Critically ill patients with diabetes and Middle East respiratory syndrome: a multi-center observational study.

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.

Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study.

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.

Noninvasive ventilation in critically ill patients with the Middle East respiratory syndrome.

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.

Macrolides in critically ill patients with Middle East Respiratory Syndrome.

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.

Critically ill healthcare workers with the middle east respiratory syndrome (MERS): A multicenter study.

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.

Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome.

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.

Critically Ill Patients With the Middle East Respiratory Syndrome: A Multicenter Retrospective Cohort Study.

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.

Surveillance of preventive measures for ventilator associated pneumonia (VAP) and its rate in Makkah Region hospitals, Saudi Arabia.

BACKGROUND/AIM: The present study aimed to assess the VAP rate and to identify VAP prevention activities in public sector hospitals situated in the Makkah Region, Saudi Arabia (SA). MATERIALS AND METHODS: In this cross-sectional study, the VAP data from 13 public sector hospitals were collected from January to December 2013 and analyzed using SPSS 16. RESULTS: The overall VAP rate in Makkah Region hospitals was 6.89 cases per 1000 ventilator-days. There was a significant difference in VAP rate among the hospitals of the Makkah Region (P < 0.001). There was no significant difference in the VAP rate among hospitals, which were using only one, two, or all three VAP preventive approaches (P = 0.26) accredited by the Joint Commission International (JCI) and Central Board for Accreditation of Health Care Institution (CBAHI) (P = 0.12), and using the form in intensive care units (ICUs) (P = 0.85). There was a significant difference in the VAP rate among hospitals having different bed capacities (P < 0.001), data regularly collected (P = 0.03), and had a team to supervise the VAP project (P = 0.04). CONCLUSION: The VAP rate in Makkah Region hospitals is 6.89 cases per 1000 ventilator-days.