Use of a remote clinical decision support service for a multicenter trial to implement prediction rules for children with minor blunt head trauma

ObjectiveTo evaluate the architecture, integration requirements, and execution characteristics of a remote clinical decision support (CDS) service used in a multicenter clinical trial. The trial tested the efficacy of implementing brain injury prediction rules for children with minor blunt head trauma.Materials and MethodsWe integrated the Epic^® electronic health record (EHR) with the Enterprise Clinical Rules Service (ECRS), a web-based CDS service, at two emergency departments. Patterns of CDS review included either a delayed, near-real-time review, where the physician viewed CDS recommendations generated by the nursing assessment, or a real-time review, where the physician viewed recommendations generated by their own documentation. A backstopping, vendor-based CDS triggered with zero delay when no recommendation was available in the EHR from the web-service. We assessed the execution characteristics of the integrated system and the source of the generated recommendations viewed by physicians.ResultsThe ECRS mean execution time was 0.74  ± 0.72 s. Overall execution time was substantially different at the two sites, with mean total transaction times of 19.67 and 3.99 s. Of 1930 analyzed transactions from the two sites, 60% (310/521) of all physician documentation-initiated recommendations and 99% (1390/1409) of all nurse documentation-initiated recommendations originated from the remote web service.DiscussionThe remote CDS system was the source of recommendations in more than half of the real-time cases and virtually all the near-real-time cases. Comparisons are limited by allowable variation in user workflow and resolution of the EHR clock.ConclusionWith maturation and adoption of standards for CDS services, remote CDS shows promise to decrease time-to-trial for multicenter evaluations of candidate decision support interventions.     

A population-based study of smoking,serum cotinine and exhaled nitric oxide among asthmatics and a healthy population in the USA

Background: Fractional concentration of exhaled nitric oxide (FeNO) is recommended by the American Thoracic Society (ATS) as a noninvasive biomarker of airway inflammation. In addition to inflammation, many factors may be associated with FeNO, particularly tobacco exposure; however, only age has been included as an influential factor for children below 12 years. Numerous studies have demonstrated negative associations between tobacco exposure and FeNO levels with self-reported data, but few with an objective assessment of smoking.

Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2007–2012 were analyzed to examine the association between FeNO and active/passive tobacco. Exposure was assessed by both self-report and serum cotinine levels among 11,160 subjects aged 6–79 years old with asthma, or without any respiratory disease.

Results: Study results indicated 28.8% lower FeNO, 95% CI [25.2%, 32.3%] and 38.1% lower FeNO, 95% CI: [28.1, 46.2] was observed among healthy and asthmatic participants with serum cotinine in the highest quartile compared to those in the lowest quartile, respectively. Self-reported smoking status and recent tobacco use were also associated with decreased FeNO. Self-reported passive smoking was significantly associated with a 1.0% decrease in FeNO 95% CI [0.0, 2.0] among asthmatic subjects but not among healthy subjects.

Conclusions: Active smoking, whether measured by self-report or serum cotinine, was associated with decreased FeNO levels. In addition to age, increased attention should be given to tobacco exposure when using FeNO as a biomarker in clinical practice. Additional research is needed to establish reference value of FeNO considering the impact of tobacco exposure.     

Changes in genetically drifted H3N2 influenza A viruses and vaccine effectiveness in adults 65 years and older during the 2016/17 season in Denmark

BackgroundIn Denmark, influenza A virus of the subtype H3N2 has been dominating the 2016/17 season, as in most countries of the Northern Hemisphere.ObjectivesThis study was conducted as part of the Danish seasonal influenza surveillance programme to genetically characterize circulating H3N2 viruses and determine the seasonal vaccine effectiveness (VE) overall in the Danish population and further on the virus cluster level.Study designInfluenza virus positive samples submitted for the national surveillance programme were genetically characterized by sequencing. VE estimates against influenza A and the circulating virus clusters were determined in patients above 65 years using the test-negative case–control design.ResultsThe genetic characterization revealed several genetically drifted viruses, which could be divided into four main clusters by the defining amino acid substitutions: 3C.2a/N121K/S144K, 3C.2a/T131K/R142K, 3C.2a1, and 3C.2a1/N121K. Some of the drifted viruses appeared to be more prominent in vaccinated or non-vaccinated individuals, respectively. Overall the adjusted VE was 7.4% (95% confidence interval (CI): −6.0–19.2) among inpatients and 19.3% (95% CI: −5.7–38.4) among outpatients, respectively. VE for the four main virus clusters was; cluster 3C.2a1: 38.8% (95% CI: −29.8–71.1), cluster 3C.2a/N121K/S144K: 9.2% (95% CI: −63.0–49.4), cluster 3C.2a/T131K/R142K: 19.0% (95% CI: −85.3–64.6), and cluster 3C.2a1/N121K: −12.2% (95%CI: −129.7–45.2).ConclusionsSeveral genetically drifted H3N2 viruses have been circulating in Denmark in the 2016-17 influenza season. An overall low VE was estimated and VE for the four main virus cluster indicate different VEs between the circulating drifted H3N2 viruses.     

Correlation of chromosome damage and promoter methylation status of the DNA repair genes MGMT and hMLH1 in Chinese vinyl chloride monomer (VCM)-exposed workers

Objective

To explore the association of the methylation status of MGMT and hMLH1 with chromosome damage induced by vinyl chloride monomer (VCM).

Materials and Methods

Methylation of MGMT and hMLH1 was measured in 101 VCM-exposed workers by methylation-specific PCR. Chromosome damage in peripheral blood lymphocytes was measured by the cytokinesis-block micronucleus assay. The subjects were divided into chromosome damaged and non-damaged groups based on the normal reference value of micronuclei frequencies determined for two control groups.

Results

MGMT promoter methylation was detectable in 5 out of 49 chromosome damaged subjects, but not in the chromosome non-damaged subjects; there was a significant difference in MGMT methylation between the two groups (p < 0.05).

Conclusions

We detected aberrant promoter methylation of MGMT in a small number of chromosome damaged VCM-exposed workers, but not in the chromosome non-damaged subjects. This preliminary observation warrants further investigation in a larger study.     

Prevalence of human herpesvirus 8 and hepatitis C virus in a rural community with a high risk for blood-borne infections in central China

Illegal blood donation in the past decade has caused human immunodeficiency virus (HIV) outbreaks in some rural areas in China. Other HIV-associated virus infections, such as those caused by human herpesvirus 8 (HHV8), in such areas are still not well defined. In order to explore HHV8 and hepatitis C virus (HCV) seroprevalence and potential risk factors in such areas, a cross-sectional study with 305 HIV-positive and 315 HIV-negative subjects recruited from a rural county in Shanxi province was conducted, in which illegal blood collection was reported. Interview questionnaires and serum testing were carried out with these participants. HCV and HHV8 seroprevalence were found to be higher in the HIV-positive than in the HIV-negative group (76.4% vs. 2.5% and 15.4% vs. 4.8%, respectively), whereas the difference in HBV seroprevalence was not significant. Co-infection with HCV and HHV8 was also more prevalent in the HIV-positive group. HIV status (OR 2.71; 95% CI 1.16–6.30) and HBV status (OR 2.56; 95% CI 1.14–5.75) were independently associated with HHV8 infection. HIV status (OR 23.03; 95% CI 9.95–53.27) and blood/plasma selling history (OR 14.57; 95% CI 7.49–28.23) were strongly associated with HCV infection. These findings demonstrate that both HHV8 and HCV infections are prevalent in this community. HIV infection is an important risk factor for both HHV8 and HCV infection. HBV infection is associated with HHV8 infection but not with HCV infection. It is possible that HHV8 and hepatitis B virus, but not HCV, have similar modes of transmission in this population.     

Traffic exposure and incident venous thromboembolism in the Atherosclerosis Risk in Communities (ARIC) Study

Summary. Background: Two recent case–control studies in Italy reported that long‐term exposure to particulate air pollution or living near major traffic roads was associated with an increased risk of deep vein thrombosis (DVT). No prospective evidence exists on the possible association between long‐term traffic‐related air pollution and incident venous thromboembolism (VTE). Objectives: To examine the association between long‐term traffic exposure and incident VTE in a population‐based prospective cohort study. Methods: We studied 13 143 middle‐aged men and women in the Atherosclerosis Risk in Communities Study without a history of DVT or pulmonary embolism at baseline examination (1987–1989). The Geographical Information System‐mapped traffic density and distance to major roads in the four study communities served as measures of traffic exposure. We examined the association between traffic exposure and incident VTE with proportional hazards regression models. Results: A total of 405 subjects developed VTE in 2005. Traffic density was not significantly associated with VTE. Relative to those in the lowest quartile of traffic density, the adjusted hazard ratios across increasing quartiles were 1.18 (95% confidence interval [CI] 0.88–1.57), 0.99 (95% CI 0.74–1.34) and 1.14 (95% CI 0.86–1.51) (P‐value for trend across quartiles = 0.64). For residents living within 150 m of major roads, as compared with subjects living further away, the adjusted hazard ratio was 1.16 (95% CI 0.95–1.42, P = 0.14). Conclusions: This first prospective study in the general population does not support an association between air pollution exposure or traffic proximity and risk of DVT. More data may be needed to clarify whether traffic or air pollution influences the risk of VTE.     

Perfluorooctane sulfonate blocked autophagy flux and induced lysosome membrane permeabilization in HepG2 cells

Perfluorooctane sulfonate (PFOS) is an emerging persistent organic pollutant widely distributed in the environment, wildlife and human. In this study, as observed under the transmission electron microscope, PFOS increased autophagosome numbers in HepG2 cells, and it was confirmed by elevated LC3-II levels in Western blot analysis. PFOS increased P62 level and chloroquine failed to further increase the expression of LC3-II after PFOS treatment, indicating that the accumulation of autophagosome was due to impaired degradation rather than increased formation. With acridine orange staining, we found PFOS caused lysosomal membrane permeabilization (LMP). In this study, autophasome formation inhibitor 3-methyladenine protected cells against PFOS toxicity, autophagy stimulator rapamycin further decreased cell viability and increased LDH release, cathepsin inhibitor did not influence cell viability of PFOS-treated HepG2 cells significantly. These further supported the notion that autophagic cell death contributed to PFOS-induced hepatotoxicity. In summary, the data of the present study revealed that PFOS induced LMP and consequent blockage of autophagy flux, leading to an excessive accumulation of the autophagosomes and turning autophagy into a destructive process eventually. This finding will provide clues for effective prevention and treatment of PFOS-induced hepatic disease.