Phosphoglycerate Dehydrogenase: Potential Therapeutic Target and Putative Metabolic Oncogene

Exemplified by cancer cells' preference for glycolysis, for example, the Warburg effect, altered metabolism in tumorigenesis has emerged as an important aspect of cancer in the past 10–20 years. Whether due to changes in regulatory tumor suppressors/oncogenes or by acting as metabolic oncogenes themselves, enzymes involved in the complex network of metabolic pathways are being studied to understand their role and assess their utility as therapeutic targets. Conversion of glycolytic intermediate 3-phosphoglycerate into phosphohydroxypyruvate by the enzyme phosphoglycerate dehydrogenase (PHGDH)—a rate-limiting step in the conversion of 3-phosphoglycerate to serine—represents one such mechanism. Forgotten since classic animal studies in the 1980s, the role of PHGDH as a potential therapeutic target and putative metabolic oncogene has recently reemerged following publication of two prominent papers near-simultaneously in 2011. Since that time, numerous studies and a host of metabolic explanations have been put forward in an attempt to understand the results observed. In this paper, I review the historic progression of our understanding of the role of PHGDH in cancer from the early work by Snell through its reemergence and rise to prominence, culminating in an assessment of subsequent work and what it means for the future of PHGDH

Pay-for-Performance and Hip Fracture Outcomes:An interrupted time series and difference-in-differences analysis in England and Scotland

Aims: Hip fractures are associated with high morbidity, mortality, and costs. One strategy for improving outcomes is to incentivize hospitals to provide better quality of care. We aimed to determine whether a pay-for-performance initiative affected hip fracture outcomes in England by using Scotland, which did not participate in the scheme, as a control.Materials and Methods: We undertook an interrupted time series study with data from all patients aged more than 60 years with a hip fracture in England (2000 to 2018) using the Hospital Episode Statistics Admitted Patient Care (HES APC) data set linked to national death registrations. Difference-in-differences (DID) analysis incorporating equivalent data from the Scottish Morbidity Record was used to control for secular trends. The outcomes were 30-day and 365-day mortality, 30-day re-admission, time to operation, and acute length of stay.Results: There were 1 037 860 patients with a hip fracture in England and 116 594 in Scotland. Both 30-day (DID -1.7%; 95% confidence interval (CI) -2.0 to -1.2) and 365-day (-1.9%; 95% CI -2.5 to -1.3) mortality fell in England post-intervention when compared with outcomes in Scotland. There were 7600 fewer deaths between 2010 and 2016 that could be attributed to interventions driven by pay-for-performance. A pre-existing annual trend towards increased 30-day re-admissions in England was halted post-intervention. Significant reductions were observed in the time to operation and length of stay.Conclusion: This study provides evidence that a pay-for-performance programme improved the outcomes after a hip fracture in England

The ED.TRAUMA Study: Evaluating the Discordance of Trauma Readmission And Unanticipated Mortality in the Assessment of Hospital Quality

Trauma is a common, high-risk, and high-cost condition that uniquely affects the health of older adults. Through this dissertation, we built on existing efforts to expand external benchmarking in trauma from a historical focus on in-hospital mortality to include a broader array of additional, long-term quality-metrics. To do so we: (1) assessed the distributions of proposed quality-metrics and ascertained their correlations with the current benchmarking standard (in-hospital mortality), (2) considered the utility of implementing proposed quality-metrics as a combined composite score and analyzed associations between hospital quality and important hospital-level risk-factors when trauma quality for older adults was defined based on (a) in-hospital mortality versus (b) composite scores, (3) investigated the potential influence of death as a semi-competing risk in the assessment of readmissions among older adult trauma patients, and (4) looked at the potential utility of implementing a process measure-based approach to long-term outcome improvement among older adults hospitalized for hip fracture based on the success of England’s Hip Fracture Best Practice Tariff. The findings from this work are hoped to have a major, direct impact on how the quality of care for older adults is measured, aiding in determining the future of clinical care for older adult trauma patients while simultaneously informing the development of meaningful and strong quality metric models with applications to both trauma and other non-trauma conditions

Political Priorities, Voting, and Political Action Committee Engagement of Emergency Medicine Trainees: A National Survey

Introduction: Medicine is increasingly influenced by politics, but physicians have historically had lower voter turnout than the general public. Turnout is even lower for younger voters. Little is known about the political interests, voting activity, or political action committee (PAC) involvement of emergency physicians in training. We evaluated EM trainees’ political priorities, use of and barriers to voting, and engagement with an emergency medicine (EM) PAC. Methods: Resident/medical student Emergency Medicine Residents’ Association members were emailed a survey between October–November 2018. Questions involved political priorities, perspective on single-payer healthcare, voting knowledge/behavior, and EM PACs participation. We analyzed data using descriptive statistics.  Results: Survey participants included 1,241 fully responding medical students and residents, with a calculated response rate of 20%. The top three healthcare priorities were as follows: 1) high cost of healthcare/price transparency; 2) decreasing the number of uninsured; and 3) quality of health insurance. The top EM-specific issue was ED crowding and boarding. Most trainees (70%) were supportive of single-payer healthcare: “somewhat favor” (36%) and “strongly favor” (34%). Trainees had high rates of voting in presidential elections (89%) but less frequent use of other voting options: 54% absentee ballots; 56% voting in state primary races; and 38% early voting. Over half (66%) missed voting in prior elections, with work cited as the most frequent (70%) barrier. While overall, half of respondents (62%) reported awareness of EM PACs, only 4% of respondents had contributed.  Conclusion: The high cost of healthcare was the top concern among EM trainees. Survey respondents had a high level of knowledge of absentee and early voting but less frequently used these options. Encouragement of early and absentee voting can improve voter turnout of EM trainees. Concerning EM PACs, there is significant room for membership growth. With improved knowledge of the political priorities of EM trainees, physician organizations and PACs can better engage future physicians

Differential access to care: The role of age, insurance, and income on race/ethnicity-related disparities in adult perforated appendix admission rates

Background: Differences in perforated appendix admission rates (PAAR) are an ambulatory-sensitive measure of access to care. While pediatric studies report disparities in PAAR, initial adult investigations suggest a lack of racial/ethnic inequity. The objectives of this study were to (1) assess for risk-adjusted, racial/ethnic differences in PAAR among adults on a national scale, (2) consider the extent to which variations (or lack thereof) are explained by age, insurance, and income, and (3) compare results within the United States population to a national segment of the population who are completely insured. Methods: According to the Agency for Healthcare Research and Quality definition of PAAR, adults (aged 18-64 years) in the 2006-2010 Nationwide Inpatient Sample were queried for the occurrence and perforation of acute appendicitis. Risk-adjusted differences were compared by race/ethnicity over 5-year age increments using logistic regression with reweighted estimating equations. Noting disparate outcomes between younger (aged 18-34 years) versus older (aged 35-64 years) adults, age-stratified variations were further considered. Results were compared relative to differences among national military/civilian-dependent patients with universal insurance and were assessed for the extent to which disparities could be explained by variations in insurance and income. Results: A total of 129,257 (weighted: 638,452) patients were included. Despite a lack of differences overall, significantly worse outcomes among younger (odds ratio point-estimates ranged from 1.11-1.32) and better outcomes among older (0.78-0.93) minority patients were found. This observation contrasted a lack of differences among completely insured military/civilian-dependent patients (n = 12,154). A total of 22.4% (non-Hispanic black versus non-Hispanic white) and 39.0% (Hispanic versus non-Hispanic white) of younger adult differences were explained by insurance-12.2% and 13.6% by income, 29.8% and 44.0% combined. Conclusion: This national assessment of differences in access to care among adults with acute appendicitis demonstrated the existence of racial/ethnic disparities in PAAR that varied with age and were partially, although incompletely, explained by variations in insurance and incom

Analgesic access for acute abdominal pain in the emergency department among racial/ethnic minority patients: A nationwide examination

Background: Prior studies of acute abdominal pain provide conflicting data regarding the presence of racial/ethnic disparities in the emergency department (ED). Objective: To evaluate race/ethnicity-based differences in ED analgesic pain management among a national sample of adult patients with acute abdominal pain based on a uniform definition. Research design/subjects/measures: The 2006-2010 CDC-NHAMCS data were retrospectively queried for patients 18 years and above presenting with a primary diagnosis of nontraumatic acute abdominal pain as defined by the American Association for the Surgery of Trauma. Independent predictors of analgesic/narcotic-specific analgesic receipt were determined. Risk-adjusted multivariable analyses were then performed to determine associations between race/ethnicity and analgesic receipt. Stratified analyses considered risk-adjusted differences by the level of patient-reported pain on presentation. Secondary outcomes included: prolonged ED-LOS (\u3e6 h), ED wait time, number of diagnostic tests, and subsequent inpatient admission. Results: A total of 6710 ED visits were included: 61.2% (n=4106) non-Hispanic white, 20.1% (n=1352) non-Hispanic black, 14.0% (n=939) Hispanic, and 4.7% (n=313) other racial/ethnic group patients. Relative to non-Hispanic white patients, non-Hispanic black patients and patients of other races/ethnicities had 22%-30% lower risk-adjusted odds of analgesic receipt [OR (95% CI)=0.78 (0.67-0.90); 0.70 (0.56-0.88)]. They had 17%-30% lower risk-adjusted odds of narcotic analgesic receipt (P\u3c0.05). Associations persisted for patients with moderate-severe pain but were insignificant for mild pain presentations. When stratified by the proportion of minority patients treated and the proportion of patients reporting severe pain, discrepancies in analgesic receipt were concentrated in hospitals treating the largest percentages of both. Conclusions: Analysis of 5 years of CDC-NHAMCS data corroborates the presence of racial/ethnic disparities in ED management of pain on a national scale. On the basis of a uniform definition, the results establish the need for concerted quality-improvement efforts to ensure that all patients, regardless of race/ethnicity, receive optimal access to pain relie

Military-to-civilian translation of battlefield innovations in operative trauma care

Background: Historic improvements in operative trauma care have been driven by war. It is unknown whether recent battlefield innovations stemming from conflicts in Iraq/Afghanistan will follow a similar trend. The objective of this study was to survey trauma medical directors (TMDs) at level 1-3 trauma centers across the United States and gauge the extent to which battlefield innovations have shaped civilian practice in 4 key domains of trauma care. Methods: Domains were determined by the use of a modified Delphi method based on multiple consultations with an expert physician/surgeon panel: (1) damage control resuscitation (DCR), (2) tourniquet use, (3) use of hemostatic agents, and (4) prehospital interventions, including intraosseous catheter access and needle thoracostomy. A corresponding 47-item electronic anonymous survey was developed/pilot tested before dissemination to all identifiable TMD at level 1-3 trauma centers across the US. Results: A total of 245 TMDs, representing nearly 40% of trauma centers in the United States, completed and returned the survey. More than half (n = 127; 51.8%) were verified by the American College of Surgeons. TMDs reported high civilian use of DCR: 95.1% of trauma centers had implemented massive transfusion protocols and the majority (67.7%) tended toward 1:1:1 packed red blood cell/fresh-frozen plasma/platelets ratios. For the other 3, mixed adoption corresponded to expressed concerns regarding the extent of concomitant civilian research to support military research and experience. In centers in which policies reflecting battlefield innovations were in use, previous military experience frequently was acknowledged. Conclusion: This national survey of TMDs suggests that military data supporting DCR has altered civilian practice. Perceived relevance in other domains was less clear. Civilian academic efforts are needed to further research and enhance understandings that foster improved trauma surgeon awareness of military-to-civilian translatio

Racial disparities in surgical outcomes: Does the level of resident surgeon play a role?

Background: Despite recognition of racial/ethnic surgical disparities, few studies have considered the role of surgical residents. This study aimed to elucidate whether disparities in postoperative outcomes are associated with the presence/level of surgical residents involved in procedures.Methods: Patients who were classified as having laparoscopic cholecystectomy, laparoscopic appendectomy, and open hernia repair in the 2005-2010 American College of Surgeons National Surgical Quality Improvement Program database were compared by level of provider (junior residents postgraduate year 1-2, senior residents, attending alone) for differences in patient demographics, clinical case-mix, and postoperative outcome information by the use of descriptive statistics and multivariable logistic regression.Results: A total of 196,770 patients met inclusion criteria. Attendings performed 43.0% of operations alone (senior residents 37.5%, junior residents 20.1%), They operated on 44.1% white, 30.1% black, and 43.9% Hispanic patients compared with 35.5%, 48.7%, and 41.3% and 20.4%, 21.3%, and 14.8% for senior and junior residents, respectively. Compared with attendings alone, senior residents were more likely to operate on black patients (adjusted odds ratio [OR] 2.02, 95% confidence interval [95% CI] 1.95-2.09) and have major (OR 1.13, 95% CI 1.06-1.21) and minor complications (OR 1.20, 95% CI 1.11-1.31). Junior residents also were more likely to operate on black patients but did not experience significantly worse outcomes.Conclusion: Greater risk-adjusted odds of complications among patients treated by senior residents need to be carefully weighed given the group\u27s higher likelihood of operating on minority patients