Cognitive Functioning in Youth with Anxiety Disorders: A Systematic Review.

Anxiety disorders are disorders involving cognition. Research on cognition in youth with anxiety can focus on cognitive content (e.g., self-talk) as well cognitive functioning. The present review examines domains of cognitive functioning (i.e., episodic memory, language, attention, executive functioning, motor skills, and visual functioning) in youth diagnosed with an anxiety disorder. A database search of Embase, PsycINFO, and PubMed yielded 28 studies that met inclusion criteria of youth aged 17 years or younger, a sample diagnosed with a principal anxiety disorder and a comparison sample of controls, a comparison between those samples, and use of a behavioral measure of neuropsychological performance. Findings did not identify any cognitive functioning strengths for anxious youth. Deficits were found in two domains (i.e., receptive language and motor skills) whereas no deficits were found in attention, visuospatial skills and one domain of executive functioning (i.e., inhibition). Most domains had mixed findings. Additional analysis indicated that anxiety disorders in youth are not associated with diminished IQ. Directions for future research are identified including (a) the prioritization of studies with larger, representative samples (b) the role of cognitive functioning as a predictor of anxiety treatment outcome (c) the examination of the effect of treatment on cognitive performance, and (d) the course of anxiety and potential impairment in cognitive functioning.

What caregivers like the most (and least) about cognitive behavioral therapy for youth anxiety: A mixed methods approach.

Cognitive behavioral therapy (CBT) is an efficacious therapy for youth anxiety disorders. Caregivers are key stakeholders in youth therapy, and their feedback on treatment can help to inform intervention personalization. This mixed-methods study applied a systematic inductive thematic analysis to identify themes among most- and least-liked CBT features reported by caregivers using open-ended responses on the Client Satisfaction Questionnaire (CSQ-8). The sample included 139 caregivers of youth ages 7-17 (M = 12.21, SD = 3.05; 59% female; 79.1% Caucasian, 5.8% Black, 2.9% Asian, 2.2% Hispanic, 7.9% Multiracial, 2.2% Other) with principal anxiety diagnoses who completed 16-sessions of CBT. CSQ-8 quantitative satisfaction scores (M = 29.18, SD = 3.30; range: 16-32) and survey-based treatment response rates (responders n = 93, 67%) were high. Most-liked treatment features included: coping skills (i.e., exposure, understanding/identifying anxiety, rewards, homework), therapist factors (interpersonal style/skill, relationship, accessibility), caregiver involvement, one-on-one time with a therapist, structure, consistency, and personally tailored treatment. Least-liked treatment features included: questionnaires, logistical barriers, telehealth, need for more sessions, non-anxiety concerns not addressed, insufficient caregiver involvement, and aspects of exposure tasks. Proportional frequencies of most- and least-liked themes differed by treatment responder status (e.g., responders cited exposure and homework as most-liked more frequently).

Adapting CBT for youth anxiety: Flexibility, within fidelity, in different settings.

Anxiety disorders are common in youth, associated with impairments in daily functioning, and often persist into adulthood when untreated. Cognitive behavioral therapy (CBT) for youth anxiety is a well-established intervention and has been modified to fit several treatment settings. Despite decades of results supporting the efficacy of CBT, there is a large gap in access to this treatment and a need to consider how it can best be administered flexibly to increase uptake and personalization. We first discuss the core components of treatment for CBT through the lens of the Coping Cat treatment. Next, we review the empirical findings regarding adjustments made for CBT for youth anxiety delivered (a) in schools, (b) in community settings, (c) through telehealth, (d) through online computer programs, and (e) by caregivers at home. In each setting, we provide specific suggestions for how to implement CBT with flexibility while maintaining fidelity.

CBT for Youth Anxiety: How Does It Fit Within Community Mental Health?

PURPOSE OF REVIEW: We review (1) the empirical literature for cognitive behavioral therapy (CBT) for youth anxiety delivered in community settings, (2) the use of online delivery methods in this process, and (3) identified barriers and facilitators to implementation of CBT for youth anxiety in community mental health clinics (CMHCs). We provide suggestions for future work. RECENT FINDINGS: Meta-analytic reviews of effectiveness studies suggest that outcomes comparable to those of efficacy studies can be achieved in community settings, particularly when in-session exposures occur. Several online programs support delivery of these services, with an evidence base that is promising. The notable barrier to the implementation of services is the cost of implementation and sustainability. Organizational factors such as leadership, culture, and climate are consistently identified as barriers and facilitators depending on their valence and appear to be related to implementation outcomes (e.g., on provider attitudes). The current findings need to be integrated into future studies, with a focus on further identifying facilitators (e.g., champions and online programs) of implementation. There is also the need for efforts to address organizational and individual barriers and to compare ways to reduce costs.

Meeting nutritional targets of critically ill patients by combined enteral and parenteral nutrition: review and rationale for the EFFORTcombo trial.

While medical nutrition therapy is an essential part of the care for critically ill patients, uncertainty exists about the right form, dosage, timing and route in relation to the phases of critical illness. As enteral nutrition (EN) is often withheld or interrupted during the intensive care unit (ICU) stay, combined EN and parenteral nutrition (PN) may represent an effective and safe option to achieve energy and protein goals as recommended by international guidelines. We hypothesise that critically ill patients at high nutritional risk may benefit from such a combined approach during their stay on the ICU. Therefore, we aim to test if an early combination of EN and high-protein PN (EN+PN) is effective in reaching energy and protein goals in patients at high nutritional risk, while avoiding overfeeding. This approach will be tested in the here-presented EFFORTcombo trial. Nutritionally high-risk ICU patients will be randomised to either high (≥2·2 g/kg per d) or low protein (≤1·2 g/kg per d). In the high protein group, the patients will receive EN+PN; in the low protein group, patients will be given EN alone. EN will be started in accordance with international guidelines in both groups. Efforts will be made to reach nutrition goals within 48-96 h. The efficacy of the proposed nutritional strategy will be tested as an innovative approach by functional outcomes at ICU and hospital discharge, as well as at a 6-month follow-up.

Selenium-Binding Protein 1 Indicates Myocardial Stress and Risk for Adverse Outcome in Cardiac Surgery.

Selenium-binding protein 1 (SELENBP1) is an intracellular protein that has been detected in the circulation in response to myocardial infarction. Hypoxia and cardiac surgery affect selenoprotein expression and selenium (Se) status. For this reason, we decided to analyze circulating SELENBP1 concentrations in patients (n = 75) necessitating cardioplegia and a cardiopulmonary bypass (CPB) during the course of the cardiac surgery. Serum samples were collected at seven time-points spanning the full surgical process. SELENBP1 was quantified by a highly sensitive newly developed immunological assay. Serum concentrations of SELENBP1 increased markedly during the intervention and showed a positive association with the duration of ischemia (ρ = 0.6, p < 0.0001). Elevated serum SELENBP1 concentrations at 1 h after arrival at the intensive care unit (post-surgery) were predictive to identify patients at risk of adverse outcome (death, bradycardia or cerebral ischemia, "endpoint 1"; OR 29.9, CI 3.3-268.8, p = 0.00027). Circulating SELENBP1 during intervention (2 min after reperfusion or 15 min after weaning from the CPB) correlated positively with an established marker of myocardial infarction (CK-MB) measured after the intervention (each with ρ = 0.5, p < 0.0001). We concluded that serum concentrations of SELENBP1 were strongly associated with cardiac arrest and the duration of myocardial ischemia already early during surgery, thereby constituting a novel and promising quantitative marker for myocardial hypoxia, with a high potential to improve diagnostics and prediction in combination with the established clinical parameters.

Prediction of Prolonged ICU Stay in Cardiac Surgery Patients as a Useful Method to Identify Nutrition Risk in Cardiac Surgery Patients: A Post Hoc Analysis of a Prospective Observational Study.

BACKGROUND: Cardiovascular surgery patients with a prolonged intensive care unit (ICU) stay may benefit most from early nutrition support. Using established scoring systems for nutrition assessment and operative risk stratification, we aimed to develop a model to predict a prolonged ICU stay ≥5 days in order to identify patients who will benefit from early nutrition interventions. METHODS: This is a retrospective analysis of a prospective observational study of patients undergoing elective valvular, coronary artery bypass grafting, or combined cardiac surgery. The nutrition risk was assessed by well-established screening tools. Patients' preoperative EuroSCORE (European System for Cardiac Operative Risk Evaluation), primary disease, and intraoperative cardiopulmonary bypass (CPB) time were included as independent variables in a multivariate logistic regression analysis to predict a prolonged ICU stay (>4 days). RESULTS: The number of cardiac surgery patients included was 1193. Multivariate analysis revealed that for prediction of ICU stay >4 days, both Nutritional Risk Screening 2002 (area under the curve (AUC): 0.716, P = .020) and Mini Nutritional Assessment (MNA) score (AUC: 0.715, P = .037) were significant, whereas for prediction of ICU stay >5 days, only the MNA score showed significant results (AUC: 0.762, P = .011). CONCLUSION: Present data provide first evidence about the combined use of EuroSCORE, primary disease, CPB time, and nutrition risk screening tools for prediction of prolonged ICU stay in cardiac surgery patients. If prospectively evaluated in adequately designed studies, this model may help to identify patients with prolonged ICU stay to initiate early postoperative nutrition therapy and thus, facilitate an enhanced recovery.

The relevance of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentration for postoperative infections and postoperative organ dysfunctions in cardiac surgery patients: The eVIDenCe study.

BACKGROUND & AIMS: Recent studies indicate that vitamin D deficiency is associated with increased morbidity and mortality in critically ill patients. Knowledge about the functional role and clinical relevance of vitamin D for patients undergoing cardiac surgery is sparse. Therefore, we investigated the clinical significance of vitamin D levels on outcome of cardiac surgery patients. METHODS: 92 patients undergoing elective cardiac surgery with cardiopulmonary arrest were included in this prospective observational pilot study. 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were measured prior to surgery, immediately postoperatively as well as 6, 12 and 24 h after surgery. We assessed postoperative organ dysfunctions, infections and death until hospital discharge. RESULTS: The serum concentration of 1,25(OH)2D significantly decreased intraoperatively by 29.3% (p < 0.001) and was significantly lower at any postoperative time point compared to baseline values, whereas 25OHD levels did not show significant changes during the observation period. Coronary artery bypass graft (CABG) patients had significant higher baseline 1,25(OH)2D values than patients with valve surgery (39.7 ± 13.9 ng/l vs. 30.1 ± 14.1 ng/l, p = 0.010) or CABG + valve surgery (39.7 ± 13.9 ng/l vs. 32.6 ± 11.8 ng/l, p = 0.044). Our data showed a significant odds ratio to develop postoperative organ dysfunction (OR 0.95; p = 0.009) and PCT levels ≥5 µg/l (OR 0.94; p = 0.046) for every ng/l increment in 1,25(OH)2D, when performing multivariable analysis and after adjusting for preoperative illness and demographics. In addition, multivariable-adjusted statistical analyses revealed that patients stayed significantly shorter on ICU (-0.21 h; p = 0.001) and in hospital (-2.6 days; p = 0.009) for every ng/l increment in 1,25(OH)2D. CONCLUSION: Our data highlight important evidence about the clinical significance of 1,25(OH)2D levels in cardiac surgery patients. Higher levels were associated with significantly less postoperative organ dysfunctions, elevated PCT levels, death and prolonged hospital stay. 1,25(OH)2D levels decreased significantly intra- and postoperatively, while serum levels of 25OHD did not. TRIAL REGISTRATION: clinicaltrials.gov (NCT02488876), registered May 1, 2015.

Remote Ischemic Preconditioning Does Not Affect the Release of Humoral Factors in Propofol-Anesthetized Cardiac Surgery Patients: A Secondary Analysis of the RIPHeart Study.

In contrast to several smaller studies, which demonstrate that remote ischemic preconditioning (RIPC) reduces myocardial injury in patients that undergo cardiovascular surgery, the RIPHeart study failed to demonstrate beneficial effects of troponin release and clinical outcome in propofol-anesthetized cardiac surgery patients. Therefore, we addressed the potential biochemical mechanisms triggered by RIPC. This is a predefined prospective sub-analysis of the randomized and controlled RIPHeart study in cardiac surgery patients (n = 40) that was recently published. Blood samples were drawn from patients prior to surgery, after RIPC of four cycles of 5 min arm ischemia/5 min reperfusion (n = 19) and the sham (n = 21) procedure, after connection to cardiopulmonary bypass (CPB), at the end of surgery, 24 h postoperatively, and 48 h postoperatively for the measurement of troponin T, macrophage migration inhibitory factor (MIF), stromal cell-derived factor 1 (CXCL12), IL-6, CXCL8, and IL-10. After RIPC, right atrial tissue samples were taken for the measurement of extracellular-signal regulated kinase (ERK1/2), protein kinase B (AKT), Glycogen synthase kinase 3 (GSK-3ß), protein kinase C (PKCε), and MIF content. RIPC did not significantly reduce the troponin release when compared with the sham procedure. MIF serum levels intraoperatively increased, peaking at intensive care unit (ICU) admission (with an increase of 48.04%, p = 0.164 in RIPC; and 69.64%, p = 0.023 over the baseline in the sham procedure), and decreased back to the baseline 24 h after surgery, with no differences between the groups. In the right atrial tissue, MIF content decreased after RIPC (1.040 ± 1.032 Arbitrary units [au] in RIPC vs. 2.028 ± 1.631 [au] in the sham procedure, p < 0.05). CXCL12 serum levels increased significantly over the baseline at the end of surgery, with no differences between the groups. ERK1/2, AKT, GSK-3ß, and PKCɛ phosphorylation in the right atrial samples were no different between the groups. No difference was found in IL-6, CXCL8, and IL10 serum levels between the groups. In this cohort of cardiac surgery patients that received propofol anesthesia, we could not show a release of potential mediators of signaling, nor an effect on the inflammatory response, nor an activation of well-established protein kinases after RIPC. Based on these data, we cannot exclude that confounding factors, such as propofol, may have interfered with RIPC.

Xenon detection in human blood: Analytical validation by accuracy profile and identification of critical storage parameters.

Xenon is a rare, mostly inert, noble gas that has applications in a wide range of fields, including medicine. Xenon acts on the human body as a useful organ-protective and anesthetic agent and has also been previously studied for potential applications in fields such as optics, aerospace and medical imaging. Recently, it was discovered that xenon can boost erythropoietin production, and it has been used as a performance-enhancing agent in international sports competitions such as the Sochi Olympic Games. Therefore, screening methods to detect the misuse of xenon by analysis of biological samples and to monitor anesthesia kinetics and efficiency are being investigated. The aim of this study was to develop and validate an analytical method to detect xenon in blood samples using gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). Preliminary studies were conducted to determine the best parameters for chromatography and mass spectrometry for xenon. The analysis was performed using the multiple reaction monitoring (MRM) mode using the transitions m/z 129 â†’ 129, 131 â†’ 131 for xenon and 84 â†’ 84, 86 â†’ 86 for krypton, which was chosen as the internal standard. The LOD of GC-MS/MS was found to be 52 pmol on-column. Calibration lines and controls were made to obtain an accuracy profile at a range of 2.08-104 nmol with a ß-expectation tolerance interval set at 80% and the acceptability limit set at ±30%. From the accuracy profile, the LOQ of 15 nmol on-column for the range of 2.08-104 nmol was obtained. The method was validated according to the guidelines of the French Society of Pharmaceutical Sciences and Techniques. The detection method was finally validated using blood from test persons subjected to a 15% or 30% xenon mixture with pure oxygen and air for 45 min. Even though the probes were already used for other projects, it was still possible to detect xenon.

Correction to: Sub-anesthetic Xenon Increases Erythropoietin Levels in Humans: A Randomized Controlled Trial.

Page 1764, Column 2, `Acknowledgements' section: The first sentence, which previously read.

Remote ischaemic preconditioning for coronary artery bypass grafting (with or without valve surgery).

BACKGROUND: Despite substantial improvements in myocardial preservation strategies, coronary artery bypass grafting (CABG) is still associated with severe complications. It has been reported that remote ischaemic preconditioning (RIPC) reduces reperfusion injury in people undergoing cardiac surgery and improves clinical outcome. However, there is a lack of synthesised information and a need to review the current evidence from randomised controlled trials (RCTs). OBJECTIVES: To assess the benefits and harms of remote ischaemic preconditioning in people undergoing coronary artery bypass grafting, with or without valve surgery. SEARCH METHODS: In May 2016 we searched CENTRAL, MEDLINE, Embase and Web of Science. We also conducted a search of ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). We also checked reference lists of included studies. We did not apply any language restrictions. SELECTION CRITERIA: We included RCTs in which people scheduled for CABG (with or without valve surgery) were randomly assigned to receive RIPC or sham intervention before surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted data and checked them for accuracy. We calculated mean differences (MDs), standardised mean differences (SMDs) and risk ratios (RR) using a random-effects model. We assessed quality of the trial evidence for all primary outcomes using the GRADE methodology. We completed a 'Risk of bias' assessment for all studies and performed sensitivity analysis by excluding studies judged at high or unclear risk of bias for sequence generation, allocation concealment and incomplete outcome data. We contacted authors for missing data. Our primary endpoints were 1) composite endpoint (including all-cause mortality, non-fatal myocardial infarction or any new stroke, or both) assessed at 30 days after surgery, 2) cardiac troponin T (cTnT, ng/L) at 48 hours and 72 hours, and as area under the curve (AUC) 72 hours (µg/L) after surgery, and 3) cardiac troponin I (cTnI, ng/L) at 48 hours, 72 hours, and as area under the curve (AUC) 72 hours (µg/L) after surgery. MAIN RESULTS: We included 29 studies involving 5392 participants (mean age = 64 years, age range 23 to 86 years, 82% male). However, few studies contributed data to meta-analyses due to inconsistency in outcome definition and reporting. In general, risk of bias varied from low to high risk of bias across included studies, and insufficient detail was provided to inform judgement in several cases. The quality of the evidence of key outcomes ranged from moderate to low quality due to the presence of moderate or high statistical heterogeneity, imprecision of results or due to limitations in the design of individual studies.Compared with no RIPC, we found that RIPC has no treatment effect on the rate of the composite endpoint with RR 0.99 (95% confidence interval (CI) 0.78 to 1.25); 2 studies; 2463 participants; moderate-quality evidence. Participants randomised to RIPC showed an equivalent or better effect regarding the amount of cTnT release measured at 72 hours after surgery with SMD -0.32 (95% CI -0.65 to 0.00); 3 studies; 1120 participants; moderate-quality evidence; and expressed as AUC 72 hours with SMD -0.49 (95% CI -0.96 to -0.02); 3 studies; 830 participants; moderate-quality evidence. We found the same result in favour of RIPC for the cTnI release measured at 48 hours with SMD -0.21 (95% CI -0.40 to -0.02); 5 studies; 745 participants; moderate-quality evidence; and measured at 72 hours after surgery with SMD -0.37 (95% CI -0.59 to -0.15); 2 studies; 459 participants; moderate-quality evidence. All other primary outcomes showed no differences between groups (cTnT release measured at 48 hours with SMD -0.14, 95% CI -0.33 to 0.06; 4 studies; 1792 participants; low-quality evidence and cTnI release measured as AUC 72 hours with SMD -0.17, 95% CI -0.48 to 0.14; 2 studies; 159 participants; moderate-quality evidence).We also found no differences between groups for all-cause mortality after 30 days, non-fatal myocardial infarction after 30 days, any new stroke after 30 days, acute renal failure after 30 days, length of stay on the intensive care unit (days), any complications and adverse effects related to ischaemic preconditioning. We did not assess many patient-centred/salutogenic-focused outcomes. AUTHORS' CONCLUSIONS: We found no evidence that RIPC has a treatment effect on clinical outcomes (measured as a composite endpoint including all-cause mortality, non-fatal myocardial infarction or any new stroke, or both, assessed at 30 days after surgery). There is moderate-quality evidence that RIPC has no treatment effect on the rate of the composite endpoint including all-cause mortality, non-fatal myocardial infarction or any new stroke assessed at 30 days after surgery, or both. We found moderate-quality evidence that RIPC reduces the cTnT release measured at 72 hours after surgery and expressed as AUC (72 hours). There is moderate-quality evidence that RIPC reduces the amount of cTnI release measured at 48 hours, and measured 72 hours after surgery. Adequately-designed studies, especially focusing on influencing factors, e.g. with regard to anaesthetic management, are encouraged and should systematically analyse the commonly used medications of people with cardiovascular diseases.

Sub-anesthetic Xenon Increases Erythropoietin Levels in Humans: A Randomized Controlled Trial.

BACKGROUND: The licensed anesthetic xenon, which exerts organ protective properties, was recently added by the World Anti-Doping Agency to the list of prohibited substances. Xenon is supposed to trigger the production of hypoxia-inducible factor 1α (HIF-1α) and subsequently erythropoietin, but data are limited to in vivo experimental work. Therefore we evaluated the effect of xenon on erythropoietin levels in healthy persons. METHODS: Twenty-four healthy volunteers were randomly assigned either to a group spontaneously breathing xenon 30 % (Xe/O2 30 %/60 %) or a group breathing control gas (N2/O2 40 %/60 %) for 45 min. Primary outcome parameters were erythropoietin levels at several time-points after exposure. Secondary outcome parameters were serum levels of testosterone, cytokines, and growth factors as well as concentrations of xenon in blood and exhalation samples measured at several time-points after exposure. In addition, hemodynamic safety parameters were monitored during exposure. RESULTS: The administration of xenon significantly increased erythropoietin levels 8 h after exposure (1.34 [±0.368]; p = 0.008), peaking at 24 h compared to the baseline values (1.45 [±0.498]; p = 0.01) and remained traceable in blood and exhalation probes until 24 h after exposure. In contrast, no significant change was observed in the control group. Measurement of stromal cell-derived factor 1 (SDF-1) revealed a significant increase of SDF-1 levels (p = 0.005), whereas no differences were observed with respect to growth factors, cytokines, or androgens. In an in vitro chemotaxis assay, endothelial progenitor cells (EPCs) showed a trend towards increased migration in serum samples received from participants after xenon exposure (p = 0.080). CONCLUSION: The present study presents first evidence about a xenon-induced effect on increased erythropoietin levels in healthy volunteers. The study was registered at the European Medicines Agency (EudraCT-number: 2014-000973-38) and at ClinicalTrials.gov (NCT number: 02129400).