Comparative Effectiveness of BNT162b2 and mRNA-1273 Vaccines in U.S. Veterans.

BACKGROUND: The messenger RNA (mRNA)-based vaccines BNT162b2 and mRNA-1273 are more than 90% effective against coronavirus disease 2019 (Covid-19). However, their comparative effectiveness for a range of outcomes across diverse populations is unknown. METHODS: We emulated a target trial using the electronic health records of U.S. veterans who received a first dose of the BNT162b2 or mRNA-1273 vaccine between January 4 and May 14, 2021, during a period marked by predominance of the SARS-CoV-2 B.1.1.7 (alpha) variant. We matched recipients of each vaccine in a 1:1 ratio according to their risk factors. Outcomes included documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, symptomatic Covid-19, hospitalization for Covid-19, admission to an intensive care unit (ICU) for Covid-19, and death from Covid-19. We estimated risks using the Kaplan-Meier estimator. To assess the influence of the B.1.617.2 (delta) variant, we emulated a second target trial that involved veterans vaccinated between July 1 and September 20, 2021. RESULTS: Each vaccine group included 219,842 persons. Over 24 weeks of follow-up in a period marked by alpha-variant predominance, the estimated risk of documented infection was 5.75 events per 1000 persons (95% confidence interval [CI], 5.39 to 6.23) in the BNT162b2 group and 4.52 events per 1000 persons (95% CI, 4.17 to 4.84) in the mRNA-1273 group. The excess number of events per 1000 persons for BNT162b2 as compared with mRNA-1273 was 1.23 (95% CI, 0.72 to 1.81) for documented infection, 0.44 (95% CI, 0.25 to 0.70) for symptomatic Covid-19, 0.55 (95% CI, 0.36 to 0.83) for hospitalization for Covid-19, 0.10 (95% CI, 0.00 to 0.26) for ICU admission for Covid-19, and 0.02 (95% CI, -0.06 to 0.12) for death from Covid-19. The corresponding excess risk (BNT162b2 vs. mRNA-1273) of documented infection over 12 weeks of follow-up in a period marked by delta-variant predominance was 6.54 events per 1000 persons (95% CI, -2.58 to 11.82). CONCLUSIONS: The 24-week risk of Covid-19 outcomes was low after vaccination with mRNA-1273 or BNT162b2, although risks were lower with mRNA-1273 than with BNT162b2. This pattern was consistent across periods marked by alpha- and delta-variant predominance. (Funded by the Department of Veterans Affairs and others.).

Estimating the effect of bariatric surgery on cardiovascular events using observational data?

BACKGROUND: Observational studies have estimated strongly protective effects of bariatric surgery on cardiovascular disease, but with oversimplified definitions of the intervention, eligibility criteria, and follow-up, which deviate from those in a randomized trial. We describe studying the effect of bariatric surgery on cardiovascular disease without introducing these sources of bias, which may not be entirely possible with existing observational data. METHODS: We propose target trials among persons with diabetes: (1) bariatric operation (vs. no operation) among individuals who have undergone pre-operative preparation (lifestyle modifications, screening) and (2) pre-operative preparation and bariatric surgery (vs. neither pre-operative nor operative component). RESULTS: We emulated both target trials using observational data of U.S. veterans. Comparing bariatric surgery with no surgery (target trial #1; 8,087 individuals), the 7-year cardiovascular risk was 18.0% (95% CI, 6.9 to 32.7) in the surgery group and 18.9% (95% CI, 17.7 to 20.1) in the no surgery group (risk difference -0.9, 95% CI -12.0 to 14.0). Comparing pre-operative components plus surgery vs. neither (target trial #2; 10,065 individuals), the 7-year cardiovascular risk was 17.4% (95% CI, 13.6 to 22.0) in the surgery group and 18.8% (95% CI, 17.8 to 19.9) in the no surgery group (risk difference -1.4, 95% CI -5.1 to 3.2). Body mass index and hemoglobin A1c were reduced with bariatric interventions in both emulations. CONCLUSIONS: Within limitations of available observational data, our estimates do not provide evidence that bariatric surgery reduces cardiovascular disease and support equipoise for a randomized trial of bariatric surgery for cardiovascular disease prevention.

Comparison of the Test-negative Design and Cohort Design With Explicit Target Trial Emulation for Evaluating COVID-19 Vaccine Effectiveness.

BACKGROUND: Observational studies are used for estimating vaccine effectiveness under real-world conditions. The practical performance of two common approaches-cohort and test-negative designs-need to be compared for COVID-19 vaccines. METHODS: We compared the cohort and test-negative designs to estimate the effectiveness of the BNT162b2 vaccine against COVID-19 outcomes using nationwide data from the United States Department of Veterans Affairs. Specifically, we (1) explicitly emulated a target trial using follow-up data and evaluated the potential for confounding using negative controls and benchmarking to a randomized trial, (2) performed case-control sampling of the cohort to confirm empirically that the same estimate is obtained, (3) further restricted the sampling to person-days with a test, and (4) implemented additional features of a test-negative design. We also compared their performance in limited datasets. RESULTS: Estimated BNT162b2 vaccine effectiveness was similar under all four designs. Empirical results suggested limited residual confounding by healthcare-seeking behavior. Analyses in limited datasets showed evidence of residual confounding, with estimates biased downward in the cohort design and upward in the test-negative design. CONCLUSION: Vaccine effectiveness estimates under a cohort design with explicit target trial emulation and a test-negative design were similar when using rich information from the VA healthcare system, but diverged in opposite directions when using a limited dataset. In settings like ours with sufficient information on confounders and other key variables, the cohort design with explicit target trial emulation may be preferable as a principled approach that allows estimation of absolute risks and facilitates interpretation of effect estimates.

Addressing the longitudinal components of surgical treatments.

Despite their pre- and postoperative components, surgical treatment strategies have typically been cast as point interventions in causal inference research. When longitudinal perioperative components affect outcomes of interest, leaving them unspecified or failing to measure adherence to them complicates the interpretation of effect estimates. Inspired by two recent landmark trials that assessed the risk of stroke or death after transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR), the PARTNER 3 trial and the Evolut Low Risk trial, we discuss possible ways that different postoperative therapies in treatment arms and incomplete adherence to those therapies can impact the interpretation of intention-to-treat effect estimates in surgical trials. We argue that surgical treatments are not necessarily point interventions, and make recommendations for improving the design and analysis of trials involving surgical interventions. Central to these recommendations is the need for investigators to specify and report adherence to longitudinal perioperative treatment components.

Early Convalescent Plasma Therapy and Mortality Among US Veterans Hospitalized With Nonsevere COVID-19: An Observational Analysis Emulating a Target Trial.

BACKGROUND: Early convalescent plasma transfusion may reduce mortality in patients with nonsevere coronavirus disease 2019 (COVID-19). METHODS: This study emulates a (hypothetical) target trial using observational data from a cohort of US veterans admitted to a Department of Veterans Affairs (VA) facility between 1 May and 17 November 2020 with nonsevere COVID-19. The intervention was convalescent plasma initiated within 2 days of eligibility. Thirty-day mortality was compared using cumulative incidence curves, risk differences, and hazard ratios estimated from pooled logistic models with inverse probability weighting to adjust for confounding. RESULTS: Of 11 269 eligible person-trials contributed by 4755 patients, 402 trials were assigned to the convalescent plasma group. Forty and 671 deaths occurred within the plasma and nonplasma groups, respectively. The estimated 30-day mortality risk was 6.5% (95% confidence interval [CI], 4.0%-9.7%) in the plasma group and 6.2% (95% CI, 5.6%-7.0%) in the nonplasma group. The associated risk difference was 0.30% (95% CI, -2.30% to 3.60%) and the hazard ratio was 1.04 (95% CI, .64-1.62). CONCLUSIONS: Our target trial emulation estimated no meaningful differences in 30-day mortality between nonsevere COVID-19 patients treated and untreated with convalescent plasma. Clinical Trials Registration. NCT04545047.

Strengthening Health Services Research Using Target Trial Emulation: An Application to Volume-Outcomes Studies.

The number of operations that surgeons have previously performed is associated with their patients' outcomes. However, this association may not be causal, because previous studies have often been cross-sectional and their analyses have not considered time-varying confounding or positivity violations. In this paper, using the example of surgeons who perform coronary artery bypass grafting, we describe (hypothetical) target trials for estimation of the causal effect of the surgeons' operative volumes on patient mortality. We then demonstrate how to emulate these target trials using data from US Medicare claims and provide effect estimates. Our target trial emulations suggest that interventions on physicians' volume of coronary artery bypass grafting operations have little effect on patient mortality. The target trial framework highlights key assumptions and draws attention to areas of bias in previous observational analyses that deviated from their implicit target trials. The principles of the presented methodology may be adapted to other scenarios of substantive interest in health services research.

Association and interplay of surgeon and hospital volume with mortality after open abdominal aortic aneurysm repair in the modern era.

OBJECTIVE: Operative volume has been used as a marker of quality. Research from previous decades has suggested minimum open abdominal aortic aneurysm (AAA) repair volume requirements for surgeons of 9 to 13 open AAA repairs annually and for hospitals of 18 open AAA repairs annually to purportedly achieve acceptable results. Given concerns regarding the decreased frequency of open repairs in the endovascular era, we examined the association of surgeon and hospital volume with the 30- and 90-day mortality in the Vascular Quality Initiative (VQI) registry. METHODS: Patients who had undergone elective open AAA repair from 2013 to 2018 were identified in the VQI registry. We performed a cross-sectional evaluation of the association between the average hospital and surgeon volume and 30-day postoperative mortality using a hierarchical Bayesian model. Cross-level interactions were permitted, and random surgeon- and hospital-level intercepts were used to account for clustering. The mortality results were adjusted by standardizing to the observed distribution of relevant covariates in the overall cohort. The outcomes were compared to the Society for Vascular Surgery guidelines recommended criteria of <5% perioperative mortality. RESULTS: A total of 3078 patients had undergone elective open AAA repair by 520 surgeons at 128 hospitals. The 30- and 90-day risks of postoperative mortality were 4.1% (n = 126) and 5.4% (n = 166), respectively. The mean surgeon volume and hospital volume both correlated inversely with the 30-day mortality. Averaged across all patients and hospitals, we found a 96% probability that surgeons who performed an average of four or more repairs per year achieved <5% 30-day mortality. Substantial interplay was present between surgeon volume and hospital volume. For example, at lower volume hospitals performing an average of five repairs annually, <5% 30-day mortality would be expected 69% of the time for surgeons performing an average of three operations annually. In contrast, at higher volume hospitals performing an average of 40 repairs annually, a <5% 30-day mortality would be expected 96% of the time for surgeons performing an average of three operations annually. As hospital volume increased, a diminishing difference occurred in 30-day mortality between lower and higher volume surgeons. Likewise, as surgeon volume increased, a diminishing difference was found in 30-day mortality between the lower and higher volume hospitals. CONCLUSIONS: Surgeons and hospitals in the VQI registry achieved mortality outcomes of <5% (Society for Vascular Surgery guidelines), with an average surgeon volume that was substantially lower compared with previous reports. Furthermore, when considering the development of minimal surgeon volume guidelines, it is important to contextualize the outcomes within the hospital volumes.

Variation in complications and mortality following ALPPS at early-adopting centers.

BACKGROUND: Various, often conflicting, estimates for post-operative morbidity and mortality following ALPPS have been reported in the literature, suggesting that considerable center-level variation exists. Some of this variation may be related to center volume and experience. METHODS: Using data from seventeen centers who were early adopters of the ALPPS technique, we estimated the variation, by center, in standardized 90-day mortality and comprehensive complication index (CCI) for patients treated between 2012 and 2018. RESULTS: We estimated that center-specific 90-day mortality following treatment with ALPPS varied from 4.2% (95% CI: 0.8, 9.9) to 29.1% (95% CI: 13.9, 50.9), and that center-specific CCI following treatment with ALPPS varied from 17.0 (95% CI: 7.5, 26.5) to 49.8 (95% CI: 38.1, 61.8). Declines in estimated 90-day mortality and CCI were observed over time, and almost all individual centers followed this trend. Patients treated at centers with a higher number of ALPPS cases performed over the prior year had a lower risk of post-operative mortality. CONCLUSION: Despite considerable center-level variation in ALPPS outcomes, perioperative outcomes following ALPPS have improved over time and treatment at higher volume centers results in a lower risk of 90-day mortality. Morbidity and mortality remain concerningly high at some centers.

Opioid Prescription Patterns for Children Following Laparoscopic Appendectomy.

OBJECTIVE: To describe variability in and consequences of opioid prescriptions following pediatric laparoscopic appendectomy. SUMMARY BACKGROUND DATA: Postoperative opioid prescribing patterns may contribute to persistent opioid use in both adults and children. METHODS: We included children <18 years enrolled as dependents in the Military Health System Data Repository who underwent uncomplicated laparoscopic appendectomy (2006-2014). For the primary outcome of days of opioids prescribed, we evaluated associations with discharging service, standardized to the distribution of baseline covariates. Secondary outcomes included refill, Emergency Department (ED) visit for constipation, and ED visit for pain. RESULTS: Among 6732 children, 68% were prescribed opioids (range = 1-65 d, median = 4 d, IQR = 3-5 d). Patients discharged by general surgery services were prescribed 1.23 (95% CI = 1.06-1.42) excess days of opioids, compared with those discharged by pediatric surgery services. Risk of ED visit for constipation (n = 61, 1%) was increased with opioid prescription [1-3 d, risk ratio (RR) = 2.46, 95% CI = 1.31-5.78; 4-6 d, RR = 1.89, 95% CI = 0.83-4.67; 7-14 d, RR = 3.75, 95% CI = 1.38-9.44; >14 d, RR = 6.27, 95% CI = 1.23-19.68], compared with no opioid prescription. There was similar or increased risk of ED visit for pain (n = 319, 5%) with opioid prescription [1-3 d, RR = 1.00, 95% confidence interval (CI) = 0.74-1.32; 4-6 d, RR = 1.31, 95% CI = 0.99-1.73; 7-14 d, RR = 1.52, 95% CI = 1.00-2.18], compared with no opioid prescription. Likewise, need for refill (n = 157, 3%) was not associated with initial days of opioid prescribed (reference 1-3 d; 4-6 d, RR = 0.96, 95% CI = 0.68-1.35; 7-14 d, RR = 0.91, 95% CI = 0.49-1.46; and >14 d, RR = 1.22, 95% CI = 0.59-2.07). CONCLUSIONS: There was substantial variation in opioid prescribing patterns. Opioid prescription duration increased risk of ED visits for constipation, but not for pain or refill.

Adjusting for adherence in randomized trials when adherence is measured as a continuous variable: An application to the Lipid Research Clinics Coronary Primary Prevention Trial.

BACKGROUND: Clinicians and patients may be more interested in per-protocol effect estimates than intention-to-treat effect estimates from randomized trials. However, per-protocol effect estimates may be biased due to insufficient adjustment for prognostic factors that predict adherence. Adjustment for this bias is possible when appropriate methods, such as inverse probability weighting, are used. But, when adherence is measured as a continuous variable, constructing these weights can be challenging. METHODS: In the placebo arm of the Lipid Research Clinics Coronary Primary Prevention Trial, we estimated the 7-year cumulative incidence of coronary heart disease under 100% adherence and 0% adherence to placebo. We used dose-response discrete-hazards models with inverse probability weighting to adjust for pre- and post-randomization covariates. We considered several continuous distributions for constructing the inverse probability weights. RESULTS: The risk difference estimate for 100% adherence compared with 0% adherence ranged from -7.7 to -6.1 percentage points without adjustment for baseline and post-baseline covariates, and ranged from -1.8 to 2.2 percentage points with adjustment using inverse probability weights, depending on the dose-response model and inverse probability weight distribution used. CONCLUSIONS: Methods which appropriately adjust for time-varying post-randomization variables can explain away much of the bias in the "effect" of adherence to placebo. When considering continuous adherence, investigators should consider several models as estimates may be sensitive to the model chosen.

Therapeutic Impact and Complications Associated with Surgical Lung Biopsy after Allogeneic Hematopoietic Stem Cell Transplantation in Children.

Hematopoietic stem cell transplantation (HSCT) in the pediatric population is associated with pulmonary complications in 25% of recipients. The role of surgical lung biopsy (SLB) remains unclear because of concerns about both the therapeutic impact and morbidity associated with the procedure. A retrospective review of consecutive allogeneic HSCT recipients at Dana-Farber and Boston Children's Hospital Cancer and Blood Disorders Center between 2006 and 2016 was performed. All recipients who underwent SLB during the study period were identified and charts reviewed for perioperative complications, histopathologic findings, and changes in therapy delivered. Pearson's chi-square test and Student's t-test (or appropriate nonparametric test) were used to evaluate the associations between perioperative complication and categorical and continuous variables, respectively. Five hundred fifty-five HSCTs were included, among which 48 SLBs (8.6%) were identified. Median follow-up time was 24 months (range, 0 to 139). Thirty-day postoperative morbidity was 16.7% and 30-day postoperative mortality 10.4% (n = 5). The overall 30-day postoperative complication rate (including mortality) was 20.8% (n = 10). No mortalities were directly attributable to SLB. Definitive diagnoses were identified in 70.8% of SLBs (n = 34), and therapeutic changes occurred in 79.2% (n = 38). Overall, 83.3% of SLBs (n = 40) either provided a diagnosis or led to a change in therapy. SLB has an acceptable risk of perioperative complications in this medically complicated and often severely ill population. In most HSCT patients, SLB aids in defining the etiology of pulmonary infiltrates and can inform therapeutic decisions in patients where noninvasive diagnostic modalities have failed to provide a definitive diagnosis.

Late-onset anorectal disease and psychosocial impact in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

BACKGROUND: The prevalence and associated psychosocial morbidity of late-onset anorectal disease after surgery and radiotherapy for the treatment of childhood cancer are not known. METHODS: A total of 25,530 survivors diagnosed between 1970 and 1999 (median age at cancer diagnosis, 6.1 years; age at survey, 30.2 years) and 5036 siblings were evaluated for late-onset anorectal disease, which was defined as a self-reported fistula-in-ano, self-reported anorectal stricture, or pathology- or medical record-confirmed anorectal subsequent malignant neoplasm (SMN) 5 or more years after the primary cancer diagnosis. Piecewise exponential models compared the survivors and siblings and examined associations between cancer treatments and late-onset anorectal disease. Multiple logistic regression with generalized estimating equations was used to evaluate associations between late-onset anorectal disease and emotional distress, as defined by the Brief Symptom Inventory 18 (BSI-18), and health-related quality of life, as defined by the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). RESULTS: By 45 years after the diagnosis, 394 survivors (fistula, n = 291; stricture, n = 116; anorectal SMN, n = 26) and 84 siblings (fistula, n = 73; stricture, n = 23; anorectal neoplasm, n = 1) had developed late-onset anorectal disease (adjusted rate ratio [RR] for survivors vs siblings, 1.2; 95% confidence interval [CI], 1.0-1.5). Among survivors, pelvic radiotherapy with ≥30 Gy within 5 years of the cancer diagnosis was associated with late-onset anorectal disease (adjusted RR for 30-49.9 Gy vs none, 1.6; 95% CI, 1.1-2.3; adjusted RR for ≥50 Gy vs none, 5.4; 95% CI, 3.1-9.2). Late-onset anorectal disease was associated with psychosocial impairment in all BSI-18 and SF-36 domains. CONCLUSIONS: Late-onset anorectal disease was more common among childhood cancer survivors who received higher doses of pelvic radiotherapy and was associated with substantial psychosocial morbidity.

The meaning of confounding adjustment in the presence of multiple versions of treatment: an application to organ transplantation.

Causal inference for treatments with many versions requires a careful specification of the versions of treatment. Specifically, the existence of multiple relevant versions of treatment has implications for the selection of confounders. To illustrate this, we estimate the effect of organ transplantation using grafts from donors who died due to anoxic drug overdose, on recipient graft survival in the US. We describe how explicitly outlining the target trial (i.e. the hypothetical randomized trial which would answer the causal question of interest) to be emulated by an observational study analysis helps conceptualize treatment versions, guides selection of appropriate adjustment variables, and helps clarify the settings in which causal effects of compound treatments will be of value to decision-makers.

Comparison of Military Health System Data Repository and American College of Surgeons National Surgical Quality Improvement Program-Pediatric.

BACKGROUND: Given the rarity of pediatric surgical disease, it is important to consider available large-scale data resources as a means to better study and understand relevant disease-processes and their treatments. The Military Health System Data Repository (MDR) includes claims-based information for > 3 million pediatric patients who are dependents of members and retirees of the United States Armed Services, but has not been externally validated. We hypothesized that demographics and selected outcome metrics would be similar between MDR and the previously validated American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P) for several common pediatric surgical operations. METHODS: We selected five commonly performed pediatric surgical operations: appendectomy, pyeloplasty, pyloromyotomy, spinal arthrodesis for scoliosis, and facial reconstruction for cleft palate. Among children who underwent these operations, we compared demographics (age, sex, and race) and clinical outcomes (length of hospital stay [LOS] and mortality) in the MDR and NSQIP-P, including all available overlapping years (2012-2014). RESULTS: Age, sex, and race were generally similar between the NSQIP-P and MDR. Specifically, these demographics were generally similar between the resources for appendectomy (NSQIP-P, n = 20,602 vs. MDR, n = 4363; median age 11 vs. 12 years; female 40% vs. 41%; white 75% vs. 84%), pyeloplasty (NSQIP-P, n = 786 vs. MDR, n = 112; median age 0.9 vs. 2 years; female 28% vs. 28%; white 71% vs. 80%), pyloromyotomy, (NSQIP-P, n = 3827 vs. MDR, n = 227; median age 34 vs. < 1 year, female 17% vs. 16%; white 76% vs. 89%), scoliosis surgery (NSQIP-P, n = 5743 vs. MDR, n = 95; median age 14.2 vs. 14 years; female 75% vs. 67%; white 72% vs. 75%), and cleft lip/palate repair (NSQIP-P, n = 6202 vs. MDR, n = 749; median age, 1 vs. 1 year; female 42% vs. 45%; white 69% vs. 84%). Length of stay and 30-day mortality were similar between resources. LOS and 30-day mortality were also similar between datasets. CONCLUSION: For the selected common pediatric surgical operations, patients included in the MDR were comparable to those included in the validated NSQIP-P. The MDR may comprise a valuable clinical outcomes research resource, especially for studying infrequent diseases with follow-up beyond the 30-day peri-operative period.

Thirty-year trends in aortofemoral bypass for aortoiliac occlusive disease.

OBJECTIVE: Endovascular intervention has supplanted open bypass as the most frequently used approach in patients with aortoiliac segment atherosclerosis. We sought to determine whether this trend together with changing demographic and clinical characteristics of patients undergoing aortobifemoral bypass (ABFB) for aortoiliac occlusive disease (AOD) have an association with postoperative outcomes. METHODS: Using a prospectively maintained institutional database, we identified patients who underwent ABFB for AOD from 1985 to 2015. Patients were divided into two cohorts: the historical cohort (HC) included patients who underwent ABFB for AOD from 1985 to 1999 and the contemporary cohort (CC) who underwent ABFB for AOD from 2000 to 2015. Medical and demographic data, procedural information, postoperative complications, and follow-up data were extracted. Cox proportional hazards regression was used to evaluate associations with the end point of primary patency. A similar analysis was performed for major adverse limb events (MALEs; the composite of above-ankle amputation, major reintervention, graft revision, or new bypass graft of the index limb) in the subset of patients with critical limb ischemia. RESULTS: There were a total of 359 cases: 226 in the HC and 133 in the CC. The CC had more women (56.4% vs 43.8%; P = .02), smokers (87.2% vs 67.7%; P = .001), and patients who failed prior aortoiliac endovascular intervention (17.3% vs 4.8%; P = .0001), but fewer patients with coronary artery disease (32.3% vs 47.3%; P = .005). Thirty-day mortality was less than 1% in both cohorts, but 10-year survival was higher in the CC (67.7% vs 52.6%; P = .02). Five-year primary, primary-assisted, and secondary patency were higher in the HC (93.3% vs 82.2%; P = .005; 93.8% vs 85.7%; P = .02; 97.5% vs 90.4%; P = .02, respectively). CC membership, decreasing age, prior aortic surgery, and decreasing graft diameter were significant independent predictors of loss of primary patency after adjustment (hazard ratio [HR], 7.03; 95% confidence interval [CI], 2.80-17.63; P < .0001; HR, 0.93; 95% CI, 0.90-0.96; P < .0001; HR, 18.80; 95% CI, 5.94-59.58; P < .0001; and HR, 0.73; 95% CI, 0.55-0.95; P = .02, respectively). Similarly, CC membership, prior aortic surgery, and decreasing graft diameter were significant independent predictors of MALE in the critical limb ischemia cohort after adjustment (HR, 21.13; 95% CI, 4.20-106.40; P = .0002; HR, 40.40; 95% CI, 3.23-505.61; P = .004; and HR, 0.51; 95% CI, 0.30-0.86; P = .01, respectively). CONCLUSIONS: Compared with the pre-endovascular era, demographic and clinical characteristics of patients undergoing ABFB for AOD in the CC have changed. Although long-term patency is slightly lower among patients in the CC during which a substantial subset of AOD patients are being treated primarily via the endovascular approach, durability remains excellent and limb salvage unchanged. After adjustment, the time period of index ABFB independently predicted primary patency and MALE, as did graft diameter and prior aortic surgery. These changing characteristics should be considered when counseling patients and benchmarking for reintervention rates and other outcomes.

Insurance status and pediatric mortality in nonaccidental trauma.

BACKGROUND: Nonaccidental trauma (NAT) is a leading cause of injury and death in early childhood. We sought to understand the association between insurance status and mortality in a national sample of pediatric NAT patients. MATERIALS AND METHODS: We performed a retrospective cohort study using the 2012-2014 National Trauma Databank. We included children ≤18 y hospitalized with NAT (The International Classification of Diseases, Ninth Revision codes: E967-968). The primary exposure was insurance status (categorized as public, private, and uninsured). The primary outcome was emergency department or inpatient mortality from NAT. RESULTS: We identified 6389 children with NAT. Mean age was 1.6 y (standard deviation 3.7), with 41% female and 42% of an ethnic or racial minority. Most were publicly insured (77%), with 17% privately insured and 6% uninsured. Mean injury severity score (ISS) was 13.9 (standard deviation 10.3). Overall, 516 (8%) patients died following NAT. Compared to patients who survived, those who died were more likely to be younger (mean age 1.0 y versus 1.6 y; P < 0.001), uninsured (13% versus 6%; P < 0.001), transferred to a higher-care facility (57% versus 49%; P < 0.001), and more severely injured (mean ISS 25.9 versus 12.8; P < 0.001). After adjusting for age, race, transfer status, and ISS, uninsured patients had 3.3-fold (95% CI = 2.4-4.6) greater odds of death compared to those with public insurance. For every 1 point increase in ISS, children had 12% (95% CI = 11%-13%) increased adjusted odds of death. CONCLUSIONS: Pediatric patients without insurance had significantly greater odds of death following NAT, compared to children with public insurance. Knowledge that uninsured children comprise an especially vulnerable population is important for targeting potential interventions.

High dose-rate brachytherapy for the treatment of lower extremity in-stent restenosis.

OBJECTIVE: Historically, edge stenosis and late thrombosis limited the effectiveness of adjunctive endovascular brachytherapy (EVBT) for in-stent restenosis (ISR) after percutaneous transluminal angioplasty (PTA) and stenting. We evaluated an updated protocol of PTA and EVBT for ISR among patients with lower extremity occlusive disease. METHODS: This is a retrospective, single-center review of patients treated with PTA and EVBT for ISR in the iliac and femoropopliteal segments between 2004 and 2012. A dose of 20 Gy was given at a depth of 0.5 mm beyond the radius of the largest PTA balloon using iridium 192, with at least 2-cm-long margins of radiation coverage proximal and distal to the injured area. Stents were assessed for patency by duplex ultrasound imaging at 1, 3, 6, 9, 12, and 18 months and then yearly. The primary end point was freedom from ≥50% restenosis in the treated segment at 6 months, 1 year, and 2 years. Patency data were estimated using the Kaplan-Meier method. Secondary end points were early and late thrombotic occlusion. RESULTS: Among 42 consecutive cases in 35 patients of EVBT for ISR in common or external iliac (9 [20.8%]) and superficial femoral or popliteal (33 [76.7%]) arteries, or both, 21 patients (50%) had claudication, asymptomatic hemodynamically significant stenoses were identified on duplex ultrasound imaging in 16 (38.1%), and 4 (9.8%) had critical limb ischemia. Mean treated length was 23.5 ± 12.3 cm over a mean duration of 16.1 ± 9.6 minutes. There was one technical failure (2.3%). Median post-EVBT follow-up time was 682 days (range, 1-2262 days). There were two (4.9%) and five (11.9%) cases of early and late thrombotic occlusions, respectively. There was one death, believed to be secondary to acute coronary syndrome. Primary, assisted primary, and secondary patency in the entire cohort was 75.2%, 89.1%, and 89.1%, respectively, at 1 year and 63.7%, 80.6%, and 85.6%, respectively, at 2 years. CONCLUSIONS: This contemporary protocol of PTA and adjunctive EVBT for lower extremity ISR, which is updated from those used in prior trials and includes a surveillance strategy that identifies at-risk stents for reintervention before occlusion, may be a promising treatment for lower extremity ISR at institutions where a close collaboration between vascular surgeons and radiation oncologists is feasible.

The role of thymectomy in the treatment of juvenile myasthenia gravis: a systematic review.

BACKGROUND: The role of thymectomy in the treatment of juvenile myasthenia gravis (JMG) is poorly defined. The objective of this systematic review was to evaluate the effect of thymectomy on survival, disease severity, and peri-operative complications for patients with JMG. METHODS: A search of MEDLINE, EMBASE, and the Cochrane Library (1/1/2000-3/1/2016) identified all English language, human studies of thymectomy for JMG. The population was patients with JMG age ≤18 years who underwent thymectomy (comparator group was unexposed to thymectomy). Outcomes included survival, disease severity, and post-operative complications. Data extraction was performed by independent reviewers. RESULTS: Sixteen retrospective studies included 1131 participants with JMG and 488 (43%) underwent thymectomy. Post-operative improvement in JMG severity occurred for 77% (n = 376/488). Comparisons of thymectomy to non-operative management were mixed. Post-operative complications were poorly recorded. Power to compare surgical approaches was limited. Outcomes specific to antibodies, surgical pathology findings, severity of JMG, and timing of thymectomy were sparse. CONCLUSIONS: Existing data regarding thymectomy for JMG are limited and entirely retrospective. The majority of patients who underwent thymectomy had improvement in disease severity and post-operative complications were rare. Prospective, multicenter study of thymectomy for JMG is warranted.

Safety of peritoneal and pleural drain placement in pediatric stem cell transplant recipients with severe veno-occlusive disease.

Hepatic VOD (veno-occlusive disease) is a serious complication of HSCT (hematopoietic stem cell transplantation) and has historically been associated with high mortality. This obstruction to hepatic flow often results in fluid collections in the peritoneal and pleural cavities. Catheter placement to drain ascites or pleural fluid may reduce intra-abdominal hypertension and/or improve respiratory parameters. The safety of these interventions among critically ill, immunocompromised children is unknown. Among 32 HSCT recipients (2000-2012) with severe VOD, we assessed the primary outcome of procedural complication from peritoneal drain placement. Twenty-four (75%) patients underwent peritoneal drain placement. No patient sustained visceral perforation or hemorrhage with drain placement. Overall mortality was 47% (n = 15). The procedure was not associated with increased overall mortality (p > 0.99). Eight (25%) peritoneal drains required replacement for malfunction. Of 24 patients with peritoneal drains, one (4%) patient had a positive culture from ascitic fluid. Eight (25%) patients underwent pleural drain placement. No pleural drain-related procedural complication or infection occurred. Four (50%) of the eight patients with pleural drains had de-escalation in oxygen requirement at drain removal, compared to time of placement. In this study, peritoneal and pleural drains were safe interventions for children with severe VOD.

Safety and efficacy of single-stage conversion of failed adjustable gastric band to laparoscopic Roux-en-Y gastric bypass: a case-control study.

BACKGROUND: We conducted the following study to evaluate the safety and efficacy of single-stage conversion of failed laparoscopic adjustable gastric band (LAGB) to laparoscopic Roux-en-Y gastric bypass (LRYGB) as compared to a cohort of primary LRYGB patients. METHODS: A single-institution, prospectively maintained bariatric database was used to retrospectively identify consecutive patients who underwent single-stage removal of LAGB with concomitant conversion to LRYGB between the years of 2007 and 2013. The study cohort was matched 1:1 for age, gender, body mass index (BMI), and approximate date of operation to patients who underwent primary LRYGB. Primary endpoints were operative time, complication rate, length of hospital stay (LOS), and percent excess BMI lost (%EBMIL) at 24-month follow-up. RESULTS: Ninety-four conversion patients met inclusion criteria. There were no statistically significant differences in the mean LOS (3.1 vs. 3.0 days, p = 0.97) or the major complication rate (3.2 vs. 1.1 %, p = 0.62) at 30 days postoperatively. Likewise, 30-day minor complication rates, including readmission, were similar between groups (7.5 vs. 6.4 %, p = 0.77). The average operative time was significantly longer for conversion compared to primary LRYGB (193.5 vs. 132 min; p < 0.01). At most recent follow-up after conversion or primary LRYGB, median %EBMIL was 61.3 and 77.3 % (p < 0.01), percent total weight loss was 23.6 and 30.5 % (p < 0.01), and percent change in BMI was 23.4 and 30.5 % (p < 0.01), respectively. Median follow-up time was 17 and 18.6 months after conversion and primary LRYGB, respectively. CONCLUSION: Single-stage conversion of LAGB to LRYGB is safe with an acceptable complication rate and similar LOS compared to primary LRYGB.