Mayur Bipin Patel

Introduction: Cognitive impairment after critical illness is a common occurrence that has a profound impact on millions of people worldwide each year. Currently, no interventions after critical illness have been found to promote cognitive recovery. Cognitive training has shown promise in other populations (eg, community-dwelling adults), predominantly in improving the trained cognitive domain (eg, memory, reasoning or executive function). In pilot work, in-person cognitive training with intensive care unit (ICU) survivors was found to not only improve the trained domain but also may reduce disabilities in daily function. Computerised cognitive rehabilitation (CCR) is a more scalable option, which we have demonstrated the feasibility of use among ICU survivors. Whether CCR is efficacious in ICU survivors remains unknown. Methods and analysis: The Returning to Everyday Tasks Utilising Rehabilitation Networks-III (RETURN-III) study is a multicentre, randomised, double-blinded, parallel group controlled trial testing the hypothesis that CCR versus active control will result in less cognitive impairment after critical illness. Adult patients who recently experienced acute respiratory failure or shock in medical and surgical ICUs at two hospitals in Nashville (TN, USA) will be enrolled. Participants will be randomised within 12 weeks of hospital discharge to a 12-week home-based programme of CCR (or control), with the goal of five 30 min sessions per week. In-person assessments will be performed at baseline, 3 months and 12 months after randomisation. The primary outcome is global cognitive function 3 months after randomisation using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score. Secondary outcomes will include 12-month RBANS global cognitive function, 3-month and 12-month subjective cognition by the Cognitive Self-Report Questionnaire, daily function related to cognition by the Functional Activities Questionnaire and processing speed/executive function by Trail Making Test part B. With an anticipated enrolment of 160 patients, the study will have at least 80% power to detect a 7-point or higher difference in RBANS cognition scores between the two groups (<0.5 SD based on age-adjusted population norms) with a type 1 error rate of 5%. Ethics and dissemination: The RETURN-III study was approved by the institutional review boards at each participating site. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences following completion of data collection. Trial registration number: NCT04353804 .

Blood transfusion before arrival at a hospital reduces mortality from traumatic hemorrhage and shock. Whether transfusion with whole blood is more beneficial than transfusion with blood components is uncertain, as are the effects of the length of time that blood products are in storage between donation and transfusion. In this pragmatic, multicenter, phase 3, cluster-randomized trial, we assigned 44 air medical bases in a 2:1 ratio to the use of up to 2 units of whole blood or as-indicated blood components (plasma, red cells, or both) for prehospital transfusion in trauma patients during 1-month blocks. The primary outcome was death from any cause within 30 days after randomization. An observational substudy assessed outcomes according to the storage age of whole blood. Of 1020 eligible patients transported to hospitals by the air bases, 715 were assigned to receive whole blood and 305 to receive blood components; 695 and 298, respectively, were included in the primary analysis. Mortality at 30 days was 25.9% in the whole-blood group and 20.5% in the component group (adjusted odds ratio, 1.24; 95% confidence interval [CI], 0.87 to 1.76; P = 0.24). No substantial between-group differences in adverse events were observed. In the observational substudy, 30-day mortality was 27.1% among 210 patients who received whole blood with a storage age of 15 to 21 days and 26.4% among 443 patients who received whole blood with a storage age of 1 to 14 days (adjusted odds ratio, 0.99; 95% CI, 0.74 to 1.32). In injured patients with hemorrhagic shock, the use of whole blood for prehospital transfusion did not result in lower 30-day mortality than the use of blood components. (Funded by the Congressionally Directed Medical Research Programs and the U.S. Army Medical Research Acquisition Activity; TOWAR ClinicalTrials.gov number, NCT04684719.).

Introduction: Nearly half of patients who receive invasive mechanical ventilation for acute respiratory failure require over 4 days of ventilator support, each day of which is associated with increased morbidity, mortality and cost. Many of these patients develop expiratory muscle atrophy and weakness, which are linked to failed extubation and weaning. We seek to test the hypothesis that exhalation synchronised abdominal functional electrical stimulation reduces mechanical ventilation duration. Methods and analysis: This pivotal superiority trial will be performed in up to 30 intensive care units (ICUs) in the USA, France, the Netherlands and Australia. Adults (≥22 years old) who have been mechanically ventilated for 24–96 hours and are expected to remain ventilated for another 24+ hours are potentially eligible. We will recruit participants until 150 successful liberations from mechanical ventilation occur. To achieve this, we estimate that a maximum of 272 participants will be randomised in a 1:1 ratio to receive 30 min of active exhalation synchronised abdominal functional electrical stimulation (vs sham). The intervention will be applied using the VentFree Respiratory Muscle Stimulator two times per day, a minimum of 5 days per week, for a maximum of 28 days or until ICU discharge. The primary outcome is time from first intervention to successful liberation from mechanical ventilation. Secondary outcomes include cough peak flow (CPF) and maximum expiratory pressure (MEP) at 24 hours post-extubation, hospital and ICU length of stay, reintubations, complications, ICU readmissions, 90-day mortality and quality of life. The participant, clinical team and outcome assessor are blinded to group allocation. A positive outcome has the potential to improve patient-centred outcomes in ICUs. Ethics and dissemination: This study was approved by local ethics institutions in the USA, Australia, France and the Netherlands. We describe the methods herein using the Standard Protocol Items for Randomised Trials framework and discuss key design decisions. The results will be disseminated through peer-reviewed journal publications, conference presentations and clinicaltrials.gov updates. Individual country-level approvals are as follows: France: Ethics committee: Comité de Protection des Personnes Ile-de-France X. Reference numbers: CPP 27-2024; RCB 2024-A00559-38. Initial approval date: 14 May 2024. Australia: Ethics committee: South Eastern Sydney Local Health District Human Research Ethics Committee. Reference number: 2022/ETH02724. Initial approval date: 21 March 2023. Netherlands: Ethics committee: Medisch Ethische Toetsings Commissie Erasmus MC. Reference numbers: MEC-2023-0364; NL84195.000.23. Initial approval date: 30 April 2024. USA: Ethics committee: WCG IRB. IRB tracking number: 20214073. Initial approval date: 13 March 2023. All participating sites are currently approved and operating under protocol version 09 or later. Trial registration number: NCT05759013 . Registered 8 March 2023.

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) syndrome are potentially fatal skin conditions frequently cared for in burn units. In a national database study, we studied the demographics and outcomes of this patient population. This retrospective cohort study included patient admissions for SJS/TEN. Patient demographics and outcomes were compared and adjusted for age, sex, inhalation injury, and percent total body surface area (TBSA). Logistical regression was used for binary outcomes, and linear regression was used for continuous outcomes. All outcomes were described in reference to the entire disease continuum (SJS/TEN) and each specific disease subcohort (SJS, SJS-TEN overlap, and TEN). Of 271 971 patients queried within the Noncommercial Burn Research Dataset, 2416 patients had a diagnosis of SJS/TEN. These patients were statistically more likely to be older (48 ± 22 years vs 36 ± 22 years), housed (1% vs 2%), females (57% vs 34%), and have a higher mean TBSA (8 ± 13% vs 7 ± 12%). In multivariable analysis, SJS/TEN was associated with increased risk of unplanned intubations (odds ratio [OR] 1.69) and pneumonia (OR 1.26), but not respiratory failure (OR 0.36). There was also an increased risk for sepsis (OR 1.43). Patients were significantly more likely to have a shorter hospital LOS (OR −3.7). There was no significant difference in mortality. In subcohort analysis, a stepwise increase in morbidity and mortality was observed when comparing SJS, SJS-TEN overlap, and TEN. Stevens–Johnson syndrome/TEN is a rare but extremely morbid disease continuum that frequently affects female patients and results in increased respiratory and alternative complications.

Hemorrhage is the leading cause of preventable death on the battlefield, yet combat medics lack clinical decision support systems to help stratify hemorrhage risk in trauma casualties. We previously trained the Automated Processing of the Physiological Registry for Assessment of Injury Severity — Hemorrhage Risk Index (APPRAISE-HRI) software to associate patterns in vital signs (heart rate and blood pressure) collected from trauma patients with three HRI levels: I (low), II (average), or III (high). To independently validate APPRAISE-HRI and obtain U.S. Food and Drug Administration (FDA) clearance, we collected trauma registry and continuous vital sign data from 5895 trauma patients (543 with hemorrhagic injuries and 5352 controls) in an emergency department or during prehospital transport to one of eight medical centers. The study outcome was hemorrhagic injury, defined by documented injuries and blood transfusion. Using the likelihood ratio to assess the ability of APPRAISE-HRI to stratify hemorrhage risk, we found that hemorrhagic patients were 6.88 times as likely as controls to be at level III, strongly suggesting the presence of hemorrhage at this level. Similarly, hemorrhagic patients were 0.18 times as likely as controls to be at level I, suggesting the absence of hemorrhage at this level. Hemorrhagic patients were almost as likely as controls to be at level II (0.70 times as likely). Subsequently, the U.S. Department of Defense obtained FDA 510(k) clearance for the artificial intelligence–enabled APPRAISE-HRI Class II device (K233249), the first software as a medical device approved for assessing hemorrhage risk in trauma patients, allowing for triage and identification of casualties who need immediate attention and evacuation. (Funded by the U.S. Army Medical Materiel Development Activity and the Combat Casualty Care Program Area Directorate (CCCPAD) of the U.S. Army Medical Research and Development Command (USAMRDC), Fort Detrick, MD and others.)

The delta shock index (ΔSI), defined as the change in shock index (SI) over time, is associated with hospital morbidity and mortality, but prehospital studies about ΔSI are limited. We investigate the association of prehospital ΔSI with mortality and resource utilization, hypothesizing that increases in SI among field trauma patients are associated with increased mortality and blood product transfusion. We performed a multicenter, retrospective, observational study from the Linking Investigators in Trauma and Emergency Services (LITES) network. We obtained data from January 2017 to June 2021. We fit logistic regression models to evaluate the association between an increase ΔSI > 0.1 and 28-day mortality and blood product transfusion within 4 hours of emergency department (ED) arrival. We used negative binomial models to evaluate the association between ΔSI > 0.1 and days in hospital, intensive care unit (ICU), and on ventilator (up to 28 days). We identified 33,219 prehospital patients. We excluded burn patients and those without documented prehospital or ED heart rate or blood pressure, resulting in 30,511 cases for analysis. In adjusted analysis for the primary outcome of 28-day mortality, patients who had a ΔSI > 0.1 based on initial vital signs were 31% more likely to die (adjusted odds ratio (AOR) of 1.31, 95% CI 1.21-1.41) compared to those patients who had a ΔSI ≤0.1. These patients also spent 16% more days in hospital (adjusted incident rate ratio (AIRR) 1.16, 95% CI 1.14-1.19), 34% more days in ICU (AIRR 1.34, 95% CI 1.28-1.41), and 61% more days on ventilator (ARR 1.61, 95% CI 1.47-1.75). Additionally, patients with a ΔSI > 0.1 had higher odds of receiving blood products (AOR 2.00, 95% CI 1.88-2.12) within 4 hours of ED arrival. Models fit excluding hypotensive patients performed similarly. An increase of greater than 0.1 in the ΔSI was associated with increased 28-day mortality; increased days in hospital, in ICU, and on ventilator; and increased need for blood product transfusion within 4 hours of ED arrival. This association held true for initially normotensive patients. Validation and implementation are needed to incorporate ΔSI into prehospital and ED triage.

Objective: To quantify health utilities of the Glasgow Outcome Scale–Extended (GOSE) states after actual traumatic brain injury (TBI). Background: Recovery after TBI is measured using the GOSE, a validated clinical trial endpoint. A recent public survey quantified the health utilities of some GOSE states after hypothetical TBI as worse than death. However, no health utilities exist for disability after actual TBI. Methods: This national computer-adaptive survey followed Enhancing the Quality and Transparency of Health Research-Checklist for Reporting Results of Internet E-Surveys guidelines and recruited adult TBI survivors (injury >1 year prior) through their available surrogates. Using a standard gamble approach in randomized order, participants gave preferences for post-TBI categorical health states ranging from GOSE 2 to GOSE 8. We calculated median (interquartile range) health utilities for each GOSE state, from −1 (worse than death) to 1 (full health), with 0 as reference (death, GOSE 1). Results: Of 515 eligible, 298 surrogates (58%) consented and completed the scenarios on TBI survivors’ behalf. TBI survivors had a current median GOSE 5 (3–7). GOSE 2, GOSE 3, and GOSE 4 were rated worse than death by 89%, 64%, and 38%, respectively. The relationship was nonlinear, and intervals were unequal between states, with a bimodal distribution for GOSE 4. Conclusions: In this index study of actual post-TBI disability, poor neurological outcomes represented by GOSE 2 to GOSE 4 were perceived as worse than death by at least one in 3 survivors. Similar to previously reported public perceptions after a hypothetical TBI, these long-term perceptions may inform earlier post-TBI shared decision-making, as well as help shape value-based research and quality of care. Level of Evidence: Level II—economic and value-based evaluations.