Optimal Dose of Intranasal Dexmedetomidine for Laceration Repair in Children: A Phase II Dose-Ranging Study.

STUDY OBJECTIVE: To determine the optimal sedative dose of intranasal dexmedetomidine for children undergoing laceration repair. METHODS: This dose-ranging study employing the Bayesian Continual Reassessment Method enrolled children aged 0 to 10 years with a single laceration (<5 cm), requiring single-layer closure, who received topical anesthetic. Children were administered 1, 2, 3, or 4 mcg/kg intranasal dexmedetomidine. The primary outcome was the proportion with adequate sedation (Pediatric Sedation State Scale score of 2 or 3 for ≥90% of the time from sterile preparation to tying of the last suture). Secondary outcomes included the Observational Scale of Behavior Distress-Revised (range: 0 [no distress] to 23.5 [maximal distress]), postprocedure length of stay, and adverse events. RESULTS: We enrolled 55 children (35/55 [64%] males; median [interquartile range {IQR}] age 4 [2, 6] years). At 1, 2, 3, and 4 mcg/kg intranasal dexmedetomidine, respectively, the proportion of participants "adequately" sedated was 1/3 (33%), 2/9 (22%), 13/21 (62%), and 12/21 (57%); the posterior mean (95% equitailed credible intervals) for the probability of adequate sedation was 0.38 (0.04, 0.82), 0.25 (0.05, 0.54), 0.61 (0.41, 0.80), and 0.57 (0.36, 0.76); the median (IQR) Observational Scale of Behavior Distress-Revised scores during suturing was 2.7 (0.3, 3), 0 (0, 3.8), 0.6 (0, 5), and 0 (0, 3.7); the median (IQR) postprocedure length of stay was 67 (60, 78), 76 (60, 100), 89 (76, 109), and 113 (76, 150) minutes. There was 1 adverse event, a decrease in oxygen saturation at 4 mcg/kg, which resolved with head repositioning. CONCLUSION: Despite limitations, such as our limited sample size and subjectivity in Pediatric Sedation State Scale scoring, sedation efficacy for 3 and 4 mcg/kg were similarly based on equitailed credible intervals suggesting either could be considered optimal.

The intranasal dexmedetomidine plus ketamine for procedural sedation in children, adaptive randomized controlled non-inferiority multicenter trial (Ketodex): a statistical analysis plan.

BACKGROUND: Procedural sedation and analgesia (PSA) is frequently required to perform closed reductions for fractures and dislocations in children. Intravenous (IV) ketamine is the most commonly used sedative agent for closed reductions. However, as children find IV insertion a distressing and painful procedure, there is need to identify a feasible alternative route of administration. There is evidence that a combination of dexmedetomidine and ketamine (ketodex), administered intranasally (IN), could provide adequate sedation for closed reductions while avoiding the need for IV insertion. However, there is uncertainty about the optimal combination dose for the two agents and whether it can provide adequate sedation for closed reductions. The Intranasal Dexmedetomidine Plus Ketamine for Procedural Sedation (Ketodex) study is a Bayesian phase II/III, non-inferiority trial in children undergoing PSA for closed reductions that aims to address both these research questions. This article presents in detail the statistical analysis plan for the Ketodex trial and was submitted before the outcomes of the trial were available for analysis. METHODS/DESIGN: The Ketodex trial is a multicenter, four-armed, randomized, double-dummy controlled, Bayesian response adaptive dose finding, non-inferiority, phase II/III trial designed to determine (i) whether IN ketodex is non-inferior to IV ketamine for adequate sedation in children undergoing a closed reduction of a fracture or dislocation in a pediatric emergency department and (ii) the combination dose for IN ketodex that provides optimal sedation. Adequate sedation will be primarily measured using the Pediatric Sedation State Scale. As secondary outcomes, the Ketodex trial will compare the length of stay in the emergency department, time to wakening, and adverse events between study arms. DISCUSSION: The Ketodex trial will provide evidence on the optimal dose for, and effectiveness of, IN ketodex as an alternative to IV ketamine providing sedation for patients undergoing a closed reduction. The data from the Ketodex trial will be analyzed from a Bayesian perspective according to this statistical analysis plan. This will reduce the risk of producing data-driven results introducing bias in our reported outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04195256 . Registered on December 11, 2019.

Hyoscine butylbromide versus acetaminophen for nonspecific colicky abdominal pain in children: a randomized controlled trial.

BACKGROUND: Less than two-thirds of children with abdominal pain in the emergency department receive analgesia. We sought to determine whether hyoscine butylbromide was superior to acetaminophen for children with nonspecific colicky abdominal pain. METHODS: We randomly allocated children aged 8-17 years with nonspecific colicky abdominal pain who presented to the pediatric emergency department of London Health Sciences Centre, London, Ontario to receive hyoscine butylbromide, 10 mg given orally, or acetaminophen, 15 mg/kg given orally (maximum 975 mg). We considered the minimal clinically important difference for the primary outcome (self-reported pain at 80 min) to be 13 mm on a 100 mm visual analogue scale. Secondary outcomes included administration of rescue analgesia, adverse effects and pain score less than 30 mm at 80 minutes. RESULTS: A total of 236 participants (120 in the hyoscine butylbromide group and 116 in the acetaminophen group) were included in the trial. The mean visual analogue scale scores at 80 minutes were 29 mm (standard deviation [SD] 26 mm) and 30 mm (SD 29 mm) with hyoscine butylbromide and acetaminophen, respectively (adjusted difference 1, 95% confidence interval -7 to 7). Rescue analgesia was administered to 4 participants (3.3%) in the hyoscine butylbromide group and 1 participant (0.9%) in the acetaminophen groups (p = 0.2). We found no significant differences in rates of adverse effects between hyoscine butylbromide (32/116 [27.6%]) and acetaminophen (28/115 [24.3]) (p = 0.5); no serious adverse effects were observed. The proportion with a pain score less than 30 mm at 80 minutes was 66 (55.0%) with hyoscine butylbromide and 63 (54.3%) with acetaminophen (p = 0.9). INTERPRETATION: Hyoscine butylbromide was not superior to acetaminophen in this setting. Both agents were associated with clinically important pain reduction, and either can be considered for children presenting to the emergency department with nonspecific colicky abdominal pain. Trial registration: Clinicaltrials.gov, no. NCT02582307.

Adaptive randomised controlled non-inferiority multicentre trial (the Ketodex Trial) on intranasal dexmedetomidine plus ketamine for procedural sedation in children: study protocol.

INTRODUCTION: Up to 40% of orthopaedic injuries in children require a closed reduction, almost always necessitating procedural sedation. Intravenous ketamine is the most commonly used sedative agent. However, intravenous insertion is painful and can be technically difficult in children. We hypothesise that a combination of intranasal dexmedetomidine plus intranasal ketamine (Ketodex) will be non-inferior to intravenous ketamine for effective sedation in children undergoing a closed reduction. METHODS AND ANALYSIS: This is a six-centre, four-arm, adaptive, randomised, blinded, controlled, non-inferiority trial. We will include children 4-17 years with a simple upper limb fracture or dislocation that requires sedation for a closed reduction. Participants will be randomised to receive either intranasal Ketodex (one of three dexmedetomidine and ketamine combinations) or intravenous ketamine. The primary outcome is adequate sedation as measured using the Paediatric Sedation State Scale. Secondary outcomes include length of stay, time to wakening and adverse effects. The results of both per protocol and intention-to-treat analyses will be reported for the primary outcome. All inferential analyses will be undertaken using a response-adaptive Bayesian design. Logistic regression will be used to model the dose-response relationship for the combinations of intranasal Ketodex. Using the Average Length Criterion for Bayesian sample size estimation, a survey-informed non-inferiority margin of 17.8% and priors from historical data, a sample size of 410 participants will be required. Simulations estimate a type II error rate of 0.08 and a type I error rate of 0.047. ETHICS AND DISSEMINATION: Ethics approval was obtained from Clinical Trials Ontario for London Health Sciences Centre and McMaster Research Ethics Board. Other sites have yet to receive approval from their institutions. Informed consent will be obtained from guardians of all participants in addition to assent from participants. Study data will be submitted for publication regardless of results. TRIAL REGISTRATION NUMBER: NCT0419525.

Evaluation of primary caregivers' perceptions on home trampoline use.

Trampolines are widely used by children, but trampoline injuries can be severe and may require hospital care or even surgery. This pilot study examined the effectiveness of an educational intervention on caregivers' perceptions of trampoline use and safety for their children. Primary caregivers were recruited from the orthopedic clinic at the Children's Hospital at our institution in 2015. Caregivers were asked to complete a survey at two time points, initially in clinic and one week post educational intervention. The educational intervention was a pamphlet outlining trampoline safety data. Data analysis occurred in 2016. From the 100 primary caregivers recruited, 39 caregivers owned a trampoline, and 10 had presented to the emergency department with their child for an injury related to trampoline use. After educational intervention, caregivers had higher rating of perceived danger associated with trampolines (6/10 vs. 8/10, p < 0.001). Additionally, a greater number of caregivers were more knowledgeable on the safe age of trampoline use (56% vs. 91%, p < 0.001) and safe number of jumpers (45% vs. 86%, p < 0.001). Finally, there was a 29% increase in the proportion of caregivers who at least agreed that trampolines are dangerous (pre: 44% vs. post: 73%, p < 0.001), however 50% of caregivers would still allow their child to use a trampoline. Overall, the results of this study show that a simple educational intervention can help to increase knowledge around safe trampoline practices and increase awareness of injury. Further, this study can act as initial evidence for future studies to implement this type of intervention long-term.

Treatment of abdominal pseudocysts and associated ventricuoperitoneal shunt failure.

PURPOSE: The purpose of this study was to determine whether drainage and revision are an effective treatment for abdominal pseudocyst associated ventriculoperitoneal (VP) shunt failure by estimating the total rate of secondary shunt failure. METHODS: We performed a retrospective review of children with hydrocephalus diagnosed with and treated for an abdominal pseudocyst at the Children's Hospital, London Health Sciences Centre (LHSC) between January 1, 2000 and May 31, 2016 (ethics approval # 108136). Patients with a VP shunt were included if (i) the development of an abdominal pseudocyst at age 2 to 18 years was identified, (ii) treatment of the pseudocyst by either interventional radiology (IR) or surgical drainage, and (iii) revision of the VP shunt. Demographic data and details of pseudocyst formation/ treatment as well as subsequent failures were identified. RESULTS: Twelve patients who had a VP shunt developed abdominal pseudocyst and met inclusion criteria. A 91% shunt failure rate after drainage and shunt revision was identified. Three patients had the pseudocyst drained in interventional radiology and then externalized due to shunt infection. Nine patients were treated by surgical revision. Ten patients experienced recurrent shunt failure following initial drainage of the pseudocyst: pseudocyst reoccurrence (n = 3), distal obstruction from adhesions (n = 1), and uncleared infection (n = 6). CONCLUSION: The results suggest that pseudocyst drainage and shunt revision is ineffective in providing long-term resolution of shunt problems.

Nonrandomized assessment of ingrown toenails treated with excision of skinfold rather than toenail (NAILTEST): An observational study of the Vandenbos procedure.

BACKGROUND: The Vandenbos procedure for ingrown toenails consists of excising the surrounding skinfold and allowing the wound to heal by secondary intention. Previous studies have documented low rates of recurrence, but patient-reported outcomes remain uncertain. METHODS: This study was a prospective, observational assessment of children and adolescents who underwent the Vandenbos procedure for one or more ingrown toenails. Standardized assessments of pain, functional status, and quality of life were completed before surgery and then one, two, and six months postoperatively. RESULTS: Thirty-nine participants (with 59 ingrown toenails) completed at least one postoperative assessment and were included in the analysis. Age ranged from 4 to 20years (mean 13.5years). Recovery time was a median of 7days for return to school or work and 23days for being able to wear enclosed shoes. Seven participants (18%) experienced one or more minor complications within the first two months of surgery. There were no recurrences. Ninety-five percent of participants and 100% of parents would recommend the Vandenbos procedure. CONCLUSIONS: We conclude that the Vandenbos procedure is associated with a low recurrence rate in children, adolescents, and young adults with ingrown toenails. Patient-reported recovery time, complication rate, functional outcomes, and satisfaction are excellent. LEVEL OF EVIDENCE: 3.

Cost analysis of nonoperative management of acute appendicitis in children.

PURPOSE: The purpose of this study was to determine if nonoperative management of acute appendicitis in children is more cost effective than appendectomy. METHODS: A retrospective review of children (6-17years) with acute appendicitis treated nonoperatively (NOM) from May 2012 to May 2015 was compared to similar patients treated with laparoscopic appendectomy (OM) (IRB#107535). Inclusion criteria included symptoms ≤48h, localized peritonitis, and ultrasound confirmation of acute appendicitis. Variables analyzed included failure rates, complications, length of stay (LOS), and cost analysis. RESULTS: 26 NOM patients (30% female, mean age 12) and 26 OM patients (73% female, mean age 11) had similar median initial LOS (24.5h (NOM) vs 16.5h (OM), p=0.076). Median total LOS was significantly longer in the NOM group (34.5h (NOM) vs 17.5 (OM), p=0.01). Median cost of appendectomy was $1416.14 (range $781.24-$2729.97). 9/26 (35%) NOM patients underwent appendectomy for recurrent appendicitis. 4/26 (15%) OM patients were readmitted (postoperative abscess (n=2), Clostridium difficile colitis (n=1), postoperative nausea/vomiting (n=1)). Median initial hospital admission costs were significantly higher in the OM group ($3502.70 (OM) vs $1870.37 (NOM), p=0.004)). However, median total hospital costs were similar for both groups ($3708.68 (OM) vs $2698.99 (NOM), p=0.065)). CONCLUSION: Although initial costs were significantly less in children with acute appendicitis managed nonoperatively, total costs were similar for both groups. The high failure rate of nonoperative management in this series contributed to the total increased cost in the NOM group. LEVEL OF EVIDENCE: 3b.

Changes in self-reported disability after performance-based tests in obese and non-obese individuals diagnosed with osteoarthritis of the knee.

PURPOSE: The purposes of this study are three-fold: (1) To examine whether the WOMAC questionnaire should be obtained before or after performance-based tests. (2) To assess whether self-reported disability scores before and after performance-based tests differ between obese and non-obese individuals. (3) To observe whether physical activity and BMI predict self-reported disability before and after performance based tests. METHODS: A longitudinal study included thirty one participants diagnosed with knee osteoarthritis (OA) using the Kellgren-Lawrence Scale by an orthopedic surgeon. RESULTS: All WOMAC scores were significantly higher after as compared to before the completion of performance-based tests. This pattern of results suggested that the WOMAC questionnaire should be administered to individuals with OA after performance-based tests. The obese OA was significantly different compared to the non-obese OA group on all WOMAC scores. Physical activity and BMI explained a significant proportion of variance of self-reported disability. CONCLUSION: Obese individuals with knee OA may over-estimate their ability to perform physical activities, and may under-estimate their level of disability compared to non-obese individuals with knee OA. In addition, self-reported physical activity seems to be a strong indicator of disability in individuals with knee OA, particularly for individuals with a sedentary life style. Implications for Rehabilitation Osteoarthritis is a progressive joint disabling condition that restricts physical function and participation in daily activities, particularity in elderly individuals. Obesity is a comorbidity commonly associated with osteoarthritis and it appears to increase self-reported disability in those diagnosed with osteoarthritis of the knee. In a relatively small sample, this study recommends that rehabilitation professionals obtain self-report questionnaires of disability after performance-based tests in obese individuals with osteoarthritis of the knee as they are more likely to give an accurate representation of their level of ability at this time.