A structured framework for improving outbreak investigation audits

Outbreak investigation is a core function of public health agencies. Suboptimal outbreak investigation endangers both public health and agency reputations. While audits of clinical medical and nursing practice are conducted as part of continuous quality improvement, public health agencies rarely make systematic use of structured audits to ensure best practice for outbreak responses, and there is limited guidance or policy to guide outbreak audit. A framework for prioritising which outbreak investigations to audit, an approach for conducting a successful audit, and a template for audit trigger questions was developed and trialled in four foodborne outbreaks and a respiratory disease outbreak in Australia. The following issues were identified across several structured audits: the need for clear definitions of roles and responsibilities both within and between agencies, improved communication between agencies and with external stakeholders involved in outbreaks, and the need for development of performance standards in outbreak investigations - particularly in relation to timeliness of response. Participants considered the audit process and methodology to be clear, useful, and non-threatening. Most audits can be conducted within two to three hours, however, some participants felt this limited the scope of the audit. The framework was acceptable to participants, provided an opportunity for clarifying perceptions and enhancing partnership approaches, and provided useful recommendations for approaching future outbreaks. Future challenges include incorporating feedback from broader stakeholder groups, for example those of affected cases, institutions and businesses; assessing the quality of a specific audit; developing training for both participants and facilitators; and building a central capacity to support jurisdictions embarking on an audit. The incorporation of measurable performance criteria or sharing of benchmark performance criteria will assist in the standardisation of outbreak investigation audit and further quality improvement

Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats

Continuing concern regarding the potential health and environmental effects of depleted uranium and lead has resulted in many countries adding tungsten alloy (WA)-based munitions to their battlefield arsenals as replacements for these metals. Because the alloys used in many munitions are relatively recent additions to the list of militarily relevant metals, very little is known about the health effects of these metals after internalization as embedded shrapnel. Previous work in this laboratory developed a rodent model system that mimicked shrapnel loads seen in wounded personnel from the 1991 Persian Gulf War. In the present study, we used that system and male F344 rats, implanted intramuscularly with pellets (1 mm × 2 mm cylinders) of weapons-grade WA, to simulate shrapnel wounds. Rats were implanted with 4 (low dose) or 20 pellets (high dose) of WA. Tantalum (20 pellets) and nickel (20 pellets) served as negative and positive controls, respectively. The high-dose WA-implanted rats (n = 46) developed extremely aggressive tumors surrounding the pellets within 4–5 months after implantation. The low-dose WA-implanted rats (n = 46) and nickel-implanted rats (n = 36) also developed tumors surrounding the pellets but at a slower rate. Rats implanted with tantalum (n = 46), an inert control metal, did not develop tumors. Tumor yield was 100% in both the low- and high-dose WA groups. The tumors, characterized as high-grade pleomorphic rhabdomyosarcomas by histopathology and immunohistochemical examination, rapidly metastasized to the lung and necessitated euthanasia of the animal. Significant hematologic changes, indicative of polycythemia, were also observed in the high-dose WA-implanted rats. These changes were apparent as early as 1 month postimplantation in the high-dose WA rats, well before any overt signs of tumor development. These results point out the need for further studies investigating the health effects of tungsten and tungsten-based alloys

Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease

Behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) dementia are characterised by progressive brain atrophy. Longitudinal MRI volumetry may help to characterise ongoing structural degeneration and support the differential diagnosis of dementia subtypes. Automated, observer-independent atlas-based MRI volumetry was applied to analyse 102 MRI data sets from 15 bvFTD, 14 AD, and 10 healthy elderly control participants with consecutive scans over at least 12 months. Anatomically defined targets were chosen a priori as brain structures of interest. Groups were compared regarding volumes at clinic presentation and annual change rates. Baseline volumes, especially of grey matter compartments, were significantly reduced in bvFTD and AD patients. Grey matter volumes of the caudate and the gyrus rectus were significantly smaller in bvFTD than AD. The bvFTD group could be separated from AD on the basis of caudate volume with high accuracy (79% cases correct). Annual volume decline was markedly larger in bvFTD and AD than controls, predominantly in white matter of temporal structures. Decline in grey matter volume of the lateral orbitofrontal gyrus separated bvFTD from AD and controls. Automated longitudinal MRI volumetry discriminates bvFTD from AD. In particular, greater reduction of orbitofrontal grey matter and temporal white matter structures after 12 months is indicative of bvFTD

Prevalence of Obesity and the Relationship between the Body Mass Index and Body Fat: Cross-Sectional, Population-Based Data

Background: Anthropometric measures such as the body mass index (BMI) and waist circumference are widely used as convenient indices of adiposity, yet there are limitations in their estimates of body fat. We aimed to determine the prevalence of obesity using criteria based on the BMI and waist circumference, and to examine the relationship between the BMI and body fat.Methodology/Principal Findings: This population-based, cross-sectional study was conducted as part of the Geelong Osteoporosis Study. A random sample of 1,467 men and 1,076 women aged 20&ndash;96 years was assessed 2001&ndash;2008. Overweight and obesity were identified according to BMI (overweight 25.0&ndash;29.9 kg/m2; obesity 30.0 kg/m2) and waist circumference (overweight men 94.0–101.9 cm; women 80.0–87.9 cm; obesity men 102.0 cm, women $88.0 cm); body fat mass was assessed using dual energy X-ray absorptiometry; height and weight were measured and lifestyle factors documented by self-report. According to the BMI, 45.1% (95%CI 42.4&ndash;47.9) of men and 30.2% (95%CI 27.4&ndash;33.0) of women were overweight and a further 20.2% (95%CI 18.0&ndash;22.4) of men and 28.6% (95%CI 25.8&ndash;31.3) of women were obese. Using waist circumference, 27.5% (95%CI 25.1&ndash;30.0) of men and 23.3% (95%CI 20.8&ndash;25.9) of women were overweight, and 29.3% (95%CI 26.9&ndash;31.7) of men and 44.1% (95%CI 41.2&ndash;47.1) of women, obese. Both criteria indicate that approximately 60% of the population exceeded recommended thresholds for healthy body habitus. There was no consistent pattern apparent between BMI and energy intake. Compared with women, BMI overestimated adiposity in men, whose excess weight was largely attributable to muscular body builds and greater bone mass. BMI also underestimated adiposity in the elderly. Regression models including gender, age and BMI explained 0.825 of the variance in percent body fat.Conclusions/Significance: As the BMI does not account for differences in body composition, we suggest that gender- and age-specific thresholds should be considered when the BMI is used to indicate adiposity.<br /

The NARCONON™ drug education curriculum for high school students: A non-randomized, controlled prevention trial

<p>Abstract</p> <p>Background</p> <p>An estimated 13 million youths aged 12 to 17 become involved with alcohol, tobacco and other drugs annually. The number of 12- to 17-year olds abusing controlled prescription drugs increased an alarming 212 percent between 1992 and 2003. For many youths, substance abuse precedes academic and health problems including lower grades, higher truancy, drop out decisions, delayed or damaged physical, cognitive, and emotional development, or a variety of other costly consequences. For thirty years the Narconon program has worked with schools and community groups providing single educational modules aimed at supplementing existing classroom-based prevention activities. In 2004, Narconon International developed a multi-module, universal prevention curriculum for high school ages based on drug abuse etiology, program quality management data, prevention theory and best practices. We review the curriculum and its rationale and test its ability to change drug use behavior, perceptions of risk/benefits, and general knowledge.</p> <p>Methods</p> <p>After informed parental consent, approximately 1000 Oklahoma and Hawai'i high school students completed a modified <it>Center for Substance Abuse Prevention (CSAP) Participant Outcome Measures for Discretionary Programs </it>survey at three testing points: baseline, one month later, and six month follow-up. Schools assigned to experimental conditions scheduled the Narconon curriculum between the baseline and one-month follow-up test; schools in control conditions received drug education after the six-month follow-up. Student responses were analyzed controlling for baseline differences using analysis of covariance.</p> <p>Results</p> <p>At six month follow-up, youths who received the Narconon drug education curriculum showed reduced drug use compared with controls across all drug categories tested. The strongest effects were seen in all tobacco products and cigarette frequency followed by marijuana. There were also significant reductions measured for alcohol and amphetamines. The program also produced changes in knowledge, attitudes and perception of risk.</p> <p>Conclusion</p> <p>The eight-module Narconon curriculum has thorough grounding in substance abuse etiology and prevention theory. Incorporating several historically successful prevention strategies this curriculum reduced drug use among youths.</p

Evasion of IFN-γ Signaling by Francisella novicida Is Dependent upon Francisella Outer Membrane Protein C

Francisella tularensis is a Gram-negative facultative intracellular bacterium and the causative agent of the lethal disease tularemia. An outer membrane protein (FTT0918) of F. tularensis subsp. tularensis has been identified as a virulence factor. We generated a F. novicida (F. tularensis subsp. novicida) FTN_0444 (homolog of FTT0918) fopC mutant to study the virulence-associated mechanism(s) of FTT0918.The ΔfopC strain phenotype was characterized using immunological and biochemical assays. Attenuated virulence via the pulmonary route in wildtype C57BL/6 and BALB/c mice, as well as in knockout (KO) mice, including MHC I, MHC II, and µmT (B cell deficient), but not in IFN-γ or IFN-γR KO mice was observed. Primary bone marrow derived macrophages (BMDM) prepared from C57BL/6 mice treated with rIFN-γ exhibited greater inhibition of intracellular ΔfopC than wildtype U112 strain replication; whereas, IFN-γR KO macrophages showed no IFN-γ-dependent inhibition of ΔfopC replication. Moreover, phosphorylation of STAT1 was downregulated by the wildtype strain, but not the fopC mutant, in rIFN-γ treated macrophages. Addition of NG-monomethyl-L-arginine, an NOS inhibitor, led to an increase of ΔfopC replication to that seen in the BMDM unstimulated with rIFN-γ. Enzymatic screening of ΔfopC revealed aberrant acid phosphatase activity and localization. Furthermore, a greater abundance of different proteins in the culture supernatants of ΔfopC than that in the wildtype U112 strain was observed.F. novicida FopC protein facilitates evasion of IFN-γ-mediated immune defense(s) by down-regulation of STAT1 phosphorylation and nitric oxide production, thereby promoting virulence. Additionally, the FopC protein also may play a role in maintaining outer membrane stability (integrity) facilitating the activity and localization of acid phosphatases and other F. novicida cell components

Incorporating concepts of inequality and inequity into health benefits analysis

BACKGROUND: Although environmental policy decisions are often based in part on both risk assessment information and environmental justice concerns, formalized approaches for addressing inequality or inequity when estimating the health benefits of pollution control have been lacking. Inequality indicators that fulfill basic axioms and agree with relevant definitions and concepts in health benefits analysis and environmental justice analysis can allow for quantitative examination of efficiency-equality tradeoffs in pollution control policies. METHODS: To develop appropriate inequality indicators for health benefits analysis, we provide relevant definitions from the fields of risk assessment and environmental justice and consider the implications. We evaluate axioms proposed in past studies of inequality indicators and develop additional axioms relevant to this context. We survey the literature on previous applications of inequality indicators and evaluate five candidate indicators in reference to our proposed axioms. We present an illustrative pollution control example to determine whether our selected indicators provide interpretable information. RESULTS AND CONCLUSIONS: We conclude that an inequality indicator for health benefits analysis should not decrease when risk is transferred from a low-risk to high-risk person, and that it should decrease when risk is transferred from a high-risk to low-risk person (Pigou-Dalton transfer principle), and that it should be able to have total inequality divided into its constituent parts (subgroup decomposability). We additionally propose that an ideal indicator should avoid value judgments about the relative importance of transfers at different percentiles of the risk distribution, incorporate health risk with evidence about differential susceptibility, include baseline distributions of risk, use appropriate geographic resolution and scope, and consider multiple competing policy alternatives. Given these criteria, we select the Atkinson index as the single indicator most appropriate for health benefits analysis, with other indicators useful for sensitivity analysis. Our illustrative pollution control example demonstrates how these indices can help a policy maker determine control strategies that are dominated from an efficiency and equality standpoint, those that are dominated for some but not all societal viewpoints on inequality averseness, and those that are on the optimal efficiency-equality frontier, allowing for more informed pollution control policies

Increased Systemic Th17 Cytokines Are Associated with Diastolic Dysfunction in Children and Adolescents with Diabetic Ketoacidosis

Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in children with T1DM, but its pathogenesis is not well understood. We studied the relationships of systemic inflammatory cytokines/chemokines and cardiac function in 17 children with T1DM during and after correction of diabetic ketoacidosis (DKA). Twenty seven of the 39 measured cytokines/chemokines were elevated at 6–12 hours into treatment of DKA compared to values after DKA resolution. Eight patients displayed at least one parameter of diastolic abnormality (DA) during acute DKA. Significant associations were present between nine of the cytokine/chemokine levels and the DA over time. Interestingly, four of these nine interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17) are associated with a Th17 mediated cell response. Both the DA and CCL7 and IL-12p40, had independent associations with African American patients. Thus, we report occurrence of a systemic inflammatory response and the presence of cardiac diastolic dysfunction in a subset of young T1DM patients during acute DKA