Presentations to the emergency department with non-medical use of benzodiazepines and Z-drugs: profiling and relation to sales data.

BACKGROUND: Non-medical use of benzodiazepines and Z-drugs is common; however, there is limited information available on the extent of harm related to this in Europe, as well as the relationship between misuse and availability. AIM: To describe presentations to the emergency department in Europe related to the recreational use of benzodiazepines and Z-drugs and compare regional differences in these presentations with legal drug sales of benzodiazepines and Z-drugs within each country. METHODS: Emergency department presentations with recreational misuse of benzodiazepines and Z-drugs were obtained from the Euro-DEN dataset for the period from October 2013 to September 2015; data extracted included demographics, clinical features, reported coused drugs, and outcome data. Sales figures obtained by QuintilesIMS™ (Atlanta, Georgia) were used to compare regional differences in the proportion of benzodiazepines and Z-drugs in the emergency department presentations and legal drug sales across Europe. RESULTS: Over the 2 years, there were 2119 presentations to the Euro-DEN project associated with recreational use of benzodiazepines and/or Z-drugs (19.3% of all Euro-DEN presentations). Presentations with 25 different benzodiazepines and Z-drugs were registered in all countries, most (1809/2340 registered benzodiazepines and Z-drugs, 77.3%) of which were prescription drugs. In 24.9%, the benzodiazepine was not specified. Where the benzodiazepine/Z-drug was known, the most frequently used benzodiazepines and Z-drugs were respectively clonazepam (29.5% of presentations), diazepam (19.9%), alprazolam (11.7%), and zopiclone (9.4%). The proportions of types of benzodiazepines/Z-drugs related to ED-presentations varied between countries. There was a moderate (Spain, UK, Switzerland) to high (France, Ireland, Norway) positive correlation between ED presentations and sales data (Spearman Row's correlation 0.66-0.80, p < 0.005), with higher correlation in countries with higher ED presentation rates. CONCLUSION: Presentations to the emergency department associated with the non-medical use of benzodiazepines and/or Z-drugs are common, with variation in the benzodiazepines and/or Z-drugs between countries. There was a moderate to high correlation with sales data, with higher correlation in countries with higher ED presentation rates. However, this is not the only explanation for the variation in non-medical use and in the harm associated with the non-medical use of benzodiazepines/Z-drugs.

Trends in intentional abuse or misuse of benzodiazepines and opioid analgesics and the associated mortality reported to poison centers across the United States from 2000 to 2014.

CONTEXT: Prior works demonstrates an increased risk of death when opioid analgesics and benzodiazepines are used concomitantly to gain a high. Using poison center data, we described trends in abuse or misuse of benzodiazepines and opioid analgesics. We quantified mortality risk associated with abuse or misuse of benzodiazepines, opioid analgesics and the combination of opioid analgesics and benzodiazepines. METHODS: This was a retrospective chart review of data from the National Poison Data System which collects information from 55 poison centers located across the United States. We identified reported cases of "intentional abuse or misuse" of benzodiazepine and/or opioid analgesic exposures. Poisson regression was used to compare the number of cases from each year between 2001 and 2014 to the year 2000. Logistic regression was used to determine whether cases exposed to both benzodiazepines and opioids had greater odds of death relative to cases exposed to opioid analgesics alone. RESULTS: From 2000 to 2014, there were 125,485 benzodiazepine exposures and 84,627 opioid exposures among "intentional abuse or misuse" cases. Of the benzodiazepine exposures, 17.3% (n = 21,660) also involved an opioid. In 2010, exposures involving both opioids and benzodiazepines were 4.26-fold (95% CI: 3.87-4.70; p < .001) higher than in 2000. The risk of death was 1.55 (95% CI: 1.01-2.37; p = .04) times greater among those who used both an opioid and a benzodiazepine compared to opioids alone. This association held after adjusting for gender and age. CONCLUSION: Intentional abuse or misuse of benzodiazepines and opioids in combination increased significantly from 2000 to 2014. Benzodiazepine abuse or misuse far exceeded cases of opioid abuse or misuse. Death was greater with co-abuse or misuse of benzodiazepines and opioids. Population-level campaigns to inform the public about the risk of death with co-abuse or misuse of benzodiazepines and opioids are urgently needed to address this overdose epidemic.

A single-arm clinical trial of a 48-hour intravenous N-acetylcysteine protocol for treatment of acetaminophen poisoning.

INTRODUCTION: Acetylcysteine prevents hepatic injury when administered soon after acetaminophen overdose. The most commonly used treatment protocols are a 72-hour oral and a 21-hour intravenous (IV) protocol. Between 1984 and 1994, 409 patients were enrolled in a study to describe the outcomes of patients who were treated using a 48-hour IV protocol. In 1991, an interim analysis reported the first 223 patients. The objective of this manuscript is to report the rates of hepatotoxicity and adverse events occurring during a 48-hour IV acetylcysteine protocol in the entire 409 patient cohort. METHODS: This was a multicenter, single-arm, open-label clinical trial enrolling patients who presented with a toxic serum acetaminophen concentration within 24 h of acute acetaminophen ingestion. Patients were treated with 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses. Serum aminotransferase activities were measured every 8 h during the protocol, and adverse events were recorded. The primary outcome was the percentage of subjects who developed hepatotoxicity defined as a peak serum aminotransferase greater than 1000 IU/L. RESULTS: Four hundred and nine patients were enrolled, and 309 met inclusion for the outcome analysis. The overall percentage of patients developing hepatotoxicity was 18.1%, and 3.4% of patients treated within 10 h developed hepatotoxicity. One acetaminophen-related death occurred in a patient treated at 22 h. Adverse events occurred in 28.9% of enrolled subjects; the most common adverse events were nausea, vomiting, and flushing, and no events were rated as serious by the investigator. CONCLUSIONS: Acetaminophen-overdosed patients treated with IV acetylcysteine administered as 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses had a low rate of hepatotoxicity and few adverse events. This protocol delivers a higher dose of acetylcysteine which may be useful in selected cases involving very large overdoses.

Serum surfactant proteins-A and -D as biomarkers in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) has a high mortality rate, and current therapies are only marginally effective. A serum biomarker that predicts clinical outcome would be useful to stage disease, indicate prognosis and the need for aggressive therapy, and help stratify patients for clinical trials. The goals of this study were to determine whether serum levels of surfactant protein-A (SP-A) or surfactant protein-D (SP-D) would distinguish between IPF and other types of interstitial lung disease and whether serum SP-A or SP-D levels predict outcome in patients with IPF. The authors found that serum SP-A and SP-D levels were significantly elevated in patients with IPF and systemic sclerosis compared to sarcoidosis, beryllium disease and normal controls, and that SP-D correlated with radiographic abnormalities in patients with IPF. In addition, the authors found that both serum SP-A and SP-D levels were highly predictive of survival in patients with IPF. This is the largest North American data set of surfactant protein measurements in idiopathic pulmonary fibrosis and the first report using multivariate analysis comparing serum surfactant proteins-A and -D to other commonly measured predictors of survival in idiopathic pulmonary fibrosis. Based on these results, the authors propose that serum surfactant proteins may prove to be useful biomarkers in patients with idiopathic pulmonary fibrosis.

Quality of life measured with a generic instrument (Short Form-36) improves following pulmonary rehabilitation in patients with COPD.

STUDY OBJECTIVES: The purpose of this study was to evaluate the effects of a 3-week comprehensive pulmonary rehabilitation program on quality of life as measured by the Short Form-36 (SF-36) in patients with COPD. DESIGN AND SETTING: We report on the outcomes of 37 consecutive patients referred for pulmonary rehabilitation at a respiratory specialty medical center. PATIENTS: Thirty-seven patients (mean age, 66 years) with COPD and severe airflow limitation (mean +/- SE FEV(1), 29.6 +/- 1.8% of predicted) were studied. INTERVENTIONS: Rehabilitation consisted of a 3-week pulmonary rehabilitation program incorporating 12 exercise sessions, each of which included bicycle ergometer exercise training, upper-extremity training, strength training, and stretching, along with psychosocial counseling and education. MEASUREMENTS AND RESULTS: The Health Status Index (SF-36) and 6-min walk test were completed before and after rehabilitation. There was an improvement in five of the nine quality-of-life subscales of the SF-36 following pulmonary rehabilitation. Although there was an improvement in functional capacity as measured by the 6-min walk, there was no correlation between improvement in quality of life and improvement in functional capacity. There was no correlation between FEV(1) and improvement in walk distance, but there was a correlation between FEV(1) and improvement in SF-36 physical function and energy/fatigue subscales. CONCLUSION: Health-related quality of life assessed by the SF-36, a general measure of quality of life, improves following an intensive 3-week pulmonary rehabilitation program. Use of the SF-36 allows comparison of the results of pulmonary rehabilitation to therapeutic interventions in patients with other medical disorders.

Occupational exposure risks in individuals with PI*Z alpha(1)-antitrypsin deficiency.

We obtained questionnaire and spirometry data from 128 alpha(1)-antitrypsin (alpha(1)AT)-deficient individuals with phenotype PI*Z to examine the relationship between chronic respiratory symptoms, airflow limitation, treatment requirements, and semiquantitative estimates of occupational exposure to dust, fumes, smoke, and gas. After adjusting for age, smoking, and prior lower respiratory tract infections, increased prevalence of chronic cough (OR = 4.69, 95% CI = 1.57-13.74, p = 0.006) and having left a job due to breathlessness (OR = 2.72, 95% CI = 1.07-6.92, p = 0.036) were seen in individuals reporting high mineral dust exposure compared with those with no exposure. Subjects reporting high mineral dust exposure also had significantly lower FEV(1) (31% predicted for high exposure versus 36% for low and 40% for unexposed, p = 0.032). The excess risk of chronic cough seen with occupational fumes or smoke exposure disappeared after adjusting for mineral dust exposure, but the association with lower FEV(1)/FVC ratio persisted (p = 0.022). Personal tobacco use was a significant risk factor for most outcome measures, but no interaction with occupational exposure was seen. These results suggest that occupational inhalational exposures are independently associated with respiratory symptoms and airflow limitation in severely alpha(1)AT-deficient individuals.

A method for the standardized offline collection of exhaled nitric oxide.

STUDY OBJECTIVES: Exhaled nitric oxide (ENO) is a noninvasive marker of airway inflammation. The purpose of this study was to compare a standardized offline ENO measurement apparatus with a validated on-line method. DESIGN: Asthmatic volunteers (n = 21) had ENO measured by the two following methods: (1) inhalation to total lung capacity (TLC) followed by exhalation at a constant flow (45 mL/s) against a high resistance, while monitoring nitric oxide (NO) and pressure on-line; and (2) inhalation to TLC and exhalation into mylar balloons via an apparatus that included the same resistance and flow rate as used in the on-line method. We also examined NO stability in mylar balloons over 48 h. MEASUREMENTS AND RESULTS: ENO values (given as geometric mean in parts per billion [ppb]; 95% confidence intervals) differed between the on-line method (69.6; 42.6 to 113.8) and the offline method (49.5; 30.9 to 79.3), indicating that the offline method gave lower ENO measures than the on-line method (p < 0.001). Furthermore, this difference between measures increased with increasing mean values. The intraclass correlation coefficient (0.931), however, showed excellent correlation between the on-line and offline methods. Within-subject repeatability, as assessed by the coefficient of repeatability (CR), was good for both the on-line and offline methods (CR, 1.09 and 1.17, respectively). Geometric mean NO concentrations (95% confidence limits) in mylar balloons containing exhalate increased from a baseline of 55.8 ppb (36.9, 84.4) to 64.5 ppb (45.6, 91.1) and 69.5 ppb (51.4, 94.0) at 24 h and 48 h, respectively. CONCLUSIONS: The offline method gave reproducible ENO values that were consistently smaller than, but showed good correlation with, values obtained with on-line ENO collection. This method is suitable for offline collection, but the measured values are not interchangeable with those obtained by on-line measurement.

Psychosocial competence of unselected young adults with sex chromosome abnormalities.

Very little is known about the adult adaptation of individuals with sex chromosome abnormalities (SCA) except for a few reports based upon biased samples of clinically identified patients. This first report from the Denver SCA study on the adult psychosocial adaptation of 36 unselected propositi, identified at birth, shows a continuation of mild psychological and social problems. Psychiatric interviews and self-reported information revealed that adaptation is quite variable, with many of the nonmosaic propositi not faring as well as their siblings, but in a few instances exceeding the success of brothers and sisters. Within this group of SCA subjects a subset demonstrated more marked pathology and a tendency to over-rate their social adaptation relative to the psychiatric interviewer, suggesting that the exclusive use of self-report questionnaires may not provide accurate assessment of psychological characteristics in this and other special populations. The full adult SCA behavioral phenotype has not yet been established but is emerging through additional reports from this and other studies of unselected SCA adults.

Methacholine challenge testing: safety of low starting FEV1. Asthma Clinical Research Network (ACRN).

STUDY OBJECTIVE: The lower limit for the baseline value to initiate methacholine bronchial hyperresponsiveness testing has not been well established. Recommendations have varied from > 1 L to above 80% of predicted. The objective was to determine if an FEV1 < 60% predicted was acceptable. DESIGN: Retrospective analysis of challenges in 88 patients with a baseline FEV1 of < 60% predicted (mean=45.8%; range, 22 to 59%. SETTING: Academic institutions. RESULTS: There were only four individuals whose FEV1 did not return to > 90% of baseline following one poststudy beta2-agonist treatment. All four responded to a second treatment. There were no adverse sequelae following challenge in any individual. Neither age (up to 79 years) nor gender influenced outcome. CONCLUSIONS: In chronic moderate to severe asthma, it appears that bronchial hyperresponsiveness testing can be safely performed even in those patients with a low baseline FEV1.