Development and Validation of the Minnesota Assessment of Pharmacogenomic Literacy (MAPL).

Ensuring that patients have an adequate understanding of pharmacogenomic (PGx) test results is a critical component of implementing precision medicine into clinical care. However, no PGx-specific validated literacy assessment has yet been developed. To address this need, we developed and validated the Minnesota Assessment of Pharmacogenomic Literacy (MAPLTM). Foundational work included a scoping review of patient and general public attitudes and experiences with pharmacogenomic testing, three focus groups, readability assessments, and review by experts and members of the general public. This resulted in a 15-item assessment designed to assess knowledge in four domains: underlying concepts, limitations, benefits, and privacy. For validation, 646 participants completed the MAPL as a part of a larger survey about pharmacogenomic research and statewide PGx implementation. Two items were deemed to be "too easy" and dropped. The remaining 13 items were retained in the final MAPL with good internal reliability (Cronbach's alpha = 0.75). Confirmatory factor analysis validated the four-domain construct of MAPL and suggested good model performance and high internal validity. The estimated coefficient loadings across 13 questions on the corresponding domains are all positive and statistically significant (p < 0.05). The MAPL covers multiple knowledge domains of specific relevance to PGx and is a useful tool for clinical and research settings where quantitative assessment of PGx literacy is of value.

Using the PhenX Toolkit to Select Standard Measurement Protocols for Your Research Study.

The goals of PhenX (consensus measures for Phenotypes and eXposures) are to promote the use of standard measurement protocols and to help investigators identify opportunities for collaborative research and cross-study analysis, thus increasing the impact of individual studies. The PhenX Toolkit (https://www.phenxtoolkit.org/) offers high-quality, well-established measurement protocols to assess phenotypes and exposures in studies with human participants. The Toolkit contains protocols representing 29 research domains and 6 specialty collections of protocols that add depth to the Toolkit in specific research areas (e.g., COVID-19, Social Determinants of Health [SDoH], Blood Sciences Research [BSR], Mental Health Research [MHR], Tobacco Regulatory Research [TRR], and Substance Abuse and Addiction [SAA]). Protocols are recommended for inclusion in the PhenX Toolkit by Working Groups of domain experts using a consensus process that includes input from the scientific community. For each PhenX protocol, the Toolkit provides a detailed description, the rationale for inclusion, and supporting documentation. Users can browse protocols in the Toolkit, search the Toolkit using keywords, or use Browse Protocols Tree to identify protocols of interest. The PhenX Toolkit provides data dictionaries compatible with the database of Genotypes and Phenotypes (dbGaP), Research Electronic Data Capture (REDCap) data submission compatibility, and data collection worksheets to help investigators incorporate PhenX protocols into their study design. The PhenX Toolkit provides resources to help users identify published studies that used PhenX protocols. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Using the PhenX Toolkit to support or extend study design.

Enrichment sampling for a multi-site patient survey using electronic health records and census data.

Objective: We describe a stratified sampling design that combines electronic health records (EHRs) and United States Census (USC) data to construct the sampling frame and an algorithm to enrich the sample with individuals belonging to rarer strata. Materials and Methods: This design was developed for a multi-site survey that sought to examine patient concerns about and barriers to participating in research studies, especially among under-studied populations (eg, minorities, low educational attainment). We defined sampling strata by cross-tabulating several socio-demographic variables obtained from EHR and augmented with census-block-level USC data. We oversampled rarer and historically underrepresented subpopulations. Results: The sampling strategy, which included USC-supplemented EHR data, led to a far more diverse sample than would have been expected under random sampling (eg, 3-, 8-, 7-, and 12-fold increase in African Americans, Asians, Hispanics and those with less than a high school degree, respectively). We observed that our EHR data tended to misclassify minority races more often than majority races, and that non-majority races, Latino ethnicity, younger adult age, lower education, and urban/suburban living were each associated with lower response rates to the mailed surveys. Discussion: We observed substantial enrichment from rarer subpopulations. The magnitude of the enrichment depends on the accuracy of the variables that define the sampling strata and the overall response rate. Conclusion: EHR and USC data may be used to define sampling strata that in turn may be used to enrich the final study sample. This design may be of particular interest for studies of rarer and understudied populations.

Implementation, adoption, and utility of family health history risk assessment in diverse care settings: evaluating implementation processes and impact with an implementation framework.

PURPOSE: This paper describes the implementation outcomes associated with integrating a family health history-based risk assessment and clinical decision support platform within primary care clinics at four diverse healthcare systems. METHODS: A type III hybrid implementation-effectiveness trial. Uptake and implementation processes were evaluated using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. RESULTS: One hundred (58%) primary care providers and 2514 (7.8%) adult patients enrolled. Enrolled patients were 69% female, 22% minority, and 32% Medicare/Medicaid. Compared with their respective clinic's population, patient-participants were more likely to be female (69 vs. 59%), older (mean age 57 vs. 49), and Caucasian (88 vs. 69%) (all p values <0.001). Female (81.3% of females vs. 78.5% of males, p value = 0.018) and Caucasian (Caucasians 90.4% vs. minority 84.1%, p value = 0.02) patient-participants were more likely to complete the study once enrolled. Patient-participant survey responses indicated MeTree was easy to use (95%), and patient-participants would recommend it to family/friends (91%). Minorities and those with less education reported greatest benefit. Enrolled providers reflected demographics of underlying provider population. CONCLUSION: Family health history-based risk assessment can be effectively implemented in diverse primary care settings and can effectively engage patients and providers. Future research should focus on finding better ways to engage young adults, males, and minorities in preventive healthcare.

Public Attitudes toward Consent and Data Sharing in Biobank Research: A Large Multi-site Experimental Survey in the US.

Individuals participating in biobanks and other large research projects are increasingly asked to provide broad consent for open-ended research use and widespread sharing of their biosamples and data. We assessed willingness to participate in a biobank using different consent and data sharing models, hypothesizing that willingness would be higher under more restrictive scenarios. Perceived benefits, concerns, and information needs were also assessed. In this experimental survey, individuals from 11 US healthcare systems in the Electronic Medical Records and Genomics (eMERGE) Network were randomly allocated to one of three hypothetical scenarios: tiered consent and controlled data sharing; broad consent and controlled data sharing; or broad consent and open data sharing. Of 82,328 eligible individuals, exactly 13,000 (15.8%) completed the survey. Overall, 66% (95% CI: 63%-69%) of population-weighted respondents stated they would be willing to participate in a biobank; willingness and attitudes did not differ between respondents in the three scenarios. Willingness to participate was associated with self-identified white race, higher educational attainment, lower religiosity, perceiving more research benefits, fewer concerns, and fewer information needs. Most (86%, CI: 84%-87%) participants would want to know what would happen if a researcher misused their health information; fewer (51%, CI: 47%-55%) would worry about their privacy. The concern that the use of broad consent and open data sharing could adversely affect participant recruitment is not supported by these findings. Addressing potential participants' concerns and information needs and building trust and relationships with communities may increase acceptance of broad consent and wide data sharing in biobank research.

Electronic medical records and genomics (eMERGE) network exploration in cataract: several new potential susceptibility loci.

PURPOSE: Cataract is the leading cause of blindness in the world, and in the United States accounts for approximately 60% of Medicare costs related to vision. The purpose of this study was to identify genetic markers for age-related cataract through a genome-wide association study (GWAS). METHODS: In the electronic medical records and genomics (eMERGE) network, we ran an electronic phenotyping algorithm on individuals in each of five sites with electronic medical records linked to DNA biobanks. We performed a GWAS using 530,101 SNPs from the Illumina 660W-Quad in a total of 7,397 individuals (5,503 cases and 1,894 controls). We also performed an age-at-diagnosis case-only analysis. RESULTS: We identified several statistically significant associations with age-related cataract (45 SNPs) as well as age at diagnosis (44 SNPs). The 45 SNPs associated with cataract at p<1×10(-5) are in several interesting genes, including ALDOB, MAP3K1, and MEF2C. All have potential biologic relationships with cataracts. CONCLUSIONS: This is the first genome-wide association study of age-related cataract, and several regions of interest have been identified. The eMERGE network has pioneered the exploration of genomic associations in biobanks linked to electronic health records, and this study is another example of the utility of such resources. Explorations of age-related cataract including validation and replication of the association results identified herein are needed in future studies.

Underutilization of Lynch syndrome screening in a multisite study of patients with colorectal cancer.

PURPOSE: The aim of this study was to examine Lynch syndrome screening of patients with metastatic colorectal cancer in integrated health-care-delivery organizations. METHODS: We determined the availability of Lynch syndrome screening criteria and actual Lynch syndrome screening in the medical records of 1,188 patients diagnosed with metastatic colorectal cancer between 2004 and 2009 at seven institutions in the Cancer Research Network. RESULTS: We found infrequent use of Lynch syndrome screening (41/1,188). Family history was available for 937 of the 1,188 patients (79%). There was sufficient information to assess Lynch syndrome risk using family history-based criteria in 719 of the 937 patients (77%) with family history documentation. In 391 individuals with a family history of a Lynch syndrome-associated cancer, 107 (27%) could not be evaluated due to missing information such as age of cancer onset. Eleven percent of patients who met the Bethesda criteria and 25% of individuals who met the Amsterdam II criteria were screened for Lynch syndrome. Recommended guidelines were adhered to during screening, but no testing method was preferred. CONCLUSION: The information required for Lynch syndrome screening decisions is routinely collected but seldom used. There is a critical gap between collection of family history and its use to guide Lynch syndrome screening, which may support a case for implementation of universal screening guidelines.

Vision-related research priorities and how to finance them.

A number of organizations have employed a consultative process with the vision community to engage relevant parties in identifying needs and opportunities for vision research. The National Eye Institute in the US and the European Commission are currently undergoing consultation to develop priorities for vision research. Once these priorities have been established, the challenge will be to identify the resources to advance these research agendas. Success rates for Federal funding for research have decreased recently in the USA, UK, and Australia. Researchers should consider various potential funding sources for their research. The universal consideration for funding is that the reason for funding should align with the mission of the funding organization. In addition to Federal research organizations that fund investigator-initiated research, other potential funding sources include nongovernmental organizations, for-profit companies, individual philanthropy, and service organizations. In addition to aligning with organizational funding priorities, researchers need to consider turn-around time and total funds available including whether an organization will cover institutional indirect costs. Websites are useful tools to find information about organizations that fund research, including grant deadlines. Collaboration is encouraged.

Health services utilization and cost of retinitis pigmentosa.

OBJECTIVE: To estimate annual per-patient health services utilization and costs of retinitis pigmentosa (RP) in the United States. METHODS: A retrospective claims analysis of patients with RP (N = 2990) and a 1:1 exactly matched cohort of non-RP patients was conducted using the MarketScan Commercial and Medicare Supplemental Databases. Individuals were continuously enrolled in a commercial health plan or employer-sponsored health insurance for at least 1 year. The following annual outcomes were analyzed using nonlinear multivariate models: inpatient hospital admissions, inpatient hospital days, emergency department visits, outpatient physician visits, and prescription drug refills and inpatient and outpatient medical, pharmacy, and total health care costs. RESULTS: Patients with RP had 0.04 more hospital admissions (P < .001), 0.19 more inpatient hospital days (P < .02), 0.05 more emergency department visits (P < .01), 2.74 more outpatient visits (P < .001), and 2.18 additional prescription drug fills (P < .001) annually compared with their non-RP counterparts. Health care expenditures were significantly higher for patients with RP, who cost $894, $4855, and $452 more for inpatient, outpatient, and pharmacy services, respectively (P < .001). Overall health care costs were $7317 more per patient per year in the RP cohort, with expenditures varying considerably by age. CONCLUSIONS: Patients with RP consume substantially greater amounts of health services with significantly higher health care costs. CLINICAL RELEVANCE: Treatments that slow, halt, or possibly restore RP-related vision loss may prove cost-effective for payers and society.

Novel measures of cardiovascular health and its association with prevalence and progression of age-related macular degeneration: the CHARM Study.

BACKGROUND: To determine if novel measures of cardiovascular health are associated with prevalence or progression of age-related macular degeneration (AMD). METHODS: Measures of the cardiovascular system: included intima media thickness (IMT), pulse wave velocity (PWV), systemic arterial compliance (SAC), carotid augmentation index (AI). For the prevalence study, hospital-based AMD cases and population-based age- and gender-matched controls with no signs of AMD in either eye were enrolled. For the progression component, participants with early AMD were recruited from two previous studies; cases were defined as progression in one or both eyes and controls were defined as no progression in either eye. RESULTS: 160 cases and 160 controls were included in the prevalence component. The upper two quartiles of SAC, implying good cardiovascular health, were significantly associated with increased risk of AMD (OR = 2.54, 95% CL = 1.29, 4.99). High PWV was associated with increased prevalent AMD. Progression was observed in 82 (32.3%) of the 254 subjects recruited for the progression component. Higher AI (worse cardiovascular function) was protective for AMD progression (OR = 0.30, 95%CL = 0.13, 0.69). Higher aortic PWV was associated with increased risk of AMD progression; the highest risk was seen with the second lowest velocity (OR = 6.22, 95% CL = 2.35, 16.46). CONCLUSION: The results were unexpected in that better cardiovascular health was associated with increased risk of prevalent AMD and progression. Inconsistent findings between the prevalence and progression components could be due to truly different disease etiologies or to spurious findings, as can occur with inherent biases in case control studies of prevalence. Further investigation of these non-invasive methods of characterizing the cardiovascular system should be undertaken as they may help to further elucidate the role of the cardiovascular system in the etiology of prevalent AMD and progression.

Clinical genetics provider real-time workflow study.

PURPOSE: Our work is the first documentation, in real time, of workflow in a general genetics department including data on patient care, research, and other activities for both clinical geneticists and genetic counselors. METHODS: All physician geneticists and genetic counselors in the medical genetics department used an electronic tool to record their activities in 15 minute increments during clinic hours, evenings, and weekends over a 10-week period. RESULTS: The average work week was 54.1 hours for physicians and 43.5 hours for genetic counselors. During clinic hours physicians spent about one-fourth of their time on direct patient care, one-fourth on other patient-related activities, one-fourth on research unrelated to individual patient care, and the remaining fourth on all other activities. However, after hours and on weekends they spent most of their time on research. Genetic counselors spent half of their time on patient-related activities, one-fourth on direct patient care, and the remainder on all other activities. The total professional time averaged 7 hours per new patient and 3.5 hours per follow-up with nearly 60% of this time devoted to patient-related activities. CONCLUSIONS: The labor intensive nature of clinical genetics, the large amount of time devoted to patient-related activities, and continuing limitations on billing by genetic counselors all contribute to the financial challenges faced by genetics departments.

Sunlight exposure assessment: can we accurately assess vitamin D exposure from sunlight questionnaires?

The purpose of this review is to summarize the peer-reviewed literature in relation to sunlight exposure assessment and the validity of using sunlight exposure questionnaires to quantify vitamin D status. There is greater variability in personal ultraviolet (UV) light exposure as the result of personal behavior than as the result of ambient UV light exposure. Although statistically significant, the correlation coefficients for the relation between personal report of sun exposure and ambient UV light measured by dosimetry (assessment of radiation dose) are relatively low. Moreover, the few studies to assess the relation between sunlight measures and serum 25-hydroxyvitamin D show low correlations. These low correlations may not be surprising given that personal factors like melanin content in skin and age also influence cutaneous synthesis of vitamin D. In summary, sunlight exposure questionnaires currently provide imprecise estimates of vitamin D status. Research should be directed to develop more objective, nonintrusive, and economical measures of sunlight exposure to quantify personal vitamin D status.

Investigating Perceived Institutional Review Board Quality and Function Using the IRB Researcher Assessment Tool.

THE INSTITUTIONAL REVIEW BOARD-RESEARCHER ASSESSMENT TOOL (IRB-RAT) was designed to assess the relative importance of various factors to the effective functioning of IRBs. We employed the IRB-RAT to gain insight into the ways in which our IRB is perceived to be deficient by those who routinely interact with our Office of Research Integrity and Protections. Respondents ranked qualities thought to be characteristic of an "ideal" IRB and then compared our IRB to that internal standard. We observed that the rate of study participation varied by role. The composite relative ranking of the 45 items that comprise the IRB-RAT differed significantly from the rank order reported by Keith-Spiegel et al. Our data furthermore suggest that role influences scoring of the IRB-RAT (e.g., investigators awarded our IRB significantly higher scores in several areas than did research coordinators). Additional research is warranted to determine if the observed role-dependent differences in the perceived quality of our IRB simply reflect the local research culture or if they are indicative of a more fundamental and generalizable difference in outlook between investigators and research coordinators.

Psychosocial work characteristics predict cardiovascular disease risk factors and health functioning in rural women: the Wisconsin Rural Women's Health Study.

BACKGROUND: The aim of the present study is to investigate the association between psychosocial work characteristics and health functioning and cardiovascular disease risk factors among rural women of central Wisconsin and compare psychosocial work characteristics between farm and nonfarm women. METHODS: Stratified sampling was used to select a random sample (n = 1500) of farm and nonfarm women aged 25 to 71 years from the Central Marshfield Epidemiologic Study Area. The baseline examination included measurements of blood pressure, height, weight, and fasting blood lipids, glucose, and insulin. Psychosocial job condition was measured with the Karasek Job Content Questionnaires (JCQ). Health functioning was assessed by the Short Form-36 Health Survey. RESULTS: The analysis of JCQ showed that nonfarm residents were more likely to have jobs with high demand and high decision latitude compared to farm residents. Also, the farm residents (40.3%) were more likely to be occupied in passive jobs (jobs with low levels of demand and control) than the nonfarm residents (26.9%). Among farm residents, psychological job demand was associated with HDL level (beta = 0.17), triglycerides (beta = 0.0), their ratio (beta = 0.005), and blood insulin level (beta = 0.014), and among nonfarm residents, psychological job demand was associated with diastolic blood pressure (beta = 0.17) and total cholesterol level (beta = 0.002). CONCLUSION: Our results showed that rural farm residents had a higher prevalence of CVD risk factors and were more likely to be occupied in jobs with low levels of demand and control. Job stress predicted more CVD risk factors among farm residents compared to nonfarm residents. Therefore, interventions reducing job strain among rural farm residents are timely and necessary.

The need for routine eye examinations.

PURPOSE: To determine the incidence and causes of vision loss to assist in the objective determination of the preferred frequency of routine screening for those with normal vision. METHODS: A prospective, population-based study of people aged 40 or more years. Standardized examination protocols were used that included presenting and best corrected visual acuity, visual field testing, and comprehensive eye examination with dilation. RESULTS: There were 2529 people with a full data set, including 1590 with a normal baseline examination. The 5-year incidence of vision loss (<6/12 presenting acuity in the worse eye) was 2.39%. Overall, 24 (63%) of 38 of those with vision loss had noticed a change in their vision, and 18 (75%) of these 24 had attended an eye examination. This left only 14 (0.88%) people who had had normal baseline examination results and had asymptomatic vision loss develop over this 5-year period. CONCLUSIONS: Frequent routine eye examinations of those with normal examination results will have a low yield and may not be cost effective. Health promotion messages should target those who notice a change in vision and those at higher risk such as those with diabetes or a family history of eye disease.

Cataract in the 21st Century: lessons from previous epidemiological research.

BACKGROUND: Cataract surgery is currently the most commonly performed ophthalmic procedure in Australia. The purpose of this paper is to review Australian data on cataract prevalence and risk factors and to project potential future demand for cataract services. METHODS: Age- and gender-specific cataract prevalence data from the Melbourne Visual Impairment Project (VIP) and the Blue Mountains Eye Study (BMES) were applied to population estimates from the Australian Bureau of Statistics. Published cataract risk factor data from the two studies were reviewed. RESULTS: Although the projected number of cataracts varies substantially based on the definition used, the relative number of cataracts will double over the next 50 years due to the aging of the population. Risk factors for cortical cataract identified in both the VIP and the BMES included female gender, sunlight exposure and myopia. Concordant findings for nuclear cataract included female gender, brown irides, cigarette smoking and myopia. The only risk factor for posterior subcapsular cataract (PSC) that was identified in both studies was myopia. Some of the discrepant findings between the two studies included alcohol intake, diabetes and medication use. DISCUSSION: These data suggest that supply and demand for cataract surgery must be considered and managed to maintain the current level of cataract surgery delivery as the number of people with cataract increases at a proportionately greater rate than the total population. The supply of cataract surgical services could be increased through an increase in the number of ophthalmologists, an increase in the efficiency with which cataract surgical services are delivered, or improved technology. The demand for cataract surgery could be decreased through the implementation of effective primary prevention strategies, although successful strategies are currently unknown and/or untested. Given our current state of knowledge about cataract, it seems most feasible immediately to alter the health service delivery side of the equation to reduce the public health burden of cataract.

Population-based assessment of refractive error in India: the Andhra Pradesh eye disease study.

PURPOSE: To assess the prevalence, distribution, and demographic associations of refractive error in the population of the southern Indian state of Andhra Pradesh. METHODS: From 94 clusters in one urban and three rural areas of Andhra Pradesh, 11 786 persons of all ages were sampled using a stratified, random, cluster, systematic sampling strategy in the Andhra Pradesh Eye Disease Study, a population-based cross-sectional study. A total of 10 293 people underwent an interview and detailed dilated eye examination. Refraction was performed by ophthalmic personnel trained in the study procedures. Objective refraction under cycloplegia was assessed for participants < or = 15 years of age and subjective refraction for those > 15 years of age. Myopia was defined as spherical equivalent worse than -0.50 D and hyperopia as spherical equivalent worse than +0.50 D. RESULTS: In the participants < or = 15 years of age, the prevalence of myopia was 3.19% (95% confidence interval [CI] 2.24-4.13%) and of hyperopia was 62.62% (95% CI 57.10-68.13%). In this age group, myopia increased with increasing age and was more prevalent in the urban study area, and hyperopia prevalence was greater in the participants < 10 years of age. In participants > 15 years of age, the prevalence of myopia was 19.45% (95% CI 17.88-21.02%) and of hyperopia was 8.38% (95% CI 6.91-9.85%). Myopia and hyperopia increased with increasing age. Myopia was more common in males, those with education higher than class 12, those with nuclear cataract, and those living in rural study areas. Hyperopia was more common in females, those with any level of formal education, and those living in the urban area and in the well-off rural study area. CONCLUSIONS: There is significant refractive error in this population. These data on the distribution and associations of refractive error can be useful for the planning of refractive eye-care services.