Comparative effectiveness of azathioprine and mycophenolate mofetil for myasthenia gravis (PROMISE-MG): a prospective cohort study.

BACKGROUND: Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. Treatment typically includes symptomatic oral cholinesterase inhibitors, immunosuppression, and immunomodulation. In addition to corticosteroids, azathioprine and mycophenolate mofetil are the most frequently used immunosuppressants in North America. We aimed to evaluate the comparative effectiveness of these two drugs, and to assess the effect of the dose and duration of treatment. METHODS: We did a prospective cohort study at 19 academic centres in Canada and the USA. We included patients (aged ≥18 years) with autoimmune myasthenia gravis, who were never treated with immunosuppressants. Treating clinicians determined the choice of medication, dose, follow-up intervals, and drug monitoring. Outcome measures and adverse events were recorded at each visit. We assessed two co-primary outcomes. The first was the patient-reported Myasthenia Gravis-Quality of Life 15-revised (MGQOL-15r) score, measured as the mean change from treatment initiation to the follow-up visit with the lowest score. A clinically meaningful reduction (CMR) in MGQOL-15r was defined as a 5-point decrease. The second was a composite clinical outcome of disease improvement (Myasthenia Gravis Foundation of America Post-Intervention Status Minimal Manifestations or better) and low adverse event burden (defined as grade ≤1 Common Terminology Criteria for Adverse Events). We also compared these outcomes in patients receiving an adequate dose and duration of azathioprine (≥2 mg/kg per day for at least 12 months) or mycophenolate mofetil (≥2 g per day for at least 8 months) and a lower dose or shorter duration of these agents. We used propensity score weighting with generalised linear regression models. This study is registered with ClinicalTrials.gov (NCT03490539). FINDINGS: Between May 1, 2018, and Aug 31, 2020, 167 patients were enrolled; 85 did not receive azathioprine or mycophenolate mofetil and were excluded. Four were excluded from outcome analyses because they had scores of 0 on an outcome measure at treatment initiation. Of the 78 patients included in analyses, 47 received mycophenolate mofetil (median follow-up 25 months [IQR 13·5-31·5]) and 31 received azathioprine (median follow-up 20 months [IQR 13-30]). The mean change in MG-QOL15r was -10·4 (95% CI -18·9 to -1·3) with mycophenolate mofetil and -6·8 (-17·2 to 3·6) with azathioprine (mean difference -3·3, 95% CI -7·7 to 1·2; p=0·15). 38 (81%) of 47 patients receiving mycophenolate mofetil and 18 (57%) of 31 receiving azathioprine had a CMR in MG-QOL15r (risk difference 24·0%; 95% CI -0·2 to 48·0; p=0·052). The clinical composite outcome was achieved in 22 (47·7%) of 47 patients who received mycophenolate mofetil and nine (28·1%) of 31 who received azathioprine (risk difference 19·6%, 95% CI -4·9 to 44·2; p=0·12). Descriptive analysis did not find a difference in the proportion of patients reaching a CMR in MG-QOL15r between the adequate dose and duration group and the lower dose or shorter duration group. Adverse events occurred in 11 (32%) of 34 patients who received azathioprine and nine (19%) of 48 who received mycophenolate mofetil. The most frequent adverse events were hepatotoxicity with azathioprine (five [15%] of 34) and gastrointestinal disturbances (seven [15%] of 48) with mycophenolate mofetil. There were no study-related deaths. INTERPRETATION: More than half of patients treated with azathioprine and mycophenolate mofetil felt their quality of life improved; no difference in clinical outcomes was noted between the two drugs. Adverse events associated with azathioprine were potentially more serious than those with mycophenolate mofetil, although mycophenolate mofetil is teratogenic. Lower than recommended doses of azathioprine might be effective, with reduced dose-dependent adverse events. More comparative effectiveness studies are required to inform treatment choices in myasthenia gravis. FUNDING: Patient-Centered Outcomes Research Institute, Myasthenia Gravis Foundation of America.

Predictors of Occlusion after Carotid Stenting.

BACKGROUND: Carotid artery stent (CAS) occlusion is a rare complication not well studied. We used a national dataset to assess real world CAS experience to determine the rate of stent occlusion. The purpose of this study was to 1) Identify risk factors associated with CAS occlusion on long-term follow-up (LTFU) and 2) Determine the adjusted odds of death/transient ischemic attack (TIA)/stroke (cerebrovascular accident (CVA)) in patients with occlusion. METHODS: The national Vascular Quality Initiative CAS dataset (2016-2021) comprised the sample. The primary endpoint was occlusion on LTFU (9-21 months postoperatively as defined by the Vascular Quality Initiative LTFU dataset) with secondary endpoint examining a composite of death/TIA/CVA. Descriptive analyses used chi-square and Wilcoxon tests for categorical and continuous variables respectively. Adjustment variables were selected a priori based on clinical expertise and univariate analyses. Multivariable logistic regression was used to model the odds of occlusion and the odds of death/TIA/CVA. Generalized estimating equations accounted for center level variation. RESULTS: During the study period, 109 occlusions occurred in 12,143 cases (0.9%). On univariate analyses, symptomatic indication, prior stroke, prior neck radiation, lesion calcification (>50%), stenosis (>80%), distal embolic protection device (compared to flow reversal), balloon size, >1 stent and current smoking at time of LTFU were predictive for occlusion. Age ≥ 65, coronary artery disease (CAD), elective status, preoperative statin, preoperative and discharge P2Y12 inhibitor, use of any protection device intraoperatively and protamine were protective. On multivariable analyses, age ≥ 65, CAD, elective status and P2Y12 inhibitor on discharge were protective for occlusion, while patients with prior radiation and those taking P2Y12 inhibitor on LTFU were at increased odds. The adjusted odds of death/TIA/CVA in patients with occlusion on LTFU were 6.05; 95% confidence interval: 3.61-10.11, P < 0.0001. CONCLUSIONS: This study provides an in-depth analysis of predictors for CAS occlusion on LTFU. On univariate analyses, variables related to disease severity (urgency, degree of stenosis, nature of lesion) and intraoperative details (balloon diameter, >1 stent) were predictive for occlusion. These variables were not statistically significant after risk adjustment. On multivariable analyses, prior neck radiation was strongly predictive of occlusion. Elective status, patient age ≥ 65, CAD, and P2Y12 inhibitor upon discharge (but not on LTFU) were protective for occlusion. Additionally, patients who developed occlusion had high odds for death/TIA/CVA. These findings provide important data to guide clinical decision-making for carotid disease management, particularly identifying high-risk features for CAS occlusion. Closer postoperative follow-up and aggressive risk factor modification in these patients may be merited.

Anesthetic Management for Ventricular Tachycardia Ablation: A National Anesthesia Clinical Outcomes Registry Analysis.

OBJECTIVES: The authors analyzed anesthetic management trends during ventricular tachycardia (VT) ablation, hypothesizing that (1) monitored anesthesia care (MAC) is more commonly used than general anesthesia (GA); (2) MAC uses significantly increased after release of the 2019 Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias; and (3) anesthetic approach varies based on patient and hospital characteristics. DESIGN: Retrospective study. SETTING: National Anesthesia Clinical Outcomes Registry data. PARTICIPANTS: Patients 18 years or older who underwent elective VT ablation between 2013 and 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Covariates were selected a priori within multivariate models, and interrupted time-series analysis was performed. Of the 15,505 patients who underwent VT ablation between 2013 and 2021, 9,790 (63.1%) received GA. After the 2019 Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias supported avoidance of GA in idiopathic VT, no statistically significant increase in MAC was evident (immediate change in intercept post-consensus statement release adjusted odds ratio 1.41, p = 0.1629; change in slope post-consensus statement release adjusted odds ratio 1.06 per quarter, p = 0.1591). Multivariate analysis demonstrated that sex, American Society of Anesthesiologists physical status, age, and geographic location were statistically significantly associated with the anesthetic approach. CONCLUSIONS: GA has remained the primary anesthetic type for VT ablation despite the 2019 Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias suggested its avoidance in idiopathic VT. Achieving widespread clinical practice change is an ongoing challenge in medicine, emphasizing the importance of developing effective implementation strategies to facilitate awareness of guideline release and subsequent adherence to and adoption of recommendations.

Outcomes of the Kawashima: A Society of Thoracic Surgeons Congenital Heart Surgery Database Analysis.

BACKGROUND: We aimed to evaluate the effect of age at operation on postoperative outcomes in children undergoing a Kawashima operation. METHODS: The Society of Thoracic Surgeons Congenital Heart Surgery Database was queried for Kawashima procedures from January 1, 2014, to June 30, 2020. Patients were stratified by age at operation in months: 0 to <4, 4 to <8, 8 to <12, and >12. Subsequently, outcomes for those in whom the Kawashima was not the index operation and for those undergoing hepatic vein incorporation (Fontan completion or hepatic vein-to-azygos vein connection) were evaluated. RESULTS: We identified 253 patients who underwent a Kawashima operation (median age, 8.6 months; median weight, 7.4 kg): 12 (4.7%), 0 to <4 months; 96 (37.9%), 4 to <8 months; 81 (32.0%), 8 to <12 months; and 64 (25.3%), >12 months. Operative mortality was 0.8% (n = 2), with major morbidity or mortality in 17.4% (n = 44), neither different across age groups. Patients <4 months had a longer postoperative length of stay (12.5 vs 9.3 days; P = .03). The Kawashima was not the index operation of the hospital admission in 15 (5.9%); these patients were younger (6.0 vs 8.4 months; P = .05) and had more preoperative risk factors (13/15 [92.9%] vs 126/238 [52.9%]; P < .01). We identified 173 patients undergoing subsequent hepatic vein incorporation (median age, 3.9 years; median weight, 15.0 kg) with operative mortality in 6 (3.5%) and major morbidity or mortality in 30 (17.3%). CONCLUSIONS: The Kawashima is typically performed between 4 and 12 months with low mortality. Morbidity and mortality were not affected by age. Hepatic vein incorporations may be higher risk than in traditional Fontan procedures, and ways to mitigate this should be sought.

Nationwide emergency department visits for pediatric traumatic spinal cord injury in the United States, 2016-2020.

Introduction: Traumatic spinal cord injury (tSCI) is a debilitating neurological condition resulting in lifelong disability for many individuals. The primary objectives of our study were to describe national trends in incident emergency department (ED) visits for tSCI among children (less than 21 years) in the United States, and to determine the proportion of visits that resulted in immediate hospitalization each year, including stratified by age and sex. Secondary objectives were to examine associations between select characteristics and hospitalization following tSCI, as well as to assess sports-related tSCIs over time, including by individual sport and geographic region. Methods: We used the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample to identify ED visits among children between January 2016 and December 2020 for incident tSCI. Diagnosis codes were used to identify tSCI and sports-related injury etiologies. Census Bureau data were used to approximate annual rates of pediatric ED visits for tSCI per 100,000 children. Unconditional logistic regression modeling assessed whether select factors were associated with hospital admission. Results: We found that the annual ED visit rate for tSCI remained relatively stable between 2016 and 2020, with approximately 2,200 new all-cause pediatric ED visits for tSCI annually. Roughly 70% of ED visits for tSCI resulted in hospitalization; most ED visits for tSCI were by older children (15-20 years) and males, who were also more often admitted to the hospital. Notable secondary findings included: (a) compared with older children (15-20 years), younger children (10-14 years) were less likely to be hospitalized immediately following an ED visit for tSCI; (b) patient sex and race were not associated with hospital admission; and (c) American tackle football was the leading cause of sports-related ED visits for tSCI among children. Our findings also suggest that the proportion of sports-related tSCI ED visits may have increased in recent years. Discussion: Future research should further examine trends in the underlying etiologies of pediatric tSCI, while assessing the effectiveness of new and existing interventions aimed at tSCI prevention.

Anesthetic Choice for Cardiovascular Implantable Electronic Device Placement and Lead Removal: A National Anesthesia Clinical Outcomes Registry Analysis.

OBJECTIVE: The authors evaluated the anesthetic approach for cardiovascular implantable electronic device (CIED) placement and transvenous lead removal, hypothesizing that monitored anesthesia care is used more frequently than general anesthesia. DESIGN: A retrospective study. SETTING: National Anesthesia Clinical Outcomes Registry data. PARTICIPANTS: Adult patients who underwent CIED (permanent cardiac pacemaker or implantable cardioverter-defibrillator [ICD]) placement or transvenous lead removal between 2010 and 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Covariates were selected a priori within multivariate models to assess predictors of anesthetic type. A total of 87,530 patients underwent pacemaker placement, 76,140 had ICD placement, 2,568 had pacemaker transvenous lead removal, and 4,861 had ICD transvenous lead extraction; 51.2%, 45.64%, 16.82%, and 45.64% received monitored anesthesia care, respectively. A 2%, 1% (both p < 0.0001), and 2% (p = 0.0003) increase in monitored anesthesia care occurred for each 1-year increase in age for pacemaker placement, ICD placement, and pacemaker transvenous lead removal, respectively. American Society of Anesthesiologists (ASA) physical status ≤III for pacemaker placement, ASA ≥IV for ICD placement, and ASA ≤III for pacemaker transvenous lead removal were 7% (p = 0.0013), 5% (p = 0.0144), and 27% (p = 0.0247) more likely to receive monitored anesthesia care, respectively. Patients treated in the Northeast were more likely to receive monitored anesthesia care than in the West for all groups analyzed (p < 0.0024). Male patients were 24% less likely to receive monitored anesthesia care for pacemaker transvenous lead removal (p = 0.0378). For every additional 10 pacemaker or ICD lead removals performed in a year, a 2% decrease in monitored anesthesia care was evident (p = 0.0271, p < 0.0001, respectively). CONCLUSIONS: General anesthesia still has a strong presence in the anesthetic management of both CIED placement and transvenous lead removal. Anesthetic choice, however, varies with patient demographics, hospital characteristics, and geographic region.

Center-level factors associated with shorter length of stay following stage 1 palliation: An analysis of the national pediatric cardiology quality improvement collaborative registry.

BACKGROUND: Stage 1 single ventricle palliation (S1P) has the longest length of stay (LOS) of all benchmark congenital heart operations. Center-level factors contributing to prolonged hospitalization are poorly defined. METHODS: We analyzed data from infants status post S1P included in the National Pediatric Cardiology Quality Improvement Collaborative Phase II registry. Our primary outcome was patient-level LOS with days alive and out of hospital before stage 2 palliation (S2P) used as a balancing measure. We compared patient and center-level characteristics across quartiles for median center LOS, and used multivariable regression to calculate center-level factors associated with LOS after adjusting for case mix. RESULTS: Of 2,510 infants (65 sites), 2037 (47 sites) met study criteria (61% male, 61% white, 72% hypoplastic left heart syndrome). There was wide intercenter variation in LOS (first quartile centers: median 28 days [IQR 19, 46]; fourth quartile: 62 days [35, 95], P < .001). Mortality prior to S2P did not differ across quartiles. Shorter LOS correlated with more pre-S2P days alive and out of hospital, after accounting for readmissions (correlation coefficient -0.48, P < .001). In multivariable analysis, increased use of Norwood with a right ventricle to pulmonary artery conduit (aOR 2.65 [1.1, 6.37]), shorter bypass time (aOR 0.99 per minute [0.98,1.0]), fewer additional cardiac operations (aOR 0.46 [0.22, 0.93]), and increased use of NG tubes rather than G tubes (aOR 7.03 [1.95, 25.42]) were all associated with shorter LOS centers. CONCLUSIONS: Modifiable center-level practices may be targets to standardize practice and reduce overall LOS across centers.

Long-term Outcomes and Anticoagulation in Mitral Valve Surgery-A Report From The Society of Thoracic Surgeons Database.

BACKGROUND: Anticoagulation after bioprosthetic mitral valve (MV) replacement (BMVR) and repair (MVrep) is controversial. We explore outcomes among BMVR and MVrep patients in The Society of Thoracic Surgeons Adult Cardiac Surgery Database based on discharge anticoagulation status. METHODS: BMVR and MVrep patients aged ≥65 years in The Society of Thoracic Surgeons Adult Cardiac Surgery Database were linked to the Centers for Medicare and Medicaid Services claims database. Long-term mortality, ischemic stroke, bleeding, and a composite of the primary end points were compared as a function of anticoagulation. Hazard ratios (HRs) were calculated using multivariable Cox regression. RESULTS: A total of 26,199 BMVR and MVrep patients were linked to the Centers for Medicare and Medicaid Services database; of these, 44%, 4%, and 52% were discharged on warfarin, non-vitamin K-dependent anticoagulant (NOAC), and no anticoagulation (no-AC; reference), respectively. Warfarin was associated with increased bleeding in the overall study cohort (HR, 1.38; 95% CI 1.26-1.52) and in the BMVR (HR, 1.32; 95% CI, 1.13-1.55) and MVrep subcohorts (HR, 1.42; 95% CI, 1.26-1.60). Warfarin was associated with decreased mortality only among BMVR patients (HR, 0.87; 95% CI, 0.79-0.96). Stroke and the composite outcome did not differ across cohorts with warfarin. NOAC use was associated with increased mortality (HR, 1.33; 95% CI 1.11-1.59), bleeding (HR, 1.37; 95% CI, 1.07-1.74), and the composite outcome (HR, 1.26; 95% CI, 1.08-1.47). CONCLUSIONS: Anticoagulation was used in fewer than half of mitral valve operations. In MVrep patients, warfarin was associated with increased bleeding and was not protective against stroke or mortality. In BMVR patients, warfarin was associated with a modest survival benefit, increased bleeding, and equivalent stroke risk. NOAC was associated with increased adverse outcomes.

Contemporary Patterns of Care in Tetralogy of Fallot: Analysis of The Society of Thoracic Surgeons Data.

BACKGROUND: Against the background of earlier studies, recent patterns in surgical management of tetralogy of Fallot (TOF) were assessed. METHODS: A retrospective review of The Society of Thoracic Surgeons (STS) Congenital Database (2010-2020) was performed on patients aged <18 years with TOF or pulmonary stenosis and primary procedure TOF surgical repair or palliation. Procedural frequencies were examined by epoch. Demographics, clinical variables, and outcomes were compared between the initial palliation and primary repair groups. Among those operated on at 0 to 60 days of age, variation in palliation rates across hospitals was assessed. RESULTS: The 12,157 operations included 11,307 repairs (93.0%) and 850 palliations (7.0%); 68.5% of all palliations were modified Blalock-Taussig-Thomas shunts. Of 1105 operations on neonates, 45.4% (502) were palliations. Among neonates, palliations declined from 49.0% (331 of 675) in epoch 1 (2010-2015) to 39.8% (171 of 430) in epoch 2 (2016-2020; P = .0026). Overall, the most prevalent repair technique (5196 of 11,307; 46.0%) was ventriculotomy with transanular patch, which was also used in 520 of 894 (58.2%) of repairs after previous cardiac operations. Patients undergoing initial palliation demonstrated more preoperative STS risk factors (50.1% vs 24.3% respectively; P < .0001) and more major morbidity and mortality than patients undergoing primary repair (21.2% vs 7.46%; P < .0001). In the 0- to 60-day age group, risk factor-adjusted palliation rates across centers varied considerably, with 32 of 99 centers performing significantly more or significantly fewer palliations than predicted on the basis of their case mix. CONCLUSIONS: Surgical palliation rates have decreased across all age groups despite increasing prevalence of risk factors. Ventriculotomy with transanular patch remains the most prevalent repair type. The considerable center-level variation in rates of palliation was not completely explained by case mix.

Dexamethasone for Inpatients With COVID-19 in a National Cohort.

Importance: Limited effective therapeutics are available to hospitalized patients with COVID-19. Clinical trials and observational studies have shown varying effects of systemic corticosteroids, including dexamethasone, in hospitalized patients with COVID-19, with limited descriptions of important patient subgroups. Objective: To examine the clinical use of dexamethasone for hospitalized patients with COVID-19 respiratory illness and to explore the heterogeneity of treatment outcomes across different subgroups. Design, Setting, and Participants: This is a retrospective, propensity score-weighted cohort study of adult patients hospitalized for at least 48 hours for COVID-19 respiratory illness between July 1, 2020, and October 31, 2021, at a large health care network of 156 hospitals across the US. Data analysis was performed from March 2022 to February 2023. Exposures: Systemic dexamethasone administered within 48 hours of either admission or escalation in oxygen support. Main Outcomes and Measures: All-cause in-hospital mortality or discharge to hospice. Results: A total of 80 699 patients who met the eligibility criteria were identified (median [IQR] age, 64 [52-76] years; 37 606 women [46.6%]); 13 230 patients (16.4%) identified as Black, 49 222 (60.9%) as White, 18 247 (22.6%) as other race, and 20 340 (25.2%) as Hispanic ethnicity. Of these patients, 13 040 (16.2%) did not require supplemental oxygen within 48 hours of admission, 56 368 (69.8%) required supplemental oxygen, 7618 (9.4%) required noninvasive positive pressure ventilation (NIPPV), and 3673 (4.6%) required mechanical ventilation (MV) and/or extracorporeal membrane oxygenation (ECMO). After adjustment by propensity score overlap weighting, early use of dexamethasone was associated with reduction in a composite outcome of in-hospital mortality or discharge to hospice for patients receiving supplemental oxygen (aOR, 0.92; 95% CI, 0.86-0.98) and MV and/or ECMO (aOR, 0.82; 95% CI, 0.68-0.99). In contrast, all-cause inpatient mortality or discharge to hospice was not lower for patients who received dexamethasone in the no supplemental oxygen group (aOR, 0.90; 95% CI, 0.78-1.03) and in the NIPPV group (aOR, 0.87; 95% CI, 0.73-1.04). Importantly, patients with more comorbidities had greater benefit from dexamethasone use. Conclusions and Relevance: In this national multicenter cohort study of inpatients with COVID-19, early administration of dexamethasone was associated with significantly reduced odds of mortality or discharge to hospice in those requiring supplemental oxygen or MV and/or ECMO but not in those requiring no supplemental oxygen or NIPPV. These results support the continued use of systemic dexamethasone in patients hospitalized with COVID-19.

Channeling of New Neuropsychiatric Drugs-Impact on Safety and Effectiveness Studies.

This study aimed to examine differential prescribing due to channeling and propensity score non-overlap over time in new versus established treatments for common neurological conditions. We conducted cross-sectional analyses on a national sample of US commercially insured adults using 2005-2019 data. We compared new users of recently approved versus established medications for management of diabetic peripheral neuropathy (pregabalin versus gabapentin), Parkinson disease psychosis (pimavanserin versus quetiapine), and epilepsy (brivaracetam versus levetiracetam). Within these drug pairs, we compared demographic, clinical, and healthcare utilization characteristics of recipients of each drug. In addition, we fit yearly propensity score models for each condition and assessed propensity score non-overlap over time. For all three drug pairs, users of the more recently approved medications more frequently had prior treatment (pregabalin = 73.9%, gabapentin = 38.7%; pimavanserin = 41.1%, quetiapine = 14.0%; brivaracetam = 93.4%, levetiracetam = 32.1%). Propensity score non-overlap and its resulting sample loss after trimming were the greatest in the first year that the more recently approved medication was available (diabetic peripheral neuropathy, 12.4% non-overlap; Parkinson disease psychosis, 6.1%; epilepsy, 43.2%) and subsequently improved. Newer neuropsychiatric therapies appear to be channeled to individuals with refractory disease or intolerance to other treatments, leading to potential confounding and biased comparative effectiveness and safety study findings when compared to established treatments. Propensity score non-overlap should be reported in comparative studies that include newer medications. When studies comparing newer and established treatments are critically needed as soon as new treatments enter the market, investigators should recognize the potential for channeling bias and implement methodological approaches like those demonstrated in this study to understand and improve this issue in such studies.

Anesthetic management for transcatheter aortic valve replacement: A national anesthesia clinical outcomes registry analysis.

Background: General anesthesia has traditionally been used in transcatheter aortic valve replacement; however, there has been increasing interest and momentum in alternative anesthetic techniques. Aims: To perform a descriptive study of anesthetic management options in transcatheter aortic valve replacements in the United States, comparing trends in use of monitored anesthesia care versus general anesthesia. Settings and Design: Data evaluated from the American Society of Anesthesiologists' (ASA) Anesthesia Quality Institute's National Anesthesia Clinical Outcomes Registry. Materials and Methods: Multivariable logistic regression was used to identify predictors associated with use of monitored anesthesia care compared to general anesthesia. Results: The use of monitored anesthesia care has increased from 1.8% of cases in 2013 to 25.2% in 2017 (p = 0.0001). Patients were more likely ages 80+ (66% vs. 61%; p = 0.0001), male (54% vs. 52%; p = 0.0001), ASA physical status > III (86% vs. 80%; p = 0.0001), cared for in the Northeast (38% vs. 22%; p = 0.0001), and residents in zip codes with higher median income ($63,382 vs. $55,311; p = 0.0001). Multivariable analysis revealed each one-year increase in age, every 50 procedures performed annually at a practice, and being male were associated with 3% (p = 0.0001), 33% (p = 0.012), and 16% (p = 0.026) increased odds of monitored anesthesia care, respectively. Centers in the Northeast were more likely to use monitored anesthesia care (all p < 0.005). Patients who underwent approaches other than percutaneous femoral arterial were less likely to receive monitored anesthesia care (adjusted odds ratios all < 0.51; all p = 0.0001). Conclusion: Anesthetic type for transcatheter aortic valve replacements in the United States varies with age, sex, geography, volume of cases performed at a center, and procedural approach.

Development of a Novel Society of Thoracic Surgeons Adult Congenital Mortality Risk Model.

BACKGROUND: Operative mortality risk models for adults with congenital heart disease (ACHD) undergoing cardiac operations are essential, given the growing population of these patients, yet they are currently unavailable. Existing adult Society of Thoracic Surgeons (STS) models exclude congenital procedures, whereas existing congenital models exclude operations for acquired disease. We aimed to develop an STS mortality risk model for ACHD patients undergoing cardiac operations. METHODS: Leveraging a comprehensive list of diagnostic and procedure codes, ACHD patients who underwent cardiac operations were identified from the STS Adult Cardiac Surgery Database (versions: v2.73, v2.81, and v2.9) between 2011 and 2019. The model was developed and validated in the ACHD population using a 60/40 development/validation split. Univariate analyses and clinical expertise informed the addition of ACHD-relevant procedure and diagnosis variables to existing STS adult risk model variables. Model performance was assessed overall and in 38 subgroups based on patient demographics, procedures, and diagnoses. RESULTS: Forty-seven procedure and diagnosis variables relevant to ACHD were added to existing STS adult risk model variables. The derived ACHD model for operative mortality was well calibrated within demographic, procedural, and diagnosis subgroups and the overall ACHD population, and discrimination in the validation cohort was excellent (C statistic, 0.815) compared with the model using only existing STS adult risk model variables (C statistic, 0.79; P < .0001). CONCLUSIONS: A novel, high-performing STS ACHD mortality risk model has been developed on the basis of contemporary patient data. The ACHD risk model represents an important expansion of the STS portfolio. Implementation with an online risk calculator is planned.

Seasonal Variation in Neurologic Hospitalizations in the United States.

OBJECTIVE: Certain neurologic diseases have been noted to vary by season, and this is important for understanding disease mechanisms and risk factors, but seasonality has not been systematically examined across the spectrum of neurologic disease, and methodologic guidance is also lacking. METHODS: Using nationally representative data from the National Inpatient Sample, a stratified 20% sample of all non-federal acute care hospitalizations in the United States, we calculated the monthly rate of hospitalization for 14 neurologic diseases from 2016 to 2018. For each disease, we assessed seasonality of hospitalization using chi-squared, Edward, and Walter-Elwood tests and seasonal time series regression models. Statistical tests were adjusted for multiple hypothesis testing using Bonferroni correction. RESULTS: Meningitis, encephalitis, ischemic stroke, intracerebral hemorrhage, Guillain-Barre syndrome, and multiple sclerosis had statistically significant seasonality according to multiple methods of testing. Subarachnoid hemorrhage, status epilepticus, myasthenia gravis, and epilepsy had significant seasonality according to Edwards and Walter-Elwood tests but not chi-square tests. Seasonal time series regression illustrated seasonal variation in all 14 diseases of interest, but statistical testing for seasonality within these models using the Kruskal-Wallis test only achieved statistical significance for meningitis. INTERPRETATION: Seasonal variation is present across the spectrum of acute neurologic disease, including some conditions for which seasonality has not previously been described, and can be examined using multiple different methods. ANN NEUROL 2023;93:743-751.

Robotic Esophagectomy Trends and Early Surgical Outcomes: The US Experience.

BACKGROUND: Recent esophagectomy trends were evaluated to describe the shift in surgical approach and outcomes using The Society of Thoracic Surgeons General Thoracic Surgery Database. METHODS: All patients who underwent an esophagectomy with gastric conduit from 2015 to 2019 were identified and analyzed according to original intended approach. After performing volume trend analysis of patients, operative outcomes were evaluated. RESULTS: Among 10,607 patients, esophagectomy was open in 5763 (54.3%), minimally invasive (MIE) in 3524 (33.2%), and robotic (RAMIE) in 1320 (12.4%). Within 5 years, MIE and RAMIE combined rose to majority approach (open from 58% to 42% of annual volume). While MIE and RAMIE were associated with higher rates of anastomotic leak, loss of conduit, pulmonary embolus, and reoperation, R0 resection and harvested number of lymph nodes exceeded those in open approaches. Operative mortality did not differ by approach (3.21% open vs 2.72% MIE vs 2.50% RAMIE; P = .2329). On multivariable analysis, RAMIE was independently associated with higher rate of anastomotic leak compared to open (adjusted odds ratio 1.53, 95% CI 1.14-2.04), while both MIE and RAMIE had lower mean length of stay. Propensity matching of 1320 pairs found a higher risk of anastomotic leak requiring surgery for RAMIE compared with MIE (adjusted odds ratio 1.39, 95% CI 1.01-1.92). CONCLUSIONS: In less than a decade, the dominant surgical approach in The Society of Thoracic Surgeons General Thoracic Surgery Database has become minimally invasive (RAMIE and MIE). While anastomotic leak and reoperation, more common in RAMIE, require a technical solution, these complications have not raised operative mortality. Further studies are needed to address long-term results and oncologic outcome.

Optimal circulatory arrest temperature for aortic hemiarch replacement with antegrade brain perfusion.

OBJECTIVE: This study sought to identify the optimal temperature for moderate hypothermic circulatory arrest in patients undergoing elective hemiarch replacement with antegrade brain perfusion. METHODS: The Society of Thoracic Surgeons adult cardiac surgery database was queried for elective hemiarch replacements using antegrade brain perfusion for aneurysmal disease (2014-2019). Generalized estimating equations and restricted cubic splines were used to determine the risk-adjusted relationships between temperature as a continuous variable and outcomes. RESULTS: Elective hemiarch replacement with antegrade brain perfusion occurred in 3898 patients at 374 centers with a median nadir temperature of 24.9°C (first quartile, third quartile = 22.0°C, 27.5°C) and median circulatory arrest time of 19 minutes (first quartile, third quartile = 14.0 minutes, 27.0 minutes). After adjustment for comorbidities, circulatory arrest time, and individual surgeon, patients cooled between 25 and 28°C had an early survival advantage compared with 24°C, whereas those cooled between 21 and 23°C had higher risks of mortality compared with 24°C. A nadir temperature of 27°C was associated with the lowest risk-adjusted odds of mortality (odds ratio, 0.62; 95% confidence interval, 0.42-0.91). A nadir temperature of 21°C had the highest risk of mortality (odds ratio, 1.4; 95% confidence interval, 1.13-1.73). Risk of experiencing a major morbidity was elevated in patients cooled between 21 and 23°C, with the highest risk occurring in patients cooled to 21°C (odds ratio, 1.12; 95% confidence interval, 1.01-1.24). CONCLUSIONS: For patients with aneurysmal disease undergoing elective hemiarch with antegrade brain perfusion, circulatory arrest with a nadir temperature of 27°C confers the greatest early survival benefit and smallest risk of postoperative morbidity.

Anesthetic choice for arteriovenous access creation: A National Anesthesia Clinical Outcomes Registry analysis.

BACKGROUND: We sought to evaluate differences in primary anesthetic type used in arteriovenous access creation with the hypothesis that administration of regional anesthesia and monitored anesthesia care (MAC) with local anesthesia as the primary anesthetic has increased over time. METHODS: National Anesthesia Clinical Outcomes Registry data were retrospectively evaluated. Covariates were selected a priori within multivariate models to determine predictors of anesthetic type in adults who underwent elective arteriovenous access creation between 2010 and 2018. RESULTS: A total of 144,392 patients met criteria; 90,741 (62.8%) received general anesthesia. The use of regional anesthesia and MAC decreased over time (8.0%-6.8%, 36.8%-27.8%, respectively; both p < 0.0001). Patients who underwent regional anesthesia were more likely to have ASA physical status >III and to reside in rural areas (52.3% and 12.9%, respectively; both p < 0.0001). Patients who underwent MAC were more likely to be older, male, receive care outside the South, and reside in urban areas (median age 65, 56.8%, 68.1%, and 70.8%, respectively; all p < 0.0001). Multivariate analysis revealed that being male, having an ASA physical status >III, and each 5-year increase in age resulted in increased odds of receiving alternatives to general anesthesia (regional anesthesia adjusted odds ratios (AORs) 1.06, 1.12, and 1.26, MAC AORs 1.09, 1.2, and 1.1, respectively; all p < 0.0001). Treatment in the Midwest, South, or West was associated with decreased odds of receiving alternatives to general anesthesia compared to the Northeast (regional anesthesia AORs 0.28, 0.38, and 0.03, all p < 0.0001; MAC 0.76, 0.13, and 0.43, respectively; all p < 0.05). CONCLUSIONS: Use of regional anesthesia and MAC with local anesthesia for arteriovenous access creation has decreased over time with general anesthesia remaining the primary anesthetic type. Anesthetic choice, however, varies with patient characteristics and geography.

Mortality and cost of post-cardiotomy extracorporeal support in the United States.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used increasingly for cardiopulmonary rescue. Despite recent advances however, post-cardiotomy shock (PCS)-ECMO survival remains comparatively poor. We sought to evaluate outcomes and define factors that predict in-hospital mortality. METHODS: We used the Nationwide Inpatient Sample (NIS) to evaluate adult hospitalizations with a primary procedure code for coronary artery bypass grafting (CABG), and/or valve procedures performed between 2013 and 2018, which also required post cardiotomy ECMO support. Patient-related factors and hospital costs were evaluated to identify those associated with in-hospital mortality. RESULTS: There were 1,247,835 admissions for cardiac surgical procedures during the study period. Post-cardiotomy shock-ECMO support was provided in 4475 (0.3%) within the study cohort. A total of 2000 (44.7%) hospitalizations involved isolated valvular procedures, 1700 (38.0%) isolated CABG, and 775 (17.3%) involved a combination of both. Overall, in-hospital mortality was 42.1% (n = 1880). Factors significantly associated with in-hospital mortality included patients with multiple comorbidities (> 7) and those undergoing combination of valve and CABG procedures. Only 26.6% of those who survived to discharge, were discharged home independently. CONCLUSION: Survival to independent home discharge is rare following PCS-ECMO. Its high mortality is associated with multiple comorbidities and combination of CABG and valve surgery.

Comparing Consumer-Directed Hospital Rankings With STS Adult Cardiac Surgery Database Outcomes.

BACKGROUND: Public interest in stratifying hospital performance has led to the proliferation of commercial, consumer-oriented hospital rankings. In cardiac surgery, little is known about how these rankings correlate with clinical registry quality ratings. METHODS: The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database was queried for isolated coronary artery bypass grafting or coronary artery bypass grafting/valve patients at hospitals among the top 100 U.S. News & World Report (USNWR) Cardiology & Heart Surgery rankings from 2016 to 2020. Hospitals were grouped into deciles by risk-adjusted observed/expected (O/E) ratios for morbidity and mortality using the STS 2018 risk models. Agreement between STS Adult Cardiac Surgery Database and USNWR ranked deciles was calculated by Bowker symmetry test. The association between each center's annual change in STS O/E ratio and change in USNWR ranking was modeled in repeated measures regression analysis. RESULTS: Inclusion criteria were met by 524 393 patients from 149 hospitals that ranked in USNWR top 100 at least once during the study period. There was no agreement between USNWR ranking and STS major morbidity and mortality O/E ratio (P > .50 for all years). Analysis of patients undergoing surgery at the 65 hospitals that were consistently ranked in the top 100 during the study period demonstrated no association between annual change in hospital ranking and change in O/E ratio (P all > .3). CONCLUSIONS: There was no agreement between annual USNWR hospital ranking and corresponding risk-adjusted STS morbidity or mortality. Furthermore, annual changes in USNWR rankings could not be accounted for using clinical outcomes. These findings suggest that factors unrelated to key surgical outcomes may be driving consumer-directed rankings.

Amphetamine-related care in the USA, 2003-2014: cross-sectional analyses examining inpatient trends and factors associated with hospitalisation outcomes.

OBJECTIVES: Although amphetamine use is a growing health problem in the USA, there are limited data on amphetamine-related hospitalisations. The primary objective of our study was to examine trends in amphetamine-related hospitalisations in the USA between 2003 and 2014, including by age and sex. Our secondary objectives were to examine whether demographic, clinical and care setting characteristics were associated with select outcomes of amphetamine-related hospitalisations, including in-hospital mortality, prolonged length of stay and leaving against medical advice. DESIGN, SETTING AND PARTICIPANTS: Using the 2003-2014 National Inpatient Sample, we estimated the rate of amphetamine-related hospitalisations for each year in the USA among individuals 18+ years of age, stratified by age and sex. Subgroup analyses examined hospitalisations due to amphetamine causes. Unconditional logistic regression modelling was used to estimate the adjusted odds of admission outcomes for sociodemographic, clinical and hospital indicators. PRIMARY AND SECONDARY OUTCOMES: Our primary outcome was amphetamine-related hospitalisations between 2003 and 2014; secondary outcomes included in-hospital mortality, prolonged length of stay and leaving against medical advice. RESULTS: Amphetamine-related hospitalisation rates increased from 27 to 69 per 100 000 population between 2003 and 2014. Annual rates were consistently greater among younger (18-44 years) individuals and men. Regional differences were observed, with admission to Western hospitals being associated with increased mortality (adjusted OR, AOR 5.07, 95% CI 1.22 to 21.04) and shorter (0-2 days) lengths of stay (AOR 0.70, 95% CI 0.58 to 0.83) compared with Northeast admissions. Males (AOR 1.26, 95% CI 1.15 to 1.38; compared with females) and self-pay (AOR 2.30, 95% CI 1.90 to 2.79; compared with private insurance) were associated with leaving against medical advice. CONCLUSIONS: Increasing rates of amphetamine-related hospitalisation risk being overshadowed by other public health crises. Regional amphetamine interventions may offer the greatest population health benefits. Future studies should examine long-term outcomes among patients hospitalised for amphetamine-related causes.