FASDetect as a machine learning-based screening app for FASD in youth with ADHD.

Fetal alcohol-spectrum disorder (FASD) is underdiagnosed and often misdiagnosed as attention-deficit/hyperactivity disorder (ADHD). Here, we develop a screening tool for FASD in youth with ADHD symptoms. To develop the prediction model, medical record data from a German University outpatient unit are assessed including 275 patients aged 0-19 years old with FASD with or without ADHD and 170 patients with ADHD without FASD aged 0-19 years old. We train 6 machine learning models based on 13 selected variables and evaluate their performance. Random forest models yield the best prediction models with a cross-validated AUC of 0.92 (95% confidence interval [0.84, 0.99]). Follow-up analyses indicate that a random forest model with 6 variables - body length and head circumference at birth, IQ, socially intrusive behaviour, poor memory and sleep disturbance - yields equivalent predictive accuracy. We implement the prediction model in a web-based app called FASDetect - a user-friendly, clinically scalable FASD risk calculator that is freely available at https://fasdetect.dhc-lab.hpi.de .

A Retrospective Pilot Study of Imagery Rehearsal Therapy Enhanced with Narrative Therapy Principles for the Treatment of Nightmares in US Military Veterans.

Introduction Chronic nightmares are a common and disabling feature of posttraumatic stress disorder (PTSD) for which broadly effective treatments are still lacking. While imagery rehearsal therapy (IRT) demonstrates benefits for patients with idiopathic nightmares and some patients with PTSD-related nightmares, research indicates it may be less beneficial for veterans. Narrative therapy (NT) is a form of psychotherapy which is client-centered and value-focused and has demonstrated benefits for PTSD patients. The application of NT principles to IRT may provide a valuable therapeutic approach for treatment in veterans. Objective To perform a retrospective chart review of veteran clients participating in a novel, brief intervention developed by the first author consisting of IRT enhanced with NT principles (N-IRT) for the treatment of nightmares. The primary outcomes were nightmare frequency and intensity, and the secondary outcome was the impact of the intervention on nightmare distress and coping, subjective sleep quality, and overall PTSD symptoms. Materials and Methods We conducted retrospective chart reviews for eight veterans referred to the first author for the treatment of nightmares, who completed N-IRT, including baseline and end-of-treatment measures. The protocol involved a single 60-minute NT-enhanced rescripting session and assigned homework to rehearse the revised dream script, and a follow-up evaluation 4 weeks later. The subjects completed a sleep and nightmare interview developed by the first author and the PTSD Checklist at baseline and after the intervention at the follow-up evaluation. Paired t -tests were conducted to test for pre-to-post differences. Results In the statistical analysis, we observed a statistically significant and clinically meaningful reduction in the frequency ( p = 0.04) and intensity of nightmares ( p = 0.001) from pretreatment to the 1-month follow-up. Measures of nightmare-associated emotional distress, the ability to cope with nightmares, sleep duration and sleep efficiency, as well as overall PTSD symptoms also demonstrated significant improvements. Conclusion These pilot data provide compelling preliminary evidence that a single-session IRT intervention modified with NT (N-IRT) is effective in reducing nightmare frequency and intensity, reducing nightmare distress, improving the act of coping with nightmares, and improving sleep quality and overall PTSD symptoms in veterans. Further investigation of this method with gold-standard clinical trial designs and larger sample sizes is indicated to confirm effectiveness and to better understand the possible mechanisms of treatment effect.

Vascular access in children requiring maintenance haemodialysis: a consensus document by the European Society for Paediatric Nephrology Dialysis Working Group

There are three principle forms of vascular access available for the treatment of children with end stage kidney disease (ESKD) by haemodialysis: tunnelled catheters placed in a central vein (central venous lines, CVLs), arteriovenous fistulas (AVF), and arteriovenous grafts (AVG) using prosthetic orbiological material. Compared with the adult literature, there are few studies in children to provide evidence based guidelines for optimal vascular access type or its management and outcomes in children with ESKD.

Vascular access in children requiring maintenance haemodialysis: a consensus document by the European Society for Paediatric Nephrology Dialysis Working Group.

BACKGROUND: There are three principle forms of vascular access available for the treatment of children with end stage kidney disease (ESKD) by haemodialysis: tunnelled catheters placed in a central vein (central venous lines, CVLs), arteriovenous fistulas (AVF), and arteriovenous grafts (AVG) using prosthetic or biological material. Compared with the adult literature, there are few studies in children to provide evidence based guidelines for optimal vascular access type or its management and outcomes in children with ESKD. METHODS: The European Society for Paediatric Nephrology Dialysis Working Group (ESPN Dialysis WG) have developed recommendations for the choice of access type, pre-operative evaluation, monitoring, and prevention and management of complications of different access types in children with ESKD. RESULTS: For adults with ESKD on haemodialysis, the principle of "Fistula First" has been key to changing the attitude to vascular access for haemodialysis. However, data from multiple observational studies and the International Paediatric Haemodialysis Network registry suggest that CVLs are associated with a significantly higher rate of infections and access dysfunction, and need for access replacement. Despite this, AVFs are used in only ∼25% of children on haemodialysis. It is important to provide the right access for the right patient at the right time in their life-course of renal replacement therapy, with an emphasis on venous preservation at all times. While AVFs may not be suitable in the very young or those with an anticipated short dialysis course before transplantation, many paediatric studies have shown that AVFs are superior to CVLs. CONCLUSIONS: Here we present clinical practice recommendations for AVFs and CVLs in children with ESKD. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system has been used to develop and GRADE the recommendations. In the absence of high quality evidence, the opinion of experts from the ESPN Dialysis WG is provided, but is clearly GRADE-ed as such and must be carefully considered by the treating physician, and adapted to local expertise and individual patient needs as appropriate.

Loss of skills and onset patterns in neurodevelopmental disorders: Understanding the neurobiological mechanisms.

Patterns of onset in Autism Spectrum Disorder, including a pattern that includes loss of previously acquired skills, have been identified since the first reports of the disorder. However, attempts to study such "regression" have been limited to clinical studies, that until recently mostly involved retrospective reports. The current report reflects discussion that occurred at an NIMH convened meeting in 2016 with the purpose of bridging clinical autism research with basic and translational work in this area. This summary describes the state of the field with respect to clinical studies, describing gaps in knowledge based on limited methods and prospective data collected. Biological mechanisms that have been shown to account for regression early in development in specific conditions are discussed, as well as potential mechanisms that have not yet been explored. Suggestions include use of model systems during the developmental period and cutting-edge methods, including non-invasive imaging that may afford opportunities for a better understanding of the neurobiological pathways that result in loss of previously-attained skills. Autism Res 2018, 11: 212-222. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Loss of previously acquired skills, or regression, has been reported in Autism Spectrum Disorder since Kanner's reports in the 1950's. The current report reflects discussion from an NIMH convened meeting in 2016 with the purpose of bridging clinical autism research with basic and translational work in this area. This summary describes the state of the field regarding clinical studies and suggests use of model systems during the developmental period and cutting-edge methods, for a better understanding of the neurobiological pathways that result in loss of previously-attained skills.

Cognitive training in mental disorders: update and future directions.

OBJECTIVE: This article reviews the conceptual basis, definitions, and evolution of cognitive training approaches for the treatment of mental disorders. METHOD: The authors review the current state of the knowledge on cognitive training in psychiatric illnesses, and its neural and behavioral targets, and summarize the factors that appear to relate to a successful response, including learner characteristics that influence clinical outcome. They also discuss methodological issues relevant to the development and testing of cognitive training approaches, with the goal of creating maximally efficient and effective approaches to training. Finally, they identify gaps in existing knowledge and outline key research directions for the future. RESULTS: While much of the early research has been conducted in schizophrenia, cognitive training has more recently been applied to a widening range of neuropsychiatric illnesses, including attention deficit hyperactivity disorder, mood disorders, and substance use disorders. Cognitive training harnesses the inherent neuroplastic capacities of the brain, targeting neural system function across psychiatric disorders, thus improving the cognitive processes that play a role in emotion regulation, clinical symptoms, and adaptive community functioning. CONCLUSIONS: Cognitive training offers considerable promise, especially given the limited efficacy of pharmacological interventions in ameliorating cognitive deficits. However, more research is needed to understand the mechanisms underlying cognitive training, predictors of response, generalization and real-world applicability, and approaches to dissemination in practice settings.

Evaluation of infusions of xylazine with ketamine or propofol to modulate recovery following sevoflurane anesthesia in horses.

OBJECTIVE: To determine whether infusion of xylazine and ketamine or xylazine and propofol after sevoflurane administration in horses would improve the quality of recovery from anesthesia. ANIMALS: 6 healthy adult horses. PROCEDURES: For each horse, anesthesia was induced by administration of xylazine, diazepam, and ketamine and maintained with sevoflurane for approximately 90 minutes (of which the last 60 minutes were under steady-state conditions) 3 times at 1-week intervals. For 1 anesthetic episode, each horse was allowed to recover from sevoflurane anesthesia; for the other 2 episodes, xylazine and ketamine or xylazine and propofol were infused for 30 or 15 minutes, respectively, after termination of sevoflurane administration. Selected cardiopulmonary variables were measured during anesthesia and recovery. Recovery events were monitored and subjectively scored. RESULTS: Cardiopulmonary variables differed minimally among treatments, although the xylazine-propofol infusion was associated with greater respiratory depression than was the xylazine-ketamine infusion. Interval from discontinuation of sevoflurane or infusion administration to standing did not differ significantly among treatments, but the number of attempts required to stand successfully was significantly lower after xylazine-propofol infusion, compared with the number of attempts after sevoflurane alone. Scores for recovery from anesthesia were significantly lower (ie, better recovery) after either infusion, compared with scores for sevoflurane administration alone. CONCLUSIONS AND CLINICAL RELEVANCE: Xylazine-ketamine or xylazine-propofol infusion significantly improved quality of recovery from sevoflurane anesthesia in horses. Xylazine-ketamine or xylazine-propofol infusions may be of benefit during recovery from sevoflurane anesthesia in horses for which a smooth recovery is particularly critical. However, oxygenation and ventilation should be monitored carefully.

Design and subject characteristics in the federally-funded citalopram trial in children with pervasive developmental disorders.

The Studies to Advance Autism Research and Treatment Network conducted a randomized trial with citalopram in children with Pervasive developmental disorders (PDDs). We present the rationale, design and sample characteristics of the citalopram trial. Subjects (128 boys, 21 girls) had a mean age of 9.3 (±3.12) years; 132 (88.6%) were diagnosed with autistic disorder (4.7% with Asperger's Disorder; 6.7% with PDD-not otherwise specified). Less than half of the subjects were intellectually disabled; 117 (78.5%) were rated Moderate or Marked on the Clinical Global Impression for Severity. Study measures were similar to previous Research Units on Pediatric Psychopharmacology trials. Subjects in this trial were slightly older and more likely to have complaints of repetitive behavior than participants in RUPP trials.

Evaluation of sedation and analgesia in standing horses after administration of xylazine, butorphanol, and subanesthetic doses of ketamine.

OBJECTIVE: To evaluate the sedative and analgesic effects of subanesthetic doses of ketamine in horses sedated with xylazine, with or without butorphanol. DESIGN: Prospective, randomized, controlled study. ANIMALS: 10 adult horses. PROCEDURES: Each horse was sedated multiple times by administration of xylazine (treatment X), xylazine and butorphanol (treatment XB), xylazine with 1 of 2 dosages of ketamine (treatment XK1 or XK2), or xylazine and butorphanol with 1 of 2 dosages of ketamine (treatment XBK1 or XBK2). Head height and various behaviors, including responses to noise, insertion of a dental float, needle prick on the flank, algometer pressure on the scapula, and bilateral carpal arthrocenteses, were evaluated. RESULTS: No significant differences were detected among sedation treatments for head height, response to noise, or response to arthrocenteses. Insertion of a dental float was easiest with treatment XBK2 and most difficult with treatments XK1 and XK2. Response to a needle prick on the flank was lowest with treatment XB and highest with treatment XK2. Tolerance to algometer pressure over the scapula was highest with treatment XBK2 and lowest with treatment X. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a subanesthetic dosage of ketamine with xylazine and butorphanol may facilitate certain procedures, such as insertion of a dental float, in horses and enhance tolerance to pressure stimulation, but it may worsen responses to acute pain, such as that caused by a needle prick. Further evaluation is needed to determine whether subanesthetic dosages of ketamine might be useful when performing certain clinical procedures in horses.

Pulmonary gas exchange and plasma lactate in horses with gastrointestinal disease undergoing emergency exploratory laparotomy: a comparison with an elective surgery horse population.

OBJECTIVE: To characterize pulmonary gas exchange and arterial lactate in horses with gastrointestinal disease undergoing anesthesia, compared with elective surgical horses, and to correlate these variables with postoperative complications and mortality. STUDY DESIGN: Prospective clinical study. ANIMALS: Horses undergoing emergency laparotomy for acute intestinal disease (n = 50) and healthy horses undergoing elective surgery in dorsal recumbency (n = 20). METHODS: Arterial blood gas analysis was performed at predetermined intervals on horses undergoing a standardized anesthetic protocol. Alveolar-arterial oxygen gradient was calculated. Predictive factors for postoperative complications and death in colic horses were determined. RESULTS: Arterial oxygen tension (P(a) O(2)) varied widely among horses in both groups. P(a) O(2) significantly increased in the colic group after exteriorization of the ascending colon. P(a) O(2) and alveolar-arterial oxygen gradient were not significantly different between groups, and neither were correlated with horse outcome. Arterial lactate in recovery ≥ 5 mmol/L was associated with a 2.25 times greater relative risk of complications and lactate ≥ 7 mmol/L was associated with a 10.5 times higher relative risk of death. CONCLUSION: Colic horses in this population were not more likely to be hypoxemic than elective horses, nor was gas exchange impaired to a greater degree in colic horses relative to controls. Arterial lactate sampled immediately after anesthetic recovery was predictive for postoperative complications and death.

Effects of intravenous administration of lidocaine on the minimum alveolar concentration of sevoflurane in horses.

OBJECTIVE: To determine effects of a continuous rate infusion of lidocaine on the minimum alveolar concentration (MAC) of sevoflurane in horses. ANIMALS: 8 healthy adult horses. PROCEDURES: Horses were anesthetized via IV administration of xylazine, ketamine, and diazepam; anesthesia was maintained with sevoflurane in oxygen. Approximately 1 hour after induction, sevoflurane MAC determination was initiated via standard techniques. Following sevoflurane MAC determination, lidocaine was administered as a bolus (1.3 mg/kg, IV, over 15 minutes), followed by constant rate infusion at 50 µg/kg/min. Determination of MAC for the lidocaine-sevoflurane combination was started 30 minutes after lidocaine infusion was initiated. Arterial blood samples were collected after the lidocaine bolus, at 30-minute intervals, and at the end of the infusion for measurement of plasma lidocaine concentrations. RESULTS: IV administration of lidocaine decreased mean ± SD sevoflurane MAC from 2.42 ± 0.24% to 1.78 ± 0.38% (mean MAC reduction, 26.7 ± 12%). Plasma lidocaine concentrations were 2,589 ± 811 ng/mL at the end of the bolus; 2,065 ± 441 ng/mL, 2,243 ± 699 ng/mL, 2,168 ± 339 ng/mL, and 2,254 ± 215 ng/mL at 30, 60, 90, and 120 minutes of infusion, respectively; and 2,206 ± 329 ng/mL at the end of the infusion. Plasma concentrations did not differ significantly among time points. CONCLUSIONS AND CLINICAL RELEVANCE: Lidocaine could be useful for providing a more balanced anesthetic technique in horses. A detailed cardiovascular study on the effects of IV infusion of lidocaine during anesthesia with sevoflurane is required before this combination can be recommended.

Comparison of the cardiovascular effects of equipotent anesthetic doses of sevoflurane alone and sevoflurane plus an intravenous infusion of lidocaine in horses.

OBJECTIVE: To compare cardiovascular effects of sevoflurane alone and sevoflurane plus an IV infusion of lidocaine in horses. Animals-8 adult horses. PROCEDURES: Each horse was anesthetized twice via IV administration of xylazine, diazepam, and ketamine. During 1 anesthetic episode, anesthesia was maintained by administration of sevoflurane in oxygen at 1.0 and 1.5 times the minimum alveolar concentration (MAC). During the other episode, anesthesia was maintained at the same MAC multiples via a reduced concentration of sevoflurane plus an IV infusion of lidocaine. Heart rate, arterial blood pressures, blood gas analyses, and cardiac output were measured during mechanical (controlled) ventilation at both 1.0 and 1.5 MAC for each anesthetic protocol and during spontaneous ventilation at 1 of the 2 MAC multiples. RESULTS: Cardiorespiratory variables did not differ significantly between anesthetic protocols. Blood pressures were highest at 1.0 MAC during spontaneous ventilation and lowest at 1.5 MAC during controlled ventilation for either anesthetic protocol. Cardiac output was significantly higher during 1.0 MAC than during 1.5 MAC for sevoflurane plus lidocaine but was not affected by anesthetic protocol or mode of ventilation. Clinically important hypotension was detected at 1.5 MAC for both anesthetic protocols. CONCLUSIONS AND CLINICAL RELEVANCE: Lidocaine infusion did not alter cardiorespiratory variables during anesthesia in horses, provided anesthetic depth was maintained constant. The IV administration of lidocaine to anesthetized nonstimulated horses should be used for reasons other than to improve cardiovascular performance. Severe hypotension can be expected in nonstimulated horses at 1.5 MAC sevoflurane, regardless of whether lidocaine is administered.

Evaluation of effects of sciatic and femoral nerve blocks in sheep undergoing stifle surgery.

The authors evaluated the effects of locally anesthetizing the sciatic and femoral nerves in sheep undergoing stifle (femorotibial) surgery (16 sheep received nerve blocks; 16 sheep underwent a nerve localization procedure but received no nerve blocks). Heart rate, mean arterial blood pressure and end-tidal isoflurane were recorded every 5 min while sheep were anesthetized. At some of the observed time points, the mean heart rate in the sheep that had received no nerve blocks was significantly higher than in the sheep that had received the nerve blocks. Postoperatively, each sheep was assigned scores for comfort and attitude, movement, flock behavior, feeding behavior and appetite and respiratory rate (based on predefined descriptions). Though the authors found no undesirable effects of this local anesthesia, beneficial effects of the nerve blocks were minimal or not readily apparent under the conditions of this study.

Effects of stress on pain in horses and incorporating pain scales for equine practice.

The stress response represents an animal's attempt to reestablish the body's homeostasis after injury, intense physical activity, or psychological strain. Two different neuroendocrine pathways may be activated in stressful situations: the hypothalamic-pituitary-adrenocortical axis, leading to increased cortisol levels, and the sympathoadrenomedullar system, leading to increased catecholamine levels. By applying some of the evaluation methods described in this article in the appropriate clinical situations, equine veterinarians can almost certainly improve their ability to recognize and manage pain in horses.

Clinical evaluation of perioperative administration of gabapentin as an adjunct for postoperative analgesia in dogs undergoing amputation of a forelimb.

OBJECTIVE: To evaluate perioperative administration of gabapentin as an adjunct for analgesia in dogs undergoing amputation of a forelimb. DESIGN: Randomized, controlled trial. ANIMALS: 30 client-owned dogs. Procedures-On the day before surgery, a baseline pain evaluation was performed in each dog by use of multiple pain assessment methods. Dogs then received gabapentin (10 mg/kg [4.5 mg/lb], PO, once, followed by 5 mg/kg [2.3 mg/lb], PO, q 12 h for 3 additional days) or a placebo. On the day of surgery, dogs were anesthetized and forelimb amputation was performed. Fentanyl was infused after surgery for 18 to 24 hours; use of other analgesics was allowed. In-hospital pain evaluations were repeated at intervals for 18 hours after surgery, and owners were asked to evaluate daily their dog's activity, appetite, and wound soreness for the first 3 days after discharge from the hospital. Results were analyzed by use of a repeated-measures ANOVA. RESULTS: Pain evaluation scores did not differ significantly between gabapentin and placebo groups in the hospital or at home after discharge. CONCLUSIONS AND CLINICAL RELEVANCE: As an adjunct to other analgesics and anesthetics, gabapentin, at the dose and frequency used in this study, did not provide a significant benefit for the management of acute perioperative pain in dogs undergoing forelimb amputation. The small sample size and number of other confounding factors, such as aggressive use of other analgesics, limited the likelihood of detecting a benefit of gabapentin. Other gabapentin doses or dosing regimens warrant further study.

Effect of intravenous ketamine and lidocaine on isoflurane requirement in sheep undergoing orthopedic surgery.

Intravenous ketamine and lidocaine infusions may be useful adjuncts to inhalation anesthesia for sheep undergoing orthopedic surgery. In this study, 50 female sheep underwent experimental stifle surgery (29 received a meniscal implant and 21 received sham surgery). To induce anesthesia in the sheep, the authors intravenously injected ketamine and diazepam. They administered isoflurane in oxygen to maintain anesthesia and used mechanical ventilation to maintain normal arterial carbon dioxide pressure. Some sheep received intravenous infusions of ketamine and lidocaine during surgery, whereas others did not. Sheep that received a meniscal implant without ketamine-lidocaine required approximately 23% greater isoflurane concentrations than sheep that were given ketamine-lidocaine. These findings suggest that intravenous infusion of ketamine and lidocaine decreases the requirement for isoflurane during orthopedic surgery on anesthetized sheep.

Medication and parent training in children with pervasive developmental disorders and serious behavior problems: results from a randomized clinical trial.

OBJECTIVE: Many children with pervasive developmental disorders (PDDs) have serious, functionally impairing behavioral problems. We tested whether combined treatment (COMB) with risperidone and parent training (PT) in behavior management is superior to medication alone (MED) in improving severe behavioral problems in children with PDDs. METHOD: This 24-week, three-site, randomized, parallel-groups clinical trial enrolled 124 children, aged 4 through 13 years, with PDDs, accompanied by frequent tantrums, self-injury, and aggression. The children were randomized 3:2 to COMB (n = 75) or MED (n = 49). The participants received risperidone monotherapy from 0.5 to 3.5 mg/day (with switch to aripiprazole if risperidone was ineffective). Parents in the COMB group (n = 75; 60.5%) received a mean of 10.9 PT sessions. The primary measure of compliance was the Home Situations Questionnaire (HSQ) score. RESULTS: Primary: intent-to-treat random effects regression showed that COMB was superior to MED on HSQ (p = .006) [effect size at week 24 (d) = 0.34]. The HSQ score declined from 4.31 (± 1.67) to 1.23 (± 1.36) for COMB compared with 4.16 (± 1.47) to 1.68 (± 1.36) for MED. Secondary: groups did not differ on Clinical Global Impressions-Improvement scores at endpoint; compared with MED, COMB showed significant reductions on Aberrant Behavior Checklist Irritability (d = 0.48; p = .01), Stereotypic Behavior (d = 0.23; p = .04), and Hyperactivity/Noncompliance subscales (d = 0.55; p = .04). Final risperidone mean dose for MED was 2.26 mg/day (0.071 mg/kg), compared with 1.98 mg/day for COMB (0.066 mg/kg) (p = .04). CONCLUSIONS: Medication plus PT resulted in greater reduction of serious maladaptive behavior than MED in children with PDDs, with a lower risperidone dose.

Cognitive-behavioral therapy for suicide prevention (CBT-SP): treatment model, feasibility, and acceptability.

OBJECTIVE: To describe the elements of a manual-based cognitive-behavioral therapy for suicide prevention (CBT-SP) and to report its feasibility in preventing the recurrence of suicidal behavior in adolescents who have recently attempted suicide. METHOD: The CBT-SP was developed using a risk reduction and relapse prevention approach and theoretically grounded in principles of cognitive-behavioral therapy, dialectical behavioral therapy, and targeted therapies for suicidal youths with depression. The CBT-SP consists of acute and continuation phases, each lasting about 12 sessions, and includes a chain analysis of the suicidal event, safety plan development, skill building, psychoeducation, family intervention, and relapse prevention. RESULTS: The CBT-SP was administered to 110 recent suicide attempters with depression aged 13 to 19 years (mean 15.8 years, SD 1.6) across five academic sites. Twelve or more sessions were completed by 72.4% of the sample. CONCLUSIONS: A specific intervention for adolescents at high risk for repeated suicide attempts has been developed and manual based, and further testing of its efficacy seems feasible.