A comparison of electronic health records and the Oregon state immunization registry for human papilloma virus vaccine delivery (2005-2022).

INTRODUCTION: Immunization Information Systems (IIS) play an important information-sharing role at the point of care, and provide vital vaccination data for research studies and policy-makers. Previous validation studies comparing the accuracy of state registry data to health records have had mixed results. METHODS: We conducted a retrospective review of EHR vaccination data for 9-17 year-old patients from 10 Oregon primary care clinics who had at least one ambulatory care visit in the past 3 years from the date of validation data collection. Data on 100 age eligible youth were captured per clinic. We compared HPV and Tdap vaccinations captured in the EHR to the Oregon ALERT IIS. All clinics were located in rural areas with both family medicine (n = 7) and pediatric (n = 3) primary care clinics. RESULTS: Overall agreement for HPV vaccination between EHR and ALERT IIS was 89.4 % (k = 0.83; p < 0.05). For Tdap vaccination overall agreement was 80.8 % (k = 0.60; p < 0.05). Pediatric clinics showed a higher overall vaccine agreement for both HPV at 93.3 % (k = 0.89; p < 0.05) and Tdap at 95.3 % (k = 0.90; p < 0.05). Among clinics that used bidirectional data exchange (only family medicine clinics), HPV agreement was higher at 91 % (k = 0.85) versus 88 % (k = 0.81; p < 0.05) and was lower for Tdap 75 % with bidirectional data exchange (k = 0.50) versus 86 % without bidirectional data exchange (k = 0.70; p < 0.05). When the EHR and ALERT IIS disagreed, ALERT ISS usually had additional vaccines. CONCLUSIONS: ALERT IIS data provides more accurate data than EHRs can provide when measuring vaccine delivery among adolescents in rural Oregon.

The use of biomonitoring data in exposure and human health risk assessment: benzene case study.

Abstract A framework of "Common Criteria" (i.e. a series of questions) has been developed to inform the use and evaluation of biomonitoring data in the context of human exposure and risk assessment. The data-rich chemical benzene was selected for use in a case study to assess whether refinement of the Common Criteria framework was necessary, and to gain additional perspective on approaches for integrating biomonitoring data into a risk-based context. The available data for benzene satisfied most of the Common Criteria and allowed for a risk-based evaluation of the benzene biomonitoring data. In general, biomarker (blood benzene, urinary benzene and urinary S-phenylmercapturic acid) central tendency (i.e. mean, median and geometric mean) concentrations for non-smokers are at or below the predicted blood or urine concentrations that would correspond to exposure at the US Environmental Protection Agency reference concentration (30 µg/m(3)), but greater than blood or urine concentrations relating to the air concentration at the 1 × 10(-5) excess cancer risk (2.9 µg/m(3)). Smokers clearly have higher levels of benzene exposure, and biomarker levels of benzene for non-smokers are generally consistent with ambient air monitoring results. While some biomarkers of benzene are specific indicators of exposure, the interpretation of benzene biomonitoring levels in a health-risk context are complicated by issues associated with short half-lives and gaps in knowledge regarding the relationship between the biomarkers and subsequent toxic effects.

Development of screening tools for the interpretation of chemical biomonitoring data.

Evaluation of a larger number of chemicals in commerce from the perspective of potential human health risk has become a focus of attention in North America and Europe. Screening-level chemical risk assessment evaluations consider both exposure and hazard. Exposures are increasingly being evaluated through biomonitoring studies in humans. Interpreting human biomonitoring results requires comparison to toxicity guidance values. However, conventional chemical-specific risk assessments result in identification of toxicity-based exposure guidance values such as tolerable daily intakes (TDIs) as applied doses that cannot directly be used to evaluate exposure information provided by biomonitoring data in a health risk context. This paper describes a variety of approaches for development of screening-level exposure guidance values with translation from an external dose to a biomarker concentration framework for interpreting biomonitoring data in a risk context. Applications of tools and concepts including biomonitoring equivalents (BEs), the threshold of toxicologic concern (TTC), and generic toxicokinetic and physiologically based toxicokinetic models are described. These approaches employ varying levels of existing chemical-specific data, chemical class-specific assessments, and generic modeling tools in response to varying levels of available data in order to allow assessment and prioritization of chemical exposures for refined assessment in a risk management context.

Case studies to test: A framework for using structural, reactivity, metabolic and physicochemical similarity to evaluate the suitability of analogs for SAR-based toxicological assessments.

A process for evaluating analogs for use in SAR (Structure-Activity Relationship) assessments was previously published (Wu et al. 2010). Subsequently, this process has been updated to include a decision tree for estrogen binding (from US EPA) and flags for developmental and reproductive toxicity (DART). This paper presents the results of blinded case studies designed to test this updated framework. The results of these case studies support the conclusion that the process outlined by Wu et al. (2010) can be successfully applied to develop surrogate values for risk assessment. The read across results generated by the process were shown to be protective when compared to the actual toxicity data. Successful application of the approach requires significant expertise as well as discipline to not overstep the boundaries of the defined analogs and the rating system. The end result of this rigor can be the inability to read across all endpoints for all chemicals resulting in data gaps that cannot be filled using read across, however, this reflects the current state of the science and is preferable to making non-protective decisions. Future work will be targeted towards expanding read across capabilities. Two examples of a broader category approach are also shown.

Refining aggregate exposure: example using parabens.

The need to understand and estimate quantitatively the aggregate exposure to ingredients used broadly in a variety of product types continues to grow. Currently aggregate exposure is most commonly estimated by using a very simplistic approach of adding or summing the exposures from all the individual product types in which the chemical is used. However, the more broadly the ingredient is used in related consumer products, the more likely this summation will result in an unrealistic estimate of exposure because individuals in the population vary in their patterns of product use including co-use and non-use. Furthermore the ingredient may not be used in all products of a given type. An approach is described for refining this aggregate exposure using data on (1) co-use and non-use patterns of product use, (2) extent of products in which the ingredient is used and (3) dermal penetration and metabolism. This approach and the relative refinement in the aggregate exposure from incorporating these data is illustrated using methyl, n-propyl, n-butyl and ethyl parabens, the most widely used preservative system in personal care and cosmetic products. When these refining factors were used, the aggregate exposure compared to the simple addition approach was reduced by 51%, 58%, 90% and 92% for methyl, n-propyl, n-butyl and ethyl parabens, respectively. Since biomonitoring integrates all sources and routes of exposure, the estimates using this approach were compared to available paraben biomonitoring data. Comparison to the 95th percentile of these data showed that these refined estimates were still conservative by factors of 2-92. All of our refined estimates of aggregate exposure are less than the ADI of 10mg/kg/day for parabens.

An evaluation of the genotoxicity of the antitussive drug Dextromethorphan.

Dextromethorphan (DMP) is an effective and widely used antitussive drug. While DMP has over a 50 year safe-marketing history, the only available genotoxicity data was an unpublished, negative Ames assay (Roche). Lack of a complete genotoxicity profile on DMP, specifically covering the chromosomal damage endpoint, prompted a regulatory request for an in vitro chromosome aberration assay. In accordance with EC and CPMP Guidance, we evaluated data for a number of chemicals with a structural relationship to DMP. DMP contains no structural alerts for genotoxicity or carcinogenicity using the Deductive Estimation of Risk from Existing Knowledge (DEREK) software tool, confirming the negative results obtained in the existing Ames assay. This is also consistent with the mostly negative genotoxicity and carcinogenicity data available on structurally related chemicals including morphine, codeine, nalbuphine, buprenorphine, naloxone, hydromorphone, levorphanol, and oxycodone. A state-of-the-science, in vitro chromosome aberration assay was also conducted, which demonstrated a lack of genotoxicity for DMP. The overall weight of evidence for DMP and its structural analogues, supports the conclusion that this class of phenanthrene-based chemicals, and DMP, in particular, are not genotoxic in vitro or in vivo, and do not represent a carcinogenic risk to patients.

Making sense of human biomonitoring data: findings and recommendations of a workshop.

The ability to measure chemicals in humans (often termed biomonitoring) is far outpacing the ability to interpret reliably these data for public health purposes, creating a major knowledge gap. Until this gap is filled, the great promise of routinely using biomonitoring data to support decisions to protect public health cannot be realized. Research is needed to link biomonitoring data quantitatively to the potential for adverse health risks, either through association with health outcomes or using information on the concentration and duration of exposure, which can then be linked to health guidelines. Developing such linkages in the risk assessment paradigm is one of the primary goals of the International Council of Chemical Associations' (ICCA) Long-Range Research Initiative (LRI) program in the area of biomonitoring. Therefore, ICCA sponsored a workshop to facilitate development of a coordinated agenda for research to enable an improved interpretation of human biomonitoring data. Discussions addressed three main topics: (1) exploration of the link between exposure, dose, and human biomonitoring data, (2) the use of computational tools to interpret biomonitoring data, and (3) the relevance of human biomonitoring data to the design of toxicological studies. Several overarching themes emerged from the workshop: (a) Interpretation and use of biomonitoring data should involve collaboration across all sectors (i.e., industry, government, and academia) and countries. (b) Biomonitoring is not a stand-alone tool, and it should be linked to exposure and toxicological dose information. (c) Effective communication is critical, because when uncertainty about the actual risks is high, the perceived risks grow in the absence of communication. (d) The scope of future biomonitoring activities encompasses a variety of research approaches - from advancing the science to fill data gaps to advancing the accessibility of the current knowledge to enable better information sharing.

The use of biomonitoring data in exposure and human health risk assessments.

Biomonitoring uses analytic methods that permit the accurate measurement of low levels of environmental chemicals in human tissues. However, depending on the intended use, biomonitoring, like all exposure tools, may not be a stand-alone exposure assessment tool for some of its environmental public health uses. Although biomonitoring data demonstrate that many environmental chemicals are absorbed in human tissues, uncertainty exists regarding if and at what concentrations many of these chemicals cause adverse health outcomes. Moreover, without exposure pathway information, it is difficult to relate biomonitoring results to sources and routes of exposure and develop effective health risk management strategies. In September 2004, the Health and Environmental Sciences Institute, U.S. Environmental Protection Agency, Centers for Disease Control and Prevention, Agency for Toxic Substances and Disease Registry, and International Council of Chemical Associations co-sponsored the International Biomonitoring Workshop, which explored the processes and information needed for placing biomonitoring data into perspective for risk assessment purposes, with special emphasis on integrating biomarker measurements of exposure, internal dose, and potential health outcome. Scientists from international governments, academia, and industry recommended criteria for applying biomonitoring data for various uses. Six case studies, which are part of this mini-monograph, were examined: inorganic arsenic, methyl eugenol, organophosphorus pesticides, perfluorooctanesulfonate, phthalates, and polybrominated diphenyl ethers. Based on the workshop and follow-up discussions, this overview article summarizes lessons learned, identifies data gaps, outlines research needs, and offers guidance for designing and conducting biomonitoring studies, as well as interpreting biomonitoring data in the context of risk assessment and risk management.

Use of biomonitoring data to evaluate methyl eugenol exposure.

Methyl eugenol is a naturally occurring material found in a variety of food sources, including spices, oils, and nutritionally important foods such as bananas and oranges. Given its natural occurrence, a broad cross-section of the population is likely exposed. The availability of biomonitoring and toxicology data offers an opportunity to examine how biomonitoring data can be integrated into risk assessment. Methyl eugenol has been used as a biomarker of exposure. An analytical method to detect methyl eugenol in human blood samples is well characterized but not readily available. Human studies indicate that methyl eugenol is short-lived in the body, and despite the high potential for exposure through the diet and environment, human blood levels are relatively low. The toxicology studies in animals demonstrate that relatively high-bolus doses administered orally result in hepatic neoplasms. However, an understanding is lacking regarding how this effect relates to the exposures that result when food containing methyl eugenol is consumed. Overall, the level of methyl eugenol detected in biomonitoring studies indicates that human exposure is several orders of magnitude lower than the lowest dose used in the bioassay. Furthermore, there are no known health effects in humans that result from typical dietary exposure to methyl eugenol.

Strategic biomonitoring initiatives: moving the science forward.

Biomonitoring programs in the United States and Europe demonstrate the vast array of data that are publicly available for the evaluation of exposure trends, identification of susceptible populations, detection of emerging chemical risks, the conduct of epidemiology studies, and evaluation of risk reduction strategies. To cultivate international discussion on these issues, the ILSI Health and Environmental Sciences Institute convened a scientific session at its annual meeting in January 2006 on "Integration of Biomonitoring Exposure Data into the Risk Assessment Process." This Forum paper presents perspectives from session speakers on the biomonitoring activities of the Centers for Disease Control and Prevention, the U.S. Environmental Protection Agency, the National Research Council Committee on Human Biomonitoring for Environmental Toxicants, the German Commission on Human Biomonitoring, and the Health and Environmental Sciences Institute Biomonitoring Technical Committee. Speakers noted that better estimates of biological concentrations of substances in the tissues of human populations can be combined with other exposure indices, as well as epidemiological and toxicologic data, to improve risk estimates. With this type of combined data, the potential also exists to define exposure levels at which hazard and risk are of minimal concern. Limitations in interpreting biomonitoring data were discussed, including the need for different criteria for applying biomonitoring data for exposure assessment, risk assessment, risk management, or disease prevention purposes. As efforts and resources are expended to improve the ability to apply biomonitoring exposure data in the risk assessment process, it is equally important to communicate the significance of such data to the public.

Ethnic differences in survival among Pacific Island patients diagnosed with cervical cancer.

BACKGROUND: It was the purpose of this study to investigate whether Pacific Island (PI) ethnicity, Micronesian and Polynesian, is an independent prognostic factor in the survival of cervical cancer in a health care system with minimal racial bias and few barriers to access to care. METHODS: Records from 1988 to 1999 were reviewed for the U.S. Military Health Care System. The medical records of women with the diagnosis of invasive cervical cancer were abstracted and clinical data recorded. A cohort analysis based on Pacific Island ethnicity was also performed on all patients treated at Tripler Army Medical Center (TAMC) during this time period. Significant differences in distribution of clinical factors were determined by Wilcoxon rank-sum test and survival analyses were performed using Kaplan-Meier actuarial statistics. RESULTS: A total of 153 patients were identified who were treated at TAMC; 74 were of PI ethnicity. An additional 1400 patients were identified throughout the military health care system during this time. Forty-eight percent of non-PI TAMC patients were Caucasian, 14% Filipino, and 13% Korean. The mean age of PI was 45 versus 40 years for their non-PI counterparts. There was no difference in the distribution of the grade of tumors among cohorts analyzed. Seventy-five percent of non-PI patients presented at an early stage while 74% of PI women presented at an advanced stage. Twenty-three percent of PI patients had positive lymph nodes, versus 7% of non-PI patients. There was no difference in the radiation dosages among patients treated with primary radiation therapy. PI patients had a significantly decreased 5-year survival, 32% versus 71%, compared to their cervical cancer patient counterparts, P < 0.001. Multivariate analysis revealed PI ethnicity to be a significant independent predictor of decreased survival, P < 0.001. CONCLUSION: PI women diagnosed with cervical cancer tend to present at an advanced age and stage with metastatic disease. They have a decreased survival that remains present after adjusting for age, stage, and grade. The poor prognosis is likely due to lack of uniform screening among this population; however, molecular etiologies and human papillomavirus could also contribute to decreased survival.