Abstract
Chronic limb-threatening ischemia (CLTI) is associated with significant morbidity, including major limb amputation, and mortality. Healing ischemic wounds is necessary to optimise vascular outcomes and can be facilitated by dedicated appointments at a wound clinic. This study aimed to estimate the association between successful wound care initiation and 6-month wound healing, with specific attention to differences by race/ethnicity. This retrospective study included 398 patients with CLTI and at least one ischaemic wound who scheduled an appointment at our wound clinic between January 2015 and July 2020. The exposure was the completion status of patients’ first scheduled wound care appointment (complete/not complete) and the primary outcome was 6-month wound healing (healed/not healed). The analysis focused on how this association was modified by race/ethnicity. We used Aalen–Johansen estimators to produce cumulative incidence curves and calculated risk ratios within strata of race/ethnicity. The final adjustment set included age, revascularization, and initial wound size. Patients had a mean age of 67 ± 14 years, were 41% female, 46% non-White and had 517 total wounds. In the overall cohort, 70% of patients completed their first visit and 34% of wounds healed within 6-months. There was no significant difference in 6-month healing based on first visit completion status for White/non-Hispanic individuals (RR [95% CI] = 1.18 [0.91, 1.45]; p-value = 0.130), while non-White individuals were roughly 3 times more likely to heal their wounds if they completed their first appointment (RR [95% CI] = 2.89 [2.66, 3.11]; p-value < 0.001). In conclusion, non-White patients were approximately three times more likely to heal their wound in 6 months if they completed their first scheduled wound care appointment while White/non-Hispanic individuals’ risk of healing was similar regardless of first visit completion status. Future efforts should focus on providing additional resources to ensure minority groups with wounds have the support they need to access and successfully initiate wound care.
Keywords: chronic limb threatening ischemia (CLTI), initiation of care, ischaemic wounds, racial disparities, time-to-event analysis, wound care, wound healing
1 |. INTRODUCTION
Chronic limb-threatening ischemia (CLTI) is associated with non-healing wounds, poor quality of life, and a significant risk of major amputation and mortality.1 Even after successful revascularization, patients with CLTI have nearly a 50% combined incidence of amputation or mortality within 3 years.2 An estimated 2 million US adults now have CLTI, and, as a result of an ageing population and increasing prevalence of atherosclerotic disease risk factors, the burden of death and disability from CLTI is expected to rise.1,3 Unfortunately, as in other health care domains, studies have repeatedly demonstrated racial and ethnic disparities in CLTI presentation and treatment. Compared to White patients, Black and Hispanic patients with CLTI present with more advanced disease and are more likely to seek care on an emergent basis.4,5 Black patients are also significantly less likely than White patients to undergo revascularization, limb-related admission, or wound debridement prior to a major amputation.6,7 Additionally, a recent study found that Black and American Indian/Alaska Native patients with CLTI were at the greatest risk for major amputation, followed by Hispanic individuals.8
In appropriate patients, revascularization remains the cornerstone of CLTI treatment1; however, optimising wound care is also a critical component of CLTI management.9 In particular, management by dedicated multidisciplinary wound care teams has been associated with a trend towards shorter wound healing time, a 60% reduction in major amputations at 1 year, and a two-fold increase in amputation-free survival.10,11 These benefits are at least partially attributable to the frequent contact with the clinical environment and earlier interventions offered by wound care teams when healing stalls or wounds get worse. We hypothesize that quickly initiating and establishing a wound care routine is an important component of improved outcomes.11 The relationship between the initiation of coordinated wound care and CLTI outcomes, and the potential effect of race/ethnicity on this relationship, have not been studied.
Our primary objective was to evaluate the effect of successful initiation of wound care, using first scheduled visit completion to represent initiation, on wound healing among patients with CLTI. Secondary outcomes of interest were major amputation and all-cause mortality. We hypothesize that patients who do not complete their first scheduled wound care appointment will have a higher risk of poor outcomes and that this effect will apply disproportionately to racial/ethnic minorities.
2 |. METHODS
2.1 |. Patient population
The parent study was a retrospective cohort of 2029 patients seeking care within the UNC health care system and diagnosed with CLTI from January 1, 2013 to December 31, 2017. A diagnosis of CLTI requires patients to meet both hemodynamic and symptomatic criteria. Hemodynamic criteria were defined as an ankle-brachial index <0.50, ankle pressure <70 mmHg, or toe pressure <50 mmHg. CLTI symptoms include rest pain, ulceration, or gangrene of the lower extremities. Patients from this parent study were then limited to patients seeking care at the UNC Wound Care Clinic and those with a known outcome status. We included those with ischaemic wounds, including neuroischaemic diabetic foot ulcers. Additional inclusion and exclusion criteria are presented in Figure 1. The final analysis sample size was 398 patients with 517 wounds. The proposed study was approved by the Institutional Review Board (IRB) at the University of North Carolina at Chapel Hill (IRB #: 20-2114).
FIGURE 1.
Inclusion/exclusion flowchart.
2.2 |. Wound care
Patients seeking care at the UNC Wound Care Clinic receive comprehensive wound management based on protocols that have been fully described elsewhere.12,13 The protocol includes optimising wound debridement, control of wound infection, and occasional use of hyperbaric oxygen and living cellular wound therapies.14 At every visit, wound sizes are monitored by measuring the maximum length, width, and depth. Podiatrists assist in the design and prescription of offloading devices for personalised wound offloading treatment. Digital photography is used at every visit to document wound healing and allow for timestamped confirmation of complete wound healing.14 Patients with severe ischaemia (toe pressure < 30 mmHg) are offered immediate revascularization (either endovascular or open surgery) unless their medical comorbidities prohibit invasive procedures. Patients with mild–moderate ischaemia most often undergo a trial of wound healing prior to consideration of revascularization; however, revascularization is offered to patients with wounds that do not respond to initial wound management and those that worsen at any time during therapy.15
2.3 |. Exposure, outcome and covariates
Completion status of a patient’s first scheduled wound care visit was the primary exposure. Administrative data reported each visit as ‘completed’, ‘cancelled’, or ‘no-show’. Our final coding of the exposure classified a completed visit as ‘completed’ or ‘cancelled’ but rescheduled within 1 week and completed that rescheduled visit and an uncompleted visit as ‘no show’ or ‘cancelled’ without rescheduling within 1 week.
The primary outcome was a dichotomous variable of wound healing within 6 months (yes/no). For our descriptive statistics, patients whose wound did not heal, underwent a major amputation prior to wound healing, or died prior to wound healing were considered not healed. For our time-to-event analyses major amputation and all-cause mortality during the study period were evaluated as competing risks to wound healing. Key covariates in this analysis were patient age (years), initial wound size (cm2), revascularization status, and race/ethnicity. All covariates were collected through manual medical chart extraction. Patients who received an open or endovascular revascularization surgery during the study period or any time during the year prior to enrolling in this study were considered to have had a revascularization. Initial wound size was recorded as the size of each wound at each patient’s first scheduled wound care visit and race was considered as racial self-classification.16 Race and ethnicity were combined due to the low number of Hispanic participants (5.4%) and was ultimately dichotomized to non-White (referent) and White/non-Hispanic due to small numbers of Asian individuals (0.4%) and those identifying as other races (6.4%). 37.5% of the population were Black or African American. Wound size was condensed into categories based on quartile cutoffs (≤1 cm2, 1.01–2.30 cm2, 2.31–9.86 cm2, >9.86 cm2).
2.4 |. Statistical analysis
Descriptive statistics were used to describe our patient population and their wounds. Student’s t-tests were used to compare the mean values of age and initial wound size and chi-square tests were used to compare the proportion of covariates, major amputation, and all-cause mortality.
We conducted a complete case analysis using the Aalen–Johansen (AJ) estimator to assess the association between first scheduled wound care visit completion and 6-month wound healing. We used an AJ estimator to account for major amputation and all-cause mortality as competing events to wound healing. We estimated cumulative incidence curves and calculated risk ratios within strata of first visit completion status, race/ethnicity, and a combination of both. These cumulative incidence curves were then compared using Gray’s tests for equality of cumulative incidence curves. Participants who did not complete their first scheduled wound care visit were used as the reference group. Some patients in our dataset presented with multiple wounds, and thus, we accounted for clustering at the person-level in our analyses. Variance estimates were calculated using bootstrapping.
The final adjustment set included age, modelled as a quadratic functional form, initial wound size (cm2), and revascularization as suspected confounders, and race/ethnicity as a suspected confounder/modifier with an interaction term for visit completion by race/ethnicity. Ischaemia grade and overall WIfI stage were not considered as confounders due to their potential collinearity with revascularization status and substantial missing data of these variables. Other covariates such as sex, smoking status, and diabetes were initially evaluated as potential confounders. However, after undergoing robust model selection using a change in estimate approach (change in risk ratio ≥0.1), these variables were ultimately excluded due to a minimal change in estimate, increased precision, and to ensure model convergence due to a relatively small sample size. We also recognise the importance of other variables such as social support, types of wound infection, and the degree of perfusion improvement after revascularization, as noted in our a priori directed acyclic graph (DAG) (Supplementary Figure 1), but this data was not available in this dataset.
Interaction between first visit completion status and race/ethnicity was assessed by comparing a saturated model with an interaction term to a main effects model without the interaction term and conducting a likelihood ratio test. Our threshold for the likelihood ratio test statistic was α = 0.05. Modification by race/ethnicity was assessed by producing stratum specific estimates and evaluating the joint effect of first visit completion and race/ethnicity. In accordance with the 6 principals outlined in the 2016 American Statistical Association’s statement on statistical significance and p-values, our interpretations were based on the magnitude of our estimates and their 95% confidence intervals (CIs) and p-values were only presented where necessary.17 All statistical analyses were performed using SAS 9.4 (Cary, NC).
3 |. RESULTS
Our cohort of 398 CLTI patients (517 wounds) had a mean age of 67 ± 14 years, 41% were female, 46% were non-White, and 69% had a history of smoking (Table 1). The average initial wound size was 25.9 ± 88.8 cm2; however, the average size of wounds that healed was 5.4 ± 17.8 cm2, while the average size of wounds that did not heal was 36.7 ± 107.5 cm2 (Difference [95% CI] = 31.3 [15.2, 47.4]). Additionally, toe wounds were more likely to heal (Difference [95% CI] = 15.0% [7.0%, 23.2%]), while heal wounds were less likely to heal (Difference [95% CI] = 8.0% [2.1%, 13.1%]) (Table 1). Seventy percent of individuals completed their first visit, 34% of wounds in the total cohort healed within 6 months, and there were 36 major amputations and 41 deaths over the study period. The median follow-up time for the cohort was 168 days (5.6 months). Non-White individuals in our cohort were significantly younger (Difference [95% CI] = 31.3 [15.2, 47.4]), less likely to have COPD (Difference [95% CI] = 17.0% [7.5%, 26.0%]) and a history of smoking (Difference [95% CI] = 14.0% [4.9%, 22.9%]), and more likely to have diabetes mellitus (Difference [95% CI] = 20.0% [11.7%, 27.8%]) compared to their White counterparts (Table 2). There was no significant difference in major amputation or death between White and non-White individuals (Difference [95% CI] = 5.5% [−0.2%, 11.6%] and 8.1% [−0.9%, 16.8%], respectively). It is important to note, however, that although non-significant non-White individuals did experience more amputations and death during the study period. Additionally, those who healed their wounds were less likely to have a subsequent amputation or die during the study period (Difference [95% CI] = 14.1% [9.5%, 18.9%] and 18.0% [8.9%, 26.2%], respectively). We calculated a likelihood ratio test statistic of 5.365 and p-value = 0.021 with 1 degree of freedom, indicating an interaction between race/ethnicity and first visit completion.
TABLE 1.
Descriptive statistics of patients and wounds that did and did not heal in 6-months.
| Total (398 patients, 517 wounds) | Healed (141 patients, 175 wounds) | Non-healed (257 patients, 342 wounds) | |
|---|---|---|---|
| Completion status of first wound clinic visit | 280 (70%) | 112 (79%) | 168 (66%) |
| Age (years) | 68 ± 14 | 67 ± 13 | 68 ± 15 |
| Sex (female) | 165 (41%) | 56 (39%) | 109 (43%) |
| Race/ethnicity (non-White) | 184 (46%) | 59 (42%) | 125 (49%) |
| Number of wounds | |||
| 1 | 307 (77%) | 113 (80%) | 194 (76%) |
| 2 | 68 (17%) | 23 (16%) | 45 (18%) |
| 3+ | 23 (6%) | 6 (4%) | 17 (7%) |
| Wound size (cm2) | 25.9 ± 88.8 | 5.4 ± 17.8 | 36.7 ± 107.5 |
| Wound location | |||
| Toe | 125 (24%) | 59 (34%) | 66 (19%) |
| Foot | 180 (35%) | 61 (35%) | 119 (35%) |
| Heel | 63 (12%) | 13 (7%) | 50 (15%) |
| Ankle | 26 (5%) | 9 (5%) | 17 (5%) |
| Leg | 123 (24%) | 33 (19%) | 90 (26%) |
| Revascularization | 113 (22%) | 49 (28%) | 64 (19%) |
| Comorbidities | |||
| Cerebrovascular disease (CVD) | 189 (47%) | 61 (43%) | 128 (50%) |
| Congestive heart failure (CHF) | 179 (45%) | 60 (42%) | 119 (46%) |
| Chronic obstructive pulmonary disorder (COPD) | 152 (38%) | 50 (35%) | 102 (40%) |
| Coronary artery disease (CAD) | 264 (66%) | 93 (65%) | 171 (67%) |
| Diabetes mellitus | 301 (76%) | 104 (73%) | 197 (77%) |
| Hyperlipidaemia | 313 (79%) | 111 (78%) | 202 (79%) |
| Hypertension | 385 (97%) | 135 (95%) | 250 (98%) |
| Obesity | 129 (32%) | 45 (32%) | 84 (33%) |
| Smoker | 276 (69%) | 101 (71%) | 175 (68%) |
Note: Patient level characteristics and comorbidities were calculated per person, while wound characteristics were calculated per wound.
TABLE 2.
Descriptive statistics of patients and wound characteristics by race/ethnicity.
| Total (398 patients, 517 wounds) | White (214 patients, 287 wounds) | Non-White (184 patients, 230 wounds) | |
|---|---|---|---|
| Completion status of first wound clinic visit | 280 (70%) | 150 (70%) | 130 (71%) |
| Age (years) | 68 ± 14 | 70 ± 13 | 65 ± 14 |
| Sex (female) | 165 (41%) | 77 (36%) | 88 (48%) |
| Outcomes | |||
| Healed | 175 (34%) | 106 (37%) | 69 (30%) |
| Major amputation | 36 (9%) | 14 (7%) | 22 (12%) |
| All-cause mortality | 41 (10%) | 28 (13%) | 13 (7%) |
| Number of wounds | |||
| 1 | 307 (77%) | 159 (74%) | 148 (80%) |
| 2 | 68 (17%) | 40 (19%) | 28 (15%) |
| 3+ | 23 (6%) | 15 (7%) | 8 (4%) |
| Wound size (cm2) | 25.9 ± 88.8 | 29.0 ± 93.1 | 22.0 ± 83.3 |
| Wound location | |||
| Toe | 125 (24%) | 59 (21%) | 66 (29%) |
| Foot | 180 (35%) | 99 (34%) | 81 (35%) |
| Heel | 62 (12%) | 37 (13%) | 26 (11%) |
| Ankle | 26 (5%) | 15 (5%) | 11 (5%) |
| Leg | 124 (24%) | 77 (27%) | 46 (20%) |
| Revascularization | 113 (22%) | 67 (23%) | 46 (20%) |
| Comorbidities | |||
| Cerebrovascular disease (CVD) | 189 (47%) | 99 (46%) | 90 (49%) |
| Congestive heart failure (CHF) | 179 (45%) | 100 (47%) | 79 (43%) |
| Chronic obstructive pulmonary disorder (COPD) | 152 (38%) | 99 (46%) | 53 (29%) |
| Coronary artery disease (CAD) | 264 (66%) | 143 (67%) | 121 (66%) |
| Diabetes mellitus | 301 (76%) | 142 (66%) | 159 (86%) |
| Hyperlipidaemia | 313 (79%) | 168 (79%) | 145 (79%) |
| Hypertension | 385 (97%) | 205 (96%) | 180 (98%) |
| Obesity | 129 (32%) | 65 (30%) | 64 (35%) |
| Smoker | 276 (69%) | 162 (76%) | 114 (62%) |
Note: Patient level characteristics and comorbidities were calculated per person, while wound characteristics were calculated per wound.
The adjusted Aalen–Johansen estimators for our primary and secondary outcomes produced 6-month risks of 28.9%, 6.7%, and 9.6% for healing, major amputation, and death, respectively (Table 3). Overall, participants who completed their first scheduled wound care appointment were 1.71 (95% CI: 1.48, 1.95; p-value < 0.001) times more likely to heal their wounds in 6 months compared to those who did not complete their first visit (Figure 2, Table 3). Although not a significant difference, non-White individuals, regardless of first visit completion status, were less likely to heal their wounds compared to their White counterparts (RR [95% CI] = 0.79 [0.55, 1.03]; p-value = 0.123).
TABLE 3.
Overall proportion of 6-month outcomes and proportion of 6-month healing by first visit completion, race/ethnicity, and a combination of the two.
| Overall primary and secondary outcomes | |||||
|---|---|---|---|---|---|
|
| |||||
| Group | Risk (95% CI)a | ||||
| Healed | 0.289 (0.231, 0.347) | ||||
| Major amputation | 0.067 (0.053, 0.081) | ||||
| All-cause mortality | 0.096 (0.076, 0.116) | ||||
| Healed | |||||
|
| |||||
| Group | Risk (95% CI) a | Risk ratio (95% CI) a | Chi-square b | df b | p-value b |
| First visit completion status | |||||
| Completed | 0.339 (0.270, 0.407) | 1.71 (1.48, 1.95) | 11.941 | 1 | <0.001 |
| Not completed | 0.198 (0.156, 0.240) | ||||
| Race/ethnicity | |||||
| Non-White | 0.254 (0.201, 0.307) | 0.79 (0.55, 1.03) | 2.377 | 1 | 0.123 |
| White | 0.321 (0.256, 0.386) | ||||
| Combined | |||||
| Completed/White | 0.336 (0.267, 0.406) | 1.18 (0.91, 1.45) | 2.295 | 1 | 0.130 |
| Not completed/White | 0.285 (0.223,0.348) | ||||
| Completed/non-White | 0.338 (0.268, 0.409) | 2.89 (2.66, 3.11) | 13.186 | 1 | <0.001 |
| Not completed/non-White | 0.117 (0.085, 0.149) | ||||
Risks calculated using AJ-estimators accounting for major amputation and death as competing events and adjusting for age, initial wound size, and revascularization. Standard errors for 95% CIs produced using bootstrapping.
Chi-square values, df, and p-values calculated using Gray's test for equality of cumulative incidence functions.
FIGURE 2.
6-Month cumulative incidence of wound healing by first visit completion status.
When stratifying the adjusted Aalen–Johansen estimator by both first visit completion status and race/ethnicity, individuals who completed their first appointment, regardless of race/ethnicity were the most likely to heal their wound(s) in 6 months (33.6% of White individuals and 33.8% of non-White individuals), while non-White individuals who did not complete their first appointment were the least likely to heal their wound(s) (11.7%) (Table 3). Stratum specific risk ratios (95% CIs) of 6-month wound healing by first visit completion status and race/ethnicity were 1.18 (0.91, 1.45), p-value = 0.130 for White/Non-Hispanic individuals and 2.89 (2.66, 3.11), p-value < 0.001 for non-White individuals (Figure 3). This indicates that there was no significant difference in 6-month healing based on first visit completion status for White individuals, while non-White individuals were 2.89 times more likely to heal their wounds if they completed their first scheduled wound care appointment.
FIGURE 3.
6-Month cumulative incidence of wound healing by first visit completion status and race/ethnicity.
4 |. DISCUSSION
In this study, we found a significant effect of race/ethnicity on the relationship between wound care initiation and wound healing in patients with ischaemic wounds, including neuroischaemic diabetic foot ulcers. In particular, only 1 in 10 non-White patients who failed to initiate wound management as scheduled healed their wounds within 6 months. This is compared to roughly 2–3 times that number in any other group. Furthermore, first visit completion was not significantly related to wound healing among White/non-Hispanic patients.
Though not previously studied in patients with CLTI, the interrelatedness of racial disparities, initiation of care, and adverse health outcomes has been demonstrated in other clinical contexts. For example, compared with White patients, Black and other non-White patients have significantly delayed care for initiation of dialysis, chemotherapy/radiation, and prenatal care, among other types of care.18–21 Independent of initiation of care, these same Black patients are also 4 times more likely to develop kidney failure, present with more advanced stages of breast, lung, and colon cancer with lower 5-year survival rates, and experience increased rates of pregnancy-related maternal complications and death when compared to their White/non-Hispanic counterparts.22–24 Similarly poor results are seen in diabetes and cancer diagnosis, care, and outcomes, among other diseases, for Hispanic/Latino individuals, American Indians/Alaskan Natives, and Asian Americans.25–29 Adjusting for delays in care attenuates but does not eliminate these relationships, suggesting that the longer time it takes to initiate care only partially explains poor outcomes among minority patients.18–21 Our results show that the combination of non-White race/ethnicity and missed first visit is associated with a very low proportion of wound healing. However, patients who completed their wound care initiation visit as scheduled had similar outcomes regardless of race, indicating that efforts to successfully initiate wound care among non-White patients may result in improved wound healing.
Some of our other results also support our main finding of racial disparities in wound care initiation and healing. The wounds that healed in 6 months were significantly smaller than the wounds that did not heal. It is important to note, however, that the average initial wound size did not differ between non-White and White/non-Hispanic participants. Considering the average initial wound size was not different by race/ethnicity supports the idea that other social factors are contributing to the disparities seen in the proportion of wound healing for non-White individuals compared to their White/non-Hispanic counterparts.
It is feasible that poor initiation of wound care is not only an indication of the patient’s struggles in the health care system, but also a sort of ‘last straw’ on the path towards poor CLTI outcomes. For example, Black patients with peripheral artery disease are less likely than White patients to be prescribed statins and antiplatelet medications.30,31 They also have more comorbidities and present with more advanced vascular disease.31 Moreover, they must contend with the numerous barriers that affect the health of racial/ethnic minority patients in the United States: low health literacy, mistrust of the health care system, lower socioeconomic status, lower rates of health insurance, competing health priorities, difficulty accessing care, poor quality of care, and others.32–34 Structural racism, both in health care and in all aspects of life, underlies and perpetuates these issues and likely also contributes to delays in initiating wound management when referred for specialised care.35
A notable strength of this study is the use of advanced time-to-event epidemiologic methods. This study is one of the first of its kind in the wound healing space to acknowledge and incorporate known competing risks into our estimate calculations using Aalen–Johansen estimators with bootstrapped confidence intervals. The use of robust model selection techniques also allowed us to maintain the precision of our estimates. Although this study has multiple strengths, it is not without limitations. Due to the small number of patients in individual racial/ethnic groups, we collapsed these strata into a binary White/non-White variable and are unable to comment on outcomes for individual minority races/ethnicities. We also recognise that the non-White group was primarily comprised of Black individuals and that the experiences of other minority groups are not necessarily homogeneous with the Black experience in the US. In addition, this study included patients treated at a single clinic at a single institution, which limits generalizability to patients outside of this clinical setting and could introduce selection bias. A larger, multi-institutional study would allow one to calculate risks for each race/ethnicity and improve generalizability. Our definition of visit completion was also unable to capture the nuanced nature as to why certain individuals may have missed their first scheduled appointment. Although we suspect that poor access to reliable transportation, lack of familial/social support, and long distance to the wound care facility, among other factors, likely contributed to these individuals missing their first scheduled visit, other studies focusing on these barriers should be conducted. Finally, it is possible that unmeasured confounders influenced our results through residual confounding bias. In particular, we were unable to measure social support, wound perfusion improvements after revascularization, and wound related characteristics beyond dimensions and healing status, which may influence both wound care initiation and outcomes of individualised medical treatments within a complex social system.
Among non-White patients with CLTI, patients who attend their first scheduled wound care appointment as scheduled are roughly three times more likely to heal their wounds within 6 months than those who miss their first appointment. White patients, however, are equally likely to heal their wounds whether or not they complete their first appointment. These findings suggest that wound care initiation is of heightened importance among non-White patients, who likely have an increased risk for poor outcomes at baseline as a result of the racial disparities in our health care system. While large-scale efforts to combat systemic racism and improve health equity are urgently needed, this study shows that reducing barriers to wound care initiation may be one way to improve outcomes for minority patients with CLTI.
Supplementary Material
FUNDING INFORMATION
Sydney Browder is funded by an NIH pre-doctoral Cardiovascular (CVD) Epidemiology Training Grant (NRSA: T32-HL007055-46).
Abbreviations:
- AJ
Aalen–Johansen
- CAD
coronary artery disease
- CHF
congestive heart failure
- CIs
confidence intervals
- CLTI
chronic limb threatening ischemia
- COPD
chronic obstructive pulmonary disorder
- CVD
cerebrovascular disease
- DAG
directed acyclic graph
- IRB
Institutional Review Board
Footnotes
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
SUPPORTING INFORMATION
Additional supporting information can be found online in the Supporting Information section at the end of this article.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.