Protocol adherence for continuously titrated interventions in randomized trials: an overview of the current methodology and case study.

BACKGROUND: The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration. DISCUSSION: Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75-80 mmHg) versus lower (60-65 mmHg) mean arterial pressure (MAP) targets for vasopressor therapy in shock. In this trial, potential protocol deviations were defined as MAP values outside the targeted range for >4 consecutive hours during vasopressor therapy without synchronous and consistent adjustments of vasopressor doses. An adjudication committee reviewed each potential deviation to determine if it was clinically-justified or not. There are four reasons for this contextual measurement and reporting of protocol adherence. First, between-arm separation is a robust measure of adherence to complex protocols. Second, adherence assessed by protocol deviations varies in function of the definition of deviations and the frequency of measurements. Third, distinguishing clinically-justified vs. not clinically-justified protocol deviations acknowledges clinically sensible bedside decision-making and offers a clear terminology before the trial begins. Finally, multiple metrics exist to report protocol deviations, which provides different information but complementary information on protocol adherence. CONCLUSIONS: In trials of interventions requiring continuous titration, metrics used for defining protocol deviations have a considerable impact on the interpretation of protocol adherence. Definitions for protocol deviations should be prespecified and correlated with between-arm separation, if it can be measured.

Surviving critical illness: what is next? An expert consensus statement on physical rehabilitation after hospital discharge.

BACKGROUND: The study objective was to obtain consensus on physical therapy (PT) in the rehabilitation of critical illness survivors after hospital discharge. Research questions were: what are PT goals, what are recommended measurement tools, and what constitutes an optimal PT intervention for survivors of critical illness? METHODS: A Delphi consensus study was conducted. Panelists were included based on relevant fields of expertise, years of clinical experience, and publication record. A literature review determined five themes, forming the basis for Delphi round one, which was aimed at generating ideas. Statements were drafted and ranked on a 5-point Likert scale in two additional rounds with the objective to reach consensus. Results were expressed as median and semi-interquartile range, with the consensus threshold set at ≤0.5. RESULTS: Ten internationally established researchers and clinicians participated in this Delphi panel, with a response rate of 80 %, 100 %, and 100 % across three rounds. Consensus was reached on 88.5 % of the statements, resulting in a framework for PT after hospital discharge. Essential handover information should include information on 15 parameters. A core set of outcomes should test exercise capacity, skeletal muscle strength, function in activities of daily living, mobility, quality of life, and pain. PT interventions should include functional exercises, circuit and endurance training, strengthening exercises for limb and respiratory muscles, education on recovery, and a nutritional component. Screening tools to identify impairments in other health domains and referral to specialists are proposed. CONCLUSIONS: A consensus-based framework for optimal PT after hospital discharge is proposed. Future research should focus on feasibility testing of this framework, developing risk stratification tools and validating core outcome measures for ICU survivors.

The Association between Frailty and Short-Term Outcomes in an Intensive Care Unit Rehabilitation Trial: An Exploratory Analysis.

BACKGROUND: Physical therapy initiated early in an ICU stay may reduce functional deficits in critically ill patients; however, the association of frailty with outcomes in those receiving early in-ICU rehabilitation is unknown. OBJECTIVE: To estimate the association between frailty and 3 outcomes in patients enrolled in an ICU randomized clinical trial (RCT). DESIGN: Exploratory secondary analyses of the CYCLE pilot RCT (NCT02377830). SETTING: 7 Canadian ICUs. PARTICIPANTS: Previously ambulatory critically ill adults. INTERVENTION: Participants were randomized to early in-bed cycling plus routine physiotherapy versus early routine physiotherapy alone. MEASUREMENTS: Using regression analyses, we modelled the association between pre-hospital Clinical Frailty Scale (CFS) scores, Physical Function in ICU Test-scored (PFIT-s), muscle strength, and mortality at hospital discharge, adjusting for illness severity (APACHE II) and the randomized intervention. We explored the influence of imputing mean PFIT-s and strength scores for decedents, and with listwise deletion of decedents in a sensitivity analysis. RESULTS: Of 66 patients, 2 had missing data, 2 had incomplete data, and 21 died by hospital discharge. At hospital discharge for 66 patients, frailty was not associated with PFIT-s (mean difference (MD) [95% CI]=0.20, [-2.08, 2.74]) or muscle strength (1.96, [-12.6, 16.6]). A sensitivity analysis yielded consistent results. Frailty was also not associated with hospital mortality (odds ratio 0.91, [0.28 to 2.93]). CONCLUSION: We found no association between pre-hospital frailty, physical function, strength, or mortality at hospital discharge in critically ill patients enrolled in an early rehabilitation trial. Larger sample sizes are needed to further explore the association of frailty with these outcomes at hospital discharge.

Dissemination and implementation of national physical activity, sedentary behaviour, and/or sleep guidelines among community-dwelling adults aged 18 years and older: a systematic scoping review and suggestions for future reporting and research.

Strategies for dissemination (purposive distribution of a guideline to specific audiences) and implementation (actions to support the general public in meeting guideline recommendations/behavioural benchmarks) of national movement guidelines (physical activity (PA), sedentary behaviour, and sleep) have yet to be synthesized. The purpose of this systematic scoping review was to identify strategies for dissemination and implementation of national PA, sedentary behaviour, and/or sleep guidelines among community-dwelling adults (aged >18 years) and/or stakeholders in Canada and analogous countries. Five search approaches (e.g., published literature, grey literature, targeted web-based, custom Google, and content expert consultation) identified records (e.g., empirical studies, organizational reports, website pages, or guideline messages) that discussed and/or evaluated dissemination or implementation strategies for a prespecified list of guidelines. A modified strategy classification system was developed to chart the data. Forty-seven reports met inclusion criteria. Dissemination strategies (n = 42) were more frequently reported than implementation strategies (n = 24). Implementation strategies were more frequently evaluated (n = 13 vs. 7 dissemination strategies) and associated with positive outcomes. The 13 studies that evaluated strategies were at high or serious risk of bias. We identified limited information about the dissemination and implementation of national movement guidelines and identified strategies were rarely evaluated. Greater efforts are required to increase the impact of guidelines among the general public and stakeholders and to build the evidence base in this field. (Open Science Framework registration: https://osf.io/4tyw3.) Novelty An adapted movement guideline dissemination and implementation strategy classification framework is provided. Knowledge translation efforts should be documented and evaluated to advance science and practice in the movement guideline field.

Hypotonic versus isotonic saline in hospitalised children: a systematic review.

BACKGROUND: The traditional recommendations which suggest that hypotonic intravenous (i.v.) maintenance fluids are the solutions of choice in paediatric patients have not been rigorously tested in clinical trials, and may not be appropriate for all children. AIMS: To systematically review the evidence from studies evaluating the safety of administering hypotonic versus isotonic i.v. maintenance fluids in hospitalised children. DATA SOURCES: Medline (1966-2006), Embase (1980-2006), the Cochrane Library, abstract proceedings, personal files, and reference lists. Studies that compared hypotonic to isotonic maintenance solutions in children were selected. Case reports and studies in neonates or patients with a pre-existing history of hyponatraemia were excluded. RESULTS: Six studies met the selection criteria. A meta-analysis combining these studies showed that hypotonic solutions significantly increased the risk of developing acute hyponatraemia (OR 17.22; 95% CI 8.67 to 34.2), and resulted in greater patient morbidity. CONCLUSIONS: The current practice of prescribing i.v. maintenance fluids in children is based on limited clinical experimental evidence from poorly and differently designed studies, where bias could possibly raise doubt about the results. They do not provide evidence for optimal fluid and electrolyte homoeostasis in hospitalised children. This systematic review indicates potential harm with hypotonic solutions in children, which can be anticipated and avoided with isotonic solutions. No single fluid rate or composition is ideal for all children. However, isotonic or near-isotonic solutions may be more physiological, and therefore a safer choice in the acute phase of illness and perioperative period.

Safety Climate Survey: reliability of results from a multicenter ICU survey.

BACKGROUND: It is important to understand the clinical properties of instruments used to measure patient safety before they are used in the setting of an intensive care unit (ICU). METHODS: The Safety Climate Survey (SCSu), an instrument endorsed by the Institute for Healthcare Improvement, the Safety Culture Scale (SCSc), and the Safety Climate Mean (SCM), a subset of seven items from the SCSu, were administered in four Canadian university affiliated ICUs. All staff including nurses, allied healthcare professionals, non-clinical staff, intensivists, and managers were invited to participate in the cross sectional survey. RESULTS: The response rate was 74% (313/426). The internal consistency of the SCSu and SCSc was 0.86 and 0.80, respectively, while the SCM performed poorly at 0.51. Because of poor internal consistency, no further analysis of the SCM was therefore performed. Test-retest reliability of the SCSu and SCSc was 0.92. Out of a maximum score of 5, the mean (SD) scores of the SCSu and SCSc were 3.4 (0.6) and 3.4 (0.7), respectively. No differences were noted between the three medical-surgical and one cardiovascular ICU. Managers perceived a significantly more positive safety climate than other staff, as measured by the SCSu and SCSc. These results need to be interpreted cautiously because of the small number of management participants. CONCLUSIONS: Of the three instruments, the SCSu and SCSc appear to be measuring one construct and are sufficiently reliable. Future research should examine the properties of patient safety instruments in other ICUs, including responsiveness to change, to ensure that they are valid outcome measures for patient safety initiatives.