The safety of repeated ketamine dosing in paediatrics: A systematic review.

BACKGROUND: Ketamine is emerging as an effective, rapidly acting antidepressant in adult research. Hypothetical concerns about its long-term safety and impact on the developing brain are limiting its research in children. However, a wealth of paediatric safety and dosing data exists for ketamine, given its extensive use globally as an anaesthetic, analgesic and sedative agent. AIMS: To evaluate the safety of repeat dosing of ketamine in children. METHODS: A systematic search of EMBASE, MEDLINE, PsycINFO, Cochrane Library and PubMed from inception to 13 April 2023 was conducted. Included studies were those reporting adverse events when ketamine was given repeatedly to children aged 5-18, for any condition. No language restrictions were applied. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline and Joanna Briggs Institute Critical Appraisal Tools Checklist for study quality assessment were used. The review process was performed independently by two reviewers. RESULTS: Five observational studies (87 patients) were included. The maximum number of doses per patient was 42, over a maximum of 4 months. There were no serious adverse events. There was no evidence of needing higher doses with time to indicate tolerance. The longest follow-up period was 6 months. There were no long-term consequences (including neurocognitive) reported within this time frame. CONCLUSIONS: These results suggest that, despite methodological limitations of the studies, ketamine is well tolerated and safe for use in children, even when given repeatedly in regimens analogous to those used for the treatment of depression in adults. This finding supports the expansion of research into the use of ketamine as a novel antidepressant in children.

A randomized, double-blind, double-dummy comparison of the efficacy and tolerability of low-dose transdermal buprenorphine (BuTrans seven-day patches) with buprenorphine sublingual tablets (Temgesic) in patients with osteoarthritis pain.

CONTEXT: Osteoarthritis (OA) is a common cause of chronic pain, particularly in the older population. Modern approaches to the management of OA pain recommend tailoring treatment to the individual. This study examines treatment options for OA pain in the form of low-dose transdermal and sublingual opioid analgesia. OBJECTIVES: The aims of this trial were to compare the efficacy and tolerability of seven-day, low-dose transdermal buprenorphine patches (BuTrans, Napp Pharmaceuticals Limited UK) with sublingual buprenorphine (Temgesic, Schering-Plough Limited UK) in patients with moderate to severe pain caused by OA of the hip(s) and/or knee(s), and to establish analgesic equivalence of the two products. METHODS: Two hundred forty-six patients with OA pain in the hip(s) and/or knee(s) were enrolled in this randomized, double-blind, parallel-group study; 110 completed the study. Patients were randomized to receive transdermal buprenorphine patches (5, 10, and 20 microg/hour) or sublingual buprenorphine (200 and 400 microg tablets). Their medication was titrated to pain control and they were treated for up to seven weeks. The main outcome measures were pain intensity (primary outcome), sleep disturbance, quality of life, and safety assessments. RESULTS: Patients' Box Scale-11 pain scores decreased between entry and assessment in both treatment groups. During the 28-day assessment period, the estimated mean treatment differences (95% confidence intervals) were 0.00 (-0.68,0.69), -0.11 (-0.85,0.63), and -0.13 (-0.95,0.68), for the morning, midday, and evening scores, respectively. All the confidence intervals were within the prespecified limits for equivalence (-1.5, 1.5). Use of escape medication was low. In both treatment groups, sleep disturbance caused by pain decreased between entry and assessment. Patients' quality of life improved during the study. Significantly fewer patients receiving the transdermal buprenorphine patches reported nausea (P=0.035), dizziness (P=0.026), and vomiting (P=0.039). CONCLUSION: In conclusion, seven-day, low-dose transdermal buprenorphine patches are as effective as sublingual buprenorphine, with a better tolerability profile.

Short-duration topical treatment of tinea pedis using terbinafine emulsion gel: results of a dose-ranging clinical trial.

BACKGROUND: In the treatment of tinea pedis, current terbinafine formulations are applied once or twice daily for 7 days. A terbinafine emulsion gel formulation has been developed to provide a 5-day treatment course for tinea pedis. OBJECTIVE: To determine the lowest effective concentration of terbinafine (1% or 3%) emulsion gel applied once daily for 5 days for the treatment of tinea pedis. METHODS: This double-blind, placebo-controlled study evaluated the efficacy of 1% and 3% terbinafine gel for 5 days in 84 outpatients with tinea pedis. The primary efficacy endpoint was the percentage of patients with effective treatment (negative microscopy and culture with only mild erythema/desquamation/pruritus [total score