Long gun violence in California versus Texas: How legislation can reduce firearm violence.

Introduction: Long guns (LGs) are uniquely implicated in firearm violence and mass shootings. On 1/1/2019 California (CA) raised the minimum age to purchase LGs from 18 to 21. This study aimed to evaluate the incidence of LG violence in CA vs. Texas (TX), a state with rising firearm usage and fewer LG regulations, hypothesizing decreased LG firearm incidents in CA vs increased rates in TX after CA LG legislation. Methods: A retrospective analysis of the Gun Violence Archive (2015-2021) was performed. An additional analysis of all firearm incidents within TX and CA was performed. CA and TX census data were used to calculate incidents of LG violence per 10,000,000 people. The primary outcome was the number of LG-related firearm incidents. Median yearly rates of LG violence per 10,000,000 people were compared for pre (2015-2018) vs post (2019-2021) CA LG legislation (Senate Bill 1100 (SB1100). Results: Median LG incidents decreased in CA post-SB1100 (4.21 vs 1.52, p < 0.001) by nearly 64 %, whereas any gun firearm violence was similar pre vs post-SB1100 (77.0 vs 74.5 median incidents, p = 0.89). In contrast, median LG incidents increased after SB1100 (4.34 vs 5.17 median incidents, p = 0.011) by nearly 35 % in TX, with any gun incidents increasing by nearly 53 % (83.48 vs 127.46, p < 0.001). Conclusion: CA LG firearm incidents decreased following SB 1100 legislation whereas the incidence in TX increased during this same time. Meanwhile, the incidence of any firearm violence remained similar in CA but increased in TX. This suggests the sharp decline in CA LG incidents may be related to SB1100. Accordingly, increasing the age to purchase a LG from 18 to 21 at a federal level may help curtail LG violence nationally.

Washington State Assault Weapon Firearm Violence Before and After Firearm Legislation Reform.

BACKGROUND: In January of 2019, Washington State (WA) passed Initiative 1639 making it illegal for persons <21 years-old to buy assault weapons (AWs). This study aimed to evaluate the effects of WA-1639 on firearm-related incidents involving AWs by those <21 years-old in WA, hypothesizing a decrease in incidents after WA-1639. METHODS: Retrospective (2016-2021) data on firearm violence (FV) events were gathered from the Gun Violence Archive. The rate of FV was weighted per 100,000 people. Total monthly incidents, injuries, and deaths were compared pre-law (January 2016-December 2018) vs post-law (January 2019-December 2021) implementation. Mann-Whitney U tests and Poisson's regression were used for analysis. RESULTS: From 4091 FV incidents (2210 (54.02%) pre-law vs 1881 (45.98%) post-law), 50 involved AWs pre- (2.3%) and 15 (.8%) post-law. Of these, 11 were committed by subjects <21 years-old pre-law and only one occurred post-law. Total incidents of FV (z = -3.80, P < .001), AW incidents (z = -4.28, P < .001), and AW incidents involving someone <21 years-old (z = -3.01, P < .01) decreased post-law. Additionally, regression analysis demonstrated the incident rate ratio (IRR) of all FV (1.23, 95% CI [1.10-1.38], P < .001), all AW FV incidents (3.42, 95% CI [1.70-6.89], P = .001), and AW incidents by subjects <21 years-old (11.53, 95% CI [1.52-87.26], P = .02) were greater pre-law vs post-law. DISCUSSION: Following implementation of WA-1639, there was a significant decrease in FV incidents and those involving AWs by individuals <21 years-old. This suggests targeted firearm legislation may help curtail FV. Further studies evaluating FV after legislation implementation in other states is needed to confirm these findings.

Domestic firearm violence against women (2018-2021).

Background: Over 50 % of US female homicides occur during domestic violence, with half involving firearms. Public health measures to control COVID-19 may have isolated individuals with abusive partners at a time when firearm sales and new firearm ownership surged. This study sought to evaluate trends in domestic firearm violence (DFV) over time, hypothesizing that rates of DFV increased in the wake of COVID-19. Materials and methods: A retrospective query of the Gun Violence Archive (2018-2021) was conducted for incidents of DFV. The primary outcome was the number of DFV-related shootings. Statistical testing, including one-way and two-way ANOVAs, was performed to compare monthly rates of DFV over time and to compare DFV per 100,000 women in states with strong versus weak gun laws. Results: Average monthly DFV incidents rose nationwide during this study's time period, though injuries and fatalities did not. States with weaker gun laws had increased incidents, deaths, and injuries from 2018 to 2021 (all p<0.05). In a two-way ANOVA, stronger gun laws were associated with fewer incidents of DFV when compared with weaker gun law states. We also found that the use of a long gun in DFV more often resulted in a victim's death when compared to a handgun (p<0.01). Conclusion: DFV incidents increased over time. States with weaker gun laws bore the brunt of the violence, demonstrating that DFV may be curtailed through legislative efforts. Methods of injury prevention aimed at preventing and reducing domestic violence and improving firearm safety may curtail DFV.

Society of Critical Care Medicine Guidelines on Recognizing and Responding to Clinical Deterioration Outside the ICU: 2023.

RATIONALE: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care hospitals have implemented systems aimed at detecting and responding to such patients. OBJECTIVES: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients. PANEL DESIGN: The 25-member panel included representatives from medicine, nursing, respiratory therapy, pharmacy, patient/family partners, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines. METHODS: We generated actionable questions using the Population, Intervention, Control, and Outcomes (PICO) format and performed a systematic review of the literature to identify and synthesize the best available evidence. We used the Grading of Recommendations Assessment, Development, and Evaluation Approach to determine certainty in the evidence and to formulate recommendations and good practice statements (GPSs). RESULTS: The panel issued 10 statements on recognizing and responding to non-ICU patients with critical illness. Healthcare personnel and institutions should ensure that all vital sign acquisition is timely and accurate (GPS). We make no recommendation on the use of continuous vital sign monitoring among unselected patients. We suggest focused education for bedside clinicians in signs of clinical deterioration, and we also suggest that patient/family/care partners' concerns be included in decisions to obtain additional opinions and help (both conditional recommendations). We recommend hospital-wide deployment of a rapid response team or medical emergency team (RRT/MET) with explicit activation criteria (strong recommendation). We make no recommendation about RRT/MET professional composition or inclusion of palliative care members on the responding team but suggest that the skill set of responders should include eliciting patients' goals of care (conditional recommendation). Finally, quality improvement processes should be part of a rapid response system. CONCLUSIONS: The panel provided guidance to inform clinicians and administrators on effective processes to improve the care of patients at-risk for developing critical illness outside the ICU.

Executive Summary: Society of Critical Care Medicine Guidelines on Recognizing and Responding to Clinical Deterioration Outside the ICU.

RATIONALE: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care facilities have implemented systems aimed at detecting and responding to such patients. OBJECTIVES: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients. PANEL DESIGN: The 25-member panel included representatives from medicine, nursing, respiratory therapy, pharmacy, patient/family partners, and clinician-methodologists with expertise in developing evidence-based clinical practice guidelines. METHODS: We generated actionable questions using the Population, Intervention, Control, and Outcomes format and performed a systematic review of the literature to identify and synthesize the best available evidence. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to determine certainty in the evidence and to formulate recommendations and good practice statements (GPSs). RESULTS: The panel issued 10 statements on recognizing and responding to non-ICU patients with critical illness. Healthcare personnel and institutions should ensure that all vital sign acquisition is timely and accurate (GPS). We make no recommendation on the use of continuous vital sign monitoring among "unselected" patients due to the absence of data regarding the benefit and the potential harms of false positive alarms, the risk of alarm fatigue, and cost. We suggest focused education for bedside clinicians in signs of clinical deterioration, and we also suggest that patient/family/care partners' concerns be included in decisions to obtain additional opinions and help (both conditional recommendations). We recommend hospital-wide deployment of a rapid response team or medical emergency team (RRT/MET) with explicit activation criteria (strong recommendation). We make no recommendation about RRT/MET professional composition or inclusion of palliative care members on the responding team but suggest that the skill set of responders should include eliciting patients' goals of care (conditional recommendation). Finally, quality improvement processes should be part of a rapid response system (GPS). CONCLUSIONS: The panel provided guidance to inform clinicians and administrators on effective processes to improve the care of patients at-risk for developing critical illness outside the ICU.

Trends in Legal Firearm Transactions: A Possible Protective Role of Gun Law Strength.

INTRODUCTION: The United States (US) holds the highest personal firearm ownership among industrialized nations, with implications for firearm-related deaths tied to increased per capita gun ownership and varying gun laws. This study examines the influence of gun law strength on legal firearm transactions, positing a correlation between stronger laws and reduced transactions. The analysis, focused on the stress-laden COVID-19 pandemic, evaluates handgun, long gun, and multiple gun transactions in 2020 and 2021 compared to 2018-2019. METHODS: The Giffords Gun Law scorecard categorized states into the top 25 "strong" and bottom 25 "weak" gun law groups. Multivariate linear regressions assessed the association between strong gun law states and monthly National Instant Criminal Background Check System (NICS) data from 2018 to 2021. The study queried NICS for handgun, long gun, and multiple gun transactions, comparing median monthly transactions in 2018 and 2019 to 2020 and 2018-2020 to 2021. RESULTS: When evaluating gun law strength through multivariate linear regression models, stronger gun law states had fewer monthly NICS transactions for handguns, long guns, and multiple guns in 2020 and 2021 versus all comparison years (all P < .05). However, from 2018-2019 to 2020 and 2018-2020 to 2021, median monthly NICS transactions per 100,000 people for all gun types increased (all P < .05). CONCLUSION: Stricter gun laws correlated with decreased firearm transactions in stronger law states, yet handgun, long gun, and multiple gun transactions increased during the pandemic years of 2020 and 2021. Therefore, strengthening firearm legislation may be protective against the proliferation of firearms, which warrants further research.

Firearm Violence Involving Adults 65 and Older During the Novel Coronavirus Disease Pandemic.

BACKGROUND: Rates of firearm violence (FV) surged during the COVID-19 pandemic. However, there is a paucity of data regarding older adults (OAs) (≥65 years old). This study aimed to evaluate patterns of FV against OAs before and after the COVID-19 pandemic, hypothesizing decreased firearm incidents, injuries, and deaths for OAs due to restricted social movement. METHODS: Retrospective (2016-2021) data for OAs were obtained from the Gun Violence Archive. The rate of FV was weighted per 10,000 OAs using annual population data from the United States Census Bureau. Mann-Whitney U tests were performed to compare annual firearm incidence rates, number of OAs killed, and number of OAs injured from 2016-2020 to 2021. RESULTS: From 944 OA-involved shootings, 842 died in 2021. The median total firearm incidents per month per 10,000 OAs decreased in 2021 vs 2016 (.65 vs .38, P < .001), 2017 (.63 vs .38, P < .001), 2018 (.61 vs .38, P < .001), 2019 (.39 vs .38, P = .003), and 2020 (.43 vs .38, P = .012). However, there was an increased median number of OAs killed in 2021 vs 2020 (.38 vs .38, P = .009), but no difference from 2016-2019 vs 2021 (all P > .05). The median number of firearm injuries decreased from 2017 to 2021 (.21 vs .19, P = .001) and 2020 to 2021 (.19 vs .19 P < .001). DISCUSSION: Firearm incidents involving OAs decreased in 2021 compared to pre-pandemic years; however, there was a slight increase in deaths compared to 2020. This may reflect increased social isolation; however, future research is needed to understand why this occurred.

Is Adolescent Obesity Associated With a Higher Risk for Pelvic Fractures in Motor Vehicle Collisions?

INTRODUCTION: The impact of obesity on the incidence of blunt pelvic fractures in adults is unclear, and adolescents may have an increased risk of fracture due to variable bone mineral density and leptin levels. Increased subcutaneous adipose tissue may provide protection, though the association between obesity and pelvic fractures in adolescents has not been studied. This study hypothesized that obese adolescents (OAs) presenting after motor vehicle collision (MVC) have a higher rate of pelvic fractures, and OAs with such fractures have a higher associated risk of complications and mortality compared to non-OAs. METHODS: The 2017-2019 Trauma Quality Improvement Program database was queried for adolescents (12-16 y old) presenting after MVC. The primary outcome was a pelvic fracture. Adolescents with a body mass index ≥30 (OA) were compared to adolescents with a body mass index <30 (non-OA). Subgroup analyses for high-risk and low-risk MVCs were performed. Multivariable logistic regression analyses were also performed adjusting for age and sex. RESULTS: From 22,610 MVCs, 3325 (14.7%) included OAs. The observed rate of pelvic fracture was similar between all OA and non-OA MVCs (10.2% versus 9.4%, P = 0.16), as well as subanalyses of minor or high-risk MVC (both P > 0.05). OAs presenting with a pelvic fracture after high-risk MVC had a similar risk of complications, pelvic surgery, and mortality compared to non-OAs (all P > 0.05). However, OAs with a pelvic fracture after minor MVC had a higher associated risk of complications (OR 2.27, CI 1.10-4.69, P = 0.03), but a similar risk of requiring pelvic surgery, and mortality (all P > 0.05). CONCLUSIONS: This national analysis found a similar observed incidence of pelvic fractures for OAs versus non-OAs involved in an MVC, including subanalyses of minor and high-risk MVC. Furthermore, there was no difference in the associated risk of morbidity and mortality except for OAs involved in a minor MVC had a higher risk of complication.

Implications of Using Chatbots for Future Surgical Education.

This quality improvement study investigates whether a chatbot can accurately answer surgery clerkship multiple-choice questions, explain incorrect answers, assess question difficulty, and generate a high-quality examination question.

Field Measures Are All You Need: Predicting Need for Surgery in Elderly Ground-Level Fall Patients via Machine Learning.

BACKGROUND: As ground-level falls (GLFs) are a significant cause of mortality in elderly patients, field triage plays an essential role in patient outcomes. This research investigates how machine learning algorithms can supplement traditional t-tests to recognize statistically significant patterns in medical data and to aid clinical guidelines. METHODS: This is a retrospective study using data from 715 GLF patients over 75 years old. We first calculated P-values for each recorded factor to determine the factor's significance in contributing to a need for surgery (P < .05 is significant). We then utilized the XGBoost machine learning method to rank contributing factors. We applied SHapley Additive exPlanations (SHAP) values to interpret the feature importance and provide clinical guidance via decision trees. RESULTS: The three most significant P-values when comparing patients with and without surgery are as follows: Glasgow Coma Scale (GCS) (P < .001), no comorbidities (P < .001), and transfer-in (P = .019). The XGBoost algorithm determined that GCS and systolic blood pressure contribute most strongly. The prediction accuracy of these XGBoost results based on the test/train split was 90.3%. DISCUSSION: When compared to P-values, XGBoost provides more robust, detailed results regarding the factors that suggest a need for surgery. This demonstrates the clinical applicability of machine learning algorithms. Paramedics can use resulting decision trees to inform medical decision-making in real time. XGBoost's generalizability power increases with more data and can be tuned to prospectively assist individual hospitals.

Aryl hydrocarbon receptor-independent activation of estrogen receptor-dependent transcription by 3-methylcholanthrene.

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that stimulates transcription directed by xenobiotic response elements upstream of target genes. Recently, AhR ligands were reported to induce formation of an AhR-estrogen receptor (ER) complex, which can bind to estrogen response elements (EREs) and stimulate transcription of ER target genes. Presently, we investigate the effect of the AhR ligands 3-methylcholanthrene (3MC), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3,3',4,4',5-pentachlorobiphenyl (BZ126) on ERE-regulated luciferase reporter activity and endogenous ER target gene expression. In MCF-7 human breast cancer cells, 3MC induced transcription of ER reporter genes containing native promoter sequences of the ER-responsive genes complement 3 and pS2 and heterologous promoters regulated by isolated EREs. Dose-response studies revealed that the concentration of 3MC required to half-maximally activate transcription (EC(50)) was >100-fold higher for an ER reporter (27-57 muM) than for an AhR reporter (86-250 nM) in both MCF-7 cells and in human endometrial cancer Ishikawa cells. 3MC also stimulated expression of the endogenous ER target genes amphiregulin, cathepsin D and progesterone receptor, albeit to a much lower extent than was achieved following stimulation with 17beta-estradiol. In Ishikawa cells, 3MC, but not BZ126 or TCDD, stimulated ERalpha-dependent reporter activity but did not induce expression of endogenous ER target genes. Finally, studies carried out in the AhR-positive rat hepatoma cell line 5L and the AhR-deficient variant BP8 demonstrated that ER reporter activity could be induced by 3MC in a manner that was independent of AhR and thus distinct from the AhR-ER 'hijacking' mechanism described recently. 3MC may thus elicit estrogenic activity by multiple mechanisms.

Simultaneous, bidirectional inhibitory crosstalk between PPAR and STAT5b.

The transcription factors peroxisome proliferator-activated receptor (PPAR) and signal transducer and activator of transcription 5 (STAT5) activate genes involved in fatty acid metabolism (PPARalpha) and adipogenesis (PPARgamma) and mediate hormonal responses important for body growth, liver gene expression, and mammary gland development (STAT5a and STAT5b). These seemingly disparate pathways are subject to mutually inhibitory crosstalk, with growth hormone (GH)-activated STAT5 able to inhibit PPAR-regulated gene transcription by approximately 80%, and conversely, ligand-activated PPAR able to inhibit STAT5-regulated transcription to a similar degree. Given the co-expression of PPAR and STAT5 in multiple tissues, we investigated whether one of the factors dominates the inhibitory crosstalk. A PPAR-responsive Renilla luciferase reporter was constructed and used to monitor PPAR transcriptional activity in COS-1 cells co-transfected with a STAT5 firefly luciferase reporter. In cells co-stimulated with GH and a PPAR agonist, STAT5b inhibited expression of the PPAR-regulated Renilla luciferase reporter, whereas PPARalpha and PPARgamma inhibited transcription of the STAT5b-regulated firefly luciferase reporter. The extent of the inhibitory crosstalk was dependent on the relative levels of expression of each transcription factor and on the relative concentrations of GH and PPAR agonist. Dose-response studies revealed that STAT5b was inhibited at an approximately 7-fold lower concentration of the PPARgamma ligand troglitazone than was required for activation of PPARgamma, indicating that only a portion of cellular PPARgamma is needed for STAT5b inhibition. Similarly, mono-(2-ethylhexyl)phthalate (MEHP), a reproductive toxicant and primary metabolite of the environmental chemical di-(2-ethylhexyl)phthalate (DEHP), inhibited STAT5b transcriptional activity with an EC50 value of 1.1 microM, corresponding to an approximately 10-fold lower concentration than required for activation of PPARgamma-dependent transcription. We conclude that the cross-inhibition between PPAR and STAT5 proceeds in a simultaneous, bidirectional manner. Exposure to phthalates and other environmental chemical activators of PPARs may thus lead to alteration of hormone-induced, STAT5-regulated gene expression in tissues such as liver, fat and breast, where both transcription factors are expressed. Conversely, STAT5-activating hormones and cytokines may modulate the responsiveness of PPARs to their foreign chemical ligands.

trans-activation of PPARalpha and induction of PPARalpha target genes by perfluorooctane-based chemicals.

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that activate target genes involved in lipid metabolism, energy homeostasis, and cell differentiation in response to diverse compounds, including environmental chemicals. The liver-expressed receptor PPARalpha mediates peroxisome proliferative responses associated with rodent hepatocarcinogenesis. Previous studies have established that certain perfluorooctanesulfonamide-based chemicals (PFOSAs) alter lipid metabolism, are hepatic peroxisome proliferators, and induce hepatocellular adenoma formation in rodents, suggesting that they activate PPARalpha. The present study investigates this question and characterizes the activation of mouse and human PPARalpha by PFOSAs. Perfluorooctanesulfonate (PFOS), an end-stage metabolite common to several PFOSAs, was found to activate both mouse and human PPARalpha in a COS-1 cell-based luciferase reporter trans-activation assay. Half-maximal activation (EC50) occurred at 13-15 microM PFOS, with no significant difference in the responsiveness of mouse and human PPARalpha. Mouse and human PPARalpha were activated by perfluorooctanesulfonamide (FOSA) over a similar concentration range; however, cellular toxicity precluded an accurate determination of EC50 values. Studies of 2-N-ethylperfluorooctanesulfonamido ethanol were less informative due to its insolubility. These findings were verified in an FAO rat hepatoma cell line that stably expresses PPARalpha, where the endogenous PPARalpha target genes peroxisomal bifunctional enzyme and peroxisomal 3-ketoacyl-CoA thiolase were activated up to approximately 10-20-fold by PFOS and FOSA. The interactions of PPARalpha with PFOS and FOSA, and the potential of these chemicals for activation of unique sets of downstream target genes, may help explain the diverse biological effects exhibited by PFOSAs and may aid in the evaluation of human and environmental risks associated with exposure to this important class of fluorochemicals.

Down-regulation of STAT5b transcriptional activity by ligand-activated peroxisome proliferator-activated receptor (PPAR) alpha and PPARgamma.

The nuclear receptor peroxisome proliferator-activated receptor (PPAR) is activated by a diverse group of acidic ligands, including many peroxisome proliferator chemicals present in the environment. Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) signaling is activated by multiple cytokines and hormones and leads to the translocation of dimerized STAT proteins to the nucleus where they activate transcription of target genes. Previous studies have shown that growth hormone (GH)-activated STAT5b can inhibit PPAR-regulated transcription. Here, we show that this inhibitory cross-talk is mutual, and that GH-induced, STAT5b-dependent beta-casein promoter-luciferase reporter gene transcription can be inhibited up to approximately 80% by ligand-activated PPARalpha or PPARgamma. Dose-response experiments showed a direct relationship between the extent of PPAR activation and the degree of inhibition of STAT5-regulated transcription. PPAR did not block STAT5b tyrosine phosphorylation or inhibit DNA-binding activity. Both PPARs inhibited the transcriptional activity of a constitutively active STAT5b mutant, indicating that inhibition occurs downstream of the GH-stimulated STAT5 activation step. Transcriptionally inactive, dominant-negative PPAR mutants did not block STAT5b inhibition by wild-type PPAR, indicating that PPAR target gene transcription is not required. PPARalpha retained its STAT5b inhibitory activity in the presence of the histone deacetylase inhibitor trichostatin, indicating that enhanced histone deacetylase recruitment does not contribute to STAT5b inhibition. PPARalpha lacking the ligand-independent AF-1 trans-activation domain failed to inhibit STAT5b, highlighting the importance of the AF-1 region in STAT5-PPAR inhibitory cross-talk. These findings demonstrate the bidirectionality of cross-talk between the PPAR and STAT pathways and provide a mechanism whereby exposure to environmental chemical activators of PPAR can suppress expression of GH target genes.