Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior: Citalopram Ineffective in Children With Autism

Context—Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders. Objectives—To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders. Design—National Institutes of Health–sponsored randomized controlled trial. Setting—Six academic centers, including Mount Sinai School of Medicine, North Shore–Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School. Participants—One hundred forty-nine volunteers 5 to 17 years old (mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram (n = 73) or placebo (n = 76). Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children\u27s Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Interventions—Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d). Main Outcome Measures—Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children\u27s Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form. Results—There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95% confidence interval, 0.61-1.51; P\u3e .99). There was no difference in score reduction on the Children\u27s Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline (mean [SD], −2.0 [3.4] points for the citalopram-treated group and −1.9 [2.5] points for the placebo group; P=.81). Citalopram usewas significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus. Conclusion—Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders. STAART Psychopharmacology Network Group Members: Rosemary Affeldt, MSW, LICSW; Denisse Ambler, MD; George Anderson, PhD; May-Lynn Andresen, RN; Grace Baranek, PhD; Jennifer Bartz, PhD; Karen Bearss, PhD; Terrence C. Bethea, MD; Jennifer Cowen, MA; Pegeen Cronin, PhD; Margaret DeRamus, BA; Robert Dimino, PhD; Tywanda Ellison, PhD; Nicole Feirsen, BA; Lilia Fenelon, BA; Anita Gordon, MSW; Danielle Halpern, PhD; Marisa B. Houser, MS; Cathy Jones, BA; Lawrence Kaplan, MD; Paul Kartheiser, MD; Robyn Keske, MSW, MPH; Young Shin Kim, MD, PhD; Kathy Koenig, MSN; Erin Kustan, BA; Kathleen Lapp, MD; Arthur Maerlender, PhD; Brenna McDonald, PsyD, MBA; Debra McQuade, PhD, MD; Shana Nichols, PhD; Roumen Nikolov, MD; Maryellen Pachler, MSN; Emily Quinn, MA; Idania Ramirez, MPH; Jennifer Richards, MD; Peter Robichaux, BA; Fay Robinson, BA; Jade Rusoff, BA; Bhavik Shah, MD; Latha Soorya, PhD; Linda Spritzer, BA; Erika Swanson, BA; Tara Tripp, MA; John Vidaver, MA; Shulamit Waldoks, BA; A. Ting Wang, PhD; Stacey Wasserman, MD; and Emily Williams, MEd

Solid Pseudopapillary Neoplasm, Pancreas Type, Presenting as a Primary Ovarian Neoplasm.

Solid pseudopapillary neoplasm has historically been associated with the pancreas, categorized as a tumor of low malignancy. Recently, solid pseudopapillary neoplasm was reported to arise as a primary ovarian tumor in 3 women. We report a fourth case identified in a 48 year-old woman with an 8-cm left ovarian mass. A left salpingo-oophorectomy was performed. Microscopic examination demonstrated a predominately cystic neoplasm comprised of solid nests of cells with an epithelioid to plasmacytoid appearance, associated with blood vessels, hemorrhage, and degenerative changes, that is, pseudopapillary structures. The tumor cells stained focally for pancytokeratin, progesterone receptor, and CD57 with diffuse nuclear expression of β-catenin. Ki-67 was 5% to 10%. Synaptophysin, inhibin, and E-cadherin stains were negative. Clinical and radiologic follow-up of our patient demonstrated no pancreatic lesions. This is a rare report of a primary ovarian solid pseudopapillary neoplasm. Prolonged follow-up is needed to determine how this case will fare clinically

and the Metabolic Syndrome in Middle-Aged Adults in the Community Soft Drink Consumption and Risk of Developing Cardiometabolic Risk Factors Soft Drink Consumption and Risk of Developing Cardiometabolic Risk Factors and the Metabolic Syndrome in Middle-Ag

Background-Consumption of soft drinks has been linked to obesity in children and adolescents, but it is unclear whether it increases metabolic risk in middle-aged individuals. Methods and Results-We related the incidence of metabolic syndrome and its components to soft drink consumption in participants in the Framingham Heart Study (6039 person-observations, 3470 in women; mean age 52.9 years) who were free of baseline metabolic syndrome. Metabolic syndrome was defined as the presence of Ն3 of the following: waist circumference Ն35 inches (women) or Ն40 inches (men); fasting blood glucose Ն100 mg/dL; serum triglycerides Ն150 mg/dL; blood pressure Ն135/85 mm Hg; and high-density lipoprotein cholesterol Ͻ40 mg/dL (men) or Ͻ50 mg/dL (women)

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics