Safety and efficacy of a propofol and ketamine based procedural sedation protocol in children with cerebral palsy undergoing botulinum toxin A injections.

Background Pediatric patients with cerebral palsy (CP) often undergo intramuscular botulinum toxin (BoNT‐A) injections. These injections can be painful and may require procedural sedation. An ideal sedation protocol has yet to be elucidated. Objective To investigate the safety and efficacy of a propofol and ketamine based sedation protocol in pediatric patients with cerebral palsy requiring BoNT‐A injections. Design This is a retrospective chart review of children with CP undergoing propofol and ketamine based sedation for injections with botulinum toxin A. Setting The sedations took place in a procedural sedation suite at a tertiary children’s hospital from Feb 2013 through Sept 2017. Patients 164 patients with diagnoses of cerebral palsy were included in this study. Methods An initial bolus of 0.5 mg/kg ketamine followed by a 2 mg/kg bolus of propofol was administered with supplemental boluses of propofol as needed to achieve deep sedation during the intramuscular BoNT‐A injections. Main Outcome Measurements Propofol dosages, adverse events, serious adverse events, and sedation time parameters were reviewed. Results 345 sedations were successfully performed on 164 patients. The median total dose of propofol was 4.7 mg/kg (IQR 3.5, 6.3). Adverse events were encountered in 10.1% of procedures including hypoxemia responsive to supplemental oxygen (9.6%) and transient apnea (1.4%). The mean procedure time, recovery time and total sedation time were 10, 11 and 33 minutes, respectively. With regard to patient variables, including age, weight, dose of propofol, sedation time, and Gross Motor Function Classification System classification, there was no association with increased incidence of adverse events. Conclusion Our sedation protocol of propofol and ketamine is safe and effective in children with cerebral palsy undergoing procedural sedation for intramuscular injections with BoNT‐A. The adverse events encountered appeared to be related to airway and respiratory complications secondary to musculoskeletal deformities, emphasizing the importance of airway monitoring and management in these patients

Intensivist-based deep sedation using propofol for pediatric outpatient flexible bronchoscopy

AIM To evaluate the safety and efficacy of sedating pediatric patients for outpatient flexible bronchoscopy. METHODS A retrospective chart review was conducted for all children, age 17 years or under who underwent flexible bronchoscopy under deep sedation in an outpatient hospital-based setting. Two sedation regimens were used; propofol only or ketamine prior to propofol. Patients were divided into three age groups; infants (less than 12 mo), toddlers (1-3 years) and children (4-17 years). Demographics, indication for bronchoscopy, sedative dosing, sedation and recovery time and adverse events were reviewed. RESULTS Of the total 458 bronchoscopies performed, propofol only regimen was used in 337 (74%) while propofol and ketamine was used in 121 (26%). About 99% of the procedures were successfully completed. Children in the propofol + ketamine group tend to be younger and have lower weight compared to the propofol only group. Adverse events including transient hypoxemia and hypotension occurred in 8% and 24% respectively. Median procedure time was 10 min while the median discharge time was 35 min. There were no differences in the indication of the procedure, propofol dose, procedure or recovery time in either sedative regimen. When compared to other age groups, infants had a higher incidence of hypoxemia. CONCLUSION Children can be effectively sedated for outpatient flexible bronchoscopy with high rate of success. This procedure should be performed under vigilance of highly trained providers

The effects of PEGylation on LNP based mRNA delivery to the eye.

Gene therapy is now an effective approach to treat many forms of retinal degeneration. Delivery agents that are cell-specific, allow for multiple dosing regimens, and have low immunogenicity are needed to expand the utility of gene therapy for the retina. We generated eight novel lipid nanoparticles (LNPs) ranging in size from 50 nm to 150 nm by changing the PEG content from 5% to 0.5%, respectively. Subretinal injections of LNP-mRNA encoding luciferase revealed that 0.5% PEG content within nanoparticles elicits the highest expression. Similar injections of LNP delivered cre mRNA into Ai9 mice revealed cell-specific protein expression in the retinal pigment epithelium (RPE), confirmed by fundus photography and immunohistochemistry of whole globe cross-sections. To investigate mechanisms of LNP delivery to the eye, we injected mCherry mRNA using the subretinal approach in apoE-/- and Mertk-/- mice. RPE transfection was observed in both mouse models suggesting that LNP intracellular delivery is not solely dependent on apolipoprotein adsorption or phagocytosis. To investigate LNP penetration, particles were delivered to the vitreous chamber via an intravitreal injection. The 0.5% PEG particles mediated the highest luciferase activity and expression was observed in the Müller glia, the optic nerve head and the trabecular meshwork, but failed to reach the RPE. Overall, particles containing less PEG (~150 nm in size) mediated the highest expression in the eye. Thus far, these particles successfully transfect RPE, Müller cells, the optic nerve head and the trabecular meshwork based on route of administration which can expand the utility of LNP-mediated gene therapies for the eye

Neighborhood-Level Factors Associated with Physical Dating Violence Perpetration: Results of a Representative Survey Conducted in Boston, MA

Neighborhood-level characteristics have been found to be associated with different forms of interpersonal violence, but studies of the relationship between these characteristics and adolescent dating violence are limited. We examined 6 neighborhood-level factors in relation to adolescent physical dating violence perpetration using both adolescent and adult assessments of neighborhood characteristics, each of which was aggregated across respondents to the neighborhood level. Data came from an in-school survey of 1,530 public high school students and a random-digit-dial telephone survey of 1,710 adult residents of 38 neighborhoods in Boston. Approximately 14.3% of the youth sample reported one or more acts of physical aggression toward a dating partner in the month preceding the survey. We calculated the odds of past-month physical dating violence by each neighborhood-level factor, adjusting for school clustering, gender, race, and nativity. In our first 6 models, we used the adolescent assessment of neighborhood factors and then repeated our procedures using the adult assessment data. Using the adolescent assessment data, lower collective efficacy (AOR = 1.95, 95% CI = 1.09–3.52), lower social control (AOR = 1.92, 95% CI = 1.07–3.43), and neighborhood disorder (AOR = 1.19, 95% CI = 1.05–1.35) were each associated with increased likelihood of physical dating violence perpetration. However, when we used the adult version of the neighborhood assessment data, no neighborhood factor predicted dating violence. The implications and limitations of these findings are discussed

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline