INTRODUCTION:We designed the Optimising Care in Critically Ill at the UCHealth by Liberalising the Target O₂ in Mechanically ventilated intensive care unit (ICU) Patients to determine the effectiveness of a multimodal educational and electronic health record order panel intervention in limiting occult hypoxaemia and hyperoxaemia in patients receiving invasive mechanical ventilation by targeting a prespecified oxygen saturation (SpO₂ 90%-96%) range. METHODS AND ANALYSIS:This trial is a pragmatic electronic health record-embedded, multisite, cluster-randomised, stepped-wedge implementation of a multimodal educational and electronic health record order panel intervention aimed at achieving a standardised intermediate target range of SpO₂ (90%-96%) or partial pressure of oxygen (PaO₂ 60-100 mm Hg) in mechanically ventilated adult patients admitted to the ICU across a 10 hospital health system that includes a large academic centre and smaller community hospitals.The primary endpoint is ventilator-free days to day 30, defined as the number of days alive and not receiving support through invasive mechanical ventilation following the first initiation of invasive mechanical ventilation in a participating ICU during the hospitalisation. Secondary outcomes include a variety of clinical endpoints: hospital-free days to day 30, all-cause mortality to day 90, need for supplemental oxygen at discharge and incidence of occult hypoxaemia and hypoxaemia. We will analyse primary and secondary endpoints using a mixed effects modelling framework, with specific distributions chosen depending on the type of outcome (eg, binary, count, ordinal, time-to-event). ETHICS AND DISSEMINATION:Research is performed under a waiver of informed consent for minimal-risk research, as approved by Colorado Multiple Institutional Review Board (24-0065). Results will be disseminated in peer-reviewed publications and at national and international conferences. TRIAL REGISTRATION NUMBER:NCT06501118.

Timely attention by home health care (HHC) and outpatient providers within one week after hospital discharge is associated with lower readmission rates among sepsis survivors. However, few patients nationwide receive this pattern of care. Improving care transitions for sepsis survivors is inhibited by barriers in sepsis identification, information transfer, care coordination, timely access to care, and patient engagement. The I-TRANSFER study was designed to address these gaps by implementing timely delivery of post-acute care (PAC) for sepsis survivors in real-world health care settings. The study aimed to identify, describe, and map the implementation strategies used to implement the I-TRANSFER care transition protocol. Five diverse health systems (16 hospitals), partnered with an affiliated HHC agency, participated in a Type 1 hybrid implementation science study. Through thematic inductive and deductive qualitative analysis, implementation determinants—barriers and facilitators—were identified, summarized, and presented back to the sites’ implementation teams. This paper reports on implementation strategies used to address barriers and implement the I-TRANSFER care transition protocol. Strategies are mapped to the Expert Recommendations for Implementing Change (ERIC) taxonomy. Implementors and researchers deployed strategies spanning 62

“Nudges” embedded in the electronic health record (EHR) facilitate desired decisions while preserving autonomy and may provide a scalable strategy to overcome the common implementation barrier of lack of knowledge about a best practice. We sought to test whether EHR-based nudges targeting two intensive care unit (ICU) clinician groups would safely increase evidence-based use of low tidal volume ventilation. We performed a stepped-wedge, cluster randomized, hybrid type 3 effectiveness-implementation trial in 12 ICUs from February 2021 to May 2023 to test three nudges targeting clinicians responsible for order entry and respiratory therapists responsible for operationalizing orders and documentation. A default ventilation order auto-populated a low tidal volume setting; an accountable justification order required a free-text justification to order high tidal volume; and an accountable justification flowsheet required a free-text justification to document delivery of high tidal volume. ICUs were randomly assigned to launch one of the two order nudges on a pre-specified date, followed by the flowsheet nudge six months thereafter. The primary outcome was fidelity to low tidal volume ventilation, defined as percentage of time during the first 72 h of ventilation with low tidal volumes. For additional contextual inquiry, we conducted qualitative interviews with ICU clinicians regarding their perspectives on low tidal volume ventilation and study nudges. The primary analysis included 4412 patients. Unadjusted median fidelity to low tidal volume ventilation was 45.7 https://clinicaltrials.gov/study/NCT04663802

Critical care quality metrics are evolving from simple mortality tracking toward patient-centered, real-time analytics. Anchored in 6 principles-meaningful, evidence-based, timely, responsive, integrated, and comparable-these metrics can drive sustained improvement when paired with advanced analytics. The challenge is to harness these tools without introducing bias, burden, or complexity. ICU leaders are pivotal in setting priorities, governing responsibly, and fostering a culture in which measurement fuels lasting gains in patient outcomes and system performance.

OBJECTIVES:Dyspnea is a common and distressing symptom; yet, how frequently and intensely mechanically ventilated patients experience dyspnea remains unclear. We performed a systematic review to identify the prevalence and severity of dyspnea in communicative, mechanically ventilated critically ill adults. We also identified factors associated with dyspnea in the short-term and long-term and potential management strategies. DATA SOURCES:We performed a systematic search of the following databases: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science Core Collection, PsycInfo, and CINAHL. DATA EXTRACTION:Our search strategy used variations of these terms: dyspnea, mechanical ventilation, and critical care. We included prospective observational studies and randomized controlled trials. Two independent reviewers screened citations and extracted data using a predrafted report form to examine dyspnea prevalence and severity, association with short-term and long-term outcomes, and interventions to mitigate dyspnea. DATA SYNTHESIS:Of 6290 records screened, we included 21 observational studies and 3 randomized controlled trials. We calculated percentages and 95% CIs for prevalence using Stata 17 se . Dyspnea was present in 475 of 1169 communicative, mechanically ventilated patients (40.6%, 95% CI, 37.8-43.5) and was found to be moderate to severe. In the lone study to examine long-term outcomes, dyspnea was associated with posttraumatic stress disorder (PTSD) at 90 days. Interventions to reduce dyspnea included: mechanical threshold inspiratory muscle training, ventilation adjustments, supplemental high-flow nasal cannula, opioids, hyperoxemia, and nonpharmacologic interventions, including music and fan therapy. CONCLUSIONS:In this systematic review, we found that dyspnea among mechanically ventilated patients is common and moderate to severe in its intensity. Dyspnea is associated with adverse long-term outcomes, including probable PTSD. Strategies to manage, or palliate, dyspnea were identified. Future study is warranted to examine how this information can be incorporated into clinical practice to improve short-term and long-term outcomes.

Rational: Procalcitonin (PCT), a host-response biomarker that rises in bacterial infections, has been shown to reduce antibiotic exposure and improve clinical outcomes in patients with sepsis. We designed and implemented a PCT clinical decision support tool including linked Day 0,1,5 orders (D0, D1, D5, respectively) into our health system's electronic health record for patients with sepsis. We examine the use and adherence to our PCT clinical decision support. Methods: In this retrospective, observational cohort study conducted across 14 hospitals, we examined the use and adherence to the PCT order panel. We compared PCT use post-implementation (3/4/2024 to 9/4/2024) to pre-implementation (3/3/2023 to 3/3/2024). We assessed adherence in two ways. First, among encounters with serial PCT values, we examined whether an ICD-10 code for sepsis was documented. Second, we reviewed the medical record of a random 10 patients pre-implementation and 30 post-implementation to evaluate antibiotic prescribing patterns. We used the chi-squared statistic to examine differences between groups and defined statistical significance as a p-value ≤0.05. Results: The pre-implementation period included 43,080 PCT orders among 29,256 patient encounters (1.47 orders/encounter). The post-implementation period included 21,393 PCT orders among 14,014 encounters (1.53 orders/encounter). Of the 21,393 post-implementation PCT orders, 7,135 (33.4%) were from the serial order panel for sepsis (2.05 orders/encounter) (Table). One-thousand twenty-five (30.8%) D5 PCTs were collected, 556 (16.6%) patients were discharged before D5, and 867 (25.9%) had D0 and D1 values <0.5ng/ml thus not warranting a trend. The number of encounters with a diagnosis of sepsis with serial PCT orders was 2,063 (41.1% of sepsis encounters) pre-implementation, compared to 696 (82.1% of sepsis encounters) post-implementation (p<0.01). Chart review of the order panel cohort showed 15 of 30 (50.0%) had a D1 PCT value of <0.5n/ml, yet only 1 (6.7%) had antibiotics discontinued. Of the 15 patients with a D1 PCT ≥0.5ng/ml, 7 (46.7%) had D5 levels and 4 (26.6%) were discharged before D5. Of the 7 patients, 3 (42.9%) had D5 PCTs <0.5ng/ml or decrease by 80% thus warranting antibiotic discontinuation; however, no patients had antibiotics discontinued. Conclusion: Following implementation of a procalcitonin order panel for patients with sepsis, more patients received serial PCT measurements. Adherence to the protocol was modest, with 53% of eligible patients having a D5 measurement obtained. However, adherence to antibiotic discontinuation according to the recommendations was poor. Strategies to increase adherence, including best practice advisories to prompt clinicians to discontinue antibiotics when appropriate, are warranted.

For decades, most critical care patients have survived hospitalisation, supporting increased attention on the long-term critical illness recovery. The term 'Post-Intensive Care Syndrome' was coined in 2012 to raise awareness of long-term impairment in physical, cognitive and/or mental health after critical illness. However, the incidence of these impairments has persisted over the past decade, reaching as high as 60% and remains a major public health problem.Aiming to set a research agenda to address evidence gaps in critical illness recovery over the next 10 years, we invited key international opinion leaders from diverse clinical and methodological backgrounds to a roundtable meeting in June 2024 to assess the progress of post-critical illness recovery research and outline a future research agenda to address the unmet needs of critical illness survivors over the next decade.An early outcome from the meeting was to conduct a thematic analysis of critical care recovery literature, which highlighted the need for effective expectation management, ongoing patient support and education throughout recovery, integration between inpatient and community care, caregiver support and opportunities to reconnect with the intensive care unit.Participants identified conceptual challenges concerning current terminology and scope, population heterogeneity and phenotyping, and outcome definitions. Methodological challenges were identified around study design, with a call to shift to contemporary trial designs, incorporating qualitative methods. Translation into clinical practice will require interdisciplinary engagement.The roundtable concluded that a roadmap should be developed to guide clinical and research efforts over the coming decade, with the aim of developing a precision recovery approach.

IntroductionCare transitions from acute to post-acute care are complex, especially for sepsis survivors. Implementation science offers valuable insights to translate best practices and improve care transitions. Our objective is to explore the context (site characteristics and personnel) and determinants (barriers, proposed strategies, and facilitators) influencing I-TRANSFER, a Type 1 hybrid implementation science study aimed at providing timely home health and outpatient visits for sepsis survivors within 1 week of hospital discharge.MethodsQualitative, descriptive design with interviews guided by the eight study objectives and the Consolidated Framework for Implementation Research. Ninety-one leaders in clinical, quality, and administrative roles caring for sepsis survivors in five healthcare systems (16 hospitals) and five affiliated home health care agencies in four states participated. Deductive and inductive thematic analysis of 61 interviews conducted using NVivo 14. Proposed strategies were mapped to the Expert Recommendations for Implementing Change (ERIC) taxonomy.ResultsA total of 32 themes emerged. Barriers included care coordination, staffing, electronic health record (EHR), information transfer, and access to care. Informants proposed ERIC strategies to address barriers such as changing record systems, facilitating relay of clinical data to providers, conducting education meetings, or revising professional roles. Facilitators occurred across several themes: EHR; information transfer; staffing; care coordination; access to care; home health policies, pathways, and processes; and quality monitoring.ConclusionThe interviews produced actionable insights for leaders, clinicians, providers, and policy makers regarding identifying sepsis through clear definitions, using the problem list and ICD-10 coding. Scheduling outpatient care, communicating to the next level of care, and providing timely follow-up and care coordination necessitates attention to staffing, tools for scheduling and quality measurement, and EHR integration for information transfer. Patient education is critical for awareness of risk and informed decision-making regarding follow-up after discharge.

Kelly, Nicholas1; Sullivan, Breandan1; Scott, Benjamin2; Wright, Franklin3; Wiktor, Arek1; Mikkelsen, Mark4; Moorer, Mandy5; Vernon, Shannon5; Brainard, Jason6 Author Information

We aimed to investigate transfer of learning, whereby previously acquired skills impact new task learning. While it has been debated whether such transfer may yield positive, negative, or no effects on performance, very little is known about the underlying neural mechanisms, especially concerning the role of inhibitory (GABA) and excitatory (Glu) (measured as Glu + glutamine (Glx)) neurometabolites, as measured by magnetic resonance spectroscopy (MRS). Participants practiced a bimanual coordination task across four days. The Experimental group trained a task variant with the right hand moving faster than the left (Task A) for three days and then switched to the opposite variant (Task B) on Day4. The control group trained Task B across four days. MRS data were collected before, during, and after task performance on Day4 in the somatosensory (S1) and visual (MT/V5) cortex. Results showed that both groups improved performance consistently across three days. On Day4, the Experimental group experienced performance decline due to negative task transfer while the control group continuously improved. GABA and Glx concentrations obtained during task performance showed no significant group-level changes. However, individual Glx levels during task performance correlated with better (less negative) transfer performance. These findings provide a first window into the neurochemical mechanisms underlying task transfer.

Gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in the human brain, has long been considered essential in human behavior in general and learning in particular. GABA concentration can be quantified using magnetic resonance spectroscopy (MRS). Using this technique, numerous studies have reported associations between baseline GABA levels and various human behaviors. However, regional GABA concentration is not fixed and may exhibit rapid modulation as a function of environmental factors. Hence, quantification of GABA levels at several time points during the performance of tasks can provide insights into the dynamics of GABA levels in distinct brain regions. This review reports on findings from studies using repeated measures (n = 41) examining the dynamic modulation of GABA levels in humans in response to various interventions in the perceptual, motor, and cognitive domains to explore associations between GABA modulation and human behavior. GABA levels in a specific brain area may increase or decrease during task performance or as a function of learning, depending on its precise involvement in the process under investigation. Here, we summarize the available evidence and derive two overarching hypotheses regarding the role of GABA modulation in performance and learning. Firstly, training-induced increases in GABA levels appear to be associated with an improved ability to differentiate minor perceptual differences during perceptual learning. This observation gives rise to the ‘GABA increase for better neural distinctiveness hypothesis’. Secondly, converging evidence suggests that reducing GABA levels may play a beneficial role in effectively filtering perceptual noise, enhancing motor learning, and improving performance in visuomotor tasks. Additionally, some studies suggest that the reduction of GABA levels is related to better working memory and successful reinforcement learning. These observations inspire the ‘GABA decrease to boost learning hypothesis’, which states that decreasing neural inhibition through a reduction of GABA in dedicated brain areas facilitates human learning. Additionally, modulation of GABA levels is also observed after short-term physical exercise. Future work should elucidate which specific circumstances induce robust GABA modulation to enhance neuroplasticity and boost performance.

A series of studies have suggested the cognitive deficits in patients with narcolepsy. The aim of the current study is to explore the correlation between abnormal GABA+/Glx ratio in sleep state and abnormal cognitive function in patients with narcolepsy using Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy (HERMES) method. This study demonstrate that the ratio of GABA+/Glx in prefrontal lobe of narcolepsy patients during N2 sleep stage were higher than that of normal control group, which may be related to their abnormal cognitive functions.

1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD. 2 Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO. *See also p. 102. The authors have disclosed that they do not have any potential conflicts of interest.

Understanding the neural, metabolic, and psychological mechanisms underlying human altruism and decision-making is a complex and important topic both for science and society. Here, we investigated whether transcranial Direct Current Stimulation (tDCS) applied to two prefrontal cortex regions, the ventromedial prefrontal cortex (vmPFC, anode) and the right dorsolateral prefrontal cortex (DLPFC, cathode) can induce changes in self-reported emotions and to modulate local metabolite concentrations. We employed in vivo quantitative MR Spectroscopy in healthy adult participants and quantified changes in GABA and Glx (glutamate + glutamine) before and after five sessions of tDCS delivered at 2 mA for 20 min (active group) and 1 min (sham group) while participants were engaged in a charitable donation task. In the active group, we observed increased levels of GABA in vmPFC. Glx levels decreased in both prefrontal regions and self-reported happiness increased significantly over time in the active group. Self-reported guiltiness in both active and sham groups tended to decrease. The results indicate that self-reported happiness can be modulated, possibly due to changes in Glx concentrations following repeated stimulation. Therefore, local changes may induce remote changes in the reward network through interactions with other metabolites, previously thought to be unreachable with noninvasive stimulation techniques.