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.

Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population

Background: Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown. Objective: To assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis. Design: Prospective propensity score (PS)–matched cohort. Setting: Swedish registers, 2005 to 2013. Participants: A PS-matched cohort of 16 668 adults (8334 who initiated statin use [6554 lipophilic and 1780 hydrophilic] and 8334 nonusers) among 63 279 eligible adults. Measurements: Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs). Results: Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], −4.8 percentage points [95% CI, −6.2 to −3.3 percentage points]; adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0% vs. 6.8%; RD, −1.2 percentage points [CI, −2.6 to 0.4 percentage points]; aHR, 0.95 [CI, 0.86 to 1.08]). The inverse association between lipophilic statins and HCC risk seemed to be dose-dependent. Compared with nonusers, 10-year HCC risk was lowest with 600 or more lipophilic statin cDDDs (8.4% vs. 2.5%; RD, −5.9 percentage points [CI, −7.6 to −4.2 percentage points]; aHR, 0.41 [CI, 0.32 to 0.61]), and 10-year mortality was significantly lower among both lipophilic (15.2% vs. 7.3%; RD, −7.9 percentage points [CI, −9.6 to −6.2 percentage points]) and hydrophilic (16.0% vs. 11.5%; RD, −4.5 percentage points [CI, −6.0 to −3.0 percentage points]) statin users. Limitation: Lack of lipid, fibrosis, or HCC surveillance data. Conclusion: In a nationwide viral hepatitis cohort, lipophilic statins were associated with significantly reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC. Primary Funding Source: None.

Recognizing the Potential for Overdiagnosis: Are High-Sensitivity Cardiac Troponin Assays an Example?

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.

Cases in Precision Medicine: Genetic Assessment After a Sudden Cardiac Death in the Family

Sudden death in a family is associated with serious anxiety among family members. Assessing the cause of death may help determine the risk for other family members, thus alleviating some anxiety. In some cases, the cause of death may be evident on autopsy; however, in cases of arrhythmias, standard autopsy will not reveal the cause of death. Evaluation of the circumstances of death, medical history of the deceased, and results of genetic testing may reveal a diagnosis. Once a diagnosis is made, relatives should receive genetic testing and clinical assessment to stratify their risk. Depending on their risk, various interventions are available, including medication, defibrillators, and lifestyle modifications.

The Jumbo Man in the Jumbo Mart

A Cost-Effectiveness Analysis of Vaccination for Prevention of Herpes Zoster and Related Complications: Input for National Recommendations

Background: The U.S. Advisory Committee on Immunization Practices recently developed recommendations for use of a new recombinant zoster vaccine (RZV). Objective: To evaluate the cost-effectiveness of vaccination with RZV compared with zoster vaccine live (ZVL) and no vaccination, the cost-effectiveness of vaccination with RZV for persons who have previously received ZVL, and the cost-effectiveness of preferential vaccination with RZV over ZVL. Design: Simulation (state-transition) model using U.S. epidemiologic, clinical, and cost data. Data Sources: Published data. Target Population: Hypothetical cohort of immunocompetent U.S. adults aged 50 years or older. Time Horizon: Lifetime. Perspective: Societal and health care sector. Intervention: Vaccination with RZV (recommended 2-dose regimen), vaccination with ZVL, and no vaccination. Outcome Measures: The primary outcome measure was the incremental cost-effectiveness ratio (ICER). Results of Base-Case Analysis: For vaccination with RZV compared with no vaccination, ICERs ranged by age from $10 000 to $47 000 per quality-adjusted life-year (QALY), using a societal perspective and assuming 100% completion of the 2-dose RZV regimen. For persons aged 60 years or older, ICERs were less than $60 000 per QALY. Vaccination with ZVL was dominated by vaccination with RZV for all age groups 60 years or older. Results of Sensitivity Analysis: Results were most sensitive to changes in vaccine effectiveness, duration of protection, herpes zoster incidence, and probability of postherpetic neuralgia. Vaccination with RZV after previous administration of ZVL yielded an ICER of less than $60 000 per QALY for persons aged 60 years or older. In probabilistic sensitivity analyses, RZV remained the preferred strategy in at least 95% of simulations, including those with 50% completion of the second dose. Limitation: Few data were available on risk for serious adverse events, adherence to the recommended 2-dose regimen, and probability of recurrent zoster. Conclusion: Vaccination with RZV yields cost-effectiveness ratios lower than those for many recommended adult vaccines, including ZVL. Results are robust over a wide range of plausible values. Primary Funding Source: Centers for Disease Control and Prevention.

San Francisco Voters End the Sale of Flavored Tobacco Products Despite Strong Industry Opposition

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.