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Gene transfer therapies utilizing adeno-associated virus (AAV) vectors involve a complex drug design with multiple components that may impact immunogenicity. Valoctocogene roxaparvovec is an AAV serotype 5 (AAV5)-vectored gene therapy for the treatment of hemophilia A that encodes a B-domain-deleted human factor VIII (FVIII) protein controlled by a hepatocyte-selective promoter. Following previous results from the first-in-human phase 1/2 clinical trial, we assessed AAV5-capsid- and transgene-derived FVIII-specific immune responses with 2 years of follow-up data from GENEr8-1, a phase 3, single-arm, open-label study in 134 adult men with severe hemophilia A. No FVIII inhibitors were detected following administration of valoctocogene roxaparvovec. Immune responses were predominantly directed toward the AAV5 capsid, with all participants developing durable anti-AAV5 antibodies. Cellular immune responses specific for the AAV5 capsid were detected in most participants by interferon-γ enzyme-linked immunosorbent spot assay 2 weeks following dose administration and declined or reverted to negative over the first 52 weeks. These responses were weakly correlated with alanine aminotransferase elevations and showed no association with changes in FVIII activity. FVIII-specific cellular immune responses were less frequent and more sporadic compared with those specific for AAV5 and showed no association with safety or efficacy parameters.
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Dependovirus , Fator VIII , Terapia Genética , Vetores Genéticos , Hemofilia A , Humanos , Hemofilia A/terapia , Hemofilia A/imunologia , Hemofilia A/genética , Dependovirus/genética , Dependovirus/imunologia , Terapia Genética/métodos , Vetores Genéticos/genética , Vetores Genéticos/administração & dosagem , Fator VIII/genética , Fator VIII/imunologia , Masculino , Adulto , Resultado do Tratamento , Transgenes , Adulto Jovem , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Pessoa de Meia-IdadeRESUMO
During pandemics, healthcare providers struggle with balancing obligations to self, family, and patients. While HIV/AIDS seemed to settle this issue, coronavirus disease 2019 (COVID-19) rekindled debates regarding treatment refusal. We searched MEDLINE, Embase, CINAHL Complete, and Web of Science using terms including obligation, refusal, HIV/AIDS, COVID-19, and pandemics. After duplicate removal and dual, independent screening, we analyzed 156 articles for quality, ethical position, reasons, and concepts. Diseases in our sample included HIV/AIDS (72.2%), severe acute respiratory syndrome (SARS) (10.2%), COVID-19 (10.2%), Ebola (7.0%), and influenza (7.0%). Most articles (81.9%, n = 128) indicated an obligation to treat. COVID-19 had the highest number of papers indicating ethical acceptability of refusal (60%, P < .001), while HIV had the least (13.3%, P = .026). Several reason domains were significantly different during COVID-19, including unreasonable risks to self/family (26.7%, P < .001) and labor rights/workers' protection (40%, P < .001). A surge in ethics literature during COVID-19 has advocated for permissibility of treatment refusal. Balancing healthcare provision with workforce protection is crucial in effectively responding to a global pandemic.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Pessoal de Saúde/ética , Infecções por HIV/tratamento farmacológico , Pandemias , Recusa do Paciente ao Tratamento/ética , Obrigações MoraisRESUMO
INTRODUCTION: Valoctocogene roxaparvovec, a gene therapy evaluated in the phase 3 GENEr8-1 trial, supports endogenous factor VIII (FVIII) production to prevent bleeding in people with severe haemophilia A. Individuals receiving emicizumab, an antibody mimicking the function of activated FVIII, were excluded from GENEr8-1 enrolment since emicizumab was an investigational therapy at the time of trial initiation. AIM: Utilize pharmacokinetic simulations to provide guidance on best practices for maintaining haemostatic control while transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec. METHODS: To estimate bleeding risk at weekly intervals following valoctocogene roxaparvovec infusion, a published emicizumab pharmacokinetic model was used to simulate emicizumab concentrations and merged with FVIII activity time-course data for participants in GENEr8-1. The analysis investigated three approved emicizumab dosing regimens for two transition scenarios that varied whether the last dose of emicizumab was administered on the same day or 4 weeks after valoctocogene roxaparvovec infusion. RESULTS: Simulations demonstrated administering the last emicizumab dose the day of valoctocogene roxaparvovec infusion and 4 weeks after offered similar levels of haemostatic control, and bleeding risk was similar for all emicizumab dosing regimens. An algorithm was developed to provide guidance for discontinuation of emicizumab. Theoretical cases based on GENEr8-1 participants are presented to illustrate how decisions may vary among individuals. CONCLUSION: Pharmacokinetic simulations demonstrated no clinically meaningful difference in bleeding risk caused by decaying emicizumab levels and rising gene therapy-derived endogenous FVIII for all examined emicizumab doses and dosing regimens. Therefore, multiple approaches can safely transition individuals from emicizumab prophylaxis to valoctocogene roxaparvovec.
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Anticorpos Biespecíficos , Anticorpos Monoclonais Humanizados , Fator VIII , Terapia Genética , Hemofilia A , Hemofilia A/tratamento farmacológico , Humanos , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Fator VIII/uso terapêutico , Terapia Genética/métodos , Hemorragia/prevenção & controle , Simulação por Computador , MasculinoRESUMO
INTRODUCTION: Valoctocogene roxaparvovec uses an adeno-associated virus serotype 5 (AAV5) vector to transfer a factor VIII (FVIII) coding sequence to individuals with severe haemophilia A, providing bleeding protection. AIM: To assess safety and efficacy of valoctocogene roxaparvovec 5-6 years post-treatment. METHODS: In a phase 1/2 trial, adult male participants with severe haemophilia A (FVIII ≤1 IU/dL) without FVIII inhibitors or anti-AAV5 antibodies received valoctocogene roxaparvovec and were followed for 6 (6 × 1013 vg/kg; n = 7) and 5 (4 × 1013 vg/kg; n = 6) years. Safety, including investigation of potential associations between a malignancy and gene therapy, and efficacy are reported. RESULTS: No new treatment-related safety signals emerged. During year 6, a participant in the 6 × 1013 vg/kg cohort was diagnosed with grade 2 parotid gland acinar cell carcinoma; definitive treatment was uncomplicated parotidectomy with lymph node dissection. Target enrichment sequencing of tumour and adjacent healthy tissue revealed low vector integration (8.25 × 10-5 per diploid cell). Integrations were not elevated in tumour samples, no insertions appeared to drive tumorigenesis, and no clonal expansion of integration-containing cells occurred. During all follow-ups, >90% decreases from baseline in annualised treated bleeds and FVIII infusion rates were maintained. At the end of years 6 and 5, mean FVIII activity (chromogenic assay) was 9.8 IU/dL (median, 5.6 IU/dL) and 7.6 IU/dL (median, 7.1 IU/dL) for the 6 × 1013 and 4 × 1013 vg/kg cohorts, respectively, representing proportionally smaller year-over-year declines than earlier timepoints. CONCLUSIONS: Valoctocogene roxaparvovec safety and efficacy profiles remain largely unchanged; genomic investigations showed no association with a parotid tumour.
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Dependovirus , Hemofilia A , Hemostáticos , Neoplasias , Proteínas Recombinantes de Fusão , Adulto , Humanos , Masculino , Hemofilia A/complicações , Fator VIII/genética , Hemorragia/prevenção & controle , Neoplasias/complicaçõesRESUMO
INTRODUCTION: Firearm-related suicides among children present a significant public health concern and a tragic loss of young lives. This study explores the relationship between firearm-related suicides, gun ownership, and state-specific gun laws. METHODS: This retrospective cohort study collected data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research on children under 18 who died by firearm-related suicides between 2009 and 2016 in all 50 states and D.C. It also utilized data from the RAND State-Level Estimates of Household Firearm Ownership. The study focused on the rate of child firearm suicide deaths per 100,000 individuals. The key variable of interest was the percentage of guns owned per household in each state. Univariable analysis was conducted to examine the association between individual gun laws and child firearm suicide mortalities, while multivariable regression, adjusting for household gun ownership and significant firearm legislation, was employed to assess connection to child firearm suicide mortality. RESULTS: From 2009 to 2016, 3903 children died from firearm-related suicides in the United States. In our analysis, 15 out of 44 firearm laws were found to be associated with reducing the rates of firearm suicides among children (P < 0.05). However, multivariable regression showed that higher state gun ownership rates were the primary predictor of increased child fatalities from firearms, with children in such states being 325% more likely to die when analyzing handgun laws and 337% more likely when analyzing long gun laws, as indicated by coefficients of 4.25 and 4.37, respectively. No state laws alone notably improved death rates. CONCLUSIONS: Gun ownership has a stronger association with child suicide rates than state-specific gun laws. Given the weight of gun ownership, future research should prioritize comprehensive public health initiatives to prevent child firearm-related suicides.
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INTRODUCTION: Surgical stabilization of rib fractures (SSRF) has been associated with lower rates of mortality and fewer respiratory complications. This study sought to evaluate the association between SSRF timing and patient outcomes. METHODS: This retrospective analysis included patients aged ≥45 y who underwent SSRF in the Trauma Quality Improvement Program database from 2016 to 2020. Primary outcome was incidence of ventilator-assisted pneumonia (VAP). Secondary outcomes included acute respiratory distress syndrome (ARDS), unplanned endotracheal intubation, in-hospital mortality, failure to rescue (FTR) after all major complications, and FTR after severe respiratory complications. Logistic regression models of outcomes on timing to SSRF were fit while controlling for age, gender, body mass index, injury severity score, flail chest, chronic obstructive pulmonary disease, congestive heart failure, and smoking. RESULTS: Among 4667 patients who received SSRF, average time to SSRF was 4.6 ± 3.2 d. Each additional day to SSRF was associated with increased odds of VAP (odds ratio [OR] 1.07, confidence interval [CI] 1.03-1.11) and intubation (OR 1.10, CI 1.08-1.13). A longer time to SSRF was associated with increased odds of ARDS (OR 1.10, CI 1.05-1.15), while no significant association was observed for in-hospital mortality (OR 0.99, CI 0.93-1.04). A longer time to SSRF was associated with decreased odds of FTR after a major complication (OR 0.90, CI 0.83-0.97) and respiratory complications (OR 0.87, CI 0.78-0.96). CONCLUSIONS: For each day that SSRF is delayed, increased odds of VAP, intubation, and ARDS were observed. Prompt intervention is crucial for preventing these complications and improving our ability to rescue patients.
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INTRODUCTION: Severe traumatic injury requires rapid and extensive deployment of resources to save the lives of the critically injured. The sequelae of traumatic injuries frequently require extensive intervention obligating patients to a complicated recovery process devoid of meaningful nutrition. In this setting, parenteral nutrition (PN) is key in enabling appropriate wound healing, recovery, and rehabilitation. We sought to examine the use of PN in adult trauma management and to highlight any disparities in the utilization of PN in adult trauma patients. METHODS: We queried the 2017-2019 Trauma Quality Improvement Program (TQIP) for adult patients (aged > 18 y) who sustained blunt or penetrating traumatic injuries and received PN as part of their hospitalization. We compared time to PN administration based on demographics. We then used a multivariable logistic regression model to identify factors associated with the use of PN. We hypothesized that PN would be less commonly employed in the uninsured and minority groups. RESULTS: We identified 2,449,498 patients with sufficient data for analysis. Of these, 1831 patients were treated with PN. On univariate analysis, PN patients were more commonly male (74.7% PN versus 60.2% non-PN; P < 0.001). PN use was more frequent in the Black population (24.3% PN versus 15.5% non-PN; P < 0.001) and less frequent in the White population (72.7% PN versus 81.2% non-PN; P < 0.001). PN use was also much more common among patients covered by Medicaid. Penetrating trauma was over twice as common among PN recipients relative to non-PN patients (% PN versus % non-PN). PN patients had higher injury severity scores (ISSs), more intensive care unit days, longer hospitalizations, and increased mortality compared to non-PN patients. PN patients were half as likely to discharge home and twice as likely to discharge to a long-term care facility. Multivariable analysis including age, race, trauma mechanism, primary payer, and ISS, demonstrated an association of PN use with increasing age (OR 1.01, P < 0.001), cases of penetrating trauma (odds ratio [OR], 2.47; P < 0.001), and patients with high ISS (OR, 0.1.06; P < 0.001). There was decreased use in Uninsured patient (OR, 0.54; P < 0.001). CONCLUSIONS: PN use following traumatic injury is rarely required. Patients treated with PN typically have a resource-intense hospital course. More severe injuries, penetrating trauma, and increased age are more likely to result in PN use. Variations in PN use are apparent based on insurance payer, further examination into allocation of hospital and intensive care resources, as it pertains to patient socioeconomic status, is warranted in light of these findings.
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Ferimentos Penetrantes , Adulto , Estados Unidos/epidemiologia , Humanos , Masculino , Ferimentos Penetrantes/terapia , Ferimentos Penetrantes/epidemiologia , Medicaid , Grupos Minoritários , Pessoas sem Cobertura de Seguro de Saúde , Nutrição Parenteral , Estudos Retrospectivos , Escala de Gravidade do FerimentoRESUMO
INTRODUCTION: Firearm injury is a public health crisis. Most victims are minorities in underserved neighborhoods. Measuring firearm injury by mortality underestimates its impact, as most victims survive to discharge. This study was done to determine if race and insurance status are associated with discharge disposition for gunshot wound (GSW)-related trauma. METHODS: Using the 2019 Trauma Quality Improvement Program database, we identified GSW patients with Abbreviated Injury Scale (AIS) = 1-3. Exclusion criteria included patients who died in hospital and routine home discharge. We compared discharge patterns of patients based on demographics (age, gender, race, ethnicity, payor, AIS, hospital designation, and length of stay [LOS]) and injury severity. Multivariable logistic regression models identified factors associated with discharge disposition. RESULTS: Our sample included 2437 patients with GSWs. On univariable analysis, Black patients were more likely to discharge to home with home health (64.1% Black versus 34.7% White; P < 0.001). White patients were more likely to discharge to skilled nursing facility (SNF) (51.4% White versus 44.6% Black; P < 0.001). Controlling for age, race, Latin ethnicity, primary payor, LOS, AIS severity, and injury severity score factors independently associated with discharge to SNF included age (0.0462, P < 0.001), Medicaid (1.136, P < 0.0003), Medicare (1.452, P < 0.001), and LOS (0.03745, P < 0.001). CONCLUSIONS: Postacute care following traumatic injuries is essential to recovery. Black GSW victims are more likely to be discharged to home health than White patients, who are more likely to be discharged to SNF. Targeted programs to reduce barriers to appropriate aftercare are necessary to eliminate this bias and improve the care of underserved populations.
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Armas de Fogo , Ferimentos por Arma de Fogo , Idoso , Humanos , Estados Unidos/epidemiologia , Alta do Paciente , Ferimentos por Arma de Fogo/epidemiologia , Instituições de Cuidados Especializados de Enfermagem , Medicare , Estudos RetrospectivosRESUMO
INTRODUCTION: As the older adult population increases, hospitals treat more older adults with injuries. After leaving, these patients suffer from decreased mobility and independence, relying on care from others. Family members often assume this responsibility, mostly informally and unpaid. Caregivers of other older adult populations have increased stress and decreased caregiver-related quality of life (CRQoL). Validated CRQoL measures are essential to capture their unique experiences. Our objective was to review existing CRQoL measures and their validity in caregivers of older adult trauma patients. METHODS: A professional librarian searched published literature from the inception of databases through August 12, 2022 in MEDLINE (via PubMed), Embase (via Elsevier), and CINAHL Complete (via EBSCO). We identified 1063 unique studies of CRQoL in caregivers for adults with injury and performed a systematic review following COnsensus-based Standards for the selection of health Measurement Instruments guidelines for CRQoL measures. RESULTS: From the 66 studies included, we identified 54 health-related quality-of-life measures and 60 domains capturing caregiver-centered concerns. The majority (83%) of measures included six or fewer CRQoL content domains. Six measures were used in caregivers of older adults with single-system injuries. There were no validated CRQoL measures among caregivers of older adult trauma patients with multisystem injuries. CONCLUSIONS: While many measures exist to assess healthcare-related quality of life, few, if any, adequately assess concerns among caregivers of older adult trauma patients. We found that CRQoL domains, including mental health, emotional health, social functioning, and relationships, are most commonly assessed among caregivers. Future measures should focus on reliability and validity in this specific population to guide interventions.
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Cuidadores , Qualidade de Vida , Ferimentos e Lesões , Humanos , Cuidadores/psicologia , Ferimentos e Lesões/psicologia , Ferimentos e Lesões/terapia , IdosoRESUMO
INTRODUCTION: Suboptimal nutrition promotes unfavorable outcomes in trauma patients, particularly among those aged 60 and over. While many institutions employ predictive energy equations to determine patients' energy requirements, mounting evidence shows these equations inaccurately estimate caloric needs. In this pilot randomized controlled trial, we sought to quantify the discrepancy between predictive equations and indirect calorimetry (IC)-the gold standard for determining energy requirements-in the older adult trauma population. METHODS: This is a nested cohort study within a pilot randomized control trial in which 32 older adult trauma patients were randomized 3:1 to receive IC-guided nutrition delivery versus standard of care. IC requirements of patients in the intervention arm were compared to Mifflin St. Jeor (MSJ), Harris-Benedict (HB), and the American Society for Parenteral and Enteral Nutrition-Society of Critical Care Medicine (ASPEN-SCCM) predictive energy equations. RESULTS: Twenty patients underwent IC to assess measured resting energy expenditure (mREE), yielding a mean (standard deviation) mREE of 23.1 ± 4.8 kcal/kg/d. MSJ and HB gave mean predictive resting energy expenditures of 17.5 ± 2.0 and 18.5 ± 2.0 kcal/kg/d in these patients, demonstrating that IC-derived values were 32.1% and 25.0% higher, respectively. When patients were stratified by body mass index (BMI), MSJ, and HB more severely underestimated caloric requirements in individuals with BMI <30 versus BMI 30-50. While the mean mREE fell within the mean predictive resting energy expenditure range prescribed by ASPEN-SCCM equations (21.4 ± 4.1 to 26.2 ± 4.3 kcal/kg/d), individuals' IC-derived values fell within their personal range in 8 of 20 cases. CONCLUSIONS: The MSJ and HB predictive energy equations consistently and significantly underpredict metabolic demands of older adult trauma patients compared to IC and perform worse in lower BMI individuals. ASPEN-SCCM equations frequently overpredict or underpredict resting energy expenditure. While these findings should be confirmed in a larger randomized control trial, this study suggests that institutions should prioritize IC to accurately identify the metabolic demands of older trauma patients.
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INTRODUCTION: Surgical stabilization of rib fractures (SSRF) is associated with lower rates of mortality and fewer complications. This study evaluates whether the decision to undergo SSRF is associated with age, race, ethnicity, and insurance status and assesses associated clinical outcomes. METHODS: This retrospective analysis included patients ≥45 y old with rib fractures who underwent SSRF in the Trauma Quality Improvement Program from 2016 to 2020. Race, ethnicity, and insurance statuses were collected. Age in years was dichotomized into two groups: 45-64 and 65+. Outcomes included ventilator-associated pneumonia, unplanned endotracheal intubation, acute respiratory distress syndrome, in-hospital mortality, failure to rescue (FTR) after major complications, and FTR after respiratory complications. Logistic regression models were fit to evaluate outcomes, controlling for gender, body mass index, Injury Severity Score, flail chest, chronic obstructive pulmonary disease, congestive heart failure, and smoking. RESULTS: Two thousand eight hundred thirty-nine patients aged 45-64 and 1828 patients aged 65+ underwent SSRF. No significant difference in clinical outcomes was noted between these groups. Analysis showed that the association of SSRF with ventilator-associated pneumonia, unplanned intubation, acute respiratory distress syndrome, in-hospital mortality, FTR after a major complication, or FTR after a respiratory complication did not vary by age (P > 0.05). Black (odds ratio [OR] 0.67; 95% confidence interval [CI]: 0.59-0.77; P < 0.001), Hispanic (OR 0.80; 95% CI: 0.71-0.91; P < 0.001), and Medicaid (OR = 0.85; 95% CI = 0.76-0.95; P = 0.005) patients were less likely to receive SSRF. CONCLUSIONS: No differences in clinical outcomes were measured between adults aged 45-64 and ≥65 who underwent SSRF. Older age should not preclude patients from receiving SSRF. Further work is needed to improve underutilization in Black, Hispanic and Medicaid patients.
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INTRODUCTION: Time-To-OR is a critical process measure for trauma performance. However, this measure has not consistently demonstrated improvement in outcome. STUDY DESIGN: Using TQIP, we identified facilities by 75th percentile time-to-OR to categorize slow, average, and fast hospitals. Using a GEE model, we calculated odds of mortality for all penetrating abdominal trauma patients, firearm injuries only, and patients with major complication by facility speed. We additionally estimated odds of mortality at the patient level. RESULTS: Odds of mortality for patients at slow facilities was 1.095; 95% CI: 0.746, 1.608; p = 0.64 compared to average. Fast facility OR = 0.941; 95% CI: 0.780, 1.133; p = 0.52. At the patient-level each additional minute of time-to-OR was associated with 1.5% decreased odds of in-hospital mortality (OR 0.985; 95% CI:0.981, 0.989; p < 0.001). For firearm-only patients, facility speed was not associated with odds of in-hospital mortality (p-value = 0.61). Person-level time-to-OR was associated with 1.8% decreased odds of in-hospital mortality (OR 0.982; 95% CI: 0.977, 0.987; p < 0.001) with each additional minute of time-to-OR. Similarly, failure-to-rescue analysis showed no difference in in-hospital mortality at the patient level (p = 0.62) and 0.4% decreased odds of in-hospital mortality with each additional minute of time-to-OR at the patient level (OR 0.996; 95% CI: 0.993, 0.999; p = 0.004). CONCLUSION: Despite the use of time-to-OR as a metric of trauma performance, there is little evidence for improvement in mortality or complication rate with improved time-to-OR at the facility or patient level. Performance metrics for trauma should be developed that more appropriately approximate patient outcome.
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Traumatismos Abdominais , Armas de Fogo , Ferimentos por Arma de Fogo , Ferimentos Penetrantes , Humanos , Estudos Retrospectivos , Hospitais , Mortalidade Hospitalar , Ferimentos Penetrantes/terapia , Escala de Gravidade do FerimentoRESUMO
INTRODUCTION: Most injured children receive trauma care outside of a pediatric trauma center. Differences in physiology, dosing, and injury pattern limit extrapolation of adult trauma principles to pediatrics. We compare US trauma center experience with pediatric and adult trauma resuscitation. MATERIALS AND METHODS: We queried the 2019 Trauma Quality Improvement Program to describe the experience of US trauma centers with pediatric (<15 y) and adult trauma. We quantified blunt, penetrating, burn, and unspecified traumas and compared minor, moderate, severe, and critical traumas (ISS 1-8 Minor, ISS 9-14 Moderate, ISS 15-24 Severe, ISS 25+ Critical). We estimated center-level volumes for adults and children. Institutional identifiers were generated based on unique center specific factors including hospital teaching status, hospital type, verification level, pediatric verification level, state designation, state pediatric designation, and bed size. RESULTS: A total of 755,420 adult and 76,449 pediatric patients were treated for traumatic injuries. There were 21 times as many critical or major injuries in adults compared to children, 17 times more moderate injuries, and 6 times more minor injuries. Children and adults presented with similar rates of blunt trauma, but penetrating injuries were more common in adults and burn injuries were more common in children. Comparing center-level data, adult trauma exceeded pediatric for every severity and mechanism. CONCLUSIONS: There is relatively limited exposure to high-acuity pediatric trauma at US centers. Investigation into pediatric trauma resuscitation education and simulation may promote pediatric readiness and lead to improved outcomes.
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Ferimentos não Penetrantes , Ferimentos Penetrantes , Criança , Humanos , Adulto , Estudos de Coortes , Melhoria de Qualidade , Escala de Gravidade do Ferimento , Ferimentos não Penetrantes/terapia , Centros de Traumatologia , Estudos RetrospectivosRESUMO
INTRODUCTION: As medical advances have significantly increased the life expectancy among older adults, the number of older patients requiring trauma care has risen proportionately. Nevertheless, it is unclear among this growing population which sociodemographic and economic factors are associated with decisions to triage and transfer to level I/II centers. This study aims to assess for any association between patient sociodemographic characteristics, triage decisions, and outcomes during acute trauma care presentations. METHODS: The National Trauma Data Bank was queried for patients aged 65 and older with an injury severity score > 15 between the years 2007 to 2017. Factors associated with subsequent levels of triage on presentation were assessed using multivariate logistic regression, and associations of levels of triage with outcomes of mortality, morbidity, and hospital length of stay are examined using logistic and linear regression models. RESULTS: Triage of 210,310 older adult trauma patients showed significant findings. American Indian patients had higher odds of being transferred to level I/II centers, while Asian, Black, and Native Hawaiian patients had lower odds of being transferred to level I/II centers when compared to Caucasian patients (P < 0.001). Regarding insurance, self-pay (uninsured) patients were less likely to be transferred to a higher level of care; however, this was also demonstrated in private insurance holders (P < 0.001). Caucasian patients had significantly higher odds of mortality, with Black patients (odds ratio [OR] 0.80 [0.75, 0.85]) and American Indian patients (OR 0.87 [0.72, 1.04]) having significantly lower odds (P < 0.001). Compared to government insurance, private insurance holders (OR 0.82 [0.80, 0.85]) also had significantly lower odds of mortality, while higher odds among self-pay were observed (OR 1.75 [1.62, 1.90]), (P < 0.001). CONCLUSIONS: Access to insurance is associated with triage decisions involving older adults sustaining trauma, with lower access increasing mortality risk. Factors such as race and gender were less likely to be associated with triage decisions. However, due to this study's retrospective design, further prospective analysis is necessary to fully assess the decisions that influence trauma triage decisions in this patient population.
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Triagem , Ferimentos e Lesões , Humanos , Idoso , Estudos Retrospectivos , Centros de Traumatologia , Morbidade , Escala de Gravidade do Ferimento , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/terapiaRESUMO
BACKGROUND: Transparency around surgeon level data may align healthcare delivery with quality care for patients. Biliary surgery includes numerous procedures performed by both general surgeons and subspecialists alike. Cholecystectomy is a common surgical procedure and an optimal cohort to measure quality outcomes within a healthcare system. METHODS: Data were collected for 5084 biliary operations performed by 68 surgeons in 11 surgical divisions in a health system including a tertiary academic hospital, two regional community hospitals, and two ambulatory surgery centers. A privacy protected dashboard was developed to compare surgeon performance and cost between July 2018 and June 2022. A sample cohort of patients ≥ 18 years who underwent cholecystectomy were compared by operative time, cost, and 30-day outcomes. RESULTS: Over 4 years, 4568 cholecystectomy procedures were performed by 57 surgeons. Operations were done by 57 surgeons in four divisions and included 3846 (84.2%) laparoscopic cholecystectomies, 601 (13.2%) laparoscopic cholecystectomies with cholangiogram, and 121 (2.6%) open cholecystectomies. Patients were admitted from the emergency room in 2179 (47.7%) cases while 2389 (52.3%) cases were performed in the ambulatory setting. Individual surgeons were compared to peers for volume, intraoperative data, cost, and outcomes. Cost was lowest at ambulatory surgery centers, yet only 4.2% of elective procedures were performed at these facilities. Prepackaged kits with indocyanine green were more expensive than cholangiograms that used iodinated contrast. The rate of emergency department visits was lowest when cases were performed at ambulatory surgery centers. CONCLUSION: Data generated from clinical dashboards can inform surgeons as to how they compare to peers regarding quality metrics such as cost, time, and complications. In turn, this may guide strategies to standardize care, optimize efficiency, provide cost savings, and improve outcomes for cholecystectomy procedures. Future application of clinical dashboards can assist surgeons and administrators to define value-based care.
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Sistema Biliar , Colecistectomia Laparoscópica , Humanos , Estudos Prospectivos , Colecistectomia , Colangiografia , Estudos RetrospectivosRESUMO
INTRODUCTION: As of yet, few studies have described the prevalence or rates of assault mortalities involving Asian victims on a national level. This study aimed to describe yearly trends and regional differences in assault mortalities among Asians. METHODS: This repeat cross-sectional study from 2009 to 2018 used data from the Mortality Multiple Cause-of-Death Public Use Record from the National Center for Health Statistics and the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research. Total and proportion of assault mortalities involving Asians or Pacific Islanders were calculated by year. Total and rates (per 100,000 Asians or Pacific Islanders) of assault mortalities among Asians or Pacific Islanders were stratified by state and county classification where deaths occurred. RESULTS: In 2009, 344 assault mortalities among Asians or Pacific Islanders accounted for 2.07% of assault-related deaths. In 2018, 366 assault mortalities among Asians or Pacific Islanders accounted for 1.96% of assault-related deaths. Furthermore, there were more assault mortalities from 2009 to 2018 among Asians or Pacific Islanders in California (n = 1116) and large central metropolitan counties (n = 1707). However, the highest rates of assault mortalities were in Alaska and Mississippi (7.1 and 6.8 per 100,000, respectively) and noncore nonmetropolitan counties (2.9 per 100,000). CONCLUSIONS: These findings emphasize the importance of studying and addressing violence toward Asians in rural regions and Southern states. Future studies should use these results as a baseline to analyze mortality data from 2019 to 2021, when available, to examine the coronavirus disease 2019 pandemic's impact on assault mortalities among Asian.
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Asiático , COVID-19 , Estudos Transversais , Humanos , Havaiano Nativo ou Outro Ilhéu do Pacífico , População Rural , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: Disparities in gun violence across race are well documented. Studying these disparities is essential to reduce preventable gun deaths. This study evaluates the relationship between sociodemographic factors and firearms used in gun deaths. MATERIALS AND METHODS: This retrospective cohort study of firearm mortalities from 2009 to 2018 used the Mortality Multiple Cause-of-Death Public Use Record from the National Center for Health Statistics. The primary outcome was the type of firearm used and the secondary outcome was autopsy status. Factors of interest include race, ethnicity, gender, marital status, age, education, and place of death. Factors significantly associated with outcomes in univariate analyses were included in separate multivariate logistic regression models for assaults, intentional self-harm, and accidents. RESULTS: A total of 276,127 firearm deaths from 2009 to 2018 were analyzed. Compared to White victims, Black victims were less likely to die from handguns (accident: odds ratio [OR] = 0.70, P < 0.05; self-harm: OR = 0.84, P < 0.001; assault: OR = 0.58, P < 0.001) and rifles, shotguns, or large firearms (accident: OR = 0.30, P < 0.001; self-harm: OR = 0.37, P < 0.001; assault: OR = 0.28, P < 0.001). Black decedents were more likely to undergo autopsy than White decedents (accident: OR = 2.14, P < 0.001; intentional self-harm: OR = 2.02, P < 0.001; assault: OR = 2.02, P < 0.001). Ethnicity, gender, marital status, age, education, and other racial identities were also associated with firearms used and autopsy rates (P < 0.05). CONCLUSIONS: Differences in firearms used and autopsy rates following gun deaths exist by race, ethnicity, gender, marital status, age, and education. Future studies should investigate the relationship between sociodemographic factors and firearms used and autopsy status following gun deaths.
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Armas de Fogo , Ferimentos por Arma de Fogo , Autopsia , Humanos , Fatores Raciais , Estudos RetrospectivosRESUMO
B-cell receptor pathway inhibitors (BCRis) have transformed treatment of chronic lymphocytic leukemia (CLL); however, the efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRis is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi before enrollment. Venetoclax was initiated at 20 mg daily, followed by intrapatient ramp-up to 400 mg daily. Primary objectives included efficacy (objective response rate [ORR]) and safety of venetoclax. The study enrolled 36 patients who previously received idelalisib (ORR, 67% [24/36]); 2 patients achieved complete remission, and 1 had complete remission with incomplete bone marrow recovery. Median progression-free survival (PFS) has not yet been reached; estimated 12-month PFS was 79%. The most common adverse events (AEs; all grades) were neutropenia (56%), diarrhea (42%), upper respiratory tract infection (39%), thrombocytopenia (36%), nausea (31%), fatigue (28%), cough (22%), rash (22%), and anemia (22%). Grade 3 or 4 AEs were primarily hematologic (neutropenia [50%], thrombocytopenia [25%], and anemia [17%]). No patients experienced tumor lysis syndrome. Venetoclax demonstrated promising clinical activity and favorable tolerability in patients with CLL whose disease progressed during or after idelalisib therapy. This trial was registered at www.clinicaltrials.gov as #NCT02141282.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/mortalidade , Purinas/administração & dosagem , Quinazolinonas/administração & dosagem , Sulfonamidas/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Purinas/efeitos adversos , Quinazolinonas/efeitos adversos , Recidiva , Sulfonamidas/efeitos adversos , Taxa de SobrevidaRESUMO
BACKGROUND: Race and insurance status have been shown to predict outcomes in pediatric bicycle traumas. It is unknown how these factors influence outcomes in adult bicycle traumas. This study aims to evaluate the association, if any, between race and insurance status with mortality in adults. METHODS: This retrospective cohort study used the National Trauma Data Bank Research Data Set for the years 2013-2015. Multivariate logistic regression models were used to determine the independent association between patient race and insurance status on helmet use and on outcomes after hospitalization for bicycle-related injury. These models adjusted for demographic factors and comorbid variables. When examining the association between race and insurance status with outcomes after hospitalization, injury characteristics were also included. RESULTS: A study population of 45,063 met the inclusion and exclusion criteria. Multivariate regression demonstrated that black adults and Hispanic adults were significantly less likely to be helmeted at the time of injury than white adults [adjusted odds ratio of helmet use for blacks 0.25 (95% CI 0.22-0.28) and for Hispanics 0.33 (95% CI 0.30-0.36) versus whites]. Helmet usage was also independently associated with insurance status, with Medicare-insured patients [AOR 0.51 (95% CI 0.47-0.56) versus private-insured patients], Medicaid-insured patients [AOR 0.18 (95% CI 0.17-0.20)], and uninsured patients [AOR 0.29 (95% CI 0.27-0.32)] being significantly less likely to be wearing a helmet at the time of injury compared with private-insured patients. Although patient race was not independently associated with hospital mortality among adult bicyclists, we found that uninsured patients had significantly higher odds of mortality [AOR 2.02 (AOR 1.31-3.12)] compared with private-insured patients. CONCLUSIONS: Minorities and underinsured patients are significantly less likely to be helmeted at the time of bicycle-related trauma when compared with white patients and those with private insurance. Public health efforts to improve the utilization of helmets during bicycling should target these subpopulations.
Assuntos
Ciclismo/lesões , Disparidades em Assistência à Saúde/estatística & dados numéricos , Grupos Minoritários/estatística & dados numéricos , Ferimentos e Lesões/mortalidade , Adolescente , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Conjuntos de Dados como Assunto , Feminino , Dispositivos de Proteção da Cabeça/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Escala de Gravidade do Ferimento , Cobertura do Seguro/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricos , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/terapia , Adulto JovemRESUMO
BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) use is frequently recommended for multimodal analgesia to reduce opioid use. We hypothesized that increased NSAID utilization will decrease opioid requirements without leading to significant complications in older adult trauma patients undergoing hip fracture repair. METHODS: An observational cross-sectional cohort study of 190,057 adult trauma patients over a 6-y period (2008-2014) in the national Premier Healthcare Database was performed. Patients aged 65 or older undergoing femur repair and hip arthroplasty following fractures due to falls were analyzed. Primary outcome was opioid use, and secondary outcomes included transfusion requirements, length of stay (LOS), and organ system dysfunction. Continuous outcomes were analyzed using mixed-effect linear regression models to assess the effect of NSAIDs on the day of surgery. Fixed effects were included for patient and hospital characteristics, comorbidities, co-treatments, and surgery. Random intercepts for each hospital were included to control for clustering. Categorical outcomes were similarly analyzed using mixed-effect logistic regression models. RESULTS: NSAIDs decreased opioids prescribed (12.01 versus 11.43 morphine milligram equivalents) (odds ratio [OR], -0.23; confidence interval [CI] = -0.41, -0.06) without overall increased bleeding (40.83% versus 43.18%; OR, 1.02; CI = 0.99, 1.05). NSAIDs were associated with reduced LOS (5.61 versus 5.96 d; CI = -0.24, -0.12), intensive care unit admissions (9.73% versus 10.59%; OR, 0.91; CI = 0.86, 0.96), and pulmonary complications (OR, 0.88; CI = 0.83, 0.93). Additionally, there was a 21% prescribing variability based solely on hospital. CONCLUSIONS: NSAIDs were associated with decreased opioid requirements, hospital LOS, and intensive care unit admissions in older adult trauma patients without overall increase in bleeding. NSAIDs should be considered in multimodal pain regimens, moreover, given prescribing variability guidelines are needed. LEVEL OF EVIDENCE: Level III, Prognostic.