Katherine M. James

Toll-like Receptor Polymorphisms and Age-Related Macular Degeneration

PURPOSE Evidence from genetic-association studies in conjunction with the demonstration of complement deposition in the retina and choroid implicates noncellular pathways of innate immunity in the pathogenesis of age-related macular degeneration (AMD). The purpose of this study was to determine whether common variation in the 10 human toll-like receptors (TLRs) alters the risk of AMD. METHODS Sixty-eight SNPs were iteratively genotyped across the TLR genes in a cohort of 577 subjects, with and without AMD. Two additional cohorts were used for replication studies. Standard genetic-association methods were used to analyze the results for association with disease and interaction with other loci. RESULTS Coding SNPs in TLR3 (rs3775291) and TLR7 (rs179008) showed association with AMD in one group (P = 0.01 and P = 0.02, respectively) before correction for multiple testing. For both SNPs, the association with AMD arose due to an excess of heterozygotes compared with homozygotes for the major allele. The two coding SNPs were not associated with AMD in another case-control cohort or an extended-family cohort. Although an intronic SNP in TLR4 was associated marginally with AMD (P = 0.03), it was not possible to replicate a previous association with the rare coding SNP D299G in this gene (P = 0.6). CONCLUSIONS Although borderline support for association between polymorphisms in TLR genes and AMD was reported for some cohorts, these initial observations of coding SNPs in TLR3, TLR4, and TLR7 were not replicated. TLR variants are unlikely to have a major impact on overall AMD risk, and the common variants studied were not associated with AMD.

Getting physicians to respond: the impact of incentive type and timing on physician survey response rates.

OBJECTIVE To study the effects of payment timing, form of payment, and requiring a social security number (SSN) on survey response rates. DATA SOURCE Third-wave mailing of a U.S. physician survey. STUDY DESIGN Nonrespondents were randomized to receive immediate U.S.

Impact of direct-to-consumer predictive genomic testing on risk perception and worry among patients receiving routine care in a preventive health clinic.

25 cash, immediate U.S.

Evaluation of Clustering and Genotype Distribution for Replication in Genome Wide Association Studies: The Age-Related Eye Disease Study

25 check, promised U.S.

How patients view probiotics: Findings from a multicenter study of patients with inflammatory bowel disease and irritable bowel syndrome

25 check, or promised U.S.

“Righteous Minds” in Health Care: Measurement and Explanatory Value of Social Intuitionism in Accounting for the Moral Judgments in a Sample of U.S. Physicians

25 check requiring an SSN. DATA COLLECTION METHODS Paper survey responses were double entered into statistical software. PRINCIPAL FINDINGS Response rates differed significantly between remuneration groups (χ(3) (2) = 80.1, p<.0001), with the highest rate in the immediate cash group (34 percent), then immediate check (20 percent), promised check (10 percent), and promised check with SSN (8 percent). CONCLUSIONS Immediate monetary incentives yield higher response rates than promised in this population of nonresponding physicians. Promised incentives yield similarly low response rates regardless of whether an SSN is requested.

Listening in on difficult conversations: an observational, multi-center investigation of real-time conversations in medical oncology

OBJECTIVE To assess the impact of direct-to-consumer (DTC) predictive genomic risk information on perceived risk and worry in the context of routine clinical care. PATIENTS AND METHODS Patients attending a preventive medicine clinic between June 1 and December 18, 2009, were randomly assigned to receive either genomic risk information from a DTC product plus usual care (n=74) or usual care alone (n=76). At intervals of 1 week and 1 year after their clinic visit, participants completed surveys containing validated measures of risk perception and levels of worry associated with the 12 conditions assessed by the DTC product. RESULTS Of 345 patients approached, 150 (43%) agreed to participate, 64 (19%) refused, and 131 (38%) did not respond. Compared with those receiving usual care, participants who received genomic risk information initially rated their risk as higher for 4 conditions (abdominal aneurysm [P=.001], Graves disease [P=.04], obesity [P=.01], and osteoarthritis [P=.04]) and lower for one (prostate cancer [P=.02]). Although differences were not significant, they also reported higher levels of worry for 7 conditions and lower levels for 5 others. At 1 year, there were no significant differences between groups. CONCLUSION Predictive genomic risk information modestly influences risk perception and worry. The extent and direction of this influence may depend on the condition being tested and its baseline prominence in preventive health care and may attenuate with time.

The moral psychology of rationing among physicians: the role of harm and fairness intuitions in physician objections to cost-effectiveness and cost-containment

Genome-wide association studies (GWASs) assess correlation between traits and DNA sequence variation using large numbers of genetic variants such as single nucleotide polymorphisms (SNPs) distributed across the genome. A GWAS produces many trait-SNP associations with low p-values, but few are replicated in subsequent studies. We sought to determine if characteristics of the genomic loci associated with a trait could be used to identify initial associations with a higher chance of replication in a second cohort. Data from the age-related eye disease study (AREDS) of 100,000 SNPs on 395 subjects with and 198 without age-related macular degeneration (AMD) were employed. Loci highly associated with AMD were characterized based on the distribution of genotypes, level of significance, and clustering of adjacent SNPs also associated with AMD suggesting linkage disequilibrium or multiple effects. Forty nine loci were highly associated with AMD, including 3 loci (CFH, C2/BF, LOC387715/HTRA1) already known to contain important genetic risks for AMD. One additional locus (C3) reported during the course of this study was identified and replicated in an additional study group. Tag-SNPs and haplotypes for each locus were evaluated for association with AMD in additional cohorts to account for population differences between discovery and replication subjects, but no additional clearly significant associations were identified. Relying on a significant genotype tests using a log-additive model would have excluded 57% of the non-replicated and none of the replicated loci, while use of other SNP features and clustering might have missed true associations.

Envelope Type and Response Rates in a Survey of Health Professionals

Background Patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) have access to a growing number of probiotic products marketed to improve digestive health. It is unclear how patients make decisions about probiotics and what role they expect their gastroenterologists to play as they consider using probiotics. Understanding patients’ knowledge, attitudes and expectations of probiotics may help gastroenterologists engage patients in collaborative discussions about probiotics. Study Focus groups were conducted with patients with IBD and IBS at the Cleveland Clinic, Mayo Clinic, and Johns Hopkins University. Inductive analytic methods were used to identify common themes and draw interpretations from focus group narratives. Results One hundred thirty-six patients participated in 22 focus groups between March and August 2009. Patients viewed probiotics as an appealing alternative to pharmaceutical drugs and understood probiotics as a more “natural,” low-risk therapeutic option. Many patients were hesitant to use them without consulting their gastroenterologists. Patients would weigh the risks and benefits of probiotics, their disease severity and satisfaction with current treatments when considering probiotic use. Conclusions Patients are interested in probiotics but have many unanswered questions about their use. Our findings suggest that patients with IBD and IBS will look to gastroenterologists and other clinicians as trustworthy advisors regarding the utility of probiotics as an alternative or supplement to pharmaceutical drugs. Gastroenterologists and other clinicians who care for patients with these diseases should be prepared to discuss the potential benefits and risks of probiotics and assist patients in making informed decisions about their use.

Assessing follow-up care after prostate-specific antigen elevation in American Indian / Alaska native men: A partnership approach

The broad diversity in physicians’ judgments on controversial health care topics may reflect differences in religious characteristics, political ideologies, and moral intuitions. We tested an existing measure of moral intuitions in a new population (U.S. physicians) to assess its validity and to determine whether physicians’ moral intuitions correlate with their views on controversial health care topics as well as other known predictors of these intuitions such as political affiliation and religiosity. In 2009, we mailed an 8-page questionnaire to a random sample of 2000 practicing U.S. physicians from all specialties. The survey included the Moral Foundations Questionnaire (MFQ30), along with questions on physicians’ judgments about controversial health care topics including abortion and euthanasia (no moral objection, some moral objection, strong moral objection). A total of 1032 of 1895 (54%) physicians responded. Physicians’ overall mean moral foundations scores were 3.5 for harm, 3.3 for fairness, 2.8 for loyalty, 3.2 for authority, and 2.7 for sanctity on a 0–5 scale. Increasing levels of religious service attendance, having a more conservative political ideology, and higher sanctity scores remained the greatest positive predictors of respondents objecting to abortion (β = 0.12, 0.23, 0.14, respectively, each p<0.001) as well as euthanasia (β = 0.08, 0.17, and 0.17, respectively, each p<0.001), even after adjusting for demographics. Higher authority scores were also significantly negatively associated with objection to abortion (β = −0.12, p<0.01), but not euthanasia. These data suggest that the relative importance physicians place on the different categories of moral intuitions may predict differences in physicians’ judgments about morally controversial topics and may interrelate with ideology and religiosity. Further examination of the diversity in physicians’ moral intuitions may prove illustrative in describing and addressing moral differences that arise in medical practice.