Hepatitis C Virus Screening and Care: Complexity of Implementation in Primary Care Practices Serving Disadvantaged Populations

Background: Hepatitis C virus (HCV) disproportionately affects disadvantaged communities. Objective: To examine processes and outcomes of Screen, Treat, Or Prevent Hepatocellular Carcinoma (STOP HCC), a multicomponent intervention for HCV screening and care in safety-net primary care practices. Design: Mixed-methods retrospective analysis. Setting: 5 federally qualified health centers (FQHCs) and 1 family medicine residency program serving low-income communities in diverse locations with largely Hispanic populations. Patients: Persons born in 1945 through 1965 (baby boomers) who had never been tested for HCV and were followed through May 2018. Intervention: The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) model guided implementation and evaluation. Test costs were covered for uninsured patients. Measurements: All practices tested patients for anti-HCV antibody (anti-HCV) and HCV RNA. For uninsured patients with chronic HCV in 4 practices, quantitative data also enabled assessment of HCV staging, specialist teleconsultation, direct-acting antiviral (DAA) treatment, and sustained virologic response (SVR). Implementation fidelity and adaptation were assessed qualitatively. Results: Anti-HCV screening was done in 13 334 of 27 700 baby boomers (48.1%, varying by practice from 19.8% to 71.3%). Of 695 anti-HCV–positive patients, HCV RNA was tested in 520 (74.8%; 48.9% to 92.9% by practice), and 349 persons (2.6% of those screened) were diagnosed with chronic HCV. In 4 FQHCs, 174 (84.9%) of 205 uninsured patients with chronic HCV had disease staging, 145 (70.7%) had teleconsultation review, 119 (58.0%) were recommended to start DAA therapy, 82 (40.0%) initiated free DAA therapy, 74 (36.1%) completed therapy (27.8% to 60.0% by practice), and 70 (94.6% of DAA completers) achieved SVR. Implementation was promoted by multilevel practice engagement, patient navigation, and anti-HCV screening with reflex HCV RNA testing. Limitation: No control practices were included, and data were missing for some variables. Conclusion: Despite a similar framework for STOP HCC implementation, performance varied widely across safety-net practices, which may reflect practice engagement as well as infrastructure or cost challenges beyond practice control. Primary Funding Source: Cancer Prevention & Research Institute of Texas and Centers for Medicare & Medicaid Services.

Comparison of Universal Versus Age-Restricted Screening of Colorectal Tumors for Lynch Syndrome Using Mismatch Repair Immunohistochemistry: A Cohort Study: Annals of Internal Medicine: Vol 171, No 1

Background: Guidelines recommend screening all patients with newly diagnosed colorectal cancer (CRC) for Lynch syndrome (LS). However, the efficiency of universal LS screening in elderly populations has not been well studied. Objective: To compare the performance of age-restricted and universal LS screening using reflex mismatch repair (MMR) immunohistochemistry (IHC) of CRC tumors. Design: Retrospective cohort study. Setting: A large, diverse, community-based health care system. Participants: 3891 persons with newly diagnosed CRC who had LS screening between 2011 and 2016. Measurements: Diagnostic yield of different LS screening strategies. Results: Sixty-three LS cases (diagnostic yield, 1.62%) were identified by universal screening, with only 5 (7.9%) detected after age 70 years and 1 (1.6%) detected after age 80 years. When all patients with CRC who had universal screening were used as the denominator, 58 LS cases (diagnostic yield, 1.49% [95% CI, 1.13% to 1.92%]) were identified in patients with CRC diagnosed at or before age 70 years, 60 LS cases (diagnostic yield, 1.54% [CI, 1.18% to 1.98%]) were identified in those with CRC diagnosed at or before age 75 years, and 62 LS cases (diagnostic yield, 1.59% [CI, 1.22% to 2.04%]) were identified in those with CRC diagnosed at or before age 80 years. Using 75 years as the upper age limit for screening missed 3 of 63 (4.8%) LS cases but resulted in 1053 (27.1%) fewer cases requiring tumor MMR IHC. Using 80 years as the upper age limit missed 1 of 63 (1.6%) LS cases and resulted in 668 (17.2%) fewer cases requiring tumor MMR IHC. Limitation: Persons who were eligible for but did not complete germline analysis were excluded from calculations of performance characteristics. Conclusion: The incremental diagnostic yield decreased substantially after age 70 to 75 years. Stopping reflex CRC screening for LS after age 80 years may be reasonable because of very low efficiency, particularly in resource-limited settings, but this merits further investigation. Studies evaluating the effect of diagnosing LS in elderly persons on their family members are needed. Primary Funding Source: Kaiser Permanente Northern California Division of Research.

Pharmacologic and Nonpharmacologic Treatments for Urinary Incontinence in Women: A Systematic Review and Network Meta-analysis of Clinical Outcomes: Annals of Internal Medicine: Vol 170, No 7

Background: Urinary incontinence (UI), a common malady in women, most often is classified as stress, urgency, or mixed. Purpose: To compare the effectiveness of pharmacologic and nonpharmacologic interventions to improve or cure stress, urgency, or mixed UI in nonpregnant women. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials (Wiley), Cochrane Database of Systematic Reviews (Wiley), EMBASE (Elsevier), CINAHL (EBSCO), and PsycINFO (American Psychological Association) from inception through 10 August 2018. Study Selection: 84 randomized trials that evaluated 14 categories of interventions and reported categorical cure or improvement outcomes. Data Extraction: 1 researcher extracted study characteristics, results, and study-level risk of bias, with verification by another independent researcher. The research team collaborated to assess strength of evidence (SoE) across studies. Data Synthesis: 84 studies reported cure or improvement outcomes (32 in stress UI, 16 in urgency UI, 4 in mixed UI, and 32 in any or unspecified UI type). The most commonly evaluated active intervention types included behavioral therapies, anticholinergics, and neuromodulation. Network meta-analysis showed that all interventions, except hormones and periurethral bulking agents (variable SoE), were more effective than no treatment in achieving at least 1 favorable UI outcome. Among treatments used specifically for stress UI, behavioral therapy was more effective than either α-agonists or hormones in achieving cure or improvement (moderate SoE); α-agonists were more effective than hormones in achieving improvement (moderate SoE); and neuromodulation was more effective than no treatment for cure, improvement, and satisfaction (high SoE). Among treatments used specifically for urgency UI, behavioral therapy was statistically significantly more effective than anticholinergics in achieving cure or improvement (high SoE), both neuromodulation and onabotulinum toxin A (BTX) were more effective than no treatment (high SoE), and BTX may have been more effective than neuromodulation in achieving cure (low SoE). Limitation: Scarce direct (head-to-head trial) evidence and population heterogeneity based on UI type, UI severity, and history of prior treatment. Conclusion: Most nonpharmacologic and pharmacologic interventions are more likely than no treatment to improve UI outcomes. Behavioral therapy, alone or in combination with other interventions, is generally more effective than pharmacologic therapies alone in treating both stress and urgency UI. Primary Funding Source: Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42017069903)

The Changing Definition of a Primary Care Provider

Acute Illness Associated With Cannabis Use, by Route of Exposure: An Observational Study: Annals of Internal Medicine: Vol 170, No 8

Background: Little is known about the relative harms of edible and inhalable cannabis products. Objective: To describe and compare adult emergency department (ED) visits related to edible and inhaled cannabis exposure. Design: Chart review of ED visits between 1 January 2012 and 31 December 2016. Setting: A large urban academic hospital in Colorado. Participants: Adults with ED visits with a cannabis-related International Classification of Diseases, Ninth or 10th Revision, Clinical Modification (ICD-9-CM or ICD-10-CM), code. Measurements: Patient demographic characteristics, route of exposure, dose, symptoms, length of stay, disposition, discharge diagnoses, and attribution of visit to cannabis. Results: There were 9973 visits with an ICD-9-CM or ICD-10-CM code for cannabis use. Of these, 2567 (25.7%) visits were at least partially attributable to cannabis, and 238 of those (9.3%) were related to edible cannabis. Visits attributable to inhaled cannabis were more likely to be for cannabinoid hyperemesis syndrome (18.0% vs. 8.4%), and visits attributable to edible cannabis were more likely to be due to acute psychiatric symptoms (18.0% vs. 10.9%), intoxication (48% vs. 28%), and cardiovascular symptoms (8.0% vs. 3.1%). Edible products accounted for 10.7% of cannabis-attributable visits between 2014 and 2016 but represented only 0.32% of total cannabis sales in Colorado (in kilograms of tetrahydrocannabinol) during that period. Limitation: Retrospective study design, single academic center, self-reported exposure data, and limited availability of dose data. Conclusion: Visits attributable to inhaled cannabis are more frequent than those attributable to edible cannabis, although the latter is associated with more acute psychiatric visits and more ED visits than expected. Primary Funding Source: Colorado Department of Public Health and Environment.

Predicting Bleeding Risk to Guide Aspirin Use for the Primary Prevention of Cardiovascular Disease: A Cohort Study: Annals of Internal Medicine: Vol 170, No 6

Background: Many prognostic models for cardiovascular risk can be used to estimate aspirin's absolute benefits, but few bleeding risk models are available to estimate its likely harms. Objective: To develop prognostic bleeding risk models among persons in whom aspirin might be considered for the primary prevention of cardiovascular disease (CVD). Design: Prospective cohort study. Setting: New Zealand primary care. Participants: The study cohort comprised 385 191 persons aged 30 to 79 years whose CVD risk was assessed between 2007 and 2016. Those with indications for or contraindications to aspirin and those who were already receiving antiplatelet or anticoagulant therapy were excluded. Measurements: For each sex, Cox proportional hazards models were developed to predict major bleeding risk; participants were censored at the earliest of the date on which they first met an exclusion criterion, date of death, or study end date (30 June 2017). The main models included the following predictors: demographic characteristics (age, ethnicity, and socioeconomic deprivation), clinical measurements (systolic blood pressure and ratio of total–high-density lipoprotein cholesterol), family history of premature CVD, medical history (smoking, diabetes, bleeding, peptic ulcer disease, cancer, chronic liver disease, chronic pancreatitis, or alcohol-related conditions), and medication use (nonsteroidal anti-inflammatory agents, corticosteroids, and selective serotonin reuptake inhibitors). Results: During 1 619 846 person-years of follow-up, 4442 persons had major bleeding events (of which 313 [7%] were fatal). The main models predicted a median 5-year bleeding risk of 1.0% (interquartile range, 0.8% to 1.5%) in women and 1.1% (interquartile range, 0.7% to 1.6%) in men. Plots of predicted-against-observed event rates showed good calibration throughout the risk range. Limitation: Hemoglobin level, platelet count, and body mass index were excluded from the main models because of high numbers of missing values, and the models were not externally validated in non–New Zealand populations. Conclusion: Prognostic bleeding risk models were developed that can be used to estimate the absolute bleeding harms of aspirin among persons in whom aspirin is being considered for the primary prevention of CVD. Primary Funding Source: The Health Research Council of New Zealand.

Cardiac and Neuromuscular Features of Patients With LMNA-Related Cardiomyopathy

Background: Mutations in the LMNA (lamin A/C) gene have been associated with neuromuscular and cardiac manifestations, but the clinical implications of these signs are not well understood. Objective: To learn more about the natural history of LMNA-related disease. Design: Observational study. Setting: 13 clinical centers in Italy from 2000 through 2018. Patients: 164 carriers of an LMNA mutation. Measurements: Detailed cardiologic and neurologic evaluation at study enrollment and for a median of 10 years of follow-up. Results: The median age at enrollment was 38 years, and 51% of participants were female. Neuromuscular manifestations preceded cardiac signs by a median of 11 years, but by the end of follow-up, 90% of the patients had electrical heart disease followed by structural heart disease. Overall, 10 patients (6%) died, 14 (9%) received a heart transplant, and 32 (20%) had malignant ventricular arrhythmias. Fifteen patients had gait loss, and 6 had respiratory failure. Atrial fibrillation and second- and third-degree atrioventricular block were observed, respectively, in 56% and 51% of patients with combined cardiac and neuromuscular manifestations and 37% and 33% of those with heart disease only. Limitations: Some of the data were collected retrospectively. Neuromuscular manifestations were more frequent in this analysis than in previous studies. Conclusion: Many patients with an LMNA mutation have neurologic symptoms by their 30s and develop progressive cardiac manifestations during the next decade. A substantial proportion of these patients will have life-threatening neurologic or cardiologic conditions. Primary Funding Source: None.

Variation Among Primary Care Physicians in 30-Day Readmissions

Background: Whether readmission rates vary by primary care physician (PCP) is unknown, although federal policy holds PCPs accountable for reducing readmissions. Objective: To determine whether 30-day readmission rates vary by PCP. Design: Retrospective cohort study using marginal models and multilevel logistic regression with 100% of data on Texas Medicare claims from 2008 to 2015. Setting: Texas. Participants: Patients discharged alive between 1 January 2008 and 30 November 2015 who had a PCP in the prior year and whose PCP had at least 50 admissions in the study period. Measurements: Readmission within 30 days of discharge. Follow-up visits with a PCP within 7 days of discharge were also measured. Results: Between 2012 and 2015, the mean risk-standardized rate of 30-day readmissions was 12.9%. Of 4230 PCPs, 1 had a readmission rate that was significantly higher than the mean and none had a significantly lower rate. The 10th and 90th percentiles of PCP readmission rates were 12.4% and 13.4%, respectively, each only 0.5 percentage point different from the mean. The 99th percentile of PCP readmission rates was 14.0%, 1.1 percentage points higher than the mean. Detecting a 1.1–percentage point difference from the mean adjusted readmission rate would require more than 3500 admissions per PCP per year. Limitations: Only fee-for-service Medicare patients in a single state were included. The authors could not account for confounders not included in Medicare databases or classify readmissions as avoidable. Conclusion: Variation in readmission rates among PCPs is very low. Programs holding PCPs accountable for readmissions may prove ineffective. Primary Funding Source: National Institutes of Health.

Medicare Spending and the Adequacy of Support With Daily Activities in Community-Living Older Adults With Disability: An Observational Study: Annals of Internal Medicine: Vol 170, No 12

Background: Identifying factors that affect variation in health care spending among older adults with disability may reveal opportunities to better address their care needs while offsetting excess spending. Objective: To quantify differences in total Medicare spending among older adults with disability by whether they experience negative consequences due to inadequate support with household activities, mobility, or self-care. Design: Observational study of in-person interviews and linked Medicare claims. Setting: United States, 2015. Participants: 3716 community-living older adults who participated in the 2015 NHATS (National Health and Aging Trends Study) and survived for 12 months. Measurements: Total Medicare spending by spending quartile in multivariable regression models that adjusted for individual characteristics. Results: Negative consequences were experienced by 18.3% of participants with disability in household activities, 25.6% with mobility disability, and 20.0% with self-care disability. Median Medicare spending was higher for those who experienced negative consequences due to household ($4866 vs. $4095), mobility ($7266 vs. $4115), and self-care ($10 935 vs. $4436) disability versus those who did not. In regression-adjusted analyses, median spending did not differ appreciably for participants who experienced negative consequences in household activities ($338 [95% CI, −$768 to $1444]), but was higher for those with mobility ($2309 [CI, $208 to $4409]) and self-care ($3187 [CI, $432 to $5942]) disability. In the bottom-spending quartile, differences were observed for self-care only ($1460 [CI, $358 to $2561]). No differences were observed in the top quartile. Limitation: This observational study could not establish causality. Conclusion: Inadequate support for mobility and self-care is associated with higher Medicare spending, especially in the middle and lower ends of the spending distribution. Better support for the care needs of older adults with disability could offset some Medicare spending. Primary Funding Source: The Commonwealth Fund.

Maternal Glycemic Control in Type 1 Diabetes and the Risk for Preterm Birth: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 170, No 10

Background: Maternal type 1 diabetes (T1D) has been linked to preterm birth and other adverse pregnancy outcomes. How these risks vary with glycated hemoglobin (or hemoglobin A1c [HbA1c]) levels is unclear. Objective: To examine preterm birth risk according to periconceptional HbA1c levels in women with T1D. Design: Population-based cohort study. Setting: Sweden, 2003 to 2014. Patients: 2474 singletons born to women with T1D and 1 165 216 reference infants born to women without diabetes. Measurements: Risk for preterm birth (<37 gestational weeks). Secondary outcomes were neonatal death, large for gestational age, macrosomia, infant birth injury, hypoglycemia, respiratory distress, 5-minute Apgar score less than 7, and stillbirth. Results: Preterm birth occurred in 552 (22.3%) of 2474 infants born to mothers with T1D versus 54 287 (4.7%) in 1 165 216 infants born to mothers without diabetes. The incidence of preterm birth was 13.2% in women with a periconceptional HbA1c level below 6.5% (adjusted risk ratio [aRR] vs. women without T1D, 2.83 [95% CI, 2.28 to 3.52]), 20.6% in those with a level from 6.5% to less than 7.8% (aRR, 4.22 [CI, 3.74 to 4.75]), 28.3% in those with a level from 7.8% to less than 9.1% (aRR, 5.56 [CI, 4.84 to 6.38]), and 37.5% in those with a level of 9.1% or higher (aRR, 6.91 [CI, 5.85 to 8.17]). The corresponding aRRs for medically indicated preterm birth (n = 320) were 5.26 (CI, 3.83 to 7.22), 7.42 (CI, 6.21 to 8.86), 11.75 (CI, 9.72 to 14.20), and 17.51 (CI, 14.14 to 21.69), respectively. The corresponding aRRs for spontaneous preterm birth (n = 223) were 1.81 (CI, 1.31 to 2.52), 2.86 (CI, 2.38 to 3.44), 2.88 (CI, 2.23 to 3.71), and 2.80 (CI, 1.94 to 4.03), respectively. Increasing HbA1c levels were associated with the study's secondary outcomes: large for gestational age, hypoglycemia, respiratory distress, low Apgar score, neonatal death, and stillbirth. Limitation: Because HbA1c levels were registered annually at routine visits, they were not available for all pregnant women with T1D. Conclusion: The risk for preterm birth was strongly linked to periconceptional HbA1c levels. Women with HbA1c levels consistent with recommended target levels also were at increased risk. Primary Funding Source: Swedish Diabetes Foundation.