Search

Landfills and wastewater treatment plants (WWTP) are point sources for many emerging contaminants, including microplastics and per- and polyfluoroalkyl substances (PFAS). Previous studies have estimated the abundance and transport of microplastics and PFAS separately in landfills and WWTPs. In addition, previous studies typically report concentrations of microplastics as particle count/L or count/g sediment, which do not provide the information needed to calculate mass balances. We measured microplastics and PFAS in four landfill-WWTP systems in Illinois, USA, and quantified mass of both contaminants in landfill leachate, WWTP influent, effluent, and biosolids. Microplastic concentrations in WWTP influent were similar in magnitude to landfill leachates, in the order of 10 2  μg plastic/L (parts-per-billion). In contrast, PFAS concentrations were higher in leachates (parts-per-billion range) than WWTP influent (parts-per-trillion range). After treatment, both contaminants had lower concentrations in WWTP effluent, although were abundant in biosolids. We concluded that WWTPs reduce PFAS and microplastics, lowering concentrations in the effluent that is discharged to nearby surface waters. However, partitioning of both contaminants to biosolids may reintroduce them as pollutants when biosolids are landfilled or used as fertilizer., Competing Interests: Declaration of competing interest There is no conflict of interest associated with this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

Introduction: There is a growing body of literature that shows geographic social vulnerability, which seeks to measure the resiliency of a community to withstand unforeseen disasters, may be associated with negative outcomes after traumatic injury. For motor vehicle collisions (MVCs) specifically, it is unknown how the resources of a patient's home environment may interact with resources of the environment where the crash occurred., Methods: We merged publicly available crash data from the state of Michigan with the Michigan Trauma Quality Improvement dataset. A social vulnerability index (SVI) score was calculated for each ZIP code and was then cross-referenced between the location of the MVC (Crash-SVI) and the patient's home address (Home-SVI). SVI was divided into quintiles, with higher numbers indicating greater vulnerability. Adjusted logistic regression models using least absolute shrinkage and selection operator for feature selection and regularization were performed sequentially using patient, vehicular, and environmental variables to identify associations between Home-SVI and Crash-SVI, with mortality and injury severity score (ISS) greater than 15 (ISS15)., Results: Between January 2020 and December 2022, a total of 14,706 patients were identified. Most MVCs (75.3% of all patients) occurred in the second through fourth quintiles of SVI. In all cases, Crash-SVI occurred most frequently within the same quintile as the patient's Home-SVI. Average crash speed limits showed a significant negative association with increasing SVI. On adjusted logistic regression, there were significantly increased odds of mortality for the fifth quintile of Home-SVI in comparison to the first quintile when adjusted for patient factors; but this lost significance after the addition of vehicular or environmental variables. In contrast, there were decreased odds of ISS15 for the highest quintiles of Crash-SVI in all logistic regression models., Conclusions: Geographic social vulnerability markers were associated with lower MVC-associated injury severity, perhaps in part because of the association with lower speed limit in these areas., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Trauma patients are at increased risk for venous thromboembolism events (VTEs). 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 (Abbreviated Injury Scale head score of 3, 4, or 5). Data were 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, and heparin >48 hours. Propensity score matching accounting for patient factors and injury characteristics was used with logistic regression modeling to evaluate in-hospital mortality, VTEs, 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% had LMWH, and 32% had heparin. Overall mortality was 8.3% and lowest among patients receiving LMWH ≤48 hours (4.1%). Venous thromboembolism event rates were lower with use of LMWH (1.6% vs. 4.5%; odds ratio, 2.98; 95% confidence interval, 1.40-6.34; p = 0.005) without increasing mortality or neurosurgical interventions. Venous thromboembolism event rates were lower with early prophylaxis (2.0% vs. 3.5%; odds ratio, 1.76; 95% confidence interval, 1.15-2.71; p = 0.01) without increasing mortality ( p = 1.0). Early VTEP was associated with more nonfatal 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)., Conclusion: 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 nonfatal neurosurgical interventions without affecting mortality. Low-molecular-weight heparin 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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Disposable e-cigarettes (vapes) are becoming increasingly popular but there are concerns about their impacts on human health, the environment and resource sustainability. A better understanding of these impacts and potential solutions requires characterisation and quantification of the materials and chemicals used in their construction. In the present study we dismantle nine types of popular, single-use vapes and analyse the components by X-ray fluorescence spectrometry and pyrolysis-gas chromatography mass spectrometry. The median dry mass of vapes was about 50 g, and the main material contribution was either plastic (up to about 80 %) or metal (up to about 85 %, and including the battery). Polycarbonate was the principal plastic used in the casing and nylon was always employed in the wick, but a range of other polymers were identified in other components used in wire insulation, sleeving, packaging, bundling and sealing. Various elements, as additives, residues or contaminants, were encountered in these parts that included As, Ba, Bi, Cr, Hg, Pb and Sb. Metal components were constructed of Al (often with Ti), stainless steel or Ni-based alloys (mainly in the coils), but other metals were often incorporated in alloys (e.g., Bi, Pb, W) or were present in trace quantities (including Co and Nb). Common metals in the Al-plastic-laminated Li-ion batteries were Cu, Co, Fe and Ni, but Au, Ba, Hg and Pb were also detected, while additional metals in the Cu-based printed circuit boards included Ag, Al, Ni, Sn, Ti and V, with traces of Ag, Bi, Mn, Nb and Pb present. The presence of toxic or potentially toxic metals in the vapes poses an environmental hazard through leaching after littering or landfilling, while metals within or in contact with the wick raise concerns about transfer to the e-liquid and exposure to the user. The overall material and chemical complexity of vapes presents challenges for safe disposal and component recycling, but the presence of critical elements, like Bi, Co, Nb, Sb, Sn, V and W, has additional implications for resource management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Calcium (Ca2+) ions are ubiquitous and indispensable signaling messengers that regulate virtually every cell function. The unique ability of Ca2+ to regulate so many different processes yet cause stimulus specific changes in cell function requires sensing and decoding of Ca2+ signals. Ca2+-sensing proteins, such as calmodulin, decode Ca2+ signals by binding and modifying the function of a diverse range of effector proteins. These effectors include the Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) enzyme, which is the core component of a signaling cascade that plays a key role in important physiological and pathophysiological processes, including brain function and cancer. In addition to its role as a Ca2+ signal decoder, CaMKK2 also serves as an important junction point that connects Ca2+ signaling with energy metabolism. By activating the metabolic regulator AMP-activated protein kinase (AMPK), CaMKK2 integrates Ca2+ signals with cellular energy status, enabling the synchronization of cellular activities regulated by Ca2+ with energy availability. Here, we review the structure, regulation, and function of CaMKK2 and discuss its potential as a treatment target for neurological disorders, metabolic disease, and cancer., (© 2024 The Author(s).)

Purpose: Pediatric cholestasis is the phenotypic expression of clinically and genetically heterogeneous disorders of bile acid synthesis and flow. Although a growing number of monogenic causes of pediatric cholestasis have been identified, the majority of cases remain undiagnosed molecularly., Methods: In a cohort of 299 pediatric participants (279 families) with intrahepatic cholestasis, we performed exome sequencing as a first-tier diagnostic test., Results: A likely causal variant was identified in 135 families (48.56%). These comprise 135 families that harbor variants spanning 37 genes with established or tentative links to cholestasis. In addition, we propose a novel candidate gene (PSKH1) (HGNC:9529) in 4 families. PSKH1 was particularly compelling because of strong linkage in 3 consanguineous families who shared a novel hepatorenal ciliopathy phenotype. Two of the 4 families shared a founder homozygous variant, whereas the third and fourth had different homozygous variants in PSKH1. PSKH1 encodes a putative protein serine kinase of unknown function. Patient fibroblasts displayed abnormal cilia that are long and show abnormal transport. A homozygous Pskh1 mutant mouse faithfully recapitulated the human phenotype and displayed abnormally long cilia. The phenotype could be rationalized by the loss of catalytic activity observed for each recombinant PSKH1 variant using in vitro kinase assays., Conclusion: Our results support the use of genomics in the workup of pediatric cholestasis and reveal PSKH1-related hepatorenal ciliopathy as a novel candidate monogenic form., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Introduction: Ventilator-associated pneumonia (VAP) is associated with increased mortality, prolonged mechanical ventilation, and longer intensive care unit stays. The rate of VAP (VAPs per 1000 ventilator days) within a hospital is an important quality metric. Despite adoption of preventative strategies, rates of VAP in injured patients remain high in trauma centers. Here, we report variation in risk-adjusted VAP rates within a statewide quality collaborative., Methods: Using Michigan Trauma Quality Improvement Program data from 35 American College of Surgeons-verified Level I and Level II trauma centers between November 1, 2020 and January 31, 2023, a patient-level Poisson model was created to evaluate the risk-adjusted rate of VAP across institutions given the number of ventilator days, adjusting for injury severity, physiologic parameters, and comorbid conditions. Patient-level model results were summed to create center-level estimates. We performed observed-to-expected adjustments to calculate each center's risk-adjusted VAP days and flagged outliers as hospitals whose confidence intervals lay above or below the overall mean., Results: We identified 538 VAP occurrences among a total of 33,038 ventilator days within the collaborative, with an overall mean of 16.3 VAPs per 1000 ventilator days. We found wide variation in risk-adjusted rates of VAP, ranging from 0 (0-8.9) to 33.0 (14.4-65.1) VAPs per 1000 d. Several hospitals were identified as high or low outliers., Conclusions: There exists significant variation in the rate of VAP among trauma centers. Investigation of practices and factors influencing the differences between low and high outlier institutions may yield information to reduce variation and improve outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Prompt acetylcysteine treatment with standard doses (300 mg/kg over 21 h in divided doses) is almost universally effective in preventing hepatotoxicity after paracetamol (acetaminophen) overdose. However, hepatotoxicity is reported despite early treatment when paracetamol concentrations exceed 300 mg/L (1,985 μmol/L) at 4 h. Prior studies evaluating high-dose acetylcysteine to treat high-risk ingestions have shown mixed results. We compared outcomes in patients with high-risk ingestions receiving standard or high-dose acetylcysteine., Methods: Records from a single poison center were reviewed from 1 January 2017 to 31 December 2022. We included cases of acute paracetamol ingestion treated with intravenous acetylcysteine with an initial paracetamol concentration above the "300 mg/L" (1,985 μmol/L) line on the Rumack-Matthew nomogram. We compared standard and high-dose acetylcysteine groups by odds ratios and multivariable logistic regression. We defined hepatotoxicity as aminotransferase activity >1,000 U/L., Results: We included 190 cases. Fifty-six percent received standard-dose acetylcysteine while 44% received high-dose acetylcysteine. Treatment within 8 h yielded no difference in hepatotoxicity between groups (odds ratio 1.67, 95% CI 0.067-42.3). Among patients treated after 8 h, hepatoxicity was more common in the high-dose group (odds ratio 3.39, 95% CI 1.25-9.2) though odds of liver failure were similar (odds ratio 2.78, 95% CI 0.89-8.69). Eighty-eight percent of patients with hepatotoxicity had elevated aminotransferase activity at presentation. No patient died or received a liver transplant., Discussion: Rates of hepatotoxicity were low in patients treated within 8 h regardless of acetylcysteine dose. Unexpectedly, high-dose acetylcysteine treatment was associated with an increased odds of hepatoxicity in those treated after 8 h, but most had abnormal aminotransferase activities at presentation and there was no difference in rates of liver failure. Limitations include the use of retrospective, voluntarily reported poison center data., Conclusions: Prompt treatment with acetylcysteine, regardless of dose, prevented hepatotoxicity in high-risk paracetamol ingestion.

Trauma activation fees are intended to help trauma centers cover the costs of providing lifesaving care at all times, but they have fallen under greater scrutiny because of a lack of regulation and wide variability in charges. We leveraged the federal Hospital Price Transparency rule to systematically describe trauma activation fees as captured in the Turquoise Health database for all Level I-III trauma centers nationally and across payer types. As of April 18, 2023, a total of 38 percent of US trauma centers published trauma activation fees. These fees varied widely by payer type. The minimum fee charged was $40 (for a Medicaid contract); the maximum fees charged were $28,356 (self-pay) and $28,893 (commercial payers). Trauma centers that were larger, metropolitan, located in the West, and associated with proprietary (investor-owned, for-profit) hospitals had higher trauma activation fees. Proprietary hospitals posted fees that were 60 percent higher than those published by public, nonfederal hospitals. Unmerited variation in trauma activation fees may suggest that the current funding strategy is equitable neither for trauma centers nor for the severely injured patients who rely on them for lifesaving care.

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2024 American Association for the Surgery of Trauma.)

Background: Knowing the mechanical properties of trabecular bone is critical for many branches of orthopaedic research. Trabecular bone is anisotropic and the principal trabecular direction is usually aligned with the load it transmits. It is therefore critical that the mechanical properties are measured as close as possible to this direction, which is often perpendicular to a curved articulating surface., Methods: This study presents a method to extract trabecular bone cores perpendicular to a curved articulating surface of the distal femur. Cutting guides were generated from computed tomography scans of 12 human distal femora and a series of cutting tools were used to release cylindrical bone cores from the femora. The bone cores were then measured to identify the angle between the bone core axis and the principal trabecular axis., Findings: The method yielded an 83% success rate in core extraction over 10 core locations per distal femur specimen. In the condyles, 97% of extracted cores were aligned with the principal trabecular direction., Interpretation: This method is a reliable way of extracting trabecular bone specimens perpendicular to a curved articular surface and could be useful across the field of orthopaedic research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2024 American Association for the Surgery of Trauma.)

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., Competing Interests: Conflict of Interest: All Journal of Trauma and Acute Care Surgery disclosure forms have been supplied and are provided as supplemental digital content (http://links.lww.com/TA/D763)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

There are places on earth that are considered to possess extreme physico-chemical characteristics as they relate to life. Surprisingly, there are microbes that have adapted various strategies that enable them to form robust communities in these environments. The microbes that live in these environments, called extremophiles, are described as being thermophilic, psychrophilic, halophilic, acidophilic, alkaliphilic, barophilic, and so on. Given that extremophiles were not discovered until relatively recently due to a view point that the environments in which they inhabited were not conducive to life, it is reasonable to conclude that the concept of extremophiles may be hard to grasp for students. Herein is described a laboratory exercise adapted from laboratory exercises that use mesophilic catalase enzymes to illustrate the influence of physico-chemical parameters on enzyme activity. Catalase is an enzyme that accelerates the degradation of hydrogen peroxide to water and oxygen gas. In addition to mesophilic catalases, the catalase from Pyrobaculum calidifontis , a hyperthermophile with an optimal growth temperature of 90°C, is used to highlight the adaptation of an enzyme to an extreme environment. A visual comparison of bubble production by the hyperthermophilic and mesophilic enzymes after heating at high temperatures dramatically illustrates differences in thermostability that will likely reinforce concepts that are given in a pre-laboratory lecture that discusses not only the extremophiles themselves but also their applications in biotechnology and possible role in the field of astrobiology., Competing Interests: The authors declare no conflict of interest.

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.

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2023 National Rural Health Association.)

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.

Superfluid 3 He is a paradigm for odd-parity Cooper pairing, ranging from neutron stars to uranium-based superconducting compounds. Recently it has been shown that 3 He, imbibed in anisotropic silica aerogel with either positive or negative strain, preferentially selects either the chiral A-phase or the time-reversal-symmetric B-phase. This control over basic order parameter symmetry provides a useful model for understanding imperfect unconventional superconductors. For both phases, the orbital quantization axis is fixed by the direction of strain. Unexpectedly, at a specific temperature T x , the orbital axis flops by 90 ∘ , but in reverse order for A and B-phases. Aided by diffusion limited cluster aggregation simulations of anisotropic aerogel and small angle X-ray measurements, we are able to classify these aerogels as either "planar" and "nematic" concluding that the orbital-flop is caused by competition between short and long range structures in these aerogels., (© 2024. The Author(s).)

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., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2023 American Association for the Surgery of Trauma.)

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., (Copyright © 2023 American Association for the Surgery of Trauma.)

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 Ca 2+ -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., (© 2023. The Author(s).)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To examine the association between intellectual disability and both severity of disease and clinical outcomes among patients presenting with common emergency general surgery (EGS) conditions., Background: Accurate and timely diagnosis of EGS conditions is crucial for optimal management and patient outcomes. Individuals with intellectual disabilities may be at increased risk of delayed presentation and worse outcomes for EGS; however, little is known about surgical outcomes in this population., Methods: Using the 2012-2017 Nationwide Inpatient Sample, we conducted a retrospective cohort analysis of adult patients admitted for 9 common EGS conditions. We performed multivariable logistic and linear regression to examine the association between intellectual disability and the following outcomes: EGS disease severity at presentation, any surgery, complications, mortality, length of stay, discharge disposition, and inpatient costs. Analyses were adjusted for patient demographics and facility traits., Results: Of 1,317,572 adult EGS admissions, 5,062 (0.38%) patients had a concurrent ICD-9/-10 code consistent with intellectual disability. EGS patients with intellectual disabilities had 31% higher odds of more severe disease at presentation compared with neurotypical patients (aOR 1.31; 95% CI 1.17-1.48). Intellectual disability was also associated with a higher rate of complications and mortality, longer lengths of stay, lower rate of discharge to home, and higher inpatient costs., Conclusion: EGS patients with intellectual disabilities are at increased risk of more severe presentation and worse outcomes. The underlying causes of delayed presentation and worse outcomes must be better characterized to address the disparities in surgical care for this often under-recognized but highly vulnerable population., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Gains in inpatient survival over the last five decades have shifted the burden of major injuries and surgical emergencies from the acute phase to their long-term sequelae. More attention has been placed on evaluation and optimization of long-term physical and mental health; however, the impact of major injuries and surgical emergencies on long-term financial well-being remains a critical blind spot for clinicians and researchers. The concept of financial toxicity encompasses both the objective financial consequences of illness and medical care as well as patients' subjective financial concerns. In this review, representatives of the Healthcare Economics Committee from the American Association for the Surgery of Trauma (1) provide a conceptual overview of financial toxicity after trauma or emergency surgery, (2) outline what is known regarding long-term economic outcomes among trauma and emergency surgery patients, (3) explore the bidirectional relationship between financial toxicity and long-term physical and mental health outcomes, (4) highlight policies and programs that may mitigate financial toxicity, and (5) identify the current knowledge gaps and critical next steps for clinicians and researchers engaged in this work., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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 (K f ) of sitagliptin from 1.69 × 10 2 to 3.82 × 10 1  mg (1-n) L n kg -1 . Sewage application at 0, 10, 50, and 100 % (V/V) also reduced the K f values from 1.69 × 10 2 to 9.17 × 10 1  mg (1-n) L n 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Out-of-pocket spending has risen for individuals with private health insurance, yet little is known about the unintended consequences that high levels of cost-sharing may have on delayed clinical presentation and financial outcomes for common emergency surgical conditions., Methods: In this retrospective analysis of claims data from a large commercial insurer (2016-2019), we identified adult inpatient admissions following emergency department presentation for common emergency surgical conditions (eg, appendicitis, cholecystitis, diverticulitis, and intestinal obstruction). Primary exposure of interest was enrollment in a high-deductible health insurance plan (HDHP). Our primary outcome was disease severity at presentation-determined using ICD-10-CM diagnoses codes and based on validated measures of anatomic severity (eg, perforation, abscess, diffuse peritonitis). Our secondary outcome was catastrophic out-of-pocket spending, defined by the World Health Organization as out-of-pocket spending >10% of annual income., Results: Among 43,516 patients [mean age 48.4 (SD: 11.9) years; 51% female], 41% were enrolled HDHPs. Despite being younger, healthier, wealthier, and more educated, HDHP enrollees were more likely to present with more severe disease (28.5% vs 21.3%, P <0.001; odds ratio (OR): 1.34, 95% CI: 1.28-1.42]); even after adjusting for relevant demographics (adjusted OR: 1.23, 95% CI: 1.18-1.31). HDHP enrollees were also more likely to incur 30-day out-of-pocket spending that exceeded 10% of annual income (20.8% vs 6.4%, adjusted OR: 3.93, 95% CI: 3.65-4.24). Lower-income patients, Black patients, and Hispanic patients were at highest risk of financial strain., Conclusions: For privately insured patients presenting with common surgical emergencies, high-deductible health plans are associated with increased disease severity at admission and a greater financial burden after discharge-especially for vulnerable populations. Strategies are needed to improve financial risk protection for common surgical emergencies., Competing Interests: This study was not directly funded by any grants or other relationships. However, the authors have the following disclosures, unrelated to the current work: J.W.S. receives funding from the Agency for Healthcare Research and Quality as principal investigator on grant K08-HS028672 and as a co-investigator on grant R01-HS027788. J.W.S. also receives salary support from Blue Cross Blue Shield of Michigan through the collaborative quality initiative known as Michigan Social Health Interventions to Eliminate Disparities (MSHIELD). P.U.N. receives salary funding through the National Clinical Scholars Program at the University of Michigan. A.M.I. receives funding from the Agency for Healthcare Research and Quality as principal investigator on grant R01-HS028606 and is a Principal at HOK architects, a global design and architecture firm. K.W.S. and Z.F. has no disclosures. A.M.F. reported being a consultant for AbbVie, Amgen, Bayer, Centivo, Community Oncology Association, EmblemHealth, Exact Sciences, Health at Scale Technologies, Lilly, Mallinckrodt, MedZed, Merck, Sempre Health, the State of Minnesota, Wellth, and Zansors; receiving research support from the Agency for Healthcare Research and Quality, Boehringer Ingelheim, the Gary and Mary West Health Policy Center, the Laura and John Arnold Foundation, the National Pharmaceutical Council, Patient-Centered Outcomes Research Institute, PhRMA, and the Michigan Department of Health and Human Services; and being coeditor of the American Journal of Managed Care , a member of the Medicare Evidence Development and Coverage Advisory Committee, and a partner in V-BID Health, LLC. J.B.D. is a cofounder of ArborMetrix Inc., a company that makes software for profiling hospital quality and efficiency. The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare surgical outcomes and expenditures at hospitals located in Health Professional Shortage Areas to nonshortage area designated hospitals among Medicare beneficiaries., Background: More than a quarter of Americans live in federally designated Health Professional Shortage Areas. Although there is growing concern that medical outcomes may be worse, far less is known about hospitals providing surgical care in these areas., Methods: Cross-sectional retrospective study from 2014 to 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. We assessed risk-adjusted outcomes using multivariable logistic regression accounting for patient factors, admission type, and year were compared for each of the 4 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., Results: Patients (mean age=75.6 years, males=44.4%) undergoing common surgical procedures in shortage area hospitals were less likely to be White (84.6% vs 88.4%, P <0.001) and less likely to have≥2 Elixhauser comorbidities (75.5% vs 78.2%, P <0.001). Patients undergoing surgery at Health Professional Shortage Area hospitals had lower risk-adjusted rates of 30-day mortality (6.05% vs 6.69%, odds ratio=0.90, CI, 0.90-0.91, P <0.001) and readmission (14.99% vs 15.74%, odds ratio=0.94, CI, 0.94-0.95, P <0.001). Medicare expenditures at Health Professional Shortage Area hospitals were also lower than nonshortage designated hospitals ($28,517 vs $29,685, difference= -$1168, P <0.001)., Conclusions: 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 underserved communities are considered., Competing Interests: J.B.D. is a cofounder of ArborMetrix, Inc., a company that makes software for profiling hospital quality and efficiency. A.M.I. is a Principal at HOK architects, a global design and architecture firm. The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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 Ca 2+ /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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Objective: To compare surgical outcomes and expenditures at critical access hospitals that do versus do not participate in a hospital network among Medicare beneficiaries., Background: 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 critical access hospitals have gone further to formally participate in a hospital network., Methods: This was a cross-sectional retrospective study from 2014 to 2018 comparing 16,128 Medicare beneficiary admissions for appendectomy, cholecystectomy, colectomy, or hernia repair at critical access hospitals that do versus do not participate in a hospital network. 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 postacute care payments., Results: Beneficiaries (average age = 75.7 years, SD = 7.4) who obtained care at critical access hospitals in a hospital network were more likely to carry ≥2 Elixhauser comorbidities (68.7% vs. 62.8%, P < 0.001). Rates of 30-day mortality were higher at critical access hospitals in a hospital network (4.30% vs. 3.81%, OR = 1.11, P < 0.001). Similarly, readmission rates were higher at critical access hospitals that were in a hospital network (15.13% vs. 14.34%, OR = 1.06, P < 0.001). Additionally, total episode payments were found to be $960 higher per patient at critical access hospitals that were in a hospital network ($23,878 vs. $22,918, P < 0.001)., Conclusions: Critical access hospitals within hospital networks 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., Competing Interests: J.B.D. is a cofounder of ArborMetrix Inc., a company that makes software for profiling hospital quality and efficiency. A.M.I. is a principal at HOK architects, a global design and architecture firm. The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Americans who reside in health professional shortage areas currently have less than half of the needed physician workforce. While the shortage designation has been associated with poor outcomes for chronic medical conditions, far less is known about outcomes after high-risk surgical procedures., Methods: We performed a retrospective review of Medicare beneficiaries living in health professional shortage areas and nonshortage areas who underwent abdominal aortic aneurysm repair, coronary artery bypass graft, esophagectomy, liver resection, pancreatectomy, or rectal resection between 2014 and 2018. Risk-adjusted multivariable logistic regression was used to determine whether rates of postoperative complications and 30-day mortality differed between patient cohorts. Beneficiary and hospital ZIP codes were used to quantify travel time to obtain care., Findings: Compared with patients living in nonshortage areas, patients living in health professional shortage areas traveled longer (median 60.0 vs 28.0 minutes, P<.001). There were no differences in risk-adjusted rates of complications (28.5% vs 28.6%, OR = 1.00, 95% CI 1.00-1.00, P = .59) and small differences in rates of 30-day mortality (4.2% vs 4.4%, OR = 0.95, 95% CI 0.95-0.95, P<.001) between beneficiaries living in shortage areas versus those not in shortage areas, respectively., Conclusions: Patients living in health professional shortage area undergoing high-risk surgery traveled more than 2 times longer for their care to obtain similar outcomes. While reassuring for clinical outcomes, additional efforts may be needed to mitigate the travel burden experienced by shortage area patients., (© 2023 National Rural Health Association.)

Objective: This study aims to identify opportunities to improve surgical equity by evaluating unmet social health needs by race, ethnicity, and insurance type., Background: Although inequities in surgical care and outcomes based on race, ethnicity, and insurance have been well documented for decades, underlying drivers remain poorly understood., Methods: 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, socioeconomic status, and unmet social health needs on health status., Results: Among a weighted sample of 14,471,501 surgical patients, 30% reported at least 1 unmet social health need. Compared with non-Hispanic White patients, non-Hispanic Black, and Hispanic patients reported higher rates of unmet social health needs. Compared with 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 [adjusted odds ratio (aOR)=2.14; 95% confidence interval (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)., Conclusions: 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., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Nuclear magnetic resonance measurements of the magnetic susceptibility of superfluid ^{3}He imbibed in anisotropic aerogel reveal anomalous behavior at low temperatures. Although the frequency shift clearly identifies a low-temperature phase as the B phase, the magnetic susceptibility does not display the expected decrease associated with the formation of the opposite-spin Cooper pairs. This susceptibility anomaly appears to be the predicted high-field behavior corresponding to the Ising-like magnetic character of surface Andreev bound states within the planar aerogel structures.

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., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://icmje.org/disclosure-of-interest/ and declare: no support from any organization for the submitted work; support from the Agency for Healthcare Research and Quality for JWS as principal investigator (grant K08-HS028672) and as a co-investigator (grant R01-HS027788). JWS also receives salary support from Blue Cross Blue Shield of Michigan through the collaborative quality initiative known as Michigan Social Health Interventions to Eliminate Disparities (MSHIELD), outside the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In urban areas, exposure to greenspace has been found to be beneficial to human health. The biodiversity hypothesis proposed that exposure to diverse ambient microbes in greener areas may be one pathway leading to health benefits such as improved immune system functioning, reduced systemic inflammation, and ultimately reduced morbidity and mortality. Previous studies observed differences in ambient outdoor bacterial diversity between areas of high and low vegetated land cover but didn't focus on residential environments which are important to human health. This research examined the relationship between vegetated land and tree cover near residence and outdoor ambient air bacterial diversity and composition. We used a filter and pump system to collect ambient bacteria samples outside residences in the Raleigh-Durham-Chapel Hill metropolitan area and identified bacteria by 16S rRNA amplicon sequencing. Geospatial quantification of total vegetated land or tree cover was conducted within 500 m of each residence. Shannon's diversity index and weighted UniFrac distances were calculated to measure α (within-sample) and β (between-sample) diversity, respectively. Linear regression for α-diversity and permutational analysis of variance (PERMANOVA) for β-diversity were used to model relationships between vegetated land and tree cover and bacterial diversity. Data analysis included 73 ambient air samples collected near 69 residences. Analysis of β-diversity demonstrated differences in ambient air microbiome composition between areas of high and low vegetated land (p = 0.03) and tree cover (p = 0.07). These relationships remained consistent among quintiles of vegetated land (p = 0.03) and tree cover (p = 0.008) and continuous measures of vegetated land (p = 0.03) and tree cover (p = 0.03). Increased vegetated land and tree cover were also associated with increased ambient microbiome α-diversity (p = 0.06 and p = 0.03, respectively). To our knowledge, this is the first study to demonstrate associations between vegetated land and tree cover and the ambient air microbiome's diversity and composition in the residential ecosystem., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2023. The Author(s).)

Abstract: The Trauma Quality Improvement Program Mortality Reporting System is an online anonymous case reporting system designed to share experiences from rare events that may have contributed to unanticipated mortality at contributing trauma centers. The Trauma Quality Improvement Program Mortality Reporting System Working Group monitors submitted cases and organizes them into emblematic themes. This report summarizes unanticipated mortality from 3 cases of airway loss in injured patients and presents strategies to mitigate these events locally, with the hope of decreasing unanticipated mortality nationwide., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Privately 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., Objective: To estimate out-of-pocket spending for non-birth-related hospitalizations among privately insured children and identify factors associated with this spending., Design, Setting, and Participants: This 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 Measures: In 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., Results: Among 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 Relevance: In 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.

Adverse financial outcomes after COVID-19 infection and hospitalization have not been assessed with appropriate comparators to account for other financial disruptions of 2020-2021. Using credit report data from 132,109 commercially insured COVID-19 survivors, we compared the rates of adverse financial outcomes for two cohorts of individuals with credit outcomes measured before and after COVID-19 infection, using an interaction term between cohort and hospitalization to test whether adverse credit outcomes changed more for hospitalized than nonhospitalized COVID-19 patients. Covariates included age group, gender, and several area-level social determinants of health. Adverse financial outcomes were significantly more common after COVID-19 infection than before COVID-19 infection, with greater increases among those hospitalized with COVID-19 (5-8 percentage points) than among nonhospitalized patients (1-3 percentage points). Future work examining longitudinal financial outcomes before and after COVID-19 infection is needed to determine the causal mechanisms of this association to reduce financial hardship from COVID-19 and other conditions., (© 2023 Society of Hospital Medicine.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)