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Although the Social Vulnerability Index (SVI) was created to identify vulnerable populations after unexpected natural disasters, its ability to identify similar groups of patients undergoing unexpected emergency surgical procedures is unknown. We sought to examine the association between SVI and outcomes after emergency general surgery.This study is a cross-sectional review of 887,193 Medicare beneficiaries who underwent 1 of 4 common emergency general surgery procedures (appendectomy, cholecystectomy, colectomy, and ventral hernia repair) performed in the urgent or emergent setting between 2014 and 2018. These data were merged with the SVI at the census-track level of residence. Risk-adjusted outcomes (30-day mortality, serious complications, readmission) were evaluated using a logistic regression model accounting for age, sex, comorbidity, year, procedure type, and hospital characteristics between high and low social vulnerability quintiles and within the 4 SVI subthemes (socioeconomic status; household composition and disability; minority status and language; and housing type and transportation).Compared with beneficiaries with low social vulnerability, Medicare beneficiaries living in areas of high social vulnerability experienced higher rates of 30-day mortality (8.56% vs 8.08%; adjusted odds ratio 1.07; p0.001), serious complications (20.71% vs 18.40%; adjusted odds ratio 1.17; p0.001), and readmissions (16.09% vs 15.03%; adjusted odds ratio 1.08; p0.001). This pattern of differential outcomes was present in subgroup analysis of all 4 SVI subthemes but was greatest in the socioeconomic status and household composition and disability subthemes.National efforts to support patients with high social vulnerability from natural disasters may be well aligned with efforts to identify communities that are particularly vulnerable to worse postoperative outcomes after emergency general surgery. Policies targeting structural barriers related to household composition and socioeconomic status may help alleviate these disparities.

ImportanceThe bidirectional association between health and financial stability is increasingly recognized.ObjectiveTo describe the association between chronic disease burden and patients’ adverse financial outcomes.Design, Setting, and ParticipantsThis cross-sectional study analyzed insurance claims data from January 2019 to January 2021 linked to commercial credit data in January 2021 for adults 21 years and older enrolled in a commercial preferred provider organization in Michigan.ExposuresThirteen common chronic conditions (cancer, congestive heart failure, chronic kidney disease, dementia, depression and anxiety, diabetes, hypertension, ischemic heart disease, liver disease, chronic obstructive pulmonary disease and asthma, serious mental illness, stroke, and substance use disorders).Main Outcomes and MeasuresAdjusted probability of having medical debt in collections, nonmedical debt in collections, any delinquent debt, a low credit score, or recent bankruptcy, adjusted for age group and sex. Secondary outcomes included the amount of medical, nonmedical, and total debt among individuals with nonzero debt.ResultsThe study population included 2 854 481 adults (38.4% male, 43.3% female, 12.9% unknown sex, and 5.4% missing sex), 61.4% with no chronic conditions, 17.7% with 1 chronic condition, 14.8% with 2 to 3 chronic conditions, 5.4% with 4 to 6 chronic conditions, and 0.7% with 7 to 13 chronic conditions. Among the cohort, 9.6% had medical debt in collections, 8.3% had nonmedical debt in collections, 16.3% had delinquent debt, 19.3% had a low credit score, and 0.6% had recent bankruptcy. Among individuals with 0 vs 7 to 13 chronic conditions, the predicted probabilities of having any medical debt in collections (7.6% vs 32%), any nonmedical debt in collections (7.2% vs 24%), any delinquent debt (14% vs 43%), a low credit score (17% vs 47%) or recent bankruptcy (0.4% vs 1.7%) were all considerably higher for individuals with more chronic conditions and increased with each added chronic condition. Among individuals with medical debt in collections, the estimated amount increased with the number of chronic conditions ($784 for individuals with 0 conditions vs $1252 for individuals with 7-13 conditions) (all P Conclusions and RelevanceThis cross-sectional study of commercially insured adults linked to patient credit report outcomes shows an association between increasing burden of chronic disease and adverse financial outcomes.

Meaningful reporting of quality metrics relies on detecting a statistical difference when a true difference in performance exists. Larger cohorts and longer time frames can produce higher rates of statistical differences. However, older data are less relevant when attempting to enact change in the clinical setting. The selection of time frames must reflect a balance between being too small (type II errors) and too long (stale data). We explored the use of power analysis to optimize time frame selection for trauma quality reporting.Using data from 22 Level III trauma centers, we tested for differences in 4 outcomes within 4 cohorts of patients. With bootstrapping, we calculated the power for rejecting the null hypothesis that no difference exists amongst the centers for different time frames. From the entire sample for each site, we simulated randomly generated datasets. Each simulated dataset was tested for whether a difference was observed from the average. Power was calculated as the percentage of simulated datasets where a difference was observed. This process was repeated for each outcome.The power calculations for the 4 cohorts revealed that the optimal time frame for Level III trauma centers to assess whether a single site's outcomes are different from the overall average was 2 years based on an 80% cutoff.Power analysis with simulated datasets allows testing of different time frames to assess outcome differences. This type of analysis allows selection of an optimal time frame for benchmarking of Level III trauma center data.

This cross-sectional study examines pre-existing financial hardship among caregivers of hospitalized children.

Americans living in Health Professional Shortage Areas (HPSA) only have 44% of the required physician workforce to service their residents. We sought to determine whether residents living in HPSA have worse surgical outcomes than those living in non-HPSA.We performed a retrospective review of 1,507,834 Medicare beneficiaries undergoing appendectomy, cholecystectomy, colectomy or hernia repair between 2014 and 2018. Multivariable logistical regression was used to determine the association of living in HPSA with rates of 30-day mortality.Compared with patients living in non-HPSA, patients living in HPSA traveled farther (median distance 35.3 miles vs. 11.7 miles, p 0.001) and longer (median 45 min vs. 20 min, p 0.001) for surgical care. Differences in rates of mortality between patients living in HPSA and non-HPSA (6.0% vs. 6.1%, OR = 0.97, 95% CI 0.97-0.97, p 0.001) were small.Medicare beneficiaries living in HPSA experience more than double the travel time and triple the travel distance to undergo common surgical procedures compared to those living in non-HPSA. For those able to overcome the travel burden, the differences in surgical outcomes were small.

Failure to rescue (FTR) is defined as mortality following a complication. Failure to rescue has come under scrutiny as a quality metric to compare trauma centers. In contrast to elective surgery, trauma has an early period of high expected mortality because of injury sequelae rather than a complication. Here, we report FTR in early and late mortality using an externally validated trauma patient database, hypothesizing that centers with higher risk-adjusted mortality rates have higher risk-adjusted FTR rates.The study included 114,220 patients at 34 Levels I and II trauma centers in a statewide quality collaborative (2016-2020) with Injury Severity Score of ≥5. Emergency department deaths were excluded. Multivariate regression models were used to produce center-level adjusted rates for mortality and major complications. Centers were ranked on adjusted mortality rate and divided into quintiles. Early deaths (within 48 hours of presentation) and late deaths (after 48 hours) were analyzed.Overall, 6.7% of patients had a major complication and 3.1% died. There was no difference in the mean risk-adjusted complication rate among the centers. Failure to rescue was significantly different across the quintiles (13.8% at the very low-mortality centers vs. 23.4% at the very-high-mortality centers, p0.001). For early deaths, there was no difference in FTR rates among the highest and lowest mortality quintiles. For late deaths, there was a twofold increase in the FTR rate between the lowest and highest mortality centers (9.7% vs. 19.3%, p0.001), despite no difference in the rates of major complications (5.9% vs. 6.0%, p = 0.42).Low-performing trauma centers have higher mortality rates and lower rates of rescue following major complications. These differences are most evident in patients who survive the first 48 hours after injury. A better understanding of the complications and their role in mortality after 48 hours is an area of interest for quality improvement efforts.Prognostic and Epidemiologic; Level III.

Evaluating the relationship between health care costs and quality is paramount in the current health care economic climate, as an understanding of value is needed to drive policy decisions. While many policy analyses are focused on the larger health care system, there is a pressing need for surgically focused economic analyses. Surgical care is costly, and innovative technology is constantly introduced into the operating room, and surgical care impacts patients' short- and long-term physical and economic well-being. Unfortunately, significant knowledge gaps exist regarding the relationship between cost, value, and economic impact of surgical interventions. Despite the plethora of health care data available in the forms of claims databases, discharge databases, and national surveys, no single source of data contains all the information needed for every policy-relevant analysis of surgical care. For this reason, it is important to understand which data are available and what can be accomplished with each of the data sets. In this article, we provide an overview of databases commonly used in surgical health services research. We focus our review on the following five categories of data: governmental claims databases, commercial claims databases, hospital-based clinical databases, state and national discharge databases, and national surveys. For each, we present a summary of the database sampling frame, clinically relevant variables, variables relevant to economic analyses, strengths, weaknesses, and examples of surgically relevant analyses. This review is intended to improve understanding of the current landscape of data available, as well as stimulate novel analyses among surgical populations. Ongoing debates over national health policy reforms may shape the delivery of surgical care for decades to come. Appropriate use of available data resources can improve our understanding of the economic impact of surgical care on our health care system and our patients.Regular Review, Level V.

Open long-bone fractures represent a complex injury within the trauma system. Guidelines recommend antibiotics be given within 60 minutes of patient arrival to the emergency department. We sought to measure and improve the timeliness of antibiotic administration at the patient, hospital, and population level within a collaborative quality initiative.Trauma collaborative quality initiative data (January 2017 to December 2020) were analyzed from 34 American College of Surgeons Committee on Trauma verified level 1 and level 2 trauma centers. Inclusion criteria were adult patients (≥16 years), injury severity score ≥5, and open tibia or femur fracture. After the baseline year, hospitals were scored annually on a pay-for-performance metric based on patients receiving antibiotics within 120 minutes of emergency department arrival. Univariate tests examined the differences between baseline and subsequent year(s) performance. A multivariable logistic regression assessed the factors associated with meeting this target time.There were 2,624 patients with an open long-bone fracture. In the baseline year (2017), 76.9% of patients received antibiotics in ≤120 minutes, with a mean time of 57.9 ± 63.3 minutes. After implementing collaborative quality initiative-wide targets, performance significantly improved in subsequent years (2018, 2019, 2020). The collaborative quality initiative achieved their goal of ≥85% of patients receiving antibiotics in ≤120 minutes in 2019 (87.9%) and 2020 (88.5%), with a mean time of 43.3 ± 54.8 minutes (P.05 vs 2017).A pay-for-performance process measure within a statewide trauma collaborative quality initiative improved the timely administration of antibiotics to patients with open fractures. Work remains to align compliance with the guideline target of60 minutes and to identify factors involved in the delay of administration.

Resting skeletal muscle generates heat for endothermy in mammals but not amphibians, while both use the same Ca 2+ -handling proteins and membrane structures to conduct excitation–contraction coupling apart from having different ryanodine receptor (RyR) isoforms for Ca 2+ release. The sarcoplasmic reticulum (SR) generates heat following Adenosine triphosphate (ATP) hydrolysis at the Ca 2+ pump, which is amplified by increasing RyR1 Ca 2+ leak in mammals, subsequently increasing cytoplasmic [Ca 2+ ] ([Ca 2+ ] cyto ). For thermogenesis to be functional, rising [Ca 2+ ] cyto must not interfere with cytoplasmic effectors of the sympathetic nervous system (SNS) that likely increase RyR1 Ca 2+ leak; nor should it compromise the muscle remaining relaxed. To achieve this, Ca 2+ activated, regenerative Ca 2+ release that is robust in lower vertebrates needs to be suppressed in mammals. However, it has not been clear whether: i) the RyR1 can be opened by local increases in [Ca 2+ ] cyto ; and ii) downstream effectors of the SNS increase RyR Ca 2+ leak and subsequently, heat generation. By positioning amphibian and malignant hyperthermia-susceptible human-skinned muscle fibers perpendicularly, we induced abrupt rises in [Ca 2+ ] cyto under identical conditions optimized for activating regenerative Ca 2+ release as Ca 2+ waves passed through the junction of fibers. Only mammalian fibers showed resistance to rising [Ca 2+ ] cyto , resulting in increased SR Ca 2+ load and leak. Fiber heat output was increased by cyclic adenosine monophosphate (cAMP)-induced RyR1 phosphorylation at Ser2844 and Ca 2+ leak, indicating likely SNS regulation of thermogenesis. Thermogenesis occurred despite the absence of SR Ca 2+ pump regulator sarcolipin. Thus, evolutionary isolation of RyR1 provided increased dynamic range for thermogenesis with sensitivity to cAMP, supporting endothermy.

The serine/threonine protein kinase calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) plays critical roles in a range of biological processes. Despite its importance, only a handful of inhibitors of CAMKK2 have been disclosed. Having a selective small molecule tool to interrogate this kinase will help demonstrate that CAMKK2 inhibition can be therapeutically beneficial. Herein, we disclose SGC-CAMKK2-1, a selective chemical probe that targets CAMKK2.

To compare surgical outcomes and expenditures at hospital network participating critical access hospitals to non-network participating critical access hospitals among Medicare beneficiaries.Critical access hospitals provide essential care to more than 80 million Americans. These hospitals, often rural, are located more than 35 miles away from another hospital and are required to maintain patient transfer agreements with other facilities capable of providing higher levels of care. Some have gone further to formally participate in a hospital network.Cross-sectional retrospective study from 2014-2018 comparing 16,128 Medicare beneficiary admissions at hospital network participating versus non-participating critical access hospitals undergoing appendectomy, cholecystectomy, colectomy, or hernia repair. Thirty-day mortality and readmissions were risk adjusted using multivariable logistic regression accounting for patient and hospital factors. Price-standardized, risk-adjusted Medicare expenditures were compared for the 30-day total episode payments consisting of index hospitalization, physician services, readmissions, and post-acute care payments.Beneficiaries (average age=75.7 y, SD=7.4) who obtained care at hospital network participating critical access hospitals were more likely to carry ≥2 Elixhauser comorbidities (68.7%vs.62.8%, P0.001). Rates of 30-day mortality were higher at hospital network participating critical access hospitals (4.30%vs.3.81%, OR=1.11, P0.001). Similarly, readmission rates were higher at hospital network participating critical access hospitals (15.13%vs.14.34%, OR=1.06, P0.001). Additionally, total episode payments were found to be $960 higher per patient at hospital network participating critical access hospitals ($23,878vs.$22,918, P0.001).Critical access hospitals within a hospital network provided care to more medically complex patients and were associated with worse clinical outcomes and higher costs among Medicare beneficiaries undergoing common general surgery operations.

To compare surgical outcomes and expenditures at hospitals located in Health Professional Shortage Areas to non-shortage area designated hospitals among Medicare beneficiaries.More than a quarter of Americans live in federally designated Health Professional Shortage Areas. While there is growing concern that medical outcomes may be worse, far less is known about hospitals providing surgical care in these areas.Cross sectional retrospective study from 2014-2018 of 842,787 Medicare beneficiary patient admissions to hospitals with and without Health Professional Shortage Area designations for common operations including appendectomy, cholecystectomy, colectomy, and hernia repair. Risk-adjusted outcomes using multivariable logistic regression accounting for patient factors, admission type, and year were compared for each of the four operations. Hospital expenditures were price-standardized, risk-adjusted 30-day surgical episode payments. Primary outcome measures included 30-day mortality, hospital readmissions, and 30-day surgical episode payments.Patients (mean age=75.6 y, males=44.4%) undergoing common surgical procedures in shortage area hospitals were less likely to be white (84.6%vs.88.4%, P0.001) and less likely to have≥2 Elixhauser comorbidities (75.5%vs.78.2%, P0.001). Patients undergoing surgery at Health Professional Shortage Area hospitals had lower risk-adjusted rates of 30-day mortality (6.05%vs.6.69%, OR=0.90, CI0.90-0.91, P0.001) and readmission (14.99%vs.15.74%, OR=0.94, CI=0.94-0.95, P0.001). Medicare expenditures at Health Professional Shortage Area hospitals were also lower than non-shortage designated hospitals ($28,517vs.$29,685, difference= -$1,168, P0.001).Patients presenting to Health Professional Shortage Area hospitals obtain safe care for common surgical procedures without evidence of higher expenditures among Medicare beneficiaries. These findings should be taken into account as current legislative proposals to increase funding for care in these under-served communities are considered.

This cross-sectional study links insurance claims and consumer credit report data to evaluate the experience of financial distress in commercially insured adults after traumatic injury.

INTRODUCTION: The taxonomy code(s) associated with each National Provider Identifier (NPI) entry should characterize the provider’s role (e.g., physician) and any specialization (e.g., orthopedic surgery). While the intent of the taxonomy system was to monitor medical appropriateness and the expertise of care provided, this system is now being used by researchers to identify providers and their practices. It is unknown how accurate the taxonomy codes are in describing a provider’s true specialization. METHODS: Department websites of orthopedic surgery and general surgery from three large academic institutions were queried for practicing surgeons. The surgeon’s specialty and subspeciality information listed was compared to the provider’s taxonomy code(s) listed on the National Plan and Provider Enumeration System (NPPES). The match rate between these data sources was evaluated based on the specialty, subspecialty, and institution. RESULTS: There were 295 surgeons (205 general surgery and 90 orthopedic surgery) and 24 relevant taxonomies (8 orthopedic and 16 general or plastic) for analysis. Of these, 294 surgeons (99%) selected their general specialty taxonomy correctly, while only 189 (64%) correctly chose an appropriate subspecialty. General surgeons correctly chose a subspecialty more often than orthopedic surgeons (70 versus 51%, P = 0.002). The institution did not affect either match rate, however there were some differences noted in subspecialty match rates inside individual departments. CONCLUSIONS: In these institutions, the NPI taxonomy is not accurate for describing a surgeon’s subspecialty or actual practice. Caution should be taken when utilizing this variable to describe a surgeon’s subspecialization as our findings might apply in other groups.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and has caused significant medical/socioeconomic impacts. Other than vaccination, effective public health measures, including contact tracing, isolation, and quarantine, is critical for deterring viral transmission, preventing infection progression and resuming normal activities. Viral transmission is affected by many factors, but the viral load and vitality could be among the most important ones. Although in vitro studies have indicated that the amount of virus isolated from infected individuals affects the successful rate of virus isolation, whether the viral load carried at the individual level would determine the transmissibility was unknown. We examined whether the cycle threshold (Ct) value, a measurement of viral load by RT-PCR assay, could differentiate the spreaders from the non-spreaders in a population of college students. Our results indicate that while at the population level the Ct value is lower, suggesting a higher viral load, in the symptomatic spreaders than that in the asymptomatic non-spreaders, there is a significant overlap in the Ct values between the two groups. Thus, Ct value, or the viral load, at the individual level could not predict the transmissibility. Instead, a sensitive method to detect the presence of virus is needed to identify asymptomatic individuals who may carry a low viral load but can still be infectious.

In this Viewpoint, the authors evaluate access to surgical care using the domains of timeliness, workforce density, infrastructure, safety, and affordability and discuss how such a framework could be applied in the United States.

This study aims to identify opportunities to improve surgical equity by evaluating unmet social health needs by race, ethnicity, and insurance type.Although inequities in surgical care and outcomes based on race, ethnicity, and insurance have been well documented for decades, underlying drivers remain poorly understood.We used the 2008-2018 National Health Interview Survey to identify adults age 18 years and older who reported surgery in the past year. Outcomes included poor health status (self-reported), socioeconomic status (income, education, employment), and unmet social health needs (food, housing, transportation). We used logistic regression models to progressively adjust for the impact of patient demographics, SES, and unmet social health needs on health status.Among a weighted sample of 14,471,501 surgical patients, 30% reported at least one unmet social health need. Compared to non-Hispanic White patients, non-Hispanic Black and Hispanic patients reported higher rates of unmet social health needs. Compared to private insurance, those with Medicaid or no insurance reported higher rates of unmet social health needs. In fully adjusted models, poor health status was independently associated with unmet social health needs: food insecurity aOR 2.14 (95% CI 1.89-2.41), housing instability aOR 1.69 (95% CI 1.51-1.89), delayed care due to lack of transportation aOR 2.58 (95% CI 2.02-3.31).Unmet social health needs vary significantly by race, ethnicity, and insurance, and are independently associated with poor health among surgical populations. As providers and policymakers prioritize improving surgical equity, unmet social health needs are potential modifiable targets.

BACKGROUND Nearly 1-in-10 trauma patients in the United States are readmitted within 30 days of discharge, with a median hospital cost of more than $8,000 per readmission. There are national efforts to reduce readmissions in trauma care, but we do not yet understand which are potentially preventable. Our study aims to quantify the potentially preventable readmissions (PPRs) in trauma care to serve as the anchor point for ongoing efforts to curb hospital readmissions and ultimately, bring preventable readmissions to zero. METHODS We identified inpatient hospitalizations after trauma and readmissions within 90 days in the 2017 National Readmissions Database (NRD). Potentially preventable readmissions were defined as the Agency for Healthcare Research and Quality-defined Ambulatory Care Sensitive Conditions, in addition to superficial surgical site infection, acute kidney injury/acute renal failure, and aspiration pneumonitis. Mean costs for these admissions were calculated using the NRD. A multivariable logistic regression model was used to characterize the relationship between patient characteristics and PPR. RESULTS A total of 1,320,083 patients were admitted for trauma care in the 2017 NRD, and 137,854 (10.4%) were readmitted within 90 days of discharge. Of these readmissions, 22.7% were potentially preventable. The mean cost was $10,001/PPR, resulting in $313,802,278 in cost to the US health care system. Of readmitted trauma patients younger than 65 years, Medicaid or Medicare patients had 2.7-fold increased odds of PPRs compared with privately insured patients. Patients of any age with congestive heart failure had 2.9 times increased odds of PPR, those with chronic obstructive pulmonary disease or complicated diabetes mellitus had 1.8 times increased odds, and those with chronic kidney disease had 1.7 times increased odds. Furthermore, as the days from discharge increased, the proportion of readmissions due to PPRs increased. CONCLUSION One-in-five trauma readmissions are potentially preventable, which account for more than $300 million annually in health care costs. Improved access to postdischarge ambulatory care may be key to minimizing PPRs, especially for those with certain comorbidities. LEVEL OF EVIDENCE Economic and value-based evaluations, level II.

Background While much of trauma care is rightly focused on improving inpatient survival, the ultimate goal of recovery is to help patients return to their daily lives after injury. Although the overwhelming majority of trauma patients in the United States survive to hospital discharge, little is known nationally regarding the postdischarge economic burden of injuries among trauma survivors. Methods We used the National Health Interview Survey from 2008 to 2017 to identify working-age trauma patients, aged 18 to 64 years, who sustained injuries requiring hospitalization. We used propensity score matching to identify noninjured respondents. Our primary outcome measure was postinjury return to work among trauma patients. Our secondary outcomes included measures of food insecurity, medical debt, accessibility and affordability of health care, and disability. Results A nationally weighted sample of 319,580 working-age trauma patients were identified. Of these patients, 51.7% were employed at the time of injury, and 58.9% of them had returned to work at the time of interview, at a median of 47 days postdischarge. Higher rates of returning to work were associated with shorter length of hospital stay, higher education level, and private health insurance. Injury was associated with food insecurity at an adjusted odds ratio (aOR) of 1.8 (95% confidence interval, 1.40-2.37), with difficulty affording health care at aOR of 1.6 (1.00-2.47), with medical debt at aOR of 2.6 (2.11-3.20), and with foregoing care due to cost at aOR of 2.0 (1.52-2.63). Working-age trauma patients had disability at an aOR of 17.6 (12.93-24.05). Conclusion The postdischarge burden of injury among working-age US trauma survivors is profound-patients report significant limitations in employment, financial security, disability, and functional independence. A better understanding of the long-term impact of injury is necessary to design the interventions needed to optimize postinjury recovery so that trauma survivors can lead productive and fulfilling lives after injury. Level of evidence Economic & Value-Based Evaluations, level II; Prognostic, level II.

The year 2020 marks the 10th anniversary of the signing of the Affordable Care Act (ACA). Perhaps the greatest overhaul of the US health care system in the past 50 y, the ACA sought to expand access to care, improve quality, and reduce health care costs. Over the past decade, there have been a number of challenges and changes to the law, which remains in evolution. While the ACA's policies were not intended to specifically target surgical care, surgical patients, surgeons, and the health systems within which they function have all been greatly affected. This article aims to provide a brief overview of the impact of the ACA on surgical patients in reference to its tripartite aim of improving access, improving quality, and reducing costs.

ImportancePrivately insured US children account for 40% of non–birth-related pediatric hospitalizations. However, there are no national data on the magnitude or correlates of out-of-pocket spending for these hospitalizations.ObjectiveTo estimate out-of-pocket spending for non–birth-related hospitalizations among privately insured children and identify factors associated with this spending.Design, Setting, and ParticipantsThis study is a cross-sectional analysis of the IBM MarketScan Commercial Database, which reports claims from 25 to 27 million privately insured enrollees annually. In the primary analysis, all non–birth-related hospitalizations of children 18 years and younger from 2017 through 2019 were included. In a secondary analysis focused on insurance benefit design, hospitalizations that could be linked to the IBM MarketScan Benefit Plan Design Database and were covered by plans with a family deductible and inpatient coinsurance requirements were analyzed.Main Outcomes and MeasuresIn the primary analysis, factors associated with out-of-pocket spending per hospitalization (sum of deductibles, coinsurance, and copayments) were identified using a generalized linear model. In the secondary analysis, variation in out-of-pocket spending was assessed by level of deductible and inpatient coinsurance requirements.ResultsAmong 183 780 hospitalizations in the primary analysis, 93 186 (50.7%) were for female children, and the median (IQR) age of hospitalized children was 12 (4-16) years. A total of 145 108 hospitalizations (79.0%) were for children with a chronic condition and 44 282 (24.1%) were covered by a high-deductible health plan. Mean (SD) total spending per hospitalization was $28 425 ($74 715). Mean (SD) and median (IQR) out-of-pocket spending per hospitalization were $1313 ($1734) and $656 ($0-$2011), respectively. Out-of-pocket spending exceeded $3000 for 25 700 hospitalizations (14.0%). Factors associated with higher out-of-pocket spending included hospitalization in quarter 1 compared with quarter 4 (average marginal effect [AME], $637; 99% CI, $609-$665) and lack of chronic conditions compared with having a complex chronic condition (AME, $732; 99% CI, $696-$767). The secondary analysis included 72 165 hospitalizations. Among hospitalizations covered by the least generous plans (deductible of $3000 or more and coinsurance of 20% or more) and most generous plans (deductible less than $1000 and coinsurance of 1% to 19%), mean (SD) out-of-pocket spending was $1974 ($1999) and $826 ($798), respectively (AME, $1123; 99% CI, $1069-$1179).Conclusions and RelevanceIn this cross-sectional study, out-of-pocket spending for non–birth-related pediatric hospitalizations were substantial, especially when they occurred early in the year, involved children without chronic conditions, or were covered by plans with high cost-sharing requirements.

WHO recommends training lay first responders (LFRs) as the first step toward formal emergency medical services development, yet no tool exists to evaluate LFR programs. We developed Prehospital Emergency Trauma Care Assessment Tool (PETCAT), a seven-question survey administered to first-line hospital-based healthcare providers, to independently assess LFR prehospital intervention frequency and quality. PETCAT surveys were administered one month pre-LFR program launch (June 2019) in Makeni, Sierra Leone and again 14 months post-launch (August 2020). Using a difference-in-differences approach, PETCAT was also administered in a control city (Kenema) with no LFR training intervention during the study period at the same intervals to control for secular trends. PETCAT measured change in both the experimental and control locations. Cronbach’s alpha, point bi-serial correlation, and inter-rater reliability using Cohen's Kappa assessed PETCAT reliability. PETCAT administration to 90 first-line, hospital-based healthcare providers found baseline prehospital intervention were rare in Makeni and Kenema prior to LFR program launch (1.2/10 vs. 1.8/10). Fourteen months post-LFR program implementation, PETCAT demonstrated prehospital interventions increased in Makeni with LFRs (5.2/10, p

Introduction Ghana implemented a National Health Insurance Scheme (NHIS) in 2003 as a step toward universal health coverage. We aimed to determine the effect of the NHIS on timeliness of care, mortality, and catastrophic health expenditure (CHE) among children with serious injuries at a trauma center in Ghana. Methods We performed a retrospective cohort study of injured children aged 0.10). Uninsured children were more likely to have a delay in care for financial reasons (17.3 vs 6.4%, p, Highlights • Despite strides toward universal health coverage with the National Health Insurance Scheme (NHIS) in Ghana, one third of injured children did not have insurance. • Families on uninsured injured children pay markedly more out-of-pocket costs than families of insured children. • Although families of uninsured children were more likely to experience catastrophic health expenditure (CHE), CHE was commonly experienced regardless of insurance. • These findings have useful implications for NHIS, agencies working toward universal health coverage, and trauma systems generally.

OBJECTIVE To determine if initial American Board of Surgery certification in general surgery is associated with better risk-adjusted patient outcomes for Medicare patients undergoing partial colectomy by an early career surgeon. BACKGROUND Board certification is a voluntary commitment to professionalism, continued learning, and delivery of high-quality patient care. Not all surgeons are certified, and some have questioned the value of certification due to limited evidence that board-certified surgeons have better patient outcomes. In response, we examined the outcomes of certified versus noncertified early career general surgeons. METHODS We identified Medicare patients who underwent a partial colectomy between 2008 and 2016 and were operated on by a non-subspecialty trained surgeon within their first 5 years of practice. Surgeon certification status was determined using the American Board of Surgery data. Generalized linear mixed models were used to control for patient-, procedure-, and hospital-level effects. Primary outcomes were the occurrence of severe complications and occurrence of death within 30 days. RESULTS We identified 69,325 patients who underwent a partial colectomy by an early career general surgeon. The adjusted rate of severe complications after partial colectomy by certified (n = 4239) versus noncertified (n = 191) early-career general surgeons was 9.1% versus 10.7% (odds ratio 0.83, P = 0.03). Adjusted mortality rate for certified versus noncertified early-career general surgeons was 4.9% versus 6.1% (odds ratio 0.79, P = 0.01). CONCLUSION Patients undergoing partial colectomy by an early career general surgeon have decreased odds of severe complications and death when their surgeon is board certified.

Background Emergency general surgery (EGS) encompasses a heterogeneous population of acutely ill patients, and standardized methods for determining disease severity are essential for comparative effectiveness research and quality improvement initiatives. The American Association for the Surgery of Trauma (AAST) has developed a grading system for the anatomic severity of 16 EGS conditions; however, little is known regarding how well these AAST EGS grades can be approximated by diagnosis codes in administrative databases. Methods We identified adults admitted for 16 common EGS conditions in the 2012 to 2017q3 National Inpatient Sample. Disease severity strata were assigned using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes based on AAST EGS anatomic severity grades. We evaluated whether assigned EGS severity (multiple strata or dichotomized into less versus more complex) were associated with in-hospital mortality, complications, length of stay, discharge disposition, and costs. Analyses were adjusted for age, sex, comorbidities, hospital traits, geography, and year. Results We identified 10,886,822 EGS admissions. The number of anatomic severity strata derived from ICD-9/10-CM codes varied by EGS condition and by year. Four conditions mapped to four strata across all years. Two conditions mapped to four strata with ICD-9-CM codes but only two or three strata with ICD-10-CM codes. Others mapped to three or fewer strata. When dichotomized into less versus more complex disease, patients with more complex disease had worse outcomes across all 16 conditions. The addition of multiple strata beyond a binary measure of complex disease, however, showed inconsistent results. Conclusion Classification of common EGS conditions according to anatomic severity is feasible with International Classification of Diseases codes. No condition mapped to five distinct severity grades, and the relationship between increasing grade and outcomes was not consistent across conditions. However, a standardized measure of severity, even if just dichotomized into less versus more complex, can inform ongoing efforts aimed at optimizing outcomes for EGS patients across the nation. Level of evidence Prognostic, level III.

The calcium-calmodulin–dependent protein kinase kinase-2 (CaMKK2) is a key regulator of cellular and whole-body energy metabolism. It is known to be activated by increases in intracellular Ca(2+), but the mechanisms by which it is inactivated are less clear. CaMKK2 inhibition protects against prostate cancer, hepatocellular carcinoma, and metabolic derangements induced by a high-fat diet; therefore, elucidating the intracellular mechanisms that inactivate CaMKK2 has important therapeutic implications. Here we show that stimulation of cAMP-dependent protein kinase A (PKA) signaling in cells inactivates CaMKK2 by phosphorylation of three conserved serine residues. PKA-dependent phosphorylation of Ser(495) directly impairs calcium-calmodulin activation, whereas phosphorylation of Ser(100) and Ser(511) mediate recruitment of 14-3-3 adaptor proteins that hold CaMKK2 in the inactivated state by preventing dephosphorylation of phospho-Ser(495). We also report the crystal structure of 14-3-3ζ bound to a synthetic diphosphorylated peptide that reveals how the canonical (Ser(511)) and noncanonical (Ser(100)) 14-3-3 consensus sites on CaMKK2 cooperate to bind 14-3-3 proteins. Our findings provide detailed molecular insights into how cAMP-PKA signaling inactivates CaMKK2 and reveals a pathway to inhibit CaMKK2 with potential for treating human diseases.

BackgroundThe WHO recommends training lay first responders (LFRs) as the first step towards establishing emergency medical services (EMS) in low-income and middle-income countries. Understanding social and financial benefits associated with responder involvement is essential for LFR programme continuity and may inform sustainable development.MethodsA mixed-methods follow-up study was conducted in July 2019 with 239 motorcycle taxi drivers, including 115 (75%) of 154 initial participants in a Ugandan LFR course from July 2016, to evaluate LFR training on participants. Semi-structured interviews and surveys were administered to samples of initial participants to assess social and economic implications of training, and non-trained motorcycle taxi drivers to gauge interest in LFR training. Themes were determined on a per-question basis and coded by extracting keywords from each response until thematic saturation was achieved.ResultsThree years post-course, initial participants reported new knowledge and skills, the ability to help others, and confidence gain as the main benefits motivating continued programme involvement. Participant outlook was unanimously positive and 96.5% (111/115) of initial participants surveyed used skills since training. Many reported sensing an identity change, now identifying as first responders in addition to motorcycle taxi drivers. Drivers reported they believe this led to greater respect from the Ugandan public and a prevailing belief that they are responsible transportation providers, increasing subsequent customer acquisition. Motorcycle taxi drivers who participated in the course reported a median weekly income value that is 24.39% higher than non-trained motorcycle taxi counterparts (pConclusionsA simultaneous delivery of sustained social and perceived financial benefits to LFRs are likely to motivate continued voluntary participation. These benefits appear to be a potential mechanism that may be leveraged to contribute to the sustainability of future LFR programmes to deliver basic prehospital emergency care in resource-limited settings.

BACKGROUND Patients are at a high risk for developing venous thromboembolism (VTE) following traumatic injury. We examined the relationship between timing of initiation of pharmacologic prophylaxis with VTE complications. METHODS Trauma quality collaborative data from 34 American College of Surgeons Committee on Trauma-verified levels I and II trauma centers were analyzed. Patients were excluded if they were on anticoagulant therapy at the time of injury, had hospitalization

Introduction:The World Health Organization (WHO; Geneva, Switzerland) recommends lay first responder (LFR) programs as a first step toward establishing formal Emergency Medical Services (EMS) in low- and middle-income countries (LMICs) to address injury. There is a scarcity of research investigating LFR program development in predominantly rural settings of LMICs.Study Objective:A pilot LFR program was launched and assessed over 12 months to investigate the feasibility of leveraging pre-existing transportation providers to scale up prehospital emergency care in rural, low-resource settings of LMICs.Methods:An LFR program was established in rural Chad to evaluate curriculum efficacy, using a validated 15-question pre-/post-test to measure participant knowledge improvement. Pre-/post-test score distributions were compared using a Wilcoxon Signed-Rank test. For test evaluation, each pre-test question was mapped to its corresponding post-test analog and compared using McNemar’s Chi-Squared Test to examine knowledge acquisition on a by-question basis. Longitudinal prehospital care was evaluated with incident reports, while program cost was tracked using a one-way sensitivity analysis. Qualitative follow-up surveys and semi-interviews were conducted at 12 months, with initial participants and randomly sampled motorcycle taxi drivers, and used a constructivist grounded theory approach to understand the factors motivating continued voluntary participation to inform future program continuity. The consolidated criteria for reporting qualitative research (COREQ) checklist was used to guide design, analysis, and reporting the qualitative results.Results:A total of 108 motorcycle taxi participants demonstrated significant knowledge improvement (P Conclusion:Lay first responder programs appear feasible and cost-effective in rural LMIC settings. Participants demonstrate significant knowledge acquisition, and after 12 months of providing emergency care, report sustained voluntary participation due to social and financial benefits, suggesting sustainability and scalability of LFR programs in low-resource settings.

Long-chain fatty acids (LCFAs) play important roles in cellular energy metabolism, acting as both an important energy source and signalling molecules1. LCFA-CoA esters promote their own oxidation by acting as allosteric inhibitors of acetyl-CoA carboxylase, which reduces the production of malonyl-CoA and relieves inhibition of carnitine palmitoyl-transferase 1, thereby promoting LCFA-CoA transport into the mitochondria for β-oxidation2,3,4,5,6. Here we report a new level of regulation wherein LCFA-CoA esters per se allosterically activate AMP-activated protein kinase (AMPK) β1–containing isoforms to increase fatty acid oxidation through phosphorylation of acetyl-CoA carboxylase. Activation of AMPK by LCFA-CoA esters requires the allosteric drug and metabolite site formed between the α-subunit kinase domain and the β-subunit. β1 subunit mutations that inhibit AMPK activation by the small-molecule activator A769662, which binds to the allosteric drug and metabolite site, also inhibit activation by LCFA-CoAs. Thus, LCFA-CoA metabolites act as direct endogenous AMPK β1–selective activators and promote LCFA oxidation.

“Surprise” out-of-network bills have come under close scrutiny, and while ambulance transportation is known to be a large component of the problem, its impact is poorly understood. We measured the ...

Objectives Loss-of-function mutations in the gene encoding the calcium-calmodulin (Ca2+ -CaM)-dependent protein kinase kinase-2 (CaMKK2) enzyme are linked to bipolar disorder. Recently, a de novo arginine to cysteine (R311C) mutation in CaMKK2 was identified from a whole exome sequencing study of bipolar patients and their unaffected parents. The aim of the present study was to determine the functional consequences of the R311C mutation on CaMKK2 activity and regulation by Ca2+ -CaM. Methods The effects of the R311C mutation on CaMKK2 activity and Ca2+ -CaM activation were examined using a radiolabeled adenosine triphosphate (ATP) kinase assay. We performed immunoblot analysis to determine whether the R311C mutation impacts threonine-85 (T85) autophosphorylation, an activating phosphorylation site on CaMKK2 that has also been implicated in bipolar disorder. We also expressed the R311C mutant in CaMKK2 knockout HAP1 cells and used immunoblot analysis and an MTS reduction assay to study its effects on Ca2+ -dependent downstream signaling and cell viability, respectively. Results The R311C mutation maps to the conserved HRD motif within the catalytic loop of CaMKK2 and caused a marked reduction in kinase activity and Ca2+ -CaM activation. The R311C mutation virtually abolished T85 autophosphorylation in response to Ca2+ -CaM and exerted a dominant-negative effect in cells as it impaired the ability of wild-type CaMKK2 to initiate downstream signaling and maintain cell viability. Conclusions The highly disruptive, loss-of-function impact of the de novo R311C mutation in human CaMKK2 provides a compelling functional rationale for being considered a potential rare monogenic cause of bipolar disorder.

The prior article in this series delved into measuring cost in acute care surgery, and this subsequent work explains in detail how quality is measured. Specifically, objective quality is based on outcome measures, both from administrative and clinical registry databases from a multitude of sources. Risk stratification is key in comparing similar populations across diseases and procedures. Importantly, a move toward focusing on subjective outcomes like patient-reported outcomes measures and financial well-being are vital to evolving surgical quality measures for the 21st century.

Despite early studies linking calcium-calmodulin protein kinase kinase 2 (CAMKK2) to prostate cancer cell migration and invasion, the role of CAMKK2 in metastasis in vivo remains unclear. Moreover, while CAMKK2 is known to regulate systemic metabolism, whether CAMKK2's effects on whole-body metabolism would impact prostate cancer progression and/or related comorbidities is not known. Here, we demonstrate that germline ablation of

The AMP-activated protein kinase (AMPK) αβγ heterotrimer is a primary cellular energy sensor and central regulator of energy homeostasis. Activating skeletal muscle AMPK with small molecule drugs improves glucose uptake and provides an opportunity for new strategies to treat type 2 diabetes and insulin resistance, with recent genetic and pharmacological studies indicating the α2β2γ1 isoform combination as the heterotrimer complex primarily responsible. With the goal of developing α2β2-specific activators, here we perform structure/function analysis of the 2-hydroxybiphenyl group of SC4, an activator with tendency for α2-selectivity that is also capable of potently activating β2 complexes. Substitution of the LHS 2-hydroxyphenyl group with polar-substituted cyclohexene-based probes resulted in two AMPK agonists, MSG010 and MSG011, which did not display α2-selectivity when screened against a panel of AMPK complexes. By radiolabel kinase assay, MSG010 and MSG011 activated α2β2γ1 AMPK with one order of magnitude greater potency than the pan AMPK activator MK-8722. A crystal structure of MSG011 complexed to AMPK α2β1γ1 revealed a similar binding mode to SC4 and the potential importance of an interaction between the SC4 2-hydroxyl group and α2-Lys31 for directing α2-selectivity. MSG011 induced robust AMPK signalling in mouse primary hepatocytes and commonly used cell lines, and in most cases this occurred in the absence of changes in phosphorylation of the kinase activation loop residue α-Thr172, a classical marker of AMP-induced AMPK activity. These findings will guide future design of α2β2-selective AMPK activators, that we hypothesise may avoid off-target complications associated with indiscriminate activation of AMPK throughout the body.

Access sensitive surgical conditions should be treated electively with optimal access but result in emergency operations when access is limited. However, the rates of emergency procedures for these conditions are unknown.Cross-sectional retrospective review of Medicare beneficiaries who underwent access sensitive surgical procedures (abdominal aortic aneurysm repair, colectomy for colorectal cancer, or incisional hernia repair) between 2014 and 2018. Risk-adjusted outcomes using a multivariable logistical regression that adjusted for patient factors (age, sex, race, and Elixhauser comorbidities), hospital characteristics (ownership, size, geographic region, surgical volume) and type of operation were compared between planned and emergency (urgent and emergent) surgical procedures. Outcome measures were rates of emergency procedures as well as associated postoperative outcomes.Of the 744,818 Medicare beneficiaries undergoing access sensitive surgical procedures, 259,541 (34.9%) were done in the emergency setting. Risk-adjusted rates of emergency surgery varied widely across hospital service areas from 23.28% (lowest decile) to 54.88% (highest decile) (Odds Ratio 4.74; P 0.001). Emergency procedures were associated with significantly higher rates of 30-d mortality (8.15% versus 3.65%, P 0.001) and readmissions (16.28% versus 12.88%, P 0.001) compared to elective procedures. Sensitivity analysis with younger and healthier beneficiaries demonstrated persistently high rates (23.3%) of emergency surgery with wide regional variation and worse patient outcomes.Emergency surgery for access sensitive surgical conditions is extremely common and varied almost fivefold across United States hospital service areas. This suggests there are opportunities to improve access for these common surgical conditions.