Endotracheal Intubation Outside the Operating Room: Year in Review 2023.

Endotracheal intubation is a common lifesaving procedure that often is performed outside the operating room in a variety of clinical scenarios. Providers who perform intubation outside the operating room have variable degrees of training, skill development, and experience. A large number of studies were published in 2023 on the topic of intubations outside the operating room across a wide variety of settings and patient populations. Here, we review relevant papers on this topic published in 2023.

Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial.

Importance: A significant need exists for new antipsychotic medications with different mechanisms of action, greater efficacy, and better tolerability than existing agents. Xanomeline is a dual M1/M4 preferring muscarinic receptor agonist with no direct D2 dopamine receptor blocking activity. KarXT combines xanomeline with the peripheral muscarinic receptor antagonist trospium chloride with the goal of reducing adverse events due to xanomeline-related peripheral muscarinic receptor activation. In prior trials, xanomeline-trospium chloride was effective in reducing symptoms of psychosis and generally well tolerated in people with schizophrenia. Objective: To evaluate the efficacy and safety of xanomeline-trospium vs placebo in adults with schizophrenia. Design, Setting, and Participants: EMERGENT-3 (NCT04738123) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 5-week trial of xanomeline-trospium in people with schizophrenia experiencing acute psychosis, conducted between April 1, 2021, and December 7, 2022, at 30 inpatient sites in the US and Ukraine. Data were analyzed from February to June 2023. Interventions: Participants were randomized 1:1 to receive xanomeline-trospium chloride (maximum dose xanomeline 125 mg/trospium 30 mg) or placebo for 5 weeks. Main Outcomes and Measures: The prespecified primary end point was change from baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measures were change from baseline to week 5 in PANSS positive subscale score, PANSS negative subscale score, PANSS Marder negative factor score, Clinical Global Impression-Severity score, and proportion of participants with at least a 30% reduction in PANSS total score. Safety and tolerability were also evaluated. Results: A total of 256 participants (mean [SD] age, 43.1 [11.8] years; 191 men [74.6%]; 156 of 256 participants [60.9%] were Black or African American, 98 [38.3%] were White, and 1 [0.4%] was Asian) were randomized (125 in xanomeline-trospium group and 131 in placebo group). At week 5, xanomeline-trospium significantly reduced PANSS total score compared with placebo (xanomeline-trospium , -20.6; placebo, -12.2; least squares mean difference, -8.4; 95% CI, -12.4 to -4.3; P < .001; Cohen d effect size, 0.60). Discontinuation rates due to treatment-emergent adverse events (TEAEs) were similar between the xanomeline-trospium (8 participants [6.4%]) and placebo (7 participants [5.5%]) groups. The most common TEAEs in the xanomeline-trospium vs placebo group were nausea (24 participants [19.2%] vs 2 participants [1.6%]), dyspepsia (20 participants [16.0%] vs 2 participants [1.6%]), vomiting (20 participants [16.0%] vs 1 participant [0.8%]), and constipation (16 participants [12.8%] vs 5 participants [3.9%]). Measures of extrapyramidal symptoms, weight gain, and somnolence were similar between treatment groups. Conclusions and Relevance: Xanomeline-trospium was efficacious and well tolerated in people with schizophrenia experiencing acute psychosis. These findings, together with the previously reported and consistent results from the EMERGENT-1 and EMERGENT-2 trials, support the potential of xanomeline-trospium to be the first in a putative new class of antipsychotic medications without D2 dopamine receptor blocking activity. Trial Registration: ClinicalTrials.gov Identifier: NCT04738123.

Predicting Academic Productivity Among American Shoulder and Elbow Surgeons (ASES) Fellowship Faculty from Publications Acquired Before and During Surgical Training.

BACKGROUND: Orthopedic residency and fellowship applicants with a strong research record are highly valued for their potential in continuing academic excellence. Despite this, the association between research productivity during training and future academic productivity as an attending orthopedic surgeon is not well-established. We assess the effects of research output during different periods of surgical training as well as residency location on long-term academic productivity as an attending shoulder and elbow surgeon. METHODS: A search of the 2022-2023 American Shoulder and Elbow Surgeons (ASES) Fellowship Directory was conducted to identify a list of orthopedic shoulder and elbow fellowship faculty members. Each surgeon's residency, fellowship and current institution of practice were determined and stratified by geographic location. Total publication counts acquired before residency, during residency, during fellowship, and after fellowship were collected for each faculty member. Attending publication rates and H-indices were calculated. A multivariate linear regression model was created, and significance was set at a P-value < 0.05. RESULTS: A total of 149 shoulder and elbow fellowship faculty members representing 34 fellowship programs were identified. The average number of total publications per surgeon was 88.8 ± 102. The average attending publication rate was 5.29 ± 6.89 publications per year. The average H-index for included surgeons was 27.8 ± 24.4. The number of publications acquired before residency (ß = 0.293; P < 0.001), during residency (ß = 0.110; P = 0.025) and during fellowship (ß = 0.593; P < 0.001) were significantly associated with an increased attending publication rate, but no association was observed with the H-index [before residency (ß = -0.221; P = 0.574), during residency (ß = 0.045; P = 0.866), during fellowship (ß = 0.198; P = 0.678)]. There were no significant differences in total publication count (P = 0.397), attending publication rate (P = 0.237), or H-index (P = 0.364) based on location of residency training. DISCUSSION: Research output before and during surgical training is predictive of continued academic productivity as a shoulder and elbow surgeon. In particular, greater productivity during surgical fellowship was most predictive of academic output as an attending. While long-term academic productivity does not seem to be influenced by the geographic location of residency training, attending surgeons practicing in the Midwest had significantly greater total publication counts and H-indices but similar annual publication rates. LEVEL OF EVIDENCE: Survey Study; Cross Sectional Design; Literature and Internet Sources.

Survey of Ventilator Waveform Interpretation Among ICU Professionals.

BACKGROUND: The interpretation of ventilator waveforms is essential for effective and safe mechanical ventilation but requires specialized training and expertise. This study aimed to investigate the ability of ICU professionals to interpret ventilator waveforms, identify areas requiring further education and training, and explore the factors influencing their interpretation skills. METHODS: We conducted an international online anonymous survey of ICU professionals (physicians, nurses, and respiratory therapists [RTs]), with ≥ 1 y of experience working in the ICU. The survey consisted of demographic information and 15 multiple-choice questions related to ventilator waveforms. Results were compared between professions using descriptive statistics, and logistic regression (expressed as odds ratios [ORs; 95% CI]) was performed to identify factors associated with high performance, which was defined by a threshold of 60% correct answers. RESULTS: A total of 1,832 professionals from 31 countries or regions completed the survey; 53% of respondents answered ≥ 60% of the questions correctly. The 3 questions with the most correct responses were related to waveforms that demonstrated condensation (90%), pressure overshoot (79%), and bronchospasm (75%). Conversely, the 3 questions with the fewest correct responses were waveforms that demonstrated early cycle leading to double trigger (43%), severe under assistance (flow starvation) (37%), and early/reverse trigger (31%). Factors significantly associated with ≥ 60% correct answers included years of ICU working experience (≥ 10 y, OR 1.6 [1.2-2.0], P < .001), profession (RT, OR 2.8 [2.1-3.7], P < .001), highest degree earned (graduate, OR 1.7 [1.3-2.2], P < .001), workplace (teaching hospital, OR 1.4 [1.1-1.7], P = .008), and prior ventilator waveforms training (OR 1.7 [1.3-2.2], P < .001). CONCLUSIONS: Slightly over half respondents correctly identified ≥ 60% of waveforms demonstrating patient-ventilator discordance. High performance was associated with ≥ 10 years of ICU working experience, RT profession, graduate degree, working in a teaching hospital, and prior ventilator waveforms training. Some discordances were poorly recognized across all groups of surveyed professionals.

Fibroblast and myofibroblast activation in normal tissue repair and fibrosis.

The term 'fibroblast' often serves as a catch-all for a diverse array of mesenchymal cells, including perivascular cells, stromal progenitor cells and bona fide fibroblasts. Although phenotypically similar, these subpopulations are functionally distinct, maintaining tissue integrity and serving as local progenitor reservoirs. In response to tissue injury, these cells undergo a dynamic fibroblast-myofibroblast transition, marked by extracellular matrix secretion and contraction of actomyosin-based stress fibres. Importantly, whereas transient activation into myofibroblasts aids in tissue repair, persistent activation triggers pathological fibrosis. In this Review, we discuss the roles of mechanical cues, such as tissue stiffness and strain, alongside cell signalling pathways and extracellular matrix ligands in modulating myofibroblast activation and survival. We also highlight the role of epigenetic modifications and myofibroblast memory in physiological and pathological processes. Finally, we discuss potential strategies for therapeutically interfering with these factors and the associated signal transduction pathways to improve the outcome of dysregulated healing.

A protective role for B-1 cells and oxidation-specific epitope IgM in lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a morbid fibrotic lung disease with limited treatment options. The pathophysiology of IPF remains poorly understood, and elucidation of the cellular and molecular mechanisms of IPF pathogenesis is key to the development of new therapeutics. B-1 cells are an innate B cell population which play an important role linking innate and adaptive immunity. B-1 cells spontaneously secrete natural IgM and prevent inflammation in several disease states. One class of these IgM recognize oxidation-specific epitopes (OSE), which have been shown to be generated in lung injury and to promote fibrosis. A main B-1 cell reservoir is the pleural space, adjacent to the typical distribution of fibrosis in IPF. In this study, we demonstrate that B-1 cells are recruited to the lung during injury where they secrete IgM to OSE (IgM OSE ). We also show that the pleural B-1 cell reservoir responds to lung injury through regulation of the chemokine receptor CXCR4. Mechanistically we show that the transcription factor Id3 is a novel negative regulator of CXCR4 expression. Using mice with B-cell specific Id3 deficiency, a model of increased B-1b cells, we demonstrate decreased bleomycin-induced fibrosis compared to littermate controls. Furthermore, we show that mice deficient in secretory IgM ( sIgM -/- ) have higher mortality in response to bleomycin-induced lung injury, which is partially mitigated through airway delivery of the IgM OSE E06. Additionally, we provide insight into potential mechanisms of IgM in attenuation of fibrosis through RNA sequencing and pathway analysis, highlighting complement activation and extracellular matrix deposition as key differentially regulated pathways.

Clinicopathological and pedigree investigation of a novel spinocerebellar neurological disease in juvenile Quarter Horses in North America.

BACKGROUND: In 2020, a novel neurologic disease was observed in juvenile Quarter Horses (QHs) in North America. It was unknown if this was an aberrant manifestation of another previously described neurological disorder in foals, such as equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM). HYPOTHESIS/OBJECTIVES: To describe the clinical findings, outcomes, and postmortem changes with Equine Juvenile Spinocerebellar Ataxia (EJSCA), differentiate the disease from other similar neurological disorders, and determine a mode of inheritance. ANIMALS: Twelve neurologically affected QH foals and the dams. METHODS: Genomic DNA was isolated and pedigrees were manually constructed. RESULTS: All foals (n = 12/12) had a history of acute onset of neurological deficits with no history of trauma. Neurological deficits were characterized by asymmetrical spinal ataxia, with pelvic limbs more severely affected than thoracic limbs. Clinicopathological abnormalities included high serum activity of gamma-glutamyl transferase and hyperglycemia. All foals became recumbent (median, 3 days: [0-18 days]), which necessitated humane euthanasia (n = 11/12, 92%; the remaining case was found dead). Histological evaluation at postmortem revealed dilated myelin sheaths and digestion chambers within the spinal cord, most prominently in the dorsal spinocerebellar tracts. Pedigree analysis revealed a likely autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: EJSCA is a uniformly fatal, rapidly progressive, likely autosomal recessive neurological disease of QHs <1 month of age in North America that is etiologically distinct from other clinically similar neurological disorders. Once the causative variant for EJSCA is validated, carriers can be identified through genetic testing to inform breeding decisions.

Comprehensive Assessment of Artificial Intelligence Tools for Driver Monitoring and Analyzing Safety Critical Events in Vehicles.

Human factors are a primary cause of vehicle accidents. Driver monitoring systems, utilizing a range of sensors and techniques, offer an effective method to monitor and alert drivers to minimize driver error and reduce risky driving behaviors, thus helping to avoid Safety Critical Events (SCEs) and enhance overall driving safety. Artificial Intelligence (AI) tools, in particular, have been widely investigated to improve the efficiency and accuracy of driver monitoring or analysis of SCEs. To better understand the state-of-the-art practices and potential directions for AI tools in this domain, this work is an inaugural attempt to consolidate AI-related tools from academic and industry perspectives. We include an extensive review of AI models and sensors used in driver gaze analysis, driver state monitoring, and analyzing SCEs. Furthermore, researchers identified essential AI tools, both in academia and industry, utilized for camera-based driver monitoring and SCE analysis, in the market. Recommendations for future research directions are presented based on the identified tools and the discrepancies between academia and industry in previous studies. This effort provides a valuable resource for researchers and practitioners seeking a deeper understanding of leveraging AI tools to minimize driver errors, avoid SCEs, and increase driving safety.

A Master Protocol Template for Pediatric ARDS Studies.

BACKGROUND: Pediatric ARDS is associated with significant morbidity and mortality. High-quality data from clinical trials in children are limited due to numerous barriers to their design and execution. Here we describe the collaborative development of a master protocol as a tool to address some of these barriers and support the conduct of pediatric ARDS studies. METHODS: Using PubMed, we performed a literature search of randomized controlled trials (RCTs) in pediatric ARDS to characterize the current state and evaluate potential benefit of harmonized master protocols. We used a multi-stakeholder, collaborative, and team science-oriented process to develop a master protocol template with links to common data elements (CDEs) for pediatric ARDS trials. RESULTS: We identified 11 RCTs that enrolled between 14-200 total subjects per trial. Interventions included mechanical ventilation, prone positioning, corticosteroids, and surfactant. Studies displayed significant heterogeneity in ARDS definition, design, inclusion and exclusion criteria, and reported outcomes. Mortality was reported in 91% of trials and ventilator-free days in 73%. The trial heterogeneity made pooled analysis unfeasible. These findings underscore the need for a method to facilitate combined analysis of future trials through standardization of trial elements. As a potential solution, we developed a master protocol, iteratively revised with input from a multidisciplinary panel of experts and organized into 3 categories: instructions and general information, templated language, and a series of text options of common pediatric ARDS trial scenarios. Finally, we linked master protocol sections to relevant CDEs previously defined for pediatric ARDS and captured in a series of electronic case report forms. CONCLUSIONS: The majority of pediatric ARDS trials identified were small and heterogeneous in study design and outcome reporting. Using a master protocol template for pediatric ARDS trials with CDEs would support combining and comparing pediatric ARDS trial findings and increase the knowledge base.

Higher return to sport and lower revision rates when performing arthroscopic Bankart repair with remplissage for anterior shoulder instability with a Hill-Sachs lesion: a meta-analysis.

BACKGROUND: Recurrent anterior shoulder instability remains the most common complication from a prior shoulder dislocation, especially among young and active individuals who engage in athletic activities. This instability can lead to repeated subluxation or dislocations of the humeral head from the glenoid fossa. The purpose of this study is to compare postoperative recurrence rates, instability-related revision and return to sport (RTS) rates between isolated arthroscopic Bankart repair (ABR) and ABR with remplissage (ABR + R) for anterior shoulder instability with subcritical glenoid bone loss (GBL) and a Hill-Sachs lesion (HSL). METHODS: PubMed, Embase, and Web of Science were searched on June 2022. Studies sought were those comparing postoperative outcomes of ABR + R versus isolated ABR for subcritical GBL and an HSL. Study quality was evaluated using the revised Cochrane tool. Redislocations, instability-related revisions, and RTS rates were extracted and pooled estimates were calculated using the random-effect model. RESULTS: Twelve studies were included with a mean follow-up of 48.2 months for isolated ABR and 43.2 months for ABR + R. The meta-analytic comparison demonstrated that ABR + R resulted in statistically significant improvement in Rowe and American Shoulder and Elbow Surgeons scores by 6.5 and 2.2 points, respectively; however, the improvements in patient-reported outcomes were not clinically meaningful. ABR + R resulted in reduced external rotation at the side by 1° which was not clinically meaningful and there was no significant difference in terms of forward elevation. ABR + R resulted in a statistically significant reduction of overall postoperative recurrences (odds ratio [OR]: 9.36), postoperative dislocations (OR: 6.28), instability-related revision (OR: 3.46), and RTS to any level (OR: 2.85). CONCLUSION: The addition of remplissage to ABR for recurrent anterior shoulder instability with subcritical GBL and HSL results in significantly lower postoperative instability recurrence, lower instability-related revisions, and higher RTS to any level.

Extensor tendon transfer for fracture-related extensor pollicis longus rupture: Long-term outcome case series.

BACKGROUND: Spontaneous rupture of the extensor pollicis longus (EPL) tendon following both nonoperative and operative treatment of distal radius fractures has been well described. PURPOSE: The purpose of this study was to assess long-term outcomes of extensor indicis proprius to EPL tendon transfers for patients following distal radius fracture and EPL tendon repair. STUDY DESIGN: Retrospective case series focusing on long-term clinical outcomes. METHODS: A retrospective review was conducted for patients who sustained a distal radius fracture and subsequently underwent extensor tendon transfer from 2005-2015 at a private practice center. Outcome measures including index finger (IF) metacarpophalangeal (MCP) and thumb interphalangeal (IP) active range of motion (ROM), digital extension against resistance, subjective complaints, and QuickDASH scores were recorded at final follow-up. RESULTS: Seven patients were included in the study. There were six females and one male subject, mean age of 54 ± 13 years at injury of EPL, and 5/7 involved the left upper extremity. For isolated function, 7/7 (100%) patients had isolated, active IF MCP extension, 6/7 (86%) could extend IF MCP and thumb IP against resistance. Mean IF MCP extension was 1° ± 2°, mean IF MCP flexion was 89° ± 2°, mean thumb IP extension was -5° ± 4°, and mean thumb IP flexion was 67° ± 15°. Mean QuickDASH score was 16 ± 14. CONCLUSIONS: This series shows good long-term functional and patient reported outcomes in patients following extensor indicis proprius to EPL tendon transfers at a single center.

Academic Output of Fellows of the American Association for Respiratory Care.

BACKGROUND: Research is critical for the advancement of respiratory care. Fellows of the American Association for Respiratory Care (FAARCs) are nominated based on their significant contributions to the respiratory care profession. Research output is potentially an important component of qualification for FAARC. The purpose of this study is to report the academic output of respiratory therapist (RT) FAARCs. METHODS: We identified FAARCs from the AARC web site. Research output was assessed by searching the Scopus and PubMed databases. We collected total research documents, citations, h-index, co-authors, and document type. We compared those with only the FAARC designation with RTs who are fellows in both the Society of Critical Care Medicine (FCCMs) and FAARC. RESULTS: We identified a total of 371 RT FAARCs, 4 RT FCCMs, and 10 with both designations. FAARCs were 70% male, 22% had a doctorate, 37% had a master's, 13% had a bachelor's, and 29% did not have a degree reported. There were no differences in sex or highest degree between FAARCs and FCCMs. FAARCs had a total of 3,724 publications and 110,207 citations while those with both designations had 1,304 publications and 43,181 citations. In Scopus, 46% of FAARCs had no publications, and 27% had ≥ 10 publications; of those with both credentials, 10% had no publications, and 70% had ≥ 10 publications. FAARCs inducted in 1998 and 1999 had significantly (P < .001) more publications than other eras. Compared to those with both credentials, FAARCs had fewer median publications (1 vs 50), lower h-index (1 vs 18), and fewer citations (1 vs 1,486), P < .001 for all. Total publications in PubMed were lower, and differences in publications were similar. CONCLUSIONS: RT FAARCs had a large number of publications and citations, although nearly half did not have any publications. Those with both FAARC and FCCM had significantly more academic output per fellow, although there are only 10 individuals with both credentials.

Coccidioides Serologic Screening Practices in Individuals With Rheumatic and Autoimmune Diseases.

OBJECTIVE: We aimed to estimate Coccidioides serologic screening rates before initiation of biologic disease-modifying antirheumatic drugs including tofacitinib (b/tsDMARDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and/or noninhaled corticosteroids. METHODS: This retrospective cohort study used 2011 to 2016 US Medicare claims data and included beneficiaries with rheumatic or autoimmune disease residing in regions within Arizona, California, and Texas endemic for Coccidioides spp. with ≥1 prescription for a b/tsDMARD, csDMARD, and/or noninhaled corticosteroid. We estimated prior-year serologic screening incidence before initiating b/tsDMARDs, csDMARD, and/or noninhaled corticosteroid. RESULTS: During 2012 to 2016, 4,331 beneficiaries filled 64,049 prescriptions for b/tsDMARDs, csDMARDs, and noninhaled corticosteroids. Arizona's estimated screening rate was 20.1% (95% confidence interval [95% CI] 14.5-25.7) in the year before prescription initiation for b/tsDMARDs, 8.1% (95% CI 6.5-9.7) before csDMARDs, and 6.9% (95% CI: 5.6-8.2) before corticosteroids. Screening rates for b/tsDMARDs (2.8%, 95% CI 0.0-6.7), csDMARDs (1.0%, 95% CI 0.0-2.0), and corticosteroids (0.8%, 95% CI: 0.4-1.1) were negligible in California and undetected in Texas. Adjusted screening rate before prescription for b/tsDMARDs in Arizona increased from 14.5% (95% CI 7.5-21.5) in 2012 to 26.7% (95% CI 17.6-35.8) in 2016. Rheumatologists prescribing b/tsDMARDs in Arizona screened more than other providers (20.9% [95% CI 13.9-27.9] vs 12.9% [95% CI 5.9-20.0]). CONCLUSION: Coccidioides serologic screening rates among Medicare beneficiaries with rheumatic/autoimmune diseases on b/tsDMARDs, csDMARDs, and noninhaled corticosteroids was low in Coccidioides spp.-US endemic regions between 2012 and 2016. Alignment of screening recommendations and clinical practice is needed.

Association between blood markers and the progression of osseointegration in percutaneous prostheses patients-A pilot study.

Patients implanted with osseointegrated (OI) prosthetic systems have reported vastly improved upper and lower extremity prosthetic function compared with their previous experience with socket-suspension systems. However, OI systems have been associated with superficial and deep-bone infections and implant loosening due, in part, to a failure of the osseointegration process. Although monitoring the osseointegration using circulating biomarkers has clinical relevance for understanding the progression of osseointegration with these devices, it has yet to be established. Ten patients were enrolled in this study. Blood samples were collected at pre-selected times, starting before implantation surgery, and continuing to 12 months after the second surgery. Bone formation markers, bone resorption markers, and circulating amino acids were measured from blood samples. A linear mixed model was generated for each marker, incorporating patient ID and age with the normalized marker value as the response variable. Post hoc comparisons were made between 1 week before Stage 1 Surgery and all subsequent time points for each marker, followed by multiple testing corrections. Serial radiographic imaging of the residual limb containing the implant was obtained during follow-up, and the cortical index (CI) was calculated for the bone at the porous region of the device. Two markers of bone formation, specifically bone-specific alkaline phosphatase (Bone-ALP) and amino-terminal propeptide of type I procollagen (PINP), exhibited significant increases when compared with the baseline levels of unloaded residual bone prior to the initial surgery, and they subsequently returned to their baseline levels by the 12-month mark. Patients who experienced clinically robust osseointegration experienced increased cortical bone thickness at the porous coated region of the device. A medium correlation was observed between Bone-ALP and the porous CI values up to PoS2-M1 (p = .056), while no correlation was observed for PINP. An increase in bone formation markers and the lack of change observed in bone resorption markers likely reflect increased cortical bone formation induced by the end-loading design of the Utah OI device used in this study. A more extensive study is required to validate the correlation observed between Bone-ALP and porous CI values.

The effects of flow settings during high-flow nasal cannula oxygen therapy for neonates and young children.

BACKGROUND: During neonatal and paediatric high-flow nasal cannula therapy, optimising the flow setting is crucial for favourable physiological and clinical outcomes. However, considerable variability exists in clinical practice regarding initial flows and subsequent adjustments for these patients. Our review aimed to summarise the impact of various flows during high-flow nasal cannula treatment in neonates and children. METHODS: Two investigators independently searched PubMed, Embase, Web of Science, Scopus and Cochrane for in vitro and in vivo studies published in English before 30 April 2023. Studies enrolling adults (≥18 years) or those using a single flow setting were excluded. Data extraction and risk of bias assessments were performed independently by two investigators. The study protocol was prospectively registered with PROSPERO (CRD42022345419). RESULTS: 38 406 studies were identified, with 44 included. In vitro studies explored flow settings' effects on airway pressures, humidity and carbon dioxide clearance; all were flow-dependent. Observational clinical studies consistently reported that higher flows led to increased pharyngeal pressure and potentially increased intrathoracic airway pressure (especially among neonates), improved oxygenation, and reduced respiratory rate and work of breathing up to a certain threshold. Three randomised controlled trials found no significant differences in treatment failure among different flow settings. Flow impacts exhibited significant heterogeneity among different patients. CONCLUSION: Individualising flow settings in neonates and young children requires consideration of the patient's peak inspiratory flow, respiratory rate, heart rate, tolerance, work of breathing and lung aeration for optimal care.

A randomized proof-of-mechanism trial of TNF antagonism for motivational anhedonia and related corticostriatal circuitry in depressed patients with high inflammation.

Chronic, low-grade inflammation has been associated with motivational deficits in patients with major depression (MD). In turn, impaired motivation has been linked to poor quality of life across psychiatric disorders. We thus determined effects of the anti-inflammatory drug infliximab-a potent tumor necrosis factor (TNF) antagonist-on behavioral and neural measures of motivation in 42 medically stable, unmedicated MD patients with a C-reactive protein > 3mg/L. All patients underwent a double-blind, placebo-controlled, single-dose, randomized clinical trial with infliximab (5mg/kg) versus placebo. Behavioral performance on an effort-based decision-making task, self-report questionnaires, and neural responses during event-related functional magnetic resonance imaging were assessed at baseline and 2 weeks following infusion. We found that relative to placebo, patients receiving infliximab were more willing to expend effort for rewards. Moreover, increase in effortful choices was associated with reduced TNF signaling as indexed by decreased soluble TNF receptor type 2 (sTNFR2). Changes in effort-based decision-making and sTNFR2 were also associated with changes in task-related activity in a network of brain areas, including dmPFC, ventral striatum, and putamen, as well as the functional connectivity between these regions. Changes in sTNFR2 also mediated the relationships between drug condition and behavioral and neuroimaging measures. Finally, changes in self-reported anhedonia symptoms and effort-discounting behavior were associated with greater responses of an independently validated whole-brain predictive model (aka "neural signature") sensitive to monetary rewards. Taken together, these data support the use of anti-inflammatory treatment to improve effort-based decision-making and associated brain circuitry in depressed patients with high inflammation.