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INTRODUCTION: Despite studies showing improved safety, efficacy, and cost-effectiveness of endoscopic resection for nonmalignant colorectal polyps, colectomy rates for nonmalignant colorectal polyps have been increasing in the United States and Europe. Given this alarming trend, we aimed to investigate whether colectomy rates for nonmalignant colorectal polyps are increasing or declining in a large, integrated, community-based healthcare system with access to advanced endoscopic resection procedures. METHODS: We identified all individuals aged 50–85 years who underwent a colonoscopy between 2008 and 2018 and were diagnosed with a nonmalignant colorectal polyp(s) at the Kaiser Permanente Northern California integrated healthcare system. Among these individuals, we identified those who underwent a colectomy for nonmalignant colorectal polyps within 12 months after the colonoscopy. We calculated annual colectomy rates for nonmalignant colorectal polyps and stratified rates by age, sex, and race and ethnicity. Changes in rates over time were tested by the Cochran-Armitage test for a linear trend. RESULTS: Among 229,730 patients who were diagnosed with nonmalignant colorectal polyps between 2008 and 2018, 1,611 patients underwent a colectomy. Colectomy rates for nonmalignant colorectal polyps decreased significantly from 125 per 10,000 patients with nonmalignant polyps in 2008 to 12 per 10,000 patients with nonmalignant polyps in 2018 ( P < 0.001 for trend). When stratified by age, sex, and race and ethnicity, colectomy rates for nonmalignant colorectal polyps also significantly declined from 2008 to 2018. DISCUSSION: In a large, ethnically diverse, community-based population in the United States, we found that colectomy rates for nonmalignant colorectal polyps declined significantly over the past decade likely because of the establishment of advanced endoscopy centers, improved care coordination, and an organized colorectal cancer screening program.

Genome-wide association studies (GWAS) have identified more than 200 susceptibility loci for breast cancer, but these variants explain less than a fifth of the disease risk. Although gene–environment interactions have been proposed to account for some of the remaining heritability, few studies have empirically assessed this. We obtained genotype and risk factor data from 46,060 cases and 47,929 controls of European ancestry from population-based studies within the Breast Cancer Association Consortium (BCAC). We built gene expression prediction models for 4,864 genes with a significant (P &lt; 0.01) heritable component using the transcriptome and genotype data from the Genotype-Tissue Expression (GTEx) project. We leveraged predicted gene expression information to investigate the interactions between gene-centric genetic variation and 14 established risk factors in association with breast cancer risk, using a mixed-effects score test. After adjusting for number of tests using Bonferroni correction, no interaction remained statistically significant. The strongest interaction observed was between the predicted expression of the C13orf45 gene and age at first full-term pregnancy (PGXE = 4.44 × 10−6). In this transcriptome-informed genome-wide gene–environment interaction study of breast cancer, we found no strong support for the role of gene expression in modifying the associations between established risk factors and breast cancer risk. Our study suggests a limited role of gene–environment interactions in breast cancer risk.

Background and Objectives: Peroxisome proliferator activated receptor-gamma agonists, such as pioglitazone (PIO) enhanced hematoma resolution and improved functional recovery in our animal model of intracerebral hemorrhage (ICH). We conducted a translational Phase II randomized, controlled clinical trial to determine the maximum tolerated dose (MTD) of PIO in patients with spontaneous ICH and to explore the rate of hematoma resolution and clinical outcome. Methods: Patients with spontaneous ICH within 24 hours of symptom onset were randomly allocated 1:1 to placebo or PIO. Patients received escalating doses of PIO daily for three days, followed by a 30mg maintenance dose for the duration of treatment. Duration of treatment was when 75% of the ICH had resolved as determined by serial MRI or 10 weeks of treatment, whichever occurred first. The primary safety outcome was mortality at Day 14. Secondary measures of safety include any mortality, symptomatic cerebral edema, congestive heart failure, edema, hypoglycemia, anemia, and hepatotoxicity. Secondary measures of efficacy include hematoma resolution and clinical outcome. The MTD was determined using the Continual Reassessment Method. Results: From March 2009 to April 2013, 84 patients (42 PIO, 42 control) were enrolled into 11 dose tiers, with a planned range from 0.1-2.0 mg/kg/d. Table 1 demonstrates preliminary baseline and clinical characteristics of patients by treatment group. Overall, 2/84 patients died within 2 weeks after ICH; however mortality rate never exceeded prespecified criteria. The study will be complete in October 2013 and the treatment team remains blinded to treatment allocation. Secondary outcomes by treatment group and the MTD of PIO will be reported. Conclusions: We have completed the treatment phase of the SHRINC Trial. Long term follow-up is on-going. These results will provide the foundation for an efficacy trial evaluating PIO as a potential treatment for patients with spontaneous ICH.

BACKGROUND: Recent genome-wide association studies (GWAS) have identified a number of novel SNPs associated with blood pressure and hypertension-related traits although studies were very large (approaching 80K participants) and effect sizes were modest with per allele effect sizes as small variants as a single millimeter of mercury difference in blood pressure. However, because hypertension is the most potent modifiable risk factor for ischemic stroke, lowering blood pressure by a few mm Hg can translate into measurable decrease in stroke risk. METHODS: We investigated 22 hypertension (HTN) associated SNPs in a case-control analysis of ischemic stroke in multiple stroke studies including the Siblings With Ischemic Stroke Study (SWISS), the Ischemic Stroke Genetics Study (ISGS), the Bio-Repository of DNA in Stroke (BRAINS), the Vitamin Intervention for Stroke Prevention (VISP) trial, and the Women's Health Initiative (WHI). SWISS/ISGS/BRAINS were analyzed together and included subtype information. Genotyping was funded through the individual studies, the Genomics and Randomized Trials Network (GARNET) consortium, and the SHARe (SNP Health Association Resource). All studies had both raw and imputed GWAS data. Analyses included the following phenotypes: all ischemic stroke, stroke subtypes, and age-at-stroke-onset and were stratified by race. Analyses were minimally adjusted for age, sex and principal components 1 & 2. Alpha was set at 0.05. RESULTS: Eleven of the SNPs from the HTN GWAS were associated with ischemic stroke in European ancestry from one or more of the study populations. Two SNPs on chromosome 12 and one on chromosome 21 were associated in multiple European ancestry cohorts. No SNP was associated in all studies. A SNP previously associated with HTN in African ancestry populations was associated with stroke in African-Americans. Analysis of subtypes found associations with small vessel disease and cardioembolic stroke but not large artery disease. The case-only age-at-stroke-onset analysis also found associations for the two SNPs on chromosome 12. CONCLUSION: These data suggest that candidate SNPs from a HTN GWAS may be associated with ischemic stroke and warrant further investigation. Racial differences were observed. Replication in populations from the other SiGN (Stroke Genetics Network), GENEVA (Gene Environment Association Studies) consortium, and the ISGC (International Stroke Genetics Consortium) studies are underway.

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) enrolled 2502 patients between December of 2000 and mid-July of 2008. We analyzed temporal changes in outcomes for both CEA and CAS over the course of this study. Methods Enrollment was divided into 3 consecutive epochs (5 years, 14 months, and 16 months), each with approximately 834 patients ( Table ). Rates for the primary outcome of death, stroke, and myocardial infarction (DSMI) and for death and stroke (DS) during the periprocedural period were calculated. Poisson regression was used to adjust rates for age, sex, dyslipidemia, and symptomatic status, all of which were found to influence outcomes. Results For CAS, there was a 26% decline in DSMI (6.2% → 4.6%) and a 35% decline in DS (5.5% → 3.6%). For both composite endpoints in CEA there was no consistent pattern ( Table ). As CREST progressed, it enrolled younger patients, more men, patients more likely to be dyslipidemic and enrolled more asymptomatic patients (all p < 0.05). Adjustment for these changes mediated the improvement in event rates for the CAS patients, and had no consistent effect on CEA event rates ( Table ). Conclusion Periprocedural safety for CAS improved over time in CREST. Changes were inconsistent for CEA. Improvements for CAS in part appear to reflect changes in patient selection related to age, sex, and risk factors, as adjustment for those variables attenuated the decline in rates. Linking rates to operator experience was not feasible because of the large number of new interventionalists and surgeons entering CREST over time.

Background: Cardiac rehabilitation (CR) is a class Ia recommendation and endorsed performance measure for the quality of care in acute myocardial infarction (AMI) survivors. While participation in CR after AMI is associated with reduced mortality, conflicting data exists on its association with health status outcomes. Methods: Using data from 2 prospective AMI registries (TRIUMPH and PREMIER), we identified patients for whom baseline and follow-up health status scores and documentation of CR participation (attendance of 1 or more sessions within 6 months post-AMI) were available. Health status was assessed by four Seattle Angina Questionnaire (SAQ) domain scores (quality of life [QoL], angina frequency [AF], treatment satisfaction [TS], and physical limitation [PL]), as well as SF-12 physical and mental health composite scores ( PCS & MCS ). We created propensity matched cohorts of CR participants and non-participants to examine the association between CR participation with health status (6 and 12 months) and all-cause mortality (up to 7 years), using conditional repeated measures and proportional hazards models, respectively. Results: Among 3,957 AMI patients from 31 sites, 2,015 patients (51%) participated in CR after discharge. Compared to non-participants, CR participants were more often Caucasian (83.6% vs. 65.4%), had higher rates of health insurance (90.6% vs. 79.3%), but clinically similar baseline SAQ and SF-12 scores in all domains. After propensity matching, all covariates were well-balanced (Standardized Difference <10 for all patient characteristics) between CR participants and non-participants. In the repeated measures analysis, the mean SAQ and SF-12 domain scores were clinically similar for both groups at 6 and 12 months after hospital discharge (Table). Using a conditional proportional hazards model, a decrease in all-cause mortality was noted in the CR participant group (HR 0.59, 95% CI [0.46, 0.75]). Conclusion: In a large, multi-center AMI cohort, we found that although CR participation seemed to improve survival, CR participants had similar health status improvements after AMI as non-participants. Further investigation is required to identify how CR programs can further maximize the health status benefits to post-AMI participants.

Background: In light of well-known deficiencies in the process of informed consent for percutaneous coronary intervention (PCI), we developed and tested a personalized consent form, PRISM; this was shown to improve patients' participation in the consent process, understanding of procedural risks, and engagement in shared decision-making when compared to original PCI consent forms. It is unknown whether patient factors traditionally known to impair the consent process, including socioeconomic status, literacy and numeracy, were associated with greater benefit from the PRISM consents. Methods: We interviewed 590 patients receiving original consent documents and 527 receiving PRISM consents and compared the rates of reviewing the consent form, recalling a risk of bleeding and engaging in discussions about stent type using hierarchical modified Poisson regression analysis. The interaction of patient factors (age, gender, education level, insurance status, literacy and numeracy) with PRISM on outcomes was assessed. Results: Overall, few patient characteristics were associated with outcomes, including review of consent forms, knowledge transfer, or engagement in shared decision-making (see Table), although older patients were less likely to discuss stent types with their doctors (RR=0.84/decade for original and 0.93/decade for PRISM). Those with more than a high school education were less likely to review original consents (RR=0.77; 95% CI=0.66, 0.89) compared to those with less education; this difference was eliminated with the PRISM consents (RR=1.0; 95%CI=0.82, 1.23; p-value for interaction = 0.01). Conclusions: PRISM consent forms led to improved participation in the consent process and knowledge transfer in a 9-center study; there was little variance by sociodemographic, economic, literacy or numeracy factors, both with original consents and with PRISM.

Background: The dominant healthcare payment model in the US, fee-for-service, provides incentives to deliver costlier care for heart failure and disincentives to deliver higher quality care. One proposed method to align cost and quality incentives is to impose financial penalties on providers when patients are readmitted within 30 days after a heart failure hospitalization. We hypothesized that this strategy might not lower overall costs, because lower readmission costs might be offset by higher non-readmission post-acute care costs. Methods: We studied cost to Medicare from 2008-09 for all heart failure hospitalizations (MS-DRG 291, 292, or 293) in the 15 healthcare delivery systems participating in the High Value Health Collaborative. We categorized costs for the 30, 90, and 180 days after the day of admission for first heart failure hospitalization in the study period into acute care costs (inpatient care, outpatient facility costs with 3 day look back window, part B professional fees), inpatient readmission cost, and non-readmission post-acute care costs (outpatient facility fee, sub-acute rehab, inpatient rehab, long term care, home health care, part B professional fees). Results: Using the most common MS DRG (DRG 292) as an example, across the 15 healthcare systems, we found wide variation in median total costs for the 30- ($6487-$11565), 90- ($8049-$18918), and 180- ($9844-$24752) day time frames. For the 30-day time frame, readmission costs ($700 - $2684) and non-readmission post-acute care costs ($477 - $6398) also showed wide variation. The Figure is a plot of these two costs, with bubbles sized to reflect the number of cases for the hospital system (30-day time frame); results were comparable for 90 and 180 days. Contrary to our hypothesis, we found no inverse relationship between readmission costs and non-readmission post-acute care costs. These data do not account for possible differences in case mix and in geographic differences in labor and facility costs. Conclusions: Non-readmission post-acute costs for heart failure are unrelated to readmission costs but were greater than readmission costs in a number of healthcare deliver systems, raising questions about the overall value to the healthcare systems of an exclusive focus on readmission as a strategy for reducing the costs of heart failure.

Introduction: Primary prevention implantable cardioverter defibrillators (ICDs) reduce mortality in select patients with left ventricular systolic dysfunction (LVSD). The occurrence of device therapies after ICD implantation in contemporary clinical practice is not well described, especially in patient subgroups designated in the Centers for Medicare and Medicaid Services (CMS) 2005 Coverage with Evidence Development (CED). Methods: The Longitudinal Study of ICDs assessed rates and correlates of device therapies (overall and those requiring shock) up to 3 years post-implant among 2540 patients with LVSD receiving first-time primary prevention ICDs in 7 US health care systems from 2006-2009. Implant data from the National Cardiovascular Data Registry ICD Registry were linked to electronic longitudinal health care system data and a novel centrally adjudicated repository of device therapies abstracted from medical records. Proportional hazard models evaluated associations with device therapies by appropriateness, adjusted for demographic and clinical factors. Results: Subjects were 26% women, 35% <65 years old, and 59% non-Hispanic white. Over a mean 26 months, 738 (29.1%) received at least 1 therapy (median 2). Estimated 3-year risk of any device therapy was 36% (24% appropriate, 12% inappropriate); for therapy requiring shock, corresponding values were 24%, 14%, 9%. The rate of appropriate therapy was higher in men than women (adjusted hazard ratio 1.84, 95% confidence interval 1.43-2.35). The rate of inappropriate therapy was higher for subjects <65 than for those >=65 years (1.40, 1.04-1.88), and lower among 2009 implants compared to 2006 (0.66, 0.46-0.95). Regarding the 3 CMS CED patient subgroups, neither ejection fraction nor heart failure symptom severity was associated with device therapy; for LVSD etiology, the rate of inappropriate therapy was nominally but not significantly higher among subjects with non-ischemic cardiomyopathy of < 9 months duration (1.38, 0.88-2.18). Conclusions: In a representative cohort of primary prevention ICD patients in usual care, rates of device therapies were somewhat lower than in landmark trials, differed by some patient characteristics, but did not differ meaningfully for CMS CED subgroups.