Age-Related Patterns of Traumatic Facial Fractures in the Appalachian Tri-state Area: A Five-Year Retrospective Study.

Introduction Traumatic facial injuries, leading to facial fractures represent a significant subset of traumatic events, with age emerging as a crucial determinant influencing both their etiology and outcomes. Understanding the age-related patterns of traumatic facial fractures is essential for developing targeted prevention and management strategies. In this context, the Appalachian tri-state area stands as an underexplored region concerning this issue, necessitating comprehensive research to elucidate the nuances of age-related traumatic facial fractures within this geographic context. Methods This retrospective study delves into the age-related patterns of traumatic facial fractures within the Appalachian tri-state area, drawing upon patient records from Cabell Huntington Hospital and Saint Mary's Medical Center spanning a five-year period. The study cohort encompasses 623 patients categorized into three age groups: individuals aged <22 years, those aged 22-65 years, and individuals over 65 years. Data analysis involves meticulous examination of mechanisms of injury, injury severity scores (ISSs), hospital length of stay, and the prevalence of surgical interventions across different age cohorts. Results Out of 623 patients, 104 (16.7%) were under 22 years old, 367 (58.9%) were between 22 and 65 years old, and 152 (24.4%) were over 65 years old. The majority were male (70%). Falls were the most common cause of facial fractures in patients over 65 (78%), while assaults were predominant in the 22-65 age group (24%), and motor vehicle collisions (MCVs) in those under 22 (34%). The median ISS and hospital stay durations were similar across age groups. 28% of patients underwent surgery, with significant variation among age groups (p<0.001): 38% for <22 years, 33% for 22-65 years, and 11% for >65 years. Mandibular fractures were more prevalent in younger patients, with rates of 12% for <22 years compared to 5.3% for >65 years. Logistic regression analysis revealed that patients aged 22-65 had 4.10 times higher odds (95% CI=2.38, 7.45, p<0.001) of undergoing surgery, while those under 22 had 5.14 times higher odds (95% CI=2.73, 10.0, p<0.001) compared to those over 65. Significant associations were found for mandibular and bilateral mandibular outcomes in patients aged 22-65 years. Discussion These findings underscore the imperative for tailored prevention strategies and age-specific treatment protocols to optimize patient outcomes. Fall prevention initiatives for the elderly and interventions addressing sports-related injuries for younger individuals are paramount. Moreover, the study highlights the necessity of specialized care protocols for elderly patients to minimize hospital stay durations and manage age-related comorbidities effectively. Moving forward, further research should address limitations, validate findings, and explore the efficacy of specific interventions, thereby paving the way for enhanced preventive measures and management strategies tailored to the diverse age cohorts affected by traumatic facial fractures in the Appalachian region.

Zavegepant nasal spray for the acute treatment of migraine: A Phase 2/3 double-blind, randomized, placebo-controlled, dose-ranging trial.

OBJECTIVE: Evaluate the efficacy, safety, and tolerability of zavegepant nasal spray in the acute treatment of migraine. BACKGROUND: Calcitonin gene-related peptide-targeting agents are a novel class of therapeutics for migraine, but none are currently available as a nonoral option for acute treatment. Zavegepant, a high-affinity, selective, and structurally unique calcitonin gene-related peptide-receptor antagonist in late-stage development, is formulated as a nasal spray for the acute treatment of migraine. METHODS: This randomized, dose-ranging, placebo-controlled, Phase 2/3 trial in adults aged ≥18 years with migraine (NCT03872453) was conducted at US study sites. Participants were randomized by an interactive web response system and treated a single attack of moderate to severe pain intensity with zavegepant nasal spray 5, 10, 20 mg, or placebo. Coprimary efficacy endpoints were pain freedom and freedom from the most bothersome symptom at 2 h postdose. RESULTS: Of the 1673 participants aged 18 to 79 years who were randomized, 1588 were treated with study medication, and 1581 (mean age 40.8 years, 85.5% female) were analyzed for efficacy: zavegepant 5 mg (n = 387), 10 mg (n = 391), 20 mg (n = 402), and placebo (n = 401). Zavegepant 10 and 20 mg were more effective than placebo on the coprimary endpoints of pain freedom at 2 h postdose (placebo: 15.5% [98.3% confidence interval (CI), 11.1, 19.8]; 10 mg: 22.5% [98.3% CI, 17.5, 27.6; p = 0.0113]; 20 mg: 23.1% [98.3% CI, 18.1, 28.2; p = 0.0055]) and freedom from the most bothersome symptom at 2 h postdose (placebo: 33.7% [98.3% CI, 28.0, 39.3]; 10 mg: 41.9% [98.3% CI, 36.0, 47.9; p = 0.0155]; 20 mg: 42.5% [98.3% CI, 36.6, 48.4; p = 0.0094]). Findings for the 5 mg dose were not significant. The most common treatment-emergent adverse events with zavegepant 10 and 20 mg and placebo were dysgeusia (13.5% to 16.1% vs. 3.5%), nausea (2.7% to 4.1% vs. 0.5%), and nasal discomfort (1.3% to 5.2% vs. 0.2%). Most adverse events were mild or moderate and resolved without treatment. There was no signal of hepatotoxicity. CONCLUSION: Zavegepant nasal spray, in single doses of 10 or 20 mg, was effective for the acute treatment of migraine, with a favorable safety profile. Additional research is needed to confirm its potential as a nonoral medication for the acute treatment of migraine.

Association of number of primary care physicians with preventable hospitalizations and premature deaths.

BACKGROUND: Primary care physicians (PCPs) may be the first providers for patients in a healthcare interaction, putting them in a unique position that may determine the health trajectory of a patient. Assessing whether PCPs improve the overall health of a community through reducing preventable hospital stays and premature deaths may provide necessary information towards improving the health outcomes at grassroots. METHODS: County-level data on the number of primary care physicians, preventable hospital stays and 'years of potential life lost' (YPLL) were obtained from the Physician Master File data of the American Medical Association, Centers for Medicare & Medicaid Services Office of Minority Health's Mapping Medicare Disparities data, and Center for Disease Control and Prevention's WONDER database, respectively. We employed linear regression model to assess the association of PCP rate with preventable hospital stays and YPLL. RESULTS: Preventable hospitalization rate in the United States was 6303.4 (95% CI, 6212.5-6394.3) hospitalizations per 100,00 population, while the average YPLL across the counties in the United States was 7792.9 (95% CI, 7697.6-7888.3) years per 100,000 population. For an increase of 1 PCP in a county, around 16 hospitalizations were prevented per 100,000 population (P = 0.001) each year. Furthermore, around 14 years of life were saved per 100,000 population for every additional PCP in a county across the United States (P < 0.001). CONCLUSION: Higher number of PCPs in a county was associated with lower hospitalizations for preventable causes and lower premature deaths. Increasing PCPs may be an important metric to improve overall health in a community.

Species-specific effects of neuregulin-1ß (cimaglermin alfa) on glucose handling in animal models and humans with heart failure.

Neuregulin-1ß is a member of the neuregulin family of growth factors and is critically important for normal development and functioning of the heart and brain. A recombinant version of neuregulin-1ß, cimaglermin alfa (also known as glial growth factor 2 or GGF2) is being investigated as a possible therapy for heart failure. Previous studies suggest that neuregulin-1ß stimulation of skeletal muscle increases glucose uptake and, specifically, sufficient doses of cimaglermin alfa acutely produce hypoglycemia in pigs. Since acute hypoglycemia could be a safety concern, blood glucose changes in the above pig study were further investigated. In addition, basal glucose and glucose disposal were investigated in mice. Finally, as part of standard clinical chemistry profiling in a single ascending-dose human safety study, blood glucose levels were evaluated in patients with heart failure after cimaglermin alfa treatment. A single intravenous injection of cimaglermin alfa at doses of 0.8mg/kg and 2.6mg/kg in mice resulted in a transient reduction of blood glucose concentrations of approximately 20% and 34%, respectively, at 2h after the treatment compared to pre-treatment levels. Similar results were observed in diabetic mice. Treatment with cimaglermin alfa also increased blood glucose disposal following oral challenge in mice. However, no significant alterations in blood glucose concentrations were found in human heart failure patients at 0.5 and 2h after treatment with cimaglermin alfa over an equivalent human dose range, based on body surface area. Taken together, these data indicate strong species differences in blood glucose handling after cimaglermin alfa treatment, and particularly do not indicate that this phenomenon should affect human subjects.

Anti-remodeling and anti-fibrotic effects of the neuregulin-1ß glial growth factor 2 in a large animal model of heart failure.

BACKGROUND: Neuregulin-1ß (NRG-1ß) is a growth factor critical for cardiac development and repair with therapeutic potential for heart failure. We previously showed that the glial growth factor 2 (GGF2) isoform of NRG-1ß improves cardiac function in rodents after myocardial infarction (MI), but its efficacy in a large animal model of cardiac injury has not been examined. We therefore sought to examine the effects of GGF2 on ventricular remodeling, cardiac function, and global transcription in post-MI swine, as well as potential mechanisms for anti-remodeling effects. METHODS AND RESULTS: MI was induced in anesthetized swine (n=23) by intracoronary balloon occlusion. At 1 week post-MI, survivors (n=13) received GGF2 treatment (intravenous, biweekly for 4 weeks; n=8) or were untreated (n=5). At 5 weeks post-MI, fractional shortening was higher (32.8% versus 25.3%, P=0.019), and left ventricular (LV) end-diastolic dimension lower (4.5 versus 5.3 cm, P=0.003) in GGF2-treated animals. Treatment altered expression of 528 genes, as measured by microarrays, including collagens, basal lamina components, and matricellular proteins. GGF2-treated pigs exhibited improvements in LV cardiomyocyte mitochondria and intercalated disk structures and showed less fibrosis, altered matrix structure, and fewer myofibroblasts (myoFbs), based on trichrome staining, electron microscopy, and immunostaining. In vitro experiments with isolated murine and rat cardiac fibroblasts demonstrate that NRG-1ß reduces myoFbs, and suppresses TGFß-induced phospho-SMAD3 as well as αSMA expression. CONCLUSIONS: These results suggest that GGF2/NRG-1ß prevents adverse remodeling after injury in part via anti-fibrotic effects in the heart.

Intravenous glial growth factor 2 (GGF2) isoform of neuregulin-1ß improves left ventricular function, gene and protein expression in rats after myocardial infarction.

AIMS: Recombinant Neuregulin (NRG)-1ß has multiple beneficial effects on cardiac myocytes in culture, and has potential as a clinical therapy for heart failure (HF). A number of factors may influence the effect of NRG-1ß on cardiac function via ErbB receptor coupling and expression. We examined the effect of the NRG-1ß isoform, glial growth factor 2 (GGF2), in rats with myocardial infarction (MI) and determined the impact of high-fat diet as well as chronicity of disease on GGF2 induced improvement in left ventricular systolic function. Potential mechanisms for GGF2 effects on the remote myocardium were explored using microarray and proteomic analysis. METHODS AND RESULTS: Rats with MI were randomized to receive vehicle, 0.625 mg/kg, or 3.25 mg/kg GGF2 in the presence and absence of high-fat feeding beginning at day 7 post-MI and continuing for 4 weeks. Residual left ventricular (LV) function was improved in both of the GGF2 treatment groups compared with the vehicle treated MI group at 4 weeks of treatment as assessed by echocardiography. High-fat diet did not prevent the effects of high dose GGF2. In experiments where treatment was delayed until 8 weeks after MI, high but not low dose GGF2 treatment was associated with improved systolic function. mRNA and protein expression analysis of remote left ventricular tissue revealed a number of changes in myocardial gene and protein expression altered by MI that were normalized by GGF2 treatment, many of which are involved in energy production. CONCLUSIONS: This study demonstrates that in rats with MI induced systolic dysfunction, GGF2 treatment improves cardiac function. There are differences in sensitivity of the myocardium to GGF2 effects when administered early vs. late post-MI that may be important to consider in the development of GGF2 in humans.