Variability in guideline-directed medical therapy across sites and operators and long-term mortality and amputation outcomes risk in patients undergoing peripheral vascular interventions.

BACKGROUND: The use of guideline-directed medical therapy (GDMT) in patients undergoing peripheral vascular interventions (PVIs) decreases the risk of death and amputation and may decrease hospital readmissions. The variability of GDMT prescription across sites and operators and the proportionality of risk is not well understood. We aimed to study the association between variability of GDMT prescription at the site and operator level and outcomes (including 90-day readmissions and 24-month all-cause mortality and major amputation). METHODS: We examined GDMT discharge rates in PVIs performed between 2017 and 2018 using Medicare-linked Vascular Quality Initiative registry. GDMT included a statin, antiplatelet therapy, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE-i/ARB) if hypertensive. Quartiles (Q1-4) of GDMT rates were documented by operators and sites and variability was quantified using median odds ratios (MOR) and intraclass correlation (ICC). The association between lower GDMT rates (per 10%) by sites and operators with 90-day readmission were calculated using logistic regression, and with 24-month mortality and major amputation using parametric survival model. Models were adjusted for patient-level factors and included sites and operators nested within sites as 2 random effects. RESULTS: GDMT rates for 17,147 patients across 223 sites and 1,263 operators ranged from 0% to 38% (Q1, MOR 1.43, 95%CI 1.39-1.47, P ≤ .001) to 57%-100% (Q4, MOR 1.48, 95%CI 1.44-1.51, P ≤ .001). Four percent of variance in GDMT use was explained by sites (ICC 3.9, 95%CI 2.9-5.3) and operators (ICC 4.1, 95%CI 3.1-5.4). A dose-response relationship was noted between lower GDMT rates and increased risk of 90-day readmission risk by sites (P = .021) and operators (P < .001). Lower GDMT prescription by site was associated with higher risk of 24-month mortality (HR = 1.07, 95%CI 1.02-1.13) and major amputation (HR = 1.08, 95%CI 1.01-1.15). Similar associations were found for GDMT use by provider (mortality HR = 1.05, 95%CI 1.02-1.08 and amputation HR = 1.04, 95%CI 1.00-1.08). CONCLUSION: Both at the operator and health system level, there was significant variability in GDMT prescription following PVI, proportionally translating into risk for readmission, mortality, and major amputation. Targeted quality efforts should prioritize both operator and site levels to improve GDMT use and outcomes for patients undergoing PVI.

Impact of early intervention on health status outcomes in peripheral artery disease patients with chronic total occlusion lesions using the PORTRAIT registry.

OBJECTIVE: To analyze the impact of noninvasive and early invasive treatments on health status in patients with lower extremity peripheral arterial disease (PAD) without and with chronic total occlusions (CTOs) after 12 months of follow-up. METHODS: Using the international (the United States, the Netherlands, and Australia) observational longitudinal Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories registry, we included patients with recent PAD symptoms between June 2011 and December 2015. We assessed the PAD-specific health status at initial visit and the 3-, 6-, and 12-month follow-up using the Peripheral Arterial Questionnaire. On a propensity matched-weighted cohort, we compared patients' characteristics by CTO status and treatment groups as early invasive (revascularization in the 3 months) vs noninvasive (exercise, medical therapies, or smoking cessation). We then assessed the health status trajectory over 12 months, as a three-way interaction between CTO status, treatment groups, and months, using a multilevel generalized linear regression model for repeated measures adjusted for baseline health status with random effects at the site and patient levels. RESULTS: We included 581 participants, with a mean age of 66.62 ± 9.33 years, 34.3% female, and 90.8% White, of whom 353 (60.8%) were without and 228 (39.2%) had a CTO lesion. Respectively, 96 (27.2%) and 70 (30.7%) patients underwent early invasive treatment (d = 0.07). Although patients with CTO were more likely to have lower resting ABI, multilevel disease, and to experience severe claudication vs their counterparts (|d| ≥ 0.20), patient health status at baseline with CTO was not different from those without CTO, with mean summary scores of 45.14 ± 20.26 vs 45.90 ± 21.24 (d = 0.04), respectively. The trajectory did not differ by CTO status (interaction CTO status × month; P = .517) and was higher in early invasive vs noninvasive treatment (treatment × month; P < .001), regardless of CTO status (CTO status × treatment; P = .981 and CTO status × treatment × month; P = .264). The score increased over time with the largest improvement occurring at 3 months in both noninvasive (non-CTO, +7.82 [95% confidence interval (CI), 4.03-11.60] and CTO, +9.27 95% CI, 4.45-14.09) and early invasive (non-CTO, +26.17 [95% CI, 20.06-32.28] and CTO, +24.52 [95% CI, 17.40-31.64] groups. The mean score in CTO vs non-CTO groups did not differ at each timepoint, with a 12-month mean score of 70.26 (95% CI, 67.87-74.65) vs 71.17 (95% CI, 65.91-76.44) (P = .99) in the noninvasive treatment and 84.93 (95% CI, 78.90-90.97) vs 79.20 (95% CI, 72.77-86.14) (P = .31) in the early invasive treatment. CONCLUSIONS: Patients with symptomatic PAD undergoing early revascularization exhibited better health status over time vs those undergoing noninvasive treatment strategy, irrespective of the presence of CTOs. The degree of the improvement was greater in the 3 months after the initial visit, especially in patients undergoing early revascularization.

Variability in short-term mortality following repair of ruptured abdominal aortic aneurysms across centers and physicians.

BACKGROUND: Variation in the care management of repairs for ruptured infrarenal abdominal aortic aneurysms between centers and physicians, such as procedural volumes, may explain differences in mortality outcomes. First, we quantified the center and physician variability associated with 30- and 90-day mortality risk after ruptured open surgical repair (rOSR) and ruptured endovascular aneurysm repair (rEVAR). Second, we explored wheter part of this variability was attributable to procedural volume at the center and physician levels. METHODS: Two cohorts including rOSR and rEVAR procedures between 2013 and 2019 were analyzed from the Vascular Quality Initiative database. Thirty- and 90-day all-cause mortality rates were derived from linked Medicare claims data. The median odds ratio (MOR) (median mortality risk from low- to high-risk cluster) and intraclass correlation coefficient (ICC) (variability attributable to each cluster) for 30- and 90-day mortality risks associated with center and physician variability were derived using patient-level adjusted multilevel logistic regression models. Procedural volume was calculated at the center and physician levels and stratified by quartiles. The models were sequentially adjusted for volumes, and the difference in ICCs (without vs with accounting for volume) was calculated to describe the center and physician variability in mortality risk attributable to volumes. RESULTS: We included 450 rOSRs (mean age, 74.5 ± 7.6 years; 23.5% female) and 752 rEVARs (76.4 ± 8.4 years; 26.1% female). After rOSRs, the 30- and 90-day mortality rates were 32.9% and 38.7%, respectively. No variability across centers and physicians was noted (30- and 90-day MORs ≈1 and ICCs ≈0%). Neither center nor physician volume was associated with 30-day (P = .477 and P = .796) or 90-day mortality (P = .098 and P = .559). After rEVAR, the 30- and 90-day mortality rates were 21.3% and 25.5%, respectively. Significant center variability (30-day MOR, 1.82 [95% confidence interval (CI), 1.33-2.22]; ICC, 11% [95% CI, 2%-36%]; and 90-day MOR, 1.76 [95% CI, 1.37-2.09]; ICC, 10% [95% CI, 3%-30%]), but negligeable variability across physicians (30- and 90-day MORs ≈1 and ICCs ≈0%) were noted. Neither center nor physician volume were associated with 30-day (P = .076 and P = .336) or 90-day mortality risk (P = .066 and P = .584). The center variability attributable to procedural volumes was negligeable (difference in ICCs, 1% for 30-day mortality; 0% for 90-day mortality). CONCLUSIONS: Variability in practice from center to center was associated with short-term mortality outcomes in rEVAR, but not for rOSR. Physician variability was not associated with short-term mortality for rOSR or rEVAR. Annualized center and physician volumes did not significantly explain these associations. Further work is needed to identify center-level factors affecting the quality of care and outcomes for ruptured abdominal aortic aneurysms.

Psychosocial and socioeconomic factors are most predictive of health status in patients with claudication.

BACKGROUND: As a key treatment goal for patients with symptomatic peripheral artery disease (PAD), improving health status has also become an important end point for clinical trials and performance-based care. An understanding of patient factors associated with 1-year PAD health status is lacking in patients with PAD. METHODS: The health status of 1073 consecutive patients with symptomatic PAD in the international multicenter PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry was measured at baseline and 1 year with the Peripheral Artery Questionnaire (PAQ). The association of 47 patient characteristics with 1-year PAQ scores was assessed using a random forest algorithm. Variables of clinical significance were retained and included in a hierarchical multivariable linear regression model predicting 1-year PAQ summary scores. RESULTS: The mean age of patients was 67.7 ± 9.3 years, and 37% were female. Variables with the highest importance ranking in predicting 1-year PAQ summary score were baseline PAQ summary score, Patient Health Questionnaire-8 depression score, Generalized Anxiety Disorder-2 anxiety score, new onset symptom presentation, insurance status, current or prior diagnosis of depression, low social support, initial invasive treatment, duration of symptoms, and race. The addition of 19 clinical variables in an extended model marginally improved the explained variance in 1-year health status (from R2 0.312 to 0.335). CONCLUSIONS: Patients' 1-year PAD-specific health status, as measured by the PAQ, can be predicted from 10 mostly psychosocial and socioeconomic patient characteristics including depression, anxiety, insurance status, social support, and symptoms. These characteristics should be validated and tested in other PAD cohorts so that this model can inform risk adjustment and prediction of PAD health status in comparative effectiveness research and performance-based care.

Comparison of mortality and amputation after lower extremity bypass versus peripheral vascular intervention in patients with chronic limb-threatening ischemia and comorbid chronic kidney disease.

OBJECTIVE: Comorbid chronic kidney disease (CKD) is associated with worse outcomes for patients with chronic limb-threatening ischemia (CLTI). However, comparative effectiveness data are limited for lower extremity bypass (LEB) vs peripheral vascular intervention (PVI) in patients with CLTI and CKD. We aimed to evaluate (1) 30-day all-cause mortality and amputation and (2) 5-year all-cause mortality and amputation for LEB vs PVI in patients with comorbid CKD. METHODS: Individuals who underwent LEB and PVI were queried from the Vascular Quality Initiative with Medicare claims-linked outcomes data. Propensity scores were calculated using 13 variables, and a 1:1 matching method was used. The mortality risk at 30 days and 5 years in LEB vs PVI by CKD was assessed using Kaplan-Meier and Cox proportional hazards models, with interaction terms added for CKD. For amputation, cumulative incidence functions and Fine-Gray models were used to account for the competing risk of death, with interaction terms for CKD added. RESULTS: Of 4084 patients (2042 per group), the mean age was 71.0 ± 10.8 years, and 69.0% were male. Irrespective of CKD status, 30-day mortality (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.63-1.42, P = .78) was similar for LEB vs PVI, but LEB was associated with a lower risk of 30-day amputation (sub-HR [sHR]: 0.66, 95% CI: 0.44-0.97, P = .04). CKD status, however, did not modify these results. Similarly, LEB vs PVI was associated with a lower risk of 5-year mortality (HR: 0.79, 95% CI: 0.71-0.88, P < .001) but no difference in 5-year amputation (sHR: 1.03, 95% CI: 0.89-1.20, P = .67). CKD status did not modify these results. CONCLUSIONS: Regardless of CKD status, patients had a lower risk of 5-year all-cause mortality and 30-day amputation with LEB vs PVI. Results may help inform preference-sensitive treatment decisions on LEB vs PVI for patients with CLTI and CKD, who may commonly be deemed too high risk for surgery.

Evaluation of short-term mortality in patients with Medicare undergoing endovascular interventions for chronic limb-threatening ischemia.

INTRODUCTION: Patients with chronic limb-threatening ischemia (CLTI) have high mortality rates after revascularization. Risk stratification for short-term outcomes is challenging. We aimed to develop machine-learning models to rank predictive variables for 30-day and 90-day all-cause mortality after peripheral vascular intervention (PVI). METHODS: Patients undergoing PVI for CLTI in the Medicare-linked Vascular Quality Initiative were included. Sixty-six preprocedural variables were included. Random survival forest (RSF) models were constructed for 30-day and 90-day all-cause mortality in the training sample and evaluated in the testing sample. Predictive variables were ranked based on the frequency that they caused branch splitting nearest the root node by importance-weighted relative importance plots. Model performance was assessed by the Brier score, continuous ranked probability score, out-of-bag error rate, and Harrell's C-index. RESULTS: A total of 10,114 patients were included. The crude mortality rate was 4.4% at 30 days and 10.6% at 90 days. RSF models commonly identified stage 5 chronic kidney disease (CKD), dementia, congestive heart failure (CHF), age, urgent procedures, and need for assisted care as the most predictive variables. For both models, eight of the top 10 variables were either medical comorbidities or functional status variables. Models showed good discrimination (C-statistic 0.72 and 0.73) and calibration (Brier score 0.03 and 0.10). CONCLUSION: RSF models for 30-day and 90-day all-cause mortality commonly identified CKD, dementia, CHF, need for assisted care at home, urgent procedures, and age as the most predictive variables as critical factors in CLTI. Results may help guide individualized risk-benefit treatment conversations regarding PVI.

Impact of comorbid opioid use disorder and major depressive disorder on healthcare utilization outcomes in patients with peripheral artery disease: A National Readmission Database analysis.

BACKGROUND: Prior research has demonstrated that individuals with peripheral artery disease (PAD) often have comorbid opioid use disorder (OUD) and major depressive disorder (MDD), with limited data regarding their impact on readmission outcomes, length of stay, and cost. This study aimed to investigate these healthcare utilization outcomes in patients with PAD who have comorbid OUD and MDD. METHODS: Data were obtained from the National Readmission Database from 2011 through 2018. The study population included all hospitalizations with PAD as the primary or secondary diagnosis, from which hospitalizations with OUD and MDD were extracted using appropriate ICD-9/10 diagnosis codes. Primary outcomes were 30-day and 90-day readmission, total cost, and total length of stay within the calendar year. We created hierarchical multivariable logistic regression models examining OUD with and without MDD, with a random effect for healthcare facility location. RESULTS: From 2011 to 2018, 13,265,817 weighted admissions with PAD were identified. These admissions were segmented into four categories: No OUD/No MDD (12,056,466), OUD/No MDD (323,762), No OUD/MDD (867,641), and OUD/MDD (17,948). The group with No OUD/No MDD was used as the reference group for all subsequent comparisons. Regarding 30-day and 90-day readmissions, patients with OUD/MDD had odds of 1.14 (95% CI 1.10, 1.18) and 1.09 (95% CI 1.06, 1.13), respectively. Patients with OUD/No MDD bore the highest median cost of $64,354 (IQR $30,797-137,074), and patients with OUD/MDD marked the lengthiest median stay of 6.01 days (IQR 2.01-13.30). CONCLUSION: This study found a significant association between these comorbidities and outcomes and therefore calls for targeted interventions and pain management strategies.

Comparison of lower extremity bypass and peripheral vascular intervention for chronic limb-threatening ischemia in the Medicare-linked Vascular Quality Initiative.

OBJECTIVE: There is a relative lack of comparative effectiveness research on revascularization for patients with chronic limb-threatening ischemia (CLTI). We examined the association between lower extremity bypass (LEB) vs peripheral vascular intervention (PVI) for CLTI and 30-day and 5-year all-cause mortality and 30-day and 5-year amputation. METHODS: Patients undergoing LEB and PVI of the below-the-knee popliteal and infrapopliteal arteries between 2014 and 2019 were queried from the Vascular Quality Initiative, and outcomes data were obtained from the Medicare claims-linked Vascular Implant Surveillance and Interventional Outcomes Network database. Propensity scores were calculated on 15 variables using a logistic regression model to control for imbalances between treatment groups. A 1:1 matching method was used. Kaplan-Meier survival curves and hierarchical Cox proportional hazards regression with a random intercept for site and operator nested in site to account for clustered data compared 30-day and 5-year all-cause mortality between groups. Thirty-day and 5-year amputation were subsequently compared using competing risk analysis to account for the competing risk of death. RESULTS: There was a total of 2075 patients in each group. The overall mean age was 71 ± 11 years, 69% were male, and 76% were white, 18% were black, and 6% were of Hispanic ethnicity. Baseline clinical and demographic characteristics in the matched cohort were balanced between groups. There was no association between all-cause mortality over 30 days and LEB vs PVI (cumulative incidence, 2.3% vs 2.3% by Kaplan Meier; log-rank P-value = .906; hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.62-1.44; P-value = .80). All-cause mortality over 5 years was lower for LEB vs PVI (cumulative incidence, 55.9% vs 60.1% by Kaplan Meier; log-rank P-value < .001; HR, 0.77; 95% CI, 0.70-0.86; P-value < .001). Accounting for competing risk of death, amputation over 30 days was also lower in LEB vs PVI (cumulative incidence function, 1.9% vs 3.0%; Fine and Gray P-value = .025; subHR, 0.63; 95% CI, 0.42-0.95; P-value = .025). There was no association between amputation over 5 years and LEB vs PVI (cumulative incidence function, 22.6% vs 23.4%; Fine and Gray P-value = .184; subHR, 0.91; 95% CI, 0.79-1.05; P-value = .184). CONCLUSIONS: In the Vascular Quality Initiative-linked Medicare registry, LEB vs PVI for CLTI was associated with a lower risk of 30-day amputation and 5-year all-cause mortality. These results will serve as a foundation to validate recently published randomized controlled trial data, and to broaden the comparative effectiveness evidence base for CLTI.

Community distress and risk of adverse outcomes after peripheral vascular intervention.

INTRODUCTION: Community distress is associated with adverse outcomes in patients with cardiovascular disease; however, its impact on clinical outcomes after peripheral vascular intervention (PVI) is uncertain. The Distressed Communities Index (DCI) is a composite measure of community distress measured at the zip code level. We evaluated the association between community distress, as measured by the DCI, and 24-month mortality and major amputation after PVI. METHODS: We used the Vascular Quality Initiative database, linked with Medicare claims data, to identify patients who underwent initial femoropopliteal PVI between 2017 and 2018. DCI scores were assigned using patient-level zip code data. The primary outcomes were 24-month mortality and major amputation. We used time-dependent receiver operating characteristic curve analysis to determine an optimal DCI value to stratify patients into risk categories for 24-month mortality and major amputation. Mixed Cox regression models were constructed to estimate the association of DCI with 24-month mortality and major amputation. RESULTS: The final cohort consisted of 16,864 patients, of whom 4734 (28.1%) were classified as having high community distress (DCI ≥70). At 24 months, mortality was elevated in patients with high community distress (30.7% vs 29.5%, P = .02), as was major amputation (17.2% vs 13.1%, P <.001). After adjusting for demographic and clinical characteristics, a 10-point higher DCI score was associated with increased risk of mortality (hazard ratio: 1.01; 95% confidence interval: 1.00-1.03) and major amputation (hazard ratio: 1.02; 95% confidence interval: 1.00-1.04). CONCLUSIONS: High community distress is associated with increased risk of mortality and major amputation after PVI.

A new cure model that corrects for increased risk of non-cancer death: analysis of reliability and robustness, and application to real-life data.

BACKGROUND: Non-cancer mortality in cancer patients may be higher than overall mortality in the general population due to a combination of factors, such as long-term adverse effects of treatments, and genetic, environmental or lifestyle-related factors. If so, conventional indicators may underestimate net survival and cure fraction. Our aim was to propose and evaluate a mixture cure survival model that takes into account the increased risk of non-cancer death for cancer patients. METHODS: We assessed the performance of a corrected mixture cure survival model derived from a conventional mixture cure model to estimate the cure fraction, the survival of uncured patients, and the increased risk of non-cancer death in two settings of net survival estimation, grouped life-table data and individual patients' data. We measured the model's performance in terms of bias, standard deviation of the estimates and coverage rate, using an extensive simulation study. This study included reliability assessments through violation of some of the model's assumptions. We also applied the models to colon cancer data from the FRANCIM network. RESULTS: When the assumptions were satisfied, the corrected cure model provided unbiased estimates of parameters expressing the increased risk of non-cancer death, the cure fraction, and net survival in uncured patients. No major difference was found when the model was applied to individual or grouped data. The absolute bias was < 1% for all parameters, while coverage ranged from 89 to 97%. When some of the assumptions were violated, parameter estimates appeared more robust when obtained from grouped than from individual data. As expected, the uncorrected cure model performed poorly and underestimated net survival and cure fractions in the simulation study. When applied to colon cancer real-life data, cure fractions estimated using the proposed model were higher than those in the conventional model, e.g. 5% higher in males at age 60 (57% vs. 52%). CONCLUSIONS: The present analysis supports the use of the corrected mixture cure model, with the inclusion of increased risk of non-cancer death for cancer patients to provide better estimates of indicators based on cancer survival. These are important to public health decision-making; they improve patients' awareness and facilitate their return to normal life.

Lower extremity symptoms and ankle-brachial index screening as predictors of cardiovascular outcomes in Black adults.

BACKGROUND: The prevalence of peripheral artery disease (PAD) and leg symptoms are higher in Black than White adults. We studied the effects of self-reported lower extremity symptoms and ankle-brachial indices (ABI) groups on outcomes. METHODS: Black participants in the Jackson Heart Study with baseline ABI and PAD symptom assessments (exertional leg pain by the San Diego Claudication questionnaire) were included. Abnormal ABI was < 0.90 or > 1.40. Participants were divided into (1) normal ABI, asymptomatic, (2) normal ABI, symptomatic, (3) abnormal ABI, asymptomatic, and (4) abnormal ABI, symptomatic to examine their associations with MACE (stroke, myocardial infarction, fatal coronary heart disease) and all-cause mortality, using Kaplan-Meier survival curves and stepwise Cox proportional hazard models adjusting for Framingham risk factors. RESULTS: Of 4586 participants, mean age was 54.6 ± 12.6 years, with 63% women. Compared with participants with normal ABI who were asymptomatic, participants with abnormal ABI and leg symptoms had highest risk of MACE (adjusted HR 2.28; 95% CI 1.62, 3.22) and mortality (aHR 1.82; 95% CI 1.32, 2.56). Participants with abnormal ABI without leg symptoms had higher risk for MACE (aHR 1.49; 95% CI 1.06, 2.11) and mortality (aHR 1.44; 95% CI 1.12, 1.99). Participants with normal ABI and no leg symptoms did not have higher risks. CONCLUSION: Among Black adults, the highest risk for adverse outcomes were in symptomatic participants with abnormal ABIs, followed by asymptomatic participants with abnormal ABIs. These findings underscore the need for further studies to screen for PAD and develop preventative approaches in Black adults with asymptomatic disease.

Patient knowledge and preferences for peripheral artery disease treatment.

BACKGROUND: Shared medical decision making requires patients' understanding of their disease and its treatment options. Peripheral artery disease (PAD) is a condition for which preference-sensitive treatments are available, but for which little is known about patients' knowledge and treatment preferences as it relates to specific treatment goals. METHODS: In a prospective, multicenter registry that involved patients with PAD experiencing claudication, the PORTRAIT Knowledge and Preferences Survey was administered at 1 year. It asks questions about PAD treatment choices, symptom relief options, disease management, and secondary prevention. PAD treatment preferences were also queried, and patients ranked 10 PAD treatment goals (1-10 Likert scale; 10 being most important). RESULTS: Among 281 participants completing the survey (44.8% women, mean age 69.6 ± 9.0 years), 54.1% knew that there was more than one way to treat PAD symptoms and 47.1% were offered more than one treatment option. Most (82.4%) acknowledged that they had to manage their PAD for the rest of their life. 'Avoid loss of toes or legs,' 'decreased risk of heart attack/stroke,' 'long-lasting treatment benefit,' 'living longer,' 'improved quality of life,' and 'doing what the doctor thinks I should do' had mean ratings > 9.0 (SD ranging between 1.21 and 2.00). More variability occurred for 'avoiding surgery.' 'cost of treatment,' 'timeline of pain relief,' and 'return to work' (SD ranging between 2.76 and 3.58). The single most important treatment goal was 'improving quality of life' (31.3%). CONCLUSIONS: Gaps exist in knowledge for patients with PAD who experience claudication, and there is a need for increased efforts to improve support for shared decision-making frameworks for symptomatic PAD.(ClinicalTrials.gov Identifier: NCT01419080).

Patient-level and external factors in the use of drug-coated balloons and drug-eluting stents in femoropopliteal endovascular interventions.

OBJECTIVE: Drug-coated balloons (DCB) and drug-eluting stents (DES) have been rapidly adopted for femoropopliteal endovascular interventions due to their favorable patency rates. It is unclear whether choice of using drug coated devices versus bare metal stents (BMS) or plain balloon angioplasty (POBA) as primary treatment in femoropopliteal disease is mostly associated with patient-level factors, safety concerns, or by operator preferences. This study sought to evaluate factors associated with their use in a contemporary dataset. METHODS: All femoropopliteal lesions treated with endovascular interventions between 2016 and 2019 from the Vascular Quality Initiative registry were included. For each procedure, a primary treatment was identified based on the following hierarchy: DES > DCB > BMS > POBA. A hierarchical logistic regression model predicting DCB or DES use included patient-level characteristics, key events (period after Centers for Medicare and Medicaid Services reimbursement change, January 2018 [vs before] and period after Katsanos meta-analysis December 2018 [vs before]), and random effects for site and operator. Operator-level variability for DCB and DES use was summarized with an adjusted median odds ratio (MOR). RESULTS: A total of 57,753 femoropopliteal endovascular procedures were included. Poor functional status (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.90-0.94), prior anticoagulant use (OR, 0.92; 95% CI, 0.87-0.97), higher Rutherford classification (OR, 0.86; 95% CI, 0.84-0.88), chronic kidney disease stage 4 or 5 (OR, 0.92; 95% CI, 0.86-0.98), and the period after the Katsanos meta-analysis publication (OR, 0.3; 95% CI, 0.29-0.32) were associated with a lower odds of DCB or DES use; whereas female sex (OR, 1.12; 95% CI,1.08-1.17), prior lesion treatment (OR, 1.17; 95% CI, 1.11-1.22), diabetes (OR, 1.07; 95% CI, 1.02-1.12), Trans-Atlantic Inter-Society Consensus class B (OR, 1.16; 95% CI, 1.09-1.24) and C (OR, 1.2; 95% CI, 1.12-1.28), and the period after the Centers for Medicare and Medicaid Services reimbursement change (OR, 1.08; 95% CI, 1.03-1.14) were associated with a higher odds of DCB or DES use. Significant variability in use was found across operators (adjusted MOR, 2.70; 95% CI, 2.55-2.85) and centers (adjusted MOR, 2.89; 95% CI, 2.50-3.27). CONCLUSIONS: DCB or DES use in femoropopliteal disease demonstrates wide variability across operators and is linked strongly with external factors, followed by anatomic lesion characteristics and a history of previous interventions. Future work needs to focus on tailoring DCB or DES use to patient and lesion characteristics and to develop appropriate use guidelines integrating these factors.

Does underlying infertility in natural conception modify the epigenetic control of imprinted genes and transposable elements in newborns?

RESEARCH QUESTION: Does the epigenetic control of imprinted genes and transposable elements at birth differ according to time to conception in natural conception and after intrauterine insemination (IUI)? DESIGN: A total of 144 singletons were included in four groups: 50 natural pregnancies obtained within 6 months after stopping contraception (group 1); 34 natural pregnancies with infertility period between 6 and 12 months (group 2); 36 pregnancies with an infertility period of more than 12 months (group 3) and 24 pregnancies obtained after IUI (group 4). RESULTS: The placental DNA methylation levels of H19/IGF2 and KCNQ1OT1 were lower in groups 2, 3 and 4 than in group 1 (P = 0.025 in the overall comparison). The DNA methylation rate for LINE-1 was higher in placentas from group 2 than in group 1 (P = 0.022). In cord blood, DNA methylation levels were not significantly different between groups except for H19/IGF2 for which the DNA methylation levels were higher in group 2 than in group 1 (H19/IGF2-seq1 and seq2: P = 0.023 and P = 0.002, respectively). In placenta tissue, compared with group 1, relative expression for SNRPN and for LINE-1 was significantly higher in group 2 (P = 0.002 and P < 0.001, respectively). The relative expression of KCNQ1 in placenta was lower in group 4 than in group 1 (P = 0.013). In cord blood, compared with group 1, the relative expression for H19 was significantly higher in group 3 (P = 0.026), and the relative expression of LINE-1 was higher in groups 2 and 3 and in group 4 (P < 0.001). CONCLUSIONS: Infertility itself, and not only ART techniques, could contribute to potential epigenetic risks for children.

Modeling excess hazard with time-to-cure as a parameter.

Cure models have been widely developed to estimate the cure fraction when some subjects never experience the event of interest. However, these models were rarely focused on the estimation of the time-to-cure, that is, the delay elapsed between the diagnosis and "the time from which cure is reached," an important indicator, for instance, to address the question of access to insurance or loans for subjects with personal history of cancer. We propose a new excess hazard regression model that includes the time-to-cure as a covariate-dependent parameter to be estimated. The model is written similarly to a Beta probability distribution function and is shown to be a particular case of the non-mixture cure models. Parameters are estimated through a maximum likelihood approach and simulation studies demonstrate good performance of the model. Illustrative applications to three cancer data sets are provided and some limitations as well as possible extensions of the model are discussed. The proposed model offers a simple and comprehensive way to estimate more accurately the time-to-cure.

Long-Term Relative Survival after Stroke: The Dijon Stroke Registry.

OBJECTIVE: The aim of this study was to assess long-term survival after stroke and to compare survival profiles of patients according to stroke subtypes, age, and sex, using relative survival (RS) method. METHODS: All patients with a first-ever stroke were prospectively recorded in the population-based Dijon Stroke Registry from 1987 to 2016. RS is the survival that would be observed if stroke was the only cause of death. Ten-year RS was estimated using a flexible parametric model of the cumulative excess mortality rate, which was obtained by matching the observed all-cause mortality in the stroke cohort to the expected mortality in the general population. A separate model was fitted for each stroke subtypes, first fitted for each age and sex separately, and then adjusted for age and sex. RESULTS: In total, 5,259 patients (mean age 74.9 ± 14.3 years, 53% women) were recorded including 4,469 ischemic strokes (IS), 655 intracerebral hemorrhages (ICH), and 135 undetermined strokes. In IS patients, unadjusted RS was 82% at 1 year and decreased to 62% at 10 years. Adjusted RS showed a lower survival in older age groups (p < 0.001), but no difference between men and women (p = 0.119). In ICH patients, unadjusted RS was 56 and 42% at 1 and 10 years, respectively, with a lower adjusted survival in older age groups (p < 0.001), but no sex differences (p = 0.184). CONCLUSION: This study showed that RS after stroke is lower in older than in younger patients but without significant sex differences, and survival profiles differ according to stroke subtypes. Since RS allows a better estimation of stroke-related death than observed survival does, especially in old patients, such a method is adapted to provide reliable information when considering long-term outcome.

Outcomes following polypectomy for malignant colorectal polyps are similar to those following surgery in the general population.

OBJECTIVE: Population-based studies on colorectal malignant polyps (MPs) are scarce. The aim of this study was to describe time trends in the incidence of colorectal MPs before and after the introduction of a colorectal mass-screening programmein 2003 and to assess outcomes (survival and recurrence) after endoscopic or surgical resection in patients with MPs. DESIGN: We included 411 patients with MPs diagnosed between 1982 and 2011 in a well-defined population. Age-standardised incidence rates were calculated. Univariate and multivariate 5-year recurrence and net survival analyses were performed according to gross morphology. RESULTS: Age-standardised incidence of MPs in patients aged 50-74 years doubled from 5.4 in 1982-2002 to 10.9 per 100 000 in 2003-2011. Pedunculated MPs were more frequently resected endoscopically (38.2%) than were sessile MPs (19.1%; p<0.001). For patients with pedunculated MPs and a pathological margin ≥1 mm, the 5 -year cumulative recurrence rate did not differ significantly between surgical and endoscopic resection (8.2% and 2.4%, respectively). For patients with sessile MPs, it was 3.0% after first-line or second-line surgical resection, 8.6% after endoscopic resection and 17.9% after transanal resection (p=0.016). The recurrence rate decreased dramatically for patients with sessile MPs from 11.3% (1982-2002) to 1.2% (2003-2009) (p=0.010) and remained stable for pedunculated MPs at 4.6% and 6.7%, respectively. Five-year net survival was 81.0% when pathological margins were <1 mm and 95.6% when ≥1 mm (p=0.024). CONCLUSION: Outcomes following polypectomy in patients with a pathological margin ≥1 mm are similar to those following surgery in the general population. Endoscopic resection needs to be completed by surgery if pathological margins are less than 1 mm.

Long-Term Mortality Predictors Using a Machine-Learning Approach in Patients With Chronic Limb-Threatening Ischemia After Peripheral Vascular Intervention.

BACKGROUND: Patients with chronic limb-threatening ischemia (CLTI) face a high long-term mortality risk. Identifying novel mortality predictors and risk profiles would enable individual health care plan design and improved survival. We aimed to leverage a random survival forest machine-learning algorithm to identify long-term all-cause mortality predictors in patients with CLTI undergoing peripheral vascular intervention. METHODS AND RESULTS: Patients with CLTI undergoing peripheral vascular intervention from 2017 to 2018 were derived from the Medicare-linked VQI (Vascular Quality Initiative) registry. We constructed a random survival forest to rank 66 preprocedural variables according to their relative importance and mean minimal depth for 3-year all-cause mortality. A random survival forest of 2000 trees was built using a training sample (80% of the cohort). Accuracy was assessed in a testing sample (20%) using continuous ranked probability score, Harrell C-index, and out-of-bag error rate. A total of 10 114 patients were included (mean±SD age, 72.0±11.0 years; 59% men). The 3-year mortality rate was 39.1%, with a median survival of 1.4 years (interquartile range, 0.7-2.0 years). The most predictive variables were chronic kidney disease, age, congestive heart failure, dementia, arrhythmias, requiring assisted care, living at home, and body mass index. A total of 41 variables spanning all domains of the biopsychosocial model were ranked as mortality predictors. The accuracy of the model was excellent (continuous ranked probability score, 0.172; Harrell C-index, 0.70; out-of-bag error rate, 29.7%). CONCLUSIONS: Our random survival forest accurately predicts long-term CLTI mortality, which is driven by demographic, functional, behavioral, and medical comorbidities. Broadening frameworks of risk and refining health care plans to include multidimensional risk factors could improve individualized care for CLTI.