Assessing response bias from missing quality of life data: The Heckman method

BACKGROUND: The objective of this study was to demonstrate the use of the Heckman two-step method to assess and correct for bias due to missing health related quality of life (HRQL) surveys in a clinical study of acute coronary syndrome (ACS) patients. METHODS: We analyzed data from 2,733 veterans with a confirmed diagnosis of acute coronary syndromes (ACS), including either acute myocardial infarction or unstable angina. HRQL outcomes were assessed by the Short-Form 36 (SF-36) health status survey which was mailed to all patients who were alive 7 months following ACS discharge. We created multivariable models of 7-month post-ACS physical and mental health status using data only from the 1,660 survey respondents. Then, using the Heckman method, we modeled survey non-response and incorporated this into our initial models to assess and correct for potential bias. We used logistic and ordinary least squares regression to estimate the multivariable selection models. RESULTS: We found that our model of 7-month mental health status was biased due to survey non-response, while the model for physical health status was not. A history of alcohol or substance abuse was no longer significantly associated with mental health status after controlling for bias due to non-response. Furthermore, the magnitude of the parameter estimates for several of the other predictor variables in the MCS model changed after accounting for bias due to survey non-response. CONCLUSION: Recognition and correction of bias due to survey non-response changed the factors that we concluded were associated with HRQL seven months following hospital admission for ACS as well as the magnitude of some associations. We conclude that the Heckman two-step method may be a valuable tool in the assessment and correction of selection bias in clinical studies of HRQL

Factors influencing patient willingness to participate in genetic research after a myocardial infarction

Abstract Background Achieving 'personalized medicine' requires enrolling representative cohorts into genetic studies, but patient self-selection may introduce bias. We sought to identify characteristics associated with genetic consent in a myocardial infarction (MI) registry. Methods We assessed correlates of participation in the genetic sub-study of TRIUMPH, a prospective MI registry (n = 4,340) from 24 US hospitals between April 2005 and December 2008. Factors examined included extensive socio-demographics factors, clinical variables, and study site. Predictors of consent were identified using hierarchical modified Poisson regression, adjusting for study site. Variation in consent rates across hospitals were quantified by the median rate ratio (MRR). Results Most subjects consented to donation of their genetic material (n = 3,484; 80%). Participation rates varied greatly between sites, from 40% to 100%. After adjustment for confounding factors, the MRR for hospital was 1.22 (95% confidence interval (CI) 1.11 to 1.29). The only patient-level factors associated with consent were race (RR 0.93 for African Americans versus whites, 95% CI 0.88 to 0.99) and body mass index (RR 1.03 for BMI ≥ 25, 95% CI 1.01 to 1.06). Conclusion Among patients with an MI there were notable differences in genetic consent by study site, but little association with patient-level factors. This suggests that variation in the way information is presented during recruitment, or other site factors, strongly influence patients' decision to participate in genetic studies.Peer Reviewe

Temporal trends in the management of severe hyperglycemia among patients hospitalized with acute myocardial infarction [abstract]

Poster sesssionBackground: Elevated blood glucose (BG) is associated with an adverse prognosis in acute myocardial infarction (AMI) patients. While guidelines recommend insulin therapy to lower markedly elevated BG in AMI patients, it is unknown whether these recommendations have impacted BG management over time. Methods: We studied 39,775 AMI patients hospitalized from 2000 to 2008 in 55 US medical centers contributing to Health Facts, a national database with extensive data on in-hospital BG and insulin use. Using all available BG measures during the hospital stay, we restricted our analysis to patients with a mean BG ≥200mg/dl and examined temporal trends in insulin use with hierarchical logistic regression models. Results: Overall, 4330 patients (11% of the entire cohort) had mean hospitalization BG ≥ 200 mg/dL and this proportion decreased from 2000 to 2008 (12% to 8%, p for trend<0.001); 75% of these patients had diabetes. In total, 61% of AMI patients with mean BG ≥ 200 received any insulin and only 16% received intravenous (IV) insulin during hospitalization. Hierarchical multivariable models showed an increased likelihood of insulin use over time (Figure). However, about one in three patients continued to receive no treatment for markedly elevated BG. Conclusions: Despite some improvement over time, insulin treatment rates among hospitalized AMI patients with severe, sustained hyperglycemia remain low. These findings likely reflect continuing uncertainty regarding optimal BG management during AMI

Novel Trial Design: CHIEF-HF

BACKGROUND: The expense of clinical trials mandates new strategies to efficiently generate evidence and test novel therapies. In this context, we designed a decentralized, patient-centered randomized clinical trial leveraging mobile technologies, rather than in-person site visits, to test the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms. METHODS: One thousand nine hundred patients will be enrolled with a medical record-confirmed diagnosis of heart failure, stratified by reduced (≤40%) or preserved (\u3e40%) ejection fraction and randomized 1:1 to 100 mg daily of canagliflozin or matching placebo. The primary outcome will be the 12-week change in the total symptom score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes will be daily step count and other scales of the Kansas City Cardiomyopathy Questionnaire. RESULTS: The trial is currently enrolling, even in the era of the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSIONS: CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is deploying a novel model of conducting a decentralized, patient-centered, randomized clinical trial for a new indication for canagliflozin to improve the symptoms of patients with heart failure. It can model a new method for more cost-effectively testing the efficacy of treatments using mobile technologies with patient-reported outcomes as the primary clinical end point of the trial

Race and beta-blocker survival benefit in patients with heart failure: an investigation of self-reported race and proportion of African genetic ancestry

BACKGROUND: It remains unclear whether beta-blockade is similarly effective in black patients with heart failure and reduced ejection fraction as in white patients, but self-reported race is a complex social construct with both biological and environmental components. The objective of this study was to compare the reduction in mortality associated with beta-blocker exposure in heart failure and reduced ejection fraction patients by both self-reported race and by proportion African genetic ancestry. METHODS AND RESULTS: Insured patients with heart failure and reduced ejection fraction (n=1122) were included in a prospective registry at Henry Ford Health System. This included 575 self-reported blacks (129 deaths, 22%) and 547 self-reported whites (126 deaths, 23%) followed for a median 3.0 years. Beta-blocker exposure (BBexp) was calculated from pharmacy claims, and the proportion of African genetic ancestry was determined from genome-wide array data. Time-dependent Cox proportional hazards regression was used to separately test the association of BBexp with all-cause mortality by self-reported race or by proportion of African genetic ancestry. Both sets of models were evaluated unadjusted and then adjusted for baseline risk factors and beta-blocker propensity score. BBexp effect estimates were protective and of similar magnitude both by self-reported race and by African genetic ancestry (adjusted hazard ratio=0.56 in blacks and adjusted hazard ratio=0.48 in whites). The tests for interactions with BBexp for both self-reported race and for African genetic ancestry were not statistically significant in any model (P\u3e0.1 for all). CONCLUSIONS: Among black and white patients with heart failure and reduced ejection fraction, reduction in all-cause mortality associated with BBexp was similar, regardless of self-reported race or proportion African genetic ancestry

Sex differences in financial barriers and the relationship to recovery after acute myocardial infarction

Background-Financial barriers to health care are associated with worse outcomes following acute myocardial infarction (AMI). Yet, it is unknown whether the prevalence of financial barriers and their relationship with post-AMI outcomes vary by sex among young adults. Methods and Results-We assessed sex differences in patient-reported financial barriers among adults aged <55 years with AMI using data from the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients study. We examined the prevalence of financial barriers and their association with health status 12 months post-AMI. Among 3437 patients, more women than men reported financial barriers to medications (22.3% vs 17.2%; P=0.001), but rates of financial barriers to services were similar (31.3% vs 28.9%; P=0.152). In multivariable linear regression models adjusting for baseline health, psychosocial status, and clinical characteristics, compared with no financial barriers, women and men with financial barriers to services and medications had worse mental functional status (Short Form-12 mental health score: mean difference [MD]=-3.28 and -3.35, respectively), greater depressive symptomatology (Patient Health Questionnaire-9: MD, 2.18 and 2.16), lower quality of life (Seattle Angina Questionnaire-Quality of Life: MD, -4.98 and -7.66), and higher perceived stress (Perceived Stress Score: MD, 3.76 and 3.90; all P<0.05). There was no interaction between sex and financial barriers. Conclusions-Financial barriers to care are common in young patients with AMI and associated with worse health outcomes 1 year post-AMI. Whereas women experienced more financial barriers than men, the association did not vary by sex. These findings emphasize the importance of addressing financial barriers to recovery post-AMI in young adults.Adam L. Beckman, Emily M. Bucholz, Weiwei Zhang, Xiao Xu, Rachel P. Dreyer, Kelly M. Strait, John A. Spertus, Harlan M. Krumholz, Erica S. Spat

Perceived Stress After Acute Myocardial Infarction: A Comparison Between Young and Middle-Aged Women Versus Men

Objective: The aim of the study was to examine how psychological stress changes over time in young and middle-aged patients after experiencing an acute myocardial infarction (AMI) and whether these changes differ between men and women. Methods: We analyzed data obtained from 2358 women and 1151 men aged 18 to 55 years hospitalized for AMI. Psychological stress was measured using the 14-item Perceived Stress Scale (PSS-14) at initial hospitalization and at 1 month and 12 months after AMI. We used linear mixed-effects models to examine changes in PSS-14 scores over time and sex differences in these changes, while adjusting for patient characteristics and accounting for correlation among repeated observations within patients. Results: Overall, patients' perceived stress decreased over time, especially during the first month after AMI. Women had higher levels of perceived stress than men throughout the 12-month period (difference in PSS-14 score = 3.63, 95% confidence interval = 3.08 to 4.18, p < .001), but they did not differ in how stress changed over time. Adjustment for patient characteristics did not alter the overall pattern of sex difference in changes of perceived stress over time other than attenuating the magnitude of sex difference in PSS-14 score (difference between women and men = 1.74, 95% confidence interval = 1.32 to 2.16, p < .001). The magnitude of sex differences in perceived stress was similar in patients with versus without post-AMI angina, even though patients with angina experienced less improvement in PSS-14 score than those without angina. Conclusions: In young and middle-aged patients with AMI, women reported higher levels of perceived stress than men throughout the first 12 months of recovery. However, women and men had a similar pattern in how perceived stress changed over time