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

Total hip arthroplasty versus hemiarthroplasty for independently mobile older adults with intracapsular hip fractures

Figure S1. PRISMA flow diagram showing identification of randomised and quasi-randomised controlled trials from previous systematic reviews. Table S1. Characteristics of excluded studies. Table S2. Characteristics of included studies. Table S3. Risk of bias assessments for included studies. (DOCX 321 kb

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

Racial Disparities in Emergency General Surgery: Do Differences in Outcomes Persist Among Universally Insured Military Patients?

Research Objective: Described as one of the most serious health problems affecting the nation, racial disparities are estimated to account for \u3e83,000 deaths, \u3e$57 billion per year. They have been identified in multiple surgical settings, including differences in outcomes by race among emergency general surgery(EGS) patients. As many minority patients are uninsured, increasing access to care is thought to be a viable solution to mitigate inequities. The objectives of this study were to determine whether racial disparities in 30/90/180day outcomes exist within a universally-insured population of military/civilian-dependent EGS patients and whether differences in outcomes differentially persist in care received at military-vs-civilian hospitals and among sponsors who are enlisted-service members-vs-officers. It also considered longer-term outcomes of care. Study Design: Risk-adjusted survival analyses using Cox proportional-hazards models assessed race-based differences in mortality, major morbidity, and readmission from index-hospital admission (discharge for readmission) through 30/90/180days. Models accounted for hospital clustering and possible biases associated with missing race (reweighted-estimating equations). Sub-analyses considered effects restricted to operative interventions, stratified by 24 EGS-diagnostic categories defined by the American Association for the Surgery of Trauma(AAST), and effect modification related to rank (SES-proxy: officers-vs-enlisted-sponsors) and military-vs-civilian-hospital care. Population Studied: Five years of national TRICARE Prime/Prime-plus data, which provides insurance to active/reserve/retired members of the US Armed Services and dependents, were queried for adults (≥18y) with primary EGS conditions, defined by the AAST. Patients who did not have an index admission between 01/01/2006-01/07/2010 (minimum 180days follow-up) or who were not continuously enrolled in TRICARE for 180days were excluded. Non-surviving patients were retained while they survived. Principal Findings: A total of 101,011 patients were included: 73.5% White, 14.5% Black, 4.4% Asian, 7.7% other. Risk-adjusted analyses reported equivalent-or-better mortality and readmission outcomes among minority patients at 30/90/180days—even when restricted to civilian hospitals where studies suggest that EGS disparities are found. Readmissions within military hospitals were lower among minority patients. Major morbidity was higher among Black versus White patients (HR[95%CI]): 30day-1.23[1.13-1.35], 90day-1.18[1.09-1.28], 180day-1.15[1.07-1.24]—a finding driven by appendiceal disorders (HR:1.69-1.70). No other diagnostic category-based HR was significant. When considered by rank, significant effects were isolated to enlisted-service members. However, given the relatively small number of patients who were (dependents of) officers, it is difficult to determine whether rank-based findings are a result of social determinants or influenced by the limited number of minority patients. Conclusions: The first of its kind to examine racial disparities in longer-term outcomes of EGS care, this longitudinal analysis of military patients demonstrated apparent mitigation of racial disparities within a universally-insured health system when compared to the overall US health system. Efforts to explain findings based on consideration of care provided in military-vs-civilian hospitals, among specific EGS-diagnostic categories, and based on sponsor rank revealed modification of the association between race and outcomes to some extent for all three. Implications for Policy or Practice: The contrast between results for universally-insured military/civilian-dependent patients and reported disparities among all US civilian patients merits consideration. The data speak to the importance of insurance-coverage in the development of disparities interventions nationwide and will help to inform policy within the DoD

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