A controlled trial of electronic automated advisory vital signs monitoring in general hospital wards*

OBJECTIVES: Deteriorating ward patients are at increased risk. Electronic automated advisory vital signs monitors may help identify such patients and improve their outcomes. SETTING: A total of 349 beds, in 12 general wards in ten hospitals in the United States, Europe, and Australia. PATIENTS: Cohort of 18,305 patients. DESIGN: Before-and-after controlled trial. INTERVENTION: We deployed electronic automated advisory vital signs monitors to assist in the acquisition of vital signs and calculation of early warning scores. We assessed their effect on frequency, type, and treatment of rapid response team calls; survival to hospital discharge or to 90 days for rapid response team call patients; overall type and number of serious adverse events and length of hospital stay. MEASUREMENTS AND MAIN RESULTS: We studied 9,617 patients before (control) and 8,688 after (intervention) deployment of electronic automated advisory vital signs monitors. Among rapid response team call patients, intervention was associated with an increased proportion of calls secondary to abnormal respiratory vital signs (from 21% to 31%; difference [95% confidence interval] 9.9 [0.1-18.5]; p = .029). Survival immediately after rapid response team treatment and survival to hospital discharge or 90 days increased from 86% to 92% (difference [95% confidence interval] 6.3 [0.0-12.6]; p = .04). Intervention was also associated with a decrease in median length of hospital stay in all patients (unadjusted p < .0001; adjusted p = .09) and more so in U.S. patients (from 3.4 to 3.0 days; unadjusted p < .0001; adjusted ratio [95% confidence interval] 1.03 [1.00-1.06]; p = .026). The time required to complete and record a set of vital signs decreased from 4.1 ± 1.3 mins to 2.5 ± 0.5 mins (difference [95% confidence interval] 1.6 [1.4-1.8]; p < .0001). CONCLUSIONS: Deployment of electronic automated advisory vital signs monitors was associated with an improvement in the proportion of rapid response team-calls triggered by respiratory criteria, increased survival of patients receiving rapid response team calls, and decreased time required for vital signs measurement and recording (NCT01197326)

Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study) : a randomised, double-blind, placebo-controlled phase 3 trial

Background There is an urgent unmet need for new therapies in amyotrophic lateral sclerosis. In a clinical study with healthy volunteers, levosimendan, a calcium sensitiser, was shown to improve neuromechanical efficiency and contractile function of the human diaphragm. We aimed to evaluate the safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis, with a focus on respiratory function. Methods The REFALS study is a randomised, double-blind, placebo-controlled phase 3 trial at 99 amyotrophic lateral sclerosis specialist centres in 14 countries worldwide. People with amyotrophic lateral sclerosis were eligible for participation if they were at least 18 years of age and had a sitting slow vital capacity (SVC) of 60-90% predicted. Participants were randomly assigned (2:1) by interactive web-response system to receive either levosimendan or placebo. The capsules for oral administration were identical in appearance to maintain blinding of participants and investigators. The primary endpoint was the change from baseline in supine SVC at 12 weeks, assessed as the percentage of predicted normal sitting SVC. The key secondary endpoint was the combined assessment of function and survival (CAFS) up to 48 weeks. Analyses were done in the intention-to-treat population, comprising all participants who were randomly assigned. This trial is registered at ClinicalTrials.gov (NCT03505021) and has been completed. An extension study (REFALS-ES; NCT03948178) has also been completed, but will be reported separately. Findings Between June 21, 2018, and June 28, 2019, 871 people were screened for the study, of whom 496 were randomly assigned either levosimendan (n=329) or placebo (n=167). Participants were followed up between June 27, 2018 and June 26, 2020, for a median duration of 50.1 (IQR 37.5-51.1) weeks. The median duration of treatment was 47.9 (IQR 26.4-48.1) weeks. Change from baseline in supine SVC at 12 weeks was -6.73% with levosimendan and -6.99% with placebo, with no significant difference between the treatments (estimated treatment difference 0.26%, 95% CI -2.03 to 2.55, p=0.83). Similarly, at week 48, CAFS did not differ between treatment groups (least squares mean change from baseline 10.69, 95% CI -15.74 to 37.12; nominal p value=0.43). The most frequent adverse events were increased heart rate (106 [33%] of 326 receiving levosimendan vs 12 [7%] of 166 receiving placebo), fall (85 [26%] vs 48 [29%]), headache (93 [29%] vs 36 [22%]), and dyspnoea (59 [18%] vs 32 [19%]). 33 (10%) participants allocated levosimendan and 20 (12%) assigned placebo died during the trial, mainly due to respiratory failure or progression of amyotrophic lateral sclerosis. Interpretation Levosimendan was not superior to placebo in maintaining respiratory function in a broad population with amyotrophic lateral sclerosis. Although levosimendan was generally well tolerated, increased heart rate and headache occurred more frequently with levosimendan than with placebo. The possibility of a clinically relevant subgroup of responsive individuals requires further evaluation