Ontogeny of midazolam glucuronidation in preterm infants

Purpose: In preterm infants, the biotransformation of midazolam (M) to 1-OH-midazolam (OHM) by cytochrome P450 3A4 (CYP3A4) is developmentally immature, but it is currently unknown whether the glucuronidation of OHM to 1-OH-midazolam glucuronide (OHMG) is also decreased. The aim of our study was to investigate the urinary excretion of midazolam and its metabolites OHM and OHMG in preterm neonates following the intravenous (IV) or oral (PO) administration of a single M dose. Methods: Preterm infants (post-natal age 3-13 days, gestational age 26-34 4/7 weeks) scheduled to undergo a stressful procedure received a 30-min IV infusion (n=15) or a PO bolus dose (n=7) of 0.1 mg/kg midazolam. The percentage of midazolam dose excreted in the urine as M, OHM and OHMG up to 6 h post-dose was determined. Results: The median percentage of the midazolam dose excreted as M, OHM and OHMG in the urine during the 6-h interval after the IV infusion was 0.44% (range 0.02-1.39%), 0.04% (0.01-0.13%) and 1.57% (0.36-7.7%), respectively. After administration of the PO bolus dose, the median percentage of M, OHM and OHMG excreted in the urine was 0.11% (0.02-0.59%), 0.02% (0.00-0.10%) and 1.69% (0.58-7.31%), respectively. The proportion of the IV midazolam dose excreted as OHMG increased significantly with postconceptional age (r=0.73, p <0.05). Conclusion: The glucuronidation of OHM appears immature in preterm infants less than 2 weeks of age. The observed increase in urinary excretion of OHMG with postconceptional age likely reflects the combined maturation of glucuronidation and renal function

Total joint arthroplasty versus trapeziectomy in the treatment of trapeziometacarpal joint arthritis:a randomized controlled trial

The aim of this double anonymized, randomized controlled trial was to determine whether total joint arthroplasty has superior outcomes than trapeziectomy 1 year after surgery for trapeziometacarpal osteoarthritis. A total of 62 women aged 40 years and older, scheduled for surgery for stage II or III osteoarthritis of the trapeziometacarpal joint, were included and randomized to trapeziectomy or total joint arthroplasty. The primary outcome was the total score of the Michigan Hand Outcomes Questionnaire. Secondary outcomes were the Michigan Hand Outcomes Questionnaire subscale scores, Disability of the Arm, Shoulder and Hand Questionnaire, active range of motion, strength, return to work, patient satisfaction and complications. Data were collected at baseline and at 3 and 12 months. At 1 year, we found no superiority of total joint arthroplasty over trapeziectomy regarding the total score of the Michigan Hand Outcomes Questionnaire. The total joint arthroplasty did show a significant advantage in strength and range of motion. Level of evidence: I. </p

Total joint arthroplasty versus trapeziectomy in the treatment of trapeziometacarpal joint arthritis:a randomized controlled trial

The aim of this double anonymized, randomized controlled trial was to determine whether total joint arthroplasty has superior outcomes than trapeziectomy 1 year after surgery for trapeziometacarpal osteoarthritis. A total of 62 women aged 40 years and older, scheduled for surgery for stage II or III osteoarthritis of the trapeziometacarpal joint, were included and randomized to trapeziectomy or total joint arthroplasty. The primary outcome was the total score of the Michigan Hand Outcomes Questionnaire. Secondary outcomes were the Michigan Hand Outcomes Questionnaire subscale scores, Disability of the Arm, Shoulder and Hand Questionnaire, active range of motion, strength, return to work, patient satisfaction and complications. Data were collected at baseline and at 3 and 12 months. At 1 year, we found no superiority of total joint arthroplasty over trapeziectomy regarding the total score of the Michigan Hand Outcomes Questionnaire. The total joint arthroplasty did show a significant advantage in strength and range of motion. Level of evidence: I. </p

Feasibility of sedation and analgesia interruption following cannulation in neonates on extracorporeal membrane oxygenation

Purpose: In most extracorporeal membrane oxygenation (ECMO) centers patients are heavily sedated to prevent accidental decannulation and bleeding complications. In ventilated adults not on ECMO, daily sedation interruption protocols improve short- and long-term outcome. This study aims to evaluate safety and feasibility of sedation interruption following cannulation in neonates on ECMO. Methods: Prospective observational study in 20 neonates (0.17-5.8 days of age) admitted for ECMO treatment. Midazolam (n = 20) and morphine (n = 18) infusions were discontinued within 30 min after cannulation. Pain and sedation were regularly assessed using COMFORT-B and visual analog scale (VAS) scores. Midazolam and/or morphine were restarted and titrated according to protocolized treatment algorithms. Results: Median (interquartile range, IQR) time without any sedatives was 10.3 h (5.0-24.1 h). Median interruption duration for midazolam was 16.5 h (6.6-29.6 h), and for morphine was 11.2 h (6.7-39.4 h). During this period no accidental extubations, decannulations or bleeding complications occurred. Conclusions: This is the first study to show that interruption of sedatives and analgesics following cannulation in neonates on ECMO is safe and feasible. Interruption times are 2-3 times longer than reported for adult ICU patients not on ECMO. Further trials are needed to substantiate these findings and evaluate short- and long-term outcomes

Prognostic Factors for Long-term Aesthetic Outcome of Infantile Haemangioma Treated with Beta-blockers

Parents of infants treated with beta-blockers for infantile haemangioma are often concerned about the long-term aesthetic outcome. This cross-sectional study assessed the influence on the long-term aesthetic outcome of characteristics of the infantile haemangioma, the beta-blocker treatment, and the infant. The study included 103 children aged 6-12 years, treated with beta-blockers (propranolol or atenolol) for infantile haemangioma during infancy (age at treatment initiation ≤1 year) for ≥6 months. Dermatologists and parents scored the Patient Observer Scar Assessment Scale, and the child scored a visual analogue scale. Dermatologists identified whether telangiectasia, fibrofatty tissue, and atrophic scar tissue were present. The long-term aesthetic outcome of infantile haemangioma was judged more negatively by dermatologists and parents in case of a superficial component, ulceration, older age at treatment initiation, higher cumulative dose, and/or shorter follow-up time. According to children, infantile haemangioma located on the head had better aesthetic outcome than infantile haemangioma located elsewhere. Close monitoring, particularly of infantile haemangioma with a superficial component, is essential for early initiation of treatment, and to prevent or treat ulceration. These outcome data can support parental counselling and guide treatment strategy.</p

Mental Health of School-Aged Children Treated with Propranolol or Atenolol for Infantile Hemangioma and Their Parents

Background: Infants with infantile hemangioma (IH) have been effectively treated with propranolol or atenolol. Concerns were raised about the mental health of these The trial registration: Netherlands Trial Register Trial NL7703.children at school age, due to central nervous system effects of propranolol and visible nature of IH. Objective: This study aimed to compare the mental health at school age of children treated with propranolol to children treated with atenolol for IHs and their parents. Methods: This two-centered cross sectional study included children aged =6 years and treated with either propranolol or atenolol for IH during infancy. Children’s outcomes were performance-based affect recognition (Dutch version of the Developmental Neuropsychological Assessment-II [NEPSY-II-NL]), parent-reported emotional and behavioral functioning (Child Behavioral Checklist [CBCL]), and health-related quality of life (KIDSCREEN27). Parents’ outcome was parenting stress (Parenting Stress Questionnaire [OBVL]). Results: Data of 105 children (36 propranolol, 69 atenolol; 6.0–11.8 years) were analyzed. Mental health outcomes did not differ between both ß-blocker groups. Although overall functioning was in line with norms, children presented specific problems concerning affect recognition, parent-reported attention, and social quality of life. Parents showed increased physical symptoms, depressive symptoms, and parent-child relationship problems. Conclusion: No difference in mental health at school age was found between children treated with propranolol or atenolol for IH. Although few overall mental health problems were found, specific problems require follow-up. Follow-up of children should be directed toward affect recognition, attention, and social functioning in daily life. Problems reported by parents could be ameliorated by mental health support during and after their infant’s ß-blocker treatment.</p