RESUMEN
BACKGROUND: Diabetes is a risk factor for infection with coronaviruses. This study describes the demographic, clinical data, and outcomes of critically ill patients with diabetes and Middle East Respiratory Syndrome (MERS). METHODS: This retrospective cohort study was conducted at 14 hospitals in Saudi Arabia (September 2012-January 2018). We compared the demographic characteristics, underlying medical conditions, presenting symptoms and signs, management and clinical course, and outcomes of critically ill patients with MERS who had diabetes compared to those with no diabetes. Multivariable logistic regression analysis was performed to determine if diabetes was an independent predictor of 90-day mortality. RESULTS: Of the 350 critically ill patients with MERS, 171 (48.9%) had diabetes. Patients with diabetes were more likely to be older, and have comorbid conditions, compared to patients with no diabetes. They were more likely to present with respiratory failure requiring intubation, vasopressors, and corticosteroids. The median time to clearance of MERS-CoV RNA was similar (23 days (Q1, Q3: 17, 36) in patients with diabetes and 21.0 days (Q1, Q3: 10, 33) in patients with no diabetes). Mortality at 90 days was higher in patients with diabetes (78.9% versus 54.7%, p < 0.0001). Multivariable regression analysis showed that diabetes was an independent risk factor for 90-day mortality (odds ratio, 2.09; 95% confidence interval, 1.18-3.72). CONCLUSIONS: Half of the critically ill patients with MERS have diabetes; which is associated with more severe disease. Diabetes is an independent predictor of mortality among critically patients with MERS.
Asunto(s)
Infecciones por Coronavirus/complicaciones , Complicaciones de la Diabetes/epidemiología , Diabetes Mellitus/epidemiología , Corticoesteroides , Adulto , Factores de Edad , Anciano , Líquido del Lavado Bronquioalveolar/virología , Estudios de Cohortes , Comorbilidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/mortalidad , Enfermedad Crítica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Nasofaringe/virología , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Arabia Saudita/epidemiología , Esputo/virología , Tráquea/virologíaRESUMEN
BACKGROUND: The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. METHODS: This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. RESULTS: Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-ß1a; none received rIFN-ß1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73-1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30-1.44]; P = .29). CONCLUSIONS: In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-ß1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.
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Antivirales/uso terapéutico , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/terapia , Interferón alfa-2/uso terapéutico , Ribavirina/uso terapéutico , Anciano , Enfermedad Crítica , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Coronavirus del Síndrome Respiratorio de Oriente Medio , Neumonía Viral/tratamiento farmacológico , ARN Viral/sangre , Estudios Retrospectivos , Arabia Saudita , Resultado del TratamientoRESUMEN
The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-ß1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-ß1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.
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Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Interferon beta-1b/uso terapéutico , Lopinavir/uso terapéutico , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Ritonavir/uso terapéutico , Antivirales/efectos adversos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/virología , Interpretación Estadística de Datos , Método Doble Ciego , Combinación de Medicamentos , Interacciones Huésped-Patógeno , Humanos , Interferon beta-1b/efectos adversos , Lopinavir/efectos adversos , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Ritonavir/efectos adversos , Arabia Saudita , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Noninvasive ventilation (NIV) has been used in patients with the Middle East respiratory syndrome (MERS) with acute hypoxemic respiratory failure, but the effectiveness of this approach has not been studied. METHODS: Patients with MERS from 14 Saudi Arabian centers were included in this analysis. Patients who were initially managed with NIV were compared to patients who were managed only with invasive mechanical ventilation (invasive MV). RESULTS: Of 302 MERS critically ill patients, NIV was used initially in 105 (35%) patients, whereas 197 (65%) patients were only managed with invasive MV. Patients who were managed with NIV initially had lower baseline SOFA score and less extensive infiltrates on chest radiograph compared with patients managed with invasive MV. The vast majority (92.4%) of patients who were managed initially with NIV required intubation and invasive mechanical ventilation, and were more likely to require inhaled nitric oxide compared to those who were managed initially with invasive MV. ICU and hospital length of stay were similar between NIV patients and invasive MV patients. The use of NIV was not independently associated with 90-day mortality (propensity score-adjusted odds ratio 0.61, 95% CI [0.23, 1.60] P = 0.27). CONCLUSIONS: In patients with MERS and acute hypoxemic respiratory failure, NIV failure was very high. The use of NIV was not associated with improved outcomes.
Asunto(s)
Infecciones por Coronavirus/complicaciones , Enfermedad Crítica , Ventilación no Invasiva/estadística & datos numéricos , Anciano , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Síndrome de Dificultad Respiratoria , Estudios Retrospectivos , Arabia Saudita , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
OBJECTIVES: Macrolides have been reported to be associated with improved outcomes in patients with viral pneumonia related to influenza and other viruses, possibly because of their immune-modulatory effects. Macrolides have frequently been used in patients with Middle East Respiratory Syndrome (MERS). This study investigated the association of macrolides with 90-day mortality and MERS coronavirus (CoV) RNA clearance in critically ill patients with MERS. METHODS: This retrospective analysis of a multicenter cohort database included 14 tertiary-care hospitals in five cities in Saudi Arabia. Multivariate logistic-regression analysis was used to determine the association of macrolide therapy with 90-day mortality, and the Cox-proportional hazard model to determine the association of macrolide therapy with MERS-CoV RNA clearance. RESULTS: Of 349 critically ill MERS patients, 136 (39%) received macrolide therapy. Azithromycin was most commonly used (97/136; 71.3%). Macrolide therapy was commonly started before the patient arrived in the intensive care unit (ICU) (51/136; 37.5%), or on day1 in ICU (53/136; 39%). On admission to ICU, the baseline characteristics of patients who received and did not receive macrolides were similar, including demographic data and sequential organ failure assessment score. However, patients who received macrolides were more likely to be admitted with community-acquired MERS (P=0.02). Macrolide therapy was not independently associated with a significant difference in 90-day mortality (adjusted odds ratio [OR]: 0.84; 95% confidence interval [CI] :0.47-1.51; P=0.56) or MERS-CoV RNA clearance (adjusted HR: 0.88; 95% CI:0.47-1.64; P=0.68). CONCLUSIONS: These findings indicate that macrolide therapy is not associated with a reduction in 90-day mortality or improvement in MERS-CoV RNA clearance.
Asunto(s)
Antibacterianos/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Macrólidos/administración & dosificación , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Adulto , Anciano , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/virología , Enfermedad Crítica/terapia , Femenino , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Estudios Retrospectivos , Arabia SauditaRESUMEN
BACKGROUND: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) leads to healthcare-associated transmission to patients and healthcare workers with potentially fatal outcomes. AIM: We aimed to describe the clinical course and functional outcomes of critically ill healthcare workers (HCWs) with MERS. METHODS: Data on HCWs was extracted from a multi-center retrospective cohort study on 330 critically ill patients with MERS admitted between (9/2012-9/2015). Baseline demographics, interventions and outcomes were recorded and compared between survivors and non-survivors. Survivors were approached with questionnaires to elucidate their functional outcomes using Karnofsky Performance Status Scale. FINDINGS: Thirty-Two HCWs met the inclusion criteria. Comorbidities were recorded in 34% (11/32) HCW. Death resulted in 8/32 (25%) HCWs including all 5 HCWs with chronic renal impairment at baseline. Non-surviving HCW had lower PaO2/FiO2 ratios 63.5 (57, 116.2) vs 148 (84, 194.3), p = 0.043, and received more ECMO therapy compared to survivors, 9/32 (28%) vs 4/24 (16.7%) respectively (p = 0.02).Thirteen of the surviving (13/24) HCWs responded to the questionnaire. Two HCWs confirmed functional limitations. Median number of days from hospital discharge until the questionnaires were filled was 580 (95% CI 568, 723.5) days. CONCLUSION: Approximately 10% of critically ill patients with MERS were HCWs. Hospital mortality rate was substantial (25%). Patients with chronic renal impairment represented a particularly high-risk group that should receive extra caution during suspected or confirmed MERS cases clinical care assignment and during outbreaks. Long-term repercussions of critical illness due to MERS on HCWs in particular, and patients in general, remain unknown and should be investigated in larger studies.
Asunto(s)
Infecciones por Coronavirus/epidemiología , Enfermedad Crítica/epidemiología , Infección Hospitalaria/epidemiología , Personal de Salud/estadística & datos numéricos , Enfermedades Profesionales/epidemiología , Adulto , Comorbilidad , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/virología , Enfermedad Crítica/terapia , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/terapia , Infección Hospitalaria/virología , Brotes de Enfermedades , Oxigenación por Membrana Extracorpórea/estadística & datos numéricos , Femenino , Mortalidad Hospitalaria , Humanos , Estado de Ejecución de Karnofsky , Masculino , Persona de Mediana Edad , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/terapia , Enfermedades Profesionales/virología , Estudios Retrospectivos , Arabia Saudita/epidemiología , Tasa de SupervivenciaRESUMEN
RATIONALE: Corticosteroid therapy is commonly used among critically ill patients with Middle East Respiratory Syndrome (MERS), but its impact on outcomes is uncertain. Analyses of observational studies often do not account for patients' clinical condition at the time of corticosteroid therapy initiation. OBJECTIVES: To investigate the association of corticosteroid therapy on mortality and on MERS coronavirus RNA clearance in critically ill patients with MERS. METHODS: ICU patients with MERs were included from 14 Saudi Arabian centers between September 2012 and October 2015. We performed marginal structural modeling to account for baseline and time-varying confounders. MEASUREMENTS AND MAIN RESULTS: Of 309 patients, 151 received corticosteroids. Corticosteroids were initiated at a median of 3.0 days (quartile 1 [Q1]-Q3, 1.0-7.0) from ICU admission. Patients who received corticosteroids were more likely to receive invasive ventilation (141 of 151 [93.4%] vs. 121 of 158 [76.6%]; P < 0.0001) and had higher 90-day crude mortality (112 of 151 [74.2%] vs. 91 of 158 [57.6%]; P = 0.002). Using marginal structural modeling, corticosteroid therapy was not significantly associated with 90-day mortality (adjusted odds ratio, 0.75; 95% confidence interval, 0.52-1.07; P = 0.12) but was associated with delay in MERS coronavirus RNA clearance (adjusted hazard ratio, 0.35; 95% CI, 0.17-0.72; P = 0.005). CONCLUSIONS: Corticosteroid therapy in patients with MERS was not associated with a difference in mortality after adjustment for time-varying confounders but was associated with delayed MERS coronavirus RNA clearance. These findings highlight the challenges and importance of adjusting for baseline and time-varying confounders when estimating clinical effects of treatments using observational studies.
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Corticoesteroides/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Cuidados Críticos/métodos , Estudios de Cohortes , Enfermedad Crítica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Arabia Saudita , Resultado del TratamientoRESUMEN
OBJECTIVES: To describe patient characteristics, clinical manifestations, disease course including viral replication patterns, and outcomes of critically ill patients with severe acute respiratory infection from the Middle East respiratory syndrome and to compare these features with patients with severe acute respiratory infection due to other etiologies. DESIGN: Retrospective cohort study. SETTING: Patients admitted to ICUs in 14 Saudi Arabian hospitals. PATIENTS: Critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection (n = 330) admitted between September 2012 and October 2015 were compared to consecutive critically ill patients with community-acquired severe acute respiratory infection of non-Middle East respiratory syndrome etiology (non-Middle East respiratory syndrome severe acute respiratory infection) (n = 222). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Although Middle East respiratory syndrome severe acute respiratory infection patients were younger than those with non-Middle East respiratory syndrome severe acute respiratory infection (median [quartile 1, quartile 3] 58 yr [44, 69] vs 70 [52, 78]; p < 0.001), clinical presentations and comorbidities overlapped substantially. Patients with Middle East respiratory syndrome severe acute respiratory infection had more severe hypoxemic respiratory failure (PaO2/FIO2: 106 [66, 160] vs 176 [104, 252]; p < 0.001) and more frequent nonrespiratory organ failure (nonrespiratory Sequential Organ Failure Assessment score: 6 [4, 9] vs 5 [3, 7]; p = 0.002), thus required more frequently invasive mechanical ventilation (85.2% vs 73.0%; p < 0.001), oxygen rescue therapies (extracorporeal membrane oxygenation 5.8% vs 0.9%; p = 0.003), vasopressor support (79.4% vs 55.0%; p < 0.001), and renal replacement therapy (48.8% vs 22.1%; p < 0.001). After adjustment for potential confounding factors, Middle East respiratory syndrome was independently associated with death compared to non-Middle East respiratory syndrome severe acute respiratory infection (adjusted odds ratio, 5.87; 95% CI, 4.02-8.56; p < 0.001). CONCLUSIONS: Substantial overlap exists in the clinical presentation and comorbidities among patients with Middle East respiratory syndrome severe acute respiratory infection from other etiologies; therefore, a high index of suspicion combined with diagnostic testing is essential component of severe acute respiratory infection investigation for at-risk patients. The lack of distinguishing clinical features, the need to rely on real-time reverse transcription polymerase chain reaction from respiratory samples, variability in viral shedding duration, lack of effective therapy, and high mortality represent substantial clinical challenges and help guide ongoing clinical research efforts.
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Infecciones por Coronavirus/epidemiología , Enfermedad Crítica , Adulto , Factores de Edad , Anciano , Alanina Transaminasa/análisis , Aspartato Aminotransferasas/análisis , Estudios de Cohortes , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/terapia , Infecciones por Coronavirus/terapia , Oxigenación por Membrana Extracorpórea/estadística & datos numéricos , Femenino , Humanos , Hipoxia/epidemiología , Unidades de Cuidados Intensivos , Leucopenia/epidemiología , Masculino , Persona de Mediana Edad , Insuficiencia Renal/epidemiología , Insuficiencia Renal/terapia , Terapia de Reemplazo Renal/estadística & datos numéricos , Respiración Artificial/estadística & datos numéricos , Insuficiencia Respiratoria/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/terapia , Estudios Retrospectivos , Arabia Saudita/epidemiología , Choque/epidemiología , Choque/terapia , Trombocitopenia/epidemiología , Vasoconstrictores/uso terapéuticoRESUMEN
The purpose of this paper is to discuss the experience of implementing innovative information technology to improve the quality of services in one of the largest Intensive Care Units in Saudi Arabia. The Intensive Care Units in King Saud Medical City (ICU-KSMC) is the main ICU in the kingdom that represents the Ministry of Health. KSMC's ICU is also considered one of the largest ICU in the world as it consists of six units with 129 beds. Leaders in KSMC's ICU have introduced and integrated three information technologies to produce powerful, accurate, and timely information systems to overcome the challenges of the ICU nature and improve the quality of service to ensure patients' safety. By 2015, ICU in KSMC has noticed a remarkable improvement in: beds' occupation and utilization, staff communication, reduced medical errors, and improved departmental work flow, which created a healthy professional work environment. Yet, ICU in KSMC has ongoing improvement projects that include future plans for more innovative information technologies' implementation in the department.
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Eficiencia Organizacional , Sistemas de Información/organización & administración , Unidades de Cuidados Intensivos/organización & administración , Mejoramiento de la Calidad/organización & administración , Ocupación de Camas , Comunicación , Humanos , Errores Médicos/prevención & control , Seguridad del Paciente , Arabia Saudita , Integración de Sistemas , Flujo de TrabajoRESUMEN
Despite significant recent improvements to our understanding of the early evolution of the Order Proboscidea (elephants and their extinct relatives), geographic sampling of the group's Paleogene fossil record remains strongly biased, with the first ~30 million years of proboscidean evolution documented solely in near-coastal deposits of northern Africa. The considerable morphological disparity that is observable among the late Eocene and early Oligocene proboscideans of northern Africa suggests that other, as yet unsampled, parts of Afro-Arabia might have served as important centers for the early diversification of major proboscidean clades. Here we describe the oldest taxonomically diagnostic remains of a fossil proboscidean from the Arabian Peninsula, a partial mandible of Omanitherium dhofarensis (new genus and species), from near the base of the early Oligocene Shizar Member of the Ashawq Formation, in the Dhofar Governorate of the Sultanate of Oman. The molars and premolars of Omanitherium are morphologically intermediate between those of Arcanotherium and Barytherium from northern Africa, but its specialized lower incisors are unlike those of other known Paleogene proboscideans in being greatly enlarged, high-crowned, conical, and tusk-like. Omanitherium is consistently placed close to late Eocene Barytherium in our phylogenetic analyses, and we place the new genus in the Family Barytheriidae. Some features of Omanitherium, such as tusk-like lower second incisors, the possible loss of the lower central incisors, an enlarged anterior mental foramen, and inferred elongate mandibular symphysis and diminutive P(2), suggest a possible phylogenetic link with Deinotheriidae, an extinct family of proboscideans whose origins have long been mysterious.