Doug Campos-Outcalt

Methods for developing evidence-based recommendations by the Advisory Committee on Immunization Practices (ACIP) of the U.S. Centers for Disease Control and Prevention (CDC).

The Advisory Committee on Immunization Practices (ACIP) provides expert external advice and guidance to the Director of the Centers for Disease Control and Prevention and the Secretary of the U.S. Department of Health and Human Services on use of vaccines and related agents for control of vaccine-preventable disease in the United States. During the October 2010 ACIP meeting, the ACIP voted to adopt a new framework for developing evidence-based recommendations that is based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Key factors considered in the development of recommendations include the balance of benefits and harms, type of evidence, values and preferences of the people affected, and health economic analyses. Category A recommendations will be made for all persons in an age- or risk-factor-based group. Category B recommendations will be made for individual clinical decision making; category B recommendations do not apply to all members of an age- or risk-factor-based group, but in the context of a clinician-patient interaction, vaccination may be found to be appropriate for a person. Evidence tables will be used to summarize the benefits and harms and the strengths and limitations of the body of evidence. The new evidence framework will enhance the ACIPs decision-making process by making it more transparent, consistent and systematic.

Motor vehicle crash fatalities by race/ethnicity in Arizona, 1990–96

Objective: To compare rates of motor vehicle crash (MVC) fatalities among different race/ethnic groups in urban and rural Arizona. Method: Using the Fatality Analysis Reporting System and the National Center for Health Statistics Multiple Cause of Death file, MVC fatalities in Arizona from 1990–96 inclusive were classified by gender, race/ethnicity, and urban or rural residence. Age adjusted rates of total, occupant, pedestrian, and alcohol related fatalities were calculated. The total MVC fatality rate for each race/ethnic group was then adjusted for proportion of rural residence. Results: Compared with non-Hispanic whites (NHWs), American Indians had raised relative risks for MVC fatality in all gender and residence subgroups. Hispanic females and rural Hispanic males had lower relative risks, as did rural African-American men. Raised relative risks for American Indian men and women included all subgroups: total, occupant, pedestrian, and alcohol related. Hispanic and African-American men both had raised relative risks of pedestrian related fatalities, and Hispanic men had a slightly higher relative risk while Hispanic women had a lower relative risks, for alcohol related fatality. Hispanic men and women and African-American men had lower occupant fatality rates. Close to half (45%) of the excess MVC fatality among American Indians can be attributed to residence in rural areas, where MVC fatality rates are higher. There were 1.85 occupants in crashes involving NHW deaths compared with 2.51 for Hispanics and 2.71 for American Indians (p<0.001). The proportion of occupants not using a seatbelt was higher in Hispanics and American Indians in both urban and rural areas. Conclusion: The major disparity in MVC fatality in Arizona is among American Indians. The higher MVC fatality rates among American Indians occur in all age groups, in both urban and rural areas, and among occupants and pedestrians. Rural residence, lower rates of seatbelt use, higher rates of alcohol related crashes, a greater number of occupants, and higher rates of pedestrian deaths all contribute to the American Indian MVC fatality disparity. High rates of pedestrian fatality occur in men in all three race/ethnic minorities in Arizona and among American Indian women. In contrast to other studies, African-Americans and Hispanics did not have raised total MVC fatality rates and compared to NHWs actually had lower rates in the rural areas of the state.

Recommendations from the EGAPP Working Group: Can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy?

Summary of recommendations: The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (EWG) found that, for patients with metastatic colorectal cancer (mCRC) who are being considered for treatment with cetuximab or panitumumab, there is convincing evidence to recommend clinical use of KRAS mutation analysis to determine which patients are KRAS mutation positive and therefore unlikely to benefit from these agents before initiation of therapy. The level of certainty of the evidence was deemed high, and the magnitude of net health benefit from avoiding potentially ineffective and harmful treatment, along with promoting more immediate access to what could be the next most effective treatment, is at least moderate.The EWG found insufficient evidence to recommend for or against BRAF V600E testing for the same clinical scenario. The level of certainty for BRAF V600E testing to guide antiepidermal growth factor receptor (EGFR) therapy was deemed low. The EWG encourages further studies of the potential value of testing in patients with mCRC who were found to have tumors that are wild type (mutation negative) for KRAS to predict responsiveness to therapy.The EWG found insufficient evidence to recommend for or against testing for mutations in NRAS, or PIK3CA, and/or loss of expression of PTEN or AKT proteins. The level of certainty for this evidence was low. In the absence of supporting evidence, and with consideration of other contextual issues, the EWG discourages the use of these tests in guiding decisions on initiating anti-EGFR therapy with cetuximab or panitumumab unless further evidence supports improved clinical outcomes.Rationale: It has been suggested that patients with mCRC whose tumors harbor certain mutations affecting EGFR pathway signaling are typically unresponsive to therapy with anti-EGFR antibodies (cetuximab and panitumumab). The EWG identified recent evidence reviews that have addressed this topic, and this recommendation statement is based on results of these reviews. In developing these recommendations the EWG considered evidence in the areas described below.Analytic validity: Although no research syntheses that have formally evaluated analytic validity of these tests were found, the EWG was able to draw the following conclusions from assessments included in the evidence reviews under consideration. There is adequate evidence that KRAS mutation analysis reliably and accurately detects common mutations (codons 12 and 13), whereas evidence was inadequate for less frequent KRAS mutations (e.g., codon 61). There is also adequate evidence that testing for BRAF V600E accurately and reliably detects the mutation. For common mutations in NRAS, PIK3CA, and expression of PTEN AKT, there is adequate evidence of accurate and reliable detection. However, much less data exist in support. Furthermore, in the specific context of mCRC, no evidence was found on the analytic validity of immunohistochemistry (IHC) assays for PTEN or AKT expression.Clinical validity: For KRAS mutation analysis, the EWG found convincing evidence for association with treatment response to anti-EGFR therapy, independent of prognostic association. For BRAF V600E mutation testing, the EWG found insufficient evidence for association with treatment response to anti-EGFR therapy independent of prognostic association. The EWG found insufficient evidence for association of results of testing for mutations in NRAS or PIK3CA, and loss of expression of PTEN or ATK proteins, with treatment response to anti-EGFR therapy.Clinical utility: For KRAS mutation analysis, the EWG found adequate evidence that improved health outcomes are achieved by avoiding ineffective chemotherapy and potential side effects and expediting access to the next most effective treatment. Inadequate evidence was found regarding association of BRAF V600E mutation testing or loss of PTEN expression with improved health outcomes among patients with mCRC undergoing anti-EGFR therapy as compared with patients with tumors bearing wild-type BRAF sequence and PTEN expression levels, respectively. No evidence was found to support improved health outcomes associated with testing results for NRAS or PIK3CA variants, or AKT protein expression levels in this clinical scenario.Contextual issues: CRC is an important and highly prevalent health problem. Improvements in mCRC outcomes associated with pharmacogenetic testing could have important clinical, and potentially public health, impacts. Adverse events related to cancer chemotherapy can be common and severe. Therefore, successfully optimizing treatment to maximize efficacy and minimize side effects is important for reducing mCRC-related morbidity and mortality.Genet Med 2013:15(7):517–527

Motor-vehicle crash fatalities among American Indians and non-Indians in Arizona, 1979 through 1988.

OBJECTIVES This study evaluated the contributions of rural residence, alcohol use, and pedestrian fatalities to the high American Indian motor-vehicle crash mortality rate in Arizona. METHODS Records from the Fatal Accident Reporting System were used to examine mortality rates between 1979 and 1988. RESULTS American Indians had increased relative risks in all motor-vehicle crash categories in all residence-gender groups. The percentage of excess mortality associated with alcohol varied from 36.8% to 66.7%, and the percentage associated with pedestrian deaths ranged from 27.2% to 55.4%. CONCLUSIONS Efforts to reduce excess motor-vehicle crash mortality among American Indians should concentrate on preventing pedestrian and alcohol-related fatalities.

Description and pilot results from a novel method for evaluating return of incidental findings from next-generation sequencing technologies

Purpose:The aim of this study was to develop, operationalize, and pilot test a transparent, reproducible, and evidence-informed method to determine when to report incidental findings from next-generation sequencing technologies.Methods:Using evidence-based principles, we proposed a three-stage process. Stage I “rules out” incidental findings below a minimal threshold of evidence and is evaluated using inter-rater agreement and comparison with an expert-based approach. Stage II documents criteria for clinical actionability using a standardized approach to allow experts to consistently consider and recommend whether results should be routinely reported (stage III). We used expert opinion to determine the face validity of stages II and III using three case studies. We evaluated the time and effort for stages I and II.Results:For stage I, we assessed 99 conditions and found high inter-rater agreement (89%), and strong agreement with a separate expert-based method. Case studies for familial adenomatous polyposis, hereditary hemochromatosis, and α1-antitrypsin deficiency were all recommended for routine reporting as incidental findings. The method requires <3 days per topic.Conclusion:We establish an operational definition of clinically actionable incidental findings and provide documentation and pilot testing of a feasible method that is scalable to the whole genome.Genet Med 15 9, 721–728.Genetics in Medicine (2013); 15 9, 721–728. doi:10.1038/gim.2013.37

The EGAPP initiative: Lessons learned

The Evaluation of Genomic Applications in Practice and Prevention Working Group was first convened in 2005 to develop and test evidence-based methods for the evaluation of genomic tests in transition from research to clinical and public health practice. Over the ensuing years, the Working Group has met 26 times, publishing eight recommendation statements, two methods papers, and one outcomes paper, as well as planning and serving as technical experts on numerous associated systematic reviews. Evaluation of Genomic Applications in Practice and Prevention methods have evolved to address implications of the proliferation of genome-wide association studies and are currently expanding to face challenges expected from clinical implementation of whole-genome sequencing tests. In this article, we review the work of the Evaluation of Genomic Applications in Practice and Prevention Working Group over the first 8 years of its existence with an emphasis on lessons learned throughout the process. It is hoped that in addition to the published methods of the Working Group, the lessons we have learned along the way will be informative to others who are producers and consumers of evidence-based guidelines in the field of genomic medicine.Genet Med 2014:16(3):217–224.

Female-to-female transmission of syphilis: A case report

Background The rate of transmission of HIV and other sexually transmitted infections from female to female is a matter of debate. Sexually transmitted disease among lesbians and female bisexuals is usually associated with sexual contact with men or intravenous drug use. There is little evidence that female-to-female transmission of syphilis can occur. Goals To demonstrate that female-to-female transmission of syphilis can occur through oral-genital sex. Study Design Case report of syphilis transmission from one female to another through oral-genital sex. Conclusion Female-to-female transmission of syphilis can occur through oral-genital sex.

Decentralization of health services in Western Highlands Province, Papua New Guinea: An attempt to administer health service at the subdistrict level

In 1990, Western Highlands Province in Papua New Guinea, decentralized the administration of health services from the province (population 264,000) to 14 districts (equivalent to subdistricts elsewhere). Two years later interviews were conducted with health workers and district and provincial heads. Productivity data were obtained from the provincial health information system and financial data from the provincial and national budgetary report. Health workers had a predominately negative opinion of the results of the decentralization. The most common complaints listed were lack of qualifications of District Assistant Secretaries, a diversion of funds to other programs, unavailability of transportation, a lack of equity in personnel between districts and a lack of adequate professional supervision. The problems which developed in this attempt at further decentralization related to a lack of professional support and oversight of health professionals, a lack of role definition for provincial and district administrators, lack of management training for district officials, inadequate oversight by local elected officials and inadequate budgets.

Vaccines Provided by Family Physicians

PURPOSE This study was conducted to document current immunization practices by family physicians. METHODS In 2008 the American Academy of Family Physicians (AAFP) conducted a survey among a random sample of 2,000 of its members who reported spending 80% or more of their time in direct patient care. The survey consisted of questions regarding the demographics of the practice, vaccines that are provided at the physicians’ clinical site, whether the practice refers patients elsewhere for vaccines, and participation in the Vaccines for Children (VFC) program. RESULTS The response rate was 38.5%, 31.8% after non–office-based respondents were deleted. A high proportion of respondents (80% or more) reported providing most routinely recommended child, adolescent, and adult vaccines at their practice sites. The exceptions were rotavirus vaccine for children and herpes zoster vaccine for adults., A significant proportion, however, reported referring elsewhere for some vaccines (44.1% for children and adolescent vaccines and 53.5% for adult vaccines), with the most frequent referral location being a public health department. A higher proportion of solo and 2-physician practices than larger practices reported referring patients. A lack of adequate payment was listed as the reason for referring patients elsewhere for vaccines by one-half of those who refer patients. One-half of responders do not participate in the VFC program. CONCLUSIONS Provision of recommended vaccines by most family physicians remains an important service. Smaller practices have more difficulty offering a full array of vaccine products, and lack of adequate payment contributes to referring patients outside the medical home. The reasons behind the lack of participation in the VFC program deserve further study.

Performances of underrepresented-minority students at the University of Arizona College of Medicine, 1987-1991

&NA; PURPOSE. To compare the academic performances of underrepresented‐minority (African American, Native American, and Hispanic) students and all other students at the University of Arizona College of Medicine. METHOD. The performances of 42 underrepresented‐minority and 368 other students who graduated between 1987 and 1991 were compared using the following variables: undergraduate science, non‐science, and overall grade‐point average (GPA); scores on the Medical College Admission Test (MCAT); subtest and total scores on the National Board of Medical Examiners (NBME) Part I and Part II examinations; and three types of evaluations from a required family practice clerkship. In addition, a comparison was made of scores on an objective structured clinical examination (OSCE) taken in the fourth year by 25 underrepresented‐minority and 165 other students. Data were analyzed using a three‐way analysis of variance and Pearson correlation analysis. RESULTS. The underrepresented‐minority students earned significantly lower GPAs and scored significantly lower on all standardized paper‐and‐pencil tests and the family practice clerkship final examination. There was no significant group difference in the family practice clerkship clinical evaluations or the majority of the OSCE scores. For both groups, overall GPAs and MCAT scores correlated equally well with NBME total scores but were not significantly corrected with OSCE scores or family practice clerkship clinical evaluations. CONCLUSION. While the underrepresented‐minority students entered medical school with significant educational disadvantages and continued to score lower than the other students on paper‐and‐pencil tests, their clinical performances on the OSCE and family practice clerkship were nearly equivalent to those of the other students.