Serious Adverse Events Reported with Dietary Supplement Use in the United States: A 2.5 Year Experience.

Dietary supplement marketers assure the safety of their products by complying with current good manufacturing practices and a host of federal regulations, including those enforced by the Food and Drug Administration (FDA). Post-market surveillance is a key part of identifying safety problems associated with dietary supplement products. FDA requires dietary supplement marketers to provide a domestic address or phone number on product labels for consumers, family members, or health care professionals to report adverse events (AEs) associated with product use and to report all serious adverse events (SAEs) to the agency within 15 business days of receipt. We aimed to evaluate the characteristics of AEs reported with dietary supplement use, including dietary supplement type and Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) that occur with reported SAEs. A total of 41,121 unique adverse event cases reported to two large, U.S.-based dietary supplement marketers in a 2.5-year period (March 1, 2014-August 31, 2016) were assessed for seriousness using established criteria. Each SAE was assigned one or more MedDRA preferred terms and system organ classes (SOC). The types of supplements most responsible for SAEs were assessed. Of the 41,121 AE cases reported, 203 (0.48%) were SAEs. SAEs tended to occur with products marketed for weight loss (69.0%) and glycemic control (19.2%). SAEs occurred most commonly in the cardiovascular, gastrointestinal, and nervous system disorder SOCs. The percentage of SAEs reported to dietary supplement marketers is low, predominantly among consumers of two types of supplements. Further study is needed among a larger cohort of supplement users to determine causal associations between types of supplement products and serious adverse events.

Point-of-Care Ultrasound Improves Shared Diagnostic Understanding Between Patients and Providers.

OBJECTIVES: Point-of-care ultrasound (POCUS) has become an integral part of the physical examination. The effect on shared understanding of adding POCUS to the traditional examination is unknown, yet this is an often-described benefit of POCUS. The primary aim of this study was to determine whether the use of POCUS improves shared understanding between providers and patients about patients' diagnoses. METHODS: This was a prospective controlled trial involving a convenience sample of hospitalized adults. Providers in the control arm performed usual care without POCUS, whereas providers in the study arm had the option to add POCUS. Surveys were administered to the subjects and their providers with questions on patient understanding of symptoms, diagnosis, and main contributors to their health problem. Two independent physicians rated the degree of shared understanding between patient and provider surveys. RESULTS: Of the 64 patients enrolled in the study, 60 had complete data. There was increased shared understanding between providers and patients with respect to their diagnosis (POCUS 9.56 ± 0.63, non-POCUS 7.62 ± 1.63, P < 0.005) and main contributors (POCUS 9.65 ± 0.77, non-POCUS 8.30 ± 1.13, P < 0.005) in the POCUS arm compared with the non-POCUS arm. Patients also increased the self-rating of their understanding of their health problem in the POCUS arm. CONCLUSIONS: These findings suggest that using POCUS improves patients' understanding of the diagnostic process. POCUS may be uniquely poised to enhance patients' understanding of and engagement in that process.

Meta-analysis of Egg Consumption and Risk of Coronary Heart Disease and Stroke.

The possible relationship between dietary cholesterol and cardiac outcomes has been scrutinized for decades. However, recent reviews of the literature have suggested that dietary cholesterol is not a nutrient of concern. Thus, we conducted a meta-analysis of egg intake (a significant contributor to dietary cholesterol) and risk of coronary heart disease (CHD) and stroke. A comprehensive literature search was conducted through August 2015 to identify prospective cohort studies that reported risk estimates for egg consumption in association with CHD or stroke. Random-effects meta-analysis was used to generate summary relative risk estimates (SRREs) for high vs low intake and stratified intake dose-response analyses. Heterogeneity was examined in subgroups where sensitivity and meta regression analyses were conducted based on increasing egg intake. A 12% decreased risk (SRRE = 0.88, 95% confidence interval [CI], 0.81-0.97) of stroke was observed in the meta-analysis of 7 studies of egg intake (high vs low; generally 1/d vs <2/wk), with little heterogeneity (p-H = 0.37, I2 = 7.50). A nonstatistically significant SRRE of 0.97 (95% CI, 0.88-1.07, p-H = 0.67, I2 = 0.00) was observed in the meta-analysis of 7 studies of egg consumption and CHD. No clear dose-response trends were apparent in the stratified intake meta-analyses or the meta regression analyses. Based on the results of this meta-analysis, consumption of up to one egg daily may contribute to a decreased risk of total stroke, and daily egg intake does not appear to be associated with risk of CHD. Key Teaching Points: • The role of egg consumption in the risk of stroke and coronary heart disease has come under scrutiny over many years. • A comprehensive meta-analysis of prospective cohort studies that reported risk estimates for egg consumption in association with CHD or stroke was performed on the peer-reviewed epidemiologic literature through August 2015. • Overall, summary associations indicate that intake of up to 1 egg daily may be associated with reduced risk of total stroke. • Overall, summary associations show no clear association between egg intake and increased or decreased risk of CHD. • Eggs are a relatively low-cost and nutrient-dense whole food that provides a valuable source of protein, essential fatty acids, antioxidants, choline, vitamins, and minerals.

Dairy consumption and CVD: a systematic review and meta-analysis.

Inverse associations between dairy consumption and CVD have been reported in several epidemiological studies. Our objective was to conduct a meta-analysis of prospective cohort studies of dairy intake and CVD. A comprehensive literature search was conducted to identify studies that reported risk estimates for total dairy intake, individual dairy products, low/full-fat dairy intake, Ca from dairy sources and CVD, CHD and stroke. Random-effects meta-analyses were used to generate summary relative risk estimates (SRRE) for high v. low intake and stratified intake dose-response analyses. Additional dose-response analyses were performed. Heterogeneity was examined in sub-group and sensitivity analyses. In total, thirty-one unique cohort studies were identified and included in the meta-analysis. Several statistically significant SRRE below 1.0 were observed, namely for total dairy intake and stroke (SRRE=0·91; 95% CI 0·83, 0·99), cheese intake and CHD (SRRE=0·82; 95% CI 0·72, 0·93) and stroke (SRRE=0·87; 95% CI 0·77, 0·99), and Ca from dairy sources and stroke (SRRE=0·69; 95% CI 0·60, 0·81). However, there was little evidence for inverse dose-response relationships between the dairy variables and CHD and stroke after adjusting for within-study covariance. The results of this meta-analysis of prospective cohort studies have shown that dairy consumption may be associated with reduced risks of CVD, although additional data are needed to more comprehensively examine potential dose-response patterns.

Mesothelioma among Motor Vehicle Mechanics: An Updated Review and Meta-analysis.

BACKGROUND: We published a meta-analysis of the association between work as a motor vehicle mechanic and mesothelioma in 2004. Since then, several relevant studies on this topic have been published. Thus, to update the state-of-the-science on this issue, we conducted a new systematic review and meta-analysis. METHODS: A comprehensive PubMed literature search through May 2014 was conducted to identify studies that reported relative risk estimates for mesothelioma among motor vehicle mechanics (in general), and those who were engaged in brake repair (specifically). Studies were scored and classified based on study characteristics. Random-effects meta-analyses generated summary relative risk estimates (SRREs) and corresponding 95% confidence intervals (CI). Heterogeneity of results was examined by calculating Q-test P-values (P-H) and I (2) estimates. Sub-group and sensitivity analyses were conducted for relevant study characteristics and quality measures. RESULTS: Ten case-control studies, one cohort study, and five proportionate mortality ratio (PMR)/standardized mortality odds ratio (SMOR) studies were identified and included in the quantitative assessment. Most meta-analysis models produced SRREs below 1.0, and no statistically significant increases in mesothelioma were observed. The SRRE for all studies was 0.80 (95% CI: 0.61-1.05) with significant heterogeneity (P-H <0.001, I (2) = 62.90). A similar SRRE was observed among the five Tier 1 studies with the highest quality ratings (SRRE = 0.76, 95% CI: 0.46-1.25), with no heterogeneity among studies (P-H = 0.912, I (2) = 0.00). Meta-analysis of the Tier 2 (n = 5) and Tier 3 (n = 6) studies resulted in SRREs of 1.09 (95% CI: 0.76-1.58) and 0.73 (95% CI: 0.49-1.08), respectively. Restricting the analysis to Tiers 1 and 2 combined resulted in an SRRE of 0.92 (95% CI: 0.72-1.29). The SRRE specific to brake work (n = 4) was 0.64 (95% CI: 0.38-1.09). CONCLUSIONS: This meta-analysis of the epidemiologic studies provides evidence that motor vehicle mechanics, including workers who were engaged in brake repair, are not at an increased risk of mesothelioma.

Red Meat and Colorectal Cancer: A Quantitative Update on the State of the Epidemiologic Science.

The potential relationship between red meat consumption and colorectal cancer (CRC) has been the subject of scientific debate. Given the high degree of resulting uncertainty, our objective was to update the state of the science by conducting a systematic quantitative assessment of the epidemiologic literature. Specifically, we updated and expanded our previous meta-analysis by integrating data from new prospective cohort studies and conducting a broader evaluation of the relative risk estimates by specific intake categories. Data from 27 independent prospective cohort studies were meta-analyzed using random-effects models, and sources of potential heterogeneity were examined through subgroup and sensitivity analyses. In addition, a comprehensive evaluation of potential dose-response patterns was conducted. In the meta-analysis of all cohorts, a weakly elevated summary relative risk was observed (1.11, 95% CI: 1.03-1.19); however, statistically significant heterogeneity was present. In general, summary associations were attenuated (closer to the null and less heterogeneous) in models that isolated fresh red meat (from processed meat), adjusted for more relevant factors, analyzed women only, and were conducted in countries outside of the United States. Furthermore, no clear patterns of dose-response were apparent. In conclusion, the state of the epidemiologic science on red meat consumption and CRC is best described in terms of weak associations, heterogeneity, an inability to disentangle effects from other dietary and lifestyle factors, lack of a clear dose-response effect, and weakening evidence over time. KEY TEACHING POINTS: •The role of red meat consumption in colorectal cancer risk has been widely contested among the scientific community.•In the current meta-analysis of red meat intake and colorectal cancer, we comprehensively examined associations by creating numerous sub-group stratifications, conducting extensive sensitivity analyses, and evaluating dose-response using several different methods.•Overall, all summary associations were weak in magnitude with no clear dose-response patterns.•Interpretation of findings from epidemiologic studies investigating diet and health outcomes involves numerous methodological considerations, such as accurately measuring food intake, dietary pattern differences across populations, food definitions, outcome classifications, bias and confounding, multicollinearity, biological mechanisms, genetic variation in metabolizing enzymes, and differences in analytical metrics and statistical testing parameters.

Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009-2010 H1N1 pandemic: summary of an ecological study.

When the influenza A (H1N1) pandemic spread across the globe from April 2009 to August 2010, many WHO Member States used antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Antivirals have been found to be effective in reducing severity and duration of influenza illness, and likely reduce morbidity; however, it is unclear whether NAIs used during the pandemic reduced H1N1 mortality. To assess the association between antivirals and influenza mortality, at an ecologic level, country-level data on supply of oseltamivir and zanamivir were compared to laboratory-confirmed H1N1 deaths (per 100 000 people) from July 2009 to August 2010 in 42 WHO Member States. From this analysis, it was found that each 10% increase in kilograms of oseltamivir, per 100 000 people, was associated with a 1·6% reduction in H1N1 mortality over the pandemic period [relative rate (RR) = 0·84 per log increase in oseltamivir supply]. Each 10% increase in kilogram of active zanamivir, per 100 000, was associated with a 0·3% reduction in H1N1 mortality (RR = 0·97 per log increase). While limitations exist in the inference that can be drawn from an ecologic evaluation, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics. This article summarises the original study described previously, which can be accessed through the following citation: Miller PE, Rambachan A, Hubbard RJ, Li J, Meyer AE, et al. (2012) Supply of Neuraminidase Inhibitors Related to Reduced Influenza A (H1N1) Mortality during the 2009-2010 H1N1 Pandemic: An Ecological Study. PLoS ONE 7(9): e43491.

Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009-2010 H1N1 pandemic: an ecological study.

BACKGROUND: The influenza A (H1N1) pandemic swept across the globe from April 2009 to August 2010 affecting millions. Many WHO Member States relied on antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Such drugs have been found to be effective in reducing severity and duration of influenza illness, and likely reduced morbidity during the pandemic. However, it is less clear whether NAIs used during the pandemic reduced H1N1 mortality. METHODS: Country-level data on supply of oseltamivir and zanamivir were used to predict H1N1 mortality (per 100,000 people) from July 2009 to August 2010 in forty-two WHO Member States. Poisson regression was used to model the association between NAI supply and H1N1 mortality, with adjustment for economic, demographic, and health-related confounders. RESULTS: After adjustment for potential confounders, each 10% increase in kilograms of oseltamivir, per 100,000 people, was associated with a 1.6% reduction in H1N1 mortality over the pandemic period (relative rate (RR) = 0.84 per log increase in oseltamivir supply). While the supply of zanamivir was considerably less than that of oseltamivir in each Member State, each 10% increase in kilogram of active zanamivir, per 100,000, was associated with a 0.3% reduction in H1N1 mortality (RR = 0.97 per log increase). CONCLUSION: While there are limitations to the ecologic nature of these data, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics.