Glucosamine-Mediated Hexosamine Biosynthesis Pathway Activation Uses ATF4 to Promote "Exercise-Like" Angiogenesis and Perfusion Recovery in PAD.

BACKGROUND: Endothelial cells (ECs) use glycolysis to produce energy. In preclinical models of peripheral arterial disease, further activation of EC glycolysis was ineffective or deleterious in promoting hypoxia-dependent angiogenesis, whereas pentose phosphate pathway activation was effective. Hexosamine biosynthesis pathway, pentose phosphate pathway, and glycolysis are closely linked. Glucosamine directly activates hexosamine biosynthesis pathway. METHODS: Hind-limb ischemia in endothelial nitric oxide synthase knockout (eNOS-/-) and BALB/c mice was used. Glucosamine (600 µg/g per day) was injected intraperitoneally. Blood flow recovery was assessed using laser Doppler perfusion imaging and angiogenesis was studied by CD31 immunostaining. In vitro, human umbilical vein ECs and mouse microvascular ECs with glucosamine, L-glucose, or vascular endothelial growth factor (VEGF165a) were tested under hypoxia and serum starvation. Cell Counting Kit-8, tube formation, intracellular reactive oxygen species, electric cell-substrate impedance sensing, and fluorescein isothiocyanate dextran permeability were assessed. Glycolysis and oxidative phosphorylation were assessed by seahorse assay. Gene expression was assessed using RNA sequencing, real-time quantitative polymerase chain reaction, and Western blot. Human muscle biopsies from patients with peripheral arterial disease were assessed for EC O-GlcNAcylation before and after supervised exercise versus standard medical care. RESULTS: On day 3 after hind-limb ischemia, glucosamine-treated versus control eNOS-/- mice had less necrosis (n=4 or 5 per group). Beginning on day 7 after hind-limb ischemia, glucosamine-treated versus control BALB/c mice had higher blood flow, which persisted to day 21, when ischemic muscles showed greater CD31 staining per muscle fiber (n=8 per group). In vitro, glucosamine versus L-glucose ECs showed improved survival (n=6 per group) and tube formation (n=6 per group). RNA sequencing of glucosamine versus L-glucose ECs showed increased amino acid metabolism (n=3 per group). That resulted in increased oxidative phosphorylation (n=8-12 per group) and serine biosynthesis pathway without an increase in glycolysis or pentose phosphate pathway genes (n=6 per group). This was associated with better barrier function (n=6-8 per group) and less reactive oxygen species (n=7 or 8 per group) compared with activating glycolysis by VEGF165a. These effects were mediated by activating transcription factor 4, a driver of exercise-induced angiogenesis. In muscle biopsies from humans with peripheral arterial disease, EC/O-GlcNAcylation was increased by 12 weeks of supervised exercise versus standard medical care (n=6 per group). CONCLUSION: In cells, mice, and humans, activation of hexosamine biosynthesis pathway by glucosamine in peripheral arterial disease induces an "exercise-like" angiogenesis and offers a promising novel therapeutic pathway to treat this challenging disorder.

Evidence for preexisting prion substrain diversity in a biologically cloned prion strain.

Prion diseases are a group of inevitably fatal neurodegenerative disorders affecting numerous mammalian species, including Sapiens. Prions are composed of PrPSc, the disease specific conformation of the host encoded prion protein. Prion strains are operationally defined as a heritable phenotype of disease under controlled transmission conditions. Treatment of rodents with anti-prion drugs results in the emergence of drug-resistant prion strains and suggest that prion strains are comprised of a dominant strain and substrains. While much experimental evidence is consistent with this hypothesis, direct observation of substrains has not been observed. Here we show that replication of the dominant strain is required for suppression of a substrain. Based on this observation we reasoned that selective reduction of the dominant strain may allow for emergence of substrains. Using a combination of biochemical methods to selectively reduce drowsy (DY) PrPSc from biologically-cloned DY transmissible mink encephalopathy (TME)-infected brain resulted in the emergence of strains with different properties than DY TME. The selection methods did not occur during prion formation, suggesting the substrains identified preexisted in the DY TME-infected brain. We show that DY TME is biologically stable, even under conditions of serial passage at high titer that can lead to strain breakdown. Substrains therefore can exist under conditions where the dominant strain does not allow for substrain emergence suggesting that substrains are a common feature of prions. This observation has mechanistic implications for prion strain evolution, drug resistance and interspecies transmission.

Effectiveness of Integrating Suicide Care in Primary Care : Secondary Analysis of a Stepped-Wedge, Cluster Randomized Implementation Trial.

BACKGROUND: Primary care encounters are common among patients at risk for suicide. OBJECTIVE: To evaluate the effectiveness of implementing population-based suicide care (SC) in primary care for suicide attempt prevention. DESIGN: Secondary analysis of a stepped-wedge, cluster randomized implementation trial. (ClinicalTrials.gov: NCT02675777). SETTING: 19 primary care practices within a large health care system in Washington State, randomly assigned launch dates. PATIENTS: Adult patients (aged ≥18 years) with primary care visits from January 2015 to July 2018. INTERVENTION: Practice facilitators, electronic medical record (EMR) clinical decision support, and performance monitoring supported implementation of depression screening, suicide risk assessment, and safety planning. MEASUREMENTS: Clinical practice and patient measures relied on EMR and insurance claims data to compare usual care (UC) and SC periods. Primary outcomes included documented safety planning after population-based screening and suicide risk assessment and suicide attempts or deaths (with self-harm intent) within 90 days of a visit. Mixed-effects logistic models regressed binary outcome indicators on UC versus SC, adjusted for randomization stratification and calendar time, accounting for repeated outcomes from the same site. Monthly outcome rates (percentage per 10 000 patients) were estimated by applying marginal standardization. RESULTS: During UC, 255 789 patients made 953 402 primary care visits and 228 255 patients made 615 511 visits during the SC period. The rate of safety planning was higher in the SC group than in the UC group (38.3 vs. 32.8 per 10 000 patients; rate difference, 5.5 [95% CI, 2.3 to 8.7]). Suicide attempts within 90 days were lower in the SC group than in the UC group (4.5 vs. 6.0 per 10 000 patients; rate difference, -1.5 [CI, -2.6 to -0.4]). LIMITATION: Suicide care was implemented in combination with care for depression and substance use. CONCLUSION: Implementation of population-based SC concurrent with a substance use program resulted in a 25% reduction in the suicide attempt rate in the 90 days after primary care visits. PRIMARY FUNDING SOURCE: National Institute of Mental Health.

Association of Egg Intake With Alzheimer's Dementia Risk in Older Adults: The Rush Memory and Aging Project.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder with increasing prevalence due to population aging. Eggs provide many nutrients important for brain health, including choline, omega-3 fatty acids, and lutein. Emerging evidence suggests that frequent egg consumption may improve cognitive performance on verbal tests, but whether consumption influences the risk of Alzheimer's dementia and AD is unknown. OBJECTIVES: To examine the association of egg consumption with Alzheimer's dementia risk among the Rush Memory and Aging Project cohort. METHODS: Dietary assessment was collected using a modified Harvard semiquantitative food frequency questionnaire. Participants' first food frequency questionnaire was used as the baseline measure of egg consumption. Multivariable adjusted Cox proportional hazards regression models were used to investigate the associations of baseline egg consumption amount with Alzheimer's dementia risk, adjusting for potential confounding factors. Subgroup analyses using Cox and logistic regression models were performed to investigate the associations with AD pathology in the brain. Mediation analysis was conducted to examine the mediation effect of dietary choline in the relationship between egg intake and incident Alzheimer's dementia. RESULTS: This study included 1024 older adults {mean [±standard deviation (SD)] age = 81.38 ± 7.20 y}. Over a mean (±SD) follow-up of 6.7 ± 4.8 y, 280 participants (27.3%) were clinically diagnosed with Alzheimer's dementia. Weekly consumption of >1 egg/wk (hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.34, 0.83) and ≥2 eggs/wk (HR: 0.53; 95% CI: 0.35, 0.81) was associated with a decreased risk of Alzheimer's dementia. Subgroup analysis of brain autopsies from 578 deceased participants showed that intakes of >1 egg/wk (HR: 0.51; 95% CI: 0.35, 0.76) and ≥2 eggs/wk (HR: 0.62; 95% CI: 0.44, 0.90) were associated with a lower risk of AD pathology in the brain. Mediation analysis showed that 39% of the total effect of egg intake on incident Alzheimer's dementia was mediated through dietary choline. CONCLUSIONS: These findings suggest that frequent egg consumption is associated with a lower risk of Alzheimer's dementia and AD pathology, and the association with Alzheimer's dementia is partially mediated through dietary choline.

24-Hour warning signs for adolescent suicide attempts.

BACKGROUND: Little is known about when youth may be at greatest risk for attempting suicide, which is critically important information for the parents, caregivers, and professionals who care for youth at risk. This study used adolescent and parent reports, and a case-crossover, within-subject design to identify 24-hour warning signs (WS) for suicide attempts. METHODS: Adolescents (N = 1094, ages 13 to 18) with one or more suicide risk factors were enrolled and invited to complete bi-weekly, 8-10 item text message surveys for 18 months. Adolescents who reported a suicide attempt (survey item) were invited to participate in an interview regarding their thoughts, feelings/emotions, and behaviors/events during the 24-hours prior to their attempt (case period) and a prior 24-hour period (control period). Their parents participated in an interview regarding the adolescents' behaviors/events during these same periods. Adolescent or adolescent and parent interviews were completed for 105 adolescents (81.9% female; 66.7% White, 19.0% Black, 14.3% other). RESULTS: Both parent and adolescent reports of suicidal communications and withdrawal from social and other activities differentiated case and control periods. Adolescent reports also identified feelings (self-hate, emotional pain, rush of feelings, lower levels of rage toward others), cognitions (suicidal rumination, perceived burdensomeness, anger/hostility), and serious conflict with parents as WS in multi-variable models. CONCLUSIONS: This study identified 24-hour WS in the domains of cognitions, feelings, and behaviors/events, providing an evidence base for the dissemination of information about signs of proximal risk for adolescent suicide attempts.

Defining "low-carb" in the scientific literature: A scoping review of clinical studies.

There remains a lack of scientific consensus on what level of carbohydrate intake constitutes low-carbohydrate diets. We conducted a scoping review to understand how low-carbohydrate diets were defined in the peer-reviewed literature. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement scoping review extension. Three electronic databases were searched for clinical studies in English. We identified 508 articles (317 randomized controlled, 99 cross-over, 33 before-and-after, 12 non-randomized, and 47 other clinical trials). Most examined effects of low-carbohydrate diets in healthy adults (62.4%), 40 to 59 years old (55.5%), with obesity or overweight (66.1%). The majority reported effects on weight or body composition (29.9%), diabetes (18.7%), or cardiovascular risk factors (12.9%) as primary outcomes. Most articles (56.9%) reported percent of energy from carbohydrates, and of those, 60.3% defined low-carbohydrate diets as being ≤30% of energy from carbohydrates. Some articles (22.9%) reported grams of carbohydrates per day, and of those, most defined low-carbohydrate diets as being under ∼100 grams of carbohydrates per day. Systematic reviews and dose-response meta-regressions utilizing patient-level data on carbohydrate intake, status markers (e.g., RQ/ketones), and health outcomes would be useful in informing consensus around a standardized definition.

The effects of vitamin D intake and status on symptom severity and quality-of-life in adults with irritable bowel syndrome (IBS): a systematic review and meta-analysis.

IMPORTANCE: Many individuals with irritable bowel syndrome (IBS) have insufficient or deficient serum 25-hydroxyvitamin D [25(OH)D] status; however, it is not clear if improved vitamin D nutritional status through higher intake can improve symptom severity and quality of life. OBJECTIVE: This systematic review and meta-analysis aimed to identify if changes in vitamin D intake or status affect symptom severity and quality of life in adults with IBS.Data Sources: MEDLINE®, Cochrane Central Register of Controlled Trials, Global Health, EMBASE, and Web-of-Science databases were systematically searched for relevant articles to August 12, 2024, in the English language.Study Selection: Clinical trials, prospective observational studies, and Mendelian randomization (MR) analyses reporting the effect of vitamin D intake or status on IBS-related outcomes were included.Data Extraction and Synthesis: Article review and data extraction were conducted by 2 authors following the PRISMA guidelines. Random effects meta-analyses and the Nutrition Quality Evaluation Strengthening Tools to assess risk of bias were employed for randomized controlled trials.Main Outcome(s) and Measure(s): Primary outcomes included measures of serum 25(OH)D status, symptom severity, and quality of life. RESULTS: 12 studies from 15 articles were included (n = 7 RCTs; n = 3 single-arm interventions; n = 2 MR). Seven study populations had deficient (<20 ng/mL) and three had insufficient (21-29 ng/mL) baseline serum 25(OH)D status. RCTs measured changes in serum 25(OH)D after 6-26 wks with 3,000 IU daily to 50,000 IU bi-weekly vitamin D dosages. Meta-analyses of low risk-of-bias RCTs revealed increased 25(OH)D levels in groups treated with oral vitamin D compared to placebo (n = 5; Pooled mean difference [95% CI]: 20.33 [12.91, 27.74] ng/mL; I2 = 97.9%). Quality of life scores improved significantly in deficient populations (n = 3; 3.19 [2.14, 4.24]; I2 = 0.0%). Non-significant decreased trends in IBS symptom severity were shown across populations (n = 6: -25.89 [-55.26, 3.48]; I2 = 92.8%). CONCLUSION: Moderate level evidence indicate vitamin D supplementation may improve status in adults with IBS and quality of life in those with deficient status at baseline.

QUESTION: Do changes in vitamin D intake or status affect symptom severity and quality of life in adults with irritable bowel syndrome?FindingsIn this systematic review and meta-analysis, moderate level evidence supports vitamin D supplementation for improving serum 25-hydroxyvitamin D status in adults with IBS and for increasing quality of life scores in those with deficient status at baseline.Meaning: Vitamin D supplementation may improve quality of life in IBS patients with deficient serum 25-hydroxyvitamin D status.

The effect of an acute aspirin challenge on intestinal permeability in healthy adults with and without prophylactic probiotic consumption: a double-blind, placebo-controlled, randomized trial.

BACKGROUND: Healthy individuals may experience increases in intestinal permeability after chronic or acute use of non-steroidal anti-inflammatory drugs, which may be attenuated by probiotics. This study investigates the effects of an acute aspirin challenge on gastroduodenal barrier function with or without prophylactic probiotic consumption. METHODS: Twenty-nine generally healthy participants (26 ± 6 years) completed a 14-week randomized, double-blind, crossover trial. A probiotic containing 2 Lactobacilli strains or placebo was administered for 3 weeks, with a 4-week washout period between crossover phases. Daily and weekly questionnaires assessing gastrointestinal function were completed for 2 weeks before until 2 weeks after each intervention to assess gastrointestinal function. Gastroduodenal permeability was assessed by urinary excretion of orally administered sucrose after 1, 2, and 3 weeks of each intervention with a 1950 mg-aspirin challenge after 2 weeks of supplementation. Stool samples were collected weekly during supplementation for detection of species of interest. RESULTS: Gastroduodenal permeability increased with aspirin challenge (Week 1: 3.4 ± 0.6 µmol vs Week 2: 9.9 ± 1.0 µmol urinary sucrose; p < 0.05). There were no differences in the change in permeability after the aspirin challenge or gastrointestinal function between interventions. CONCLUSION: The acute aspirin challenge significantly increased intestinal permeability similarly in both groups, and prophylactic probiotic consumption was unable to prevent the loss in this particular model.

Effects of Chatbot Components to Facilitate Mental Health Services Use in Individuals With Eating Disorders Following Online Screening: An Optimization Randomized Controlled Trial.

OBJECTIVE: Few individuals with eating disorders (EDs) receive treatment. Innovations are needed to identify individuals with EDs and address care barriers. We developed a chatbot for promoting services uptake that could be paired with online screening. However, it is not yet known which components drive effects. This study estimated individual and combined contributions of four chatbot components on mental health services use (primary), chatbot helpfulness, and attitudes toward changing eating/shape/weight concerns ("change attitudes," with higher scores indicating greater importance/readiness). METHODS: Two hundred five individuals screening with an ED but not in treatment were randomized in an optimization randomized controlled trial to receive up to four chatbot components: psychoeducation, motivational interviewing, personalized service recommendations, and repeated administration (follow-up check-ins/reminders). Assessments were at baseline and 2, 6, and 14 weeks. RESULTS: Participants who received repeated administration were more likely to report mental health services use, with no significant effects of other components on services use. Repeated administration slowed the decline in change attitudes participants experienced over time. Participants who received motivational interviewing found the chatbot more helpful, but this component was also associated with larger declines in change attitudes. Participants who received personalized recommendations found the chatbot more helpful, and receiving this component on its own was associated with the most favorable change attitude time trend. Psychoeducation showed no effects. DISCUSSION: Results indicated important effects of components on outcomes; findings will be used to finalize decision making about the optimized intervention package. The chatbot shows high potential for addressing the treatment gap for EDs.

Eating disorder symptoms and comorbid mental health risk among teens recruited to a digital intervention research study via two online approaches.

INTRODUCTION: It is crucial to identify and evaluate feasible, proactive ways to reach teens with eating disorders (EDs) who may not otherwise have access to screening or treatment. This study aimed to explore the feasibility of recruiting teens with EDs to a digital intervention study via social media and a publicly available online ED screen, and to compare the characteristics of teens recruited by each approach in an exploratory fashion. METHOD: Teens aged 14-17 years old who screened positive for a clinical/subclinical ED or at risk for an ED and who were not currently in ED treatment completed a baseline survey to assess current ED symptoms, mental health comorbidities, and barriers to treatment. Bivariate analyses were conducted to examine differences between participants recruited via social media and those recruited after completion of a widely available online EDs screen (i.e., National Eating Disorders Association [NEDA] screen). RESULTS: Recruitment of teens with EDs using the two online approaches was found to be feasible, with 934 screens completed and a total of 134 teens enrolled over 6 months: 77% (n = 103) via social media 23% (n = 31) via the NEDA screen. Mean age of participants (N = 134) was 16 years old, with 49% (n = 66) identifying as non-White, and 70% (n = 94) identifying as a gender and/or sexual minority. Teens from NEDA reported higher ED psychopathology scores (medium effect size) and more frequent self-induced vomiting and driven exercise (small effect sizes). Teens from NEDA also endorsed more barriers to treatment, including not feeling ready for treatment and not knowing where to find a counselor or other resources (small effect sizes). DISCUSSION: Online recruitment approaches in this study reached a large number of teens with an interest in a digital intervention to support ED recovery, demonstrating the feasibility of these outreach methods. Both approaches reached teens with similar demographic characteristics; however, teens recruited from NEDA reported higher ED symptom severity and barriers to treatment. Findings suggest that proactive assessment and intervention methods should be developed and tailored to meet the needs of each of these groups. PUBLIC SIGNIFICANCE: This study examined the feasibility of recruiting teens with EDs to a digital intervention research study via social media and NEDA's online screen, and demonstrated differences in ED symptoms among participants by recruitment approach.

Action recommendations review in community-based therapy and depression and anxiety outcomes: a machine learning approach.

BACKGROUND: While the positive impact of homework completion on symptom alleviation is well-established, the pivotal role of therapists in reviewing these assignments has been under-investigated. This study examined therapists' practice of assigning and reviewing action recommendations in therapy sessions, and how it correlates with patients' depression and anxiety outcomes. METHODS: We analyzed 2,444 therapy sessions from community-based behavioral health programs. Machine learning models and natural language processing techniques were deployed to discern action recommendations and their subsequent reviews. The extent of the review was quantified by measuring the proportion of session dialogues reviewing action recommendations, a metric we refer to as "review percentage". Using Generalized Estimating Equations modeling, we evaluated the correlation between this metric and changes in clients' depression and anxiety scores. RESULTS: Our models achieved 76% precision in capturing action recommendations and 71.1% in reviewing them. Using these models, we found that therapists typically provided clients with one to eight action recommendations per session to engage in outside therapy. However, only half of the sessions included a review of previously assigned action recommendations. We identified a significant interaction between the initial depression score and the review percentage (p = 0.045). When adjusting for this relationship, the review percentage was positively and significantly associated with a reduction in depression score (p = 0.032). This suggests that more frequent review of action recommendations in therapy relates to greater improvement in depression symptoms. Further analyses highlighted this association for mild depression (p = 0.024), but not for anxiety or moderate to severe depression. CONCLUSIONS: An observed positive association exists between therapists' review of previous sessions' action recommendations and improved treatment outcomes among clients with mild depression, highlighting the possible advantages of consistently revisiting therapeutic homework in real-world therapy settings. Results underscore the importance of developing effective strategies to help therapists maintain continuity between therapy sessions, potentially enhancing the impact of therapy.

Machine learning and Bayesian network analyses identifies associations with insomnia in a national sample of 31,285 treatment-seeking college students.

BACKGROUND: A better understanding of the relationships between insomnia and anxiety, mood, eating, and alcohol-use disorders is needed given its prevalence among young adults. Supervised machine learning provides the ability to evaluate which mental disorder is most associated with heightened insomnia among U.S. college students. Combined with Bayesian network analysis, probable directional relationships between insomnia and interacting symptoms may be illuminated. METHODS: The current exploratory analyses utilized a national sample of college students across 26 U.S. colleges and universities collected during population-level screening before entering a randomized controlled trial. We used a 4-step statistical approach: (1) at the disorder level, an elastic net regularization model examined the relative importance of the association between insomnia and 7 mental disorders (major depressive disorder, generalized anxiety disorder, social anxiety disorder, panic disorder, post-traumatic stress disorder, anorexia nervosa, and alcohol use disorder); (2) This model was evaluated within a hold-out sample. (3) at the symptom level, a completed partially directed acyclic graph (CPDAG) was computed via a Bayesian hill-climbing algorithm to estimate potential directionality among insomnia and its most associated disorder [based on SHAP (SHapley Additive exPlanations) values)]; (4) the CPDAG was then tested for generalizability by assessing (in)equality within a hold-out sample using structural hamming distance (SHD). RESULTS: Of 31,285 participants, 20,597 were women (65.8%); mean (standard deviation) age was 22.96 (4.52) years. The elastic net model demonstrated clinical significance in predicting insomnia severity in the training sample [R2 = .44 (.01); RMSE = 5.00 (0.08)], with comparable performance in the hold-out sample (R2 = .33; RMSE = 5.47). SHAP values indicated that the presence of any mental disorder was associated with higher insomnia scores, with major depressive disorder as the most important disorder associated with heightened insomnia (mean |SHAP|= 3.18). The training CPDAG and hold-out CPDAG (SHD = 7) suggested depression symptoms presupposed insomnia with depressed mood, fatigue, and self-esteem as key parent nodes. CONCLUSION: These findings provide insights into the associations between insomnia and mental disorders among college students and warrant further investigation into the potential direction of causality between insomnia and depression. TRIAL REGISTRATION: Trial was registered on the National Institute of Health RePORTER website (R01MH115128 || 23/08/2018).

Vitamin D-Do Diet Recommendations for Health Remain Strong?

How will the scientific community and authoritative bodies define future nutritional requirements for vitamin D? At the International Symposium on Nutritional Aspects of Musculoskeletal Health, the authors debated the strength of current evidence for setting vitamin D intake recommendations from diet: the positive side of the strength of the evidence (PRO) suggests there is a physiological requirement for vitamin D and the opposing view (CON) that in light of negative results from large, recent trials, particularly those with fractures and bone health outcomes, we are left rudderless. Should we provide recommendations based on empiric treatment of vitamin D for most groups and conditions? It is becoming increasingly evident that vitamin D plays a role in many physiological functions and processes associated with long-term human health; however, to what extent are these benefits apparent beyond what is needed for adequate nutritional status, measured as serum 25-hydroxyvitamin D levels, for active calcium absorption? The meeting attendees voted for the PRO vs. CON position at the end of the session.

Depth-resolved water temperature measurements using Raman LiDAR.

We present the retrieval of depth-resolved temperature measurements in water using Raman LiDAR. Using a 5 m pipe of laboratory water, we recover non-homogeneous temperature profiles with a temperature accuracy ranging between 0.35°C and 0.85°C, and a position resolution of 28 cm.

Peri-operative cardiac arrest: epidemiology and clinical features of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. Here we report the results of the 12-month registry, from 16 June 2021 to 15 June 2022, focusing on epidemiology and clinical features. We reviewed 881 cases of peri-operative cardiac arrest, giving an incidence of 3 in 10,000 anaesthetics (95%CI 3.0-3.5 per 10,000). Incidence varied with patient and surgical factors. Compared with denominator survey activity, patients with cardiac arrest: included more males (56% vs. 42%); were older (median (IQR) age 60.5 (40.5-80.5) vs. 50.5 (30.5-70.5) y), although the age distribution was bimodal, with infants and patients aged > 66 y overrepresented; and were notably more comorbid (73% ASA physical status 3-5 vs. 27% ASA physical status 1-2). The surgical case-mix included more weekend (14% vs. 11%), out-of-hours (19% vs. 10%), non-elective (65% vs. 30%) and major/complex cases (60% vs. 28%). Cardiac arrest was most prevalent in orthopaedic trauma (12%), lower gastrointestinal surgery (10%), cardiac surgery (9%), vascular surgery (8%) and interventional cardiology (6%). Specialities with the highest proportion of cases relative to denominator activity were: cardiac surgery (9% vs. 1%); cardiology (8% vs. 1%); and vascular surgery (8% vs. 2%). The most common causes of cardiac arrest were: major haemorrhage (17%); bradyarrhythmia (9%); and cardiac ischaemia (7%). Patient factors were judged a key cause of cardiac arrest in 82% of cases, anaesthesia in 40% and surgery in 35%.

The incidence of potentially serious complications during non-obstetric anaesthetic practice in the United Kingdom: an analysis from the 7th National Audit Project (NAP7) activity survey.

Complications and critical incidents arising during anaesthesia due to patient, surgical or anaesthetic factors, may cause harm themselves or progress to more severe events, including cardiac arrest or death. As part of the 7th National Audit Project of the Royal College of Anaesthetists, we studied a prospective national cohort of unselected patients. Anaesthetists recorded anonymous details of all cases undertaken over 4 days at their site through an online survey. Of 416 hospital sites invited to participate, 352 (85%) completed the survey. Among 24,172 cases, 1922 discrete potentially serious complications were reported during 1337 (6%) cases. Obstetric cases had a high reported major haemorrhage rate and were excluded from further analysis. Of 20,996 non-obstetric cases, 1705 complications were reported during 1150 (5%) cases. Circulatory events accounted for most complications (616, 36%), followed by airway (418, 25%), metabolic (264, 15%), breathing (259, 15%), and neurological (41, 2%) events. A single complication was reported in 851 (4%) cases, two complications in 166 (1%) cases and three or more complications in 133 (1%) cases. In non-obstetric elective surgery, all complications were 'uncommon' (10-100 per 10,000 cases). Emergency (urgent and immediate priority) surgery accounted for 3454 (16%) of non-obstetric cases but 714 (42%) of complications with severe hypotension, major haemorrhage, severe arrhythmias, septic shock, significant acidosis and electrolyte disturbances all being 'common' (100-1000 per 10,000 cases). Based on univariate analysis, complications were associated with: younger age; higher ASA physical status; male sex; increased frailty; urgency and extent of surgery; day of the week; and time of day. These data represent the rates of potentially serious complications during routine anaesthesia care and may be valuable for risk assessment and patient consent.

Peri-operative cardiac arrest: management and outcomes of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. We report the results of the 12-month registry phase, from 16 June 2021 to 15 June 2022, focusing on management and outcomes. Among 881 cases of peri-operative cardiac arrest, the initial rhythm was non-shockable in 723 (82%) cases, most commonly pulseless electrical activity. There were 665 (75%) patients who survived the initial event and 384 (52%) who survived to hospital discharge. A favourable functional outcome (based on modified Rankin Scale score) was reported for 249 (88%) survivors. Outcomes varied according to arrest rhythm. The highest rates of survival were seen for bradycardic cardiac arrests with 111 (86%) patients surviving the initial event and 77 (60%) patients surviving the hospital episode. The lowest survival rates were seen for patients with pulseless electrical activity, with 312 (68%) surviving the initial episode and 156 (34%) surviving to hospital discharge. Survival to hospital discharge was worse in patients at the extremes of age with 76 (40%) patients aged > 75 y and 9 (45%) neonates surviving. Hospital survival was also associated with surgical priority, with 175 (88%) elective patients and 176 (37%) non-elective patients surviving to discharge. Outcomes varied with the cause of cardiac arrest, with lower initial survival rates for pulmonary embolism (5, 31%) and bone cement implantation syndrome (9, 45%), and hospital survival of < 25% for pulmonary embolism (0), septic shock (13, 24%) and significant hyperkalaemia (1, 20%). Overall care was rated good in 464 (53%) cases, and 18 (2%) cases had overall care rated as poor. Poor care elements were present in a further 245 (28%) cases. Care before cardiac arrest was the phase most frequently rated as poor (92, 11%) with elements of poor care identified in another 186 (21%) cases. These results describe the management and outcomes of peri-operative cardiac arrest in UK practice for the first time.

Accessibility and Utility of an Electronic Self-Guided Safety Plan for Adolescents.

OBJECTIVE: Suicidal thoughts and behaviors are a leading cause of death, injury, and hospitalization among adolescents. Few evidence-based interventions exist, and these tend to be inaccessible for most youth. Electronic safety plan interventions represent a new avenue to disseminate an evidence-based suicide prevention tool. However, it is not clear whether youth find electronic, self-guided safety plans helpful, nor whether they will use the resulting safety card when experiencing suicidal thoughts or urges. This study examines adolescents' perceptions and use of an electronic, self-guided safety plan intervention. METHOD: We recruited 322 adolescents with a past-year history of suicidal thoughts or behaviors, ages 13-17 (55.9% white and non-Hispanic; majority reporting diverse sexual orientations and genders) online via social media to participate in this two-part longitudinal study. At baseline, participants completed the electronic safety plan interventions and reported on key aspects of its usefulness and areas of improvement. Participants reported their use and perceptions of the plan one month later. RESULTS: Results suggested that adolescents understood, liked, and believed they would use a self-guided safety plan. One month later, about ⅓ of youth who experienced suicidal thoughts or urges used their safety card. Open-ended responses highlighted several features that adolescents enjoyed, including clarity, ease of use, and privacy. Participants also highlighted key areas for improvement, including formatting and language. CONCLUSION: This study provides initial support for adolescent use of electronic self-guided safety plans. Next steps include updating this intervention based on youth feedback and testing the effectiveness of this tool using gold standard research methods.

A Prospective Examination of the Interpersonal-Psychological Theory of Suicidal Behavior in Adolescents.

OBJECTIVE: Given the large and complex array of suicide risk factors, theoretical frameworks are critical to furthering our understanding of risk. This study prospectively examined several key constructs of the interpersonal-psychological theory of suicidal behavior (IPTS) in a large, geographically diverse sample of U.S. adolescents. METHOD: Conducted in collaboration with the Pediatric Emergency Care Applied Research Network, adolescents, ages 12 to 17, were recruited from emergency departments. Baseline and 6-month follow-up samples were comprised of 6,448 (59% female sex) and 2,009 (64% female sex) adolescents, with self-identified race/ethnicity as follows (baseline/follow-up): White (52%/54%), Black (22%/23%), Multiracial (6%/6%), American Indian (3%/3%), other/unknown race (15%/14%), and Latinx (25%/23%). Youth and parents completed adolescent suicide risk surveys at baseline and 6-month follow-up (retention, 69%). Latent class analysis was used to identify classes of painful and provocative events (PPE), considered a precursor to acquired capability. RESULTS: In keeping with IPTS tenets, thwarted belongingness (TB), perceived burdensomeness (PB), and the interaction between TB and PB were each significant predictors of suicidal ideation at baseline and follow-up. However, only PB and PPE were significant predictors of cross-sectional suicide attempts and only TB and PPE were significant predictors of prospective suicide attempts in models that adjusted for baseline suicidal ideation. The three-way interaction among PB, TB and PPE was nonsignificant. CONCLUSIONS: Results from this large-scale prospective study suggest the importance of TB, PB, and PPE to our understanding of suicidal thoughts and suicide attempts among adolescents, pointing to promising prevention and intervention targets.

Association of behavioural and social-communicative profiles in children with 16p11.2 copy number variants: a multi-site study.

BACKGROUND: Despite the established knowledge that recurrent copy number variants (CNVs) at the 16p11.2 locus BP4-BP5 confer risk for behavioural and language difficulties, limited research has been conducted on the association between behavioural and social-communicative profiles. The current study aims to further delineate the prevalence, nature and severity of, and the association between, behavioural and social-communicative features of school-aged children with 16p11.2 deletion syndrome (16p11.2DS) and 16p11.2 duplication (16p11.2Dup). METHODS: A total of 68 individuals (n = 47 16p11.2DS and n = 21 16p11.2Dup) aged 6-17 years participated. Standardised intelligence tests were administered, and behavioural and social-communicative skills were assessed by standardised questionnaires. Scores of both groups were compared with population norms and across CNVs. The influence of confounding factors was investigated, and correlation analyses were performed. RESULTS: Compared with the normative sample, children with 16p11.2DS showed high rates of social responsiveness (67%) and communicative problems (69%), while approximately half (52%) of the patients displayed behavioural problems. Children with 16p11.2Dup demonstrated even higher rates of social-communicative problems (80-90%) with statistically significantly more externalising and overall behavioural challenges (89%). In both CNV groups, there was a strong positive correlation between behavioural and social-communicative skills. CONCLUSIONS: School-aged children with 16p11.2 CNVs show high rates of behavioural, social responsiveness and communicative problems compared with the normative sample. These findings point to the high prevalence of autistic traits and diagnoses in these CNV populations. Moreover, there is a high comorbidity between behavioural and social-communicative problems. Patients with difficulties in both domains are vulnerable and need closer clinical follow-up and care.