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A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease.

ABSTRACT: Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD.A randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared with condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Preplanned co-primary outcomes were anxiety and depression scales 12 months after disclosure.Three hundred and forty-three adults (mean age 58.3, range 33-86 years, 71% female, 23% African American) were randomly assigned to the SP-GC protocol (n = 115), CP-GC protocol (n = 116), or CP-MD protocol (n = 112). Mean postdisclosure scores on all outcomes were well below cut-offs for clinical concern across protocols. Comparing CP-GC with SP-GC, the 97.5% upper confidence limits at 12 months after disclosure on co-primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all P < .001 on noninferiority tests), establishing noninferiority for condensed protocols. Results were similar between European Americans and African Americans.These data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information.

SUBMITTER: Green RC

PROVIDER: S-EPMC4461546 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease.

Green Robert C RC Christensen Kurt D KD Cupples L Adrienne LA Relkin Norman R NR Whitehouse Peter J PJ Royal Charmaine D M CD Obisesan Thomas O TO Cook-Deegan Robert R Linnenbringer Erin E Butson Melissa Barber MB Fasaye Grace-Ann GA Levinson Elana E Roberts J Scott JS

Alzheimer's & dementia : the journal of the Alzheimer's Association 20141209 10

<h4>Introduction</h4>Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD.<h4>Methods</h4>A randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first-degree ...[more]

PMID: 25499536

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Project description:Background:Germline genetic testing is standard practice in oncology. Outcomes of telephone disclosure of a wide range of cancer genetic test results, including multigene panel testing (MGPT) are unknown. Methods:Patients undergoing cancer genetic testing were recruited to a multicenter, randomized, noninferiority trial (NCT01736345) comparing telephone disclosure (TD) of genetic test results with usual care, in-person disclosure (IPD) after tiered-binned in-person pretest counseling. Primary noninferiority outcomes included change in knowledge, state anxiety, and general anxiety. Secondary outcomes included cancer-specific distress, depression, uncertainty, satisfaction, and screening and risk-reducing surgery intentions. To declare noninferiority, we calculated the 98.3% one-sided confidence interval of the standardized effect; t tests were used for secondary subgroup analyses. Only noninferiority tests were one-sided, others were two-sided. Results:A total of 1178 patients enrolled in the study. Two hundred eight (17.7%) participants declined random assignment due to a preference for in-person disclosure; 473 participants were randomly assigned to TD and 497 to IPD; 291 (30.0%) had MGPT. TD was noninferior to IPD for general and state anxiety and all secondary outcomes immediately postdisclosure. TD did not meet the noninferiority threshold for knowledge in the primary analysis, but it did meet the threshold in the multiple imputation analysis. In secondary analyses, there were no statistically significant differences between arms in screening and risk-reducing surgery intentions, and no statistically significant differences in outcomes by arm among those who had MGPT. In subgroup analyses, patients with a positive result had statistically significantly greater decreases in general anxiety with telephone disclosure (TD -0.37 vs IPD +0.87, P = .02). Conclusions:Even in the era of multigene panel testing, these data suggest that telephone disclosure of cancer genetic test results is as an alternative to in-person disclosure for interested patients after in-person pretest counseling with a genetic counselor.

Project description:BackgroundThe apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial.MethodsWe randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's disease to receive the results of their own APOE genotyping (disclosure group) or not to receive such results (nondisclosure group). We measured symptoms of anxiety, depression, and test-related distress 6 weeks, 6 months, and 1 year after disclosure or nondisclosure.ResultsThere were no significant differences between the two groups in changes in time-averaged measures of anxiety (4.5 in the disclosure group and 4.4 in the nondisclosure group, P=0.84), depression (8.8 and 8.7, respectively; P=0.98), or test-related distress (6.9 and 7.5, respectively; P=0.61). Secondary comparisons between the nondisclosure group and a disclosure subgroup of subjects carrying the APOE epsilon4 allele (which is associated with increased risk) also revealed no significant differences. However, the epsilon4-negative subgroup had a significantly lower level of test-related distress than did the epsilon4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the epsilon4-positive and epsilon4-negative subgroups. Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures (P<0.001 for both comparisons).ConclusionsThe disclosure of APOE genotyping results to adult children of patients with Alzheimer's disease did not result in significant short-term psychological risks. Test-related distress was reduced among those who learned that they were APOE epsilon4-negative. Persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure. (ClinicalTrials.gov number, NCT00571025.)

Project description:ImportancePostdischarge video-based virtual visits are a growing aspect of surgical care and have dramatically increased in the setting of the coronavirus disease 2019 (COVID-19) pandemic.ObjectiveTo evaluate the outcomes of all-cause 30-day hospital encounter proportion among patients who have a postdischarge video-based virtual visit follow-up compared with in-person follow-up.Design, setting, and participantsRandomized, active, controlled noninferiority trial in an urban setting, including patients from a small community hospital and a large, tertiary care hospital. Patients who underwent minimally invasive appendectomy or cholecystectomy by a group of surgeons who cover emergency general surgery at these 2 hospitals were included. Patients undergoing elective and nonelective procedures were included.InterventionsPatients were randomized in a 2:1 fashion to video-based virtual visit or in-person visit.Main outcomes and measuresThe primary outcome is the percentage of patients with 30-day hospital encounter, and we hypothesized that there would not be a significant increase in the 30-day hospital encounter proportion for patients who receive video-based virtual postdischarge care compared with patients who receive standard (in-person) care. Hospital encounter includes emergency department visit, observation, or inpatient admission.ResultsA total of 1645 patients were screened; 289 patients were randomized to the virtual group and 143 to the in-person group. Fifty-three patients crossed over to the in-person follow-up group. The percentage of patients who had a hospital encounter was noninferior for virtual visits (12.8% vs 13.3% for in-person, Δ 0.5% with 1-sided 95% CI, -∞ to 5.2%). The amount of time patients spent with the clinician (mean of 8.4 minutes virtual vs 7.8 minutes in-person; P = .30) was not different, but the median overall postoperative visit time was 27.5 minutes shorter (95% CI, -33.5 to -24.0).Conclusions and relevancePostdischarge video-based virtual visits did not increase hospital encounter proportions and provided shorter overall time commitment but equal time with the surgical team member. This information will help surgeons and patients feel more confident in using video-based virtual visits.Trial registrationClinicalTrials.gov Identifier: NCT03258177.

Project description:BackgroundProponents of consumer genetic tests claim that the information can positively impact health behaviors and aid in chronic disease prevention. However, the effects of disclosing genetic information on dietary intake behavior are not clear.MethodsA double-blinded, parallel group, 2:1 online randomized controlled trial was conducted to determine the short- and long-term effects of disclosing nutrition-related genetic information for personalized nutrition on dietary intakes of caffeine, vitamin C, added sugars, and sodium. Participants were healthy men and women aged 20-35 years (n = 138). The intervention group (n = 92) received personalized DNA-based dietary advice for 12-months and the control group (n = 46) received general dietary recommendations with no genetic information for 12-months. Food frequency questionnaires were collected at baseline and 3- and 12-months after the intervention to assess dietary intakes. General linear models were used to compare changes in intakes between those receiving general dietary advice and those receiving DNA-based dietary advice.ResultsCompared to the control group, no significant changes to dietary intakes of the nutrients were observed at 3-months. At 12-months, participants in the intervention group who possessed a risk version of the ACE gene, and were advised to limit their sodium intake, significantly reduced their sodium intake (mg/day) compared to the control group (-287.3 ± 114.1 vs. 129.8 ± 118.2, p = 0.008). Those who had the non-risk version of ACE did not significantly change their sodium intake compared to the control group (12-months: -244.2 ± 150.2, p = 0.11). Among those with the risk version of the ACE gene, the proportion who met the targeted recommendation of 1500 mg/day increased from 19% at baseline to 34% after 12 months (p = 0.06).ConclusionsThese findings demonstrate that disclosing genetic information for personalized nutrition results in greater changes in intake for some dietary components compared to general population-based dietary advice.Trial registrationClinicalTrials.gov NCT01353014.

Project description:BackgroundThe enrollment into clinical trials of persons at risk for autosomal dominant Alzheimer's disease (ADAD) in whom the onset of disease can be accurately predicted facilitates the interpretation of outcomes (e.g., biomarkers, treatment efficacy). Attitudes toward involvement in such studies are biased by intrinsic cultural and social characteristics. Our objective was to study how demographic factors such as country of residence, age, sex, schooling, parenthood, and urbanization affect attitudes towards participation in hypothetical clinical trials in Mexican families at risk for ADAD living either in Mexico or in the United States.MethodsParticipants were 74 members of different families known to harbor an ADAD mutation living in Mexico (n = 50) or in the United States (n = 24). Participants were asked, in a written questionnaire, their interest in participating in four hypothetical clinical trial scenarios of increasing perceived invasiveness. The questionnaire then asked about their willingness should there be a 50% chance of being assigned to a placebo group. The influences of demographic variables on decisions were performed using Wilcoxon rank-sum for continuous variables and Fisher's exact test for categorical variables.ResultsParticipants who live in Mexico, who have or plan to have children, who do not attend or do not plan to attend school, and who live in rural areas gave more positive responses regarding their willingness to participate compared to those living in the U.S. The 50% chance of being in a placebo group increased the willingness to participate for family members living in Mexico. The main reason for participation was to help future generations, while the main reasons for refusal were not wanting to undergo genetic testing and consideration of adverse effects.ConclusionsWe found a higher level of willingness to participate in clinical trials among persons living in rural Mexico and our data suggest that altruism towards future generations is a major motivation, though this was balanced against concerns regarding side effects. Our results emphasize the importance of sharing information and assessing its understanding in potential participants with diverse backgrounds in the nature of ADAD and regarding the design of clinical trials prior to their enrollment in such studies.

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A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease.

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A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease.

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