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Background/Objectives: Adolescents with autonomic disorders who attend Intensive Interdisciplinary Pain Treatment (IIPT) programs report improvements in functioning. However, it is unclear whether they experience corresponding improvements in physiological measures. As such, the aim of this pilot study was to examine changes in physiological measures in youth attending an IIPT program who demonstrated excessive postural tachycardia on an active stand test. The secondary goal was to examine associations between physiological measurements and self-reported measures of chronic orthostatic intolerance (cOI) and functioning. Methods: At admission and discharge, eighteen adolescents and young adults (AYAs) attending IIPT (M age = 17.39 years; SD = 2.15 years) completed an active stand test, measures of breathing rate and muscle tension, as well as self-reported measures of cOI symptoms and functioning. Results: AYAs showed significant reduction in active stand test heart rate increase (p < 0.001; d = 1.07) and maximum heart rate (p = 0.002, d = 0.76) from admission to discharge. Improvements were also observed in resting respiration rate (p = 0.001, d = 89) and resting trapezoid tension (p = 0.03, d = 0.49). Although patients showed significant improvements on self-report measures of functioning (p < 0.001, d = 1.78), changes on subjective report of cOI symptoms did not reach significance. Exploratory analyses that only included patients with a POTS diagnosis were consistent with the overall results. Conclusions: Youth who demonstrated excessive postural tachycardia on active stand test at admission to an IIPT showed significant improvements from admission to discharge in their active stand maximum heart rate and heart rate increase, as well as respiration rate, muscle tension, and reports of their functioning. Future research is necessary to examine the mechanisms of change that contribute to symptom improvement.

Summary: The development of clinical practice guidelines is an evolving field. In response to the need for consistent, evidence-based medical practice, the American Clinical Neurophysiology Society identified the need to update the Society's guideline development process. The American Clinical Neurophysiology Society Guidelines Committee created an action plan with the goal of improving transparency and rigor for future guidelines and bringing existing guidelines to current standards. This article provides an overview of the new American Clinical Neurophysiology Society standards for the creation of clinical guidance documents, including clinical guidelines, technical standards, and consensus statements. This process is rooted in the importance of clinical guidance documents and their significance in the context of current behests for updated standards for practicing clinical neurophysiology. The need and rationale for updating the guideline development process from its prior state were described. The updated American Clinical Neurophysiology Society categories for clinical guidance and recommendations were defined and compared. Finally, the new process is summarized, focusing on methodologies, authorship, and conflicts of interest.

Introduction: The safety and efficacy of intravenous thrombolysis (IVT) in cervical artery dissection-related acute ischemic stroke (CeAD-AIS) remains unclear. We performed a retrospective study of data from the National Inpatient Sample investigating outcomes in CeAD-AIS patients treated with and without IVT. Methods: We included adult patients with CeAD-AIS hospitalized between 2016 to 2019. CeAD-AIS was defined by concurrent CeAD and AIS diagnoses, identified with ICD-10 codes. The primary outcome was home discharge. The safety outcomes were inpatient death and intracerebral hemorrhage (ICH). We used survey-weighted multivariable adjusted logistic regressions comparing the groups (IVT versus no IVT), followed by interaction analyses to examine for effect modifications based on age, medical history, stroke severity, and endovascular treatment. Results: Between 2016-2019, 1,360 (12.1%) of 11,285 CeAD-AIS patients received IVT. Patients treated with IVT- had higher NIH Stroke Scale (NIHSS) scores (median 8 [4-17] versus 3 [1-11]; p < 0.001). In adjusted analyses, treatment with IVT was associated with a greater odds of home discharge (adjusted odds ratio [aOR] 1.49; 95% confidence interval [CI] 1.09-2.05, p = 0.014), but not ICH (aOR 0.90, 95% CI 0.43-1.86, p = 0.773) or inpatient death (aOR 1.22, 95% CI 0.72-2.06, p = 0.454). In interaction analyses, stroke severity significantly interacted with IVT ( p for interaction = 0.001), where IVT was significantly associated with increased likelihood of home discharge in patients with moderate to severe strokes (NIHSS > 4) (aOR 2.28, 95% CI 1.59-3.26, p < 0.001) but not in those with mild stroke (NIHSS 0-4) (aOR 1.03 95% CI 0.62-1.70, p = 0.922). Conclusion: IVT improved the likelihood of home discharge in patients with CeAD-AIS without increasing the risk of inpatient death or ICH.

Introduction Optimal hospital bed utilization requires innovative patient care models. We studied a novel hospitalist model utilizing telemedicine to facilitate collaboration with affiliated emergency departments (EDs) and support medical triage and care of ED patients with high likelihood of hospital admission. Methods Telehospitalists based at a tertiary care facility collaborated with four community EDs in the same healthcare network between January 1, 2022, and April 30, 2023. Telehospitalists supported ED clinicians in medical care decisions and facilitated patient disposition. Emergency department length of stay (LOS) and disposition were evaluated, as were hospital LOS, 30-day readmission, and in-hospital mortality. For patients discharged from the ED, 7-day ED readmission and subsequent hospitalization were evaluated. Results Telehospitalists discussed 550 “admit-likely” patients with ED clinicians: 105 patients (19.1%) discharged from the ED and avoided admission; 322 patients (58.5%) were admitted to local or nearby community hospitals; 123 patients (22.4%) transferred to the tertiary care facility. Emergency department LOS differed significantly among disposition groups, including patients discharged home (10.2 h), admitted to local hospitals (12.6 h), and transferred to tertiary care hospitalist services (14.9 h; p < 0.001). Hospital LOS and in-hospital mortality were not significantly different among disposition groups. Patients admitted locally had lower 30-day readmission compared to those transferred to tertiary care facility (odds ratio = 0.59 [0.36, 0.99], p = 0.048). Discussion Telehospitalists as triage clinicians is an innovative approach to support local ED clinicians and patients. Telehospitalists optimized hospital bed utilization and healthcare system resources by facilitating safe discharges to home and expediting tertiary care transfers when necessary.

Importance Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. Objective To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia. Design, Setting, and Participants Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024. Main Outcomes and Measures Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms. Results In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI. Conclusions and Relevance Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumulation may commonly underlie depressive symptoms in late life.

Abstract Background Tumor necrosis factor-like ligand 1A (TL1A) is upregulated in inflammatory bowel disease and believed to promote inflammation and intestinal fibrosis. RO7790121, an anti-TL1A antibody, showed promising results in the phase IIa TUSCANY trial.1 Here we report post-hoc analyses of patient-reported outcomes from the TUSCANY-2 trial. Methods This phase IIb, multicenter, randomized, double-blind, treat-through, dose-ranging study evaluated RO7790121 in patients (pts) aged 18–75 years with moderately to severely active ulcerative colitis (UC) (total Mayo score [MS] ≥6, endoscopic subscore ≥2). Pts were randomized to receive subcutaneous (SC) RO7790121 50mg, 150mg, 450mg or matched placebo (PBO) monthly during the 12-week induction period, and SC RO7790121 50mg, 150mg or 450mg monthly during the 40-week treat-through maintenance period. To assess efficacy of RO7790121 in supporting pts achieving early symptomatic improvement, rectal bleeding (RB), stool frequency (SF) and partial modified MS (RB+SF) were evaluated at baseline and Weeks 2, 4, 8, 12 and 14. The exploratory endpoint of symptomatic remission, defined as a RB subscore of 0 and a SF subscore of 0 or 1, was assessed throughout induction. Safety was assessed throughout the study. Results Overall, 245 pts received ≥1 dose of RO7790121 or PBO. At Week 2, pts receiving RO7790121 were more likely to report a RB subscore of 0 (34% RO7790121; 20% PBO) and less likely to report a RB subscore of 2 or 3 (25% RO7790121; 40% PBO) (Figure). Improvements in SF increased from Week 2 and throughout induction, with ~60% of pts receiving RO7790121 reporting a SF subscore of 0 or 1 at Weeks 12 and 14, vs ~40% for PBO. Greater rates of symptomatic remission were observed in pts receiving RO7790121 vs PBO throughout induction and from Week 2 (17.5% RO7790121; 8.9% PBO) (Table). Treatment-emergent adverse events (TEAEs) were reported during induction in 117/245 pts, the most common (reported in ≥5% of pts in any treatment group) were nausea, urinary tract infection and UC (highest in the 50mg arm), anemia (highest in the placebo arm) and fatigue, headache and pyrexia (highest in the 450mg arm). Serious TEAEs were reported in ten pts during induction (PBO=4; 50mg=3; 450mg=3); two were treatment related (PBO=1; 450mg=1). There were six treatment discontinuations due to TEAEs and a generally similar safety profile was observed during the maintenance period. Conclusion Greater and earlier improvements in RB and SF were observed in pts receiving RO7790121 vs PBO. These results indicate early symptom relief and a favorable safety profile for pts treated with RO7790121, supporting its further clinical development. RO7790121 is currently being evaluated in phase III studies (NCT06589986 and NCT06588855). References 1.Danese S, Klopocka M, Scherl EJ, et al. Anti-TL1A antibody PF-06480605 safety and efficacy for ulcerative colitis: A phase 2a single-arm study. Clin GastroenterolHepatol. 2021;19(11):2324-2332.e6. http://doi.org/10.1016/j.cgh.2021.06.011

Importance Eligibility criteria for randomized clinical trials (RCTs) are designed to select clinically relevant patient populations. However, not all eligibility criteria are strongly justified, potentially excluding marginalized groups, and limiting the generalizability of trial findings. Objective To summarize and evaluate the justification of exclusion criteria in published RCTs in critical care medicine. Evidence Review A systematic sampling review of parallel-group RCTs published in the top 5 general internal medicine journals by impact factor ( The Lancet, New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal, and Annals of Internal Medicine ) between January 1, 2018, and February 23, 2023, was conducted. RCTs enrolling adults in intensive care units (ICUs) and RCTs enrolling critically ill patients who required life-sustaining interventions typically initiated in the ICU were included. All study exclusion criteria were categorized as either poorly justified, potentially justified, or strongly justified, adapting previously established criteria, independently and in duplicate. Findings In total, 225 studies were identified, 75 of which were included. The median (IQR) number of exclusion criteria per trial was 19 (14-24), with 1455 total exclusion criteria. Common exclusion criteria were related to the risk of adverse reaction to interventions (302 criteria [20.8%]), followed by inability to obtain consent (120 criteria [8.2%]), and treatment limitation decisions (97 criteria [6.7%]). Most exclusion criteria were either strongly justified (1080 criteria [74.2%]) or potentially justified (297 criteria [20.4%]), whereas 5.4% (78 criteria) were poorly justified. Of the 78 poorly justified exclusion criteria, the most common were pregnancy (19 criteria [24.4%]), communication barriers (11 criteria [14.1%]), lactation (10 criteria [12.8%]), and lack of health insurance (10 criteria [12.8%]). Overall, 45 of 75 studies (60.0%) had at least 1 poorly justified exclusion criteria. Conclusions and Relevance Most exclusion criteria in critical care medicine RCTs were strongly justifiable. Across poorly justified criteria, the most common exclusions were pregnant or lactating persons, those with communication barriers, and individuals without health insurance. This highlights the need to carefully consider exclusion criteria when designing trials to minimize the inappropriate exclusion of participants and enhance generalizability.

ImportanceBlood culture (BC) use benchmarks in US hospitals have not been defined.ObjectiveTo characterize BC use in adult intensive care units (ICUs) and wards in US hospitals.Design, Setting, and ParticipantsA retrospective cross-sectional study of BC use in adult medical ICUs, medical-surgical ICUs, medical wards, and medical-surgical wards from acute care hospitals from the 4 US geographic regions was conducted. Critical access hospitals, less than 6 months of BC data, and non-US hospitals were excluded. The study included BC use data from September 1, 2019, to August 31, 2021. Data were analyzed from February 23 to July 14, 2024.Main Outcomes and MeasuresThe primary outcome was BC use per 1000 patient-days. Adjusted means with 95% CIs were calculated using mixed-effects negative binomial regression models adjusted for unit type, hospital bed size, geographic region, seasonality, and state COVID-19 case load, with random intercepts accounting for clustering at unit and hospital levels. Secondary outcomes included blood culture positivity, single BCs, BC contamination, and minimum threshold for BC use where blood culture positivity would be optimized.ResultsA total of 362 327 blood cultures were analyzed from 27 medical ICUs, 35 medical-surgical ICUs, 121 medical wards, and 109 medical-surgical wards from 48 hospitals in 19 states and the District of Columbia. The adjusted mean BC use per 1000 patient-days was 273.1 (95% CI, 270.2-275.9) for medical ICUs, 146.0 (95% CI, 144.5-147.5) for medical-surgical ICUs, 80.3 (95% CI, 79.8-80.7) for medical wards, and 65.1 for medical-surgical wards. Blood culture use was significantly higher across all 4 unit types in hospitals with more than 500 beds compared with 500 or less beds and in the West-Midwest compared with other regions. Single blood culture and positive blood culture rates were below 10% across all 4 unit types. Of the 292 units, 97% had a mean BC contamination rate within 3% of the recommended threshold, and 51% were within 1%. The minimum BC use thresholds (ie, BC use below this number may represent undertesting) were 120 BCs per 1000 patient-days for medical ICUs, 80 BCs per 1000 patient-days for medical-surgical ICUs, and 30 BCs per 1000 patient-days for medical-surgical wards.Conclusions and RelevanceThe findings of this study suggest that blood culture positivity may help determine appropriate BC use for individual unit types.