Understanding the financial cost of cancer clinical trial participation.

BACKGROUND: Though financial hardship is a well-documented adverse effect of standard-of-care cancer treatment, little is known about out-of-pocket costs and their impact on patients participating in cancer clinical trials. This study explored the financial effects of cancer clinical trial participation. METHODS: This cross-sectional analysis used survey data collected in December 2022 and May 2023 from individuals with cancer previously served by Patient Advocate Foundation, a nonprofit organization providing social needs navigation and financial assistance to US adults with a chronic illness. Surveys included questions on cancer clinical trial participation, trial-related financial hardship, and sociodemographic data. Descriptive and bivariate analyses were conducted using Cramer's V to estimate the in-sample magnitude of association. Associations between trial-related financial hardship and sociodemographics were estimated using adjusted relative risks (aRR) and corresponding 95% confidence intervals (CI) from modified Poisson regression models with robust standard errors. RESULTS: Of 650 survey respondents, 18% (N = 118) reported ever participating in a cancer clinical trial. Of those, 47% (n = 55) reported financial hardship as a result of their trial participation. Respondents reporting trial-related financial hardship were more often unemployed or disabled (58% vs. 43%; V = 0.15), Medicare enrolled (53% vs. 40%; V = 0.15), and traveled >1 h to their cancer provider (45% vs. 17%; V = 0.33) compared to respondents reporting no hardship. Respondents who experienced trial-related financial hardship most often reported expenses from travel (reported by 71% of respondents), medical bills (58%), dining out (40%), or housing needs (40%). Modeling results indicated that respondents traveling >1 h vs. ≤30 min to their cancer provider had a 2.2× higher risk of financial hardship, even after adjusting for respondent race, income, employment, and insurance status (aRR = 2.2, 95% CI 1.3-3.8). Most respondents (53%) reported needing $200-$1000 per month to compensate for trial-related expenses. Over half (51%) of respondents reported less willingness to participate in future clinical trials due to incurred financial hardship. Notably, of patients who did not participate in a cancer clinical trial (n = 532), 13% declined participation due to cost. CONCLUSION: Cancer clinical trial-related financial hardship, most often stemming from travel expenses, affected almost half of trial-enrolled patients. Interventions are needed to reduce adverse financial participation effects and potentially improve cancer clinical trial participation.

Primary or Delayed Repair for Complete Atrioventricular Septal Defect, Tetralogy of Fallot, and Ventricular Septal Defect: Relationship to Country Economic Status.

OBJECTIVE: Primary repair in the first six months of life is routine for tetralogy of Fallot, complete atrioventricular septal defect, and ventricular septal defect in high-income countries. The objective of this analysis was to understand the utilization and outcomes of palliative and reparative procedures in high versus middle-income countries. METHODS: The World Database of Pediatric and Congenital Heart Surgery identified patients who underwent surgery for: tetralogy of Fallot, complete atrioventricular septal defect, and ventricular septal defect. Patients were categorized as undergoing primary repair, repair after prior palliation, or palliation only. Country economic status was categorized as lower middle, upper middle, and high, defined by the World Bank. Multiple logistic regression models were utilized to identify independent predictors of hospital mortality. RESULTS: Economic categories included high (n = 571, 5.3%), upper middle (n = 5,342, 50%), and lower middle (n = 4,793, 49.7%). The proportion of patients and median age with primary repair were: tetralogy of Fallot, 88.6%, 17.7 months; complete atrioventricular septal defect, 83.4%, 7.7 months; and ventricular septal defect, 97.1%, ten months. Age at repair was younger in high income countries (P < .0001). Overall mortality after repair was lowest in high income countries. Risk factors for hospital mortality included prematurity, genetic syndromes, and urgent or emergent operations (all P < .05). CONCLUSIONS: Primary repair was selected in >90% of patients, but definitive repair was delayed in lower and upper middle income countries compared with high-income countries. Repair after prior palliation versus primary repair was not a risk factor for hospital mortality. Initial palliation continues to have a small but important role in the management of these three specific congenital heart defects.

Medical Expenditures Among Medicare Beneficiaries with Statin-Associated Adverse Effects Following Myocardial Infarction.

PURPOSE: Compare medical expenditures among adults with statin-associated adverse effects (SAAE) and high statin adherence (HSA) following myocardial infarction (MI). METHODS: We analyzed expenditures in 2016 US dollars among Medicare beneficiaries with SAAE (n = 1741) and HSA (n = 55,567) who were ≥ 66 years of age and initiated moderate/high-intensity statins following an MI in 2007-2013. SAAE were identified through a claims-based algorithm, which included down-titrating statins and initiating ezetimibe, switching to ezetimibe monotherapy, having a rhabdomyolysis or antihyperlipidemic adverse event followed by statin down-titration or discontinuation, or switching between ≥ 3 statin types within 365 days following MI. HSA was defined by having a statin available to take for ≥ 80% of the days in the 365 days following MI. RESULTS: Expenditures among beneficiaries with SAAE and HSA were $40,776 (95% CI $38,329-$43,223) and $26,728 ($26,482-$26,974), respectively, in the 365 days following MI, and $34,238 ($31,396-$37,080) and $29,053 ($28,605-$29,500), respectively, for every year after the first 365 days. Multivariable-adjusted ratios comparing expenditures among beneficiaries with SAAE versus HSA in the first 365 days and after the first 365 days following MI were 1.51 (95% CI 1.43-1.59) and 1.23 (1.12-1.34), respectively. Inpatient and outpatient expenditures were higher among beneficiaries with SAAE versus HSA during and after the first 365 days following MI. Compared to beneficiaries with HSA, medication expenditures among those with SAAE were similar in the 365 days following MI, but higher afterwards. Other medical expenditures were higher among beneficiaries with SAAE versus HSA. CONCLUSION: SAAE are associated with increased expenditures following MI compared with HSA.

National patterns in intensity and frequency of outpatient care for apparent treatment-resistant hypertension.

BACKGROUND: Apparent treatment-resistant hypertension (aTRH) is associated with an increased risk of adverse cardiovascular outcomes. We studied the frequency and intensity of care for aTRH among participants aged 65 years and older in the US-based REGARDS study linked with Medicare claims. METHODS: Blood pressure (BP) was measured twice and averaged. aTRH was defined by the use of ≥3 classes of antihypertensive medication and uncontrolled BP (UaTRH, systolic/diastolic BP ≥140/90 mmHg), or ≥4 classes with controlled BP (CaTRH). Participants were categorized as not having aTRH (no aTRH), CaTRH or UaTRH. RESULTS: Among 4650 participants with hypertension, 468 (10.1%) had UaTRH, 247 (5.3%) had CaTRH, and 3935 (84.6%) had hypertension but did not have aTRH. For hypertension-related visits, those with UaTRH saw primary care physicians and cardiologists more frequently than those without aTRH (mean primary care visits per year: 2.77 vs 2.27, P<.001; cardiologists: 0.50 vs 0.35, P=.014). Among those with UaTRH, CaTRH, and no aTRH, respectively 73.5%, 68.0%, and 67.5% had >1 hypertension-related visit per year. Among those with UaTRH, males vs females (prevalence ratio=0.78; 95% CI 0.69-0.89), whites vs blacks (0.88; 95% CI 0.78-0.99), and current smokers vs non-smokers (0.66; 95% CI 0.48-0.89) were less likely to receive >1 hypertension-related visit per year. Diagnostic intensity, measured by testing for end organ damage and secondary hypertension, was similar between groups. CONCLUSIONS: Many people with UaTRH are not seen more than once per year for hypertension and may benefit from increased care.

Performance of the Atherosclerotic Cardiovascular Disease Pooled Cohort Risk Equations by Social Deprivation Status.

BACKGROUND: The atherosclerosis cardiovascular disease (ASCVD) Pooled Cohort risk equations have shown different calibration across US populations with varied levels of social deprivation. METHODS AND RESULTS: We analyzed the calibration and discrimination of the Pooled Cohort risk equations by social deprivation status among 9066 REGARDS (REasons for Geographic And Racial Differences in Stroke) study participants not taking statins for whom ASCVD risk may lead to statin initiation. Patients were aged 45 to 79 years, had no ASCVD or diabetes mellitus, and had a low-density lipoprotein cholesterol level 70 to 189 mg/dL. Social deprivation was defined using 3 indicators: annual household income <$25 000, less than a high school education, and living without a partner. At baseline in 2003-2007, 54.6%, 27.4%, and 18.0% of participants had 0, 1, and 2 or 3 indicators showing deprivation, respectively. From baseline through December 2012, 457 participants developed ASCVD (nonfatal/fatal stroke, myocardial infarction, or coronary heart disease death). Predicted and observed ASCVD incidence per 1000 person-years were 8.02 and 6.23 (95% CI, 5.31-7.31), respectively, among participants with 0 indicators of deprivation (Hosmer-Lemeshow P=0.01); 8.05 and 6.61 (95% CI, 5.29-8.24), respectively, with 1 indicator (P=0.09); and 9.83 and 11.40 (95% CI, 9.23-14.05), respectively, with 2 or 3 indicators (P=0.12). The C-index (95% CI) was 0.72 (0.69-0.75), 0.73 (0.69-0.78), and 0.70 (0.65-0.75) among participants with 0, 1, and 2 or 3 indicators of deprivation, respectively. The net reclassification improvement after adding deprivation data to the Pooled Cohort risk equations was modest (0.12; 95% CI, 0.03-0.21). CONCLUSIONS: The Pooled Cohort risk equations have good calibration among individuals with social deprivation but overestimate ASCVD risk among those with less social deprivation.

Cardiovascular Health and Healthcare Utilization and Expenditures Among Medicare Beneficiaries: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study.

BACKGROUND: Better cardiovascular health is associated with lower cardiovascular disease risk. METHODS AND RESULTS: We determined the association between cardiovascular health and healthcare utilization and expenditures in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. We included 6262 participants ≥65 years with Medicare fee-for-service coverage for the year after their baseline study visit in 2003-2007. Cardiovascular health at baseline was assessed using the American Heart Association's Life's Simple 7 (LS7) metric, which includes 7 factors: cigarette smoking, physical activity, diet, body mass index, blood pressure, cholesterol, and glucose. Healthcare utilization and expenditures were ascertained using Medicare claims in the year following baseline. Overall, 17.2%, 31.1%, 29.0%, 16.4% and 6.4% of participants had 0 to 1, 2, 3, 4, and 5 to 7 ideal LS7 factors, respectively. The multivariable-adjusted relative risk (95% confidence interval [CI]) for having any inpatient and outpatient encounters comparing participants with 5 to 7 versus 0 to 1 ideal LS7 factors were 0.55 (0.39, 0.76) and 1.00 (0.98, 1.02), respectively. Among participants with 0 to 1 and 5 to 7 ideal LS7 factors, mean inpatient expenditures were $3995 and $1250, respectively, mean outpatient expenditures were $5166 and $2853, respectively, and mean total expenditures were $9147 and $4111, respectively. After multivariable adjustment, the mean (95% CI) cost difference comparing participants with 5 to 7 versus 0 to 1 ideal LS7 factors was -$2551 (-$3667, -$1435) for inpatient, -$2410 (-$3089, -$1731) for outpatient, and -$5016 (-$6577, -$3454) for total expenditures. CONCLUSIONS: Better cardiovascular health is associated with lower risk for inpatient encounters and lower inpatient and outpatient healthcare expenditures.

Short-Term Risk of Serious Fall Injuries in Older Adults Initiating and Intensifying Treatment With Antihypertensive Medication.

BACKGROUND: Antihypertensive medication use has been associated with an increased risk of falls in some but not all studies. Few data are available on the short-term risk of falls after antihypertensive medication initiation and intensification. METHODS AND RESULTS: We examined the association between initiating and intensifying antihypertensive medication and serious fall injuries in a case-crossover study of 90 127 Medicare beneficiaries who were ≥65 years old and had a serious fall injury between July 1, 2007, and December 31, 2012, based on emergency department and inpatient claims. Antihypertensive medication initiation was defined by a prescription fill with no fills in the previous year. Intensification was defined by the addition of a new antihypertensive class, and separately, titration by the addition of a new class or increase in dosage of a current class. Exposures were ascertained for the 15 days before the fall (case period) and six 15-day earlier periods (control periods). Overall, 272, 1508, and 3113 Medicare beneficiaries initiated, added a new class of antihypertensive medication or titrated therapy within 15 days of their serious fall injury. The odds for a serious fall injury was increased during the 15 days after antihypertensive medication initiation (odds ratio, 1.36 [95% confidence interval, 1.19-1.55]), adding a new class (odds ratio, 1.16 [95% confidence interval, 1.10-1.23]), and titration [odds ratio, 1.13 [95% confidence interval, 1.08-1.18]). These associations were attenuated beyond 15 days. CONCLUSIONS: Antihypertensive medication initiation and intensification was associated with a short-term, but not long-term, increased risk of serious fall injuries among older adults.

Burden of Coronary Heart Disease Rehospitalizations Following Acute Myocardial Infarction in Older Adults.

PURPOSE: Studies of prognosis following acute myocardial infarction (AMI) conventionally examine the first recurrent coronary heart disease (CHD) event which may not adequately characterize the full burden of CHD hospitalizations. We therefore examined the cumulative number of CHD rehospitalizations following AMI among older adults in the United States. METHODS: We conducted a retrospective cohort study of 78,085 Medicare beneficiaries aged ≥66 years without recent CHD history who were hospitalized for AMI in 2000-2010. Counts of CHD rehospitalizations over a maximum of 10 years of follow-up were calculated. Characteristics were assessed through claims and enrollment information and associations with CHD rehospitalizations were evaluated using Poisson models. RESULTS: Over 25 % of beneficiaries were aged ≥85 years, 55 % were women, and 89 % were white. Comorbidities were common, including diabetes (22.9 %), hypertension (46.7 %), heart failure (10.3 %), and chronic obstructive pulmonary disease (19.2 %). Following AMI, 16,078 beneficiaries (20.6 %) were hospitalized for CHD a total of 23,132 times. Among those who experienced at least one CHD rehospitalization, 35.9 % had ≥2 CHD rehospitalizations (n = 5773, 7.4 % of all beneficiaries with AMI) in the ensuing decade. Associations of demographics, comorbidities, and index hospitalization characteristics with rates of first and total CHD rehospitalizations were largely similar. Age ≥85 years versus 66-69 years was more strongly associated with first (rate ratio [RR] 1.43) than total (RR 1.35) CHD rehospitalization (p < 0.05), as was male versus female sex (RR 1.13 and 1.07). CONCLUSIONS: Emphasizing the first recurrent CHD rehospitalization underestimates the burden of disease experienced among older adults with AMI.

Trends in the Use of Nonstatin Lipid-Lowering Therapy Among Patients With Coronary Heart Disease: A Retrospective Cohort Study in the Medicare Population 2007 to 2011.

BACKGROUND: Nonstatin lipid-lowering therapy is adjunctive therapy for high-risk individuals on statins or monotherapy among those who cannot tolerate statins. OBJECTIVES: This study determined time trends between 2007 and 2011 for statin and nonstatin lipid-lowering therapy (niacin, fibrates, bile acid sequestrants, and ezetimibe) use among Medicare beneficiaries with coronary heart disease (CHD) in light of emerging clinical trial evidence. METHODS: We conducted a retrospective cohort study using the national 5% random sample of Medicare beneficiaries (n = 310,091). We created 20 cohorts of individuals with CHD, representing calendar quarters from 2007 through 2011, to assess trends in use of statins and nonstatin lipid-lowering medications. RESULTS: Statin use increased from 53.1% to 58.8% between 2007 and 2011. Ezetimibe use peaked at 12.1% and declined to 4.6% by the end of 2011, declining among both patients on statins (18.4% to 6.2%) and not on statins (5.0% to 2.4%). Fibrate use increased from 4.2% to 5.0%, bile acid sequestrants did not change significantly, and niacin use increased from 1.5% to 2.4% and then declined in late 2011. Use of nonstatin lipid-lowering therapy was less common at older age, among African Americans, patients with heart failure, and patients with a higher Charlson comorbidity score. Nonstatin lipid-lowering therapy use was more common among men and patients with diabetes, those who had cardiologist visits, and among those taking statins. CONCLUSIONS: Declining ezetimibe and niacin use but not fibrate therapy among Medicare beneficiaries with CHD coincides with negative clinical trial results for these agents.

Trends in mortality and recurrent coronary heart disease events after an acute myocardial infarction among Medicare beneficiaries, 2001-2009.

BACKGROUND: Few contemporary studies examine trends in recurrent coronary heart disease (CHD) events and mortality after acute myocardial infarction (AMI) and whether these trends vary by race or sex. METHODS: We used data from the national 5% random sample of Medicare fee-for-service beneficiaries for 1999 to 2010. We included beneficiaries who experienced an AMI (International Classification of Disease [ICD] 9 410.xx, except 410.x2) between January 1, 2001, and December 31, 2009. Each beneficiary's first AMI was included as their index event. Outcomes included all-cause mortality, recurrent AMI, and recurrent CHD events during the 365days after discharge for the index AMI. To examine secular trends, we pooled calendar years into 3 periods (2001-2003, 2004-2006, and 2007-2009). RESULTS: Among 48,688 beneficiaries with index AMIs from 2001 to 2009, we observed decreases in the age-adjusted rates for mortality (-3.8% for each 3-year period, 95% CI -6.1% to -1.6%, P trend = .001), recurrent AMI (-15.0%, 95% CI -18.6% to -11.2%, P trend < .001), and recurrent CHD events (-11.1%, 95% CI -14.0% to -8.0%, P trend < .001) in the 365days after the index AMI. In 2007 to 2009, blacks had excess risk relative to whites for mortality and recurrent AMI (black/white incidence rate ratio of 1.38 for mortality [95% CI 1.21-1.57] and 1.38 for recurrent AMI [95% CI 1.07-1.79]). CONCLUSIONS: Despite overall favorable trends in lower mortality and recurrent events after AMI, efforts are needed to reduce racial disparities.