Association of timing and agent for VTE prophylaxis in patients with severe traumatic brain injury on VTE, mortality, neurosurgical intervention, and discharge disposition.

BACKGROUND: Trauma patients are at increased risk for venous thromboembolism events (VTE). The decision of when to initiate VTE chemoprophylaxis (VTEP) and with what agent remains controversial in patients with severe traumatic brain injury (TBI). METHODS: This comparative effectiveness study evaluated the impact of timing and agent for VTEP on outcomes for patients with severe TBI (AIS Head = 3,4, or 5). Data was collected at 35 Level 1 and 2 trauma centers from January 1, 2017 to June 1, 2022. Patients were placed into analysis cohorts: No VTEP, low-molecular weight heparin (LMWH) ≤ 48 hours, LMWH>48 hours, Heparin≤48 hours, Heparin>48 hours. Propensity score matching accounting for patient factors and injury characteristics was used with logistic regression modeling to evaluate in-hospital mortality, VTE events, and discharge disposition. Neurosurgical intervention after initiation of VTEP was used to evaluate extension of intracranial hemorrhage. RESULTS: Of 12,879 patients, 32% had no VTEP, 36% LMWH, and 32% Heparin. Overall mortality was 8.3% and lowest among patients receiving LMWH≤48 hours (4.1%). VTE rates were lower with use of LMWH (1.6 vs 4.5%, OR 2.98, 95% CI 1.40-6.34, p = 0.005) without increasing mortality or neurosurgical interventions. VTE rates were lower with early prophylaxis (2.0 vs 3.5%, OR 1.76, 95% CI 1.15-2.71, p = 0.01) without increasing mortality (p = 1.0). Early VTEP was associated with more non-fatal intracranial operations (p < 0.001). However, patients undergoing neurosurgical intervention after VTEP initiation had no difference in rates of mortality, withdrawal of care, or unfavorable discharge disposition (p = 0.7, p = 0.1, p = 0.5). CONCLUSIONS: In patients with severe TBI, LMWH usage was associated with lower VTE incidence without increasing mortality or neurosurgical interventions. Initiation of VTEP≤48 hours decreased VTE incidence and increased non-fatal neurosurgical interventions without affecting mortality. LMWH is the preferred VTEP agent for severe TBI, and initiation ≤48 hours should be considered in relation to these risks and benefits. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level III.

Characterizing Trauma Patients with Delays in Orthopaedic Process Measures.

INTRODUCTION: Early operative intervention in orthopaedic injuries is associated with decreased morbidity and mortality. Relevant process measures (e.g. femoral shaft fixation <24 hours) are used in trauma quality improvement programs to evaluate performance. Currently, there is no mechanism to account for patients who are unable to undergo surgical intervention (i.e. physiologically unstable). We characterized the factors associated with patients who did not meet these orthopaedic process measures. METHODS: A retrospective cohort study of patients from 35 ACS-COT verified Level 1 and Level 2 trauma centers was performed utilizing quality collaborative data (2017-2022). Inclusion criteria were adult patients (≥18 years), ISS ≥5, and a closed femoral shaft or open tibial shaft fracture classified via the Abbreviated Injury Scale version 2005 (AIS2005). Relevant factors (e.g. physiologic) associated with a procedural delay >24 hours were identified through a multivariable logistic regression and the effect of delay on inpatient outcomes was assessed. A sub-analysis characterized the rate of delay in "healthy patients". RESULTS: We identified 5,199 patients with a femoral shaft fracture and 87.5% had a fixation procedure, of which 31.8% had a delay, and 47.1% of those delayed were "healthy." There were 1,291 patients with an open tibial shaft fracture, 92.2% had fixation, 50.5% had an irrigation and debridement and 11.2% and 18.7% were delayed, respectively. High ISS, older age and multiple medical comorbidities were associated with a delay in femur fixation, and those delayed had a higher incidence of complications. CONCLUSIONS: There is a substantial incidence of surgical delays in some orthopaedic trauma process measures that are predicted by certain patient characteristics, and this is associated with an increased rate of complications. Understanding these factors associated with a surgical delay, and effectively accounting for them, is key if these process measures are to be used appropriately in quality improvement programs. LEVEL OF EVIDENCE: Level III; Therapeutic/Care Management.

Financial toxicity part II: A practical guide to measuring and tracking long-term financial outcomes among acute care surgery patients.

ABSTRACT: Acute care surgery (ACS) patients are frequently faced with significant long-term recovery and financial implications that extend far beyond their hospitalization. While major injury and emergency general surgery (EGS) emergencies are often viewed solely as acute moments of crisis, the impact on patients can be lifelong. Financial outcomes after major injury or emergency surgery have only begun to be understood. The Healthcare Economics Committee from the American Association for the Surgery of Trauma previously published a conceptual overview of financial toxicity in ACS, highlighting the association between financial outcomes and long-term physical recovery. The aims of second-phase financial toxicity review by the Healthcare Economics Committee of the American Association for the Surgery of Trauma are to (1) understand the unique impact of financial toxicity on ACS patients; (2) delineate the current limitations surrounding measurement domains of financial toxicity in ACS; (3) explore the "when, what and how" of optimally capturing financial outcomes in ACS; and (4) delineate next steps for integration of these financial metrics in our long-term patient outcomes. As acute care surgeons, our patients' recovery is often contingent on equal parts physical, emotional, and financial recovery. The ACS community has an opportunity to impact long-term patient outcomes and well-being far beyond clinical recovery.

Higher Rates Of Emergency Surgery, Serious Complications, And Readmissions In Primary Care Shortage Areas, 2015-19.

Primary care physicians are often the first to screen and identify patients with access-sensitive surgical conditions that should be treated electively. These conditions require surgery that is preferably planned (elective), but, when access is limited, treatment may be delayed and worsening symptoms lead to emergency surgery (for example, colectomy for cancer, abdominal aortic aneurysm repair, and incisional hernia repair). We evaluated the rates of elective versus emergency surgery for patients with three access-sensitive surgical conditions living in primary care Health Professional Shortage Areas during 2015-19. Medicare beneficiaries in more severe primary care shortage areas had higher rates of emergency surgery compared with rates in the least severe shortage areas (37.8 percent versus 29.9 percent). They were also more likely to have serious complications (14.9 percent versus 11.7 percent) and readmissions (15.7 percent versus 13.5 percent). When we accounted for areas with a shortage of surgeons, the findings were similar. Taken together, these findings suggest that residents of areas with greater primary care workforce shortages may also face challenges in accessing elective surgical care. As policy makers consider investing in Health Professional Shortage Areas, our findings underscore the importance of primary care access to a broader range of services.

Health Insurance Status and Unplanned Surgery for Access-Sensitive Surgical Conditions.

Importance: Access-sensitive surgical conditions, such as abdominal aortic aneurysm, ventral hernia, and colon cancer, are ideally treated with elective surgery, but when left untreated have a natural history requiring an unplanned operation. Patients' health insurance status may be a barrier to receiving timely elective care, which may be associated with higher rates of unplanned surgery and worse outcomes. Objective: To evaluate the association between patients' insurance status and rates of unplanned surgery for these 3 access-sensitive surgical conditions and postoperative outcomes. Design, Setting, and Participants: This cross-sectional cohort study examined a geographically broad patient sample from the Healthcare Cost and Utilization Project State Inpatient Databases, including data from 8 states (Arizona, Colorado, Florida, Kentucky, Maryland, North Carolina, Washington, and Wisconsin). Participants were younger than 65 years who underwent abdominal aortic aneurysm repair, ventral hernia repair, or colectomy for colon cancer between 2016 and 2020. Patients were stratified into groups by insurance status. Data were analyzed from June 1 to July 1, 2023. Exposure: Health insurance status (private insurance, Medicaid, or no insurance). Main Outcomes and Measures: The primary outcome was the rate of unplanned surgery for these 3 access-sensitive conditions. Secondary outcomes were rates of postoperative outcomes including inpatient mortality, any hospital complications, serious complications (a complication with a hospital length of stay longer than the 75th percentile for that procedure), and hospital length of stay. Results: The study included 146 609 patients (mean [SD] age, 50.9 [10.3] years; 73 871 females [50.4%]). A total of 89 018 patients (60.7%) underwent elective surgery while 57 591 (39.3%) underwent unplanned surgery. Unplanned surgery rates varied significantly across insurance types (33.14% for patients with private insurance, 51.46% for those with Medicaid, and 72.60% for those without insurance; P < .001). Compared with patients with private insurance, patients without insurance had higher rates of inpatient mortality (1.29% [95% CI, 1.04%-1.54%] vs 0.61% [0.57%-0.66%]; P < .001), higher rates of any complications (19.19% [95% CI, 18.33%-20.05%] vs 12.27% [95% CI, 12.07%-12.47%]; P < .001), and longer hospital stays (7.27 [95% CI, 7.09-7.44] days vs 5.56 [95% CI, 5.53-5.60] days, P < .001). Conclusions and Relevance: Findings of this cohort study suggest that uninsured patients more often undergo unplanned surgery for conditions that can be treated electively, with worse outcomes and longer hospital stays compared with their counterparts with private health insurance. As efforts are made to improve insurance coverage, tracking elective vs unplanned surgery rates for access-sensitive surgical conditions may be a useful measure to assess progress.

The invisible scars: Unseen financial complications worsen every aspect of long-term health in trauma survivors.

BACKGROUND: Trauma survivors are susceptible to experiencing financial toxicity (FT). Studies have shown the negative impact of FT on chronic illness outcomes. However, there is a notable lack of data on FT in the context of trauma. We aimed to better understand prevalence, risk factors, and impact of FT on trauma long-term outcomes. METHODS: Adult trauma patients with an Injury Severity Score (ISS) ≥9 treated at Level I trauma centers were interviewed 6 months to 14 months after discharge. Financial toxicity was considered positive if patients reported any of the following due to the injury: income loss, lack of care, newly applied/qualified for governmental assistance, new financial problems, or work loss. The Impact of FT on Patient Reported Outcome Measure Index System (PROMIS) health domains was investigated. RESULTS: Of 577 total patients, 44% (254/567) suffered some form of FT. In the adjusted model, older age (odds ratio [OR], 0.4; 95% confidence interval [95% CI], 0.2-0.81) and stronger social support networks (OR, 0.44; 95% CI, 0.26-0.74) were protective against FT. In contrast, having two or more comorbidities (OR, 1.81; 95% CI, 1.01-3.28), lower education levels (OR, 1.95; 95% CI, 95%, 1.26-3.03), and injury mechanisms, including road accidents (OR, 2.69; 95% CI, 1.51-4.77) and intentional injuries (OR, 4.31; 95% CI, 1.44-12.86) were associated with higher toxicity. No significant relationship was found with ISS, sex, or single-family household. Patients with FT had worse outcomes across all domains of health. There was a negative linear relationship between the severity of FT and worse mental and physical health scores. CONCLUSION: Financial toxicity is associated with long-term outcomes. Incorporating FT risk assessment into recovery care planning may help to identify patients most in need of mitigative interventions across the trauma care continuum to improve trauma recovery. Further investigations to better understand, define, and address FT in trauma care are warranted. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Improving outcomes in emergency general surgery: Construct of a collaborative quality initiative.

BACKGROUND: Emergency general surgery conditions are common, costly, and highly morbid. The proportion of excess morbidity due to variation in health systems and processes of care is poorly understood. We constructed a collaborative quality initiative for emergency general surgery to investigate the emergency general surgery care provided and guide process improvements. METHODS: We collected data at 10 hospitals from July 2019 to December 2022. Five cohorts were defined: acute appendicitis, acute gallbladder disease, small bowel obstruction, emergency laparotomy, and overall aggregate. Processes and inpatient outcomes investigated included operative versus nonoperative management, mortality, morbidity (mortality and/or complication), readmissions, and length of stay. Multivariable risk adjustment accounted for variations in demographic, comorbid, anatomic, and disease traits. RESULTS: Of the 19,956 emergency general surgery patients, 56.8% were female and 82.8% were White, and the mean (SD) age was 53.3 (20.8) years. After accounting for patient and disease factors, the adjusted aggregate mortality rate was 3.5% (95% confidence interval [CI], 3.2-3.7), morbidity rate was 27.6% (95% CI, 27.0-28.3), and the readmission rate was 15.1% (95% CI, 14.6-15.6). Operative management varied between hospitals from 70.9% to 96.9% for acute appendicitis and 19.8% to 79.4% for small bowel obstruction. Significant differences in outcomes between hospitals were observed with high- and low-outlier performers identified after risk adjustment in the overall cohort for mortality, morbidity, and readmissions. The use of a Gastrografin challenge in patients with a small bowel obstruction ranged from 10.7% to 61.4% of patients. In patients who underwent initial nonoperative management of acute cholecystitis, 51.5% had a cholecystostomy tube placed. The cholecystostomy tube placement rate ranged from 23.5% to 62.1% across hospitals. CONCLUSION: A multihospital emergency general surgery collaborative reveals high morbidity with substantial variability in processes and outcomes among hospitals. A targeted collaborative quality improvement effort can identify outliers in emergency general surgery care and may provide a mechanism to optimize outcomes. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Understanding the impacts of rural hospital closures: A scoping review.

PURPOSE: Rural hospitals are closing at unprecedented rates, with hundreds more at risk of closure in the coming 2 years. Multiple federal policies are being developed and implemented without a salient understanding of the emerging literature evaluating rural hospital closures and its impacts. We conducted a scoping review to understand the impacts of rural hospital closure to inform ongoing policy debates and research. METHODS: A comprehensive search strategy was devised by library faculty to collate publications using the PRISMA extension for scoping reviews. Two coauthors then independently performed title and abstract screening, full text review, and study extraction. FINDINGS: We identified 5054 unique citations and assessed 236 full texts for possible inclusion in our narrative synthesis of the literature on the impacts of rural hospital closure. Twenty total original studies were included in our narrative synthesis. Key domains of adverse impacts related to rural hospital closure included emergency medical service transport, local economies, availability and utilization of emergency care and hospital services, availability of outpatient services, changes in quality of care, and workforce and community members. However, significant heterogeneity existed within these findings. CONCLUSIONS: Given the significant heterogeneity within our findings across multiple domains of impact, we advocate for a tailored approach to mitigating the impacts of rural hospital closures for policymakers. We also discuss crucial knowledge gaps in the evidence base-especially with respect to quality measures beyond mortality. The synthesis of these findings will permit policymakers and researchers to understand, and mitigate, the harms of rural hospital closure.

Multicenter evaluation of financial toxicity and long-term health outcomes after injury.

BACKGROUND: Despite the growing awareness of the negative financial impact of traumatic injury on patients' lives, the association between financial toxicity and long-term health-related quality of life (hrQoL) among trauma survivors remains poorly understood. METHODS: Patients from nine trauma centers participating in a statewide trauma quality collaborative had responses from longitudinal survey data linked to inpatient trauma registry data. Financial toxicity was defined based on patient-reported survey responses regarding medical debt, work or income loss, nonmedical financial strain, and forgone care due to costs. A financial toxicity score ranging from 0 to 4 was calculated. Health-related quality of life was assessed using the EuroQol 5 Domain tool. Multivariable regression models evaluated the association between financial toxicity and hrQoL outcomes while adjusting for patient demographics, injury severity and inpatient treatment intensity, and health systems variables. RESULTS: Among the 403 patients providing 510 completed surveys, rates of individual financial toxicity elements ranged from 21% to 46%, with 65% of patients experiencing at least one element of financial toxicity. Patients with any financial toxicity had worse summary measures of hrQoL and higher rates of problems in all five EuroQol 5 Domain domains ( p < 0.05 for all). Younger age, lower household income, lack of insurance, more comorbidities, discharge to a facility, and air ambulance transportation were independently associated with higher odds of financial toxicity ( p < 0.05 for all). Injury traits and inpatient treatment intensity were not independently associated with financial toxicity. CONCLUSION: A majority of trauma survivors in this study experienced some level of financial toxicity, which was independently associated with worse risk-adjusted health outcomes across all hrQoL measures. Risk factors for financial toxicity are not related to injury severity or treatment intensity but rather to sociodemographic variables and measures of prehospital and posthospital health care resource utilization. Targeted interventions and policies are needed to address financial toxicity and ensure optimal recovery for trauma survivors. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Linking Trauma Registry Patients With Insurance Claims: Creating a Longitudinal Patient Record.

INTRODUCTION: Trauma registries and their quality improvement programs only collect data from the acute hospital admission, and no additional information is captured once the patient is discharged. This lack of long-term data limits these programs' ability to affect change. The goal of this study was to create a longitudinal patient record by linking trauma registry data with third party payer claims data to allow the tracking of these patients after discharge. METHODS: Trauma quality collaborative data (2018-2019) was utilized. Inclusion criteria were patients age ≥18, ISS ≥5 and a length of stay ≥1 d. In-hospital deaths were excluded. A deterministic match was performed with insurance claims records based on the hospital name, date of birth, sex, and dates of service (±1 d). The effect of payer type, ZIP code, International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis specificity and exact dates of service on the match rate was analyzed. RESULTS: The overall match rate between these two patient record sources was 27.5%. There was a significantly higher match rate (42.8% versus 6.1%, P < 0.001) for patients with a payer that was contained in the insurance collaborative. In a subanalysis, exact dates of service did not substantially affect this match rate; however, specific International Classification of Diseases, Tenth Revision, Clinical Modification codes (i.e., all 7 characters) reduced this rate by almost half. CONCLUSIONS: We demonstrated the successful linkage of patient records in a trauma registry with their insurance claims. This will allow us to the collect longitudinal information so that we can follow these patients' long-term outcomes and subsequently improve their care.

Association of Childbirth With Medical Debt.

We evaluated the association between childbirth and having medical debt in collections and examined differences by neighborhood socioeconomic status. Among a statewide cohort of commercially insured pregnant (n=14,560) and postpartum (n=12,157) adults, having medical debt in collections was more likely among postpartum individuals compared with pregnant individuals (adjusted odds ratio [aOR] 1.36, 95% CI 1.27-1.46) and those in lowest-income neighborhoods compared with all others (aOR 2.18, 95% CI 2.02-2.35). Postpartum individuals in lowest-income neighborhoods had the highest predicted probabilities of having medical debt in collections (28.9%, 95% CI 27.5-30.3%), followed by pregnant individuals in lowest-income neighborhoods (23.2%, 95% CI 22.0-24.4%), followed by all other postpartum and pregnant people (16.1%, 95% CI 15.4-16.8% and 12.5%, 95% CI 11.9-13.0%, respectively). Our findings suggest that current peripartum out-of-pocket costs are objectively more than many commercially insured families can afford, leading to medical debt. Policies to reduce maternal-infant health care spending among commercially insured individuals may mitigate financial hardship and improve birth equity.

CaMKK2 as an emerging treatment target for bipolar disorder.

Current pharmacological treatments for bipolar disorder are inadequate and based on serendipitously discovered drugs often with limited efficacy, burdensome side-effects, and unclear mechanisms of action. Advances in drug development for the treatment of bipolar disorder remain incremental and have come largely from repurposing drugs used for other psychiatric conditions, a strategy that has failed to find truly revolutionary therapies, as it does not target the mood instability that characterises the condition. The lack of therapeutic innovation in the bipolar disorder field is largely due to a poor understanding of the underlying disease mechanisms and the consequent absence of validated drug targets. A compelling new treatment target is the Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) enzyme. CaMKK2 is highly enriched in brain neurons and regulates energy metabolism and neuronal processes that underpin higher order functions such as long-term memory, mood, and other affective functions. Loss-of-function polymorphisms and a rare missense mutation in human CAMKK2 are associated with bipolar disorder, and genetic deletion of Camkk2 in mice causes bipolar-like behaviours similar to those in patients. Furthermore, these behaviours are ameliorated by lithium, which increases CaMKK2 activity. In this review, we discuss multiple convergent lines of evidence that support targeting of CaMKK2 as a new treatment strategy for bipolar disorder.

Impact of state opioid laws on prescribing in trauma patients.

BACKGROUND: Excessive opioid prescribing has resulted in opioid diversion and misuse. In July 2018, Michigan's Public Act 251 established a state-wide policy limiting opioid prescriptions for acute pain to a 7-day supply. Traumatic injury increases the risk for new persistent opioid use, yet the impact of prescribing policy in trauma patients remains unknown. To determine the relationship between policy enactment and prescribing in trauma patients, we compared oral morphine equivalents prescribed at discharge before and after implementation of Public Act 251. METHODS: In this cross-sectional study, adult patients who received any oral opioids at discharge from a Level 1 trauma center between January 1, 2016, and June 30, 2021, were identified. The exposure was patients admitted starting July 1, 2018. Inpatient oral morphine equivalents per day 48 hours before discharge and discharge prescription oral morphine equivalents per day were calculated. Student's t test and an interrupted time series analysis were performed to compare mean oral morphine equivalents per day pre- and post-policy. Multivariable risk adjustment accounted for patient/injury factors and inpatient oral morphine equivalent use. RESULTS: A total of 3,748 patients were included in the study (pre-policy n = 1,685; post-policy n = 2,063). Implementation of the prescribing policy was associated with a significant decrease in mean discharge oral morphine equivalents per day (34.8 ± 49.5 vs 16.7 ± 32.3, P < .001). After risk adjustment, post-policy discharge prescriptions differed by -19.2 oral morphine equivalents per day (95% CI -21.7 to -16.8, P < .001). The proportion of patients obtaining a refill prescription 30 days post-discharge did not increase after implementation (0.38 ± 0.48 vs 0.37 ± 0.48, P = .7). CONCLUSION: Discharge prescription amounts for opioids in trauma patients decreased by approximately one-half after the implementation of opioid prescribing policies, and there was no compensatory increase in subsequent refill prescriptions. Future work is needed to evaluate the effect of these policies on the adequacy of pain management and functional recovery after injury.

Association between Medicare eligibility at age 65 years and in-hospital treatment patterns and health outcomes for patients with trauma: regression discontinuity approach.

OBJECTIVE: To determine whether health systems in the United States modify treatment or discharge decisions for otherwise similar patients based on health insurance coverage. DESIGN: Regression discontinuity approach. SETTING: American College of Surgeons' National Trauma Data Bank, 2007-17. PARTICIPANTS: Adults aged between 50 and 79 years with a total of 1 586 577 trauma encounters at level I and level II trauma centers in the US. INTERVENTIONS: Eligibility for Medicare at age 65 years. MAIN OUTCOME MEASURES: The main outcome measure was change in health insurance coverage, complications, in-hospital mortality, processes of care in the trauma bay, treatment patterns during hospital admission, and discharge locations at age 65 years. RESULTS: 1 586 577 trauma encounters were included. At age 65, a discontinuous increase of 9.6 percentage points (95% confidence interval 9.1 to 10.1) was observed in the share of patients with health insurance coverage through Medicare at age 65 years. Entry to Medicare at age 65 was also associated with a decrease in length of hospital stay for each encounter, of 0.33 days (95% confidence interval -0.42 to -0.24 days), or nearly 5%), which coincided with an increase in discharges to nursing homes (1.56 percentage points, 95% confidence interval 0.94 to 2.16 percentage points) and transfers to other inpatient facilities (0.57 percentage points, 0.33 to 0.80 percentage points), and a large decrease in discharges to home (1.99 percentage points, -2.73 to -1.27 percentage points). Relatively small (or no) changes were observed in treatment patterns during the patients' hospital admission, including no changes in potentially life saving treatments (eg, blood transfusions) or mortality. CONCLUSIONS: The findings suggest that differences in treatment for otherwise similar patients with trauma with different forms of insurance coverage arose during the discharge planning process, with little evidence that health systems modified treatment decisions based on patients' coverage.

Financial outcomes after pediatric critical illness among commercially insured families.

Critical illness results in subjective financial distress for families, but little is known about objective caregiver finances after a child's pediatric intensive care unit (PICU) hospitalization. Using statewide commercial insurance claims linked to cross-sectional commercial credit data, we identified caregivers of children with PICU hospitalizations in January-June 2020 and January-June 2021. Credit data included delinquent debt, debt in collections (medical and non-medical), low credit score (< 660), and a composite of any debt or poor credit and were measured in January 2021 for all caregivers. For the 2020 cohort ("post-PICU"), credit outcomes in January 2021 were measured at least 6 months following PICU hospitalization and reflect financial status after the hospitalization. For the 2021 cohort (comparison), financial outcomes were measured prior to their child's PICU hospitalization and therefore reflect pre-hospitalization financial status. We identified 2032 caregivers, 1017 post-PICU caregivers and 1015 comparison cohort caregivers, of which 1016 and 1014 were matched to credit data, respectively. Post-PICU caregivers had higher adjusted odds of having any delinquent debt [aOR 1.25; 95%CI 1.02-1.53; p = 0.03] and having a low credit score [aOR 1.29; 95%CI 1.06-1.58; p = 0.01]. However, there was no difference in the amount of delinquent debt or debt in collections among those with nonzero debt. Overall, 39.5% and 36.5% of post-PICU and comparator caregivers, respectively, had delinquent debt, debt in collections or poor credit. Many caregivers of critically ill children have financial debt or poor credit during hospitalization and post-discharge. However, caregivers may be at higher risk for poor financial status following their child's critical illness.

CaMKK2 is not involved in contraction-stimulated AMPK activation and glucose uptake in skeletal muscle.

OBJECTIVE: The AMP-activated protein kinase (AMPK) gets activated in response to energetic stress such as contractions and plays a vital role in regulating various metabolic processes such as insulin-independent glucose uptake in skeletal muscle. The main upstream kinase that activates AMPK through phosphorylation of α-AMPK Thr172 in skeletal muscle is LKB1, however some studies have suggested that Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) acts as an alternative kinase to activate AMPK. We aimed to establish whether CaMKK2 is involved in activation of AMPK and promotion of glucose uptake following contractions in skeletal muscle. METHODS: A recently developed CaMKK2 inhibitor (SGC-CAMKK2-1) alongside a structurally related but inactive compound (SGC-CAMKK2-1N), as well as CaMKK2 knock-out (KO) mice were used. In vitro kinase inhibition selectivity and efficacy assays, as well as cellular inhibition efficacy analyses of CaMKK inhibitors (STO-609 and SGC-CAMKK2-1) were performed. Phosphorylation and activity of AMPK following contractions (ex vivo) in mouse skeletal muscles treated with/without CaMKK inhibitors or isolated from wild-type (WT)/CaMKK2 KO mice were assessed. Camkk2 mRNA in mouse tissues was measured by qPCR. CaMKK2 protein expression was assessed by immunoblotting with or without prior enrichment of calmodulin-binding proteins from skeletal muscle extracts, as well as by mass spectrometry-based proteomics of mouse skeletal muscle and C2C12 myotubes. RESULTS: STO-609 and SGC-CAMKK2-1 were equally potent and effective in inhibiting CaMKK2 in cell-free and cell-based assays, but SGC-CAMKK2-1 was much more selective. Contraction-stimulated phosphorylation and activation of AMPK were not affected with CaMKK inhibitors or in CaMKK2 null muscles. Contraction-stimulated glucose uptake was comparable between WT and CaMKK2 KO muscle. Both CaMKK inhibitors (STO-609 and SGC-CAMKK2-1) and the inactive compound (SGC-CAMKK2-1N) significantly inhibited contraction-stimulated glucose uptake. SGC-CAMKK2-1 also inhibited glucose uptake induced by a pharmacological AMPK activator or insulin. Relatively low levels of Camkk2 mRNA were detected in mouse skeletal muscle, but neither CaMKK2 protein nor its derived peptides were detectable in mouse skeletal muscle tissue. CONCLUSIONS: We demonstrate that pharmacological inhibition or genetic loss of CaMKK2 does not affect contraction-stimulated AMPK phosphorylation and activation, as well as glucose uptake in skeletal muscle. Previously observed inhibitory effect of STO-609 on AMPK activity and glucose uptake is likely due to off-target effects. CaMKK2 protein is either absent from adult murine skeletal muscle or below the detection limit of currently available methods.

Defining the emergency general surgery patient population in the era of ICD-10 : Evaluating an established crosswalk from ICD-9 to ICD-10 diagnosis codes.

INTRODUCTION: In 2015, the United States moved from the International Classification of Diseases, Ninth Revision ( ICD-9 ), to the International Classification of Diseases, Tenth Revision ( ICD-10 ), coding system. The American Association for the Surgery of Trauma Committee on Severity Assessment and Patient Outcomes previously established a list of ICD-9 diagnoses to define the field of emergency general surgery (EGS). This study evaluates the general equivalence mapping (GEM) crosswalk to generate an equivalent list of ICD-10 -coded EGS diagnoses. METHODS: The GEM was used to generate a list of ICD-10 codes corresponding to the American Association for the Surgery of Trauma ICD-9 EGS diagnosis codes. These individual ICD-9 and ICD-10 codes were aggregated by surgical area and diagnosis groups. The volume of patients admitted with these diagnoses in the National Inpatient Sample in the ICD-9 era (2013-2014) was compared with the ICD-10 volumes to generate observed to expected ratios. The crosswalk was manually reviewed to identify the causes of discrepancies between the ICD-9 and ICD-10 lists. RESULTS: There were 485 ICD-9 codes, across 89 diagnosis categories and 11 surgical areas, which mapped to 1,206 unique ICD-10 codes. A total of 196 (40%) ICD-9 codes have an exact one-to-one match with an ICD-10 code. The median observed to expected ratio among the diagnosis groups for a primary diagnosis was 0.98 (interquartile range, 0.82-1.12). There were five key issues identified with the ability of the GEM to crosswalk ICD-9 EGS diagnoses to ICD-10 : (1) changes in admission volumes, (2) loss of necessary modifiers, (3) lack of specific ICD-10 code, (4) mapping to a different condition, and (5) change in coding nomenclature. CONCLUSION: The GEM provides a reasonable crosswalk for researchers and others to use when attempting to identify EGS patients in with ICD-10 diagnosis codes. However, we identify key issues and deficiencies, which must be accounted for to create an accurate patient cohort. This is essential for ensuring the validity of policy, quality improvement, and clinical research work anchored in ICD-10 coded data. LEVEL OF EVIDENCE: Diagnostic Test/Criteria; Level III.

Influence of biosolids and sewage effluent application on sitagliptin soil sorption.

Biosolids and sewage effluent application to agricultural fields is becoming a win-win practice as both an economical waste management strategy and a source of nutrients and organic matter for plant growth. However, these organic wastes contain a variety of trace chemicals of environmental concern such as pharmaceuticals and personal care products (PPCPs), which may pose a risk to agricultural fields and ecosystems. This work aims to investigate the sorption of sitagliptin on four agricultural soils, evaluate the effects of biosolids and sewage effluent application, and elucidate the main sorption mechanism of the pharmaceutical on soils. The sorption study revealed that the sorption capacities of sitagliptin on different soils were positively related to the contents of soil organic matter and negatively associated with soil pH values. The application of biosolids and sewage effluent decreased the sorption capacity of sitagliptin, which may be attributed to the loading of dissolved organic matter derived from organic wastes. The Freundlich isotherm model demonstrated that the addition of biosolids from 0 to 100 % (W/W) consistently decreased the sorption affinity (Kf) of sitagliptin from 1.69 × 102 to 3.82 × 101 mg(1-n) Ln kg-1. Sewage application at 0, 10, 50, and 100 % (V/V) also reduced the Kf values from 1.69 × 102 to 9.17 × 101 mg(1-n) Ln kg-1. Attenuated Total Reflection (ATR)-Infrared (IR) spectroscopy analyses suggested that electrostatic interactions between carbonyl and amino groups of sitagliptin and the negatively charged soil surface are the main sorption mechanisms. In a co-solute system, the sorption affinity of sitagliptin on the soil decreased with increasing metformin concentrations, suggesting that competitive sorption may reduce the sorption capacity of individual contaminants in soil systems containing multiple PPCPs.