tobacco smoke among smoking and nonsmoking Israeli adults and to identify differences in ETS exposure among nonsmokers by socio-demographic factors. Methods We analyzed urinary cotinine data from the first Israeli human biomonitoring study conducted in 2011. In-person questionnaires included data on socio-demographic and active smoking status. Cotinine levels were measured using a gas chromatography–mass spectrometry procedure. We calculated creatinine-adjusted urinary cotinine geometric means (GM) among smokers and nonsmokers, and by socio-demographic, smoking habits and dietary factors. We analyzed associations, in a univariable and multivariable analysis, between socio-demographic variables and proportions of urinary cotinine ≥1 μg/l (Limit of Quantification = LOQ) or ≥4 μg/l. Results Cotinine levels were significantly higher among 91 smokers (GM = 89.7 μg/g creatinine; 95% confidence interval [CI]: 47.4-169.6) than among 148 nonsmokers (GM = 1.3; 1.1-1.7). Among exclusive waterpipe smokers, cotinine levels were relatively high (GM = 53.4; 95% CI 12.3-232.7). ETS exposure was widespread as 62.2% of nonsmokers had levels ≥ LOQ, and was higher in males (75.8%) than in females (52.3%). In a multivariable model, urinary cotinine ≥ LOQ was higher in males (Prevalence ratio [PR] = 1.30; 95% CI: 1.02-1.64, p = 0.032) and in those with lower educational status (PR = 1.58; 1.04-2.38, p = 0.031) and decreased with age (PR = 0.99; 0.98-1.00, p = 0.020, per one additional year). There were no significant differences by ethnicity, residence type or country of birth. Conclusions Our findings indicate widespread ETS exposure in the nonsmoking Israeli adult population, especially among males, and younger and less educated participants. These findings demonstrate the importance of human biomonitoring, were instrumental in expanding smoke-free legislation implemented in Israel on July 2012 and will serve as a baseline to measure the impact of the new legislation

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Pre-Conception Dyslipidemia Is Associated with Development of Preeclampsia and Gestational Diabetes Mellitus.

The association between glucose intolerance, elevated blood pressure and abnormal lipid levels is well established and comprises the basis of metabolic syndrome pathophysiology. We hypothesize that abnormal preconception lipid levels are associated with the increased risk of severe pregnancy complications such as preeclampsia and gestational diabetes mellitus.We included all singleton deliveries (n = 27,721) of women without known cardiovascular morbidity and preeclampsia and gestational diabetes mellitus during previous pregnancies. Association between preconception low high density lipoprotein cholesterol (HDLc level≤50 mg/dL), high triglycerides (level≥150 mg/dL) and the primary outcome (composite of gestational diabetes mellitus/or preeclampsia) was assessed using Generalized Estimation Equations.Primary outcome of preeclampsia and/or gestational diabetes was observed in a total of 3,243 subjects (11.7%). Elevated triglycerides and low HDLc were independently associated with the primary outcome: with odds ratio (OR) of 1.61 (95% CI 1.29-2.01) and OR = 1.33 (95% CI 1.09-1.63), respectively, after adjusting for maternal age, weight, blood pressure, repeated abortions, fertility treatments and fasting glucose. There was an interaction between the effects of HDLc≤50 mg/dL and triglycerides≥150 mg/dL with an OR of 2.69 (95% CI 1.73-4.19).Our analysis showed an increased rate of preeclampsia and/or gestational diabetes in women with low HDLc and high triglycerides values prior to conception. In view of the severity of these pregnancy complications, we believe this finding warrants a routine screening for the abnormal lipid profile among women of a child-bearing age

Novel Approaches to Air Pollution Exposure and Clinical Outcomes Assessment in Environmental Health Studies

An accurate assessment of pollutants’ exposure and precise evaluation of the clinical outcomes pose two major challenges to the contemporary environmental health research. The common methods for exposure assessment are based on residential addresses and are prone to many biases. Pollution levels are defined based on monitoring stations that are sparsely distributed and frequently distanced far from residential addresses. In addition, the degree of an association between outdoor and indoor air pollution levels is not fully elucidated, making the exposure assessment all the more inaccurate. Clinical outcomes’ assessment, on the other hand, mostly relies on the access to medical records from hospital admissions and outpatients’ visits in clinics. This method differentiates by health care seeking behavior and is therefore, problematic in evaluation of an onset, duration, and severity of an outcome. In the current paper, we review a number of novel solutions aimed to mitigate the aforementioned biases. First, a hybrid satellite-based modeling approach provides daily continuous spatiotemporal estimations with improved spatial resolution of 1 × 1 km2 and 200 × 200 m2 grid, and thus allows a more accurate exposure assessment. Utilizing low-cost air pollution sensors allowing a direct measurement of indoor air pollution levels can further validate these models. Furthermore, the real temporal-spatial activity can be assessed by GPS tracking devices within the individuals’ smartphones. A widespread use of smart devices can help with obtaining objective measurements of some of the clinical outcomes such as vital signs and glucose levels. Finally, human biomonitoring can be efficiently done at a population level, providing accurate estimates of in-vivo absorbed pollutants and allowing for the evaluation of body responses, by biomarkers examination. We suggest that the adoption of these novel methods will change the research paradigm heavily relying on ecological methodology and support development of the new clinical practices preventing adverse environmental effects on human health

An Integrated and Interdisciplinary Model for Predicting the Risk of Injury and Death in Future Earthquakes.

A comprehensive technique for earthquake-related casualty estimation remains an unmet challenge. This study aims to integrate risk factors related to characteristics of the exposed population and to the built environment in order to improve communities' preparedness and response capabilities and to mitigate future consequences.An innovative model was formulated based on a widely used loss estimation model (HAZUS) by integrating four human-related risk factors (age, gender, physical disability and socioeconomic status) that were identified through a systematic review and meta-analysis of epidemiological data. The common effect measures of these factors were calculated and entered to the existing model's algorithm using logistic regression equations. Sensitivity analysis was performed by conducting a casualty estimation simulation in a high-vulnerability risk area in Israel.the integrated model outcomes indicated an increase in the total number of casualties compared with the prediction of the traditional model; with regard to specific injury levels an increase was demonstrated in the number of expected fatalities and in the severely and moderately injured, and a decrease was noted in the lightly injured. Urban areas with higher populations at risk rates were found more vulnerable in this regard.The proposed model offers a novel approach that allows quantification of the combined impact of human-related and structural factors on the results of earthquake casualty modelling. Investing efforts in reducing human vulnerability and increasing resilience prior to an occurrence of an earthquake could lead to a possible decrease in the expected number of casualties