Global Cancer Surgery: pragmatic solutions to improve cancer surgery outcomes worldwide.

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.

Cost-Effectiveness Analysis of Adjuvant Therapy for BRAF-Mutant Resected Stage III Melanoma in Medicare Patients.

BACKGROUND: Adjuvant therapy for stage III melanoma improves several measures of patient survival. However, decisions regarding inclusion of adjuvant therapies in the formularies of public payers necessarily consider the cost-effectiveness of those treatments. The objective of this study is to evaluate the cost-effectiveness of four recently approved adjuvant therapies for BRAF-mutant stage III melanoma in the Medicare patient population. METHODS: In this cost-effectiveness analysis, a Markov microsimulation model was used to simulate the healthcare trajectory of patients randomized to receive either first-line targeted therapy (dabrafenib-trametinib) or immunotherapy (ipilimumab, nivolumab, or pembrolizumab). The base case was a 65-year-old Medicare patient with BRAF V600E-mutant resected stage III melanoma. Possible health states included recurrence-free survival, adverse events, local recurrence, distant metastases, and death. Transition probabilities were determined from published clinical trials. Costs were estimated from reimbursement rates reported by CMS and the Red Book drug price database. Primary outcomes were costs (US$), life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Model robustness was evaluated using one-way and probabilistic sensitivity analyses. RESULTS: Dabrafenib-trametinib provided 1.83 QALYs over no treatment and 0.23 QALYs over the most effective immunotherapy, pembrolizumab. Dabrafenib-trametinib was associated with an ICER of $95,758/QALY over no treatment and $285,863/QALY over pembrolizumab. Pembrolizumab yielded an ICER of $68,396/QALY over no treatment and dominated other immunotherapies. CONCLUSIONS: Pembrolizumab is cost-effective at a conventional willingness-to-pay (WTP) threshold, but dabrafenib-trametinib is not. Though dabrafenib-trametinib offers incremental QALYs, optimization of drug pricing is necessary to ensure dabrafenib-trametinib is accessible at an acceptable WTP threshold.

Social Media Responses to Elective Surgery Cancellations in the Wake of COVID-19.

OBJECTIVE: To assess public response to cancellations of elective surgeries following the American College of Surgeons' (ACS) recommendation on March 13. METHODS: We queried text comments from Reddit, a social media platform and the fifth most popular website in the United States. Comments were manually reviewed to assess for relevance to elective surgery in the United States during the global coronavirus outbreak, whether the text was written by a healthcare worker (HCW), whether the user was based in the United States, and whether the text documented cancellations of surgery, expected cancellations of surgery, or surgery ongoing after the ACS announcement. Analysis of overall sentiment and negativity in comment text was performed using the Valence Aware Dictionary for sEntiment Reasoning (VADER), a validated natural language processing tool previously used in studies of health behaviors using social media. Non-parametric tests were used for subgroup comparisons based on posting date and characteristics identified during manual review. RESULTS: Following manual review, 1272 comments were included for analysis. Overall sentiment among non-HCWs became significantly more negative following the ACS announcement (P = 0.037). Overall sentiment did not significantly differ between HCWs and non-HCWs prior to the ACS announcement (P = 0.98), but non-HCW sentiment became significantly more negative than HCW sentiment after the announcement (P = 0.027). Negativity scores in posts describing cancellations were significantly higher among posts written by non-HCWs than HCWs (P = 0.028). CONCLUSIONS: Cancellation of elective surgeries had an adverse emotional impact on non-HCWs. This finding highlights the importance of access to elective surgery to patients' emotional well-being.

Causes, Diagnostic Testing, and Treatments Related to Clinical Deterioration Events among High-Risk Ward Patients.

OBJECTIVE: Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized. Therefore, we aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review. DESIGN: Multicenter retrospective observational study. SETTING: Inpatient medical-surgical wards at four health systems from 2006-2020 PATIENTS: Randomly selected patients (1,000 from each health system) with clinical deterioration, defined by reaching the 95th percentile of a validated early warning score, electronic Cardiac Arrest Risk Triage (eCART), were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical deterioration was confirmed by a trained reviewer or marked as a false alarm if no deterioration occurred for each patient. For true deterioration events, the condition causing deterioration, relevant diagnostic tests ordered, and treatments provided were collected. Of the 4,000 included patients, 2,484 (62%) had clinical deterioration confirmed by chart review. Sepsis was the most common cause of deterioration (41%; n=1,021), followed by arrhythmia (19%; n=473), while liver failure had the highest in-hospital mortality (41%). The most common diagnostic tests ordered were complete blood counts (47% of events), followed by chest x-rays (42%), and cultures (40%), while the most common medication orders were antimicrobials (46%), followed by fluid boluses (34%), and antiarrhythmics (19%). CONCLUSIONS: We found that sepsis was the most common cause of deterioration, while liver failure had the highest mortality. Complete blood counts and chest x-rays were the most common diagnostic tests ordered, and antimicrobials and fluid boluses were the most common medication interventions. These results provide important insights for clinical decision-making at the bedside, training of rapid response teams, and the development of institutional treatment pathways for clinical deterioration. KEY POINTS: Question: What are the most common diagnoses, diagnostic test orders, and treatments for ward patients experiencing clinical deterioration? Findings: In manual chart review of 2,484 encounters with deterioration across four health systems, we found that sepsis was the most common cause of clinical deterioration, followed by arrythmias, while liver failure had the highest mortality. Complete blood counts and chest x-rays were the most common diagnostic test orders, while antimicrobials and fluid boluses were the most common treatments. Meaning: Our results provide new insights into clinical deterioration events, which can inform institutional treatment pathways, rapid response team training, and patient care.

Causes, Diagnostic Testing, and Treatments Related to Clinical Deterioration Events Among High-Risk Ward Patients.

IMPORTANCE: Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized. OBJECTIVES: We aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter retrospective observational study in inpatient medical-surgical wards at four health systems from 2006 to 2020. Randomly selected patients (1000 from each health system) with clinical deterioration, defined by reaching the 95th percentile of a validated early warning score, electronic Cardiac Arrest Risk Triage, were included. MAIN OUTCOMES AND MEASURES: Clinical deterioration was confirmed by a trained reviewer or marked as a false alarm if no deterioration occurred for each patient. For true deterioration events, the condition causing deterioration, relevant diagnostic tests ordered, and treatments provided were collected. RESULTS: Of the 4000 included patients, 2484 (62%) had clinical deterioration confirmed by chart review. Sepsis was the most common cause of deterioration (41%; n = 1021), followed by arrhythmia (19%; n = 473), while liver failure had the highest in-hospital mortality (41%). The most common diagnostic tests ordered were complete blood counts (47% of events), followed by chest radiographs (42%) and cultures (40%), while the most common medication orders were antimicrobials (46%), followed by fluid boluses (34%) and antiarrhythmics (19%). CONCLUSIONS AND RELEVANCE: We found that sepsis was the most common cause of deterioration, while liver failure had the highest mortality. Complete blood counts and chest radiographs were the most common diagnostic tests ordered, and antimicrobials and fluid boluses were the most common medication interventions. These results provide important insights for clinical decision-making at the bedside, training of rapid response teams, and the development of institutional treatment pathways for clinical deterioration.

Alignment of RVU Targets With Operating Room Block Time.

Background: Surgeon productivity is measured in relative value units (RVUs). The feasibility of attaining RVU productivity targets requires surgeons to have enough allocated block time to generate RVUs. However, it is unknown how much block time is required for surgeons to attain specific RVU targets. We aimed to estimate the effect of surgeon and practice environment characteristics (SPECs) on block time needed to attain fixed RVU targets. Methods: We computationally simulated individual surgeons' annual caseloads under a variety of SPECs in the following way. First, empirical case data were sampled from ACS NSQIP in accordance with surgeon specialty, case-mix complexity, and RVU target. Surgeons' operating schedules were then constructed according to the block length, turnover time, and scheduling flexibility of the practice environment. These 6 SPECs were concurrently varied over their ranges for a 6-way sensitivity analysis. Results: Annual operating schedules for 60,000,000 surgeons were simulated. The number of blocks required to attain RVU targets varied significantly with surgeon specialty and increased with increased case-mix complexity, increased turnover time, and decreased scheduling flexibility. Intraspecialty variation in block requirement with variation in environmental characteristics exceeded interspecialty variation with fixed environmental characteristics. Multivariate linear models predicted block utilization across surgical specialties with consideration for the stated factors. An online tool is shared with which to apply these results to one's particular practice. Conclusions: Block time required to attain RVU targets varies widely with SPECs; intraspecialty variation exceeds interspecialty variation. The feasibility of attaining RVU targets requires alignment between targets and allocated operating time with consideration for surgical specialty and other practice conditions.

Cost Implications of Insurance Associated Disparities in Post-Acute Traumatic Brain and Spinal Cord Injury Rehabilitation.

Abstract Post-acute care after spinal cord injury (SCI) or traumatic brain injury (TBI) influences neurological function regained. Inpatient rehabilitation facilities (IRFs) have more intensive care and result in lower mortality and better functional outcomes compared with skilled nursing facilities (SNFs). This study sought to quantify inpatient rehabilitation access by insurance and estimate the cost implications. We conducted a retrospective observational cohort study utilizing 2015-2017 California Office of Statewide Health Planning and Development database of injured adults with SCI and/or TBI. The primary predictor was insurance status. The outcome was discharge destination (home, IRFs, SNFs, long-term acute care [LTAC]) modeled using multi-variable multinomial mixed-effects logistic regression controlling for age, diagnosis, Weighted Elixhauser Comorbidity Index, and New Injury Severity Score. Cost of care for discharge to IRFs versus SNFs was estimated by adjusted quantile regression. Cost simulation predicted the adjusted cost difference if all publicly insured participants were discharged to an IRF. We identified 83,230 patients with an injury mechanism and a primary acute care hospitalization diagnosis of TBI (90.9%), SCI (8.3%), or both (0.8%) who were discharged to an IRF, SNF, LTAC, or home. Publicly insured patients were more likely than privately insured patients to go to SNFs versus IRFs (odds ratio [OR]: 2.17, 95% confidence interval [CI 2.01-2.34]). Sub-group analysis of 6416 participants showed an adjusted median total cost difference of $18,461 (95% CI [$5,908-$38,064]) and adjusted cost-per-day of the post-acute encounter of $1,045 (95% CI [$752-$2,399]) higher for discharge to IRFs versus SNFs. Cost simulation demonstrated an additional adjusted cost of $364M annually for universal IRF access for the publicly insured. Publicly insured SCI and TBI Californians are less frequently discharged to IRFs compared with their privately insured counterparts resulting in a lower short-term cost of care. However, the consequences of decreased intensive rehabilitation utilization in terms of functional recovery and long-term cost implications require further investigation.

Confluence of theory and experiment reveals the catalytic mechanism of the Varkud satellite ribozyme.

The Varkud satellite ribozyme catalyses site-specific RNA cleavage and ligation, and serves as an important model system to understand RNA catalysis. Here, we combine stereospecific phosphorothioate substitution, precision nucleobase mutation and linear free-energy relationship measurements with molecular dynamics, molecular solvation theory and ab initio quantum mechanical/molecular mechanical free-energy simulations to gain insight into the catalysis. Through this confluence of theory and experiment, we unify the existing body of structural and functional data to unveil the catalytic mechanism in unprecedented detail, including the degree of proton transfer in the transition state. Further, we provide evidence for a critical Mg2+ in the active site that interacts with the scissile phosphate and anchors the general base guanine in position for nucleophile activation. This novel role for Mg2+ adds to the diversity of known catalytic RNA strategies and unifies functional features observed in the Varkud satellite, hairpin and hammerhead ribozyme classes.