Development of a novel measure of advanced cancer patients' perceived utility of secondary germline findings from tumor genomic profiling.

Objective: Tumor genomic profiling (TGP) can inform advanced cancer patients' treatment decisions, and also reveal secondary germline findings-information about inherited risks for cancer and other disorders. We sought to develop a measure of patient perceptions of the clinical and personal utility of secondary germline findings. Methods: We developed a draft survey based on literature and patient interview data (n=40). We evaluated and refined the survey through cognitive interviews with advanced cancer patients who received secondary germline findings from TGP (n=10). The survey was psychometrically validated with data from two independent samples of advanced cancer patients undergoing TGP (total n=349). Results: Cognitive interviews offered opportunities for survey refinement and confirmation of its comprehensible nature. Exploratory and confirmatory factor analysis of the survey identified 16 items across three subscales with strong internal consistency (Cronbach's alpha ≥0.79): perceived utility for others, perceived utility for self and health, and confidence in secondary findings. Conclusion: We developed a novel valid scale with promise for measuring advanced cancer patients' perceptions of the utility of secondary germline findings. Innovation: We offer a new patient-derived measure of perceived utility of and confidence in secondary germline findings with potential applications for precision oncology research and clinical communication.

Clinical Impact of a Rapid Genetic Testing Model for Advanced Prostate Cancer Patients.

PURPOSE: Genetic testing may alter clinical management for individuals with metastatic prostate cancer by identifying additional therapies. Traditional counseling models are unlikely to enable time-sensitive therapeutic decision-making. This study aimed to determine the feasibility and clinical impact of an alternative hereditary genetic testing model. MATERIALS AND METHODS: As part of a multicenter, single-arm prospective trial, individuals with advanced prostate cancer were referred by their oncologist for testing of 14 genes associated with hereditary prostate cancer. Pretest education (brochure and video) was provided in the oncology clinic. Questionnaires assessing participant satisfaction with both pretest education and decision to undergo genetic testing were collected. A genetic counselor contacted participants by phone to obtain family history and discuss results. Medical records were queried to determine whether a change in clinical management was discussed. RESULTS: Of 501 participants consented to germline analysis, 51 (10.2%) had at least 1 pathogenic/likely pathogenic variant. Change in treatment was discussed with 22/48 (45.8%) of eligible participants who tested positive. Feasibility of this model was assessed by participant satisfaction and turnaround time. Average±SD satisfaction with the pretest education (15.5±2.2, 4-20 scale) and with the decision to undergo genetic testing (17.1±2.9, 4-20 scale) were both high. Results were returned 20 days (median) after sample collection. CONCLUSIONS: Oncologist-initiated germline genetic testing in collaboration with a genetic counselor is a feasible approach to testing advanced prostate cancer patients with impactful clinical actionability. The testing model and educational material serve as resources to clinicians treating prostate cancer patients.

Attitudes toward preimplantation genetic testing and quality of life among individuals with hereditary diffuse gastric cancer syndrome.

BACKGROUND: Hereditary Diffuse Gastric Cancer (HDGC) syndrome is an autosomal dominant hereditary cancer predisposition associated with germline pathogenic/likely pathogenic variants in the CDH1 gene. Identifying early stage HDGC is difficult, and prophylactic measures can be effective in preventing incidence. Preimplantation Genetic Testing (PGT) can provide information about CDH1 variant status, HDGC risk, and limit familial transmission of CDH1 variants. To date, however, little is known about the attitudes of individuals with CDH1 variants towards PGT. METHODS: Given that little is known about the reproductive attitudes of individuals with HDGC, we recruited participants with CDH1 variants from a familial gastric cancer registry and administered a cross-sectional survey with open- and closed-ended response items. We assessed attitudes regarding PGT and the effect of HDGC on quality of life. RESULTS: Participants (n = 21) were predominantly partnered (61.9%), had a personal cancer history (71.4%), and had biological children (71.4%). Interest in learning about PGT was high; 66.7% of participants were interested in PGT and 90.5% approved of healthcare providers discussing PGT with individuals with CDH1 variants. Attitudes regarding personal use were varied. Among all participants, 35% would not, 25% were uncertain, and 40% would use PGT. Personal philosophy and preferences for family and reproduction were key factors related to PGT attitudes. HDGC had moderate effects on participants' quality of life, including social relationships, health behaviors, and emotional experiences including worry about cancer risk and guilt regarding familial implications. CONCLUSION: PGT was identified by participants as acceptable for use in a variety of contexts and benefits of reproductive counseling involving PGT may extend beyond CDH1 carriers to family members' reproductive behaviors. Dispositions towards PGT are governed by personal philosophy or belief systems. These findings can help guide providers counseling individuals with CDH1 variants.

Marijuana Use and In-Hospital Outcomes After Percutaneous Coronary Intervention in Michigan, United States.

OBJECTIVES: The aim of this study was to evaluate the association between reported marijuana use and post-percutaneous coronary intervention (PCI) in-hospital outcomes. BACKGROUND: Marijuana use is increasing as more states in the United States legalize its use for recreational and medicinal purposes. Little is known about the frequency of use and relative safety of marijuana among patients presenting for PCI. METHODS: The authors analyzed Blue Cross Blue Shield of Michigan Cardiovascular Consortium PCI registry data between January 1, 2013, and September 30, 2016. One-to-one propensity matching and multivariable logistic regression were used to adjust for differences between patients with or without reported marijuana use, and rates of post-PCI complications were compared. RESULTS: Among 113,477 patients, 3,970 reported marijuana use. Compared with those without reported marijuana use, patients with reported marijuana use were likely to be younger (53.9 years vs 65.8 years), to use tobacco (73.0% vs 26.8%), to present with ST-segment elevation myocardial infarction (27.3% vs 15.9%), and to have fewer cardiovascular comorbidities. After matching, compared with patients without reported marijuana use, those with reported marijuana use experienced significantly higher risks for bleeding (adjusted odds ratio [aOR]: 1.54; 95% confidence interval [CI]: 1.20-1.97; P < 0.001) and cerebrovascular accident (aOR: 11.01; 95% CI: 1.32-91.67; P = 0.026) and a lower risk for acute kidney injury (aOR: 0.61; 95% CI: 0.42-0.87; P = 0.007). There were no significant differences in risks for transfusion and death. CONCLUSIONS: A modest fraction of patients undergoing PCI used marijuana. Reported marijuana use was associated with higher risks for cerebrovascular accident and bleeding and a lower risk for acute kidney injury after PCI. Clinicians and patients should be aware of the higher risk for post-PCI complications in these patients.

Uptake and acceptability of a mainstreaming model of hereditary cancer multigene panel testing among patients with ovarian, pancreatic, and prostate cancer.

PURPOSE: To address demands for timely germline information to guide treatments, we evaluated experiences of patients with ovarian, pancreatic, and prostate cancer with a mainstreaming genetic testing model wherein multigene panel testing was ordered by oncologists with standardized pretest patient education, and genetic counselors delivered results and post-test genetic counseling via telephone. METHODS: Among 1,203 eligible patients, we conducted a prospective single-arm study to examine patient uptake and acceptability (via self-report surveys at baseline and three weeks and three months following result return) of this mainstreaming model. RESULTS: Only 10% of eligible patients declined participation. Among 1,054 tested participants, 10% had pathogenic variants (PV), 16% had variants of uncertain significance (VUS), and 74% had no variant identified (NV). Participants reported high initial acceptability, including high satisfaction with their testing decision. Variability over time in several outcomes existed for participants with PV or NV: those with NV experienced a temporary increase in depression (pTime < 0.001; pTime2 < 0.001), and those with PV experienced a small increase in genetic testing distress (p = 0.03). Findings suggested that result type, sex, and cancer type were also associated with outcomes including clinical depression and uncertainty. CONCLUSION: This mainstreaming model may offer a feasible approach for extending access to germline genetic information.

Institutional Variability in Patient Radiation Doses ≥5 Gy During Percutaneous Coronary Intervention.

OBJECTIVES: The aim of this study was to evaluate institutional variability in high radiation doses during percutaneous coronary intervention (PCI). BACKGROUND: It is unknown whether radiation safety practices are optimally applied across institutions performing PCI. METHODS: Using data from a large statewide registry, PCI discharges between July 1, 2016, and March 31, 2018, with a procedural air kerma (AK) recorded were analyzed. PCI procedures were grouped by the performing hospital, and institutional frequency of procedural AK ≥5 Gy was calculated. Fitted hierarchical Bayesian modeling was performed to identify variables independently associated with an AK ≥5 Gy. The performing hospital was included as a random effect in the hierarchical model. RESULTS: Among 36,201 PCI procedures at 28 hospitals, procedural AK was ≥5 Gy in 1,477 cases (4.1%), ≥10 Gy in 185 (0.5%), and ≥15 Gy in 105 (0.3%). The institutional frequency of procedural AK ≥5 Gy ranged from 0.0% to 10.9%. Bayesian modeling identified body mass index, dyslipidemia, diabetes, prior coronary bypass surgery, use of mechanical circulatory support, and the performing hospital as independent predictors of an AK ≥5 Gy. The median odds ratio for the performing hospital, representing an estimate of the contribution of interhospital variability in determining the odds of having a procedural AK ≥5 Gy, was 3.08 (95% confidence interval: 3.01 to 3.16). CONCLUSIONS: Wide variability exists in the institutional frequency of procedural AK ≥5 Gy during PCI. After accounting for patient characteristics and procedural variables, the performing hospital appears to be a major factor in determining patient radiation dose in contemporary PCI.

Illustrating Cancer Risk: Patient Risk Communication Preferences and Interest regarding a Novel BRCA1/2 Genetic Risk Modifier Test.

INTRODUCTION: Genetic risk modifier testing (GRMT), an emerging form of genetic testing based on common single nucleotide polymorphisms and polygenic risk scores, has the potential to refine estimates of BRCA1/2 mutation carriers' breast cancer risks. However, for women to benefit from GRMT, effective approaches for communicating this novel risk information are needed. OBJECTIVE: To evaluate patient preferences regarding risk communication materials for GRMT. METHODS: We developed four separate presentations (panel of genes, icon array, verbal risk estimate, graphical risk estimate) of hypothetical GRMT results, each using varying risk communication strategies to convey different information elements including number of risk modifier variants present, variant prevalence among BRCA1/2 carriers, and implications and uncertainties of test results for cancer risk. Thirty BRCA1/2 carriers evaluated these materials (randomized to low, moderate, or high breast cancer risk versions). Qualitative and quantitative data were obtained through in-person interviews. RESULTS: Across risk versions, participants preferred the presentation of the graphical risk estimate, often in combination with the verbal risk estimate. Interest in GRMT was high; 76.7% of participants wanted their own GRMT. Participants valued the potential for GRMT to clarify their cancer susceptibility and provide actionable information. Many (65.5%) anticipated that GRMT would make risk management decisions easier. CONCLUSIONS: Women with BRCA1/2 mutations could be highly receptive to GRMT, and the minimal amount of necessary information to be included in result risk communication materials includes graphical and verbal estimates of future cancer risk. Findings will inform clinical translation of GRMT in a manner consistent with patients' preferences.

ELECTIVE PERCUTANEOUS CORONARY INTERVENTIONS--A COMPARISION OF EFFICACY OF CLOPIDOGREL AND PRASUGREL.

BACKGROUND: Percutaneous coronary interventions are almost always preceded by the loading dose of platelets inhibiter drugs such as clopidogrel or prasugrel and followed by maintenance therapy to decrease the mortality and morbidity due to stent thrombosis. This study was conducted to compare the efficacy of clopidogrel and prasugrel for inhibiting platelet aggregation among patients undergoing elective percutaneous coronary intervention. METHODS: This randomized controlled trial study was done in Department of Cardiology, Postgraduate Medical Institute Govt. Lady Reading Hospital Peshawar. A total of 148 patients were randomly allocated to either group-A containing 74 patients using clopidogrel or group-B containing 74 patients using prasugrel RESULTS: Group-A had 55 (74.3%) male and 19 (25.7%) females while group-B had 56(75.7%) males and 18 (24.3%) females (p=0.85). Mean age was 54.9 +/- 11.2 years in group-A and was 57.7 +/- 8.7 years in group-B (p=0.09). Mean body weight was 71.8?6.4 Kg in group-A and 70.8 +/- 6.3 Kg in group-B (p=0.35). Mean Baseline platelet aggregation before drug administration was 10.43 +/- 1.9 ohm in group-A while 10.12 +/- 2.2 ohm in group-B (p=0.36). Mean Follow up platelet aggregation 6 hours after drug administration was 5.88 +/- 2.9 in group-A while it was 3.47 +/- 1.8 ohm in group-B (p=0.001). Mean Difference between basal and follow up platelet aggregation +/-SD was 52.9649 +/- 24.77 in group-A while it was 82.25 +/- 14.34 in group-B (p=0.001). 63(85.15%) of group-A had inhibition of platelets aggregation >10% as compare to 72(97.3%) of group-B had inhibition of platelets aggregation >10% (p=0.009). CONCLUSION: Prasugrel is more efficacious than clopidogrel in term of inhibition of platelets aggregation.