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1.
Chest ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33819472

RESUMO

BACKGROUND: Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition. RESEARCH QUESTION: Does a single high-dose (540,000 IU) enteral treatment of vitamin D3 given shortly after hospital admission in vitamin D deficient, critically-ill patients improve long-term global cognition or executive function? STUDY DESIGN AND METHODS: This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment versus placebo in critically-ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status. Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median (interquartile range) of 443 (390, 482) days after randomization and compared using multivariable proportional odds regression. Adjusted odds ratios (ORs) >1.0 would indicate better outcomes in the vitamin D3 group compared with placebo. RESULTS: Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 and 48 patients randomized to placebo. The adjusted median (95%CI) RBANS score at follow-up was 79.6 (73.0, 84.0) in the vitamin D3 group and 82.1 (74.7, 84.6) in the placebo group (adjusted OR, 0.83; 95%CI, 0.50 to 1.38). The adjusted median (95%CI) executive function composite score was 8.1 (6.8, 9.0) and 8.7 (7.4, 9.3), respectively (adjusted OR, 0.72; 95%CI, 0.36 to 1.42). INTERPRETATION: In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function.

2.
Trials ; 22(1): 221, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743799

RESUMO

BACKGROUND: Convalescent plasma is being used widely as a treatment for coronavirus disease 2019 (COVID-19). However, the clinical efficacy of COVID-19 convalescent plasma is unclear. METHODS: The Passive Immunity Trial for Our Nation (PassITON) is a multicenter, placebo-controlled, blinded, randomized clinical trial being conducted in the USA to provide high-quality evidence on the efficacy of COVID-19 convalescent plasma as a treatment for adults hospitalized with symptomatic disease. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days are eligible. Enrolled patients are randomized in a 1:1 ratio to 1 unit (200-399 mL) of COVID-19 convalescent plasma that has demonstrated neutralizing function using a SARS-CoV-2 chimeric virus neutralization assay. Study treatments are administered in a blinded fashion and patients are followed for 28 days. The primary outcome is clinical status 14 days after study treatment as measured on a 7-category ordinal scale assessing mortality, respiratory support, and return to normal activities of daily living. Key secondary outcomes include mortality and oxygen-free days. The trial is projected to enroll 1000 patients and is designed to detect an odds ratio ≤ 0.73 for the primary outcome. DISCUSSION: This trial will provide the most robust data available to date on the efficacy of COVID-19 convalescent plasma for the treatment of adults hospitalized with acute moderate to severe COVID-19. These data will be useful to guide the treatment of COVID-19 patients in the current pandemic and for informing decisions about whether developing a standardized infrastructure for collecting and disseminating convalescent plasma to prepare for future viral pandemics is indicated. TRIAL REGISTRATION: ClinicalTrials.gov NCT04362176 . Registered on 24 April 2020.


Assuntos
/terapia , Hospitalização , /patogenicidade , /diagnóstico , /virologia , Interações Hospedeiro-Patógeno , Humanos , Imunização Passiva , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
3.
Crit Care Med ; 49(4): e360-e368, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33566467

RESUMO

OBJECTIVES: Although early recognition of sepsis is vital to improving outcomes, the diagnosis may be missed or delayed in many patients. Acute kidney injury is one of the most common organ failures in patients with sepsis but may not be apparent on presentation. Novel biomarkers for acute kidney injury might improve organ failure recognition and facilitate earlier sepsis care. DESIGN: Retrospective, international, Sapphire study. SETTING: Academic Medical Center. PATIENTS: Adults admitted to the ICU without evidence of acute kidney injury at time of enrollment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We stratified patients enrolled in the Sapphire study into three groups-those with a clinical diagnosis of sepsis (n = 216), those with infection without sepsis (n = 120), and those without infection (n = 387) at enrollment. We then examined 30-day mortality stratified by acute kidney injury within each group. Finally, we determined the operating characteristics for kidney stress markers (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) for prediction of acute kidney injury as a sepsis-defining organ failure in patients with infection without a clinical diagnosis of sepsis at enrollment. Combining all groups, 30-day mortality was 23% for patients who developed stage 2-3 acute kidney injury within the first 3 days compared with 14% without stage 2-3 acute kidney injury. However, this difference was greatest in the infection without sepsis group (34% vs 11%; odds ratio, 4.09; 95% CI, 1.53-11.12; p = 0.005). Using a (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) cutoff of 2.0 units, 14 patients (11.7%), in the infection/no sepsis group, tested positive of which 10 (71.4%) developed stage 2-3 acute kidney injury. The positive test result occurred a median of 19 hours (interquartile range, 0.8-34.0 hr) before acute kidney injury manifested by serum creatinine or urine output. Similar results were obtained using a cutoff of 1.0 for any stage of acute kidney injury. CONCLUSIONS: Use of the urinary (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) test could identify acute kidney injury in patients with infection, possibly helping to detect sepsis, nearly a day before acute kidney injury is apparent by clinical criteria.

4.
Crit Care Med ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33591001

RESUMO

Sepsis is defined as a dysregulated host response to infection that leads to life-threatening acute organ dysfunction. It afflicts approximately 50 million people worldwide annually and is often deadly, even when evidence-based guidelines are applied promptly. Many randomized trials tested therapies for sepsis over the past 2 decades, but most have not proven beneficial. This may be because sepsis is a heterogeneous syndrome, characterized by a vast set of clinical and biologic features. Combinations of these features, however, may identify previously unrecognized groups, or "subclasses" with different risks of outcome and response to a given treatment. As efforts to identify sepsis subclasses become more common, many unanswered questions and challenges arise. These include: 1) the semantic underpinning of sepsis subclasses, 2) the conceptual goal of subclasses, 3) considerations about study design, data sources, and statistical methods, 4) the role of emerging data types, and 5) how to determine whether subclasses represent "truth." We discuss these challenges and present a framework for the broader study of sepsis subclasses. This framework is intended to aid in the understanding and interpretation of sepsis subclasses, provide a mechanism for explaining subclasses generated by different methodologic approaches, and guide clinicians in how to consider subclasses in bedside care.

5.
Support Care Cancer ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33483789

RESUMO

PURPOSE: Many patients with cancer seek care for pain in the emergency department (ED). Prospective research on cancer pain in this setting has historically been insufficient. We conducted this study to describe the reported pain among cancer patients presenting to the ED, how pain is managed, and how pain may be associated with clinical outcomes. METHODS: We conducted a multicenter cohort study on adult patients with active cancer presenting to 18 EDs in the USA. We reported pain scores, response to medication, and analgesic utilization. We estimated the associations between pain severity, medication utilization, and the following outcomes: 30-day mortality, 30-day hospital readmission, and ED disposition. RESULTS: The study population included 1075 participants. Those who received an opioid in the ED were more likely to be admitted to the hospital and were more likely to be readmitted within 30 days (OR 1.4 (95% CI: 1.11, 1.88) and OR 1.56 (95% CI: 1.17, 2.07)), respectively. Severe pain at ED presentation was associated with increased 30-day mortality (OR 2.30, 95% CI: 1.05, 5.02), though this risk was attenuated when adjusting for clinical factors (most notably functional status). CONCLUSIONS: Patients with severe pain had a higher risk of mortality, which was attenuated when correcting for clinical characteristics. Those patients who required opioid analgesics in the ED were more likely to require admission and were more at risk of 30-day hospital readmission. Future efforts should focus on these at-risk groups, who may benefit from additional services including palliative care, hospice, or home-health services.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33405338

RESUMO

BACKGROUND: Symptoms of mild COVID-19 illness are non-specific and may persist for prolonged periods. Effects on quality of life of persistent poor physical or mental health associated with COVID-19 are not well understood. METHODS: Adults aged ≥18 years with laboratory-confirmed COVID-19 and matched control patients who tested negative for SARS-CoV-2 infection at outpatient facilities associated with 11 medical centers in the United States were interviewed to assess symptoms, illness duration, and health-related quality of life. Duration of symptoms, health-related quality of life measures, and days of poor physical health by symptoms experienced during illness were compared between case patients and controls using Wilcoxon rank-sum tests. Symptoms associated with COVID-19 case status were evaluated by multivariable logistic regression. RESULTS: Among 320 participants included, 157 were COVID-19 cases and 163 were SARS-CoV-2 negative controls. Loss of taste or smell was reported by 63% of cases and 6% of controls and was strongly associated with COVID-19 in logistic regression models (adjusted odds ratio [aOR] = 32.4; 95% confidence interval [CI], 12.6-83.1). COVID-19 cases were more likely than controls to have experienced fever, body aches, weakness, or fatigue during illness, and to report ≥1 persistent symptom more than 14 days after symptom onset (50% vs 32%, P < .001). Cases reported significantly more days of poor physical health during the past 14 days than controls (P < .01). CONCLUSIONS: Differentiating COVID-19 from other acute illnesses will require widespread diagnostic testing, especially during influenza seasons. Persistent COVID-19-related symptoms may negatively affect quality of life, even among those initially presenting with mild illness.

7.
MMWR Morb Mortal Wkly Rep ; 69(47): 1762-1766, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33237893

RESUMO

Most persons infected with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), develop virus-specific antibodies within several weeks, but antibody titers might decline over time. Understanding the timeline of antibody decline is important for interpreting SARS-CoV-2 serology results. Serum specimens were collected from a convenience sample of frontline health care personnel at 13 hospitals and tested for antibodies to SARS-CoV-2 during April 3-June 19, 2020, and again approximately 60 days later to assess this timeline. The percentage of participants who experienced seroreversion, defined as an antibody signal-to-threshold ratio >1.0 at baseline and <1.0 at the follow-up visit, was assessed. Overall, 194 (6.0%) of 3,248 participants had detectable antibodies to SARS-CoV-2 at baseline (1). Upon repeat testing approximately 60 days later (range = 50-91 days), 146 (93.6%) of 156 participants experienced a decline in antibody response indicated by a lower signal-to-threshold ratio at the follow-up visit, compared with the baseline visit, and 44 (28.2%) experienced seroreversion. Participants with higher initial antibody responses were more likely to have antibodies detected at the follow-up test than were those who had a lower initial antibody response. Whether decay in these antibodies increases risk for reinfection and disease remains unanswered. However, these results suggest that serology testing at a single time point is likely to underestimate the number of persons with previous SARS-CoV-2 infection, and a negative serologic test result might not reliably exclude prior infection.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Recursos Humanos em Hospital/estatística & dados numéricos , Pneumonia Viral/imunologia , Adulto , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Estados Unidos/epidemiologia
8.
JAMA ; 324(21): 2165-2176, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33165621

RESUMO

Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration: ClinicalTrials.gov: NCT04332991.

9.
MMWR Morb Mortal Wkly Rep ; 69(44): 1648-1653, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33151918

RESUMO

Since March 2020, large-scale efforts to reduce transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), have continued. Mitigation measures to reduce workplace exposures have included work site policies to support flexible work site options, including telework, whereby employees work remotely without commuting to a central place of work.* Opportunities to telework have varied across industries among U.S. jobs where telework options are feasible (1). However, little is known about the impact of telework on risk for SARS-CoV-2 infection. A case-control investigation was conducted to compare telework between eligible symptomatic persons who received positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results (case-patients, 153) and symptomatic persons with negative test results (control-participants, 161). Eligible participants were identified in outpatient health care facilities during July 2020. Among employed participants who reported on their telework status during the 2 weeks preceding illness onset (248), the percentage who were able to telework on a full- or part-time basis was lower among case-patients (35%; 42 of 120) than among control-participants (53%; 68 of 128) (p<0.01). Case-patients were more likely than were control-participants to have reported going exclusively to an office or school setting (adjusted odds ratio [aOR] = 1.8; 95% confidence interval [CI] = 1.2-2.7) in the 2 weeks before illness onset. The association was also observed when further restricting to the 175 participants who reported working in a profession outside the critical infrastructure† (aOR = 2.1; 95% CI = 1.3-3.6). Providing the option to work from home or telework when possible, is an important consideration for reducing the risk for SARS-CoV-2 infection. In industries where telework options are not available, worker safety measures should continue to be scaled up to reduce possible worksite exposures.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Avaliação de Sintomas , Telecomunicações/estatística & dados numéricos , Trabalho/estatística & dados numéricos , Adolescente , Adulto , Instituições de Assistência Ambulatorial , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estados Unidos/epidemiologia , Adulto Jovem
10.
J Am Coll Emerg Physicians Open ; 1(5): 880-886, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33145536

RESUMO

Background: A significant number of patients who present to the emergency department (ED) following a fall or with other injuries require evaluation by a physical therapist. Traditionally, once emergent conditions are excluded in the ED, these patients are admitted to the hospital for evaluation by a physical therapist to determine whether they should be transferred to a sub-acute rehabilitation facility, discharged, require services at home, or require further inpatient care. Case management is typically used in conjunction with a physical therapist to determine eligibility for recommended services and to aid in placement. Objective: To evaluate the benefit of using ED-based physical therapist and case management services in lieu of routine hospital admission. Methods: Retrospective, observational study of consecutive patients presenting to an urban, tertiary care academic medical center ED between December 1, 2017, and November 30, 2018, who had a physical therapist consult placed in the ED. We additionally evaluated which of these patients were placed into ED observation for physical therapist consultation, how many required case management, and ED disposition: discharged home from the ED or ED observation with or without services, placed in a rehabilitation facility, or admitted to the hospital. Results: During the 12-month study period, 1296 patients (2.4% of the total seen in the ED) were assessed by a physical therapist. The mean age was 75.5 ± 15.2 and 832 (64.2%) were female. Case management was involved in 91.8% of these cases. The final patient disposition was as follows: admission 24.3% (95% CI = 22.1-26.7%), home discharge with or without services 47.8% (95% CI = 45.1-50.5%), rehabilitation (rehab) setting 27.9% (95% CI = 25.6%-30.4). The median (interquartile range) time in observation was 13.1 (6.0-20.3), 9.9 (1.8-15.8), and 18.4 (14.1-24.8) hours for patients admitted, discharged home, or sent to rehabilitation (P < 0.001). Among the 979 patients discharged home or sent to rehabilitation, 17 (1.7%) returned to the ED within 72 hours and were ultimately admitted. Conclusion: Given that the standard of care would otherwise be an admission to the hospital for 1 day or more for all patients requiring physical therapist consultation, an ED-based physical therapy and case management system serves as a viable method to substantially decrease hospital admissions and potentially reduce resource use, length of hospital stay, and cost both to patients and the health care system.

11.
N Engl J Med ; 383(20): 1907-1919, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33017106

RESUMO

BACKGROUND: Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis. METHODS: We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith. RESULTS: In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50). CONCLUSIONS: For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).


Assuntos
Antibacterianos/uso terapêutico , Apendicectomia , Apendicite/tratamento farmacológico , Apendicite/cirurgia , Apêndice/cirurgia , Absenteísmo , Administração Intravenosa , Adulto , Antibacterianos/efeitos adversos , Apendicectomia/estatística & dados numéricos , Apendicite/complicações , Apêndice/patologia , Impacção Fecal , Feminino , Nível de Saúde , Hospitalização/estatística & dados numéricos , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento
12.
Clin Infect Dis ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32974644

RESUMO

With rapid and accurate molecular influenza testing now widely available in clinical settings, influenza vaccine effectiveness (VE) studies can prospectively select participants for enrollment based on real-time results rather than enrolling all eligible patients regardless of influenza status, as in the traditional test-negative design (TND). Thus, we explore advantages and disadvantages of modifying the TND for estimating VE by using real-time, clinically available viral testing results paired with acute respiratory infection eligibility criteria for identifying influenza cases and test-negative controls prior to enrollment. This modification, which we have called the real-time test-negative design (rtTND), has the potential to improve influenza VE studies by optimizing the case-to-test-negative control ratio, more accurately classifying influenza status, improving study efficiency, reducing study cost, and increasing study power to adequately estimate VE. Important considerations for limiting biases in the rtTND include the need for comprehensive clinical influenza testing at study sites and accurate influenza tests.

13.
Ann Emerg Med ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32988649

RESUMO

Patients frequently visit the emergency department with conditions that place them at risk of worse outcomes when accompanied by coagulopathy. Routine tests of coagulation-prothrombin time, partial thromboplastin time, platelets, and fibrinogen-have shortcomings that limit their use in providing emergency care. One alternative is to investigate coagulation disturbance with viscoelastic monitoring (VEM), a coagulation test that measures the timing and strength of blood clot development in real time. VEM is widely used and studied in cardiac surgery, liver transplant surgery, anesthesia, and trauma. In this article, we review the technique of VEM and the biologic rationale of using it in addition to routine tests of coagulation in emergency clinical situations. Then, we review the evidence (or lack thereof) for using VEM in the diagnosis and treatment of specific conditions. Finally, we describe the limitations of the test and future directions for clinical use and research in emergency medicine.

14.
Ann Surg ; 272(4): 604-610, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32932316

RESUMO

OBJECTIVES: Sepsis and sterile both release "danger signals' that induce the systemic inflammatory response syndrome (SIRS). So differentiating infection from SIRS can be challenging. Precision diagnostic assays could limit unnecessary antibiotic use, improving outcomes. METHODS: After surveying human leukocyte cytokine production responses to sterile damage-associated molecular patterns (DAMPs), bacterial pathogen-associated molecular patterns, and bacteria we created a multiplex assay for 31 cytokines. We then studied plasma from patients with bacteremia, septic shock, "severe sepsis," or trauma (ISS ≥15 with circulating DAMPs) as well as controls. Infections were adjudicated based on post-hospitalization review. Plasma was studied in infection and injury using univariate and multivariate means to determine how such multiplex assays could best distinguish infective from noninfective SIRS. RESULTS: Infected patients had high plasma interleukin (IL)-6, IL-1α, and triggering receptor expressed on myeloid cells-1 (TREM-1) compared to controls [false discovery rates (FDR) <0.01, <0.01, <0.0001]. Conversely, injury suppressed many mediators including MDC (FDR <0.0001), TREM-1 (FDR <0.001), IP-10 (FDR <0.01), MCP-3 (FDR <0.05), FLT3L (FDR <0.05), Tweak, (FDR <0.05), GRO-α (FDR <0.05), and ENA-78 (FDR <0.05). In univariate studies, analyte overlap between clinical groups prevented clinical relevance. Multivariate models discriminated injury and infection much better, with the 2-group random-forest model classifying 11/11 injury and 28/29 infection patients correctly in out-of-bag validation. CONCLUSIONS: Circulating cytokines in traumatic SIRS differ markedly from those in health or sepsis. Variability limits the accuracy of single-mediator assays but machine learning based on multiplexed plasma assays revealed distinct patterns in sepsis- and injury-related SIRS. Defining biomarker release patterns that distinguish specific SIRS populations might allow decreased antibiotic use in those clinical situations. Large prospective studies are needed to validate and operationalize this approach.


Assuntos
Citocinas/sangue , Sepse/sangue , Sepse/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Relatórios Anuais como Assunto , Diagnóstico Diferencial , Cirurgia Geral , Testes Hematológicos/métodos , Humanos , Estudos Prospectivos , Sepse/imunologia , Sociedades Médicas , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Estados Unidos
15.
MMWR Morb Mortal Wkly Rep ; 69(35): 1221-1226, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32881855

RESUMO

Health care personnel (HCP) caring for patients with coronavirus disease 2019 (COVID-19) might be at high risk for contracting SARS-CoV-2, the virus that causes COVID-19. Understanding the prevalence of and factors associated with SARS-CoV-2 infection among frontline HCP who care for COVID-19 patients are important for protecting both HCP and their patients. During April 3-June 19, 2020, serum specimens were collected from a convenience sample of frontline HCP who worked with COVID-19 patients at 13 geographically diverse academic medical centers in the United States, and specimens were tested for antibodies to SARS-CoV-2. Participants were asked about potential symptoms of COVID-19 experienced since February 1, 2020, previous testing for acute SARS-CoV-2 infection, and their use of personal protective equipment (PPE) in the past week. Among 3,248 participants, 194 (6.0%) had positive test results for SARS-CoV-2 antibodies. Seroprevalence by hospital ranged from 0.8% to 31.2% (median = 3.6%). Among the 194 seropositive participants, 56 (29%) reported no symptoms since February 1, 2020, 86 (44%) did not believe that they previously had COVID-19, and 133 (69%) did not report a previous COVID-19 diagnosis. Seroprevalence was lower among personnel who reported always wearing a face covering (defined in this study as a surgical mask, N95 respirator, or powered air purifying respirator [PAPR]) while caring for patients (5.6%), compared with that among those who did not (9.0%) (p = 0.012). Consistent with persons in the general population with SARS-CoV-2 infection, many frontline HCP with SARS-CoV-2 infection might be asymptomatic or minimally symptomatic during infection, and infection might be unrecognized. Enhanced screening, including frequent testing of frontline HCP, and universal use of face coverings in hospitals are two strategies that could reduce SARS-CoV-2 transmission.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Recursos Humanos em Hospital/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Centros Médicos Acadêmicos , Adulto , Doenças Assintomáticas , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Infecção Hospitalar/prevenção & controle , Feminino , Humanos , Transmissão de Doença Infecciosa do Profissional para o Paciente/prevenção & controle , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Equipamento de Proteção Individual/estatística & dados numéricos , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Estudos Soroepidemiológicos , Estados Unidos/epidemiologia
16.
MMWR Morb Mortal Wkly Rep ; 69(36): 1258-1264, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32915165

RESUMO

Community and close contact exposures continue to drive the coronavirus disease 2019 (COVID-19) pandemic. CDC and other public health authorities recommend community mitigation strategies to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1,2). Characterization of community exposures can be difficult to assess when widespread transmission is occurring, especially from asymptomatic persons within inherently interconnected communities. Potential exposures, such as close contact with a person with confirmed COVID-19, have primarily been assessed among COVID-19 cases, without a non-COVID-19 comparison group (3,4). To assess community and close contact exposures associated with COVID-19, exposures reported by case-patients (154) were compared with exposures reported by control-participants (160). Case-patients were symptomatic adults (persons aged ≥18 years) with SARS-CoV-2 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing. Control-participants were symptomatic outpatient adults from the same health care facilities who had negative SARS-CoV-2 test results. Close contact with a person with known COVID-19 was more commonly reported among case-patients (42%) than among control-participants (14%). Case-patients were more likely to have reported dining at a restaurant (any area designated by the restaurant, including indoor, patio, and outdoor seating) in the 2 weeks preceding illness onset than were control-participants (adjusted odds ratio [aOR] = 2.4; 95% confidence interval [CI] = 1.5-3.8). Restricting the analysis to participants without known close contact with a person with confirmed COVID-19, case-patients were more likely to report dining at a restaurant (aOR = 2.8, 95% CI = 1.9-4.3) or going to a bar/coffee shop (aOR = 3.9, 95% CI = 1.5-10.1) than were control-participants. Exposures and activities where mask use and social distancing are difficult to maintain, including going to places that offer on-site eating or drinking, might be important risk factors for acquiring COVID-19. As communities reopen, efforts to reduce possible exposures at locations that offer on-site eating and drinking options should be considered to protect customers, employees, and communities.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Busca de Comunicante , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Exposição Ambiental/efeitos adversos , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Adolescente , Adulto , Instituições de Assistência Ambulatorial , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estados Unidos/epidemiologia , Adulto Jovem
17.
MMWR Morb Mortal Wkly Rep ; 69(30): 993-998, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32730238

RESUMO

Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2.


Assuntos
Assistência Ambulatorial , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Assistência à Saúde/organização & administração , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Recuperação de Função Fisiológica , Adolescente , Adulto , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
18.
MMWR Morb Mortal Wkly Rep ; 69(26): 841-846, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32614810

RESUMO

Descriptions of coronavirus disease 2019 (COVID-19) in the United States have focused primarily on hospitalized patients. Reports documenting exposures to SARS-CoV-2, the virus that causes COVID-19, have generally been described within congregate settings, such as meat and poultry processing plants (1) and long-term care facilities (2). Understanding individual behaviors and demographic characteristics of patients with COVID-19 and risks for severe illness requiring hospitalization can inform efforts to reduce transmission. During April 15-May 24, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had positive reverse transcription-polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 in outpatient and inpatient settings at 11 U.S. academic medical centers in nine states. Respondents were contacted 14-21 days after SARS-CoV-2 testing and asked about their demographic characteristics, underlying chronic conditions, symptoms experienced on the date of testing, and potential exposures to SARS-CoV-2 during the 2 weeks before illness onset (or the date of testing among those who did not report symptoms at the time of testing). Among 350 interviewed patients (271 [77%] outpatients and 79 [23%] inpatients), inpatients were older, more likely to be Hispanic and to report dyspnea than outpatients. Fewer inpatients (39%, 20 of 51) reported a return to baseline level of health at 14-21 days than did outpatients (64%, 150 of 233) (p = 0.001). Overall, approximately one half (46%) of patients reported known close contact with someone with COVID-19 during the preceding 2 weeks. This was most commonly a family member (45%) or a work colleague (34%). Approximately two thirds (64%, 212 of 333) of participants were employed; only 35 of 209 (17%) were able to telework. These findings highlight the need for screening, case investigation, contact tracing, and isolation of infected persons to control transmission of SARS-CoV-2 infection during periods of community transmission. The need for enhanced measures to ensure workplace safety, including ensuring social distancing and more widespread use of cloth face coverings, are warranted (3).


Assuntos
Infecções por Coronavirus/diagnóstico , Pacientes Internados/estatística & dados numéricos , Pacientes Ambulatoriais/estatística & dados numéricos , Pneumonia Viral/diagnóstico , Centros Médicos Acadêmicos , Adulto , Idoso , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Fatores de Risco , Fatores Socioeconômicos , Estados Unidos/epidemiologia
19.
Ann Am Thorac Soc ; 17(9): 1144-1153, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32492354

RESUMO

The ORCHID (Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease) trial is a multicenter, blinded, randomized trial of hydroxychloroquine versus placebo for the treatment of adults hospitalized with coronavirus disease (COVID-19). This document provides the rationale and background for the trial and highlights key design features. We discuss five novel challenges to the design and conduct of a large, multicenter, randomized trial during a pandemic, including 1) widespread, off-label use of the study drug before the availability of safety and efficacy data; 2) the need to adapt traditional procedures for documentation of informed consent during an infectious pandemic; 3) developing a flexible and robust Bayesian analysis incorporating significant uncertainty about the disease, outcomes, and treatment; 4) obtaining indistinguishable drug and placebo without delaying enrollment; and 5) rapidly obtaining administrative and regulatory approvals. Our goals in describing how the ORCHID trial progressed from study conception to enrollment of the first patient in 15 days are to inform the development of other high-quality, multicenter trials targeting COVID-19. We describe lessons learned to improve the efficiency of future clinical trials, particularly in the setting of pandemics. The ORCHID trial will provide high-quality, clinically relevant data on the safety and efficacy of hydroxychloroquine for the treatment of COVID-19 among hospitalized adults.Clinical trial registered with www.clinicaltrials.gov (NCT04332991).


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Pandemias , Pneumonia Viral/tratamento farmacológico , Adulto , Antimaláricos/administração & dosagem , Infecções por Coronavirus/epidemiologia , Relação Dose-Resposta a Droga , Hospitalização/tendências , Humanos , Pneumonia Viral/epidemiologia , Método Simples-Cego , Resultado do Tratamento
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