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BACKGROUND: Clinical data on patients admitted to hospital with coronavirus disease 2019 (COVID-19) provide clinicians and public health officials with information to guide practice and policy. The aims of this study were to describe patients with COVID-19 admitted to hospital and intensive care, and to investigate predictors of outcome to characterize severe acute respiratory infection. METHODS: This observational cohort study used Canadian data from 32 selected hospitals included in a global multisite cohort between Jan. 24 and July 7, 2020. Adult and pediatric patients with a confirmed diagnosis of COVID-19 who received care in an intensive care unit (ICU) and a sampling of up to the first 60 patients receiving care on hospital wards were included. We performed descriptive analyses of characteristics, interventions and outcomes. The primary analyses examined in-hospital mortality, with secondary analyses of the length of hospital and ICU stay. RESULTS: Between January and July 2020, among 811 patients admitted to hospital with a diagnosis of COVID-19, the median age was 64 (interquartile range [IQR] 53-75) years, 495 (61.0%) were men, 46 (5.7%) were health care workers, 9 (1.1%) were pregnant, 26 (3.2%) were younger than 18 years and 9 (1.1%) were younger than 5 years. The median time from symptom onset to hospital admission was 7 (IQR 3-10) days. The most common symptoms on admission were fever, shortness of breath, cough and malaise. Diabetes, hypertension and cardiac, kidney and respiratory disease were the most common comorbidities. Among all patients, 328 received care in an ICU, admitted a median of 0 (IQR 0-1) days after hospital admission. Critically ill patients received treatment with invasive mechanical ventilation (88.8%), renal replacement therapy (14.9%) and extracorporeal membrane oxygenation (4.0%); 26.2% died. Among those receiving mechanical ventilation, 31.2% died. Age was an influential predictor of mortality (odds ratio per additional year of life 1.06, 95% confidence interval 1.03-1.09). INTERPRETATION: Patients admitted to hospital with COVID-19 commonly had fever, respiratory symptoms and comorbid conditions. Increasing age was associated with the development of critical illness and death; however, most critically ill patients in Canada, including those requiring mechanical ventilation, survived and were discharged from hospital.

IMPORTANCE: Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported. OBJECTIVE: To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU). DESIGN, SETTING, AND PARTICIPANTS: Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020). INTERVENTIONS: Enteral L rhamnosus GG (1 × 10(10) colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU. MAIN OUTCOMES AND MEASURES: The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality. RESULTS: Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, –2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P

IntroductionVentilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile–associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.Methods and analysisThe objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer’s perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital ‘hoteling’ costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.Ethics and disseminationStudy approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.Trial registration numberNCT01782755; Pre-results.

We performed a meta-analysis to evaluate whether stress ulcer prophylaxis with histamine-2-receptor antagonists or antacids reduces mortality in critically ill patients. It appears that sucralfate results in a lower incidence of nosocomial pneumonia than either antacids or histamine-2-receptor antagonists. With respect to mortality, strong trends favored sucralfate over both antacids and histamine-receptor antagonists.

To evaluate the pattern and predictive value of serum cortisol levels in severe septic shock, we studied 20 consecutive critically ill patients with severe sepsis. Serum cortisol levels were measured at time of diagnosis, at 12 and 24 hours, and daily for 5 days. Underlying diagnoses included pneumonia (n = 9), urosepsis (n = 5), peritonitis (n = 4), and cellulitis (n = 2). Two patterns of cortisol secretion were identified. In Group A, serum cortisol levels were greater than 400 nmol/L and gradually decreased (n = 14). In Group B, levels were less than 400 nmol/L and remained below normal (n = 6). In Group A, 2 patients died (14.3%), whereas in Group B, 5 died (83.3%) (p < 0.05). The Simplified Acute Physiology Score (SAPS) was higher, intitial serum cortisol levels were lower, and serum lactate levels were higher in the nonsurvivors. In a logistical regression model, SAPS was the only independent predictor of death; when this variable was removed from the model, decreased initial serum cortisol was also predictive. Increased serum lactate was strongly associated with mortality. There appears to be an association between decreased initial serum cortisol and mortality in patients with severe septic shock.

Diclectin® (DCL) is an effective antiemetic used for relief of nausea and vomiting in pregnancy. It is unknown whether DCL is effective in the prevention of postoperative nausea and vomiting (PONV). We conducted a randomized, stratified, double-blind placebo-controlled trial to examine the incidence of PONV in women undergoing elective laparoscopic tubal ligation in the day surgery setting. DCL (doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg) was administered orally the night before surgery, the morning of surgery, and upon hospital discharge. We enrolled 146 women in the trial, 127 of whom were included in the effectiveness analysis and 102 of whom were included in the efficacy analysis. We did not detect a difference in the incidence of nausea and vomiting in the first six hours postoperatively after adjusting for additional antiemetics administered. Patients receiving DCL as compared with placebo were significantly less likely to experience vomiting six to 24 hr postoperatively [5/59 (8.5%)vs 14/55 (25.4%),P < 0.0 17], Treated patients tended to return to work earlier than those who received placebo (1.74vs 3.7 daysP = NS). Perioperative oral DCL reduces the incidence of postoperative vomiting in women undergoing elective laparoscopic tubal ligation, and may accelerate return to work.

To determine the use of ventilator circuit and secretion management strategies in France and Canada.Binational cross-sectional survey.Intensive care unit (ICU) directors in French and Canadian university hospitals.We compared responses between countries regarding the use of seven circuit and secretion strategies, the rationales against their use, decisional responsibility for these strategies, whether ventilator-associated pneumonia (VAP) practice was audited, and whether VAP prevention guidelines addressing these strategies were used.The response rate was 72/84 (85.7%) for French and 31/32 (96.9%) for Canadian ICUs. Endotracheal intubation was predominantly oral in both countries. Changing the ventilator circuits only for every new patient was more frequent in France than in Canada (p.0001). Heated humidifiers were used more in Canada than France (p = .0003). Closed endotracheal suctioning was used more frequently in Canada (p.0001). In both countries, subglottic secretion drainage and kinetic beds were rarely used. Semirecumbent positioning was reported more often by French than Canadian ICUs (p = .003). Reasons for nonuse of these strategies included adverse effects (heat and moisture exchangers), cost (kinetic beds), lack of convincing benefit (subglottic secretion drainage), and nurse inconvenience (semirecumbency). Decisional responsibility for each strategy differed among institutions. VAP prevention practice was periodically reviewed in 53% of French and 68% of Canadian ICUs (p = .20). VAP prevention guidelines were used in 64% and 30% of these ICUs, respectively (p = .002).Our study does not support the notion that published recommendations substantially impact reported use of several ventilator circuit and secretion management strategies. Based on the use of more frequent ventilator circuit changes, closed suctioning systems, heated humidifiers, and respiratory therapists, ventilator circuit and secretion management practice appears more costly in Canada than in France.

Purpose. —To resolve discrepancies in previous systematic overviews and provide estimates of the effect of stress ulcer prophylaxis on gastrointestinal bleeding, pneumonia, and mortality in critically ill patients. Data Identification. —Computerized search of published and unpublished research, bibliographies, pharmaceutical and personal files, and conference abstract reports. Study Selection. —Independent review of 269 articles identified 63 relevant randomized trials for inclusion. Data Abstraction. —We made independent, duplicate assessment of the methodologic quality, population, intervention, and outcomes of each trial. Results. —The source of discrepancies between prior meta-analyses included incomplete identification of relevant studies, differential inclusion of non—English language and nonrandomized trials, different definitions of bleeding, provision of additional information through direct correspondence with authors, and different statistical methods. The current overview demonstrates that prophylaxis with histamine2-receptor antagonists decreases the incidence of overt gastrointestinal bleeding (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.42 to 0.79) and clinically important bleeding (OR, 0.44; 95% CI, 0.22 to 0.88). There is a trend toward decreased overt bleeding when antacids are compared with no therapy (OR, 0.66; 95% CI, 0.37 to 1.17). Histamine2-receptor antagonists and antacids are associated with a trend toward lower clinically important bleeding rates than sucralfate is. There is a trend toward an increased risk of pneumonia associated with histamine2-receptor antagonists as compared with no prophylaxis (OR, 1.25; 95% CI, 0.78 to 2.00). Sucralfate is associated with a lower incidence of nosocomial pneumonia when compared with antacids (OR, 0.80; 95% CI, 0.56 to 1.15) and histamine2-receptor antagonists (OR, 0.77; 95% CI, 0.60 to 1.01). Sucralfate is also associated with a reduced mortality rate (OR, 0.73; 95% CI, 0.54 to 0.97) relative to antacids and to histamine2-receptor antagonists (OR, 0.83; 95% CI, 0.63 to 1.09). Conclusions. —Our results emphasize the need for registries to include all randomized trials and demonstrate the importance of explicit methodology for systematic reviews. There is strong evidence of reduced clinically important gastrointestinal bleeding with histamine2-receptor antagonists. Sucralfate may be as effective in reducing bleeding as gastric pH—altering drugs and is associated with lower rates of pneumonia and mortality. However, the data are insufficient to determine the net effect of sucralfate compared with no prophylaxis. (JAMA. 1996;275:308-314)

Objectives: To examine the oxygen-prescribing habits and monitoring patterns on a medical teaching ward and to review the literature in this area. Design: A continuous quality improvement study. Setting: A 29-bed medical clinical teaching unit in a 453-bed university-affiliated tertiary care hospital. Patients: We studied 50 consecutive patients who required 79 oxygen treatments. Methods: We recorded the indication, prescriber, documentation of prior hypoxemia, method and mode of delivery, oxygenation assessment after initiation, and duration of therapy. Results: Patients received oxygen for a mean (±SD) of 4.7±4.5 days. Oxygen therapy was ordered on a continuous basis 60.3% of the time. It was ordered by house staff in 54 cases (68%); nurses initiated oxygen therapy in 14 cases (18%) but discontinued it more often than any other health care workers. The most common indications for starting oxygen therapy were dyspnea and tachypnea. In 15 patients (30%), none of the American College of Chest Physicians and National Heart, Lung, and Blood Institute criteria for starting oxygen therapy were fulfilled. For 16 patients (32%), arterial blood gas values were measured within 1 hour of oxygen administration; for 29 patients, oximetry was performed. For 9 patients (18%), no testing of adequate oxygenation was performed within 24 hours. Oxygenation status was assessed daily for 23 patients (46%). Conclusions: Oxygen prescribing and monitoring practices were suboptimal on our busy medical teaching ward. Practice guidelines based on best available evidence are needed to increase the efficiency of oxygen use. A physiologic, multidisciplinary educational focus on the benefits and hazards of supplemental oxygen is necessary, and randomized trials of such educational interventions should be conducted. Arch Intern Med. 1996;156:1797-1801

Purpose. —To resolve discrepancies in previous systematic overviews and provide estimates of the effect of stress ulcer prophylaxis on gastrointestinal bleeding, pneumonia, and mortality in critically ill patients. Data Identification. —Computerized search of published and unpublished research, bibliographies, pharmaceutical and personal files, and conference abstract reports. Study Selection. —Independent review of 269 articles identified 63 relevant randomized trials for inclusion. Data Abstraction. —We made independent, duplicate assessment of the methodologic quality, population, intervention, and outcomes of each trial. Results. —The source of discrepancies between prior meta-analyses included incomplete identification of relevant studies, differential inclusion of non—English language and nonrandomized trials, different definitions of bleeding, provision of additional information through direct correspondence with authors, and different statistical methods. The current overview demonstrates that prophylaxis with histamine2-receptor antagonists decreases the incidence of overt gastrointestinal bleeding (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.42 to 0.79) and clinically important bleeding (OR, 0.44; 95% CI, 0.22 to 0.88). There is a trend toward decreased overt bleeding when antacids are compared with no therapy (OR, 0.66; 95% CI, 0.37 to 1.17). Histamine2-receptor antagonists and antacids are associated with a trend toward lower clinically important bleeding rates than sucralfate is. There is a trend toward an increased risk of pneumonia associated with histamine2-receptor antagonists as compared with no prophylaxis (OR, 1.25; 95% CI, 0.78 to 2.00). Sucralfate is associated with a lower incidence of nosocomial pneumonia when compared with antacids (OR, 0.80; 95% CI, 0.56 to 1.15) and histamine2-receptor antagonists (OR, 0.77; 95% CI, 0.60 to 1.01). Sucralfate is also associated with a reduced mortality rate (OR, 0.73; 95% CI, 0.54 to 0.97) relative to antacids and to histamine2-receptor antagonists (OR, 0.83; 95% CI, 0.63 to 1.09). Conclusions. —Our results emphasize the need for registries to include all randomized trials and demonstrate the importance of explicit methodology for systematic reviews. There is strong evidence of reduced clinically important gastrointestinal bleeding with histamine2-receptor antagonists. Sucralfate may be as effective in reducing bleeding as gastric pH—altering drugs and is associated with lower rates of pneumonia and mortality. However, the data are insufficient to determine the net effect of sucralfate compared with no prophylaxis. (JAMA. 1996;275:308-314)