Clinical characteristics of exposures to liquid laundry detergent packets.

INTRODUCTION: Our objective was to describe the characteristics of liquid laundry detergent packet (LDP) exposures and to develop referral and treatment recommendations. METHODS: This retrospective cohort study investigated LDP exposures reported to the National Poison Data System from January 1, 2013 through June 30, 2014. Three medical toxicologists reviewed the most significant exposures (n = 450). RESULTS: Of 17,857 reported LDP exposures, 13,307 involved only an LDP (no other substance) and were followed to a known medical outcome. The median age was 2 years (range 12 days to 100 years). Approximately 10% of exposures reported a major or moderate effect. The most common symptom was vomiting (51.7%; n = 6875), but stridor or aspiration pneumonia and respiratory depression secondary to central nervous system effects also occurred. Two pediatric and two adult deaths occurred, but no causal mechanism leading to death could be identified in any of the deaths. CONCLUSIONS: LDPs occasionally produce a toxidrome of vomiting, stridor, hypoxia, and sedation with metabolic acidosis and respiratory failure. These symptoms and the availability of LDPs highlight the need for referral and treatment recommendations and efforts to minimize unintentional exposures. Review of data from US poison centers may provide referral and treatment recommendations that improve patient outcomes.

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 model to improve the accuracy of US Poison Center data collection.

CONTEXT: Over 2 million human exposure calls are reported annually to United States regional poison information centers. All exposures are documented electronically and submitted to the American Association of Poison Control Center's National Poison Data System. This database represents the largest data source available on the epidemiology of pharmaceutical and non-pharmaceutical poisoning exposures. The accuracy of these data is critical; however, research has demonstrated that inconsistencies and inaccuracies exist. OBJECTIVE: This study outlines the methods and results of a training program that was developed and implemented to enhance the quality of data collection using acetaminophen exposures as a model. METHODS: Eleven poison centers were assigned randomly to receive either passive or interactive education to improve medical record documentation. A task force provided recommendations on educational and training strategies and the development of a quality-measurement scorecard to serve as a data collection tool to assess poison center data quality. Poison centers were recruited to participate in the study. Clinical researchers scored the documentation of each exposure record for accuracy. Results. Two thousand two hundred cases were reviewed and assessed for accuracy of data collection. After training, the overall mean quality scores were higher for both the passive (95.3%; + 1.6% change) and interactive intervention groups (95.3%; + 0.9% change). Data collection accuracy improved modestly for the overall accuracy score and significantly for the substance identification component. There was little difference in accuracy measures between the different training methods. CONCLUSION: Despite the diversity of poison centers, data accuracy, specifically substance identification data fields, can be improved by developing a standardized, systematic, targeted, and mandatory training process. This process should be considered for training on other important topics, thus enhancing the value of these data in relation to public health safety.

Misuse of benzodiazepines and Z-drugs in the UK.

Benzodiazepines and Z-drugs are commonly prescribed for insomnia and anxiety syndromes and there is increasing concern regarding their misuse. Using an internet-based questionnaire we found that of 1500 respondents 7.7% (n = 116) had misused one or more of these medications. Almost 15% of those misusing at least one of these drugs did so once weekly or more often. The main reasons reported for their use were to help sleep (66.4%), to cope with stress (37.1%) and/or to get high (31.0%). A total of 31% obtained the medications from multiple sources; healthcare professionals (55.2%) and friends/family (39.7%) most commonly. Our study can be used to inform prevention measures for their misuse.

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.

Indoor airborne bacterial communities are influenced by ventilation, occupancy, and outdoor air source.

Architects and engineers are beginning to consider a new dimension of indoor air: the structure and composition of airborne microbial communities. A first step in this emerging field is to understand the forces that shape the diversity of bioaerosols across space and time within the built environment. In an effort to elucidate the relative influences of three likely drivers of indoor bioaerosol diversity - variation in outdoor bioaerosols, ventilation strategy, and occupancy load - we conducted an intensive temporal study of indoor airborne bacterial communities in a high-traffic university building with a hybrid HVAC (mechanically and naturally ventilated) system. Indoor air communities closely tracked outdoor air communities, but human-associated bacterial genera were more than twice as abundant in indoor air compared with outdoor air. Ventilation had a demonstrated effect on indoor airborne bacterial community composition; changes in outdoor air communities were detected inside following a time lag associated with differing ventilation strategies relevant to modern building design. Our results indicate that both occupancy patterns and ventilation strategies are important for understanding airborne microbial community dynamics in the built environment.

The effects of paracetamol (acetaminophen) on hepatic tests in patients who chronically abuse alcohol - a randomized study.

BACKGROUND: Retrospective accounts suggest that therapeutic doses of paracetamol can produce severe hepatic injury in patients with putative high-risk conditions, including alcoholism and infectious hepatitis. Metabolism of paracetamol to its hepatotoxic metabolite is enhanced in patients who abuse alcohol, who also have compromised liver defences from depressed hepatic glutathione. AIM: To determine the effect of paracetamol on serum liver tests of newly abstinent subjects who abuse alcohol, including subjects with hepatitis C infection. METHODS: A randomized, double-blind, placebo-controlled study. Adult alcohol abusers with a current drinking episode longer than 7 days received either placebo or paracetamol 4 g/day for 5 days. RESULTS: Of 142 subjects enrolled, 74 received paracetamol and 68 received placebo. Mean ALT activity during treatment increased from 48 to 62 IU/L in the paracetamol group and from 47 to 49 IU/L in the placebo group. Maximum ALT was 238 and 249 IU/L in the paracetamol and control groups respectively. The INR remained unchanged and serum bilirubin decreased in both groups. Subgroup analyses for subjects with alcoholic hepatitis, hepatitis C virus antibody and other subgroups showed no statistical difference between groups. CONCLUSION: Administration of paracetamol 4 g/day appears safe in newly abstinent patients who abuse alcohol.

The utility of visual function questionnaire in the assessment of the impact of diabetic retinopathy on vision-related quality of life.

AIMS: To determine whether the Visual Function Questionnaire-25 (VFQ) is a more accurate instrument for assessing vision related quality of life (VRQOL) than visual acuity (VA) in patients with diabetic retinopathy. To compare VRQOL between patients with non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). METHODS: We administered the VFQ and Vision Preference Value Scale (VPVS) to 104 patients. With VPVS as the gold standard in our study, we used Pearson's correlation and multiple linear regression analysis to assess whether VFQ is a more accurate measure of VRQOL than VA. Spearman correlation coefficients were used to assess which VFQ subscales correlated strongly with VPVS. Patients with NPDR and PDR were compared using VFQ. RESULTS: The Pearson's correlation coefficient between VPVS and VFQ was 0.49 (P<0.01) and between VPVS and VA was 0.33 (P<0.01). In multivariable linear models, VFQ explained a higher proportion of the variance in VPVS than VA. The VFQ subscales with the strongest Spearman coefficients to VPVS scores were role differences, near activities, distance activities, mental function and dependence. In these subscales, patients with PDR vsNPDR suffered a 25-30 point loss (100-point scale). CONCLUSIONS: VFQ is a superior measure of VRQOL for patients with diabetic retinopathy because it better captures mental and emotional aspects of the disease as well as visual function. Subjects with PDR vsNPDR suffer significant loss of VRQOL.

An integrative framework for stochastic, size-structured community assembly.

We present a theoretical framework to describe stochastic, size-structured community assembly, and use this framework to make community-level ecological predictions. Our model can be thought of as adding biological realism to Neutral Biodiversity Theory by incorporating size variation and growth dynamics, and allowing demographic rates to depend on the sizes of individuals. We find that the species abundance distribution (SAD) is insensitive to the details of the size structure in our model, demonstrating that the SAD is a poor indicator of size-dependent processes. We also derive the species biomass distribution (SBD) and find that the form of the SBD depends on the underlying size structure. This leads to a prescription for testing multiple, intertwined ecological predictions of the model, and provides evidence that alternatives to the traditional SAD are more closely tied to certain ecological processes. Finally, we describe how our framework may be extended to make predictions for more general types of community structure.

Vision-related quality of life in patients with diabetic macular oedema.

AIMS: The aim of this study was to determine the impact of diabetic macular oedema (DME) on the quality of life (QOL) in patients with type 2 diabetes mellitus. METHODS: The study was a prospective, consecutive, non-comparative case series. An observational study evaluated the quality of vision and vision-specific QOL using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Mean VFQ-25 subscale scores in type 2 diabetic study patients were compared with mean VFQ-25 subscale score in groups of patients with type 1 diabetic retinopathy (T1DR) and varying degrees of age-related macular degeneration (ARMD), glaucoma and cataracts and in reference populations. RESULTS: Thirty-three patients completed the NEI VFQ-25. The mean age of the study population was 64 years. When performing a comparison of those patients with DME versus those with isolated T1DR we found that for the general health subscale, the DME versus T1DR group means were 42+/-4.4 versus 61+/-1.0 respectively. The DME versus T1DR quality of vision categorical mean scores were 69+/-4.1 versus 93+/-3.9. The DME versus T1DR VR-QOL categorical mean scores were 62+/-5.0 versus 93+/-1.0. The DME group was significantly worse in each of these three categories compared with the T1DR group (p<0.01). An additional analysis was performed to examine the differences in VR-QOL in the DME group versus varying common ocular diseases, including age-related macular degeneration (ARMD), glaucoma, cataracts and disease-free reference groups. The mean values of VFQ-25 subscale in the DME group were significantly lower then the glaucoma group in ten of 12 subscales, the cataract group in 11 of 12 subscales, and the reference group in 12 of 12 subscales. However, the mean values of VFQ-25 subscale in the DME group were only significantly different from the ARMD group in three of 12 subscales. CONCLUSIONS: Type 2 diabetes patients with macular oedema experience a decreased VR-QOL compared with type 1 diabetic patients with diabetic retinopathy, glaucoma or cataracts. However, VR-QOL in type 2 diabetic patients with macular oedema was similar to those individuals with ARMD.

A randomized trial to determine the change in alanine aminotransferase during 10 days of paracetamol (acetaminophen) administration in subjects who consume moderate amounts of alcohol.

BACKGROUND: Previous studies have suggested that therapeutic doses of paracetamol (acetaminophen) are safe in alcoholic patients when administered for up to 3 days. However, 14 days of therapeutic doses of paracetamol has been associated with an increase in serum transaminases. AIM: To determine the effect of 10 days of the maximal therapeutic dose of paracetamol on serum alanine aminotransferase (ALT) activity in subjects who consume 1 to 3 alcoholic beverages per day. METHODS: This was a randomized, double blind, placebo-controlled trial. Subjects took 4 g of paracetamol (or placebo) daily for 10 days. Serum aspartate aminotransferase (AST), ALT, bilirubin and INR were measured at baseline, day 4 and day 11. Symptoms potentially related to liver injury were also recorded. RESULTS: Paracetamol and placebo groups had no change from baseline values at day 4, but the paracetamol group had an increase in mean ALT at day 11 of 8.7 IU/L. No subject developed symptoms of liver injury or met predefined criteria for hepatotoxicity or liver failure. CONCLUSION: Therapeutic dosing of paracetamol administered for 10 days appears to elevate serum ALT in moderate drinkers, but does not produce clinically evident liver injury.

The effect of acetaminophen (four grams a day for three consecutive days) on hepatic tests in alcoholic patients--a multicenter randomized study.

BACKGROUND: Hepatic failure has been associated with reported therapeutic use of acetaminophen by alcoholic patients. The highest risk period for alcoholic patients is immediately after discontinuation of alcohol intake. This period exhibits the largest increase in CYP2E1 induction and lowest glutathione levels. Our hypothesis was that common liver tests would be unaffected by administration of the maximum recommended daily dosage of acetaminophen for 3 consecutive days to newly-abstinent alcoholic subjects. METHODS: Adult alcoholic subjects entering two alcohol detoxification centers were enrolled in a prospective double-blind, randomized, placebo-controlled trial. Subjects were randomized to acetaminophen, 4 g/day, or placebo for 3 consecutive days. The study had 95% probability of detecting a 15 IU/L difference in serum ALT. RESULTS: A total of 443 subjects were enrolled: 308 (258 completed) received acetaminophen and 135 subjects (114 completed) received placebo. Study groups did not differ in demographics, alcohol consumption, nutritional status or baseline laboratory assessments. The peak mean ALT activity was 57 +/- 45 IU/L and 55 +/- 48 IU/L in the acetaminophen and placebo groups, respectively. Subgroup analyses for subjects presenting with an elevated ALT, subjects fulfilling a diagnosis of alcoholic hepatitis and subjects attaining a peak ALT greater than 200 IU/L showed no statistical difference between the acetaminophen and control groups. The one participant developing an increased international normalized ratio was in the placebo group. CONCLUSION: Alcoholic patients treated with the maximum recommended daily dose of acetaminophen for 3 consecutive days did not develop increases in serum transaminase or other measures of liver injury. Treatment of pain or fever for 3 days with acetaminophen appears safe in newly-abstinent alcoholic patients, such as those presenting for acute medical care.

A prospective observational study of 5-, 7-, and 10-day antibiotic treatment for acute otitis media.

OBJECTIVE: To compare 5-, 7- and 10-day duration of antibiotic therapy for acute otitis media (AOM) in children. STUDY DESIGN AND SETTING: Prospective nonrandomized 1-year evaluation of 3 treatment durations for AOM in a private pediatric setting. Outcomes assessed at 14 +/- 4 days after start of therapy with clinical response categorized as cure, improvement, or failure. RESULTS: A total of 2172 children were studied; 46.4% were < or =2-years-old. Antibiotics used were amoxicillin (61.9% of patients), trimethoprim/sulfamethoxazole (11.7%), cephalosporins (14.2%), amoxicillin/clavulanate (5.2%), and macrolides/azalides (4.8%). No overall difference in outcome was observed comparing the 5-day (n = 707), 7-day (n = 423), or 10-day (n = 1042) treatments, including children < or =2-years-old. However, in the subset who had an episode of AOM in the preceding month, outcome differed; 5-day treatment was followed by more frequent failure than 10-day treatment (P < 0.001). In logistic regression analysis, variables identified as contributing to a cure were: >2-years-old (P < 0.0001), no AOM in the preceding month (P = 0.07), or preceding 12 months (P = 0.03). CONCLUSIONS: Our study supports the transition from 10 to 5 days for standard AOM antibiotic treatment duration in most patients. A 10-day regimen may be superior in children who have experienced an episode of AOM within the preceding month, a known risk factor for resistant bacterial infection in the otitis-prone patient.

Sequence diversity and antigenic polymorphism in the Plasmodium yoelii p235 high molecular mass rhoptry proteins and their genes.

A gene family in Plasmodium yoelii YM encodes p235, a group of high molecular mass erythrocyte-binding rhoptry proteins. Sequence analysis of 6 cDNA clones from the 3' end of expressed p235 genes divided them into two groups corresponding to genes on chromosomes 1, and 5 and 6, respectively. Twelve partial p235 protein sequences, derived from cDNA sequences from the region with greatest protein sequence similarity to Plasmodium vivax RBP2, fell into three groups, together with one chimeric sequence. A comparison of these cDNA sequences with genomic DNA sequences from the same region suggested that only a subset of the gene repertoire is expressed. Three genomic DNA clones, derived from the 5' end of p235 genes designated E1, E2, and E5 and located on chromosome 5/6, were also obtained and aligned with sequences from the known E8 and E3 genes. In the region of overlap there was only approximately 27% protein sequence identity, indicating that the sequences in this p235 N-terminal region are more diverse than at the C-terminal end. This sequence variation in the expressed genes did not result in antigenically different rhoptry proteins as detected with a panel of p235-specific mAbs. Only one schizont out of 500 examined with mAb 25.86 appeared to be an antigenic variant, with all of the developing merozoites in this schizont being mAb 25.86 negative. No other antigenic variants were detected with the other antibodies, and therefore it is likely that these antibodies recognise conserved epitopes.

Views of Earth's magnetosphere with the image satellite.

The IMAGE spacecraft uses photon and neutral atom imaging and radio sounding techniques to provide global images of Earth's inner magnetosphere and upper atmosphere. Auroral imaging at ultraviolet wavelengths shows that the proton aurora is displaced equatorward with respect to the electron aurora and that discrete auroral forms at higher latitudes are caused almost completely by electrons. Energetic neutral atom imaging of ions injected into the inner magnetosphere during magnetospheric disturbances shows a strong energy-dependent drift that leads to the formation of the ring current by ions in the several tens of kiloelectron volts energy range. Ultraviolet imaging of the plasmasphere has revealed two unexpected features-a premidnight trough region and a dayside shoulder region-and has confirmed the 30-year-old theory of the formation of a plasma tail extending from the duskside plasmasphere toward the magnetopause.

Enhanced pneumocystis carinii activity of new primaquine analogues.

New analogues of the venerable antimalarial drug primaquine have been synthesized and bioassayed in vivo against Pneumocystis carinii, a life-threatening infection common among immunosuppressed patients. Two of these new compounds are significantly more active than primaquine itself, and provide new information for future drug design and development in this area.

Corticotropin-releasing hormone type I receptor messenger ribonucleic acid and protein levels in the ovine fetal pituitary: ontogeny and effect of chronic cortisol administration.

In sheep, the ACTH secretory response to CRH in vivo or in vitro changes as a function of development, with peak responses occurring several weeks before term (145 days of gestation). CRH-stimulated ACTH secretion is mediated via the G protein-coupled CRH type I (CRH R1) receptor. We used a quantitative ribonuclease protection assay and Western immunoblotting to determine messenger RNA (mRNA) and protein levels of the CRH R1 receptor in immature and mature fetuses and adults. In addition, we precociously elevated fetal plasma cortisol levels to determine whether the fetal CRH R1 receptor is sensitive to increases in plasma cortisol. CRH R1 receptor mRNA levels decreased markedly throughout gestation and into the transition to adult life (immature fetus, 1.24+/-0.17; mature fetus, 0.75+/-0.13; adult, 0.18+/-0.093 pg/microg total anterior pituitary RNA). Also, continuous cortisol infusion in immature fetuses significantly decreased CRH R1 mRNA levels by 41%. Similar decreases were noted in protein levels. Thus, the decreased ACTH response to CRH stimulation during late gestation may be related to decreased CRH R1 receptor expression. In addition, plasma cortisol levels may influence corticotroph responsiveness to CRH by decreasing CRH R1 receptor expression.