A systematic review of the impact of sedation practice in the ICU on resource use, costs and patient safety.

INTRODUCTION: Patients in intensive care units (ICUs) often receive sedation for prolonged periods. In order to better understand the impact of sub-optimal sedation practice on outcomes, we performed a systematic review, including observational studies and controlled trials which were conducted in sedated patients in the ICU and which compared the impact of changes in or different protocols for sedation management on economic and patient safety outcomes. METHODS: We searched Medline, Embase and CINAHL online literature databases from 1988 to 15th May 2008 and hand searched conferences. English-language studies set in the ICU, in sedated adult humans on mechanical ventilation, which reported the impact of sedation practice on cost and resource use and patient safety outcomes, were included. All abstracts were reviewed twice by two independent reviewers, with all conflicts resolved by a third reviewer, to check that they met the review inclusion criteria. Full-text papers of all included studies were retrieved and again reviewed twice against inclusion criteria. Data were doubly extracted from studies. Study aims, design, population, and outcomes including duration of mechanical ventilation, length of stay in ICU and hospital, costs and rates of mortality and adverse events were extracted. Due to heterogeneity between study designs and outcomes reported, no quantitative data synthesis such as meta-analysis was possible. RESULTS: Included studies varied in design, patient population and aim, with the majority being before-after studies. Overall, studies showed that improvements in sedation practice, such as the introduction of guidelines and protocols, or daily interruption of sedation, were associated with improvements in outcomes including ICU and hospital length of stay, duration of mechanical ventilation, and costs. Mortality and the incidence of nosocomial infections were also reduced. CONCLUSIONS: Systematic interventions to improve sedation practice and maintain patients at an optimal sedation level in the ICU may improve patient outcomes and optimize resource usage.

The incidence of sub-optimal sedation in the ICU: a systematic review.

INTRODUCTION: Patients in intensive care units (ICUs) are generally sedated for prolonged periods. Over-sedation and under-sedation both have negative effects on patient safety and resource use. We conducted a systematic review of the literature in order to establish the incidence of sub-optimal sedation (both over- and under-sedation) in ICUs. METHODS: We searched Medline, Embase and CINAHL (Cumulative Index to Nursing and Allied Health Literature) online literature databases from 1988 to 15 May 2008 and hand-searched conferences. English-language studies set in the ICU, in sedated adult humans on mechanical ventilation, which reported the incidence of sub-optimal sedation, were included. All abstracts were reviewed twice by two independent reviewers, with all conflicts resolved by a third reviewer, to check that they met the review inclusion criteria. Full papers of all included studies were retrieved and were again reviewed twice against inclusion criteria. Data were doubly extracted. Study aims, design, population, comparisons made, and data on the incidence of sub-optimal, optimal, over-sedation or under-sedation were extracted. RESULTS: There was considerable variation between included studies in the definition of optimal sedation and in the scale or method used to assess sedation. Across all included studies, a substantial incidence of sub-optimal sedation was reported, with a greater tendency toward over-sedation. CONCLUSIONS: Our review suggests that improvements in the consistent definition and measurement of sedation may improve the quality of care of patients within the ICU.

Patient-reported outcomes from a randomized phase III trial of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis.

BACKGROUND: The phase III MONARCH randomized controlled trial (NCT02332590) demonstrated that in patients with rheumatoid arthritis (RA), sarilumab (anti-interleukin-6 receptor monoclonal antibody) monotherapy is superior to adalimumab monotherapy in reducing disease activity and signs and symptoms of RA, as well as in improving physical function, with similar rates of adverse and serious adverse events. We report the effects of sarilumab versus adalimumab on patient-reported outcomes (PROs). METHODS: Patients with active RA intolerant of, or inadequate responders to, methotrexate were randomized to sarilumab 200 mg plus placebo every 2 weeks (q2w; n = 184) or adalimumab 40 mg plus placebo q2w (n = 185). Dose escalation to weekly administration of adalimumab or matching placebo was permitted at week 16. PROs assessed at baseline and weeks 12 and 24 included patient global assessment of disease activity (PtGA), pain and morning stiffness visual analogue scales (VASs), Health Assessment Questionnaire Disability Index (HAQ-DI), 36-item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Rheumatoid Arthritis Impact of Disease (RAID), and rheumatoid arthritis-specific Work Productivity Survey (WPS-RA). Between-group differences in least-squares mean (LSM) changes from baseline were analyzed. p < 0.05 was considered significant for PROs in a predefined hierarchy. For PROs not in the hierarchy, nominal p values are provided. Proportions of patients reporting improvements greater than or equal to the minimal clinically important difference (MCID) and achieving normative values were assessed. RESULTS: At week 24, sarilumab treatment resulted in significantly greater LSM changes from baseline than adalimumab monotherapy in HAQ-DI (p < 0.005), PtGA (p < 0.001), pain VAS (p < 0.001), and SF-36 Physical Component Summary (PCS) (p < 0.001). Greater LSM changes were reported for sarilumab than for adalimumab in RAID (nominal p < 0.001), morning stiffness VAS (nominal p < 0.05), and WPS-RA (nominal p < 0.005). Between-group differences in FACIT-F and SF-36 Mental Component Summary (MCS) were not significant. More patients reported improvements greater than or equal to the MCID in HAQ-DI (nominal p < 0.01), RAID (nominal p < 0.01), SF-36 PCS (nominal p < 0.005), and morning stiffness (nominal p < 0.05), as well as greater than or equal to the normative values in HAQ-DI (p < 0.05), with sarilumab versus adalimumab. CONCLUSIONS: In parallel with the clinical efficacy profile previously reported, sarilumab monotherapy resulted in greater improvements across multiple PROs than adalimumab monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02332590 . Registered on 5 January 2015.

Sarilumab improves patient-reported outcomes in rheumatoid arthritis patients with inadequate response/intolerance to tumour necrosis factor inhibitors.

OBJECTIVE: To evaluate effects of the anti-interleukin-6 receptor monoclonal antibody sarilumab administered with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on patient-reported outcomes (PROs) in the TARGET trial in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitors (TNF-IR). METHODS: 546 patients (81.9% female, mean age 52.9 years) were randomised to placebo, sarilumab 150 or 200 mg subcutaneously every 2 weeks + csDMARDs. PROs included patient global assessment (PtGA); pain and morning stiffness visual analogue scales; Health Assessment Questionnaire Disability Index (HAQ-DI); Short Form-36 Health Survey (SF-36); FACIT-Fatigue (FACIT-F); Work Productivity Survey-Rheumatoid Arthritis (WPS-RA) and Rheumatoid Arthritis Impact of Disease (RAID). Changes from baseline at weeks 12 and 24 were analysed using a mixed model for repeated measures; post hoc analyses included percentages of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores ≥ normative values. RESULTS: Sarilumab + csDMARDs doses resulted in improvements from baseline at week 12 vs placebo + csDMARDs in PtGA, pain, HAQ-DI, SF-36 and FACIT-F that were maintained at week 24. Sarilumab improved morning stiffness and reduced the impact of RA on work, family, social/leisure activities participation (WPS-RA) and on patients' lives (RAID). Percentages of patients reporting improvements ≥MCID and ≥ normative scores were greater with sarilumab than placebo. CONCLUSIONS: In patients with TNF-IR RA, 150 and 200 mg sarilumab + csDMARDs resulted in clinically meaningful patient-reported benefits on pain, fatigue, function, participation and health status at 12 and 24 weeks that exceeded placebo + csDMARDs, and were consistent with the clinical profile previously reported. TRIAL REGISTRATION NUMBER: NCT01709578; Results.