Ian Michael Ball

Purpose: To determine the relationship between patient characteristics and treatment fidelity in adult ICU patients enrolled in the CYCLE Pilot randomized controlled trial. Method: We conducted a secondary analysis of a pilot trial in which patients were randomly assigned to in-bed cycling plus usual physiotherapy (PT) or usual PT alone. We calculated protocol fidelity for each patient as the proportion of planned days when the assigned treatment was delivered or did not occur due to medical instability. Using multiple linear regression, we assessed the association of protocol fidelity with admission severity of illness, sex, assigned treatment, baseline comorbidities, and frailty. Results: Sixty-six patients were enrolled in this pilot trial (36 cycling, 30 usual PT) with a median (1st–3rd quartiles) protocol fidelity of 100% (83%–100%), 89% (75%–100%) in cycling and 100% (90%–100%) in usual PT. By regression analysis, assignment to in-bed cycling plus usual PT was associated with a 9.7% (95% CI: –17.8, –1.5) lower protocol fidelity compared to usual PT alone. Conclusions: We found those in the usual PT group had higher protocol fidelity; no other associations were found. This study offers an analytic approach for trialists to assess treatment fidelity for rehabilitation interventions in clinical trials.

In comatose patients at risk of death by neurologic criteria (DNC), spinal-mediated movements (SMM) and movements of unclear neuroanatomic origin (MUO) are

Testosterone for the Management of Traumatic Hemorrhage: A Systematic Review Wang JB, Russel J, Law B, Boersma D, Iansavitchene A, Laverty C, Priestap F, Smith S, Vogt K, Ball IM Ahead of Print. Publication Type: Journal Article Background: Testosterone may assist in traumatic hemostasis given its well-established role in erythropoiesis, platelet activation, and vasoconstriction; […] Testosterone for the Management of Traumatic Hemorrhage: A Systematic Review Wang JB, Russel J, Law B, Boersma D, Iansavitchene A, Laverty C, Priestap F, Smith S, Vogt K, Ball IM Ahead of Print. Publication Type: Journal Article Background: Testosterone may assist in traumatic hemostasis given its well-established role in erythropoiesis, platelet activation, and vasoconstriction; […]

OBJECTIVE: To determine the impact of using dynamic measures of fluid responsiveness in guiding the resuscitation of adult patients with sepsis and septic shock. DATA SOURCE: We searched MEDLINE, Embase, and unpublished sources from inception to February 3, 2025. STUDY SELECTION: We included randomized controlled trials (RCTs) that evaluated the use of dynamic measures of fluid responsiveness to guide resuscitation compared with any other method in patients with sepsis and septic shock. DATA EXTRACTION: We collected data regarding study and patient characteristics, definitions of fluid responsiveness, modality for assessing fluid responsiveness, and outcome data. We performed a random-effects meta-analysis and rated the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation framework. DATA SYNTHESIS: We included nine eligible RCTs (n = 698 patients). The use of dynamic measures of fluid responsiveness to guide IV fluid (IVF) administration of patients with septic shock probably reduces 28-day mortality (relative risk] 0.61; 95% CI, 0.42–0.90, moderate certainty), may reduce the risk of acute kidney injury (AKI) (RR 0.66; 95% CI, 0.44–0.98, low certainty), and cumulative fluid balance on day 3 (mean difference –1.57L; 95% CI, –2.44 L to –0.69 L, low certainty). The use of dynamic measures of fluid responsiveness has an uncertain effect on ICU mortality, ICU and hospital length of stay, need for and duration of mechanical ventilation, need for renal replacement therapy, vasoactive medication administration, duration of vasopressor use, and IVF administration on day 1. CONCLUSIONS: In adult patients with sepsis and septic shock, using dynamic measures of fluid responsiveness may improve survival and reduce the risk of AKI. Future studies should evaluate the impact of this intervention on other important clinical outcomes and determine the comparative efficacy of specific modalities for assessing fluid responsiveness.

Objective: This is a pilot study to determine the feasibility of a multicentre stepped wedge cluster randomized trial of implementing the 2013 World Society of the Intraabdominal Compartment Syndrome (WSACS) guidelines as an intervention to treat intraabdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in critically ill patients. Design: Single-centre before-and-after trial, with an observation / baseline period of 3 months followed by a 9-month intervention period. Setting: A 35 bed medical-surgical-trauma intensive care unit in a tertiary level, Canadian hospital. Patients: Recruitment from consecutively admitted adult intensive care unit patients. Intervention: In the intervention period, treatment teams were prompted to implement WSACS interventions in all patients diagnosed with IAH. Measurements and Main Results: 129 patients were recruited, 59 during the observation period and 70 during the intervention period. Only 17.0% and 12.9%, respectively, met diagnostic criteria for IAH. Many recruited patients did not have intraabdominal pressures measured regularly per study protocol. There was no difference in ICU mortality for patients in either cohort or between those with and without IAH. Conclusions: The incidence of IAH in our patient population has decreased significantly since 2015. This is likely due to a significant change in routine care of critically ill patients, especially with respect to judicious goal-directed fluid resuscitation. Patient recruitment and protocol adherence in this study were low, exacerbated by other staffing and logistical pressures during the study period. We conclude that a larger multicentre trial is unlikely to yield evidence of a detectable treatment effect.

Background: Survivors of critical illness are at risk of developing physical dysfunction following intensive care unit (ICU) discharge. ICU-based rehabilitation interventions, such as early in-bed cycle ergometry, may improve patients’ short-term physical function. Objective: Before unblinding and trial database lock, we describe a prespecified statistical analysis plan (SAP) for the CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) randomized controlled trial (RCT). Methods: CYCLE is a 360-patient, international, multicenter, open-label, parallel-group RCT (1:1 ratio) with blinded primary outcome assessment at 3 days post-ICU discharge. The principal investigator and statisticians of CYCLE prepared this SAP with approval from the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes (including adverse events) and describes the planned primary, secondary, and subgroup analyses. The primary outcome of the CYCLE trial is the Physical Function Intensive Care Unit Test-scored (PFIT-s) at 3 days post-ICU discharge. The PFIT-s is a reliable and valid performance-based measure. We plan to use a frequentist statistical framework for all analyses. We will conduct a linear regression to evaluate the primary outcome, incorporating randomization as an independent variable and adjusting for age (≥65 years versus <65 years) and center. The regression results will be reported as mean differences in PFIT-s scores with corresponding 95% CIs and P values. We consider a 1-point difference in PFIT-s score to be clinically important. Additionally, we plan to conduct 3 subgroup analyses: age (≥65 years versus <65 years), frailty (Baseline Clinical Frailty Scale ≥5 versus <5), and sex (male versus female). Results: CYCLE was funded in 2017, and enrollment was completed in May 2023. Data analyses are complete, and the first results were submitted for publication in 2024. Conclusions: We developed and present an SAP for the CYCLE RCT and will adhere to it for all analyses. This study will add to the growing body of evidence evaluating the efficacy and safety of ICU-based rehabilitation interventions. Trial Registration: ClinicalTrials.gov NCT03471247; https://clinicaltrials.gov/ct2/show/NCT03471247 and NCT02377830; https://clinicaltrials.gov/ct2/show/NCT02377830 International Registered Report Identifier (IRRID): RR1-10.2196/54451

The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).