Giffe T. Johnson

Prognostic Performance of Metabolic Indexes in Predicting Onset of Type 1 Diabetes

OBJECTIVE In this investigation we evaluated nine metabolic indexes from intravenous glucose tolerance tests (IVGTTs) and oral glucose tolerance tests (OGTTs) in an effort to determine their prognostic performance in predicting the development of type 1 diabetes in those with moderate risk, as defined by familial relation to a type 1 diabetic individual, a positive test for islet cell antibodies and insulin autoantibody, but normal glucose tolerance. RESEARCH DESIGN AND METHODS Subjects (n = 186) who had a projected risk of 25–50% for developing type 1 diabetes within 5 years were followed until clinical diabetes onset or the end of the study as part of the Diabetes Prevention Trial–Type 1. Prognostic performance of the metabolic indexes was determined using receiver operating characteristic (ROC) curve and survival analyses. RESULTS Two-hour glucose from an OGTT most accurately predicted progression to disease compared with all other metabolic indicators with an area under the ROC curve of 0.67 (95% CI 0.59–0.76), closely followed by the ratio of first-phase insulin response (FPIR) to homeostasis model assessment of insulin resistance (HOMA-IR) with an area under the curve value of 0.66. The optimal cutoff value for 2-h glucose (114 mg/dl) maintained sensitivity and specificity values >0.60. The hazard ratio for those with 2-h glucose ≥114 mg/dl compared with those with 2-h glucose <114 mg/dl was 2.96 (1.67–5.22). CONCLUSIONS The ratio of FPIR to HOMA-IR from an IVGTT provided accuracy in predicting the development of type 1 diabetes similar to that of 2-h glucose from an OGTT, which, because of its lower cost, is preferred. The optimal cutoff value determined for 2-h glucose provides additional guidance for clinicians to identify subjects for potential prevention treatments before the onset of impaired glucose tolerance.

Assessment of community healthcare providers ability and willingness to respond to emergencies resulting from bioterrorist attacks

Introduction: Previous findings have demonstrated that preparedness and planning within the public health system are inadequately developed to respond to an act of biological or chemical terrorism. Materials and Methods: This investigation used Internet-based surveys to assess the level of preparedness (PL) and willingness to respond (WTR) to a bioterrorism attack, and identify factors that predict PL and WTR among Florida community healthcare providers. Invitations were sent to 22,800 healthcare providers in Florida, which resulted in 2,279 respondents. Results: Respondents included physicians (n=604), nurses (n=1,152), and pharmacists (n=486). The results indicated that only 32% of Florida healthcare providers were competent and willing to respond to a bioterrorism attack, 82.7% of providers were willing to respond in their local community, and 53.6% within the State. Respondents were more competent in administrative skills than clinical knowledge (62.8% vs. 45%). Areas in which respondents had the highest competency were the initiation of treatment and recognition of their clinical and administrative roles. Areas in which respondents showed the lowest competency were the ability to identify cases and the ability to communicate risk to others. About 55% of the subjects had previous bioterrorism training and 31.5% had conducted emergency drills. Gender, race, previous training and drills, perceived threats of bioterrorism attack, perceived benefits of training and drills, and feeling prepared were all predictors of overall preparedness. Conclusions: The findings suggest that only one-third of Florida community healthcare providers were prepared for a bioterrorism attack, which is an insufficient response rate to effectively respond to a bioterrorism incident.

Airborne asbestos exposure during light aircraft brake replacement

Asbestos containing materials are a component of many vehicle brake systems, including those found in some light aircraft. To characterize the asbestos exposure that results from the installation and maintenance of these components, an aircraft fitted with asbestos containing brake pads had brake changes performed while both area and personal air samples were taken. The brake changing process took place in a closed, unventilated aircraft hanger and all operations were performed according to the manufacturers recommended procedure. Personal air samples did not detect any measurable amount of asbestos fibers during the brake changing or subsequent cleanup procedures. Analysis of personal samples (n=9) using phase contrast microscopy indicated airborne fiber concentrations at or below 0.003f/ml as 8-h time weighted averages (TWAs) and less than 0.069f/ml averaged over 28-30min sampling periods. Airborne chrysotile fibers were detected by two area air samples with fiber concentrations remaining at or below 0.0013f/ml over an 8-h TWA. These results indicate that normal brake changing work practices on aircraft with asbestos containing brake pads does not produce a harmful level of asbestos exposure for aircraft mechanics.

Comment on: Effects of Decabrominated Diphenyl Ether (PBDE 209) Exposure at Different Developmental Periods on Synaptic Plasticity in the Dentate Gyrus of Adult Rats In Vivo

Xing et al. (2009) exposed Wistar rats to decabromodiphenyl ether (PBDE 209; CASRN 1163-19-5) during five developmental periods: pregnancy, lactation via mother’s milk (indirect dosing), lactation via gavage (direct dosing), postweaning (direct dosing), and prenatal to life (indirect dosing during gestation and lactation and direct dosing postweaning). All animals were evaluated on postnatal day 60. The authors reported that exposure during lactation was the most sensitive period for causing effects on postsynaptic cell excitability. In the Materials and Methods section, the authors stated: ‘‘[t]he animals in each group consisted of three to four litters with both sexes (the ratio of males to females was ~1:1) to avoid the effects of litters and sexes.’’ For the input/output functions, paired-pulse reactions, long-term potentiation, and PBDE 209 concentrations in the hippocampus, however, the authors reported an ‘‘n’’ of 5, 7, 8, 9, 10, or 13 for the respective treatment groups (Xing et al., 2009). Thus, Xing et al. (2009) utilized an average of 1–2 (n 1⁄4 5), 1–3 (n 1⁄4 7), 2–3 (n 1⁄4 8), 2–3 (n 1⁄4 9), 2–4 (n 1⁄4 10), or 3–4 (n 1⁄4 13) littermates as independent values per treatment group. This study is based on a clustered experimental design, and data analysis must control for litter effects. The U.S. Environmental Protection Agency recently cosponsored two expert working groups on statistical considerations for use in developmental neurotoxicity testing and for direct dosing preweaning animals (Holson et al., 2008; Moser et al., 2005; Zoetis and Walls, 2003). These expert groups concluded that the litter must be used as the experimental and statistical unit regardless of whether animals are dosed indirectly or directly. Based on the number of litters used by Xing et al. (2009), their reported sample size should be an ‘‘n’’ of 3 or 4, with values from littermates treated as replicates within each litter. Failing to control for litter effects can have a profound impact on data analysis and resulting conclusions. For example, the rate of type I or false-positive errors has been reported to triple the nominal 0.05 alpha level when as few as two pups per litter were used as independent measures (Holson and Pearce, 1992). Because Xing et al. (2009) utilized varying numbers of pups from the same litter per treatment group as independent values, their results may be reflective of litter effects, inflating the significance of test article–related effects. It is noteworthy that the in vivo studies cited by Xing et al. (2009) as support that PBDEs cause developmental neurotoxicity also failed to control for litter effects (Eriksson et al., 2001, 2002; Fischer et al., 2008; Viberg et al., 2003a,b 2004, 2007, 2008). Furthermore, PBDE 209 was evaluated using the most recent validated test guideline for developmental neurotoxicity (OECD, 2007). This study utilized doses ranging from 1 mg/kg/day to 1000 mg/kg/day and was unable to replicate the effects reported by Viberg et al. (2003b, 2007) (Hardy et al., 2009). In conclusion, Xing et al. (2009) failed to control for litter effects in analyzing data arising from a clustered experimental design. If the authors tracked which pups came from which litters per treatment group, their data may be reanalyzed to determine to what degree the effect they attributed to the treatment was a result of uncontrolled litter effects. In the absence of such a reanalysis, data by Xing et al. (2009) are of questionable relevance for risk assessment.

Etiological characterization of acute poisonings in the emergency department.

Introduction: An investigation of emergency department (ED) poisonings was conducted to characterize poisoning demographics and evaluate correlations with select co-morbidities. Methods: The study population evaluated consisted of 649 poisoning cases admitted between 2004 and 2007 to an inner-city, level 1 emergency department. Results: Ethnicity, age, and gender had a substantial impact on the population distribution as poisoning cases were predominantly African Americans (79.9%) between 36 and 45 years old with a 1:3 male to female ratio. Intentional illicit drug overdose was the most prevalent cause of poisoning, heroin being the most frequent substance found in 35.4% (n = 230) of cases, followed by cocaine overdose at 31.7% (n = 206), concomitant heroin and cocaine overdose at 4.3% (n = 28), multiple drug poisoning at 5.5% (n = 36), and antidepressant/antipsychotic poisoning at 6% (n = 39). Significant correlations were found between heroin poisoning and asthma (F = 20.29, DF = 1, P = 0.0001), cocaine poisoning and hypertension (F = 33.34, DF = 1, P = 0.0001), and cocaine poisoning and cardiovascular disease (F = 35.34, DF = 1, P = 0.0001). A change in the pattern of illicit drug use from injection to inhalation was detected and the resulting increase of inhalation and insufflation of illicit substances may partially explain the correlation found between heroin use and asthma. Conclusions: These results provide supporting evidence that deliberate poisoning with illicit drugs remains a serious healthcare issue that significantly aggravates co-morbidities and raises treatment costs by increasing both the rate of hospitalization and hospital length of stay.

“Pressured to prescribe” The impact of economic and regulatory factors on South-Eastern ED physicians when managing the drug seeking patient

Objective: The purpose of this study was to elicit the opinions of Emergency Department (ED) physicians, currently practicing in the United States, regarding the impact of economic and regulatory factors on their management of patients exhibiting “drug seeking” behavior. Methods: A descriptive, cross-sectional study, utilizing a convenience sample of ED physicians located in Florida and Georgia was conducted for a period of 2 months. The inclusion criteria specified that any ED physician, currently practicing within the United States, could participate. Results: Of the ED physicians surveyed (n = 141), 71% reported a perceived pressure to prescribe opioid analgesics to avoid administrative and regulatory criticism and 98% related patient satisfaction scores as being too highly emphasized by reimbursement entities as a means of evaluating their patient management. Rising patient volumes and changes in the healthcare climate were cited by ED physicians as impacting their management of patients exhibiting “drug seeking” behavior. Conclusions: The ED physician faces unique challenges in changing healthcare and economic climates. Requirements to address pain as the “fifth vital sign,” patient satisfaction based reimbursement metrics and an economically driven rise in ED patient volume, may have inadvertently created an environment conducive to exploitation by prescription opioid abusers. There is an identified need for the development of continuing medical education and standardized regulatory and legislative protocols to assist ED physicians in the appropriate management of patients exhibiting “drug seeking” behavior.

Risk characterization of vapor intrusion in former manufactured gas plant sites

Soil vapor intrusion (SVI) has recently garnered much interest as a potential exposure route for occupants of properties overlying and surrounding former Manufactured Gas Plants (MGPs). This investigation evaluates SVI at 10 commercial buildings and 26 single family and multi-family residential properties overlying and/or adjacent to three former MGPs. SVI was evaluated in three categories according to thickness of the vadose zones: no vadose zone; 0-6 feet thick, and 6-25 feet thick. Indoor and outdoor air, and soil vapor samples were analyzed for volatile organic compounds (VOCs). Comparative risks were evaluated based on maximum and mean concentrations for benzene, toluene, ethylbenzene, and xylenes relative to background levels. All calculated Hazard Indices were less than 1 or were comparable to mean and maximum background levels. Cancer risks for exposure to benzene ranged from 9.75×10(-6) to 4.52×10(-4). Comparative background cancer risk from benzene exposure not related to former MGP sites ranged from 9.9×10(-6) to 3.59×10(-3). The results did not identify evidence of MGP-related soil vapor intrusion from any of the 36 sites. No increased public health risks were associated with occupied residential or commercial properties overlying or surrounding MGPs.

Airborne asbestos exposures associated with work on asbestos fire sleeve materials.

Asbestos-containing fire sleeves have been used as a fire protection measure for aircraft fluid hoses. This investigation was conducted to determine the level of airborne asbestos fiber exposure experienced by mechanics who work with fire sleeve protected hoses. Duplicate testing was performed inside a small, enclosed workroom during the fabrication of hose assemblies. Personal air samples taken during this work showed detectable, but low airborne asbestos fiber exposures. Analysis of personal samples (n=9) using phrase contract microscopy (PCM) indicated task duration airborne fiber concentrations ranging from 0.017 to 0.063 fibers per milliliter (f/ml) for sampling durations of 167-198 min, and 0.022-0.14 f/ml for 30 min samples. Airborne chrysotile fibers were detected for four of these nine personal samples, and the resulting asbestos adjusted airborne fiber concentrations ranged from 0.014 to 0.025 f/ml. These results indicate that work with asbestos fire sleeve and fire sleeve protected hose assemblies, does not produce regulatory noncompliant levels of asbestos exposure for persons who handle, cut and fit these asbestos-containing materials.

A novel method for deriving thresholds of toxicological concern for vaccine constituents

Abstract Safety assessment evaluating the presence of impurities, residual materials, and contaminants in vaccines is a focus of current research. Thresholds of toxicological concern (TTCs) are mathematically modeled levels used for assessing the safety of many food and medication constituents. In this study, six algorithms are selected from the open-access ToxTree software program to derive a method for calculating TTCs for vaccine constituents: In Vivo Rodent Micronucleus assay/LD50, Benigni–Bossa/LD50, Cramer Extended/LD50, In Vivo Rodent Micronucleus assay/TDLo, Benigni–Bossa/TDLo, and the Cramer Extended/TDLo. Using an initial dataset (n = 197) taken from INCHEM, RepDose, RTECS, and TOXNET, the chemicals were divided into two families: “positive” – based on the presence of structures associated with adverse outcomes, or “negative” – no such structures or having structures that appear to be protective of health. The final validation indicated that the Benigni–Bossa/LD50 method is the most appropriate for calculating TTCs for vaccine constituents. Final TTCs were designated as 18.06 μg/person and 20.61 μg/person for the Benigni–Bossa/LD50 positive and negative structural families, respectively.

Human Health Risk Characterization of Petroleum Coke Calcining Facility Emissions

Calcining processes including handling and storage of raw petroleum coke may result in Particulate Matter (PM) and gaseous emissions. Concerns have been raised over the potential association between particulate and aerosol pollution and adverse respiratory health effects including decrements in lung function. This risk characterization evaluated the exposure concentrations of ambient air pollutants including PM10 and gaseous pollutants from a petroleum coke calciner facility. The ambient air pollutant levels were collected through monitors installed at multiple locations in the vicinity of the facility. The measured and modeled particulate levels in ambient air from the calciner facility were compared to standards protective of public health. The results indicated that exposure levels were, on occasions at sites farther from the facility, higher than the public health limit of 150 μg/m(3) 24-h average for PM10. However, the carbon fraction demonstrated that the contribution from the calciner facility was de minimis. Exposure levels of the modeled SO2, CO, NOx and PM10 concentrations were also below public health air quality standards. These results demonstrate that emissions from calcining processes involving petroleum coke, at facilities that are well controlled, are below regulatory standards and are not expected to produce a public health risk.