Real-World Efficacy and Safety of Extended-Release Methylphenidate (PRC-063) in the Treatment of ADHD in Pediatric and Adult Subjects: Results of a Phase IV Multicenter Comparison With Lisdexamfetamine Dimesylate.

OBJECTIVE: To evaluate the real-world efficacy, safety, and functional outcomes of PRC-063 (multilayer-release methylphenidate) versus lisdexamfetamine (LDX) in ADHD subjects in a phase IV, open-label study. METHOD: The primary endpoint was the change in the ADHD-DSM-5 Rating Scale (ADHD-5-RS) total score from baseline to Month 4. Secondary endpoints included a non-inferiority comparison between PRC-063 and LDX and measures of functioning and evening behavior. RESULTS: One hundred forty-three pediatric and 112 adult subjects were enrolled. Mean ADHD-5-RS scores (standard deviation) were reduced in pediatric (-16.6 [10.4]) and adult (-14.8 [10.6]) subjects treated with PRC-063 (p < .001). PRC-063 was non-inferior to LDX in the pediatric population but not in the adult population. Significant improvements were demonstrated in quality of life and functionality. Both medications were well-tolerated; more adverse events led to study discontinuation in pediatric subjects treated with LDX versus PRC-063. CONCLUSION: PRC-063 and LDX significantly improved ADHD symptomatology and functioning and were well-tolerated.

Chromosome 20p Partial De Novo Duplication Identified in a Female Paediatric Patient with Characteristic Facial Dysmorphism and Behavioural Anomalies.

Copy number variations (CNVs) involving the JAG1 gene are rare and infrequently reported in the scientific literature. Recently, a generally healthy young patient presenting with a history of behavioural concerns was referred to us. Herein, we discuss the patient, a 7-year-old female possessing a 0.797 Mb microduplication within the short arm of chromosome 20 at band 12.2. The patient generates considerable curiosity due to the rarity of her case, which includes a de novo partial duplication involving the JAG1 gene. The patient exhibits a wide range of symptoms including facial dysmorphism (dolichocephaly, round face, tented philtrum, anteverted nares, and micrognathia), clinodactyly, and an inborn congenital heart defect. She presented with behavioural concerns including ADHD-I, SPD, motor clumsiness, and poor self-regulation. Deletions in JAG1 are often linked to Alagille Syndrome; however, complete duplications have not been specifically identified as disease-causing. JAG1 mutations are reported alongside various clinical features including facial dysmorphology, heart defects, vertebral abnormalities, and ocular dysmorphic features (strabismus, epicanthal folds, and slanted palpebral fissures). This particular microduplication is rare, and thus, limited data exist regarding its significance. To our knowledge, most reported duplications are larger than 0.797 Mb. This may define a critical region causing phenotypical changes in some patient cases.

Paternal organic solvent exposure and adverse pregnancy outcomes: a meta-analysis.

BACKGROUND: Organic solvents are widely used, but conflicting reports exist concerning paternal exposure and adverse pregnancy outcomes. We conducted a meta-analysis to assess the risks of spontaneous abortions (SAs) and major malformations (MMs) after paternal exposure to organic solvents. METHODS: Medline, Toxline, Reprotox, and Embase from 1966 to 2003 were searched. Two independent reviewers searched for cohort and case-control studies in any language on adult human males exposed chronically to any organic solvent. Two non-blinded independent extractors used a standardized form for data extraction; disagreements were resolved through consensus discussion. RESULTS: Forty-seven studies were identified; 32 exclusions left 14 useable studies. Overall random effects odds ratios and 95% confidence intervals (CI95%) were 1.30 (CI95%: 0.81-2.11, N=1,248) for SA, 1.47 (CI95%: 1.18-1.83, N=384,762) for MMs, 1.86 (CI95%: 1.40-2.46, N=180,242) for any neural tube defect, 2.18 (CI95%: 1.52-3.11, N=107,761) for anencephaly, and 1.59 (CI95%: 0.99-2.56, N=96,517; power=56.3%) for spina bifida. CONCLUSIONS: Paternal exposure to organic solvents is associated with an increased risk for neural tube defects but not SAs.

Child neurodevelopmental outcome and maternal occupational exposure to solvents.

BACKGROUND: Many women of reproductive age are employed in industries involving exposure to organic solvents. Animal toxicological studies and human case reports demonstrate that high exposure to solvents causes neurodevelopmental toxicity in exposed offspring. Data from occupationally exposed women and their children are few. OBJECTIVE: To compare the cognitive, language, and motor performance and the behavioral achievements of children whose mothers were exposed occupationally to organic solvents during pregnancy with those of a matched unexposed control group. PARTICIPANTS: Thirty-two pregnant women occupationally exposed to organic solvents were recruited during pregnancy and followed up. Their offspring (age range, 3-9 years) were tested for cognitive functioning (IQ), language, visual-motor functioning, and behavioral functioning and were compared with a matched unexposed control group that was recruited and tested in a similar manner. Examiners were blinded to the exposure status. RESULTS: Mothers occupationally exposed to organic solvents did not differ significantly from matched controls in demographic variables. After controlling for potential confounding because of maternal IQ and maternal education, children exposed in utero to organic solvents obtained lower scores on subtests of intellectual, language, motor, and neurobehavioral functioning. CONCLUSIONS: In utero exposure to organic solvents is associated with poorer performance on some specific subtle measures of neurocognitive function, language, and behavior. Reducing exposure in pregnancy is merited until more refined risk assessment is possible. Further studies that address exposure to specific solvents, dose, and gestational timing of exposure are needed.

Prospective observational study on the incidence of medication errors during simulated resuscitation in a paediatric emergency department.

OBJECTIVES: To characterise the incidence and nature of medication errors during paediatric resuscitations. DESIGN: A prospective observational study of simulated emergencies. SETTING: Emergency department of a tertiary paediatric hospital. PARTICIPANTS: Teams that included a clinician who commonly leads "real" resuscitations, at least two assisting physicians, and two or three paediatric nurses. INTERVENTIONS: The teams conducted eight mock resuscitations, including ordering medications. Exercises were videotaped and drugs ordered and administered during the resuscitation were recorded. Syringes and drugs prepared during the resuscitation were collected and analysed for concentrations and actual amounts. MAIN OUTCOME MEASURES: Number and type of drug errors. RESULTS: Participants gave 125 orders for medications. In 21 (17%) of the orders the exact dose was not specified. Nine dosing errors occurred during the ordering phase. Of these errors, five were intercepted before the drug reached the patient. Four 10-fold errors were identified. In nine (16%) out of 58 syringes analysed, measured drug concentrations showed a deviation of at least 20% from the ordered dose. A large deviation (at least 50%) from the expected dose was found in four (7%) cases. CONCLUSIONS: Medication errors commonly occur during all stages of paediatric resuscitation. Many errors could be detected only by analysing syringe content, suggesting that such errors may be a major source of morbidity and mortality in resuscitated children.