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Background: Enrollment of Medicare beneficiaries in medicare advantage (MA) plans has been steadily increasing. Prior research has shown differences in healthcare access and outcomes based on Medicare enrollment status. This study sought to compare utilization of minimally invasive colorectal cancer (CRC) surgery and postoperative outcomes between MA and Fee-for-Service (FFS) beneficiaries., Methods: A retrospective cohort study of beneficiaries  ≥ 65.5 years of age enrolled in FFS and MA plans was performed of patients undergoing a CRC resection from 2016 to 2019. The primary outcome was operative approach, defined as minimally invasive (laparoscopic) or open. Secondary outcomes included robotic assistance, hospital length-of-stay, mortality, discharge disposition, and hospital readmission. Using balancing weights, we performed a tapered analysis to examine outcomes with adjustment for potential confounders., Results: MA beneficiaries were less likely to have lymph node (12.9 vs 14.4%, p < 0.001) or distant metastases (15.5% vs 17.0%, p < 0.001), and less likely to receive chemotherapy (6.2% vs 6.7%, p < 0.001), compared to FFS beneficiaries. MA beneficiaries had a higher risk-adjusted likelihood of undergoing laparoscopic CRC resection (OR 1.12 (1.10-1.15), p < 0.001), and similar rates of robotic assistance (OR 1.00 (0.97-1.03), p = 0.912), compared to FFS beneficiaries. There were no differences in risk-adjusted length-of-stay (β coefficient 0.03 (- 0.05-0.10), p = 0.461) or mortality at 30-60-and 90-days (OR 0.99 (0.95-1.04), p = 0.787; OR 1.00 (0.96-1.04), p = 0.815; OR 0.98 (0.95-1.02), p = 0.380). MA beneficiaries had a lower likelihood of non-routine disposition (OR 0.77 (0.75-0.78), p < 0.001) and readmission at 30-60-and 90-days (OR 0.76 (0.73-0.80), p < 0.001; OR 0.78 (0.75-0.81), p < 0.001; OR 0.79 (0.76-0.81), p < 0.001)., Conclusions: MA beneficiaries had less advanced disease at the time of CRC resection and a greater likelihood of undergoing a laparoscopic procedure. MA enrollment is associated with improved health outcomes for elderly beneficiaries undergoing operative treatment for CRC., (© 2024. The Author(s).)

Background: Longer time to surgery (TTS) is associated with worse survival in patients with breast cancer. Whether this association has encouraged more prompt care delivery remains unknown., Methods: The National Cancer Database was used to identify patients ≥18 years of age diagnosed with clinical stage 0-III breast cancer between 2006 and 2019 for whom surgery was the first mode of treatment. A linear-by-linear test for trend assessed median TTS across the interval. Adjusted linear regression modeling was used to examine TTS trends across patient subgroups., Results: Overall, 1,435,584 patients met the inclusion criteria. The median age was 63 years (interquartile range [IQR] 53-72), 84.3% of patients were White, 91.1% were non-Hispanic, and 99.2% were female. The median TTS in 2006 was 26 days (IQR 16-39) versus 39 days in 2019 (IQR 27-56) [p < 0.001]. In a multivariable linear regression model, TTS increased significantly, with an annual increase of 0.83 days (95% confidence interval 0.82-0.85; p < 0.001). A consistent, significant increase in TTS was observed on subgroup analyses by surgery type, reconstruction, patient race, hospital type, and disease stage. Black race, Hispanic ethnicity, and having either Medicaid or being uninsured were significantly associated with prolonged TTS, as were mastectomy and reconstructive surgery., Conclusions: Despite evidence that longer TTS is associated with poorer outcomes in patients with breast cancer, TTS has steadily increased, which may be particularly detrimental to marginalized patients. Further studies are needed to ensure the delivery of timely care to all patients., (© 2024. The Author(s).)

Background: Paraesophageal hernia repairs (PEHRs) have high rates of radiographic recurrence, with some patients requiring repeat operation. This study characterizes patients who underwent PEHR to identify the factors associated with postoperative symptom improvement and radiographic recurrence. We furthermore use propensity score matching to compare patients undergoing initial and reoperative PEHR to identify the factors predictive of recurrence or need for reoperation., Methods: After IRB approval, patients who underwent PEHR at a tertiary care center between January 2018 and December 2022 were identified. Patient characteristics, preoperative imaging, operative findings, and postoperative outcomes were recorded. A computational generalization of inverse propensity score weight was then used to construct populations of initial and redo PEHR patients with similar covariate distributions., Results: A total of 244 patients underwent PEHR (78.7% female, mean age 65.4 ± 12.3 years). Most repairs were performed with crural closure (81.4%) and fundoplication (71.7%) with 14.2% utilizing mesh. Postoperatively, 76.5% of patients had subjective symptom improvement and of 157 patients with postoperative imaging, 52.9% had evidence of radiographic recurrence at a mean follow-up of 10.4 ± 13.6 months. Only 4.9% of patients required a redo operation. Hernia type, crural closure, fundoplication, and mesh usage were not predictors of radiographic recurrence or symptom improvement (P > 0.05). Propensity weight score analysis of 50 redo PEHRs compared to a matched cohort of 194 initial operations revealed lower rates of postoperative symptom improvement (P < 0.05) but no differences in need for revision, complication rates, ED visits, or readmissions., Conclusions: Most PEHR patients have symptomatic improvement with minimal complications and reoperations despite frequent radiographic recurrence. Hernia type, crural closure, fundoplication, and mesh usage were not significantly associated with recurrence or symptom improvement. Compared to initial PEHR, reoperative PEHRs had lower rates of symptom improvement but similar rates of recurrence, complications, and need for reoperation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In a clustered observational study, a treatment is assigned to groups and all units within the group are exposed to the treatment. We develop a new method for statistical adjustment in clustered observational studies using approximate balancing weights, a generalization of inverse propensity score weights that solve a convex optimization problem to find a set of weights that directly minimize a measure of covariate imbalance, subject to an additional penalty on the variance of the weights. We tailor the approximate balancing weights optimization problem to the clustered observational study setting by deriving an upper bound on the mean square error and finding weights that minimize this upper bound, linking the level of covariate balance to a bound on the bias. We implement the procedure by specializing the bound to a random cluster-level effects model, leading to a variance penalty that incorporates the signal-to-noise ratio and penalizes the weight on individuals and the total weight on groups differently according to the the intra-class correlation., (© 2024 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Objective: Many emergency general surgery (EGS) conditions can be managed operatively or nonoperatively, with outcomes that vary by diagnosis. We hypothesized that operative management would lead to higher in-hospital costs but to cost savings over time., Background: EGS conditions account for $28 billion in health care costs in the United States annually. Compared with scheduled surgery, patients who undergo emergency surgery are at increased risk of complications, readmissions, and death, with accompanying costs of care that are up to 50% higher than elective surgery. Our prior work demonstrated that operative management had variable impacts on clinical outcomes depending on the EGS condition., Methods: This was a nationwide, retrospective study using fee-for-service Medicare claims data. We included patients 65.5 years of age or older with a principal diagnosis for an EGS condition 7/1/2015-6/30/2018. EGS conditions were categorized as: colorectal, general abdominal, hepatopancreaticobiliary (HPB), intestinal obstruction, and upper gastrointestinal. We used near-far matching with a preference-based instrumental variable to adjust for confounding and selection bias. Outcomes included Medicare payments for the index hospitalization and at 30, 90, and 180 days., Results: Of 507,677 patients, 30.6% received an operation. For HPB conditions, costs for operative management were initially higher but became equivalent at 90 and 180 days. For all others, operative management was associated with higher inpatient costs, which persisted, though narrowed, over time. Out-of-pocket costs were nearly equivalent for operative and nonoperative management., Conclusions: Compared with nonoperative management, costs were higher or equivalent for operative management of EGS conditions through 180 days, which could impact decision-making for clinicians, patients, and health systems in situations where clinical outcomes are similar., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This comparative effectiveness study examined outcomes of operative vs. non-operative management for emergency general surgery (EGS) conditions in patients with recent cancer treatment (RT)., Methods: Medicare beneficiaries with a history of colorectal cancer hospitalized for an EGS condition (2016-2018) were identified. RT was defined as chemotherapy/radiation within 3 months prior to admission. Instrumental variable analysis assessed the impact of management on mortality and readmissions among survivors (30d, 60d, and 90d), for patients in whom there was clinical equipoise regarding optimal management strategy., Results: Of 26,097 patients, 13% had undergone RT. In both the RT and non-RT groups, the optimal management strategy was uncertain in 14%. Operative management conferred increased risk of mortality but not readmission in patients with RT compared to those without (90d mortality:+43%, p ​= ​0.03; 90d readmission:+7.1%, p ​= ​0.776)., Conclusions: In patients with RT for whom there is clinical equipoise regarding EGS management, operative intervention increases risk of mortality., Competing Interests: Declaration of competing interest Sara P. Ginzberg, Christopher J. Wirtalla, Luke J. Keele, Heather Wachtel, Elinore J. Kaufman, and Rachel R. Kelz have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: The benefit of primary care physician (PCP) follow-up as a potential means to reduce readmissions in hospitalized patients has been found in other medical conditions and among patients receiving high-risk surgery. However, little is known about the implications of PCP follow-up for patients with an emergency general surgery (EGS) condition., Objective: To evaluate the association between PCP follow-up and 30-day readmission rates after hospital discharge for an EGS condition., Design, Setting, and Participants: This cohort study used data from the Centers for Medicare & Medicaid Services Master Beneficiary Summary File, Inpatient, Carrier (Part B), and Durable Medical Equipment files for beneficiaries aged 66 years or older who were hospitalized with an EGS condition that was managed operatively or nonoperatively between September 1, 2016, and November 30, 2018. Eligible patients were enrolled in Medicare fee-for-service, admitted through the emergency department with a primary diagnosis of an EGS condition, and received a general surgery consultation during the admission. Data were analyzed between July 11, 2022, and June 5, 2023., Exposure: Follow-up with a PCP within 30 days after hospital discharge for the index admission., Main Outcomes and Measures: The primary outcome was readmission within 30 days after discharge for the index admission. An inverse probability weighted regression model was used to estimate the risk-adjusted association of PCP follow-up with 30-day readmission. The secondary outcome was readmission within 30 days after discharge stratified by treatment type (operative vs nonoperative treatment) during their index admission., Results: The study included 345 360 Medicare beneficiaries (mean [SD] age, 74.4 [12.0] years; 187 804 females [54.4%]) hospitalized with an EGS condition. Of these, 156 820 patients (45.4%) had a follow-up PCP visit, 108 544 (31.4%) received operative treatment during their index admission, and 236 816 (68.6%) received nonoperative treatment. Overall, 58 253 of 332 874 patients (17.5%) were readmitted within 30 days after discharge for the index admission. After risk adjustment and propensity weighting, patients who had PCP follow-up had 67% lower odds of readmission (adjusted odds ratio [AOR], 0.33; 95% CI, 0.31-0.36) compared with patients without PCP follow-up. After stratifying by treatment type, patients who were treated operatively during their index admission and had subsequent PCP follow-up within 30 days after discharge had 79% reduced odds of readmission (AOR, 0.21; 95% CI, 0.18-0.25); a similar association was seen among patients who were treated nonoperatively (AOR, 0.36; 95% CI, 0.34-0.39). Infectious conditions, heart failure, acute kidney failure, and chronic kidney disease were among the most frequent diagnoses prompting readmission overall and among operative and nonoperative treatment groups., Conclusions and Relevance: In this cohort study, follow-up with a PCP within 30 days after discharge for an EGS condition was associated with a significant reduction in the adjusted odds of 30-day readmission. This association was similar for patients who received operative care or nonoperative care during their index admission. In patients aged 66 years or older with an EGS condition, primary care coordination after discharge may be an important tool to reduce readmissions.

Background: Clinically localized Merkel cell carcinoma (MCC) is commonly treated with surgical excision and radiotherapy. The relationship between time to adjuvant radiotherapy and overall survival (OS) remains understudied., Methods: This retrospective study used data from the National Cancer Database (2006-2019). Patients with clinically localized MCC who received surgical excision and adjuvant radiotherapy were included. Multivariate regressions were used to account for various patient and tumor factors. The primary outcome was 5-year OS, and the secondary outcome was time from diagnosis to adjuvant radiation (TTR)., Results: Of the 1965 patients included, most were male (n = 1242, 63.2%) and white (n = 1915, 97.5%), and the median age was 74 years (interquartile range [IQR]: 66-81). The median TTR was 83 days (IQR: 65-106). A total of 83.6% of patients received radiotherapy to the primary site, 21.3% to the draining nodal basin, 17.1% to both, and 12.2% whose target location of radiotherapy was not recorded in the data. TTR of ≥79 days (the 45th percentile) was associated with worse OS on both univariate and multivariate analyses (log-rank p = 0.0014; hazard ratio [HR]: 1.258, 95% confidence interval [CI]: 1.055-1.500, p = 0.010). This persisted on sub-analyses of patients <80 years old (n = 1407; HR: 1.380, 95% CI: 1.080-1.764, p = 0.010) and of patients with Charlson comorbidity index (CCI) of 0 (n = 1411; HR: 1.284, 95% CI: 1.034-1.595, p = 0.024). Factors associated with delayed TTR included greater age (p = 0.039), male sex (p = 0.04), CCI > 1 (p = 0.036), academic facility (p < 0.001), rural county (p = 0.034), AJCC T2 stage (p = 0.010), negative margins (p = 0.017), 2+ pathologically positive regional nodes (p = 0.011), and margin size >2 cm (p = 0.015)., Conclusions: Delayed radiotherapy (≥79 days) was associated with worse OS of MCC patients. Further study in controlled cohorts is needed to ascertain this relationship., (© 2023 Wiley Periodicals LLC.)

Introduction: Analyzing hospital-free days (HFDs) offers a patient-centered approach to health services research. We hypothesized that, within emergency general surgery (EGS), multimorbidity would be associated with fewer HFDs, whether patients were managed operatively or nonoperatively., Methods: EGS patients were identified using national Medicare claims data (2015-2018). Patients were classified as multimorbid based on the presence of a Qualifying Comorbidity Set and stratified by treatment: operative (received surgery within 48 h of index admission) and nonoperative. HFDs were calculated through 180 d, beginning on the day of index admission, as days alive and spent outside of a hospital, an Emergency Department, or a long-term acute care facility. Univariate comparisons were performed using Kruskal-Wallis tests and risk-adjusted HFDs were compared between multimorbid and nonmultimorbid patients using multivariable zero-inflated negative binomial regression models., Results: Among 174,891 operative patients, 45.5% were multimorbid. Among 398,756 nonoperative patients, 59.2% were multimorbid. Multimorbid patients had fewer median HFDs than nonmultimorbid patients among operative and nonoperative cohorts (P < 0.001). At 6 mo, among operative patients, multimorbid patients had 6.5 fewer HFDs (P < 0.001), and among nonoperative patients, multimorbid patients had 7.9 fewer HFDs (P < 0.001). When length of stay was included as a covariate, nonoperative multimorbid patients still had 7.9 fewer HFDs than nonoperative, nonmultimorbid patients (P < 0.001)., Conclusions: HFDs offer a patient-centered, composite outcome for claims-based analyses. For EGS patients, multimorbidity was associated with less time alive and out of the hospital, especially when patients were managed nonoperatively., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We present a practical guide for the analysis of regression discontinuity (RD) designs in biomedical contexts. We begin by introducing key concepts, assumptions, and estimands within both the continuity-based framework and the local randomization framework. We then discuss modern estimation and inference methods within both frameworks, including approaches for bandwidth or local neighborhood selection, optimal treatment effect point estimation, and robust bias-corrected inference methods for uncertainty quantification. We also overview empirical falsification tests that can be used to support key assumptions. Our discussion focuses on two particular features that are relevant in biomedical research: (i) fuzzy RD designs, which often arise when therapeutic treatments are based on clinical guidelines, but patients with scores near the cutoff are treated contrary to the assignment rule; and (ii) RD designs with discrete scores, which are ubiquitous in biomedical applications. We illustrate our discussion with three empirical applications: the effect CD4 guidelines for anti-retroviral therapy on retention of HIV patients in South Africa, the effect of genetic guidelines for chemotherapy on breast cancer recurrence in the United States, and the effects of age-based patient cost-sharing on healthcare utilization in Taiwan. Complete replication materials employing publicly available data and statistical software in Python, R and Stata are provided, offering researchers all necessary tools to conduct an RD analysis., (© 2023 John Wiley & Sons Ltd.)

Importance: Sixty-five million individuals in the US live in primary care shortage areas with nearly one-third of Medicare patients in need of a primary care health care professional. Periodic health examinations and preventive care visits have demonstrated a benefit for surgical patients; however, the impact of primary care health care professional shortages on adverse outcomes from surgery is largely unknown., Objective: To determine if preoperative primary care utilization is associated with postoperative mortality following an emergency general surgery (EGS) operation among Black and White older adults., Design, Setting, and Participants: This was a retrospective cohort study that took place at US hospitals with an emergency department. Participants were Medicare patients aged 66 years or older who were admitted from the emergency department for an EGS condition between July 1, 2015, and June 30, 2018, and underwent an operation on hospital day 0, 1, or 2. The analysis was performed during December 2022. Patients were classified into 1 of 5 EGS condition categories based on principal diagnosis codes; colorectal, general abdominal, hepatopancreatobiliary, intestinal obstruction, or upper gastrointestinal. Mixed-effects multivariable logistic regression was used in the risk-adjusted models. An interaction term model was used to measure effect modification by race., Exposure: Primary care utilization in the year prior to presentation for an EGS operation., Main Outcome and Measures: In-hospital, 30-day, 60-day, 90-day, and 180-day mortality., Results: A total of 102 384 patients (mean age, 73.8 [SD, 11.5] years) were included in the study. Of those, 8559 were Black (8.4%) and 93 825 were White (91.6%). A total of 88 340 patients (86.3%) had seen a primary care physician in the year prior to their index hospitalization. After risk adjustment, patients with primary care exposure had 19% lower odds of in-hospital mortality than patients without primary care exposure (odds ratio [OR], 0.81; 95% CI, 0.72-0.92). At 30 days patients with primary care exposure had 27% lower odds of mortality (OR, 0.73; 95% CI, 0.67-0.80). This remained relatively stable at 60 days (OR, 0.75; 95% CI, 0.69-0.81), 90 days (OR, 0.74; 95% CI, 0.69-0.81), and 180 days (OR, 0.75; 95% CI, 0.70-0.81). None of the interactions between race and primary care physician exposure for mortality at any time interval were significantly different., Conclusions and Relevance: In this observational study of Black and White Medicare patients, primary care utilization had no impact on in-hospital mortality for Black patients, but was associated with decreased mortality for White patients. Primary care utilization was associated with decreased mortality for both Black and White patients at 30, 60, 90 and 180 days.

Introduction: Prior studies have sought to describe Emergency General Surgery (EGS) burden, but a detailed description of resource utilization for both operative and nonoperative management of EGS conditions has not been undertaken., Methods: Patient and hospital characteristics were extracted from Medicare data, 2015-2018. Operations, nonsurgical procedures, and other resources (i.e., radiology) were defined using Current Procedural Terminology codes., Results: One million eight hundred two thousand five hundred forty-five patients were included in the cohort. The mean age was 74.7 y and the most common diagnoses were upper gastrointestinal. The majority of hospitals were metropolitan (75.1%). Therapeutic radiology services were available in 78.4% of hospitals and operating rooms or endoscopy suites were available in 92.5% of hospitals. There was variability in resource utilization across EGS subconditions, with hepatobiliary (26.4%) and obstruction (23.9%) patients most frequently undergoing operation., Conclusions: Treatment of EGS diseases in older adults involves several interventional resources. Changes in EGS models, acute care surgery training, and interhospital care coordination may be beneficial to the treatment of EGS patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To understand how multimorbidity impacts operative versus nonoperative management of emergency general surgery (EGS) conditions., Background: EGS is a heterogenous field, encompassing operative and nonoperative treatment options. Decision-making is particularly complex for older patients with multimorbidity., Methods: Using an instrumental variable approach with near-far matching, this national, retrospective observational cohort study of Medicare beneficiaries examines the conditional effects of multimorbidity, defined using qualifying comorbidity sets, on operative versus nonoperative management of EGS conditions., Results: Of 507,667 patients with EGS conditions, 155,493 (30.6%) received an operation. Overall, 278,836 (54.9%) were multimorbid. After adjustment, multimorbidity significantly increased the risk of in-hospital mortality associated with operative management for general abdominal patients (+9.8%; P = 0.002) and upper gastrointestinal patients (+19.9%, P < 0.001) and the risk of 30-day mortality (+27.7%, P < 0.001) and nonroutine discharge (+21.8%, P = 0.007) associated with operative management for upper gastrointestinal patients. Regardless of multimorbidity status, operative management was associated with a higher risk of in-hospital mortality among colorectal patients (multimorbid: + 12%, P < 0.001; nonmultimorbid: +4%, P = 0.003), higher risk of nonroutine discharge among colorectal (multimorbid: +42.3%, P < 0.001; nonmultimorbid: +55.1%, P < 0.001) and intestinal obstruction patients (multimorbid: +14.6%, P = 0.001; nonmultimorbid: +14.8%, P = 0.001), and lower risk of nonroutine discharge (multimorbid: -11.5%, P < 0.001; nonmultimorbid: -11.9%, P < 0.001) and 30-day readmissions (multimorbid: -8.2%, P = 0.002; nonmultimorbid: -9.7%, P < 0.001) among hepatobiliary patients., Conclusions: The effects of multimorbidity on operative versus nonoperative management varied by EGS condition category. Physicians and patients should have honest conversations about the expected risks and benefits of treatment options, and future investigations should aim to understand the optimal management of multimorbid EGS patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Inverse probability weights are commonly used in epidemiology to estimate causal effects in observational studies. Researchers often focus on either the average treatment effect or the average treatment effect on the treated with inverse probability weighting estimators. However, poor overlap in the baseline covariates between the treated and control groups can produce extreme weights that can result in biased treatment effect estimates. One alternative to inverse probability weights are overlap weights, which target the population with the most overlap on observed covariates. Although estimates based on overlap weights produce less bias in such contexts, the causal estimand can be difficult to interpret. An alternative to model-based inverse probability weights are balancing weights, which directly target imbalances during the estimation process, rather than model fit. Here, we explore whether balancing weights allow analysts to target the average treatment effect on the treated in cases where inverse probability weights lead to biased estimates due to poor overlap. We conduct three simulation studies and an empirical application. We find that balancing weights often allow the analyst to still target the average treatment effect on the treated even when overlap is poor. We show that although overlap weights remain a key tool, more familiar estimands can sometimes be targeted by using balancing weights., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Lack of insurance has been independently associated with an increased risk of in-hospital mortality after abdominal aortic aneurysm repair, possibly due to worse control of comorbidities and delays in diagnosis and treatment. Medicaid expansion has improved insurance rates and access to care, potentially benefiting these patients. We sought to assess the association between Medicaid expansion and outcomes after abdominal aortic aneurysm repair., Methods: A retrospective analysis of Healthcare Cost and Utilization Project State Inpatient Databases data from 14 states between 2012 and 2018 was conducted. The sample was restricted to first-record abdominal aortic aneurysm repairs in adults under age 65 in states that expanded Medicaid on January 1, 2014 (Medicaid expansion group) or had not expanded before December 31, 2018 (non-expansion group). The Medicaid expansion and non-expansion groups were compared between pre-expansion (2012-2013) and post-expansion (2014-2018) time periods to assess baseline demographic and operative differences. We used difference-in-differences multivariable logistic regression adjusted for patient factors, open vs endovascular repair, and standard errors clustered by state. Our primary outcome was in-hospital mortality. Outcomes were stratified by insurance type., Results: We examined 8995 patients undergoing abdominal aortic aneurysm repair, including 3789 (42.1%) in non-expansion states and 5206 (57.9%) in Medicaid expansion states. Rates of Medicaid insurance were unchanged in non-expansion states but increased in Medicaid expansion states post-expansion (non-expansion: 10.9% to 9.8%; P = .346; expansion: 9.7% to 19.7%; P < .001). One in 10 patients from both non-expansion and Medicaid expansion states presented with ruptured aneurysms, which did not change over time. Rates of open repair decreased in both non-expansion and Medicaid expansion states over time (non-expansion: 25.1% to 19.2%; P < .001; expansion: 25.2% to 18.4%; P < .001). On adjusted difference-in-differences analysis between expansion and non-expansion states pre-to post-expansion, Medicaid expansion was associated with a 1.02% absolute reduction in in-hospital mortality among all patients (95% confidence interval, -1.87% to -0.17%; P = .019). Additionally, among patients who were either on Medicaid or were uninsured (ie, the patients most likely to be impacted by Medicaid expansion), a larger 4.17% decrease in in-hospital mortality was observed (95% confidence interval, -6.47% to -1.87%; P < .001). In contrast, no significant difference-in-difference in mortality was observed for privately insured patients., Conclusions: Medicaid expansion was associated with decreased in-hospital mortality after abdominal aortic aneurysm repair among all patients and particularly among patients who were either on Medicaid or were uninsured. Our results provide support for improved access to care for patients undergoing abdominal aortic aneurysm repair through Medicaid expansion., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Many emergency general surgery (EGS) conditions can be managed both operatively or nonoperatively; however, it is unknown whether the decision to operate affects Black and White patients differentially., Methods: We identified a nationwide cohort of Black and White Medicare beneficiaries, hospitalized for common EGS conditions from July 2015 to June 2018. Using near-far matching to adjust for measurable confounding and an instrumental variable analysis to control for selection bias associated with treatment assignment, we compare outcomes of operative and nonoperative management in a stratified population of Black and White patients. Outcomes included in-hospital mortality, 30-day mortality, nonroutine discharge, and 30-day readmissions. An interaction test based on a t test was used to determine the conditional effects of operative versus nonoperative management between Black and White patients., Results: A total of 556,087 patients met inclusion criteria, of which 59,519 (10.7%) were Black and 496,568 (89.3%) were White. Overall, 165,932 (29.8%) patients had an operation and 390,155 (70.2%) were managed nonoperatively. Significant outcome differences were seen between operative and nonoperative management for some conditions; however, no significant differences were seen for the conditional effect of race on outcomes., Conclusions: The decision to manage an EGS patient operatively versus nonoperatively has varying effects on surgical outcomes. These effects vary by EGS condition. There were no significant conditional effects of race on the outcomes of operative versus nonoperative management among universally insured older adults hospitalized with EGS conditions., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine the effect of operative versus nonoperative management of emergency general surgery conditions on short-term and long-term outcomes., Background: Many emergency general surgery conditions can be managed either operatively or nonoperatively, but high-quality evidence to guide management decisions is scarce., Methods: We included 507,677 Medicare patients treated for an emergency general surgery condition between July 1, 2015, and June 30, 2018. Operative management was compared with nonoperative management using a preference-based instrumental variable analysis and near-far matching to minimize selection bias and unmeasured confounding. Outcomes were mortality, complications, and readmissions., Results: For hepatopancreaticobiliary conditions, operative management was associated with lower risk of mortality at 30 days [-2.6% (95% confidence interval: -4.0, -1.3)], 90 days [-4.7% (-6.50, -2.8)], and 180 days [-6.4% (-8.5, -4.2)]. Among 56,582 intestinal obstruction patients, operative management was associated with a higher risk of inpatient mortality [2.8% (0.7, 4.9)] but no significant difference thereafter. For upper gastrointestinal conditions, operative management was associated with a 9.7% higher risk of in-hospital mortality (6.4, 13.1), which increased over time. There was a 6.9% higher risk of inpatient mortality (3.6, 10.2) with operative management for colorectal conditions, which increased over time. For general abdominal conditions, operative management was associated with 12.2% increased risk of inpatient mortality (8.7, 15.8). This effect was attenuated at 30 days [8.5% (3.8, 13.2)] and nonsignificant thereafter., Conclusions: The effect of operative emergency general surgery management varied across conditions and over time. For colorectal and upper gastrointestinal conditions, outcomes are superior with nonoperative management, whereas surgery is favored for patients with hepatopancreaticobiliary conditions. For obstructions and general abdominal conditions, results were equivalent overall. These findings may support patients, clinicians, and families making these challenging decisions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Regional lymph node micrometastases from Merkel cell carcinoma (MCC) can be treated with completion lymph node dissection (CLND) and/or radiation therapy (RT). It is unclear how these options compare in terms of survival benefits for patients., Patients and Methods: This retrospective cohort study used data from years 2012-2019 of the National Cancer Database. Patients with MCC and clinically negative, but pathologically positive, lymph node metastases who received RT to and/or CLND of the regional lymph node basin were included. Inverse probability weight balancing was performed using covariates followed by Cox proportional hazards modeling for survival analysis., Results: A total of 962 patients were included [median (interquartile range) age, 74 (67-80) years, 662 (68.8%) male patients, 926 (96.3%) white patients]. The majority (63%, n = 606) had a CLND only, while 18% (n = 173) had RT only, and 19% (n = 183) had both CLND and RT. From 2016 to 2019, usage of RT only increased from 10% to 31.8%. Multivariate analysis demonstrated that treatment modality was not associated with survival [RT versus CLND, hazard ratio (HR) 0.842, 95% confidence interval (CI) 0.621-1.142, p = 0.269, RT+CLND versus CLND, HR 1.029, 95% CI 0.775-1.367, p = 0.844]. This persisted after balancing weights (RT versus CLND, HR 0.837, 95% CI 0.614-1.142, p = 0.262, RT+CLND versus CLND, HR 1.085, 95% CI 0.801-1.470, p = 0.599)., Conclusions: The usage of RT for nodal micrometastasis in MCC is increasing as compared with CLND. This strategy appears to be safe, with no significant difference in survival outcomes., (© 2023. Society of Surgical Oncology.)

Importance: Variation in outcomes across hospitals adversely affects surgical patients. The use of high-quality hospitals varies by population, which may contribute to surgical disparities., Objective: To simulate the implications of data-driven hospital selection for social welfare among patients who underwent colorectal cancer surgery., Design, Setting, and Participants: This economic evaluation used the hospital inpatient file from the Florida Agency for Health Care Administration. Surgical outcomes of patients who were treated between January 1, 2016, and December 31, 2018 (training cohort), were used to estimate hospital performance. Costs and benefits of care at alternative hospitals were assessed in patients who were treated between January 1, 2019, and December 31, 2019 (testing cohort). The cohorts comprised patients 18 years or older who underwent elective colorectal resection for benign or malignant neoplasms. Data were analyzed from March to October 2022., Exposures: Using hierarchical logistic regression, we estimated the implications of hospital selection for in-hospital mortality risk in patients in the training cohort. These estimates were applied to patients in the testing cohort using bayesian simulations to compare outcomes at each patient's highest-performing and chosen local hospitals. Analyses were stratified by race and ethnicity to evaluate the potential implications for equity., Main Outcomes and Measures: The primary outcome was the mean patient-level change in social welfare, a composite measure balancing the value of reduced mortality with associated costs of care at higher-performing hospitals., Results: A total of 21 098 patients (mean [SD] age, 67.3 [12.0] years; 10 782 males [51.1%]; 2232 Black [10.6%] and 18 866 White [89.4%] individuals) who were treated at 178 hospitals were included. A higher-quality local hospital was identified for 3057 of 5000 patients (61.1%) in the testing cohort. Selecting the highest-performing hospital was associated with a 26.5% (95% CI, 24.5%-29.0%) relative reduction and 0.24% (95% CI, 0.23%-0.25%) absolute reduction in mortality risk. A mean amount of $1953 (95% CI, $1744-$2162) was gained in social welfare per patient treated. Simulated reassignment to a higher-quality local hospital was associated with a 23.5% (95% CI, 19.3%-32.9%) relative reduction and 0.26% (95% CI, 0.21%-0.30%) absolute reduction in mortality risk for Black patients, with $2427 (95% CI, $1697-$3158) gained in social welfare., Conclusions and Relevance: In this economic evaluation, using procedure-specific hospital performance as the primary factor in the selection of a local hospital for colorectal cancer surgery was associated with improved outcomes for both patients and society. Surgical outcomes data can be used to transform care and guide policy in colorectal cancer.

Background and Objectives: Type II diabetes mellitus (T2DM) can lead to an immunosuppressed state, but whether T2DM is associated with worse outcomes for patients with melanoma has not been well studied., Methods: Consecutive patients diagnosed with clinical stage I-II cutaneous melanoma who underwent sentinel lymph node biopsy at a single institution (2007-2016) were identified. Melanoma characteristics and recurrence/survival outcomes were compared between patients with and without T2DM at the time of melanoma diagnosis., Results: Of 1128 patients evaluated, 111 (9.8%) had T2DM (n = 94 [84.7%] non-insulin dependent [NID-T2DM]; n = 17 [15.3%] insulin dependent [ID-T2DM]). T2DM patients were more likely to be older (odds ratio [OR] 1.04, p < 0.001), male (OR 2.15, p = 0.003), have tumors >1.0 mm (OR 1.88, p = 0.023), and have microsatellitosis (OR 2.29, p = 0.030). Five-year cumulative incidence of melanoma recurrence was significantly higher for patients with ID-T2DM (46.7% ID-T2DM vs. 25.7% NID-T2DM vs. 17.1% no T2DM, p < 0.001), and on multivariable analysis, ID-T2DM was independently associated with melanoma recurrence (hazard ratio 2.57, p = 0.015). No difference in 5-year disease-specific survival was observed between groups., Conclusions: ID-T2DM appears to be associated with more advanced melanoma and increased risk for melanoma recurrence. Further study as to whether this reflects differences in tumor biology or host factors is warranted., (© 2022 Wiley Periodicals LLC.)

Importance: A surgical consultation is a critical first step in the care of patients with emergency general surgery conditions. It is unknown if Black Medicare patients and White Medicare patients receive surgical consultations at similar rates when they are admitted from the emergency department., Objective: To determine whether Black Medicare patients have similar rates of surgical consultations when compared with White Medicare patients after being admitted from the emergency department with an emergency general surgery condition., Design, Setting, and Participants: This was a retrospective cohort study that took place at US hospitals with an emergency department and used a computational generalization of inverse propensity score weight to create patient populations with similar covariate distributions. Participants were Medicare patients age 65.5 years or older admitted from the emergency department for an emergency general surgery condition between July 1, 2015, and June 30, 2018. The analysis was performed during February 2022. Patients were classified into 1 of 5 emergency general surgery condition categories based on principal diagnosis codes: colorectal, general abdominal, hepatopancreatobiliary, intestinal obstruction, and upper gastrointestinal., Exposures: Black vs White race., Main Outcomes and Measures: Receipt of a surgical consultation after admission from the emergency department with an emergency general surgery condition., Results: A total of 1 686 940 patients were included in the study. Of those included, 214 788 patients were Black (12.7%) and 1 472 152 patients were White (87.3%). After standardizing for medical and diagnostic imaging covariates, Black patients had 14% lower odds of receiving a surgical consultation (odds ratio [OR], 0.86; 95% CI, 0.85-0.87) with a risk difference of -3.17 (95% CI, -3.41 to -2.92). After standardizing for socioeconomic covariates, Black patients remained at an 11% lower odds of receiving a surgical consultation compared with similar White patients (OR, 0.89; 95% CI, 0.88-0.90) with a risk difference of -2.49 (95% CI, -2.75 to -2.23). Additionally, when restricting the analysis to Black patients and White patients who were treated in the same hospitals, Black patients had 8% lower odds of receiving a surgical consultation when compared with White patients (OR, 0.92; 95% CI, 0.90-0.93) with a risk difference of -1.82 (95% CI, -2.18 to -1.46)., Conclusions and Relevance: In this study, Black Medicare patients had lower odds of receiving a surgical consultation after being admitted from the emergency department with an emergency general surgery condition when compared with similar White Medicare patients. These disparities in consultation rates cannot be fully attributed to medical comorbidities, insurance status, socioeconomic factors, or individual hospital-level effects.

Background: Electronic health records (EHRs) offer opportunities for comparative effectiveness research to inform decision making. However, to provide useful evidence, these studies must address confounding and treatment effect heterogeneity according to unmeasured prognostic factors. Local instrumental variable (LIV) methods can help studies address these challenges, but have yet to be applied to EHR data. This article critically examines a LIV approach to evaluate the cost-effectiveness of emergency surgery (ES) for common acute conditions from EHRs., Methods: This article uses hospital episodes statistics (HES) data for emergency hospital admissions with acute appendicitis, diverticular disease, and abdominal wall hernia to 175 acute hospitals in England from 2010 to 2019. For each emergency admission, the instrumental variable for ES receipt was each hospital's ES rate in the year preceding the emergency admission. The LIV approach provided individual-level estimates of the incremental quality-adjusted life-years, costs and net monetary benefit of ES, which were aggregated to the overall population and subpopulations of interest, and contrasted with those from traditional IV and risk-adjustment approaches., Results: The study included 268,144 (appendicitis), 138,869 (diverticular disease), and 106,432 (hernia) patients. The instrument was found to be strong and to minimize covariate imbalance. For diverticular disease, the results differed by method; although the traditional approaches reported that, overall, ES was not cost-effective, the LIV approach reported that ES was cost-effective but with wide statistical uncertainty. For all 3 conditions, the LIV approach found heterogeneity in the cost-effectiveness estimates across population subgroups: in particular, ES was not cost-effective for patients with severe levels of frailty., Conclusions: EHRs can be combined with LIV methods to provide evidence on the cost-effectiveness of routinely provided interventions, while fully recognizing heterogeneity., Highlights: This article addresses the confounding and heterogeneity that arise when assessing the comparative effectiveness from electronic health records (EHR) data, by applying a local instrumental variable (LIV) approach to evaluate the cost-effectiveness of emergency surgery (ES) versus alternative strategies, for patients with common acute conditions (appendicitis, diverticular disease, and abdominal wall hernia).The instrumental variable, the hospital's tendency to operate, was found to be strongly associated with ES receipt and to minimize imbalances in baseline characteristics between the comparison groups.The LIV approach found that, for each condition, there was heterogeneity in the estimates of cost-effectiveness according to baseline characteristics.The study illustrates how an LIV approach can be applied to EHR data to provide cost-effectiveness estimates that recognize heterogeneity and can be used to inform decision making as well as to generate hypotheses for further research.

Background: Little is known about the impact of multimorbidity on long-term outcomes for older emergency general surgery patients., Study Design: Medicare beneficiaries, age 65 and older, who underwent operative management of an emergency general surgery condition were identified using Centers for Medicare & Medicaid claims data. Patients were classified as multimorbid based on the presence of a Qualifying Comorbidity Set (a specific combination of comorbid conditions known to be associated with increased risk of in-hospital mortality in the general surgery setting) and compared with those without multimorbidity. Risk-adjusted outcomes through 180 days after discharge from index hospitalization were calculated using linear and logistic regressions., Results: Of 174,891 included patients, 45.5% were identified as multimorbid. Multimorbid patients had higher rates of mortality during index hospitalization (5.9% vs 0.7%, odds ratio [OR] 3.05, p &lt; 0.001) and through 6 months (17.1% vs 3.4%, OR 2.33, p &lt; 0.001) after discharge. Multimorbid patients experienced higher rates of readmission at 1 month (22.9% vs 11.4%, OR 1.48, p &lt; 0.001) and 6 months (38.2% vs 21.2%, OR 1.48, p &lt; 0.001) after discharge, lower rates of discharge to home (42.5% vs 74.2%, OR 0.52, p &lt; 0.001), higher rates of discharge to rehabilitation/nursing facility (28.3% vs 11.3%, OR 1.62, p &lt; 0.001), greater than double the use of home oxygen, walker, wheelchair, bedside commode, and hospital bed (p &lt; 0.001), longer length of index hospitalization (1.33 additional in-patient days, p &lt; 0.001), and higher costs through 6 months ($5,162 additional, p &lt; 0.001)., Conclusions: Older, multimorbid patients experience worse outcomes, including survival and independent function, after emergency general surgery than nonmultimorbid patients through 6 months after discharge from index hospitalization. This information is important for setting recovery expectations for high-risk patients to improve shared decision-making., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy for which factors predictive of disease-specific survival (DSS) are poorly defined., Methods: Patients from six centers (2005-2020) with clinical stage I-II MCC who underwent sentinel lymph node (SLN) biopsy were included. Factors associated with DSS were identified using competing-risks regression analysis. Risk-score modeling was established using competing-risks regression on a training dataset and internally validated by point assignment to variables., Results: Of 604 patients, 474 (78.5%) and 128 (21.2%) patients had clinical stage I and II disease, respectively, and 189 (31.3%) had SLN metastases. The 5-year DSS rate was 81.8% with a median follow-up of 31 months. Prognostic factors associated with worse DSS included increasing age (hazard ratio [HR] 1.03, p = 0.046), male sex (HR 3.21, p = 0.021), immune compromise (HR 2.46, p = 0.013), presence of microsatellites (HR 2.65, p = 0.041), and regional nodal involvement (1 node: HR 2.48, p = 0.039; ≥2 nodes: HR 2.95, p = 0.026). An internally validated, risk-score model incorporating all of these factors was developed with good performance (AUC 0.738). Patients with ≤ 4.00 and > 4.00 points had 5-year DSS rates of 89.4% and 67.2%, respectively. Five-year DSS for pathologic stage I/II patients with > 4.00 points (n = 49) was 79.8% and for pathologic stage III patients with ≤ 4.00 points (n = 62) was 90.3%., Conclusions: A risk-score model, including patient and tumor factors, based on DSS improves prognostic assessment of patients with clinically localized MCC. This may inform surveillance strategies and patient selection for adjuvant therapy trials., (© 2022. Society of Surgical Oncology.)

Background: Little is known about the impact of multimorbidity on outcomes for older emergency general surgery patients., Objective: The aim was to understand whether having multiple comorbidities confers the same amount of risk as specific combinations of comorbidities (multimorbidity) for a patient undergoing emergency general surgery., Research Design: Retrospective observational study using state discharge data., Subjects: Medicare beneficiaries who underwent an operation for an emergency general surgery condition in New York, Florida, or Pennsylvania (2012-2013)., Measures: Patients were classified as multimorbid using Qualifying Comorbidity Sets (QCSs). Outcomes included in-hospital mortality, hospital length of stay and discharge status., Results: Of 312,160 patients, a large minority (37.4%) were multimorbid. Non-QCS patients did not have a specific combination of comorbidities to satisfy a QCS, but 64.1% of these patients had 3+ comorbid conditions. Multimorbidity was associated with increased in-hospital mortality (10.5% vs. 3.9%, P <0.001), decreased rates of discharge to home (16.2% vs. 37.1%, P <0.001), and longer length of stay (10.4 d±13.5 vs. 6.7 d±9.3, P <0.001) when compared with non-QCS patients. Risks varied between individual QCSs., Conclusions: Multimorbidity, defined by satisfying a specific QCS, is strongly associated with poor outcomes for older patients requiring emergency general surgery in the United States. Variation in risk of in-hospital mortality, discharge status, and length of stay between individual QCSs suggests that multimorbidity does not carry the same prognostic weight as having multiple comorbidities-the specifics of which are important in setting expectations for individual, complex patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

In some cluster randomized trials, subjects may not comply with their assigned treatment status. Such treatment noncompliance can create opportunities for spillover effects within clusters. Little research has focused on what can be learned in such context. This article provides a non-technical review of recent work on the complications that arise in cluster randomized trials where some units within treated clusters do not comply with treatment but the treatment spillovers over to these units. We motivate concepts using a hypothetical vaccine cluster randomized trial. We review that standard instrumental variable methods cannot recover the complier average causal effect in the presence of these spillovers. In fact, we review that without additional assumptions, little can be learned about compliance effects or spillover effects. We discuss one additional assumption that allows for bounds on a key causal effect. We also outline an estimator for these bounds.

Background: Results of an earlier retrospective study from our institution suggested that patients with triple negative breast cancer (TNBC) who had preoperative MRI may have had an improved local recurrence rate (LRR) after breast conserving surgery (BCS). We aimed to clarify the impact of preoperative MRI on surgical outcomes in an expanded TNBC cohort treated by BCS in a contemporary era., Methods: Our study cohort comprised 648 patients with TNBC who underwent BCS between 2009 and 2018. Demographic and clinical characteristics were compared between those with (n = 292, 45.1%) and without (n = 356, 54.9%) preoperative MRI. Multivariable logistic regression was performed to assess the association of preoperative MRI with surgical outcomes., Results: The crude LRR of 3.5% was lower than previously reported. Univariable analyses demonstrated that the LRR and re-excision rates in the MRI and no-MRI groups were 3.4 and 3.7%, 21.6% and 27.2%, p = 0.876 and p = 0.10, respectively. Multivariable logistic regression analyses demonstrated that preoperative MRI was not associated with a lower LRR: odds ratio (OR) = 1.42 (p = 0.5). During our study period, new margin guidelines and shave margins practice were adopted in 2014 and 2015. To account for their effects, the year of diagnosis/surgery and other clinical variables were adjusted in multivariable logistic regression and inverse probability weighting models to demonstrate that preoperative MRI remained associated with a lower re-excision risk, OR 0.56, p = 0.04l; and a lower re-excision rate, 23.15% versus 36.0%, p < 0.01, respectively., Conclusions: Our findings suggested that patients with TNBC anticipating BCS may benefit from preoperative MRI., (© 2022. Society of Surgical Oncology.)

Background: Although high volume centers (HVC) equate to improved outcomes in rectal cancer, the impact of surgical volume related to race is less defined., Methods: Patients who underwent surgical resection for stage I-III rectal adenocarcinoma were divided into cohorts based on race and hospital surgical volume. Outcomes were analyzed following 1:1 propensity-score matching using logistic, Poisson, and Cox regression analyses with marginal effects., Results: Fifty-four thousand one hundred and eighty-four (91.5%) non-Black and 5043 (8.5%) Black patients underwent resection of rectal cancer. Following 1:1 matching of non-Black (N = 5026) and Black patients, 5-year overall survival (OS) of Black patients was worse (72% vs. 74.4%, average marginal effects [AME] 0.66, p = 0.04) than non-Black patients. When compared to non-Black patients managed at HVCs, Black patients had worse OS (70.1% vs. 74.7%, AME 1.55, p = 0.03), but this difference was not significant when comparing OS between non-Black and Black patients managed at HVCs (72.3% vs. 74.7%, AME 0.62, p = 0.06). Length of stay was longer among Black and HVC patients across all cohorts. There was no difference across cohorts in 90-day mortality., Conclusions: Although racial disparities exist in rectal cancer, this disparity appears to be ameliorated when patients are managed at HVCs., (© 2021 Wiley Periodicals LLC.)

Background: In many randomized controlled trials, a substantial proportion of patients do not comply with the treatment protocol to which they have been randomly assigned. Randomized controlled trials are required to report results according to the intention-to-treat estimand, but recent methodological guidance recognizes the importance of estimating other causal quantities., Methods: This article outlines an analytical framework for randomized controlled trials with non-compliance. We apply the ICH E9 (R1) addendum and combine it with the potential outcomes framework to define key estimands, outline the major assumptions for identification of each estimand, and highlight the assumptions that cannot be verified from the randomized controlled trial data. We contrast the assumptions and estimates in a re-analysis of the REFLUX trial. We report alternative estimates for the effectiveness of receipt of laparoscopic surgery versus medical management for patients with gastro-intestinal reflux disease., Results: The article finds that adjusted as-treated and per-protocol estimates were similar in magnitude to those based intention-to-treat methods. Instrumental variable estimates of the complier average causal effect were larger, with wider confidence intervals., Conclusion: We recommend that in randomized controlled trials with non-compliance, studies should outline which estimand is most relevant to the study context, evaluate key assumptions, and present estimates from a range of methods as a sensitivity analysis.

Background: Adequate lymphadenectomy with at least 16 nodes retrieved at the time of gastrectomy is a quality measure recommended to ensure adequate staging. The minimum nodal retrieval recommended after receipt of neoadjuvant chemotherapy (NACT) is less defined., Methods: Patients with clinical stages 1 to 3 gastric adenocarcinoma who received NACT and surgical resection were identified from the 2004-2015 National Cancer Database. The optimal nodal harvest number was calculated with Cox spline regression modeling. Cohorts with a nodal harvest higher or lower than this number were 1:1 propensity score-matched. Overall survival (OS) was analyzed using Kaplan-Meier survival estimates., Results: Among 4337 patients receiving NACT, the optimal minimal nodal harvest at gastrectomy was 23 nodes. Compared with the patients who had fewer than 23 nodes retrieved, the patients with at least 23 nodes examined (n = 1073, 24.7%) were more likely to be female (26.1% vs 22%; p = 0.006) and non-white (29.3% vs 18.5%; p < 0.0001), to have a Charlson-Deyo score of 0 (71.5% vs 66.8%; p = 0.005), and to have undergone resection at an academic facility (67.9% vs 51.5%; p < 0.0001). The patients with at least 23 nodes examined had higher proportions of high-grade tumor (62% vs 57.4%; p = 0.030), pT3 or pT4 tumor (56.3% vs 48.7%; p < 0.0001), body tumor (21.3% vs 12.5%; p < 0.0001), or antrum/pylorus tumor (15.3% vs 11.4%; p < 0.0001). The patients with at least 23 nodes were more likely to have lymph node metastases identified (61% vs 51%; p < 0.0001). After matching, the patients with at least 23 nodes (n = 990) demonstrated an improved 5-year OS (57.9% vs 49%; p = 0.001)., Conclusions: The extent of lymphadenectomy during gastrectomy for gastric adenocarcinoma should not be reduced after NACT because adequate lymph node retrieval remains important for prognostication., (© 2021. Society of Surgical Oncology.)

Background and Aim: This study quantifies how changes in healthcare utilization and delivery during the first months of the COVID-19 pandemic have altered the presentation, treatment, and management of patients with gastrointestinal (GI) malignancies within an academic health system., Methods and Results: Patients diagnosed with a GI malignancy (ICD10: C15-C26) who received medical care within the health system during the observation period (first 44 weeks of 2019 and 2020) were identified for a retrospective cohort study. Deidentified patient encounter parameters were collected for this observation period and separated into pre-pandemic (weeks 1-10) and early pandemic (weeks 11-20) study periods. Difference-in-difference analyses adjusted for week-specific and year-specific effects quantified the impact of the COVID-19 pandemic on care delivery between pre-pandemic and early pandemic study periods in 2020. Across all GI malignancies, the COVID-19 pandemic has been associated with a significant decline in the number of patients with new patient visits (NPVs) (p = 1.2 × 10 -4 ), Radiology encounters (p = 1.9 × 10 -7 ), Surgery encounters (p = 1.6 × 10 -3 ), Radiation Oncology encounters (p = 4.1 × 10 -3 ), and infusion visits (6.1 × 10 -5 ). Subgroup analyses revealed cancer-specific variations in changes to delivery. Patients with colorectal cancer (CRC) had the most significant decrease in NPVs (p = 7.1 × 10 -5 ), which was significantly associated with a concomitant decrease in colonoscopies performed during the early pandemic period (r 2  = 0.722, p = 2.1 × 10 -10 )., Conclusions: The COVID-19 pandemic has been associated with significant disruptions to care delivery. While these effects were appreciated broadly across GI malignancies, CRC, diagnosed and managed by periodic screening, has been affected most acutely., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: National medical/surgical organizations have recommended the use of neoadjuvant endocrine therapy (NET) to bridge surgery delay of weeks to months for patients with hormone receptor positive (HR+) breast cancer during the ongoing coronavirus disease 2019 (COVID-19) pandemic. The effects of NET of varying durations on pathologic response are unclear. Using the National Cancer Database (NCDB), we evaluated objective response to short (< 9 weeks), moderate (9-27 weeks), and long (> 27 weeks) duration of NET., Patients and Methods: The study cohort included female patients diagnosed with nonmetastatic invasive HR+ breast cancer, stratifying by those who received NET versus no NET between 2004 and 2016. Pathologic response was grouped into four categories (complete, downstaged, stable, upstaged) by comparing clinical and pathologic staging data. Objective response to NET included complete, downstaged, and stable pathologic response. Clinical characteristics were compared using χ 2 and analysis of variance (ANOVA) tests. Multivariable logistic regression was used to determine factors associated with NET use and objective response according to NET duration., Results: A minority (1.2%) received NET in our cohort. Factors associated with NET use included older age, non-Black patients, more advanced clinical stage, higher comorbidity score, government insurance, and lobular histology. Objective response rate (ORR) was 56.7%, 52.1%, and 49.0% after short, moderate, and long NET duration, respectively., Conclusion: Short NET duration did not result in an inferior ORR. Future study to evaluate the interaction between surgery delay and NET use on clinical outcome will provide insights into the safety of NET to bridge potential surgery delay in patients with HR+ breast cancer., (© 2021. Society of Surgical Oncology.)

Introduction: National guidelines specify against immediate breast reconstruction (IBR) among inflammatory breast cancer (IBC) patients. However, limited data exist regarding this practice. We report practice patterns and oncologic outcomes among nonmetastatic IBC patients receiving trimodality therapy, with or without IBR., Methods: Using the National Cancer Database, we identified nonmetastatic IBC patients treated with trimodality therapy from 2004 to 2016. Primary outcome was overall survival (OS), assessed on unadjusted analysis using Kaplan-Meier estimates and on adjusted analysis using multivariable Cox proportional hazards and inverse probability weighting (IPW) models. OS analysis was also conducted with propensity score matched (PSM) cohorts. Secondary outcomes included IBR utilization rates, time to postmastectomy radiotherapy (PMRT), and surgical outcomes., Results: 6589 women were included, including 5954 (90.4%) non-reconstructed and 635 (9.6%) IBR. Among IBR recipients, 250 (39.4%) underwent autologous reconstruction, 171 (26.9%) underwent implant-based reconstruction, and 214 (33.7%) unspecified. IBR utilization increased from 6.3% to 10.1% from 2004 to 2016 at a 4% average annual growth rate (P < 0.001). Median follow-up was 43 and 45 months for IBR and non-reconstructed patients, respectively (P = 0.29). On Cox multivariable analysis, IBR was associated with improved OS (HR 0.63, 95% CI 0.44-0.90, P = 0.01), but this association was not significant on IPW analysis (P = 0.06). In PSM cohorts, this association remained significant (HR 0.60, 95% CI 0.40-0.92, P = 0.02). Margin status, time to PMRT, 30-day readmission, and 30-/90-day mortality did not differ between groups (all P > 0.05)., Conclusion: Although not endorsed by national guidelines, IBR is increasing among IBC patients; however, more granular data are needed to determine oncologic safety., (© 2021. Society of Surgical Oncology.)

Importance: Childhood suicidality (ie, suicidal ideation or attempts) rates are increasing, and attention-deficit/hyperactivity disorder (ADHD) and externalizing symptoms are common risk factors associated with suicidality. More data are needed to describe associations of ADHD pharmacotherapy with childhood suicidality., Objective: To investigate the associations of ADHD pharmacotherapy with externalizing symptoms and childhood suicidality., Design, Setting, and Participants: In this cohort study, cross-sectional and 1-year-longitudinal associations were examined using data (collected during 2016-2019) from the Adolescent Brain Cognitive Development (ABCD) Study, a large, diverse US sample of children aged 9 to 11 years. Data analysis was performed from November to December 2020., Exposures: Main and interaction associations of externalizing symptoms (hyperactivity ADHD symptoms, oppositional defiant, and conduct disorder symptoms) and ADHD medication treatment (methylphenidate and amphetamine derivatives, α-2-agonists, and atomoxetine) at baseline assessment., Main Outcomes and Measures: Child-reported suicidality (past and present at baseline; current at longitudinal assessment). Covariates were age, sex, race/ethnicity, parents' education, marital status, and concomitant child psychiatric pharmacotherapy (antidepressants and antipsychotics)., Results: Among 11 878 children at baseline assessment (mean [SD] age, 9.9 [0.6] years; 6196 boys [52.2%]; 8805 White [74.1%]), 1006 (8.5%) were treated with ADHD medication and 1040 (8.8%) reported past or current suicidality. Externalizing symptoms (median [range], 1 [0-29] symptom count) were associated with suicidality (for a change of 1 SD in symptoms, odds ratio [OR], 1.34; 95% CI, 1.26-1.42; P < .001), as was ADHD medication treatment (OR, 1.32; 95% CI, 1.06-1.64; P = .01). ADHD medication use was associated with less suicidality in children with more externalizing symptoms (significant symptom-by-medication interaction, B = -0.250; SE = 0.086; P = .004), such that for children who were not receiving ADHD medications, there was an association between more externalizing symptoms and suicidality (for a change of 1 SD in symptoms, OR, 1.42; 95% CI, 1.33-1.52; P < .001); however, for children who were receiving ADHD medication, there was no such association (OR, 1.15; 95% CI, 0.97-1.35; P = .10). The association with medication remained even when covarying for multiple confounders, including risk and protective factors for suicidality in ABCD, and was replicated in 1-year longitudinal follow-up. Sensitivity analyses matching participants with high numbers of externalizing symptoms taking and not taking ADHD medication treatment confirmed its association with less suicidality., Conclusions and Relevance: These findings suggest that ADHD medication treatment is associated with less suicidality in children with substantial externalizing symptoms and may be used to inform childhood suicide prevention strategies.

Background: Surface mining has become a significant method of coal mining in the Central Appalachian region of the eastern United States alongside the traditional underground mining. Concerns have been raised about the health effects of this surface mining, particularly mountaintop removal mining where coal is mined upon steep mountaintops by removing the mountaintop through clearcutting forests and explosives., Methods: We used a control group design with a pretest and a posttest to assess the associations of surface mining in Central Appalachia with low birth weight and other adverse birth outcomes. The pretest period is 1977-1989, a period of low surface mining activity. We consider three posttest periods: 1990-1998, 1999-2011 and 2012-2017, with 1999-2011 as the primary analysis and the other periods as secondary analyses. Surface mining in Central Appalachia increased after 1989, partly resulting from the Clean Air Act Amendments of 1990 which made surface mining in Appalachia more financially attractive. For the primary analysis, we fit a logistic regression model of the primary outcome (low birth weight, <2500 g) on dummy variables for county and year; individual level maternal/infant covariates (maternal race, maternal age, infant sex and whether birth was a multiple birth); and the amount of surface mining during the year of the birth in the maternal county of residence., Results: Our analysis sample consisted of 783,328 infants -- 482,284 infants born from 1977 to 2017 to women residing in substantial surface mining activity counties and 301,044 infants born from 1977 to 2017 to women residing in matched control counties. Compared to the pre-period of low surface mining from 1977 to 1989, for the primary analysis posttest period of 1999-2011, there was an estimated relative increase in low birth weight in surface mining counties compared to matched control counties that was not statistically significant (odds ratio for a 5 percentage point increase in area disturbed by surface mining: 1.07, 95% confidence interval (0.96, 1.20), p-value: .22). For the secondary analysis posttest period of 1990-1998, there was no increase (odds ratio: 0.91, 95% confidence interval: (0.74, 1.13), p-value: .41). For the secondary analysis posttest period of 2012-2017, there was a statistically significant relative increase (odds ratio: 1.28, 95% confidence interval: (1.08, 1.50), p-value: .004). Qualitatively similar results were found for the outcomes of very low birth weight, preterm birth and small-for-gestational age., Conclusions: We examined the hypothesis that surface mining activity in Central Appalachia contributes to low birth weight using an observational study. We found evidence in secondary analyses that surface mining was associated with low birth weight in the 2012-2017 time period and potentially beginning in the early to mid 2000's. Evidence for an association was not found prior to 2000. A potential explanation for this pattern of association is that surface mining caused an increase in low birth weight but its onset was delayed. Future research is needed to clarify the findings and if replicated, identify the mechanism necessary to mitigate the impacts of mining on adverse birth outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Much evidence in comparative effectiveness research is based on observational studies. Researchers who conduct observational studies typically assume that there are no unobservable differences between the treatment groups under comparison. Treatment effectiveness is estimated after adjusting for observed differences between comparison groups. However, estimates of treatment effectiveness may be biased because of misspecification of the statistical model. That is, if the method of treatment effect estimation imposes unduly strong functional form assumptions, treatment effect estimates may be inaccurate, leading to inappropriate recommendations about treatment decisions. We compare the performance of a wide variety of treatment effect estimation methods for the average treatment effect. We do so within the context of the REFLUX study from the United Kingdom. In REFLUX, participants were enrolled in either an randomized controlled trial (RCT) or an observational study arm. In the RCT, patients were randomly assigned to either surgery or medical management. In the patient preference arm, participants selected to either have surgery or medical management. We attempt to recover the treatment effect estimate from the RCT using the data from the patient preference arms of the study. We vary the method of treatment effect estimation and record which methods are successful and which are not. We apply more than 20 different methods, including standard regression models as well as advanced machine learning methods. We find that simple propensity score matching methods provide the least accurate estimates versus the RCT benchmark. We find variation in performance across the other methods, with some, but not all recovering the experimental benchmark. We conclude that future studies should use multiple methods of estimation to fully represent uncertainty according to the choice of estimation approach.

Background: The COVID-19 pandemic has resulted in large-scale healthcare restrictions to control viral spread, reducing operating room censuses to include only medically necessary surgeries. The impact of restrictions on which patients undergo surgical procedures and their perioperative outcomes is less understood., Methods: Adult patients who underwent medically necessary surgical procedures at our institution during a restricted operative period due to the COVID-19 pandemic (March 23-April 24, 2020) were compared to patients undergoing procedures during a similar time period in the pre-COVID-19 era (March 25-April 26, 2019). Cardinal matching and differences in means were utilized to analyze perioperative outcomes., Results: 857 patients had surgery in 2019 (pre-COVID-19) and 212 patients had surgery in 2020 (COVID-19). The COVID-19 era cohort had a higher proportion of patients who were male (61.3% vs. 44.5%, P < 0.0001), were White (83.5% vs. 68.7%, P < 0.001), had private insurance (62.7% vs. 54.3%, p 0.05), were ASA classification 4 (10.9% vs. 3%, P < 0.0001), and underwent oncologic procedures (69.3% vs. 42.7%, P < 0.0001). Following 1:1 cardinal matching, COVID-19 era patients (N = 157) had a decreased likelihood of discharge to a nursing facility (risk difference-8.3, P < 0.0001) and shorter median length of stay (risk difference-0.6, p 0.04) compared to pre-COVID-19 era patients. There was no difference between the two patient cohorts in overall morbidity and 30-day readmission., Conclusions: COVID-19 restrictions on surgical operations were associated with a change in the racial and insurance demographics in patients undergoing medically necessary surgical procedures but were not associated with worse postoperative morbidity. Further study is necessary to better identify the causes for patient demographic differences.

Background: Periampullary malignancies are often unresectable tumors that frequently cause biliary or duodenal obstruction. Advances in endoscopic and percutaneous options have lessened the need for operative palliation. Nevertheless, many patients are still found to be unresectable at the time of exploration, making palliative bypass a consideration. Several prior studies have examined the morbidity of operative palliation, but many were conducted over lengthy time periods, and few have examined the impact of these procedures on future therapy. This study is a contemporary analysis of the short- and long-term outcomes of palliative bypass procedures for unresectable periampullary malignancies at a single high-volume institution., Methods: We identified a contemporary cohort of patients in whom a pancreatoduodenectomy was planned for periampullary malignancy but instead underwent an aborted procedure. Patients were divided into 5 procedure groups: laparoscopy only, laparotomy with or without cholecystectomy, gastrointestinal bypass, biliary bypass, and double bypass (gastrointestinal and biliary). Data regarding the patient cohort, procedures, morbidity/mortality, and the interval to initiation of systemic therapy were collected prospectively and reviewed retrospectively., Results: Between July 2011 and November 2018, 128 out of 615 (17%) patients had an aborted pancreatoduodenectomy; 113 out of 128 patients had pancreatic adenocarcinoma, and 86 (67.1%) had duodenal or biliary obstruction at the time of operation. Patients who underwent laparoscopy only (n = 34) had no operative complications and a 90-day mortality of 6%; 88% of these patients went on to receive systemic therapy (median 21 days postprocedure). Double bypass was associated with a far lesser complication rate than in prior studies; 17% of patients had some complication(s), but only 9% had a severe complication. The 90-day all-cause mortality was 13%, and only 71% of these patients went on to receive systemic therapy (median 47 days postprocedure). Notably, 27 out of 34 (79%) of patients who underwent laparoscopy alone needed additional procedures for local obstruction, whereas only 5 out of 42 (12%) double bypass patients needed additional interventions. Median survival for the entire cohort was 10.3 months., Conclusion: Palliative procedures in this cohort had a far lesser complication rate than that of historical series. Palliative procedures, however, delayed systemic therapy, and a fair number of patients never received additional treatments. Palliative procedures markedly decreased the need for future interventions. Intraoperative decisions regarding palliative procedures must incorporate the functional status and motivations of the patient; these procedures are increasingly safe but may still affect survival., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Instrumental variable (IV) analyses are becoming common in health services research and epidemiology. Most IV analyses use naturally occurring instruments, such as distance to a hospital. In these analyses, investigators must assume that the instrument is as-if randomly assigned. This assumption cannot be tested directly, but it can be falsified. Most IV falsification tests compare relative prevalence or bias in observed covariates between the instrument and exposure. These tests require investigators to make covariate-by-covariate judgments about the validity of the IV design. Often, only some covariates are well-balanced, making it unclear whether as-if randomization can be assumed for the instrument. We propose an alternative falsification test that compares IV balance or bias with the balance or bias that would have been produced under randomization. A key advantage of our test is that it allows for global balance measures as well as easily interpretable graphical comparisons. Furthermore, our test does not rely on parametric assumptions and can be used to validly assess whether the instrument is significantly closer to being as-if randomized than the exposure. We demonstrate our approach using data from (SPOT)light, a prospective cohort study carried out in 48 National Health Service hospitals in the United Kingdom between November 1, 2010, and December 31, 2011. This study used bed availability in the intensive care unit as an instrument for admission to the intensive care unit., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The 21-gene recurrence score (RS) is an established predictor of recurrence for early stage, hormone receptor positive breast cancer. The association between RS and other risk factors such as obesity has not been fully explored. We hypothesized that patients with obesity may present with primary breast cancers with higher recurrence scores., Methods: We identified 1546 patients who have body mass index (BMI) recorded around the time of RS assay. Obesity was classified as per CDC definitions of overweight (BMI 25-30 kg/m 2 ) and obesity (BMI >30 kg/m 2 ). RS was assessed as a continuous variable and according to pre- and post-TAILORx classifications. Kaplan Meier survival analysis was employed to assess the interaction between RS and BMI on overall survival (OS) and disease-free survival (DFS)., Results: In univariate analyses, the median RS in patients with overweight was 15, which was significantly lower than the median RS (16) of patients with normal weight (p = 0.03). The overall recurrence rate of patients with obesity was 4.1%, which was significantly worse than the overall recurrence rate of patients with normal and overweight of 2.6% and 1.5%, respectively (p = 0.05). In multivariate analyses using the inverse probability weighted regression adjustment (IPWRA) method to adjust for imbalances between subgroups, patients with overweight or obesity had significantly lower RS than patients with normal weight, correlating to an average decrease in RS value of 2.37 and 1.71, respectively (both p < 0.01). A similar relationship was seen between BMI categories and RS as a categorical variable stratified according to pre- or post-TAILORx categories. This inverse effect was predominantly seen in post-menopausal patients. Despite the generally lower RS in patients with obesity, a high RS in these patients is associated with diminished DFS (p = 0.04)., Conclusion: Tumors in post-menopausal women with higher BMI generally have lower RS. DFS is significantly worse in women with obesity whose RS ≥ 30. The reasons for poor outcomes for postmenopausal patients with obesity despite lower presenting RS merits further study., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Prior to the advent of Oncotype DX 21-gene recurrence score (oDX) assay, the National Comprehensive Cancer Network (NCCN) guideline supported omission of adjuvant chemotherapy in patients with ≤ 1 cm (T1b) hormone receptor-positive (HR +), human epidermal growth factor receptor 2 (HER2-) node tumors. However, around 30% of these patients would have an oDX recurrence score that warrants consideration of adjuvant chemotherapy. To clarify the potential benefit of oDX in these patients, we performed a retrospective analysis comparing clinical outcomes of women with T1a or T1b, N0 HR + HER2- according to performance of oDX., Patients and Methods: After receiving institutional review board (IRB) approval, an institutional database was queried to identify patients with HR + HER2- ≤ T1bN0 tumors (n = 2307) diagnosed between 2009 and 2018. Patients were further stratified by recurrence score (RS) defined as low (< 18), intermediate (18-30), or high (> 30). Log-rank, Kaplan-Meier, and inverse probability of treatment weighting (IPW) analyses were used to compare disease-free survival (DFS) and overall survival (OS) across groups., Results: Performance of oDX (n = 1149, 49.8%) was associated with larger tumors, younger age, and White race. On univariate analysis, performance of oDX was associated with improved OS (P < 0.01). On multivariate IPW analysis, performance of oDX lengthened DFS by an average of 16.5 months, while OS was similar between groups (P < 0.01 and P = 0.73). The improved DFS was mainly driven by those with tumors ≥ T1b., Conclusions: Overall, outcomes were excellent regardless of oDX testing. Performance of oDX testing was associated with improved DFS in patients with tumors ≥ T1b. Our results support routine use of oDX testing in patients with tumors ≥ T1b.

Background: Hyperbilirubinemia is commonly observed in patients requiring pancreatoduodenectomy (PD). Thus far, literature regarding the danger of operating in the setting of hyperbilirubinemia is equivocal. What remains undefined is at what specific level of bilirubin there is an adverse safety profile for undergoing PD. The aim of this study is to identify the optimal safety profile of patients with hyperbilirubinemia undergoing PD., Patients and Methods: The present work analyzed 803 PDs from 2004 to 2018. A generalized additive model was used to determine cutoff values of total serum bilirubin (TB) that were associated with increases in adverse outcomes, including 90-day mortality. Subgroup comparisons and biliary stent-specific analyses were performed for patients with TB below and above the cutoff., Results: TB of 13 mg/dL was associated with an increase in 90-day mortality (P = 0.043) and was the dominant risk factor on multivariate logistic regression [odds ratio (OR) 8.193, P = 0.001]. Increased TB levels were also associated with reoperations, number of complications per patient, and length of stay. Patients with TB greater than or equal to 13 mg/dL (TB ≥ 13) who received successful biliary decompression through stenting had less combined death and serious morbidity (P = 0.048)., Conclusions: Preoperative TB ≥ 13 mg/dL was associated with increased 90-day mortality after PD. Reducing a TB ≥ 13 is generally recommended before proceeding to surgery.

Background: We aim to compare the clinical outcomes of patients with early-stage HER2+ breast cancer treated with adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC)., Methods: Patients with non-metastatic HER2+ breast cancer treated from 2009 to 2018 at our institution comprised our study cohort (n = 1254). Pathologic complete response (pCR) was defined as the absence of invasive disease in the breast and axilla after NAC. Log-rank, Kaplan-Meier, and inverse probability of treatment weighting were used to assess differences in disease-free and overall survival between groups stratified by AC vs. NAC and pCR vs. non-pCR., Results: The majority received AC (n = 787 or 62.8%) while 467 (37.2%) patients received NAC. Median follow up for AC and NAC groups was 46 and 28 months, respectively. The crude disease-free survival and overall survival of our study cohort were 92.2% and 89.1% for AC, 89.1% and 82.2% for NAC pCR, and 68.1% and 60.0% for NAC non-pCR, respectively. For clinical stage ≥IIB patients, NAC conferred a positive but statistically nonsignificant treatment effect over AC in multivariate analysis., Conclusions: After adjusting for imbalances in our subgroups, we found that, regardless of the sequence of chemotherapy (AC vs. NAC), patients with early-stage HER2+ breast cancer had excellent outcomes., (© 2019 Wiley Periodicals, Inc.)

Background: Instrumental variable (IV) analysis can estimate treatment effects in the presence of residual or unmeasured confounding. In settings wherein measures of baseline risk severity are unavailable, IV designs are, therefore, particularly appealing, but, where established measures of risk severity are available, it is unclear whether IV methods are preferable., Objective: We compared regression with an IV design to estimate the effect of intensive care unit (ICU) transfer on mortality in a study with well-established measures of risk severity., Research Design: We use ICU bed availability at the time of assessment for ICU transfer as an instrument. Bed availability increases the chance of ICU admission, contains little information about patient characteristics, and it is unlikely that bed availability has any direct effect on in-hospital mortality., Subjects: We used a cohort study of deteriorating ward patients assessed for critical care unit admission, in 49 UK National Health Service hospitals between November 1, 2010, and December 31, 2011., Measures: Detailed demographic, physiological, and comorbidity data were collected for all patients., Results: The risk adjustment methods reported that, after controlling for all measured covariates including measures of risk severity, ICU transfer was associated with higher 28-day mortality, with a risk difference of 7.2% (95% confidence interval=5.3%-9.1%). The IV estimate of ICU transfer was -5.4% (95% confidence interval=-47.1% to 36.3%) and applies to the subsample of patients whose transfer was "encouraged" by bed availability., Conclusions: IV estimates indicate that ICU care is beneficial but are imprecisely estimated. Risk-adjusted estimates are more precise but, even with a rich set of covariates, report that ICU care is harmful.

Background: Sepsis is a leading cause of morbidity and mortality after surgery. Most studies regarding sepsis do not differentiate between patients who have had recent surgery and those without. Few data exist regarding the risk factors for poor outcomes in pediatric postsurgical sepsis. Our hypothesis is pediatric postsurgical, and medical patients with severe sepsis have unique risk factors for mortality., Methods: Data were extracted from a secondary analysis of an international point prevalence study of pediatric severe sepsis. Sites included 128 pediatric intensive care units from 26 countries. Pediatric patients with severe sepsis were categorized into those who had recent surgery (postsurgical sepsis) versus those that did not (medical sepsis) before sepsis onset. Multivariable logistic regression models were used to determine risk factors for mortality., Results: A total of 556 patients were included: 138 with postsurgical and 418 with medical sepsis. In postsurgical sepsis, older age, admission from the hospital ward, multiple organ dysfunction syndrome at sepsis recognition, and cardiovascular and respiratory comorbidities were independent risk factors for death. In medical sepsis, resource-limited region, hospital-acquired infection, multiple organ dysfunction syndrome at sepsis recognition, higher Pediatric Index of Mortality-3 score, and malignancy were independent risk factors for death., Conclusions: Pediatric patients with postsurgical sepsis had different risk factors for mortality compared with medical sepsis. This included a higher mortality risk in postsurgical patients presenting to the intensive care unit from the hospital ward. These data suggest an opportunity to develop and test early warning systems specific to pediatric sepsis in the postsurgical population., (Copyright © 2019. Published by Elsevier Inc.)

Objectives: Thiamine deficiency may propagate lactate production by limiting pyruvate dehydrogenase activity, and studies suggest benefit for thiamine administration in septic adults. We studied the effect of thiamine on physiologic and clinical outcomes for children with septic shock and hyperlactatemia., Design: Retrospective matched cohort study., Setting: Single academic PICU., Patients: Six thiamine-treated cases and nine matched controls., Interventions: None., Measurements and Main Results: The primary outcome was change in blood lactate from prethiamine (T0, cases) or maximum (T0, controls) lactate through 24 hours later (T24). Secondary outcomes were change in lactate over 48 hours (T48) and 72 hours (T72), time to lactate normalization, changes in vasoactive-inotrope score, organ dysfunction severity (daily Pediatric Logistic Organ Dysfunction 2 score), and creatinine, PICU length of stay, and hospital mortality. Lactate was greater than 5 mmol/L for a median of 39 hours (range, 16.1-64.3 hr) prior to thiamine administration for cases compared with 3.4 hours (range, 0-22.9 hr) prior to maximum lactate for controls (p = 0.002). There was no difference in median (interquartile range) change in lactate from T0 to T24 between thiamine-treated cases and controls (-9.0, -17.0 to -5.0 vs -7.2, -9.0 to -5.3 mmol/L, p = 0.78), with both groups exhibiting a rapid decrease in lactate. There were also no differences in secondary outcomes between groups., Conclusions: Treatment of pediatric septic shock with thiamine was followed by rapid improvement in physiologic and clinical outcomes after prolonged hyperlactatemia. Although we are not able to infer that thiamine provided benefit over usual care, the rapid decline in lactate after thiamine despite a prolonged period of hyperlactatemia raises the possibility that thiamine helped to reverse lactate production.

Purpose: A recent study reported that time to adjuvant chemotherapy (TTC) > 30 days was significantly associated with worse OS and DFS in triple-negative breast cancer (TNBC). Earlier studies, however, found that worse outcomes were associated with TTC > 60 days or > 90 days. As the trend for mastectomy with reconstruction continues to rise, TTC of < 30 days is often not feasible due to wound-healing issues in some of these patients. To elucidate the impact of TTC, we sought to evaluate the clinical outcomes associated with TTC in a contemporary cohort treated for TNBC at a single institution., Methods: A single-institution database was queried to identify nonmetastatic TNBC patients who received adjuvant chemotherapy from 2009 to 2018. TTC was defined as interval between date of surgery and adjuvant chemotherapy start date. Median TTC was used to divide our cohort into four quartiles; ≤ 31, 32-42, 43-56,  and > 56 days. Logrank, Kaplan-Meier, and inverse probability weighting (IPW) tests were used to analyze disease-free (DFS) and overall survival (OS)., Results: The mean TTC of our study cohort (n = 724) was 48 days (median TTC = 42 days). Black race, mastectomy without adjuvant radiation, and mastectomy with immediate reconstruction were associated with delayed TTC (all p-values < 0.01). In multivariate IPW analysis, TTC > 56 (n = 173) days did not impact DFS or OS compared to TTC ≤ 31 (n = 198) days (p = 0.27 and p = 0.21, respectively). Similar results were seen during subgroup analysis for groups identified as higher risk for delayed TTC., Conclusion: Our results demonstrated that TTC was not significant or significantly associated with DFS or OS in patient receiving chemotherapy for operable TNBC. Our results were reassuring for patients electing mastectomy with immediate reconstruction, who may experience a longer TTC.