Prescription Benzodiazepine Use in Privately Insured U.S. Children and Adolescents.

INTRODUCTION: Benzodiazepines are commonly prescribed in the U.S. but entail safety concerns, including dependency. In pediatrics, many indications lack trial data. Authors aimed to describe youth initiating prescription benzodiazepine treatment, identify potential indications and prescribing concerns, estimate the duration of treatment by potential indication, and identify factors that predict long-term use. METHODS: The study cohort included children (aged 3-12 years) and adolescents (aged 13-17 years) initiating prescription benzodiazepine treatment (≥3 days' supply) from January 2010 to September 2015 in a U.S. commercial claims database. Potential indications included selected ICD-9-CM diagnoses (≤30 days prior). Long-term (≥6 months) benzodiazepine treatment was estimated with Kaplan-Meier estimation and modified Poisson regression identified independent predictors of long-term benzodiazepine treatment (analysis completed in 2018). RESULTS: Of 24,504 children and 61,046 adolescents initiating benzodiazepines, 62% of the children and 68% of the adolescents had a potential indication. Anxiety disorders were the most common indication, with mental health indications more common among adolescents (45%) than children (23%) and epilepsy and movement disorders higher in children. Recent opioid prescriptions were common before benzodiazepine initiation (children, 22%; adolescents, 21%). Six percent of the initiators became long-term benzodiazepine users. Potential indication, provider contact, psychotropic medication, and chronic conditions independently predicted long-term benzodiazepine treatment in adolescents and children. CONCLUSIONS: U.S. children and adolescents are prescribed benzodiazepines for various mental health and other medical conditions, many lacking evidence of pediatric efficacy. Long-term benzodiazepine treatment, concurrent opioid prescriptions, psychotropic use, and prior substance use disorder diagnoses suggest safety risks among some youth prescribed benzodiazepines.

Esophageal Cooling Device Versus Other Temperature Modulation Devices for Therapeutic Normothermia in Subarachnoid and Intracranial Hemorrhage.

Achieving and maintaining normothermia (NT) after subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) often require temperature modulating devices (TMD). Shivering is a common adverse effect of TMDs that can lead to further costs and complications. We evaluated an esophageal TMD, the EnsoETM (Attune Medical, Chicago, IL), to compare NT performance, shiver burden, and cost of shivering interventions with existing TMDs. Patients with SAH or ICH and refractory fever were treated with the EnsoETM. Patient demographics, temperature data, shiver severity, and amounts and costs of medications used for shiver management were prospectively collected. Controls who received other TMDs were matched for age, gender, and body surface area to EnsoETM recipients, and similar retrospective data were collected. All patients were mechanically ventilated. Fever burden was calculated as areas of curves of time spent above 37.5°C or 38°C. Demographics, temperature data, and costs of EnsoETM recipients were compared with recipients of other TMDs. Eight EnsoETM recipients and 24 controls between October 2015 and November 2016 were analyzed. There were no differences between the two groups in demographics or patient characteristics. No difference was found in temperature at initiation (38.7°C vs. 38.5°C, p = 0.4) and fever burden above 38°C (-0.44°C × hours vs. -0.53°C × hours, p = 0.47). EnsoETM recipients showed a nonsignificant trend in taking longer to achieve NT than other TMDs (5.4 hours vs. 2.9 hours, p = 0.07). EnsoETM recipients required fewer shiver interventions than controls (14 vs. 30, p = 0.02). EnsoETM recipients incurred fewer daily costs than controls ($124.27 vs. $232.76, p = 0.001). The EnsoETM achieved and maintained NT in SAH and ICH patients and was associated with less shivering and lower pharmaceutical costs than other TMDs. Further studies in larger populations are needed to determine the EnsoETM's efficacy in comparison to other TMDs.

Proximity of off-premise alcohol outlets and heavy alcohol consumption: a cohort study.

BACKGROUND: Availability of alcohol has been associated with alcohol consumption in cross-sectional studies. We examined longitudinally whether change in proximity to off-premise (i.e., no consumption on the premises) beer and liquor outlets is associated with heavy alcohol consumption. METHODS: Distances from 54,778 Finnish Public Sector study participants' homes to the nearest off-premise beer and liquor outlets were calculated using Global Positioning System-coordinates. Between-individual analyses were used to study the effects of distance to the nearest outlet on heavy alcohol use, and within-individual analyses to study the effects of a change in distance on change in heavy use. RESULTS: Mean follow-up time in 2000-2009 was 6.8 (standard deviation 2.0) years. In a between-individual analysis, decrease from ≥500 m to <500 m (vs. remained ≥500 m) in the distance to the nearest beer outlet increased the likelihood of incident heavy alcohol use in women (odds ratio 1.23, 95% CI 1.05-1.44), but not in men. In a within-individual analysis decrease from 500 m to 0m in log-transformed continuous distance to the nearest beer outlet increased the odds of heavy alcohol consumption in women by 13% (odds ratio 1.13, 95% CI 1.01-1.27). For the corresponding change in distance to liquor outlet the increase was 3% (odds ratio 1.03, 95% CI 0.97-1.09). CONCLUSIONS: Change in distance from home to the nearest off-premise alcohol outlet affects the risk of heavy alcohol consumption in women. This evidence supports policies that restrict physical availability of alcohol.

Mortality of harmful drinkers increased after reduction of alcohol prices in northern Finland: a 10-year follow-up of head trauma subjects.

OBJECTIVE: Alcohol-related mortality may be influenced by the level of alcohol consumption. We investigated the effect of alcohol price reduction on mortality in a cohort of 827 subjects with head injury. METHODS: We used the Finnish National Hospital Discharge Register to identify all diagnoses recorded during hospital and health center visits for survivors of the index injury during a follow-up of 10 years. Mortality data were gathered from death records obtained from the Official Cause-of-Death Statistics. Cox proportional hazards model was used to identify independent predictors for death. Kaplan-Meier survival curves were used to characterize the effect of alcohol price reduction on mortality of harmful and non-harmful drinkers. RESULTS: Alcohol-related deaths increased after the reduction of alcohol prices on March 1, 2004. Subjects recorded as harmful drinkers during the follow-up period were significantly (p < 0.001) more likely than others to die after the price reduction. Older age (HR 1.06, 95% CI 1.05-1.07), moderate-to-severe brain injury (HR 2.39, 95% CI 1.59-3.60) and harmful drinking recorded after the index trauma (HR 2.59, 95% CI 1.62-4.62) were significant (p < 0.001) predictors for death. CONCLUSION: We conclude that a political decision to lower the price of alcohol may cause a significant increase in the death rate of harmful drinkers.

Stimuli produced by observing responses make rats' ethanol self-administration more resistant to price increases.

RATIONALE: Observing responses bring sensory receptors into contact with environmental stimuli. In the observing-response procedure, periods in which an operant response (e.g. pressing a lever) is reinforced by drug deliveries alternate with periods in which this response is never reinforced (i.e. extinction). These alternating periods of drug availability versus extinction are not signaled. Observing responses (i.e. presses on a second lever) produce brief stimuli signaling whether drug is available or not for responses on the first lever. Little is known about how parameters of the drug reinforcer affect drug-stimulus observing. OBJECTIVES: The effects of changes in the unit price (responses/reinforcer magnitude) of self-administered ethanol on rats' observing were examined. Also, the effects of an observing-response-produced ethanol stimulus on ethanol consumption were examined by comparing consumption during signaled and unsignaled periods of ethanol availability. METHODS: Rats self-administered oral ethanol in the observing-response procedure. The unit price of ethanol in the observing-response procedure was increased by increasing the response requirement for ethanol across conditions. RESULTS: Observing and response rates on the ethanol lever increased and then decreased with increases in the unit price of ethanol. However, ethanol-lever responding and ethanol consumption during periods when ethanol was available were less sensitive to increases in price when the observing-response-produced ethanol stimulus was present. CONCLUSIONS: Observing varies as an orderly function of unit price of a drug reinforcer, and drug stimuli produced by observing responses can make drug consumption less sensitive to increases in price. This procedure may provide an animal model of both attending to drug stimuli and the resultant effects of these stimuli on drug taking.

Effects of bremazocine on self-administration of smoked cocaine base and orally delivered ethanol, phencyclidine, saccharin, and food in rhesus monkeys: a behavioral economic analysis.

There is increasing evidence that kappa-opioid receptor agonists modulate cocaine-maintained behavior, and limited findings implicate the involvement of kappa-opioid receptors in ethanol-maintained behaviors. The purpose of the present study was to investigate the effects of bremazocine, a kappa-opioid agonist, on the self-administration of smoked cocaine base and oral ethanol in rhesus monkeys (Macaca mulatta). To determine the selectivity of bremazocine, the effects of bremazocine pretreatment on the oral self-administration of phencyclidine (PCP), saccharin, and food were also examined. Adult male rhesus monkeys were trained to self-administer oral ethanol, PCP, saccharin (n = 8), food (n = 6), or smoked cocaine base (n = 6) and water during daily sessions. Bremazocine (0.00032-, 0.001-, and 0.0025-mg/kg i.m.) injections were given 15 min before session. The 4 days of stable behavior before pretreatment served as baseline. Demand curves (consumption x fixed ratio; FR) were obtained for smoked cocaine base, ethanol, and PCP by varying the cost (FR) of drug deliveries and measuring consumption (deliveries). Bremazocine (0.001 mg/kg) was administered at each FR value in nonsystematic order. Results indicate that bremazocine dose dependently reduced cocaine, ethanol, PCP, and saccharin intake. Food intake was affected less by bremazocine than the other substances in five of the six monkeys. Generally, bremazocine treatment reduced the demand for cocaine, ethanol, and PCP as well as other measures of response strength. These results extend the findings that kappa-agonists reduce the self-administration of drug and nondrug reinforcers to smoked cocaine base and oral ethanol, PCP, and saccharin in rhesus monkeys.