Coronavirus Disease 2019 Infections Among Emergency Health Care Personnel: Impact on Delivery of United States Emergency Medical Care, 2020.

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.

Concussion severity and functional outcome using biomarkers in children and youth involved in organized sports, recreational activities and non-sport related incidents.

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 .

Evaluation of Glial and Neuronal Blood Biomarkers Compared With Clinical Decision Rules in Assessing the Need for Computed Tomography in Patients With Mild Traumatic Brain Injury.

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.

Oral 5-Day Lefamulin for Outpatient Management of Community-Acquired Bacterial Pneumonia: Post-hoc Analysis of the Lefamulin Evaluation Against Pneumonia (LEAP) 2 Trial.

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 II‒IV. 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 2‒3. Early clinical response (at 96 ± 24 h) and investigator assessment of clinical response success rates at test of cure (5‒10 days after last study drug dose) were high and similar in both groups among all (lefamulin, 91% vs. moxifloxacin, 89‒90%), PORT risk class III/IV (89‒91% vs. 88‒91%), and CURB-65 score 2‒3 (87‒90% vs. 82‒88%) 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 2‒3.

A Case of Brown Widow Envenomation in Central Florida.

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.

Evaluating glial and neuronal blood biomarkers GFAP and UCH-L1 as gradients of brain injury in concussive, subconcussive and non-concussive trauma: a prospective cohort study.

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.

Analysis of Pooled Phase III Efficacy Data for Delafloxacin in Acute Bacterial Skin and Skin Structure Infections.

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.

Oral beta-lactams applied to uncomplicated infections of skin and skin structures.

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.

Cefdinir vs. cephalexin for mild to moderate uncomplicated skin and skin structure infections in adolescents and adults.

OBJECTIVES: To compare the efficacy and safety of cefdinir to that of cephalexin in adolescents and adults with mild to moderate uncomplicated skin and skin structure infections (USSSI). RESEARCH DESIGN AND METHODS: This was an investigator-blinded, multicenter study in which patients at least 13 years of age with USSSI were randomized to receive 10 days of cefdinir 300 mg twice daily (BID) or cephalexin 250 mg four times daily (QID). Patients were evaluated at baseline, by telephone on Days 3-5, and during office visits on Days 12-14 (end-of-therapy [EOT] visit) and Days 17-24 (test-of-cure [TOC] visit). MAIN OUTCOME MEASURES: Clinical response was evaluated at the TOC visit. Patient reported outcomes, including a usefulness questionnaire, were also assessed. RESULTS: Three hundred and ninety-one patients were treated. The treatment groups were well matched with regard to demographic characteristics and types of infection. Abscess(es) (26%), wound infection (24%), and cellulitis (21%) were the most common infections. At the TOC visit, the clinical cure rate for both treatment groups was 89% (151/170 for cefdinir and 154/174 for cephalexin) in clinically evaluable patients (95% CI for difference in cure rates [-6.7 to 7.3]). In the intent-to-treat analysis, cure rates were 83% for cefdinir vs. 82% for cephalexin. Clinical cure rates for infections caused by methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus were 93% (37/40) and 92% (35/38) for cefdinir vs. 91% (29/32) and 90% (37/41) for cephalexin (p > 0.999 comparing treatment groups for MSSA; p > 0.999 for MRSA). The usefulness questionnaire demonstrated that cefdinir was more highly rated in the mean composite score (87.4 vs. 83.6, p = 0.04), with the difference primarily due to the respondents' preference for the convenience of taking the study medication (mean score 93.5 vs. 74.1 for cephalexin, p < 0.001). The study had the following limitations: the requirement for culture at baseline likely skewed the enrollment of patients towards those with abscesses; the results of culture in patients with USSSIs are often nonspecific; in some patients entering the study with a diagnosis of cellulitis, the cellulitis was associated with an abscess; and, incision and drainage (I&D), spontaneous drainage, and needle aspiration are likely to have contributed to clinical response for purulent infections, and in particular MRSA-associated infections. Both study drugs were well tolerated. The most common treatment-related adverse events were diarrhea (10% cefdinir, 4% cephalexin, p = 0.017), nausea (3% and 6%, respectively, p = 0.203), and vaginal mycosis (3% and 6% of females, respectively, p = 0.500). CONCLUSIONS: This study demonstrated that empiric coverage of USSSIs with cephalosporin therapy remains an appropriate clinical strategy. MRSA infections responded well in both arms of the study, suggesting that the choice of a cephalosporin did not adversely affect patient outcome. However, cephalosporins do not have accepted, clinically relevant in vitro activity against MRSA. Hence, the clinical response rates seen in this study against MRSA infections must be interpreted with caution. Cefdinir was more highly rated than cephalexin in a composite usefulness assessment.

A liquid adhesive bandage for the treatment of minor cuts and abrasions.

BACKGROUND: Octyl-2-cyanoacrylate is U.S. Food and Drug Administration (FDA) approved for the closure of incisions and lacerations. In animal studies, a more flexible formulation of octyl-2-cyanoacrylate suitable for cuts and abrasions produced faster healing of partial thickness wounds than traditional bandages. OBJECTIVE: To evaluate the effectiveness of a more flexible octyl-2-cyanoacrylate liquid adhesive bandage for the treatment of minor cuts and abrasions. METHODS: One hundred sixty-two volunteers with recent minor cuts or abrasions were recruited and randomized to treatment with either liquid adhesive bandage (LAB) or a control device (Band-Aid brand adhesive bandage, sheer, 2.5 cm). The primary efficacy criterion was complete healing at day 12. Secondary efficacy criteria were the ability of patients to properly apply LAB, and the ability of LAB to stop bleeding, to reduce pain, and to remain on the wound. RESULTS: At day 12 there was no statistical difference between the number of completely healed wounds in the LAB and the bandage-treated patients (P =.493). The ability of patients, as rated by investigators, to effectively apply the LAB device and the bandage was not significantly different (P =.165). Only the LAB provided significant hemostasis (P =.0001) and pain relief (P =.002). CONCLUSION: In this randomized, controlled trial, the LAB was as effective as the control at promoting healing as measured by complete healing at day 12. The LAB was easy to use and gave rapid control of bleeding and pain, forming a film that stayed on wounds well.