Clinical Trial Diversity, Equity, and Inclusion: Roadmap of the Cardiothoracic Surgical Trials Network.

BACKGROUND: There is a recognized lack of diversity among patients enrolled in cardiovascular interventional and surgical trials. Diverse patient representation in clinical trials is necessary to enhance generalizability of findings, which may lead to better outcomes across broader populations. The Cardiothoracic Surgical Trials Network (CTSN) recently developed a plan of action to increase diversity among participating investigators and trial participants and is the focus of this review. METHODS: A review of literature and enrollment data from CTSN trials was conducted. RESULTS: CTSN completed more than a dozen major clinical trials (2008-2022), enrolling >4000 patients, of whom 30% were women, 11% were non-White, and 5.6% were Hispanic. CTSN also completed trials of hospitalized patients with coronavirus disease 2019, wherein enrollment was more diverse, with 42% women, and 58% were Asian, Black, Hispanic, or from another underrepresented racial group. The discrepancy in diversity of enrollment between cardiac surgery trials and coronavirus disease trials highlights the need for a more comprehensive understanding of (1) the prevalence of underlying disease requiring cardiac interventions across broad populations, (2) differences in access to care and referral for cardiac surgery, and (3) barriers to enrollment in cardiac surgery trials. CONCLUSIONS: Committed to diversity, CTSN's multifaceted action plan includes developing site-specific enrollment targets, collecting social determinants of health data, understanding reasons for nonparticipation, recruiting sites that serve diverse populations, emphasizing greater diversity among clinical trial teams, and implicit bias training. The CTSN will prospectively assess how these interventions influence enrollment as we work to ensure trial participants are more representative of the communities we serve.

Randomized Trials in Cardiac Surgery: JACC Review Topic of the Week.

Compared with randomized controlled trials (RCTs) in medical specialties, RCTs in cardiac surgery face specific issues. Individual and collective equipoise, rapid evolution of the surgical techniques, as well as difficulties in obtaining funding, and limited education in clinical epidemiology in the surgical community are among the most important challenges in the design phase of the trial. Use of complex interventions and learning curve effect, differences in individual operators' expertise, difficulties in blinding, and slow recruitment make the successful completion of cardiac surgery RCTs particularly challenging. In fact, over the course of the last 20 years, the number of cardiac surgery RCTs has declined significantly. In this review, a team of surgeons, trialists, and epidemiologists discusses the most important challenges faced by RCTs in cardiac surgery and provides a list of suggestions for the successful design and completion of cardiac surgery RCTs.

Racial Disparities in Resection of Early Stage Non-Small Cell Lung Cancer: Variability Among Surgeons.

BACKGROUND: Racial disparities in resection of non-small cell lung cancer (NSCLC) are well documented. Patient-level and system-level factors only partially explain these findings. Although physician-related factors have been suggested as mediators, empirical evidence for their contribution is limited. OBJECTIVE: To determine if racial disparities in receipt of thoracic surgery persisted after patients had a surgical consultation and whether there was a physician contribution to disparities in care. METHODS: The authors identified 19,624 patients with stage I-II NSCLC above 65 years of age from the Surveillance-Epidemiology and End-Results-Medicare database. They studied black and white patients evaluated by a surgeon within 6 months of diagnosis. They assessed for racial differences in resection rates among surgeons using hierarchical linear modeling. Our main outcome was receipt of NSCLC resection. A random intercept was included to test for variability in resection rates across surgeons. Interaction between patient race and the random surgeon intercept was used to evaluate for heterogeneity between surgeons in resection rates for black versus white patients. RESULTS: After surgical consultation, black patients were less likely to undergo resection (adjusted odds ratio, 0.57; 95% confidence interval, 0.47-0.69). Resection rates varied significantly between surgeons (P<0.001). A significant interaction between the surgeon intercept and race (P<0.05) showed variability beyond chance across surgeons in resection rates of black versus white patients. When the model included thoracic surgery specifalization the physician contribution to disparities in care was decreased. CONCLUSIONS: Racial disparities in resection of NSCLC exist even among patients who had access to a surgeon. Heterogeneity between surgeons in resection rates between black and white patients suggests a physician's contribution to observed racial disparities. Specialization in thoracic surgery attenuated this contribution.

Cost-effectiveness of coronary artery bypass grafting plus mitral valve repair versus coronary artery bypass grafting alone for moderate ischemic mitral regurgitation.

OBJECTIVE: The Cardiothoracic Surgical Trials Network reported that left ventricular reverse remodeling at 2 years did not differ between patients with moderate ischemic mitral regurgitation randomized to coronary artery bypass grafting plus mitral valve repair (n = 150) or coronary artery bypass grafting alone (n = 151). To address health resource use implications, we compared costs and quality-adjusted survival. METHODS: We used individual patient data from the Cardiothoracic Surgical Trials Network trial on survival, hospitalizations, quality of life, and US hospitalization costs to estimate cumulative costs and quality-adjusted life years. A microsimulation model was developed to extrapolate to 10 years. Bootstrap and deterministic sensitivity analyses were performed to address uncertainty. RESULTS: In-hospital costs were $59,745 for coronary artery bypass grafting plus mitral valve repair versus $51,326 for coronary artery bypass grafting alone (difference $8419; 95% uncertainty interval, 2259-18,757). Two-year costs were $81,263 versus $67,341 (difference 13,922 [2370 to 28,888]), and quality-adjusted life years were 1.35 versus 1.30 (difference 0.05; -0.04 to 0.14), resulting in an incremental cost-effectiveness ratio of $308,343/quality-adjusted life year for coronary artery bypass grafting plus mitral valve repair. At 10 years, its costs remained higher ($107,733 vs $88,583, difference 19,150 [-3866 to 56,826]) and quality-adjusted life years showed no difference (-0.92 to 0.87), with 5.08 versus 5.08. The likelihood that coronary artery bypass grafting plus mitral valve repair would be considered cost-effective at 10 years based on a cost-effectiveness threshold of $100K/quality-adjusted life year did not exceed 37%. Only when this procedure reduces the death rate by a relative 5% will the incremental cost-effectiveness ratio fall below $100K/quality-adjusted life year. CONCLUSIONS: The addition of mitral valve repair to coronary artery bypass grafting for patients with moderate ischemic mitral regurgitation is unlikely to be cost-effective. Only if late mortality benefits can be demonstrated will it meet commonly used cost-effectiveness criteria.

Different Lifestyle Interventions in Adults From Underserved Communities: The FAMILIA Trial.

BACKGROUND: The current trends of unhealthy lifestyle behaviors in underserved communities are disturbing. Thus, effective health promotion strategies constitute an unmet need. OBJECTIVES: The purpose of this study was to assess the impact of 2 different lifestyle interventions on parents/caregivers of children attending preschools in a socioeconomically disadvantaged community. METHODS: The FAMILIA (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health) study is a cluster-randomized trial involving 15 Head Start preschools in Harlem, New York. Schools, and their children's parents/caregivers, were randomized to receive either an "individual-focused" or "peer-to-peer-based" lifestyle intervention program for 12 months or control. The primary outcome was the change from baseline to 12 months in a composite health score related to blood pressure, exercise, weight, alimentation, and tobacco (Fuster-BEWAT Score [FBS]), ranging from 0 to 15 (ideal health = 15). To assess the sustainability of the intervention, this study evaluated the change of FBS at 24 months. Main pre-specified secondary outcomes included changes in FBS subcomponents and the effect of the knowledge of presence of atherosclerosis as assessed by bilateral carotid/femoral vascular ultrasound. Mixed-effects models were used to test for intervention effects. RESULTS: A total of 635 parents/caregivers were enrolled: mean age 38 ± 11 years, 83% women, 57% Hispanic/Latino, 31% African American, and a baseline FBS of 9.3 ± 2.4 points. The mean within-group change in FBS from baseline to 12 months was ∼0.20 points in all groups, with no overall between-group differences. However, high-adherence participants to the intervention exhibited a greater change in FBS than their low-adherence counterparts: 0.30 points (95% confidence interval: 0.03 to 0.57; p = 0.027) versus 0.00 points (95% confidence interval: -0.43 to 0.43; p = 1.0), respectively. Furthermore, the knowledge by the participant of the presence of atherosclerosis significantly boosted the intervention effects. Similar results were sustained at 24 months. CONCLUSIONS: Although overall significant differences were not observed between intervention and control groups, the FAMILIA trial highlights that high adherence rates to lifestyle interventions may improve health outcomes. It also suggests a potential contributory role of the presentation of atherosclerosis pictures, providing helpful information to improve future lifestyle interventions in adults.

Cost-Effectiveness of Mitral Valve Repair Versus Replacement for Severe Ischemic Mitral Regurgitation: A Randomized Clinical Trial From the Cardiothoracic Surgical Trials Network

BACKGROUND: The CTSN (Cardiothoracic Surgical Trials Network) recently reported no difference in left ventricular end-systolic volume index or in survival at 2 years between patients with severe ischemic mitral regurgitation (MR) randomized to mitral valve repair or replacement. However, replacement provided more durable correction of MR and fewer cardiovascular readmissions. Yet, costeffectiveness outcomes have not been addressed. METHODS AND RESULTS: We conducted a cost-effectiveness analysis of the surgical treatment of ischemic MR based on the CTSN trial (n=126 for repair; n=125 for replacement). Patient-level data on readmissions, survival, qualityof- life, and US hospital costs were used to estimate costs and quality-adjusted life years per patient over the trial duration and a 10-year time horizon. We performed microsimulation for extrapolation of outcomes beyond the 2 years of trial data. Bootstrap and deterministic sensitivity analyses were done to address parameter uncertainty. In-hospital cost estimates were $78 216 for replacement versus $72 761 for repair (difference: $5455; 95% uncertainty interval [UI]: −7784­21 193) while 2-year costs were $97 427 versus $96 261 (difference: $1166; 95% UI: −16 253­17 172), respectively. Quality-adjusted life years at 2 years were 1.18 for replacement versus 1.23 for repair (difference: −0.05; 95% UI: −0.17 to 0.07). Over 5 and 10 years, the benefits of reduction in cardiovascular readmission rates with replacement increased, and survival minimally improved compared with repair. At 5 years, cumulative costs and quality-adjusted life years showed no difference on average, but by 10 years, there was a small, uncertain benefit for replacement: $118 023 versus $119 837 (difference: −$1814; 95% UI: −27 144 to 22 602) and qualityadjusted life years: 4.06 versus 3.97 (difference: 0.09; 95% UI: −0.87 to 1.08). After 10 years, the incremental cost-effectiveness of replacement continued to improve. CONCLUSIONS: Our cost-effectiveness analysis predicts potential savings in cost and gains in quality-adjusted survival at 10 years when mitral valve replacement is compared with repair for severe ischemic MR. These projected benefits, however, were small and subject to variability. Efforts to further delineate predictors of long-term outcomes in patients with severe ischemic MR are needed to optimize surgical decisions for individual patients, which should yield more cost-effective care. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00807040.

The Relationship Between Psychological Symptoms and Ventricular Assist Device Implantation.

CONTEXT: Ventricular assist devices (VADs) improve quality of life in advanced heart failure patients, but there are little data exploring psychological symptoms in this population. OBJECTIVE: This study examined the prevalence of psychiatric symptoms and disease over time in VAD patients. METHODS: This prospective multicenter cohort study enrolled patients immediately before or after VAD implant and followed them up to 48 weeks. Depression and anxiety were assessed with Patient-Reported Outcomes Measurement Information System Short Form 8a questionnaires. The panic disorder, acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) modules of the Structured Clinical Interview for the DSM were used. RESULTS: Eighty-seven patients were enrolled. After implant, depression and anxiety scores decreased significantly over time (P = 0.03 and P < 0.001, respectively). Two patients met criteria for panic disorder early after implantation, but symptoms resolved over time. None met criteria for ASD or PTSD. CONCLUSIONS: Our study suggests VADs do not cause serious psychological harms and may have a positive impact on depression and anxiety. Furthermore, VADs did not induce PTSD, panic disorder, or ASD in this cohort.

Diabetes and the Association of Postoperative Hyperglycemia With Clinical and Economic Outcomes in Cardiac Surgery.

OBJECTIVE: The management of postoperative hyperglycemia is controversial and generally does not take into account pre-existing diabetes. We analyzed clinical and economic outcomes associated with postoperative hyperglycemia in cardiac surgery patients, stratifying by diabetes status. RESEARCH DESIGN AND METHODS: Multicenter cohort study in 4,316 cardiac surgery patients operated on in 2010. Glucose was measured at 6-h intervals for 48 h postoperatively. Outcomes included cost, hospital length of stay (LOS), cardiac and respiratory complications, major infections, and death. Associations between maximum glucose levels and outcomes were assessed with multivariable regression and recycled prediction analyses. RESULTS: In patients without diabetes, increasing glucose levels were associated with a gradual worsening of outcomes. In these patients, hyperglycemia (≥180 mg/dL) was associated with an additional cost of $3,192 (95% CI 1,972 to 4,456), an additional hospital LOS of 0.8 days (0.4 to 1.3), an increase in infections of 1.6% (0.5 to 2.8), and an increase in respiratory complications of 2.6% (0.0 to 5.3). However, among patients with insulin-treated diabetes, optimal outcomes were associated with glucose levels considered to be hyperglycemic (180 to 240 mg/dL). This level of hyperglycemia was associated with cost reductions of $6,225 (-12,886 to -222), hospital LOS reductions of 1.6 days (-3.7 to 0.4), infection reductions of 4.1% (-9.1 to 0.0), and reductions in respiratory complication of 12.5% (-22.4 to -3.0). In patients with non-insulin-treated diabetes, outcomes did not differ significantly when hyperglycemia was present. CONCLUSIONS: Glucose levels <180 mg/dL are associated with better outcomes in most patients, but worse outcomes in patients with diabetes with a history of prior insulin use. These findings support further investigation of a stratified approach to the management of patients with stress-induced postoperative hyperglycemia based on prior diabetes status.

Serum Free Light Chain Assessment Early After Stem Cell Transplantation as a Prognostic Factor in Multiple Myeloma.

BACKGROUND: Multiple myeloma is an incurable cancer commonly treated with stem cell transplantation (SCT). Response is traditionally evaluated 100 days after SCT, both to allow for hematopoietic reconstitution and due to immunoglobulins' long half-lives. Free light chains (FLC) have significantly shorter half-lives and may provide evidence of response or treatment failure earlier after SCT. PATIENTS AND METHODS: We retrospectively studied 83 consecutive patients with multiple myeloma who underwent SCT and found 69 who had FLC measured 30 or 60 days after SCT. Using conventional FLC response criteria, we considered a patient to be at high risk for early relapse if he or she failed to experience a partial response by day 30 or 60. RESULTS: After a median overall follow-up of only 335 days, these high-risk patients had significantly shorter progression-free survival (median, 98 vs. 335 days, P = .001) and overall survival (366 days vs. median not reached, P = .016). CONCLUSION: Early FLC assessment either 1 or 2 months after SCT using standard FLC response criteria was able to identify a subset of patients at high risk of early relapse, and these patients may benefit from earlier interventions.

Costs associated with health care-associated infections in cardiac surgery.

BACKGROUND: Health care-associated infections (HAIs) are the most common noncardiac complications after cardiac surgery and are associated with increased morbidity and mortality. Current information about their economic burden is limited. OBJECTIVES: This research was designed to determine the cost associated with major types of HAIs during the first 2 months after cardiac surgery. METHODS: Prospectively collected data from a multicenter, observational study of the Cardiothoracic Surgery Clinical Trials Network, in which patients were monitored for infections for 65 days after surgery, were merged with related financial data routinely collected by the University HealthSystem Consortium. Incremental length of stay (LOS) and cost associated with HAIs were estimated using generalized linear models, with adjustments for patient demographics, clinical history, baseline laboratory values, and surgery type. RESULTS: Among 4,320 cardiac surgery patients (mean age: 64 ± 13 years), 119 (2.8%) experienced a major HAI during the index hospitalization. The most common HAIs were pneumonia (48%), sepsis (20%), and Clostridium difficile colitis (18%). On average, the estimated incremental cost associated with a major HAI was nearly $38,000, of which 47% was related to intensive care unit services. The incremental LOS was 14 days. Overall, there were 849 readmissions; among these, 8.7% were attributed to major HAIs. The cost of readmissions due to major HAIs was, on average, nearly threefold that of readmissions not related to HAIs. CONCLUSIONS: Hospital cost, LOS, and readmissions are strongly associated with HAIs. These associations suggest the potential for large reductions in costs if HAIs following cardiac surgery can be reduced. (Management Practices and the Risk of Infections Following Cardiac Surgery; NCT01089712).

Escalation of socioeconomic disparities among patients with colorectal cancer receiving advanced surgical treatment.

BACKGROUND: As tumor burden increases in colorectal cancer, treatment complexity progresses from colectomy to hepatectomy and lastly to cytoreductive surgery with heated intraperitoneal chemotherapy (CRS-HIPEC). The aim of this study was to evaluate whether disparities exist in the access to progressively more complex surgical treatment options. METHODS: Patients undergoing surgery for colorectal cancer were grouped by treatment type: group 1 (n = 224) underwent colectomy for nonmetastatic disease, group 2 (n = 112) underwent hepatectomy for liver metastasis, and group 3 (n = 112) underwent CRS-HIPEC for carcinomatosis. RESULTS: Whites were predominant in the HIPEC group (71.4 %) compared to the hepatectomy (67.9 %) and colectomy (57.6 %) groups (p = 0.025). The majority of the privately insured patients were in the HIPEC group (70.5 %) compared to the hepatectomy (56.2 %) and colectomy (30.4 %) groups (p < 0.0001). Distance traveled to the hospital was farthest on average in the HIPEC group (104.6 ± 258.3 km) compared to the hepatectomy (29.0 ± 28.0 km) or colectomy (26.4  ± 66.2 km) group (p < 0.0001). Mean household income also varied between the three groups, with HIPEC patients earning $56,957 (±24,124), hepatectomy patients earning $56,999 (±28,588), and colectomy patients earning ($51,518 ± 24,201) (p = 0.0503) on average per year. The HIPEC cohort contained a higher proportion of English speakers (90.2 %) than the other groups (hepatectomy 87.9 %, colectomy 85.3 %); however, this difference was not statistically significant (p = 0.43). CONCLUSIONS: CRS-HIPEC is not accessed equally across all socioeconomic groups. Patients undergoing HIPEC were most often white, English speaking, and privately insured; had a higher mean income; and had traveled the greatest distances on average to access surgical care.