RESUMO
INTRODUCTION: The use of intravenous (IV) acetaminophen (APAP) postoperatively in older adults may be a beneficial strategy. We implemented a multimodal pain management approach in our hospital in 2015, with IV APAP being the first-line therapy. MATERIALS AND METHODS: This was a retrospective, single-center, observational cohort study of polytrauma, orthopedic surgical patients aged ≥50 y. Patients admitted in 2017, postimplementation of pain protocol, were categorized as the exposed patients. Patients in the year 2014 served as the historical cohort. The two primary outcomes evaluated were postoperative opioid consumption in morphine milligram equivalents (MMEs) and patient pain scores. RESULTS: In total, 121 eligible patients were identified for this study; 22 historical control patients and 99 exposed patients. We observed a significant reduction in postoperative opioid use up to 48 h postoperatively (20.9 ± 27 versus 4.3 ± 12.4 MME [P < 0.05] at 24 h and 19.8 ± 31.2 versus 2.1 ± 11.3 MME [P < 0.05] at 48 h, respectively). The mean opioid consumption remained significantly lower in patient subgroup of age ≥74 y with no difference in the mean pain scores (1.5 ± 1.5 versus 1.9 ± 1.6 [P = 0.48] at 24 h and 1.5 ± 1.8 versus 2.0 ± 1.5 [P = 0.21] at 48 h postoperatively in the historical versus exposed cohort, respectively). Exposed patients had a shorter hospital length of stay than control patients (5.0 [3, 7] versus 6.5 [5, 9.5] d; P = 0.01). CONCLUSIONS: The use of multimodal pain management with IV APAP as first-line therapy was associated with reduced opioid use in the perioperative setting for older adults with polytrauma.
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Traumatismo Múltiplo , Transtornos Relacionados ao Uso de Opioides , Acetaminofen/uso terapêutico , Idoso , Analgésicos Opioides/uso terapêutico , Humanos , Traumatismo Múltiplo/complicações , Traumatismo Múltiplo/cirurgia , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a noted complication among geriatric hip fracture patients. This complication results in negative outcomes for both the patients and the institution providing care. Screening measures to identify predisposing factors, with early diagnosis and treatment of urinary tract infection (UTI) present on admission, may lead to reduced rates of CAUTI. OBJECTIVE: The goals of this study were to determine the prevalence of UTI on admission among geriatric hip fracture patients and whether routine screening for UTI or predisposing factors at presentation resulted in reduced rates of CAUTI. METHODS: A retrospective observational study of geriatric hip fracture patients from January 2017 to December 2018 at a Level I trauma center was performed. Rates of UTI on admission and CAUTI were calculated using routine admission urinalysis. RESULTS: Of the 183 patients in the sample, 36.1% had UTI on admission and 4.4% of patients developed CAUTI. There were no significant differences in patient demographics, comorbidities, and complications between those with UTI on admission and those without. CONCLUSIONS: Urinary tract infection on admission may be present among a large portion of geriatric hip fracture patients, leading to increased rates of CAUTI. Routine screening for UTI and its predisposing factors at admission can identify these patients earlier and lead to earlier treatments and prevention of CAUTI.
Assuntos
Infecções Relacionadas a Cateter , Infecção Hospitalar , Fraturas do Quadril , Infecções Urinárias , Idoso , Catéteres , Fraturas do Quadril/diagnóstico , Fraturas do Quadril/epidemiologia , Humanos , Estudos Retrospectivos , Centros de Traumatologia , Infecções Urinárias/diagnóstico , Infecções Urinárias/epidemiologia , Infecções Urinárias/prevenção & controleRESUMO
OBJECTIVE: To assess the impact of preassigning a single bed in the surgical intensive care unit (SICU) for the next trauma admission. BACKGROUND: Prolonged emergency department (ED) dwell time before admission to a critical care unit has an adverse effect on patient outcomes and is often due to the lack of an available bed in the intensive care unit (ICU). METHODS: A "Bed Ahead" policy was instituted at an urban level 1 Trauma Public Safety Net Teaching Hospital to preassign 1 SICU bed for the next trauma patient who warrants a critical care admission. A retrospective review of all trauma patients admitted to the SICU before and after implementation of this policy was performed to assess the impact on ED dwell time, ICU and hospital lengths of stay, complications, and in-hospital mortality. RESULTS: ED length of stay (ED-LOS); ICU length of stay (ICU-LOS); hospital length of stay (HLOS); complications; and in-hospital mortality were compared before (PRE) and after (POST)implementation of the Bed Ahead policy. Statistically significant improvements were seen in the POST period for ED-LOS, HLOS, complications, and in-hospital mortality. CONCLUSIONS: Preassigning 1 ICU for the yet to arrive next injured patient decreases ED dwell times, complications, HLOS, and in-hospital mortality.
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Serviço Hospitalar de Emergência/organização & administração , Unidades de Terapia Intensiva/organização & administração , Tempo de Internação/estatística & dados numéricos , Política Organizacional , Admissão do Paciente/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Complicações Pós-Operatórias , Estudos Retrospectivos , Centros de TraumatologiaRESUMO
The mechanism by which poor maternal nutrition can affect the long-term health of offspring is poorly understood. In mice, we previously found that maternal high-fat diet (HFD) exposure results in reduced fetal growth regardless of maternal genotype. We tested our hypothesis that maternal HFD-induced inflammation contributes to metabolic disease susceptibility of the offspring via alterations in the placenta. The effect of maternal genotype, diet, and treatment with the anti-inflammatory compound N-acetylcysteine (NAC) on placental morphologic features was investigated. Placentas from wild-type dams maintained on a HFD but not those heterozygous (+/-) for Glut4 (Slc2a4) on the same diet had an increase in decidual inflammation and vasculopathy occurring together. NAC administration resulted in amelioration of HFD-induced decidual vasculopathy independent of offspring genotype and sex. Consistent with these morphologic improvements, placentas from HFD dams treated with NAC had decreased mRNA and immunostaining of IL-1ß and monocyte chemoattractant protein-1, decreased mRNA of inflammatory genes, and increased mRNA of Vegfa. These results strongly suggest consumption of an HFD results in vascular changes in placenta reflected by alterations in expression of pivotal vascular developmental markers and inflammatory genes all of which are ameliorated by NAC. These placental changes play a key role in the increased programed metabolic disease of HFD-exposed offspring.
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Acetilcisteína/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Inflamação/prevenção & controle , Placenta/efeitos dos fármacos , Complicações na Gravidez/prevenção & controle , Doenças Vasculares/prevenção & controle , Animais , Modelos Animais de Doenças , Feminino , Inflamação/complicações , Inflamação/patologia , Masculino , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Camundongos , Camundongos Transgênicos , Placenta/patologia , Gravidez , Complicações na Gravidez/etiologia , Doenças Vasculares/complicações , Doenças Vasculares/patologiaRESUMO
BACKGROUND: The aim of this study is to evaluate recent national trends in the clinical characteristics, management, and outcomes of patients with isolated axillary artery injuries. METHODS: The National Trauma Data Bank was queried to identify records submitted from 2011 to 2015 that contained an ICD-9-CM diagnosis code for an injury to axillary artery (903.01) and an external cause of injury code indicating blunt or penetrating trauma. Records that contained a diagnosis code for an injury to an additional blood vessel (900.00-903.00, 903.2-904.9), an injury to a nonupper extremity or unclassifiable body region, or whose operative management could not be discerned were excluded. The final study sample included 221 patients with isolated axillary artery injury. The patient's clinical management was the primary outcome of interest. The study sample was stratified by trauma type, and descriptive statistics were performed on all variables. RESULTS: Seventy-one percent of patients received operative management. Patients with penetrating injury were 24% more likely to be managed operatively than bluntly injured patients (76.9% vs. 62.1%, P = 0.0178). In operatively managed patients, the open repair rate was 82.8% and endovascular repair rate was 10.2%. Graft repair was performed most often (28.0%), followed by placement of a temporary intravenous shunt (17.8%) and surgical occlusion (10.2%). Surgical vessel occlusion was significantly more likely to be performed on patients with penetrating injury than with blunt injury (14.6% vs. 1.9%, P = 0.0124). Patients with penetrating injury had significantly shorter median emergency department length of stay (87.0 min vs. 152.0 min, P < 0.0001), intensive care unit length of stay (2.0 days vs. 3.0 days, P < 0.0388), hospital length of stay (4.0 days vs. 5.0 days, P = 0.0026), and time-to-operative management (1.6 hr vs. 3.9 hr, P < 0.001) compared to bluntly injured patients. Patients with blunt injury had a higher reportable in-hospital complication rate (13.8% vs. 6.0%, P = 0.0477). The overall mortality rate was 3.1% for isolated axillary artery injuries and did not significantly differ by trauma type. CONCLUSIONS: Axillary artery injury is more often caused by penetrating trauma. Despite introduction of novel endovascular techniques, the majority of patients with isolated axillary artery injury are managed using open repair. Penetrating axillary artery injury is significantly more likely to be managed using open repair and by surgical occlusion. Patients with blunt injury have higher complication rates and longer hospital length of stays. The mortality rate is lower than previously published.
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Artéria Axilar/cirurgia , Implante de Prótese Vascular/tendências , Procedimentos Endovasculares/tendências , Técnicas Hemostáticas/tendências , Tempo para o Tratamento/tendências , Lesões do Sistema Vascular/terapia , Ferimentos não Penetrantes/terapia , Ferimentos Penetrantes/terapia , Adolescente , Adulto , Idoso , Artéria Axilar/diagnóstico por imagem , Artéria Axilar/lesões , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/mortalidade , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/mortalidade , Feminino , Técnicas Hemostáticas/efeitos adversos , Técnicas Hemostáticas/instrumentação , Técnicas Hemostáticas/mortalidade , Humanos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/mortalidade , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/mortalidade , Ferimentos Penetrantes/diagnóstico por imagem , Ferimentos Penetrantes/mortalidade , Adulto JovemRESUMO
BACKGROUND: Length of hospital stay (LOS) for hip fracture treatments is associated with mortality. In addition to patient demographic and clinical factors, hospital and payer type may also influence LOS, and thus mortality, among hip fracture patients; accordingly, outcome disparities between groups may arise from where patients are treated and from their health insurance type. The purpose of this study was to examine if where hip fracture patients are treated and how they pay for their care is associated with outcome disparities between patient groups. Specifically, we examined whether LOS differed between patients treated at safety-net and non-safety-net hospitals and whether LOS was associated with patients' insurance type within each hospital category. METHODS: A sample of 48,948 hip fracture patients was extracted from New York State's Statewide Planning and Research Cooperative System (SPARCS), 2014-2016. Using means comparison and X2 tests, differences between safety-net and non-safety-net hospitals on LOS and patient characteristics were examined. Relationships between LOS and hospital category (safety-net or non-safety-net) and LOS and insurance type were further evaluated through negative binomial regression models. RESULTS: LOS was statistically (p ≤ 0.001) longer in safety-net hospitals (7.37 days) relative to non-safety-net hospitals (6.34 days). Treatment in a safety-net hospital was associated with a LOS that was 11.7% (p = 0.003) longer than in a non-safety-net hospital. Having Medicaid was associated with a longer LOS relative to having commercial health insurance. CONCLUSION: Where hip fracture patients are treated is associated with LOS and may influence outcome disparities between groups. Future research should examine whether outcome differences between safety-net and non-safety-net hospitals are associated with resource availability and hospital payer mix.
Assuntos
Disparidades em Assistência à Saúde , Fraturas do Quadril/terapia , Tempo de Internação/estatística & dados numéricos , Provedores de Redes de Segurança/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Seguro Saúde/estatística & dados numéricos , Masculino , Medicaid/estatística & dados numéricos , Pessoa de Meia-Idade , New York , Estados Unidos , Adulto JovemRESUMO
A surgical post-acute treatment unit (SPA) was developed for acutely injured elderly patients who no longer warranted acute care in an intensive care setting to decrease complications by focusing increased bedside attention to cognition, nutrition, respiration, and mobilization. A retrospective review was performed comparing patients 65 years and older with isolated rib fractures treated before the SPA was opened with patients treated in the SPA. The 2 populations were comparable except the SPA group had a higher mean Injury Severity Score. Nine complications occurred in the pre-SPA group, and no complications occurred in the SPA patient population. Four patients in the pre-SPA group died compared with zero deaths for the SPA group. The rates of complications and mortality between elderly patients with isolated rib fractures were not statistically different between patients treated with a traditional admission to an inpatient ward and patients admitted to the SPA, even though the SPA patients had significantly more severe chest injuries. Establishing a physical environment to support the needs of elderly trauma patients with isolated rib fractures who no longer need the intensive care unit (ICU) is effective in decreasing the complications and unplanned returns to the ICU.
Assuntos
Cuidados Críticos/métodos , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/prevenção & controle , Fraturas das Costelas/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva , Masculino , New York/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Hip fractures in patients 65 years and older are associated with significant morbidity and mortality. With the steady increase in the elderly population, we implemented an evidence-based clinical practice guideline for the management of hip fractures to optimize patient care and surgical outcomes. AIMS: To evaluate the effects of a multidisciplinary hip fracture care pathway on patient outcomes in the care of elderly patients. METHODS: A retrospective analysis of the differences in outcomes prior to (January-October 2014) and after (November 2014-April 2016) implementation of a hip fracture care pathway at a regional Level I trauma center was performed. RESULTS: There were 80 patients in the pre-pathway group and 191 patients in the post-pathway group with an average age of 83.18 ± 8.24 years. The analysis demonstrated that the post-pathway group had a lower incidence of in-hospital complications (9.95 vs 30.00%; p ≤ 0.001), shorter emergency room length of stay (3.76 ± 2.43 vs 6.78 ± 2.88 h; p ≤ 0.0001), and shorter overall hospital length of stay (5.03 ± 3.46 vs 7.44 ± 6.66 days; p = 0.0028). The in-hospital mortality rate was similar between groups (4.71 vs 6.25%; p = 0.6018). DISCUSSION: The development of a multidisciplinary approach to the care of elderly patients with hip fractures improved morbidity and showed a downward trend in mortality. CONCLUSIONS: Elderly patients with hip fractures treated at our trauma center had improved clinical outcomes after the implementation of a multidisciplinary care pathway.
Assuntos
Fraturas do Quadril/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Quadril/mortalidade , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Estudos Retrospectivos , Centros de TraumatologiaRESUMO
BACKGROUND: A performance improved project identified elderly trauma patients to have a disproportionate incidence of complications. AIMS: The purpose of this study was to assess the efficacy of a small specialty care unit to decrease complications in patients who no longer warrant care in an intensive care unit (ICU). METHODS: A surgical post-acute treatment unit (SPA) was developed with focused attention to cognition, nutrition, respiration, and mobilization needs of patients who no longer had physiologic need for an intensive care unit environment, but were still in need of increased attention at the bedside. RESULTS: While ICU and hospital lengths of stay were unchanged, patients placed in the SPA experienced less complications and required less unplanned ICU re-admissions. DISCUSSION: Geriatric patients, especially the elderly, are not simply old adults. They have unique needs as a consequence of the aging process, which can be encompassed by four pillars of intercession: cognition, nutrition, respiration, and mobilization. CONCLUSIONS: By adapting a physical environment supported by bedside attention to address the interwoven needs of geriatric and elderly patients who no longer care in an ICU, complications and unplanned return admissions to the ICU can be decreased. LEVEL OF EVIDENCE: III.
Assuntos
Cuidados Críticos/métodos , Fraturas do Quadril/terapia , Complicações Pós-Operatórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação , Masculino , Cuidados Pós-Operatórios/métodos , Período Pós-Operatório , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: To evaluate whether the emergency department usage of head computed tomography (CT) on pediatric patients with minor head trauma changed after publication of the Pediatric Emergency Care Applied Research Network (PECARN) head CT guidelines and to identify risk factors associated with performing head CT on patients without a PECARN guideline indication. METHODS: This retrospective study included 484 patients 18 years of age or younger who presented to the emergency department with head injury and a total Glasgow Coma Scale score ≥ 14 between September 2005 and July 2014. Based on the guideline publication date of September 2009, the study cohort was stratified into pre-guideline and post-guideline groups. Head CT performance, indications, and findings were compared between study periods. Logistic regression was used to identify risk factors associated with performing a non-indicated head CT. RESULTS: The rate of head CTs performed did not significantly change in the post-guideline period (96.6% vs. 95.7%, p = 0.63). There was no significant difference in the proportion of head CTs performed in patients with indications for head CT (100.0% vs. 100.0%) nor in patients without an indication for head CT (85.7% vs. 82.6%, p = 0.65) between the study periods. Females were significantly more likely to have a non-indicated head CT (OR: 2.73, 95% CI: 1.67-4.45) performed. CONCLUSIONS: Head CT ordering practices for pediatric patients with head injury did not change at a level I trauma center after publication of the PECARN head CT guidelines.
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Traumatismos Craniocerebrais/diagnóstico por imagem , Serviço Hospitalar de Emergência/normas , Fidelidade a Diretrizes , Guias de Prática Clínica como Assunto , Tomografia Computadorizada por Raios X/normas , Adolescente , Criança , Pré-Escolar , Escala de Coma de Glasgow , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Fatores de Risco , Centros de TraumatologiaRESUMO
PURPOSE: To evaluate massive transfusion protocol practices by trauma type at a level I trauma center. METHODS: A retrospective analysis was performed on a sample of 76 trauma patients with MTP activation between March 2010 and January 2015 at a regional trauma center. Patient demographics, transfusion practices, and clinical outcomes were compared by type of trauma sustained. RESULTS: Penetrating trauma patients who required MTP activation were significantly younger, had lower injury severity score (ISS), higher probability of survival (POS), decreased mortality, and higher Glasgow Coma scale (GCS) compared to blunt trauma patients. Overall, the mortality rate was 38.16%. The most common injury sustained among blunt trauma patients was head injury (36.21%), whereas the majority of the penetrating trauma patients sustained abdominal injuries (55.56%). Although the admission coagulation parameters and timing of coagulopathy were not significantly different between the two groups of patients, a significantly higher proportion of penetrating trauma patients received high plasma content therapy relative to blunt trauma patients (p < 0.01). CONCLUSION: Despite the use of the same MTP for all injured patients requiring massive transfusion, significant differences existed between blunt trauma patients and penetrating trauma patients. These differences in transfusion characteristics and outcomes following MTP activation underscore the complexity of implementing MTPs and warrant vigilant transfusion practices to improve outcomes in trauma patients.
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Transfusão de Sangue/métodos , Hemorragia/diagnóstico , Hemorragia/terapia , Mortalidade Hospitalar/tendências , Centros de Traumatologia/organização & administração , Ferimentos e Lesões/terapia , Centros Médicos Acadêmicos , Adulto , Estudos de Coortes , Feminino , Escala de Coma de Glasgow , Hemorragia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , New York , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/mortalidade , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/mortalidade , Ferimentos não Penetrantes/terapia , Ferimentos Penetrantes/diagnóstico , Ferimentos Penetrantes/mortalidade , Ferimentos Penetrantes/terapia , Adulto JovemRESUMO
Nurses are at the forefront of our health care delivery system and have been reported to exhibit a high level of burnout. Burnout and stress in trauma nurses at a safety-net hospital can negatively impact patient care. Safety-net hospitals are confronted with unique social, financial, as well as resource problems that can potentially make the work environment frustrating. The purpose of this study was to explore the levels of burnout, stress, and job satisfaction in nurses providing care to trauma patients at a Level I safety-net trauma center. A cross-sectional survey design was used to investigate principal factors including personal and professional demographics, burnout, perceived stress, and job satisfaction. Trauma nurses working at a Level I safety-net trauma center are stressed and exhibited moderate degree of burnout. The extent of emotional exhaustion experienced by the nurses varied with work location and was highest in surgical intensive care unit nurses. The level of job satisfaction in terms of opportunities for promotion differed significantly by race and the health status of the nurses. Satisfaction with coworkers was lowest in those nurses between the ages of 60-69 years. Female nurses were more satisfied with their coworkers than male nurses. In addition, the study revealed that significant relationships exist among perceived stress, burnout, and job satisfaction. Work environment significantly impacts burnout, job satisfaction, and perceived stress experienced by trauma nurses in a safety-net hospital. Nursing administration can make an effort to understand the levels of burnout and strategically improve work environment for trauma nurses in order to minimize stressors leading to attrition and enhance job satisfaction.
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Esgotamento Profissional/psicologia , Satisfação no Emprego , Estresse Psicológico/epidemiologia , Inquéritos e Questionários , Ferimentos e Lesões/enfermagem , Adulto , Enfermagem de Cuidados Críticos , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recursos Humanos de Enfermagem Hospitalar/psicologia , Saúde Ocupacional , Medição de Risco , Provedores de Redes de Segurança/organização & administração , Centros de Traumatologia/organização & administração , Estados UnidosRESUMO
Premature delivery occurs in 12% of all births, and accounts for nearly half of long-term neurological morbidity, and 60% to 80% of perinatal mortality. Despite advances in obstetrics and neonatology, the rate of premature delivery has increased approximately 12% since 1990. The single most common cause of spontaneous preterm birth is infection. Several lines of evidence have demonstrated the role of endothelin-1 as both a constrictor of uterine myometrial smooth muscle and a proinflammatory mediator. Endothelin-1 activates the phospholipase C pathway, leading to activation of protein kinase C and, in turn, sphingosine kinase (SphK). The inhibition of SphK has been recently shown to control the proinflammatory response associated with sepsis. We show herein, for the first time, that SphK inhibition prevents inflammation-associated preterm birth in a murine model. Rescue of pups from premature abortion with an SphK inhibitor occurs by suppression of the proinflammatory cytokines tumor necrosis factor α, Il-1ß, and Il-6 and attenuation of polymorphonuclear inflammatory cells into the placental labyrinth. Moreover, we postulate that inhibition of SphK leads to suppression of endothelin-converting enzyme-1 expression, indicating the presence of an endothelin-converting enzyme 1/endothelin 1-SphK positive feedback loop. This work introduces a novel approach for the control of infection-triggered preterm labor, a condition for which there is no effective treatment.
Assuntos
Citocinas/metabolismo , Inibidores Enzimáticos/uso terapêutico , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Placenta/metabolismo , Nascimento Prematuro/prevenção & controle , Animais , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Feminino , Inflamação/metabolismo , Lipopolissacarídeos , Camundongos , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Placenta/efeitos dos fármacos , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/metabolismoRESUMO
The proinflammatory response leads to various types of pathologic pathways, including the development of preterm birth. Preterm birth occurs in 12% of deliveries in the United States and causes more than 70% of perinatal morbidity and mortality. The most common cause of spontaneous preterm birth is intrauterine infection in the mother. There is accumulating evidence indicating that the release of proinflammatory cytokines plays a critical role in the pathogenesis of inflammation-associated premature delivery. We found that the common organic solvent, N,N-dimethylacetamide (DMA), prevents endotoxin-induced preterm birth in timed pregnant C57BL/6 embryonic day (E)15.5 mice and rescues their pups from spontaneous abortion at doses many-fold lower than those currently used clinically and in a dose-dependent fashion. We also provide histologic evidence that DMA suppresses the endotoxin-triggered proinflammatory response by significantly attenuating inflammatory cell infiltration of placental tissue. Furthermore, immunoblotting analysis of placental tissue harvested from our murine models revealed DMA-mediated regulation of expression of the proinflammatory cytokines IL-1ß, tumor necrosis factor α, and IL-6, and increased expression of the regulatory inflammatory cytokine IL-10. By using in vitro studies, we provide evidence that DMA suppresses macrophage function and that this small molecule prevents nuclear translocation of nuclear factor-kB. These results suggest that DMA represents a newly discovered, nontoxic therapy for a broad range of inflammatory disorders.
Assuntos
Acetamidas/farmacologia , Anti-Inflamatórios/farmacologia , Citocinas/efeitos dos fármacos , Endotoxinas/toxicidade , Nascimento Prematuro/prevenção & controle , Animais , Feminino , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/efeitos dos fármacos , Gravidez , Nascimento Prematuro/induzido quimicamenteRESUMO
Background and Aims: Real-world analyses on burden of illness in patients with alpha-1 antitrypsin deficiency (AATD) are limited. We investigated the real-world burden of liver-related clinical events among adult and pediatric patients with AATD in the USA. Methods: This was a retrospective, observational analysis of administrative claims data from the IQVIA PharMetrics® Plus and Ambulatory Electronic Medical Records databases from 2011 to 2022. Patients had a diagnosis of liver and/or lung disease with ≥180 days of continuous enrollment in the IQVIA PharMetrics Plus database before and ≥90 days after their first diagnosis. Follow-up time was assigned to the AATD with liver disease health state or AATD with both liver and lung disease health state (for patients aged ≥18 years only). Baseline demographic characteristics and liver-related clinical events of interest were reported. Results: Of 5136 eligible patients, 771 adult and 123 pediatric patients contributed time to the AATD with liver disease health state; 541 adults contributed time to the AATD with both liver and lung disease health state. Among adults, patients with both liver and lung disease had higher rates of liver-related clinical events than patients with liver disease alone. Ascites was the most frequently observed clinical event among adults in both health states, and the median time to the composite of any liver-related clinical event was 26.5 days among all adults combined. Across all pediatric age groups, ascites, gastrointestinal bleed and hepatic encephalopathy were more common than spontaneous bacterial peritonitis and hepatocellular carcinoma, but median time to liver-related clinical event varied by age group at index date and type of event. No liver transplantations occurred in patients aged 6-17 years. Conclusion: Diagnosed AATD with liver disease carries a substantial burden on adult and pediatric patients; new treatment options are warranted to avoid disease progression to decompensating events.
RESUMO
Aim: To evaluate all-cause and liver-associated healthcare resource utilization (HCRU) and costs among patients with alpha-1 antitrypsin deficiency (AATD) with liver disease (LD) and/or lung disease (LgD). Materials & methods: This was a retrospective analysis of linked administrative claims data from the IQVIA PharMetrics® Plus and the IQVIA Ambulatory Electronic Medical Records (AEMR) databases from 1 July 2021 to 31 January 2022. Patients with AATD in the IQVIA PharMetrics Plus database were included with ≥1 inpatient or ≥2 outpatient medical claims ≥90 days apart with a diagnosis of AATD, or with records indicating a protease inhibitor (Pi)*ZZ/Pi*MZ genotype in the IQVIA AEMR database with linkage to IQVIA PharMetrics Plus. For a patient's identified continuous enrollment period, patient time was assigned to health states based on the initial encounter with an LD/LgD diagnosis. A unique index date was defined for each health state, and HCRU and costs were calculated per person-year (PPY). Results: Overall, 5136 adult and pediatric patients from the IQVIA PharMetrics Plus and IQVIA AEMR databases were analyzed. All-cause and liver-associated HCRU and costs were substantially higher following onset of LD/LgD. All-cause cost PPY ranged from US $11,877 in the absence of either LD/LgD to US $74,015 in the presence of both LD and LgD. Among liver transplant recipients in the AATD with LD health state, liver-associated total costs PPY were US $87,329 1-year pre-transplantation and US $461,752 1-year post-transplantation. In the AATD with LgD and AATD with LD and LgD health states, patients who received augmentation therapy were associated with higher all-cause total costs PPY and lower liver-associated total costs PPY than their counterparts who did not receive augmentation therapy. Conclusion: Patients with AATD had increased HCRU and healthcare costs in the presence of LD and/or LgD. HCRU and healthcare costs were highest in the AATD with LD and LgD health state.
Assuntos
Hepatopatias , Pneumopatias , Deficiência de alfa 1-Antitripsina , Humanos , Deficiência de alfa 1-Antitripsina/economia , Deficiência de alfa 1-Antitripsina/complicações , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Hepatopatias/economia , Estados Unidos , Adulto , Estudos Longitudinais , Pneumopatias/economia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Idoso , Adulto Jovem , Adolescente , Recursos em Saúde/estatística & dados numéricos , Recursos em Saúde/economiaRESUMO
BACKGROUND: Background incidence rates (IRs) of health outcomes in Lyme disease endemic regions are useful to contextualize events reported during Lyme disease vaccine clinical trials or post-marketing. The objective of this study was to estimate and compare IRs of health outcomes in Lyme disease endemic versus non-endemic regions in the US during pre-COVID and COVID era timeframes. METHODS: IQVIA PharMetrics® Plus commercial claims database was used to estimate IRs of 64 outcomes relevant to vaccine safety monitoring in the US during January 1, 2017-December 31, 2019 and January 1, 2020-December 31, 2021. Analyses included all individuals aged ≥ 2 years with ≥ 1 year of continuous enrollment. Outcomes were defined by International Classification of Diseases Clinical Modification, 10th Revision (ICD-10-CM) diagnosis codes. IRs and 95 % confidence intervals (CIs) were calculated for each outcome and compared between endemic vs. non-endemic regions, and pre-COVID vs. COVID era using IR ratios (IRR). RESULTS: The study population included 8.7 million (M) in endemic and 27.8 M in non-endemic regions. Mean age and sex were similar in endemic and non-endemic regions. In both study periods, the IRs were statistically higher in endemic regions for anaphylaxis, meningoencephalitis, myocarditis/pericarditis, and rash (including erythema migrans) as compared with non-endemic regions. Conversely, significantly lower IRs were observed in endemic regions for acute kidney injury, disseminated intravascular coagulation, heart failure, myelitis, myopathies, and systemic lupus erythematosus in both study periods. Most outcomes were statistically less frequent during the COVID-era. CONCLUSION: This study identified potential differences between Lyme endemic and non-endemic regions of the US in background IRs of health conditions during pre-COVID and COVID era timeframes to inform Lyme disease vaccine safety monitoring. These regional and temporal differences in background IRs should be considered when contextualizing possible safety signals in clinical trials and post-marketing of a vaccine targeted at Lyme disease prevention.
Assuntos
Vacinas contra Doença de Lyme , Doença de Lyme , Humanos , Incidência , Doença de Lyme/epidemiologia , Fatores de Risco , Avaliação de Resultados em Cuidados de SaúdeRESUMO
BACKGROUND: Although published clinical decision rules have identified indications for the use of head CT in children with mild traumatic brain injury, practices vary. OBJECTIVE: This study seeks to evaluate whether the utilization of head CT in pediatric trauma patients presenting with mTBI varies between American College of Surgeons verified pediatric trauma centers (ACS-PTC) and adult-only trauma centers (ACS-AOTC). MATERIAL AND METHODS: A retrospective cohort study of 24,104 trauma patients, ≤17, who presented to the emergency department at 337 ACS verified level I/II trauma centers with isolated mTBI was conducted using National Trauma Data Bank records (2011-2015). Multivariable logistic regression was used to compare the odds of a patient receiving a head CT when treated at an ACS-PTC vs. an ACS-AOTC, controlling for demographic, injury, and hospital-level confounders. Effect modification by loss of consciousness was assessed and adjusted head CT odds were recalculated in patients stratified by LOC status. RESULTS: There was no significant difference in the adjusted odds of receiving a head CT at an ACS-PTC vs. an ACS-AOTC (odds ratio: 0.98, 95% confidence interval: 0.92-1.04). However, in patients who had a LOC, the adjusted OR of receiving a head CT at an ACS-PTC vs ACS-AOTC was 0.71 (95% confidence interval: 0.65-0.78). CONCLUSION: Children presenting to the emergency department of an ACS-verified level I or II trauma center with mTBI who had a loss of consciousness are less likely to receive a head CT at an ACS verified pediatric trauma center than at an ACS verified adult-only trauma center.
Assuntos
Concussão Encefálica , Adulto , Criança , Humanos , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/epidemiologia , Centros de Traumatologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , InconsciênciaRESUMO
BACKGROUND: Delayed-onset carpal tunnel syndrome (DCTS) can develop weeks and months after distal radius fracture (DRFx). A better understanding of the risk factors of DCTS can guide surgeon's decision making regarding the management of DRFx and also provides another discussion point to be had with elderly patients when discussing outcomes of nonoperative management. METHODS: We reviewed 216 nonoperatively managed DRFx between June 2015 and January 2019 at a single level 1 trauma center and senior author's office. We identified 26 patients who developed DCTS at a minimum of 6 weeks after DRFx, which constituted our case group. The remaining 190 patients served as the control group (non-carpal tunnel syndrome [CTS]). Differences between case and control group were evaluated through univariate and multivariate analyses. RESULTS: The prevalence of DCTS among nonoperatively managed DRFx was 12%. In univariate analysis, volar tilt (VT) and teardrop angle (TDA) were significant independent predictors of development of DCTS. Multivariate logistic regression analysis determined that the odds of developing CTS increased by 12% and 24% for each degree of decrease in VT and TDA, respectively. No other significant risk factors were identified. CONCLUSIONS: Decreasing VT and TDA are the most significant risk factors associated with DCTS in nonoperatively managed DRFx. These are simple and reliable radiographic measurements that provide significant prognostic value. These parameters can be used to guide surgeon decision making regarding management of DRFx in the elderly while aiding patient expectations and outcomes following nonoperative management of DRFx.
Assuntos
Síndrome do Túnel Carpal , Fraturas do Rádio , Idoso , Síndrome do Túnel Carpal/complicações , Síndrome do Túnel Carpal/etiologia , Humanos , Prognóstico , Fraturas do Rádio/complicações , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/terapia , Fatores de RiscoRESUMO
Preterm birth accounts for the majority of perinatal mortality worldwide, and there remains no FDA-approved drug to prevent it. Recently, we discovered that the common drug excipient, N,N-dimethylacetamide (DMA), delays inflammation-induced preterm birth in mice by inhibiting NF-κB. Since we reported this finding, it has come to light that a group of widely used, structurally related aprotic solvents, including DMA, N-methyl-2-pyrrolidone (NMP) and dimethylformamide (DMF), have anti-inflammatory efficacy. We show here that DMF suppresses LPS-induced TNFα secretion from RAW 264.7 cells and IL-6 and IL-8 secretion from HTR-8 cells at concentrations that do not significantly affect cell viability. Like DMA, DMF protects IκBα from degradation and prevents the p65 subunit of NF-κB from translocating to the nucleus. In vivo, DMF decreases LPS-induced inflammatory cell infiltration and expression of TNFα and IL-6 in the placental labyrinth, all to near baseline levels. Finally, DMF decreases the rate of preterm birth in LPS-induced pregnant mice (P<.0001) and the rate at which pups are spontaneously aborted (P<.0001). In summary, DMF, a widely used solvent structurally related to DMA and NMP, delays LPS-induced preterm birth in a murine model without overt toxic effects. Re-purposing the DMA/DMF/NMP family of small molecules as anti-inflammatory drugs is a promising new approach to delaying or reducing the incidence of inflammation-induced preterm birth and potentially attenuating other inflammatory disorders as well.