In October 2002, a workshop was held in Ancona, Italy, to reach a Consensus on the management of Cushing’s syndrome. The workshop was organized by the University of Ancona and sponsored by the ...Pituitary Society, the European Neuroendocrine Association, and the Italian Society of Endocrinology. Invited international participants included almost 50 leading endocrinologists with specific expertise in the management of Cushing’s syndrome. The consensus statement on diagnostic criteria and the diagnosis and treatment of complications of this syndrome reached at the workshop is hereby summarized.
Attention-deficit hyperactivity disorder (ADHD) is a common paediatric neurodevelopmental disorder with substantial effect on families and society. Alternatives to traditional care, including novel ...digital therapeutics, have shown promise to remediate cognitive deficits associated with this disorder and may address barriers to standard therapies, such as pharmacological interventions and behavioural therapy. AKL-T01 is an investigational digital therapeutic designed to target attention and cognitive control delivered through a video game-like interface via at-home play for 25 min per day, 5 days per week for 4 weeks. This study aimed to assess whether AKL-T01 improved attentional performance in paediatric patients with ADHD.
The Software Treatment for Actively Reducing Severity of ADHD (STARS-ADHD) was a randomised, double-blind, parallel-group, controlled trial of paediatric patients (aged 8–12 years, without disorder-related medications) with confirmed ADHD and Test of Variables of Attention (TOVA) Attention Performance Index (API) scores of −1·8 and below done by 20 research institutions in the USA. Patients were randomly assigned 1:1 to AKL-T01 or a digital control intervention. The primary outcome was mean change in TOVA API from pre-intervention to post-intervention. Safety, tolerability, and compliance were also assessed. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02674633 and is completed.
Between July 15, 2016, and Nov 30, 2017, 857 patients were evaluated and 348 were randomly assigned to receive AKL-T01 or control. Among patients who received AKL-T01 (n=180 52%; mean SD age, 9·7 1·3 years) or control (n=168 48%; mean SD age, 9·6 1·3 years), the non-parametric estimate of the population median change from baseline TOVA API was 0·88 (95% CI 0·24–1·49; p=0·0060). The mean (SD) change from baseline on the TOVA API was 0·93 (3·15) in the AKL-T01 group and 0·03 (3·16) in the control group. There were no serious adverse events or discontinuations. Treatment-related adverse events were mild and included frustration (5 3% of 180) and headache (3 2% of 180). Patient compliance was a mean of 83 (83%) of 100 expected sessions played (SD, 29·2 sessions).
Although future research is needed for this digital intervention, this study provides evidence that AKL-T01 might be used to improve objectively measured inattention in paediatric patients with ADHD, while presenting minimal adverse events.
Sponsored by Akili Interactive Labs.
Objective
To examine experiences of racial/ethnic discrimination among Latinos in the United States, which broadly contribute to their poor health outcomes.
Data Source and Study Design
Data come ...from a nationally representative, probability‐based telephone survey including 803 Latinos and a comparison group of 902 non‐Hispanic white US adults, conducted January—April 2017.
Methods
We calculated the percent of Latinos reporting discrimination in several domains, including health care. We used logistic regression to compare the Latino‐white difference in odds of discrimination, and among Latinos only to examine variation by socioeconomic status and country of birth.
Principal Findings
One in five Latinos (20 percent) reported experiencing discrimination in clinical encounters, while 17 percent avoided seeking health care for themselves or family members due to anticipated discrimination. A notable share of Latinos also reported experiencing discrimination with employment (33 percent applying for jobs; 32 percent obtaining equal pay/promotions), housing (31 percent), and police interactions (27 percent). In adjusted models, Latinos had significantly higher odds than whites for reporting discrimination in health care visits (OR: 3.18, 95% CI: 1.61, 6.26) and across several other domains. Latinos with college degrees had significantly higher odds of reporting discrimination in multiple domains than those without college degrees, with few differences between foreign‐born and US‐born Latinos.
Conclusions
Latinos in the United States report experiencing widespread discrimination in health care and other areas of their lives, at significantly higher levels than whites. Being born in the United States and earning a college degree are not protective against discrimination, suggesting that further health and social policy efforts to eliminate discrimination are needed.
Objective
To examine experiences of racial discrimination among black adults in the United States, which broadly contribute to their poor health outcomes.
Data Source and Study Design
Data come from ...a nationally representative, probability‐based telephone survey including 802 non‐Hispanic black and a comparison group of 902 non‐Hispanic white US adults, conducted January–April 2017.
Methods
We calculated the percent of blacks reporting discrimination in several domains, including health care. We used logistic regression to compare the black‐white difference in odds of discrimination, and among blacks only to examine variation by socioeconomic status, gender, and neighborhood racial composition.
Principal Findings
About one‐third of blacks (32 percent) reported experiencing discrimination in clinical encounters, while 22 percent avoided seeking health care for themselves or family members due to anticipated discrimination. A majority of black adults reported experiencing discrimination in employment (57 percent in obtaining equal pay/promotions; 56 percent in applying for jobs), police interactions (60 percent reported being stopped/unfairly treated by police), and hearing microaggressions (52 percent) and racial slurs (51 percent). In adjusted models, blacks had significantly higher odds than whites of reporting discrimination in every domain. Among blacks, having a college degree was associated with higher odds of experiencing overall institutional discrimination.
Conclusions
The extent of reported discrimination across several areas of life suggests a broad pattern of discrimination against blacks in America, beyond isolated experiences. Black‐white disparities exist on nearly all dimensions of experiences with public and private institutions, including health care and the police. Evidence of systemic discrimination suggests a need for more active institutional interventions to address racism in policy and practice.
The objective of this study was to evaluate short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting ...behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these.
This 8-week, double-blind, randomized, placebo-controlled, parallel-group study was conducted of children and adolescents (aged 6-17 years) with autistic disorder. Patients were randomly assigned (1:1) to flexibly dosed aripiprazole (target dosage: 5, 10, or 15 mg/day) or placebo. Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression-Improvement score (CGI-I). Safety and tolerability were also assessed.
Ninety-eight patients were randomly assigned to receive placebo (n = 51) or aripiprazole (n = 47). Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with aripiprazole than with placebo from week 1 through week 8. Aripiprazole demonstrated significantly greater global improvements than placebo, as assessed by the mean CGI-I score from week 1 through week 8; however, clinically significant residual symptoms may still persist for some patients. Discontinuation rates as a result of adverse events (AEs) were 10.6% for aripiprazole and 5.9% for placebo. Extrapyramidal symptom-related AE rates were 14.9% for aripiprazole and 8.0% for placebo. No serious AEs were reported. Mean weight gain was 2.0 kg on aripiprazole and 0.8 kg on placebo at week 8.
Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated.
To evaluate the efficacy, safety, and tolerability of the selective serotonin norepinephrine inhibitor duloxetine in children and adolescents with generalized anxiety disorder (GAD).
Youth aged 7 ...through 17 years with a primary diagnosis of GAD were treated with flexibly dosed duloxetine (30-120 mg daily, n = 135) or placebo (n = 137) for 10 weeks, followed by open-label duloxetine (30-120mg daily) for 18 weeks. Efficacy measures included the Pediatric Anxiety Rating Scale (PARS), Clinical Global Impression-Severity (CGI-Severity) scale, and Children's Global Assessment Scale (CGAS). Safety measures included the Columbia-Suicide Severity Rating Scale (C-SSRS) as well as vital signs and electrocardiographic and laboratory monitoring.
On the primary efficacy measure (PARS severity for GAD), mean improvement from baseline to 10 weeks was statistically significantly greater for duloxetine (-9.7) compared with placebo (-7.1, p ≤ .001, Cohen's d: 0.5). Symptomatic response (50% improvement on the PARS severity for GAD), remission (PARS severity for GAD ≤8), and functional remission (CGAS >70) rates for the duloxetine group (59%, 50%, 37%, respectively) were statistically significantly greater than for the placebo group (42%, 34%, 24%, respectively, p ≤ .05) during acute treatment. Changes in systolic and diastolic blood pressure and discontinuation because of adverse events did not statistically differ between the duloxetine and placebo groups, although gastrointestinal-related adverse events, oropharyngeal pain, dizziness, cough, and palpitations were reported with a statistically significantly greater incidence for the duloxetine group compared with the placebo group. Mean changes in pulse and weight for the duloxetine group (+6.5 beats/min, -0.1 kg, respectively) were statistically different from the placebo group (+2.0 beats/min, +1.1 kg, respectively, p ≤ .01).
In this study, duloxetine was superior to placebo on the primary efficacy analysis of mean change from baseline to week 10 on the PARS severity for GAD score, and safety results were consistent with the known safety profile of duloxetine in pediatric and adult patients. Clinical trial registration information-A Study in Pediatric Participants With Generalized Anxiety Disorder; http://clinicaltrials.gov; NCT01226511.
Psychotropic medications are commonly prescribed to people with intellectual disability. We reviewed current evidence-based pharmacotherapy options and recent updates to guide clinicians in their ...medication management plans.
Antipsychotics, particularly risperidone, appear to be effective in reducing problem behaviors in children with intellectual disability. Evidence in adults is inconclusive. Methylphenidate appears to be effective, and α-agonists appear promising in reducing attention-deficit hyperactivity disorder symptoms. Lithium might be effective in reducing aggression. Evidence is limited to support the use of antiepileptic drugs, anxiolytics, and naltrexone for management of problem behaviors. Antidepressants may be poorly tolerated and might not be effective in reducing repetitive/stereotypic behaviors.In recent trials, glutamatergic and GABAergic agents for fragile X syndrome, and acetylcholinesterase inhibitors for Down's syndrome, failed to show efficacy. Growth hormone treatment might improve cognition and behavior in Prader-Willi syndrome population. Results from oxytocin trials on social behaviors are inconclusive albeit promising. Melatonin appears to improve sleep. Most trials of dietary supplements did not show benefits.
Evidence-based pharmacotherapy options in people with intellectual disability are limited, and many agents can cause substantial adverse events. For this reason, clinicians should consider pharmacotherapy as only a part of comprehensive treatment, and regularly assess drug effects, adverse events, and the feasibility of decreasing dose or withdrawing medications.
To evaluate the efficacy and safety of vortioxetine in adolescents with major depressive disorder (MDD).
After 4 weeks of single-blind lead-in treatment with a Brief Psychosocial Intervention (BPI) ...plus placebo, patients (aged 12-17 years) with MDD (DSM-5) who did not meet response criteria (Children’s Depression Rating Scale–Revised CDRS-R; total score ≥40 plus <40% reduction and a Parent Global Assessment score >2) were randomized 1:1:1:1 to 8 weeks of BPI plus double-blind treatment with vortioxetine 10 mg, vortioxetine 20 mg, fluoxetine 20 mg, or placebo. The primary endpoint was change from randomization in CDRS-R total score at week 8; the primary comparison was the average effect of 2 vortioxetine doses vs placebo.
Of 784 patients enrolled in the lead-in, 616 were randomized. At week 8, the mean change in CDRS-R total score averaged for vortioxetine doses was –18.01 (SE = 0.98) and the mean difference vs placebo was 0.21 (P = .878; not significant). For fluoxetine, the mean change in CDRS-R total score was –21.95 and the mean difference vs placebo was –3.73 (P = .015). Treatment-emergent adverse events occurring in ≥5% of patients in either vortioxetine arm and at least twice more frequently than placebo were nausea, headache, vomiting, and dizziness.
Patients in all groups showed reduction in CDRS-R scores by the end of the study, with no difference between combined doses of vortioxetine and placebo. The primary endpoint was not met, thereby rendering the study negative. The overall favorable safety profile of vortioxetine in an adolescent patient population was consistent with that seen in adults.
Active Reference (Fluoxetine) Fixed-Dose Study of Vortioxetine in Paediatric Patients Aged 12 to 17 Years With Major Depressive Disorder (MDD); http://clinicaltrials.gov; NCT02709746.
The Supplemental Nutrition Assistance Program (SNAP), the largest federal nutrition assistance program, provides financial assistance for food purchases to 40 million Americans and has an annual ...budget of more than $65 billion (https://bit.ly/ 2K3g0l5). Although SNAP benefits can be used to purchase any food or nonalcoholic beverage, with the exception of hot or pre-prepared foods, there is strong interest among public health advocates and policymakers in identifying evidence-based SNAP policies that will promote healthier participant purchases.1
To examine the proposed disruptive mood dysregulation disorder (DMDD) diagnosis in a child psychiatric outpatient population. Evaluation of DMDD included 4 domains: clinical phenomenology, ...delimitation from other diagnoses, longitudinal stability, and association with parental psychiatric disorders.
Data were obtained from 706 children aged 6-12 years who participated in the Longitudinal Assessment of Manic Symptoms (LAMS) study (sample was accrued from November 2005 to November 2008). DSM-IV criteria were used, and assessments, which included diagnostic, symptomatic, and functional measures, were performed at intake and at 12 and 24 months of follow-up. For the current post hoc analyses, a retrospective diagnosis of DMDD was constructed using items from the K-SADS-PL-W, a version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children, which resulted in criteria closely matching the proposed DSM-5 criteria for DMDD.
At intake, 26% of participants met the operational DMDD criteria. DMDD+ vs DMDD- participants had higher rates of oppositional defiant disorder (relative risk RR = 3.9, P < .0001) and conduct disorder (RR = 4.5, P < .0001). On multivariate analysis, DMDD+ participants had higher rates of and more severe symptoms of oppositional defiant disorder (rate and symptom severity P values < .0001) and conduct disorder (rate, P < .0001; symptom severity, P = .01), but did not differ in the rates of mood, anxiety, or attention-deficit/hyperactivity disorders or in severity of inattentive, hyperactive, manic, depressive, or anxiety symptoms. Most of the participants with oppositional defiant disorder (58%) or conduct disorder (61%) met DMDD criteria, but those who were DMDD+ vs DMDD- did not differ in diagnostic comorbidity, symptom severity, or functional impairment. Over 2-year follow-up, 40% of the LAMS sample met DMDD criteria at least once, but 52% of these participants met criteria at only 1 assessment. DMDD was not associated with new onset of mood or anxiety disorders or with parental psychiatric history.
In this clinical sample, DMDD could not be delimited from oppositional defiant disorder and conduct disorder, had limited diagnostic stability, and was not associated with current, future-onset, or parental history of mood or anxiety disorders. These findings raise concerns about the diagnostic utility of DMDD in clinical populations.
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