A randomized, double-blind, placebo-controlled study of histone deacetylase type 6 inhibition for the treatment of painful diabetic peripheral neuropathy.

Introduction: Current treatments for painful diabetic peripheral neuropathy (DPN) are insufficiently effective for many individuals and do not treat nonpain signs and symptoms. The enzyme histone deacetylase type 6 (HDAC6) may play a role in the pathophysiology of painful DPN, and inhibition of HDAC6 has been proposed as a potential treatment. Objectives: To assess the efficacy and safety of the novel HDAC6 inhibitor ricolinostat for the treatment of painful diabetic peripheral neuropathy. Methods: We conducted a 12-week randomized, double-blind, placebo-controlled phase 2 study of the efficacy of ricolinostat, a novel selective HDAC6 inhibitor, in 282 individuals with painful DPN. The primary outcome was the change in the patient-reported pain using a daily diary, and a key secondary outcome was severity of nonpain neuropathic signs using the Utah Early Neuropathy Scale (UENS) score. Results: At the 12-week assessment, changes in average daily pain and UENS scores were not different between the ricolinostat and placebo groups. Conclusion: These results do not support the use of the HDAC6 inhibitor ricolinostat as a treatment for neuropathic pain in DPN for periods up to 12 weeks.

Indoor environmental exposures among children with asthma seen in an urban emergency department.

BACKGROUND: Current guidelines for asthma management emphasize the control of environmental irritants and allergens within the home. Understanding the prevalence of indoor home exposures within such a population may be important for any emergency department (ED) program that seeks to improve the quality of its asthma care and patient education. OBJECTIVE: We sought to determine the prevalence of indoor home exposures in a cohort of children with moderate to severe asthma who were treated in an urban pediatric ED and to correlate these exposures with household income, prior asthma morbidity, health care utilization, and quality of life (QoL). METHODS: We enrolled a cohort of children with chronic asthma who were 12 months through 17 years of age and who had at least one other unscheduled visit for asthma within the previous 6 months. Trained research assistants interviewed the children's parent or guardian regarding the prevalence of home exposures to environmental tobacco smoke (ETS) and common allergens. In addition, data were collected on each patient's prior asthma history, morbidity, health care utilization, medication use, and QoL. RESULTS: Of the 488 eligible children enrolled, 60.0% were <6 years of age, 63.9% were male, 85.9% were black, 68.4% were publicly insured, and 51.8% had >3 ED visits in the previous 12 months. Home exposure to ETS and potential allergens was high. Exposure to cockroach allergen was significantly associated with household income. Coexistence of exposures was common: significantly more patients reporting ETS exposure also reported exposure to cockroach allergen and mold than those not reporting ETS exposure. Poorer QoL was significantly associated with cockroach exposure, although this effect was limited to those also exposed to ETS. Higher rates of unscheduled health care utilization and persistent asthma symptoms were not associated with exposures. CONCLUSION: Additional investigation is necessary to clarify the role of exposure-avoidance measures as a component of ED-based interventions for asthma care.

Improved asthma outcomes in a high-morbidity pediatric population: results of an emergency department-based randomized clinical trial.

OBJECTIVE: To determine if an emergency department-based asthma follow-up clinic could improve outcomes within a high-morbidity pediatric population. DESIGN: Prospective, randomized clinical trial with 6 months of follow-up. SETTING: Emergency department of an urban pediatric medical center. PARTICIPANTS: Convenience sample of 488 patients aged 12 months to 17 years, inclusive, with prior physician-diagnosed asthma and 1 or more other unscheduled visits in the previous 6 months and/or 1 or more hospitalizations in the prior 12 months. INTERVENTION: Single follow-up clinic visit focusing on 3 domains: asthma self-monitoring and management, environmental modification and trigger control, and linkages and referrals to ongoing care. MAIN OUTCOME MEASURES: The primary outcome measure was unscheduled visits for acute asthma care. Secondary outcomes included compliance with a medical plan and asthma quality of life. Analysis was by intention to treat with adjustment for baseline differences. RESULTS: Of those randomized to the clinic visit, 172 (70.5%) of 244 attended. The intervention group had significantly fewer mean unscheduled visits for asthma care during follow-up (1.39 vs 2.34; relative risk [RR] = 0.60 [95% confidence interval (CI), 0.46-0.77]). At 6 months, significantly more patients in the intervention group reported use of inhaled corticosteroids in the prior 2 days (49.3% vs 26.5%; RR = 2.03 [95% CI, 1.57-2.62]), no limitation in daytime quality of life (43.8% vs 34.4%; RR = 1.36 [95% CI, 1.06-1.73]), and no functional limitations in quality of life (49.8% vs 40.8%; RR = 1.33 [95% CI, 1.08-1.63]). CONCLUSION: Attendance in the follow-up clinic was high. The intervention decreased subsequent unscheduled health care use while improving compliance and quality of life.