RESUMO
STUDY OBJECTIVE: In the early months of the coronavirus disease 2019 (COVID-19) pandemic and before vaccine availability, there were concerns that infected emergency department (ED) health care personnel could present a threat to the delivery of emergency medical care. We examined how the pandemic affected staffing levels and whether COVID-19 positive staff were potentially infectious at work in a cohort of US ED health care personnel in 2020. METHODS: The COVID-19 Evaluation of Risks in Emergency Departments (Project COVERED) project was a multicenter prospective cohort study of US ED health care personnel conducted from May to December 2020. During surveillance, health care personnel completed weekly electronic surveys and underwent periodic serology and nasal reverse transcription polymerase chain reaction testing for SARS-CoV-2, and investigators captured weekly data on health care facility COVID-19 prevalence and health care personnel staffing. Surveys asked about symptoms, potential exposures, work attendance, personal protective equipment use, and behaviors. RESULTS: We enrolled 1,673 health care personnel who completed 29,825 person weeks of surveillance. Eighty-nine (5.3%) health care personnel documented 90 (0.3%; 95% confidence interval [CI] 0.2% to 0.4%) person weeks of missed work related to documented or concerns for COVID-19 infection. Health care personnel experienced symptoms of COVID-19 during 1,256 (4.2%) person weeks and worked at least one shift whereas symptomatic during 1,042 (83.0%) of these periods. Seventy-five (4.5%) participants tested positive for SARS-CoV-2 during the surveillance period, including 43 (57.3%) who indicated they never experienced symptoms; 74 (98.7%; 95% CI 90.7% to 99.9%) infected health care personnel worked at least one shift during the initial period of infection, and 71 (94.7%) continued working until laboratory confirmation of their infection. Physician staffing was not associated with the facility or community COVID-19 levels within any time frame studied (Kendall tau's 0.02, 0.056, and 0.081 for no shift, one-week time shift, and 2-week time shift, respectively). CONCLUSIONS: During the first wave of the pandemic, COVID-19 infections in ED health care personnel were infrequent, and the time lost from the workforce was minimal. Health care personnel frequently reported for work while infected with SARS-CoV-2 before laboratory confirmation. The ED staffing levels were poorly correlated with facility and community COVID-19 burden.
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COVID-19 , Serviço Hospitalar de Emergência , Pessoal de Saúde , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Estados Unidos/epidemiologia , Estudos Prospectivos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Masculino , Adulto , Pessoal de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Equipamento de Proteção Individual/provisão & distribuição , Equipamento de Proteção Individual/estatística & dados numéricos , Pandemias , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controleRESUMO
This prospective multicenter study evaluated differences in concussion severity and functional outcome using glial and neuronal biomarkers glial Fibrillary Acidic (GFAP) and Ubiquitin C-terminal Hydrolase (UCH-L1) in children and youth involved in non-sport related trauma, organized sports, and recreational activities. Children and youth presenting to three Level 1 trauma centersfollowing blunt head trauma with a GCS 15 with a verified diagnosis of a concussion were enrolled within 6 hours of injury. Traumatic intracranial lesions on CT scan and functional outcome within 3 months of injury were evaluated. 131 children and youth with concussion were enrolled, 81 in the no sports group, 22 in the organized sports group and 28 in the recreational activities group. Median GFAP levels were 0.18, 0.07, and 0.39 ng/mL in the respective groups (p = 0.014). Median UCH-L1 levels were 0.18, 0.27, and 0.32 ng/mL respectively (p = 0.025). A CT scan of the head was performed in 110 (84%) patients. CT was positive in 5 (7%), 4 (27%), and 5 (20%) patients, respectively. The AUC for GFAP for detecting +CT was 0.84 (95%CI 0.75-0.93) and for UCH-L1 was 0.82 (95%CI 0.71-0.94). In those without CT lesions, elevations in UCH-L1 were significantly associated with unfavorable 3-month outcome. Concussions in the 3 groups were of similar severity and functional outcome. GFAP and UCH-L1 were both associated with severity of concussion and intracranial lesions, with the most elevated concentrations in recreational activities .
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Concussão Encefálica , Traumatismos Cranianos Fechados , Adolescente , Biomarcadores , Concussão Encefálica/diagnóstico por imagem , Criança , Proteína Glial Fibrilar Ácida , Humanos , Estudos ProspectivosRESUMO
BACKGROUND: Safe and effective oral antibiotics are needed for outpatient management of moderate to severe community-acquired bacterial pneumonia (CABP). OBJECTIVE: We describe a post-hoc analysis of adults with CABP managed as outpatients from the Lefamulin Evaluation Against Pneumonia (LEAP) 2 double-blind, noninferiority, phase 3 clinical trial. METHODS: LEAP 2 compared the efficacy and safety of oral lefamulin 600 mg every 12 h (5 days) vs. oral moxifloxacin 400 mg every 24 h (7 days) in adults (inpatients and outpatients) with Pneumonia Outcomes Research Team (PORT) risk classes IIâIV. RESULTS: Overall, 41% (151 of 368) of patients receiving lefamulin and 43% (159 of 368) of patients receiving moxifloxacin started treatment as outpatients-44% and 40%, respectively, were PORT risk class III/IV, and 21% in both groups had CURB-65 scores of 2â3. Early clinical response (at 96 ± 24 h) and investigator assessment of clinical response success rates at test of cure (5â10 days after last study drug dose) were high and similar in both groups among all (lefamulin, 91% vs. moxifloxacin, 89â90%), PORT risk class III/IV (89â91% vs. 88â91%), and CURB-65 score 2â3 (87â90% vs. 82â88%) outpatients. Few outpatients (lefamulin, 2.6%; moxifloxacin, 2.5%) discontinued the study drug because of treatment-emergent adverse events (TEAEs). No outpatient in the lefamulin group was hospitalized for a TEAE, compared with 5 patients (3%), including two deaths, in the moxifloxacin group. CONCLUSIONS: These data suggest that 5 days of oral lefamulin can be given in lieu of fluoroquinolones for outpatient treatment of adults with CABP and PORT risk class III/IV or CURB-65 scores of 2â3.
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Infecções Comunitárias Adquiridas , Pneumonia Bacteriana , Compostos Policíclicos , Adulto , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Diterpenos , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Humanos , Pacientes Ambulatoriais , Pneumonia Bacteriana/tratamento farmacológico , TioglicolatosRESUMO
BACKGROUND: Delafloxacin is an oral or intravenous (IV) antibiotic indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI), including both gram-positive (including methicillin-resistant Staphylococcus aureus [MRSA]) and gram-negative organisms. Chemically distinct from other quinolones, delafloxacin exhibits enhanced potency, particularly against gram-positive pathogens. The integration of efficacy data across the Phase III ABSSSI studies is presented here and allows for additional examination of results across subgroups. METHODS: Results of 2 multicenter, randomized, double-blind trials of 1510 adults with ABSSSI were pooled for this analysis. Subjects in the vancomycin arm received 15 mg/kg, plus 1-2 g of aztreonam every 12 hours. Delafloxacin was dosed at 300 mg IV every 12 hours in Study 302; dosing in Study 303 was 300 mg IV every 12 hours for 3 days, with a mandatory, blinded switch to delafloxacin at 450 mg orally every 12 hours. The primary endpoint was objective response (OR), defined as a ≥20% reduction of lesion spread of erythema area at the primary infection site at 48 to 72 hours (±2 hours), in the absence of clinical failure. Investigator-assessed response, based on the resolution of signs and symptoms at follow-up (FU; Day 14 ± 1) and late follow-up (LFU; Day 21- 28), were secondary endpoints. RESULTS: In the intent-to-treat analysis set, the OR was 81.3% in the delafloxacin arm and 80.7% in the comparator arm (mean treatment difference 0.8%, 95% confidence interval -3.2% to 4.7). Results for OR in the defined subgroups showed delafloxacin to be comparable to vancomycin/aztreonam. Investigator-assessed success was similar at FU (84.7% versus 84.1%) and LFU (82.0% versus 81.7%). Delafloxacin was comparable to vancomycin/aztreonam in the eradication of MRSA, at 98.1% versus 98.0%, respectively, at FU. The frequencies of treatment-emergent adverse events between the groups were similar. CONCLUSIONS: Overall, IV/oral delafloxacin fixed-dose monotherapy was non-inferior to IV vancomycin/aztreonam combination therapy and was well tolerated in each Phase III study, as well as in the pooled analysis, regardless of endpoint or analysis population.
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Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/microbiologia , Administração Intravenosa , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Oritavancin is a lipoglycopeptide with bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and prolonged half-life allow for single-dose treatment. METHODS: We conducted a randomized, double-blind trial in which adults with acute bacterial skin and skin-structure infections received either a single intravenous dose of 1200 mg of oritavancin or a regimen of intravenous vancomycin twice daily for 7 to 10 days. Three efficacy end points were tested for noninferiority. The primary composite end point was defined as cessation of spreading or reduction in lesion size, absence of fever, and no need for administration of a rescue antibiotic 48 to 72 hours after administration of oritavancin. Secondary end points were clinical cure 7 to 14 days after the end of treatment, as determined by a study investigator, and a reduction in lesion size of 20% or more 48 to 72 hours after administration of oritavancin. RESULTS: The modified intention-to-treat population comprised 475 patients who received oritavancin and 479 patients who received vancomycin. All three efficacy end points met the prespecified noninferiority margin of 10 percentage points for oritavancin versus vancomycin: primary end point, 82.3% versus 78.9% (95% confidence interval [CI] for the difference, -1.6 to 8.4 percentage points); investigator-assessed clinical cure, 79.6% versus 80.0% (95% CI for the difference, -5.5 to 4.7 percentage points); and proportion of patients with a reduction in lesion area of 20% or more, 86.9% versus 82.9% (95% CI for the difference, -0.5 to 8.6 percentage points). Efficacy outcomes measured according to type of pathogen, including methicillin-resistant Staphylococcus aureus, were similar in the two treatment groups. The overall frequency of adverse events was also similar, although nausea was more common among those treated with oritavancin. CONCLUSIONS: A single dose of oritavancin was noninferior to twice-daily vancomycin administered for 7 to 10 days for the treatment of acute bacterial skin and skin-structure infections caused by gram-positive pathogens. (Funded by the Medicines Company; SOLO I ClinicalTrials.gov number, NCT01252719.).
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Antibacterianos/administração & dosagem , Glicopeptídeos/administração & dosagem , Dermatopatias Bacterianas/tratamento farmacológico , Vancomicina/administração & dosagem , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Glicopeptídeos/efeitos adversos , Humanos , Infusões Intravenosas , Análise de Intenção de Tratamento , Lipoglicopeptídeos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Dermatopatias Bacterianas/microbiologia , Vancomicina/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSIs) are a cause of significant morbidity and therapy can be a burden to the healthcare system. New antibiotics that simplify treatment and avoid hospitalization are needed. This study compared the safety and efficacy of a single intravenous infusion of 1500 mg of dalbavancin to the 2-dose regimen. METHODS: This study was a randomized, double-blind trial in patients aged >18 years with ABSSSIs. Patients were randomized to dalbavancin 1500 mg either as a single intravenous (IV) infusion or 1000 mg IV on day 1 followed 1 week later by 500 mg IV. The primary endpoint was a ≥20% reduction in the area of erythema at 48-72 hours in the intent-to-treat population. Noninferiority was to be declared if the lower limit of the 95% confidence interval (CI) on the difference in the outcomes was greater than -10%. Clinical outcome was also assessed at days 14 and 28. RESULTS: Six hundred ninety-eight patients were randomized. Demographic characteristics were similar on each regimen, although there were more patients with methicillin-resistant Staphylococcus aureus (MRSA) at baseline on the 2-dose regimen (36/210 [17.1%] vs 61/220 [27.7%]). Dalbavancin delivered as a single dose was noninferior to a 2-dose regimen (81.4% vs 84.2%; difference, -2.9% [95% CI, -8.5% to 2.8%]). Clinical outcomes were also similar at day 14 (84.0% vs 84.8%), day 28 (84.5% vs 85.1%), and day 14 in clinically evaluable patients with MRSA in a baseline culture (92.9% vs 95.3%) in the single- and 2-dose regimens, respectively. Treatment-emergent adverse events occurred in 20.1% of the single-dose patients and 19.9% on the 2-dose regimen. CONCLUSIONS: A single 1500-mg infusion of dalbavancin is noninferior to a 2-dose regimen, has a similar safety profile, and removes logistical constraints related to delivery of the second dose. CLINICAL TRIALS REGISTRATION: NCT02127970.
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Antibacterianos/uso terapêutico , Dermatopatias Bacterianas/tratamento farmacológico , Teicoplanina/análogos & derivados , Doença Aguda , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Masculino , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-Idade , Infecções Estafilocócicas/tratamento farmacológico , Teicoplanina/administração & dosagem , Teicoplanina/efeitos adversos , Teicoplanina/uso terapêuticoAssuntos
COVID-19 , Ivermectina , Antiparasitários/uso terapêutico , Humanos , SARS-CoV-2 , Resultado do TratamentoRESUMO
Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal hydrolase (UCH-L1) have been FDA-approved for clinical use in mild and moderate traumatic brain injury (TBI). Understanding sex differences in their diagnostic accuracy over time will help inform clinical practice. We sought to evaluate the sex differences in the temporal profile of GFAP and UCH-L1 in a large cohort of trauma patients presenting to the emergency department. To compare the biomarkers' diagnostic accuracy in male versus female patients for detecting mild TBI (MTBI), and traumatic intracranial lesions on head CT. This prospective cohort study enrolled female and male adult trauma patients presenting to a Level 1 Trauma Center. All patients underwent rigorous screening to determine whether or not they had experienced a MTBI. Of 3025 trauma patients assessed, 1030 met eligibility criteria and 446 declined. Initial blood samples were obtained in 584 patients enrolled within 4 h of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180-h post-injury. The main outcomes included the diagnostic accuracy in detection of MTBI and traumatic intracranial lesions on head CT scan. A total of 1831 samples were drawn in 584 patients over 7 days, 362 (62%) were male and 222 (38%) were female. The pattern of elevation was similar in both sexes. Although the pattern of elevation was similar between male and female for both biomarkers, male patients had significantly higher concentrations of UCH-L1 compared to female patients at several timepoints post-injury, particularly within 24 h of injury. There were no significant differences in diagnostic accuracy for detecting MTBI or for detecting CT lesions between male and female patients at any timepoint for both GFAP and UCH-L1. Although patterns of GFAP and UCH-L1 release in trauma patients over a week post-injury was similar between the sexes, there were significantly higher concentrations of UCH-L1 in males at several timepoints post-injury. Despite this, the overall diagnostic accuracies of both GFAP and UCH-L1 over time for detecting MTBI and CT lesions were not significantly different between male and female trauma patients.
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Concussão Encefálica , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Adolescente , Idoso , Idoso de 80 Anos ou mais , Caracteres Sexuais , Concussão Encefálica/diagnóstico , BiomarcadoresRESUMO
STUDY OBJECTIVE: This study examines whether serum levels of glial fibrillary acidic protein breakdown products (GFAP-BDP) are elevated in patients with mild and moderate traumatic brain injury compared with controls and whether they are associated with traumatic intracranial lesions on computed tomography (CT) scan (positive CT result) and with having a neurosurgical intervention. METHODS: This prospective cohort study enrolled adult patients presenting to 3 Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score of 9 to 15. Control groups included normal uninjured controls and trauma controls presenting to the emergency department with orthopedic injuries or a motor vehicle crash without traumatic brain injury. Blood samples were obtained in all patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for GFAP-BDP (nanograms/milliliter). RESULTS: Of the 307 patients enrolled, 108 were patients with traumatic brain injury (97 with GCS score 13 to 15 and 11 with GCS score 9 to 12) and 199 were controls (176 normal controls and 16 motor vehicle crash controls and 7 orthopedic controls). Receiver operating characteristic curves demonstrated that early GFAP-BDP levels were able to distinguish patients with traumatic brain injury from uninjured controls with an area under the curve of 0.90 (95% confidence interval [CI] 0.86 to 0.94) and differentiated traumatic brain injury with a GCS score of 15 with an area under the curve of 0.88 (95% CI 0.82 to 0.93). Thirty-two patients with traumatic brain injury (30%) had lesions on CT. The area under these curves for discriminating patients with CT lesions versus those without CT lesions was 0.79 (95% CI 0.69 to 0.89). Moreover, the receiver operating characteristic curve for distinguishing neurosurgical intervention from no neurosurgical intervention yielded an area under the curve of 0.87 (95% CI 0.77 to 0.96). CONCLUSION: GFAP-BDP is detectable in serum within an hour of injury and is associated with measures of injury severity, including the GCS score, CT lesions, and neurosurgical intervention. Further study is required to validate these findings before clinical application.
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Lesões Encefálicas/sangue , Encéfalo/patologia , Proteína Glial Fibrilar Ácida/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas/patologia , Lesões Encefálicas/terapia , Estudos de Casos e Controles , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Centros de Traumatologia , Adulto JovemRESUMO
Importance: In 2018, the combination of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) levels became the first US Food and Drug Administration-approved blood test to detect intracranial lesions after mild to moderate traumatic brain injury (MTBI). How this blood test compares with validated clinical decision rules remains unknown. Objectives: To compare the performance of GFAP and UCH-L1 levels vs 3 validated clinical decision rules for detecting traumatic intracranial lesions on computed tomography (CT) in patients with MTBI and to evaluate combining biomarkers with clinical decision rules. Design, Setting, and Participants: This prospective cohort study from a level I trauma center enrolled adults with suspected MTBI presenting within 4 hours of injury. The clinical decision rules included the Canadian CT Head Rule (CCHR), New Orleans Criteria (NOC), and National Emergency X-Radiography Utilization Study II (NEXUS II) criteria. Emergency physicians prospectively completed data forms for each clinical decision rule before the patients' CT scans. Blood samples for measuring GFAP and UCH-L1 levels were drawn, but laboratory personnel were blinded to clinical results. Of 2274 potential patients screened, 697 met eligibility criteria, 320 declined to participate, and 377 were enrolled. Data were collected from March 16, 2010, to March 5, 2014, and analyzed on August 11, 2021. Main Outcomes and Measures: The presence of acute traumatic intracranial lesions on head CT scan (positive CT finding). Results: Among enrolled patients, 349 (93%) had a CT scan performed and were included in the analysis. The mean (SD) age was 40 (16) years; 230 patients (66%) were men, 314 (90%) had a Glasgow Coma Scale score of 15, and 23 (7%) had positive CT findings. For the CCHR, sensitivity was 100% (95% CI, 82%-100%), specificity was 33% (95% CI, 28%-39%), and negative predictive value (NPV) was 100% (95% CI, 96%-100%). For the NOC, sensitivity was 100% (95% CI, 82%-100%), specificity was 16% (95% CI, 12%-20%), and NPV was 100% (95% CI, 91%-100%). For NEXUS II, sensitivity was 83% (95% CI, 60%-94%), specificity was 52% (95% CI, 47%-58%), and NPV was 98% (95% CI, 94%-99%). For GFAP and UCH-L1 levels combined with cutoffs at 67 and 189 pg/mL, respectively, sensitivity was 100% (95% CI, 82%-100%), specificity was 25% (95% CI, 20%-30%), and NPV was 100%; with cutoffs at 30 and 327 pg/mL, respectively, sensitivity was 91% (95% CI, 70%-98%), specificity was 20% (95% CI, 16%-24%), and NPV was 97%. The area under the receiver operating characteristic curve (AUROC) for GFAP alone was 0.83; for GFAP plus NEXUS II, 0.83; for GFAP plus NOC, 0.85; and for GFAP plus CCHR, 0.88. The AUROC for UCH-L1 alone was 0.72; for UCH-L1 plus NEXUS II, 0.77; for UCH-L1 plus NOC, 0.77; and for UCH-L1 plus CCHR, 0.79. The GFAP biomarker alone (without UCH-L1) contributed the most improvement to the clinical decision rules. Conclusions and Relevance: In this cohort study, the CCHR, the NOC, and GFAP plus UCH-L1 biomarkers had equally high sensitivities, and the CCHR had the highest specificity. However, using different cutoff values reduced both sensitivity and specificity of GFAP plus UCH-L1. Use of GFAP significantly improved the performance of the clinical decision rules, independently of UCH-L1. Together, the CCHR and GFAP had the highest diagnostic performance.
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Concussão Encefálica , Lesões Encefálicas Traumáticas , Adulto , Biomarcadores , Concussão Encefálica/diagnóstico , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Canadá , Regras de Decisão Clínica , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos , Tomografia Computadorizada por Raios XRESUMO
Latrodectus geometricus, also known as the brown widow or brown button spider, is an unrenowned relative of the American black widow. While brown widow envenomation is generally thought of as mild, it does have the potential to lead to moderate or severe features similar to black widow bites. We report a case of brown widow envenomation that led to a moderate reaction including rash, local pain, pain radiating proximally in the extremity and nausea. Poison control was consulted for aid in spider identification. The patient was treated for pain control and muscle relaxation and monitored for eight hours. After proper tetanus prophylaxis, the patient was successfully discharged home with well-controlled, but continued mild symptoms. This case highlights a little-known, but clinically relevant species of widow spider with a wide distribution. Expeditious identification and treatment of brown widow bites can increase patient comfort, satisfaction, and discharge rates.
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OBJECTIVES: To evaluate the ability of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) to detect concussion in children and adult trauma patients with a normal mental status and assess biomarker concentrations over time as gradients of injury in concussive and non-concussive head and body trauma. DESIGN: Large prospective cohort study. SETTING: Three level I trauma centres in the USA. PARTICIPANTS: Paediatric and adult trauma patients of all ages, with and without head trauma, presenting with a normal mental status (Glasgow Coma Scale score of 15) within 4 hours of injury. Rigorous screening for concussive symptoms was conducted. Of 3462 trauma patients screened, 751 were enrolled and 712 had biomarker data. Repeated blood sampling was conducted at 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180 hours postinjury in adults. MAIN OUTCOMES: Detection of concussion and gradients of injury in children versus adults by comparing three groups of patients: (1) those with concussion; (2) those with head trauma without overt signs of concussion (non-concussive head trauma controls) and (3) those with peripheral (body) trauma without head trauma or concussion (non-concussive body trauma controls). RESULTS: A total of 1904 samples from 712 trauma patients were analysed. Within 4 hours of injury, there were incremental increases in levels of both GFAP and UCH-L1 from non-concussive body trauma (lowest), to mild elevations in non-concussive head trauma, to highest levels in patients with concussion. In concussion patients, GFAP concentrations were significantly higher compared with body trauma controls (p<0.001) and with head trauma controls (p<0.001) in both children and adults, after controlling for multiple comparisons. However, for UCH-L1, there were no significant differences between concussion patients and head trauma controls (p=0.894) and between body trauma and head trauma controls in children. The AUC for initial GFAP levels to detect concussion was 0.80 (0.73-0.87) in children and 0.76 (0.71-0.80) in adults. This differed significantly from UCH-L1 with AUCs of 0.62 (0.53-0.72) in children and 0.69 (0.64-0.74) in adults. CONCLUSIONS: In a cohort of trauma patients with normal mental status, GFAP outperformed UCH-L1 in detecting concussion in both children and adults. Blood levels of GFAP and UCH-L1 showed incremental elevations across three injury groups: from non-concussive body trauma, to non-concussive head trauma, to concussion. However, UCH-L1 was expressed at much higher levels than GFAP in those with non-concussive trauma, particularly in children. Elevations in both biomarkers in patients with non-concussive head trauma may be reflective of a subconcussive brain injury. This will require further study.
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OBJECTIVES: Altitude-related otic barotrauma and its symptoms have been identified from air-travel, scuba diving, and hyperbaric chambers, but not in skydiving. It is not known whether skydiving-related otic barotrauma could cause symptoms severe enough for medical attention or be implicated in skydiving-related accidents. This study assessed the effect of altitude change on middle ear pressures in skydivers by comparing changes in pressure before and after a skydive, pressure changes in those who developed middle ear symptoms vs. those who did not, and pressures in those who attempted equalization vs. not. METHODS: This prospective observational cohort enrolled skydivers on random days in Deland, FL. A tympanometer was used to measure middle ear pressures in decapascals (daPa) on the ground before and after skydiving. RESULTS: Average middle ear pressures in 69 subjects were significantly different before (-23.5 daPa) and after (-70.5 daPa) the skydive. There were 13 subjects (18.8%) who had middle ear symptoms after descent, but there were no statistically significant differences in ear pressure changes in those with (-57.5 daPa) and without (-44.2 daPa) symptoms after their jump. There was, however, a significant difference in pressure in those jumpers who did (-32.7 daPa) and did not (-75.7 daPa) equalize successfully after their jump. CONCLUSIONS: Rapid skydiving descent from high altitudes causes negative middle ear pressure changes. The ability to equalize ear pressures after a jump had a large impact on the change in ear pressure. However, the change in middle ear pressure was not associated with the presence of middle ear symptoms.
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Barotrauma/etiologia , Orelha Média/lesões , Esportes/fisiologia , Testes de Impedância Acústica , Adulto , Altitude , Traumatismos em Atletas/etiologia , Traumatismos em Atletas/fisiopatologia , Barotrauma/diagnóstico , Barotrauma/fisiopatologia , Orelha Média/fisiopatologia , Feminino , Humanos , MasculinoRESUMO
Uncomplicated skin and skin structure infections (uSSSIs) include impetigo, erysipelas, folliculitis, simple abscesses, and cellulitis. Their common bacterial causative agents include Staphylococcus aureus and Streptococcus pyogenes. Current guidelines predate the widespread occurrences of methicillin-resistant S. aureus (MRSA) as a community-acquired pathogen and include dicloxacillin, cephalexin, erythromycin, clindamycin, and amoxicillin/clavulanic acid, all orally, or mupirocin ointment applied topically, for impetigo. For other uSSSI, recommendations are based on the probability of the infection being caused by MRSA. If methicillin-susceptible S. aureus (MSSA) are known or suspected, the oral agents recommended include clindamycin, dicloxacillin, cephalexin, doxycycline, minocycline, and trimethoprim-sulfamethoxazole (SXT). For MRSA, recommended oral agents are linezolid, clindamycin, doxycycline, minocycline, and SXT. Because community-acquired MRSA infections now predominate in patients with abscesses in the United States, agents recommended for MRSA should be used for this indication. Local susceptibility patterns should guide empiric therapy. However, no placebo-controlled trials of uSSSI are available, and the evidence used to generate these recommendations is based on comparative noninferiority studies, often with wide noninferiority margins and confidence intervals. The evidence used in developing current guidelines therefore has significant limitations. Further studies, such as superiority outcome studies, placebo-controlled studies, measurement of time to resolution, or other novel approaches, are needed to resolve these treatment dilemmas. Until such studies are performed, the best surrogate available for predicting clinical outcome is application of pharmacokinetic and pharmacodynamic principles; these describe in vivo drug behavior and allow determination of susceptibility breakpoints for predicting in vivo antimicrobial efficacy via attainment of antimicrobial targets.
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Antibacterianos/administração & dosagem , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , beta-Lactamas/administração & dosagem , Administração Oral , Ensaios Clínicos como Assunto , Humanos , Resistência a Meticilina/efeitos dos fármacos , Guias de Prática Clínica como Assunto , Dermatopatias Bacterianas/tratamento farmacológicoRESUMO
This study examined the performance of serum ubiquitin C-terminal hydrolase (UCH-L1) in detecting traumatic intracranial lesions on computed tomography (CT) scan (+CT) in children and youth with mild and moderate TBI (mmTBI) and assessed its performance in trauma control patients without head trauma. This prospective cohort study enrolled children and youth presenting to three level 1 trauma centers after blunt head trauma and a Glasgow Coma Scale (GCS) score of 9-15 as well as trauma control patients with GCS 15 that did not have blunt head trauma. The primary outcome measure was the presence of intracranial lesions on initial CT scan. Blood samples were obtained in all patients within 6 h of injury and measured by enzyme-linked immunosorbent assay ELISA for UCH-L1 (ng/mL). A total of 256 children and youth were enrolled in the study and had serum samples drawn within 6 h of injury for analysis; 196 had blunt head trauma and 60 were trauma controls. CT scan of the head was performed in 151 patients and traumatic intracranial lesions on CT scan were evident in 17 (11%), all of whom had a GCS of 13-15. The area under the receiver operating characteristic curve (AUC) for UCH-L1 in detecting children and youth with traumatic intracranial lesions on CT was 0.83 (95% confidence interval [CI], 0.73-0.93). In those presenting with a GCS of 15, the AUC for detecting lesions was 0.83 (95% CI, 0.72-0.94). Similarly, in children under 5 years of age, the AUC was 0.79 (95% CI, 0.59-1.00). Performance for detecting intracranial lesions at a UCH-L1 cut-off level of 0.18 ng/mL yielded a sensitivity of 100%, a specificity of 47%, and a negative predictive value of 100%. UCH-L1 showed good performance in infants and toddlers younger than 5 years and performed well in children and youth with a GCS score of 15. Before clinical application, further study in larger cohort of children and youth with mild TBI is warranted.
Assuntos
Concussão Encefálica/diagnóstico , Encéfalo/diagnóstico por imagem , Traumatismos Cranianos Fechados/diagnóstico , Tomografia Computadorizada por Raios X , Ubiquitina Tiolesterase/sangue , Adolescente , Biomarcadores/sangue , Concussão Encefálica/sangue , Concussão Encefálica/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Escala de Coma de Glasgow , Traumatismos Cranianos Fechados/sangue , Traumatismos Cranianos Fechados/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
In adults, glial fibrillary acidic protein (GFAP) has been shown to out-perform S100ß in detecting intracranial lesions on computed tomography (CT) in mild traumatic brain injury (TBI). This study examined the ability of GFAP and S100ß to detect intracranial lesions on CT in children and youth involved in trauma. This prospective cohort study enrolled a convenience sample of children and youth at two pediatric and one adult Level 1 trauma centers following trauma, including both those with and without head trauma. Serum samples were obtained within 6 h of injury. The primary outcome was the presence of traumatic intracranial lesions on CT scan. There were 155 pediatric trauma patients enrolled, 114 (74%) had head trauma and 41 (26%) had no head trauma. Out of the 92 patients who had a head CT, eight (9%) had intracranial lesions. The area under the receiver operating characteristic curve (AUC) for distinguishing head trauma from no head trauma for GFAP was 0.84 (0.77-0.91) and for S100ß was 0.64 (0.55-0.74; p<0.001). Similarly, the AUC for predicting intracranial lesions on CT for GFAP was 0.85 (0.72-0.98) versus 0.67 (0.50-0.85) for S100ß (p=0.013). Additionally, we assessed the performance of GFAP and S100ß in predicting intracranial lesions in children ages 10 years or younger and found the AUC for GFAP was 0.96 (95% confidence interval [CI] 0.86-1.00) and for S100ß was 0.72 (0.36-1.00). In children younger than 5 years old, the AUC for GFAP was 1.00 (95% CI 0.99-1.00) and for S100ß 0.62 (0.15-1.00). In this population with mild TBI, GFAP out-performed S100ß in detecting head trauma and predicting intracranial lesions on head CT. This study is among the first published to date to prospectively compare these two biomarkers in children and youth with mild TBI.
Assuntos
Lesões Encefálicas/sangue , Lesões Encefálicas/diagnóstico por imagem , Proteína Glial Fibrilar Ácida/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Adolescente , Adulto , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Centros de Traumatologia , Adulto JovemRESUMO
IMPORTANCE: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have been widely studied and show promise for clinical usefulness in suspected traumatic brain injury (TBI) and concussion. Understanding their diagnostic accuracy over time will help translate them into clinical practice. OBJECTIVES: To evaluate the temporal profiles of GFAP and UCH-L1 in a large cohort of trauma patients seen at the emergency department and to assess their diagnostic accuracy over time, both individually and in combination, for detecting mild to moderate TBI (MMTBI), traumatic intracranial lesions on head computed tomography (CT), and neurosurgical intervention. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study enrolled adult trauma patients seen at a level I trauma center from March 1, 2010, to March 5, 2014. All patients underwent rigorous screening to determine whether they had experienced an MMTBI (blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9-15). Of 3025 trauma patients assessed, 1030 met eligibility criteria for enrollment, and 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within 4 hours of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 hours after injury. MAIN OUTCOMES AND MEASURES: Diagnosis of MMTBI, presence of traumatic intracranial lesions on head CT scan, and neurosurgical intervention. RESULTS: A total of 1831 blood samples were drawn from 584 patients (mean [SD] age, 40 [16] years; 62.0% [362 of 584] male) over 7 days. Both GFAP and UCH-L1 were detectible within 1 hour of injury. GFAP peaked at 20 hours after injury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at 8 hours after injury and declined rapidly over 48 hours. Over the course of 1 week, GFAP demonstrated a diagnostic range of areas under the curve for detecting MMTBI of 0.73 (95% CI, 0.69-0.77) to 0.94 (95% CI, 0.78-1.00), and UCH-L1 demonstrated a diagnostic range of 0.30 (95% CI, 0.02-0.50) to 0.67 (95% CI, 0.53-0.81). For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 (95% CI, 0.67-0.92) to 0.97 (95% CI, 0.93-1.00)for GFAP and 0.31 (95% CI, 0-0.63) to 0.77 (95% CI, 0.68-0.85) for UCH-L1. For distinguishing patients with and without a neurosurgical intervention, the range for GFAP was 0.91 (95% CI, 0.79-1.00) to 1.00 (95% CI, 1.00-1.00), and the range for UCH-L1 was 0.50 (95% CI, 0-1.00) to 0.92 (95% CI, 0.83-1.00). CONCLUSIONS AND RELEVANCE: GFAP performed consistently in detecting MMTBI, CT lesions, and neurosurgical intervention across 7 days. UCH-L1 performed best in the early postinjury period.
Assuntos
Concussão Encefálica/sangue , Concussão Encefálica/diagnóstico por imagem , Proteína Glial Fibrilar Ácida/sangue , Ubiquitina Tiolesterase/sangue , Ferimentos e Lesões/sangue , Ferimentos e Lesões/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Concussão Encefálica/complicações , Concussão Encefálica/cirurgia , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Escala de Resultado de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Fatores de Tempo , Tomografia Computadorizada por Raios X , Ferimentos e Lesões/complicações , Ferimentos e Lesões/cirurgia , Adulto JovemRESUMO
In this prospective, double-blind, multicentre trial, adult patients with complicated skin and skin structure infection (cSSSI) randomly received sequential intravenous (i.v.)/oral (p.o.) moxifloxacin (400 mg once a day) or a control regimen of i.v. piperacillin-tazobactam (3.0/0.375 g every 6 h) followed by p.o. amoxicillin-clavulanate (800 mg every 12 h), each for 7-14 days. Clinical cure rates at the test-of-cure visit (10-42 days post therapy) for the efficacy-valid population were 79% (143/180) for the moxifloxacin-treated group and 82% (153/187) for the control group (95% confidence interval, -12.04, 3.29). Bacteriological eradication rates for Staphylococcus aureus, the most prevalent organism, were 78% and 80%, respectively. The incidence of drug-related adverse events was similar for both groups (31% moxifloxacin, 30% control). Sequential i.v./p.o. moxifloxacin was as effective and well tolerated as i.v. piperacillin-tazobactam followed by p.o. amoxicillin-clavulanate in treating patients with cSSSI.
Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Antibacterianos/administração & dosagem , Compostos Aza/administração & dosagem , Quinolinas/administração & dosagem , Dermatopatias Bacterianas/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Antibacterianos/efeitos adversos , Compostos Aza/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Farmacorresistência Bacteriana , Tolerância a Medicamentos , Feminino , Fluoroquinolonas , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/efeitos adversos , Ácido Penicilânico/análogos & derivados , Piperacilina/administração & dosagem , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Estudos Prospectivos , Quinolinas/efeitos adversos , Segurança , Dermatopatias Bacterianas/microbiologiaRESUMO
OBJECTIVES: This study examined the performance of serum glial fibrillary acidic protein (GFAP) in detecting traumatic intracranial lesions on computed tomography (CT) scan in children and youth with mild and moderate traumatic brain injury (TBI) and assessed its performance in trauma control patients without head trauma. METHODS: This prospective cohort study enrolled children and youth presenting to three Level I trauma centers following blunt head trauma with Glasgow Coma Scale (GCS) scores of 9 to 15, as well as trauma control patients with GCS scores of 15 who did not have blunt head trauma. The primary outcome measure was the presence of intracranial lesions on initial CT scan. Blood samples were obtained in all patients within 6 hours of injury and measured by enzyme-linked immunosorbent assay for GFAP (ng/mL). RESULTS: A total of 257 children and youth were enrolled in the study and had serum samples drawn within 6 hours of injury for analysis: 197 had blunt head trauma and 60 were trauma controls. CT scan of the head was performed in 152 patients and traumatic intracranial lesions on CT scan were evident in 18 (11%), all of whom had GCS scores of 13 to 15. When serum levels of GFAP were compared in children and youth with traumatic intracranial lesions on CT scan to those without CT lesions, median GFAP levels were significantly higher in those with intracranial lesions (1.01, interquartile range [IQR] = 0.59 to 1.48) than those without lesions (0.18, IQR = 0.06 to 0.47). The area under the receiver operating characteristic curve (AUC) for GFAP in detecting children and youth with traumatic intracranial lesions on CT was 0.82 (95% confidence interval [CI] = 0.71 to 0.93). In those presenting with GCS scores of 15, the AUC for detecting lesions was 0.80 (95% CI = 0.68 to 0.92). Similarly, in children under 5 years old the AUC was 0.83 (95% CI = 0.56 to 1.00). Performance for detecting intracranial lesions at a GFAP cutoff level of 0.15 ng/mL yielded a sensitivity of 94%, a specificity of 47%, and a negative predictive value of 98%. CONCLUSIONS: In children and youth of all ages, GFAP measured within 6 hours of injury was associated with traumatic intracranial lesions on CT and with severity of TBI. Further study is required to validate these findings before clinical application.