Investigating the impact of suboptimal prescription of preoperative antiplatelets and statins on race and ethnicity-related disparities in major limb amputation.

BACKGROUND: Non-Hispanic Black and Hispanic patients with symptomatic PAD may receive different treatments than White patients with symptomatic PAD. The delivery of guideline-directed medical treatment may be a modifiable upstream driver of race and ethnicity-related disparities in outcomes such as limb amputation. The purpose of our study was to investigate the prescription of preoperative antiplatelets and statins in producing disparities in the risk of amputation following revascularization for symptomatic peripheral artery disease (PAD). METHODS: We used data from the Vascular Quality Initiative, a vascular procedure-based registry in the United States (2011-2018). We estimated the probability of preoperative antiplatelet and statin prescriptions and 1-year incidence of amputation. We then estimated the amputation risk difference between race/ethnicity groups that could be eliminated under a hypothetical intervention. RESULTS: Across 100,579 revascularizations, the 1-year amputation risk was 2.5% (2.4%, 2.6%) in White patients, 5.3% (4.9%, 5.6%) in Black patients, and 5.3% (4.7%, 5.9%) in Hispanic patients. Black (57.5%) and Hispanic patients (58.7%) were only slightly less likely than White patients (60.9%) to receive antiplatelet and statin therapy. However, the effect of antiplatelets and statins was greater in Black and Hispanic patients such that, had all patients received these medications, the estimated risk difference comparing Black to White patients would have reduced by 8.9% (-2.9%, 21.9%) and the risk difference comparing Hispanic to White patients would have been reduced by 17.6% (-0.7%, 38.6%). CONCLUSION: Even though guideline-directed care appeared evenly distributed by race/ethnicity, increasing access to such care may decrease health care disparities in major limb amputation.

Disparities in healthcare utilization by insurance status among patients with symptomatic peripheral artery disease.

BACKGROUND: Peripheral artery disease (PAD) is a common circulatory disorder associated with increased hospitalizations and significant health care-related expenditures. Among patients with PAD, insurance status is an important determinant of health care utilization, treatment of disease, and treatment outcomes. However, little is known about PAD-costs differences across different insurance providers. In this study we examined possible disparities in length of stay and total charge of inpatient hospitalizations among patients with PAD by insurance type. METHODS: We conducted a cross-sectional analysis of length of stay and total charge by insurance provider for all hospitalizations for individuals with PAD in South Carolina (2010-2018). Cross-classified multilevel modeling was applied to account for the non-nested hierarchical structure of the data, with county and hospital included as random effects. Analyses were adjusted for patient age, race/ethnicity, county, year of admission, admission type, all-patient refined diagnostic groups, and Charlson comorbidity index. RESULTS: Among 385,018 hospitalizations for individuals with PAD in South Carolina, the median length of stay was 4 days (IQR: 5) and the median total charge of hospitalization was $43,232 (IQR: $52,405). Length of stay and total charge varied significantly by insurance provider. Medicare patients had increased length of stay (IRR = 1.08, 95 CI%: 1.07, 1.09) and higher total charges (ß: 0.012, 95% CI: 0.007, 0.178) than patients with private insurance. Medicaid patients also had increased length of stay (IRR = 1.26, 95% CI: 1.24,1.28) but had lower total charges (ß: -0.022, 95% CI: -0.003. -0.015) than patients with private insurance. CONCLUSIONS: Insurance status was associated with inpatient length of stay and total charges in patients with PAD. It is essential that Medicare and Medicaid individuals with PAD receive proper management and care of their PAD, particularly in the primary care settings, to prevent hospitalizations and reduce the excess burden on these patients.

Healthy volunteers in US phase I clinical trials: Sociodemographic characteristics and participation over time.

BACKGROUND: Increasing the diversity of research participants is an important focus of clinical trials. However, little is known regarding who enrolls as healthy volunteers in Phase I clinical trials, which test the safety and tolerability of investigational new drugs. Despite the risk, healthy volunteers can derive no medical benefit from their participation, and they are financially compensated for enrolling. OBJECTIVE: This study's purpose is to describe sociodemographic characteristics and clinical trial participation histories of healthy people who enroll in US Phase I trials. METHODS: The HealthyVOICES Project (HVP) is a longitudinal study of healthy individuals who have enrolled in Phase I trials. We describe self-reported sociodemographic information and Phase I trial history from HVP recruitment (May-December 2013) through the project's end three years later (December 2016). Trial experiences are presented as medians and quartiles. RESULTS: The HVP included 178 participants. Nearly three-fourths of participants were male, and two-thirds were classified as racial and ethnic minorities. We found that some groups of participants were more likely to have completed a greater number of clinical trials over a longer timeframe than others. Those groups included participants who were male, Black, Hispanic, 30-39-years-old, unemployed, had received vocational training in a trade, or had annual household incomes of less than $25,000. Additionally, the greater the number of clinical trials participants had completed, the more likely they were to continue screening for new trials over the course of three years. Participants who pursued clinical trials as a full-time job participated in the greatest number of trials and were the most likely to continuing screening over time. IMPLICATIONS: Participation as a healthy volunteer in US Phase I trials is driven by social inequalities. Disadvantaged groups tend to participate in a greater number of clinical trials and participate longer than more privileged groups.

Geographic Disparities in Readmissions for Peripheral Artery Disease in South Carolina.

Readmissions constitute a major health care burden among peripheral artery disease (PAD) patients. This study aimed to 1) estimate the zip code tabulation area (ZCTA)-level prevalence of readmission among PAD patients and characterize the effect of covariates on readmissions; and (2) identify hotspots of PAD based on estimated prevalence of readmission. Thirty-day readmissions among PAD patients were identified from the South Carolina Revenue and Fiscal Affairs Office All Payers Database (2010-2018). Bayesian spatial hierarchical modeling was conducted to identify areas of high risk, while controlling for confounders. We mapped the estimated readmission rates and identified hotspots using local Getis Ord (G*) statistics. Of the 232,731 individuals admitted to a hospital or outpatient surgery facility with PAD diagnosis, 30,366 (13.1%) experienced an unplanned readmission to a hospital within 30 days. Fitted readmission rates ranged from 35.3 per 1000 patients to 370.7 per 1000 patients and the risk of having a readmission was significantly associated with the percentage of patients who are 65 and older (0.992, 95%CI: 0.985-0.999), have Medicare insurance (1.013, 1.005-1.020), and have hypertension (1.014, 1.005-1.023). Geographic analysis found significant variation in readmission rates across the state and identified priority areas for targeted interventions to reduce readmissions.

Peripheral Artery Disease Prevalence and Incidence Estimated From Both Outpatient and Inpatient Settings Among Medicare Fee-for-Service Beneficiaries in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Outpatient ascertainment of peripheral artery disease (PAD) is rarely considered in the measurement of PAD clinical burden; therefore, the clinical burden of PAD likely has been underestimated while contributing to a decreased awareness of PAD in comparison to other circulatory system disorders. METHODS AND RESULTS: The purpose of this study was to estimate the age-standardized annual period prevalence and incidence of PAD in the outpatient and inpatient settings using data from the Atherosclerosis Risk in Communities (ARIC) study linked with Centers for Medicare and Medicaid Services claims. The majority (>70%) of all PAD encounters occurred in the outpatient setting. The weighted mean age-standardized prevalence and incidence of outpatient PAD was 11.8% (95% CI 11.5-12.1) and 22.4 per 1000 person-years (95% CI 20.8-24.0), respectively. Black patients had higher weighted mean age-standardized prevalence (15.6%; 95% CI 14.6-16.4) compared with white patients (11.4%; 95% CI 11.1-11.7). Black women had the highest weighted mean age-standardized prevalence (16.9%; 95% CI 16.0-17.8). Black patients also had a higher incidence rate of PAD (31.3 per 1000 person-years; 95% CI 27.3-35.4) compared with white patients (25.4 per 1000 person-years; 95% CI 23.5-27.3). PAD prevalence and incidence did not differ by sex alone. CONCLUSIONS: This study provides comprehensive estimates of PAD in the inpatient and outpatient settings where the majority of PAD burden was found. PAD is an important circulatory system disorder similar in prevalence to stroke and coronary heart disease.

Peering into the pharmaceutical "pipeline": investigational drugs, clinical trials, and industry priorities.

In spite of a growing literature on pharmaceuticalization, little is known about the pharmaceutical industry's investments in research and development (R&D). Information about the drugs being developed can provide important context for existing case studies detailing the expanding--and often problematic--role of pharmaceuticals in society. To access the pharmaceutical industry's pipeline, we constructed a database of drugs for which pharmaceutical companies reported initiating clinical trials over a five-year period (July 2006-June 2011), capturing 2477 different drugs in 4182 clinical trials. Comparing drugs in the pipeline that target diseases in high-income and low-income countries, we found that the number of drugs for diseases prevalent in high-income countries was 3.46 times higher than drugs for diseases prevalent in low-income countries. We also found that the plurality of drugs in the pipeline was being developed to treat cancers (26.2%). Interpreting our findings through the lens of pharmaceuticalization, we illustrate how investigating the entire drug development pipeline provides important information about patterns of pharmaceuticalization that are invisible when only marketed drugs are considered.

Tracking the pharmaceutical pipeline: clinical trials and global disease burden.

Aggregate data about pharmaceutical research and development (R&D) tend to examine Phase III trials. Hence, there are few published data about investigational drugs in earlier phases of clinical development that might fail. It is also unclear how well R&D corresponds to disease burden. We track the pharmaceutical pipeline using data from industry publications that provide otherwise unreported information about industry-sponsored clinical trials. The sample includes 2,477 unique drug entities in 4,182 clinical trials. The majority of drugs targeted neoplasms (26.20%), neurological diseases/diseases of the sense organs (13.48%), infectious and parasitic diseases (10.5%), and endocrine, metabolic, nutrition, and immunity disorders (9.45%). Less than 6% of drugs targeted diseases of the circulatory system, which represent the most prevalent causes of global mortality. Detailing the pharmaceutical pipeline, our findings suggest that pharmaceutical development does not adequately address global disease burden. Future research on the under-reported details of Phase I and II clinical trials is needed to understand how the industry operates and how its resource-allocation matches global health concerns.

United States private-sector physicians and pharmaceutical contract research: a qualitative study.

BACKGROUND: There have been dramatic increases over the past 20 years in the number of nonacademic, private-sector physicians who serve as principal investigators on US clinical trials sponsored by the pharmaceutical industry. However, there has been little research on the implications of these investigators' role in clinical investigation. Our objective was to study private-sector clinics involved in US pharmaceutical clinical trials to understand the contract research arrangements supporting drug development, and specifically how private-sector physicians engaged in contract research describe their professional identities. METHODS AND FINDINGS: We conducted a qualitative study in 2003-2004 combining observation at 25 private-sector research organizations in the southwestern United States and 63 semi-structured interviews with physicians, research staff, and research participants at those clinics. We used grounded theory to analyze and interpret our data. The 11 private-sector physicians who participated in our study reported becoming principal investigators on industry clinical trials primarily because contract research provides an additional revenue stream. The physicians reported that they saw themselves as trial practitioners and as businesspeople rather than as scientists or researchers. CONCLUSIONS: Our findings suggest that in addition to having financial motivation to participate in contract research, these US private-sector physicians have a professional identity aligned with an industry-based approach to research ethics. The generalizability of these findings and whether they have changed in the intervening years should be addressed in future studies. Please see later in the article for the Editors' Summary.

Challenging assumptions about minority participation in US clinical research.

Although extensive research addresses minorities' low participation in clinical research, most focuses almost exclusively on therapeutic trials. The existing literature might mask important issues concerning minorities' participation in clinical trials, and minorities might actually be overrepresented in phase I safety studies that require the participation of healthy volunteers. It is critical to consider the entire spectrum of clinical research when discussing the participation of disenfranchised groups; the literature on minorities' distrust, poor access, and other barriers to trial participation needs reexamination. Minority participation in clinical trials is an important topic in public health discussions because this representation touches on issues of equality and the elimination of disparities, which are core values of the field.

Effects of increased vascular surgical specialization on general surgery trainees, practicing surgeons, and the provision of vascular surgical care.

BACKGROUND: Vascular surgical education for general surgery residents is concerning as endovascular interventions increase and vascular surgery expands. The purpose of this study was to examine the effects these factors have on vascular surgery case numbers for general surgery residents and statewide surgeons and to report on former general surgery residents' perceptions of vascular surgery in training and practice. STUDY DESIGN: Case numbers for all general surgery residents graduating from the Greenville Hospital System from 1991 to 2007 and for the vascular surgery fellows graduating from 2003 to 2007 were obtained. A database identified case numbers and physician specialty for vascular procedures from 1997 through 2006. A survey gained perspectives of graduated general surgery residents on the vascular experience during residency and practice and on postresidency vascular caseload. RESULTS: There was significant decline in resident participation in open abdominal aortic aneurysm (22.4 versus 7.7), carotid endarterectomy (37.2 versus 31.1), aortobifemoral bypass (18.6 versus 5.5), and lower extremity bypass (42.8 versus 19.1). Numbers for dialysis access creation (49.0 versus 57.1) were maintained. Statewide, comparing 1997 with 2006, the percentages of procedures performed by vascular surgeons were: abdominal aortic aneurysm (29.3% versus 49%; p < 0.001), carotid endarterectomy (28.9% versus 45.5%; p < 0.001), and dialysis access (4.6% versus 12.3%; p=0.020). The survey of general surgery graduates revealed lower extremity bypass, carotid endarterectomy, abdominal aortic aneurysm, and dialysis access are important in training. Dialysis access was the most common operation performed by the general surgery graduates. CONCLUSIONS: There is a trend toward vascular surgeons and vascular residents performing most open vascular cases. Currently practicing surgeons believe there is value to vascular exposure for general surgeons in training, and vascular surgery should remain in general surgery training.

Abdominal CT scanning in reproductive-age women with right lower quadrant abdominal pain: does its use reduce negative appendectomy rates and healthcare costs?

Although acute appendicitis is the most frequent cause of the acute abdomen in the United States, its accurate diagnosis in reproductive-age women remains difficult. Problems in making the diagnosis are evidenced by negative appendectomy rates in this group of 20 per cent to 45 per cent. Abdominal CT scanning has been used in diagnosing acute appendicitis, but its reliability and usefulness remains controversial. There is concern that the use of CT scanning to make this diagnosis leads to increased and unwarranted healthcare charges and costs. The purpose of our study is to determine if abdominal CT scanning is an effective test in making the diagnosis of acute appendicitis in reproductive-age women (age, 16-49 years) with right lower quadrant abdominal pain and to determine if its use is cost-effective. From January 2003 to December 2006, 439 patients were identified from our academic surgical database and confirmed by chart review as undergoing an appendectomy with a pre- or postoperative diagnosis of acute appendicitis. Data, including age, presence and results of preoperative abdominal CT scans, operative findings, and pathology reports were reviewed. Comparison of patients receiving a preoperative CT scan with those who did not was performed using chi-squared analysis. In the subgroup of reproductive-age women, there was a significant difference in negative appendectomy rates of 17 per cent in the group that received abdominal CT scans versus 42 per cent in the group that did not (P < 0.038). After accounting for the patient and insurance company costs, abdominal CT scan savings averaged $1412 per patient. Abdominal CT scanning is a reliable, useful, and cost-effective test for evaluating right lower quadrant abdominal pain and making the diagnosis of acute appendicitis in reproductive-age women.

Surgical revascularization in patients with end-stage renal disease: results using a new paradigm in outcomes assessment.

Studies evaluating the outcome of surgical revascularization (SR) for critical limb ischemia in patients who have end-stage renal disease (ESRD) have differed widely in their findings and conclusions. Differences in definitions of success are largely responsible for the varying outcomes. We developed a method of outcomes assessment that incorporates four all-inclusive endpoints to define success. These include primary graft patency to the point of wound healing, postoperative survival of at least 6 months, limb salvage of at least 1 year, and maintenance of ambulatory status of at least 6 months. The purpose of this study was to use this novel method of defining success to determine the outcome of SR in patients with ESRD. From 1998 to 2004, 40 patients (52 limbs) with ESRD and tissue loss underwent SR for limb salvage. Secondary graft patency and limb salvage rates at 36 months were 54.7 per cent and 53 per cent, respectively. When considering each of the four components used to define success separately, success encouragingly ranged between 60 per cent (patent graft until wound healing) and 87.5 per cent (survival for 6 months). However, if all parameters were combined, clinical success was achieved in only 40 per cent (16/40) of patients. Coronary artery disease was the only factor found to significantly reduce success (P = 0.04). In conclusion, using this multiparameter definition of success, which combines four rather modest outcome milestones, favorable outcome occurred in the minority of cases. This study challenges our current method of analyzing success and questions our therapeutic approach to patients with critical limb ischemia and ESRD.

Critical analysis of clinical success after surgical bypass for lower-extremity ischemic tissue loss using a standardized definition combining multiple parameters: a new paradigm of outcomes assessment.

BACKGROUND: Success after surgical revascularization of the lower extremities, traditionally defined by graft patency or limb salvage, fails to consider other intuitive measures of importance. The purpose of the study was to construct a more comprehensive definition of clinical success and to identify clinical predictors of failure. STUDY DESIGN: For the purpose of this study, clinical success was defined as achieving all of the following criteria: graft patency to the point of wound healing; limb salvage for 1 year; maintenance of ambulatory status for 1 year; and survival for 6 months. Between 1998 and 2004, 331 consecutive patients undergoing bypass for Rutherford III critical limb ischemia were measured for clinical success. Bivariate and logistic regression analyses were performed to determine demographic differences between success and failure. RESULTS: Despite achieving acceptable graft patency (72.7% at 36 months) and limb salvage (73.3% at 36 months), clinical success combining all 4 defined parameters was only 44.4%. Independent predictors of failure included impaired ambulatory status at presentation (odds ratio [OR] = 6.44), presence of infrainguinal disease (OR = 3.93), end-stage renal disease (OR = 2.48), presence of gangrene (OR = 2.40), and hyperlipidemia (OR = 0.56). Probability of failure in patients possessing every predictor except hyperlipidemia at presentation was 97% (OR = 150.6). CONCLUSIONS: Despite achieving acceptable graft patency and limb salvage, fewer than half of the patients achieved success when using a definition combining multiple parameters. A reappraisal of our current approach to critical limb ischemia in certain high-risk patients is warranted.