Effect of a Digital Health Intervention on Receipt of Colorectal Cancer Screening in Vulnerable Patients: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 168, No 8

Background: Screening for colorectal cancer (CRC) reduces mortality, yet more than one third of age-eligible Americans are unscreened. Objective: To examine the effect of a digital health intervention, Mobile Patient Technology for Health–CRC (mPATH-CRC), on rates of CRC screening. Design: Randomized clinical trial. (ClinicalTrials.gov: NCT02088333) Setting: 6 community-based primary care practices. Participants: 450 patients (223 in the mPATH-CRC group and 227 in usual care) scheduled for a primary care visit and due for routine CRC screening. Intervention: An iPad application that displays a CRC screening decision aid, lets patients order their own screening tests, and sends automated follow-up electronic messages to support patients. Measurements: The primary outcome was chart-verified completion of CRC screening within 24 weeks. Secondary outcomes were ability to state a screening preference, intention to receive screening, screening discussions, and orders for screening tests. All outcome assessors were blinded to randomization. Results: Baseline characteristics were similar between groups; 37% of participants had limited health literacy, and 53% had annual incomes less than $20 000. Screening was completed by 30% of mPATH-CRC participants and 15% of those receiving usual care (logistic regression odds ratio, 2.5 [95% CI, 1.6 to 4.0]). Compared with usual care, more mPATH-CRC participants could state a screening preference, planned to be screened within 6 months, discussed screening with their provider, and had a screening test ordered. Half of mPATH-CRC participants (53%; 118 of 223) “self-ordered” a test via the program. Limitation: Participants were English speakers in a single health care system. Conclusion: A digital health intervention that allows patients to self-order tests can increase CRC screening. Future research should identify methods for implementing similar interventions in clinical care. Primary Funding Source: National Cancer Institute.

Should This Patient Receive Aspirin?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 167, No 11

Aspirin exerts antiplatelet effects through irreversible inhibition of cyclooxygenase-1, whereas its anticancer effects may be due to inhibition of cyclooxygenase-2 and other pathways. In 2009, the U.S. Preventive Services Task Force endorsed aspirin for primary prevention of cardiovascular disease. However, aspirin's role in cancer prevention is still emerging, and no groups currently recommend its use for this purpose. To help physicians balance the benefits and harms of aspirin in primary disease prevention, the Task Force issued a guideline titled, “Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer” in 2016. In the evidence review conducted for the guideline, cardiovascular disease mortality and colorectal cancer mortality were significantly reduced among persons taking aspirin. However, there was no difference in nonfatal stroke, cardiovascular disease mortality, or all-cause mortality, nor in total cancer mortality, among those taking aspirin. Aspirin users were found to be at increased risk for major gastrointestinal bleeding. In this Beyond the Guidelines, the guideline is reviewed and 2 experts discuss how they would apply it to a 57-year-old man considering starting aspirin for primary prevention. Our experts review the data on which the guideline is based, discuss how they would balance the benefits and harms of aspirin therapy, and explain how they would incorporate shared decision making into clinical practice.

Benefits of Direct-Acting Antivirals for Hepatitis C

The Value-Based Payment Modifier: Program Outcomes and Implications for Disparities

Background: When risk adjustment is inadequate and incentives are weak, pay-for-performance programs, such as the Value-Based Payment Modifier (Value Modifier [VM]) implemented by the Centers for Medicare & Medicaid Services, may contribute to health care disparities without improving performance on average. Objective: To estimate the association between VM exposure and performance on quality and spending measures and to assess the effects of adjusting for additional patient characteristics on performance differences between practices serving higher-risk and those serving lower-risk patients. Design: Exploiting the phase-in of the VM on the basis of practice size, regression discontinuity analysis and 2014 Medicare claims were used to estimate differences in practice performance associated with exposure of practices with 100 or more clinicians to full VM incentives (bonuses and penalties) and exposure of practices with 10 or more clinicians to partial incentives (bonuses only). Analyses were repeated with 2015 claims to estimate performance differences associated with a second year of exposure above the threshold of 100 or more clinicians. Performance differences were assessed between practices serving higher- and those serving lower-risk patients after standard Medicare adjustments versus adjustment for additional patient characteristics. Setting: Fee-for-service Medicare. Patients: Random 20% sample of beneficiaries. Measurements: Hospitalization for ambulatory care–sensitive conditions, all-cause 30-day readmissions, Medicare spending, and mortality. Results: No statistically significant discontinuities were found at the threshold of 10 or more or 100 or more clinicians in the relationship between practice size and performance on quality or spending measures in either year. Adjustment for additional patient characteristics narrowed performance differences by 9.2% to 67.9% between practices in the highest and those in the lowest quartile of Medicaid patients and Hierarchical Condition Category scores. Limitation: Observational design and administrative data. Conclusion: The VM was not associated with differences in performance on program measures. Performance differences between practices serving higher- and those serving lower-risk patients were affected considerably by additional adjustments, suggesting a potential for Medicare's pay-for-performance programs to exacerbate health care disparities. Primary Funding Source: The Laura and John Arnold Foundation and National Institute on Aging.

Long-Term Effectiveness of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality in Women and Men: A Randomized Trial: Annals of Internal Medicine: Vol 168, No 11

Background: The long-term effects of sigmoidoscopy screening on colorectal cancer (CRC) incidence and mortality in women and men are unclear. Objective: To determine the effectiveness of flexible sigmoidoscopy screening after 15 years of follow-up in women and men. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT00119912) Setting: Oslo and Telemark County, Norway. Participants: Adults aged 50 to 64 years at baseline without prior CRC. Intervention: Screening (between 1999 and 2001) with flexible sigmoidoscopy with and without additional fecal blood testing versus no screening. Participants with positive screening results were offered colonoscopy. Measurements: Age-adjusted CRC incidence and mortality stratified by sex. Results: Of 98 678 persons, 20 552 were randomly assigned to screening and 78 126 to no screening. Adherence rates were 64.7% in women and 61.4% in men. Median follow-up was 14.8 years. The absolute risks for CRC in women were 1.86% in the screening group and 2.05% in the control group (risk difference, −0.19 percentage point [95% CI, −0.49 to 0.11 percentage point]; HR, 0.92 [CI, 0.79 to 1.07]). In men, the corresponding risks were 1.72% and 2.50%, respectively (risk difference, −0.78 percentage point [CI, −1.08 to −0.48 percentage points]; hazard ratio [HR], 0.66 [CI, 0.57 to 0.78]) (P for heterogeneity = 0.004). The absolute risks for death from CRC in women were 0.60% in the screening group and 0.59% in the control group (risk difference, 0.01 percentage point [CI, −0.16 to 0.18 percentage point]; HR, 1.01 [CI, 0.77 to 1.33]). The corresponding risks for death from CRC in men were 0.49% and 0.81%, respectively (risk difference, −0.33 percentage point [CI, −0.49 to −0.16 percentage point]; HR, 0.63 [CI, 0.47 to 0.83]) (P for heterogeneity = 0.014). Limitation: Follow-up through national registries. Conclusion: Offering sigmoidoscopy screening in Norway reduced CRC incidence and mortality in men but had little or no effect in women. Primary Funding Source: Norwegian government and Norwegian Cancer Society.

Interventions to Improve Follow-up of Positive Results on Fecal Blood Tests: A Systematic Review: Annals of Internal Medicine: Vol 167, No 8

Background: Fecal immunochemical testing is the most commonly used method for colorectal cancer screening worldwide. However, its effectiveness is frequently undermined by failure to obtain follow-up colonoscopy after positive test results. Purpose: To evaluate interventions to improve rates of follow-up colonoscopy for adults after a positive result on a fecal test (guaiac or immunochemical). Data Sources: English-language studies from the Cochrane Central Register of Controlled Trials, PubMed, and Embase from database inception through June 2017. Study Selection: Randomized and nonrandomized studies reporting an intervention for colonoscopy follow-up of asymptomatic adults with positive fecal test results. Data Extraction: Two reviewers independently extracted data and ranked study quality; 2 rated overall strength of evidence for each category of study type. Data Synthesis: Twenty-three studies were eligible for analysis, including 7 randomized and 16 nonrandomized studies. Three were at low risk of bias. Eleven studies described patient-level interventions (changes to invitation, provision of results or follow-up appointments, and patient navigators), 5 provider-level interventions (reminders or performance data), and 7 system-level interventions (automated referral, precolonoscopy telephone calls, patient registries, and quality improvement efforts). Moderate evidence supported patient navigators and provider reminders or performance data. Evidence for system-level interventions was low. Seventeen studies reported the proportion of test-positive patients who completed colonoscopy compared with a control population, with absolute differences of −7.4 percentage points (95% CI, −19 to 4.3 percentage points) to 25 percentage points (CI, 14 to 35 percentage points). Limitation: More than half of studies were at high or very high risk of bias; heterogeneous study designs and characteristics precluded meta-analysis. Conclusion: Patient navigators and giving providers reminders or performance data may help improve colonoscopy rates of asymptomatic adults with positive fecal blood test results. Current evidence about useful system-level interventions is scant and insufficient. Primary Funding Source: National Cancer Institute. (PROSPERO: CRD42016048286)

Curing Hepatitis C Virus Infection: Best Practices From the U.S. Department of Veterans Affairs

The U.S. Department of Veterans Affairs (VA) is the nation's largest care provider for hepatitis C virus (HCV)–infected patients and is uniquely suited to inform national efforts to eliminate HCV. An extensive array of delivery of services, policy guidance, outreach efforts, and funding has broadened the reach and capacity of the VA to deliver direct-acting antiviral (DAA) HCV therapy, supported by an infrastructure to effectively implement change and informed by extensive population health data analysis. The VA has treated more than 92 000 HCV-infected veterans since all-oral DAAs became available in January 2014, with cure rates exceeding 90%; only 51 000 veterans in VA care are known to remain potentially eligible for treatment. Key actions advancing the VA's aggressive treatment of HCV infection that are germane to non-VA settings include expansion of treatment capacity through the use of nonphysician providers, video telehealth, and electronic technologies; expansion of integrated care to address psychiatric and substance use comorbidities; and electronic data tools for patient tracking and outreach. A critical component of effective implementation has been building infrastructure through the creation of regional multidisciplinary HCV Innovation Teams, whose system redesign efforts have produced innovative HCV practice models addressing gaps in care while providing more efficient and effective HCV management for the populations they serve. Financing for HCV treatment and infrastructure resources coupled with reduced drug prices has been paramount to the VA's success in curing HCV infection. The VA is poised to share and extend best practices to other health care organizations and providers delivering HCV care, contributing to a concerted effort to reduce the overall burden of HCV infection.

Novel Stool-Based Protein Biomarkers for Improved Colorectal Cancer Screening: A Case–Control Study: Annals of Internal Medicine: Vol 167, No 12

Background: The fecal immunochemical test (FIT) for detecting hemoglobin is used widely for noninvasive colorectal cancer (CRC) screening, but its sensitivity leaves room for improvement. Objective: To identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRC and advanced adenomas. Design: Case–control study. Setting: Colonoscopy-controlled referral population from several centers. Participants: 315 stool samples from one series of 12 patients with CRC and 10 persons without colorectal neoplasia (control samples) and a second series of 81 patients with CRC, 40 with advanced adenomas, and 43 with nonadvanced adenomas, as well as 129 persons without colorectal neoplasia (control samples); 72 FIT samples from a third independent series of 14 patients with CRC, 16 with advanced adenomas, and 18 with nonadvanced adenomas, as well as 24 persons without colorectal neoplasia (control samples). Measurements: Stool samples were analyzed by mass spectrometry. Classification and regression tree (CART) analysis and logistic regression analyses were performed to identify protein combinations that differentiated CRC or advanced adenoma from control samples. Antibody-based assays for 4 selected proteins were done on FIT samples. Results: In total, 834 human proteins were identified, 29 of which were statistically significantly enriched in CRC versus control stool samples in both series. Combinations of 4 proteins reached sensitivities of 80% and 45% for detecting CRC and advanced adenomas, respectively, at 95% specificity, which was higher than that of hemoglobin alone (P < 0.001 and P = 0.003, respectively). Selected proteins could be measured in small sample volumes used in FIT-based screening programs and discriminated between CRC and control samples (P < 0.001). Limitation: Lack of availability of antibodies prohibited validation of the top protein combinations in FIT samples. Conclusion: Mass spectrometry of stool samples identified novel candidate protein biomarkers for CRC screening. Several protein combinations outperformed hemoglobin in discriminating CRC or advanced adenoma from control samples. Proof of concept that such proteins can be detected with antibody-based assays in small sample volumes indicates the potential of these biomarkers to be applied in population screening. Primary Funding Source: Center for Translational Molecular Medicine, International Translational Cancer Research Dream Team, Stand Up to Cancer (American Association for Cancer Research and the Dutch Cancer Society), Dutch Digestive Foundation, and VU University Medical Center.

Hearing From the Silent Epidemic

Concentration of Potentially Preventable Spending Among High-Cost Medicare Subpopulations: An Observational Study: Annals of Internal Medicine: Vol 167, No 10

Background: Little is known about whether potentially preventable spending is concentrated among a subset of high-cost Medicare beneficiaries. Objective: To determine the proportion of total spending that is potentially preventable across distinct subpopulations of high-cost Medicare beneficiaries. Design: Beneficiaries in the highest 10% of total standardized individual spending were defined as “high-cost” patients, using a 20% sample of Medicare fee-for-service claims from 2012. The following 6 subpopulations were defined using a claims-based algorithm: nonelderly disabled, frail elderly, major complex chronic, minor complex chronic, simple chronic, and relatively healthy. Potentially preventable spending was calculated by summing costs for avoidable emergency department visits using the Billings algorithm plus inpatient and associated 30-day postacute costs for ambulatory care–sensitive conditions (ACSCs). The amount and proportion of potentially preventable spending were then compared across the high-cost subpopulations and by individual ACSCs. Setting: Medicare. Participants: 6 112 450 Medicare beneficiaries. Measurements: Proportion of spending deemed potentially preventable. Results: In 2012, 4.8% of Medicare spending was potentially preventable, of which 73.8% was incurred by high-cost patients. Despite making up only 4% of the Medicare population, high-cost frail elderly persons accounted for 43.9% of total potentially preventable spending ($6593 per person). High-cost nonelderly disabled persons accounted for 14.8% of potentially preventable spending ($3421 per person) and the major complex chronic group for 11.2% ($3327 per person). Frail elderly persons accounted for most spending related to admissions for urinary tract infections, dehydration, heart failure, and bacterial pneumonia. Limitation: Potential misclassification in the identification of preventable spending and lack of detailed clinical data in administrative claims. Conclusion: Potentially preventable spending varied across Medicare subpopulations, with the majority concentrated among frail elderly persons. Primary Funding Source: The Commonwealth Fund.