RESUMO
OBJECTIVE: To determine the association of nirmatrelvir/ritonavir (NMV/r) with hospitalization or death within 30 days as compared with untreated controls previously uninfected and nonhospitalized. METHODS: We used a matched cohort design using inverse probability of treatment weight (IPTW). Individuals prescribed NMV/r within 3 days of COVID-19 diagnosis were compared with IPTW-based untreated controls. Variables for IPTW included age, race, sex, body mass index, geographic location, vaccination status, and multiple comorbidities. Additional analyses were conducted on NMV/r-treated and propensity score-matched untreated controls. RESULTS: Among 7615 individuals prescribed NMV/r and 62 077 controls identified between 1 January 2022 and 25 February 2023, the risk of hospitalization/death was lower among NMV/r-treated persons vs untreated controls (243 vs 3468 events; absolute risk difference [ARD], -2.36 [95% CI, -2.57 to -2.14]). The difference was significant for those >60 and ≤60 years old (ARD, -3.86 [95% CI, -4.19 to -3.54] vs -0.27 [95% CI, -0.51 to -0.03]) and for persons asymptomatic and symptomatic (ARD, -7.09 [95% CI, -7.62 to -6.55] vs -1.46 [95% CI, -1.66 to -1.25]). Significant benefit was observed among individuals unvaccinated and vaccinated, with or without a booster dose. CONCLUSIONS: NMV/r is associated with a significant reduction in 30-day hospitalization or death among individuals previously uninfected and nonhospitalized.
Assuntos
COVID-19 , Lactamas , Leucina , Nitrilas , Prolina , Humanos , Pessoa de Meia-Idade , Tratamento Farmacológico da COVID-19 , Teste para COVID-19 , Estudos de Coortes , Ritonavir/uso terapêutico , Hospitalização , Pontuação de Propensão , Antivirais/uso terapêuticoRESUMO
BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).
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Anticorpos Monoclonais Humanizados/uso terapêutico , Tratamento Farmacológico da COVID-19 , Receptores de Interleucina-6/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , COVID-19/complicações , COVID-19/mortalidade , COVID-19/terapia , Estado Terminal , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Razão de Chances , Respiração ArtificialRESUMO
BACKGROUND: Clinical benefit of molnupiravir (MPV) in coronavirus disease 2019 (COVID-19)-infected subpopulations is unclear. METHODS: We used a matched cohort study design to determine the rate of hospitalization or death within 30 days of COVID-19 diagnosis among MPV treated and untreated controls. Participants were nonhospitalized, previously uninfected Veterans with a first confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection between 1 January and 31 August 2022, who were prescribed MPV within 3 days of COVID-19 diagnosis, and matched individuals who were not prescribed MPV. RESULTS: Among 1459 matched pairs, the incidence of hospitalization/death was not different among MPV treated versus untreated controls (48 vs 44 cases; absolute risk difference [ARD], 0.27; 95% confidence interval [CI], -.94 to 1.49). No benefit was observed among those >60 or ≤60 years old (ARD, 0.27; 95% CI, -1.25 to 1.79 vs ARD, -0.29; 95% CI, -1.22 to 1.80), those with specific comorbidities, or by vaccination status. A significant benefit was observed in asymptomatic but not in symptomatic persons (ARD, -2.80; 95% CI, -4.74 to -.87 vs ARD, 1.12; 95% CI -.31 to 2.55). Kaplan-Meier curves did not show a difference in proportion of persons who were hospitalized or died among MPV treated compared with untreated controls (logrank P = .7). CONCLUSIONS: MPV was not associated with a reduction in hospitalization or death within 30 days of COVID-19 diagnosis. A subgroup of patients presenting without symptoms experienced a benefit.
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COVID-19 , Humanos , Pessoa de Meia-Idade , SARS-CoV-2 , Teste para COVID-19 , Estudos de Coortes , HospitalizaçãoRESUMO
BACKGROUND: Breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections after vaccination have been reported. Outcomes among persons with breakthrough infection are poorly understood. METHODS: We identified all veterans with a confirmed SARS-CoV-2 infectionâ >14 days after the second dose of an mRNA vaccine between 15 December 2020 and 30 June 2021 and propensity score-matched unvaccinated controls with SARS-CoV-2 infection. The primary outcome was severe/critical disease, defined as admission to an intensive care unit, need for mechanical ventilation, or death within 28 days of diagnosis or during index hospitalization. RESULTS: Among 502 780 vaccinated and 599 974 unvaccinated persons, there were 2332 (0.5%) breakthrough infections in the vaccinated group and 40 540 (6.8%) infections in the unvaccinated group over a follow-up period of 69 083 person-days in each group. Among these groups, we identified 1728 vaccinated persons with breakthrough infection (cases) and 1728 propensity score-matched unvaccinated controls with infection. Among the former, 95 (5.5%) persons met the criteria for severe/critical disease, while 200 (11.6%) persons met the criteria among the latter group. The incidence rate for severe/critical disease per 1000 person-days (95% confidence interval [CI]) was .55 (.45-.68) among vaccinated persons with breakthrough infection and 1.22 (1.07-1.41) among the unvaccinated matched controls who developed infection (Pâ <â .0001). Risk was higher; the hazard ratio (95% CI) with increasing age per 10-year increase was 1.25 (1.11-1.41); for those withâ >4 comorbidities, it was 2.85 (1.49-5.43), while being vaccinated was associated with strong protection against severe/critical disease (HR, 0.41; 95% CI: .32-.52). CONCLUSIONS: The rate of severe/critical disease is higher among older persons and those withâ >4 comorbidities but lower among fully vaccinated persons with breakthrough infection compared with unvaccinated controls who develop infection.
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COVID-19 , SARS-CoV-2 , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Hospitalização , Humanos , Fatores de Risco , Vacinação , Vacinas Sintéticas , Vacinas de mRNARESUMO
BACKGROUND: The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may be less effective against the Omicron variant than against earlier variants. With recent resurgence of SARS-CoV-2 cases, the role of booster doses of the vaccine needs to be highlighted. METHODS: Using a retrospective cohort study design emulating a target trial, we determined the relative vaccine effectiveness (RVE) of a homologous booster dose of a SARS-CoV-2 messenger RNA (mRNA) vaccine compared with the primary vaccine series alone in preventing infection, hospitalization, and intensive care unit admission, and death in the Department of Veterans Affairs healthcare system in the United States. Among infection-free survivors who received 2 doses of a mRNA vaccine before 30 April 2021, we identified those who received a booster between 22 September and 25 December 2021 and matched them 1:1 with individuals who did not receive a booster. RESULTS: Among 2 384 272 previously uninfected persons with 2 doses of an mRNA vaccine by 30 April 2021, we identified 462 950 booster recipients between 22 September and 25 December 2021, who were matched 1:1 with non-booster recipients. The RVE (95% confidence interval) was 19% (17%-22%) for confirmed infection, 52% (46%-57%) for hospitalization, and 83% (65%-92%) for intensive care unit admission or death. Recipients of the mRNA-1273 vaccine had a lower cumulative incidence of infections and hospitalizations than recipients of the BNT162b2 vaccine (log-rank P <.001 for both comparisons). CONCLUSIONS: While the RVE of SARS-CoV-2 mRNA booster vaccine dose in preventing infection against the Omicron variant is low, it is substantial in preventing hospitalization and high in preventing the most severe/critical disease.
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COVID-19 , Vacinas , Humanos , SARS-CoV-2 , Vacina de mRNA-1273 contra 2019-nCoV , Vacina BNT162 , Estudos Retrospectivos , Eficácia de Vacinas , RNA , RNA Mensageiro , Vacinas contra COVID-19RESUMO
BACKGROUND: Persons on chronic hemodialysis have a significantly diminished humoral immune response to SARS-CoV-2 vaccines. Whether this translates to reduced vaccine effectiveness (VE) is unknown. METHODS: We used the US Department of Veterans Affairs COVID-19 Shared Data Resource to identify all veterans who were tested for SARS-CoV-2 between 26 January and 31 August 2021. Using International Classification of Diseases, 10th edition, codes and attendance at a dialysis clinic/center, we identified those who were on chronic hemodialysis. We used a test-negative, case-control design using a doubly robust logistic regression model to determine the VE of the BNT-162b2 (Pfizer) or mRNA-1273 (Moderna) vaccines in preventing confirmed SARS-CoV-2 infection. RESULTS: Among 847 199 veterans tested for SARS-CoV-2 between 26 January and 31 August 2021, there were 6076 veterans on chronic hemodialysis. Among those, we identified 1270 cases (580 fully vaccinated) and 2959 controls (2120 fully vaccinated). The overall VE >14 days after the second dose in preventing documented infection was 68.2% (95% CI: 62.6-72.9%). VE was 68.9% (95% CI: 61.9-74.7%) for Pfizer BNT-162b2 and 66.7% (95% CI: 58.9-73.0%) for Moderna mRNA-1273 vaccine. There was no difference in VE by age (<70 vs >70 years), race, or sex. There were no events recorded in persons with a Charlson's comorbidity index score <2. CONCLUSIONS: VE of 2 doses of current mRNA vaccines in preventing SARS-CoV-2 infection in persons on chronic hemodialysis is lower than historic VE rates in the general population. Effects of additional doses in improving VE in this special population need further study.
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COVID-19 , Vacinas Virais , Vacina de mRNA-1273 contra 2019-nCoV , Idoso , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Diálise Renal , SARS-CoV-2 , Vacinas Sintéticas , Vacinas de mRNARESUMO
BACKGROUND: Knowledge of the vaccine effectiveness (VE) of a third or booster vaccine dose in preventing SARS-CoV-2 infection or its consequences is critical in developing recommendations for their use. We determined relative VE of 3 vs 2 doses of an mRNA vaccine in preventing symptomatic SARS-CoV-2 infection, hospitalization, and severe/critical disease. METHODS: Among veterans who had received 2 doses of an mRNA vaccine by 30 April 2021, we identified those who received a third dose of the same vaccine between 22 September and 24 November 2021 and 1:1 matched controls who had not received their third dose by then. Using Cox proportional hazards model, we calculated adjusted hazards ratios for symptomatic infection, hospitalization, and intensive care unit (ICU) admission or death after SARS-CoV-2-positive test. RESULTS: Among 2â 321â 366 veterans who received 2 doses of Pfizer BNT-162b2 or Moderna mRNA-1273 vaccine by 30 April 2021, we matched 395â 686 persons who received a third dose of the same vaccine between 22 September and 24 November 2021 to controls who did not receive a third dose. Adjusted HRs (95% CI) were .15 (.11-.21) for symptomatic infection and .18 (.13-.26) for hospitalizations for 3 vs 2 doses, corresponding to relative VE of 85% and 82%. Five ICU admissions or deaths were observed (4 among recipients of 2 doses). There was no difference in VE between BNT162b2 versus mRNA-1273 recipients. CONCLUSIONS: A third dose of a SARS-CoV-2 mRNA vaccine is associated with high VE against symptomatic infection, hospitalization, and critical disease in the pre-Omicron era.
Assuntos
COVID-19 , Vacinas Virais , Vacina de mRNA-1273 contra 2019-nCoV , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , SARS-CoV-2 , Eficácia de Vacinas , Vacinas Sintéticas , Vacinas de mRNARESUMO
BACKGROUND: With the emergency use authorization of multiple vaccines against SARS-CoV-2 infection, data are urgently needed to determine their effectiveness in a real-world setting. OBJECTIVE: To evaluate the short-term effectiveness of vaccines in preventing SARS-CoV-2 infection. DESIGN: Test-negative case-control study using conditional logistic regression. SETTING: U.S. Department of Veterans Affairs health care system. PARTICIPANTS: All veterans who had testing for SARS-CoV-2 infection between 15 December 2020 and 4 March 2021 and no confirmed infection before 15 December 2020. INTERVENTION: SARS-CoV-2 vaccination with either the BNT-162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine as part of routine clinical care. MEASUREMENTS: Effectiveness of vaccination against confirmed SARS-CoV-2 infection. RESULTS: Among 54 360 persons who tested positive and 54 360 propensity score-matched control participants, the median age was 61 years, 83.6% were male, and 62% were White. Median body mass index was 31 kg/m2 among those who tested positive and 30 kg/m2 among those who tested negative. Among those who tested positive, 9800 (18.0%) had been vaccinated; among those who tested negative, 17 825 (32.8%) had been vaccinated. Overall vaccine effectiveness 7 or more days after the second dose was 97.1% (95% CI, 96.6% to 97.5%). Effectiveness was 96.2% (CI, 95.5% to 96.9%) for the Pfizer-BioNTech BNT-162b2 vaccine and 98.2% (CI, 97.5% to 98.6%) for the Moderna mRNA-1273 vaccine. Effectiveness remained above 95% regardless of age group, sex, race, or presence of comorbidities. LIMITATIONS: Predominantly male population; lack of data on disease severity, mortality, and effectiveness by SARS-CoV-2 variants of concern; and short-term follow-up. CONCLUSION: Currently used vaccines against SARS-CoV-2 infection are highly effective in preventing confirmed infection in a high-risk population in a real-world setting. PRIMARY FUNDING SOURCE: None.
Assuntos
Vacinas contra COVID-19 , COVID-19/prevenção & controle , Veteranos , Vacina de mRNA-1273 contra 2019-nCoV , Idoso , Vacina BNT162 , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Fatores de Risco , SARS-CoV-2 , Serviços de Saúde para Veteranos MilitaresRESUMO
OBJECTIVES: To assess for the first time the safety and pharmacokinetics of an antiprogrammed cell death-ligand 1 immune checkpoint inhibitor (BMS-936559; Bristol-Myers Squibb, Princeton, NJ) and its effect on immune biomarkers in participants with sepsis-associated immunosuppression. DESIGN: Randomized, placebo-controlled, dose-escalation. SETTING: Seven U.S. hospital ICUs. STUDY POPULATION: Twenty-four participants with sepsis, organ dysfunction (hypotension, acute respiratory failure, and/or acute renal injury), and absolute lymphocyte count less than or equal to 1,100 cells/µL. INTERVENTIONS: Participants received single-dose BMS-936559 (10-900 mg; n = 20) or placebo (n = 4) infusions. Primary endpoints were death and adverse events; key secondary endpoints included receptor occupancy and monocyte human leukocyte antigen-DR levels. MEASUREMENTS AND MAIN RESULTS: The treated group was older (median 62 yr treated pooled vs 46 yr placebo), and a greater percentage had more than 2 organ dysfunctions (55% treated pooled vs 25% placebo); other baseline characteristics were comparable. Overall mortality was 25% (10 mg dose: 2/4; 30 mg: 2/4; 100 mg: 1/4; 300 mg: 1/4; 900 mg: 0/4; placebo: 0/4). All participants had adverse events (75% grade 1-2). Seventeen percent had a serious adverse event (3/20 treated pooled, 1/4 placebo), with none deemed drug-related. Adverse events that were potentially immune-related occurred in 54% of participants; most were grade 1-2, none required corticosteroids, and none were deemed drug-related. No significant changes in cytokine levels were observed. Full receptor occupancy was achieved for 28 days after BMS-936559 (900 mg). At the two highest doses, an apparent increase in monocyte human leukocyte antigen-DR expression (> 5,000 monoclonal antibodies/cell) was observed and persisted beyond 28 days. CONCLUSIONS: In this first clinical evaluation of programmed cell death protein-1/programmed cell death-ligand 1 pathway inhibition in sepsis, BMS-936559 was well tolerated, with no evidence of drug-induced hypercytokinemia or cytokine storm, and at higher doses, some indication of restored immune status over 28 days. Further randomized trials on programmed cell death protein-1/programmed cell death-ligand 1 pathway inhibition are needed to evaluate its clinical safety and efficacy in patients with sepsis.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo , Sepse/tratamento farmacológico , Idoso , Citocinas , Relação Dose-Resposta a Droga , Feminino , Humanos , Fatores Imunológicos , Masculino , Pessoa de Meia-Idade , Sepse/imunologiaRESUMO
OBJECTIVE: To describe the contemporary epidemiology of pediatric sepsis in children with chronic disease, and the contribution of chronic diseases to mortality. We examined the incidence and hospital mortality of pediatric sepsis in a nationally representative sample and described the contribution of chronic diseases to hospital mortality. STUDY DESIGN: We analyzed the 2013 Nationwide Readmissions Database using a retrospective cohort design. We included non-neonatal patients <19 years of age hospitalized with sepsis. We examined patient characteristics, the distribution of chronic disease, and the estimated national incidence, and described hospital mortality. We used mixed effects logistic regression to explore the association between chronic diseases and hospital mortality. RESULTS: A total of 16 387 admissions, representing 14 243 unique patients, were for sepsis. The national incidence was 0.72 cases per 1000 per year (54 060 cases annually). Most (68.6%) had a chronic disease. The in-hospital mortality was 3.7% overall-0.7% for previously healthy patients and 5.1% for patients with chronic disease. In multivariable analysis, oncologic, hematologic, metabolic, neurologic, cardiac and renal disease, and solid organ transplantation were associated with increased in-hospital mortality. CONCLUSIONS: More than 2 of 3 children admitted with sepsis have ≥1 chronic disease and these patients have a higher in-hospital mortality than previously healthy patients. The burden of sepsis in hospitalized children is greatest in pediatric patients with chronic disease.
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Efeitos Psicossociais da Doença , Sepse/epidemiologia , Adolescente , Criança , Pré-Escolar , Doença Crônica , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Incidência , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Estudos Retrospectivos , Fatores de Risco , Sepse/etiologia , Estados Unidos/epidemiologiaAssuntos
Sistema Cardiovascular , Sepse , Humanos , Sepse/complicações , Sepse/epidemiologia , SobreviventesAssuntos
Antígeno B7-H1 , Sepse , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Morte Celular , HumanosRESUMO
BACKGROUND: Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease. METHODS: We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively. RESULTS: After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%-39%) compared to baseline (p<0.0001). CONCLUSIONS: LHRH superagonists decrease PSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therapy.
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Androgênios/deficiência , Hormônio Liberador de Gonadotropina/farmacologia , Antígeno Prostático Específico/sangue , Adolescente , Adulto , Interpretação Estatística de Dados , Reações Falso-Negativas , Hormônio Liberador de Gonadotropina/administração & dosagem , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Testosterona/sangue , Fatores de Tempo , Adulto JovemRESUMO
Severe hypokalemia is a potentially life-threatening disorder and is associated with variable degrees of skeletal muscle weakness, even to the point of paralysis. On rare occasions, diaphragmatic paralysis from hypokalemia can lead to respiratory arrest. There may also be decreased motility of smooth muscle, manifesting with ileus or urinary retention. Rarely, severe hypokalemia may result in rhabdomyolysis. Other manifestations of severe hypokalemia include alteration of cardiac tissue excitability and conduction. Hypokalemia can produce electrocardiographic changes such as U waves, T-wave flattening, and arrhythmias, especially if the patient is taking digoxin. Common causes of hypokalemia include extrarenal potassium losses (vomiting and diarrhea) and renal potassium losses (eg, hyperaldosteronism, renal tubular acidosis, severe hyperglycemia, potassium-depleting diuretics) as well as hypokalemia due to potassium shifts (eg, insulin administration, catecholamine excess, familial periodic hypokalemic paralysis, thyrotoxic hypokalemic paralysis). Although the extent of diuretic misuse in professional bodybuilding is unknown, it may be regarded as substantial. Hence, diuretics must always be considered as a cause of hypokalemic paralysis in bodybuilders.
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Hipopotassemia/complicações , Paralisia/etiologia , Levantamento de Peso , Adulto , Diuréticos/efeitos adversos , Eletrocardiografia , Serviço Hospitalar de Emergência , Furosemida/efeitos adversos , Coração/fisiopatologia , Humanos , Hipopotassemia/induzido quimicamente , Hipopotassemia/fisiopatologia , Masculino , Paralisia/induzido quimicamente , Paralisia/fisiopatologiaRESUMO
OBJECTIVE: Teaching ultrasound (US) guidance for placement of peripheral intravenous (PIV) catheters requires significant time for synchronous didactic and hands-on training. The investigators assessed the feasibility of an asynchronous model for critical care nurses to learn the novel skill of US-guided PIV placement. Secondary outcomes included the percentage of successful attempts and number of sticks per attempt for anatomy versus US-guided approaches. METHODS: The investigators built a self-contained training cart for learners to practice and record their performance. Training occurred asynchronously. The learners recorded data from PIV attempts. Participants completed pre- and post-training surveys. Data from this prospective observational cohort was analyzed for descriptive and comparative statistics, using Kirkpatrick's Model for evaluation of this educational intervention. RESULTS: During a 6 month period, 21 nurses completed the asynchronous training, with eight recording their PIV placements. 81.0% of the training occurred outside of a Monday to Friday 9AM-5PM period. There were 64 attempts by anatomy approach and 84 with US-guidance. The anatomic approach was successful in 35.9% of attempts with a mean of 1.5 sticks (SD 1.0, Range 1-5). The US-guided approach had a statistically significant greater rate of success (77.4%; p < 0.001) with a mean of 1.2 sticks (SD 1.2, range 1-2, p < 0.01). Participants reported increased confidence in US-guided PIV placement and enjoyment with this method of learning. CONCLUSIONS: Asynchronous learning model with cart-based instruction and practice is a feasible means for nurses to learn US-guided PIV placement. Significant outcomes were seen across Kirkpatrick levels I-IV for educational outcome assessment.