Objective: To evaluate the safety of low doses of quetiapine when used for insomnia. Data Sources: A literature search was performed using PubMed and EMBASE (January 1990-November 2011) using the terms quetiapine, insomnia, sleep, low-dose, subtherapeutic, safety, and weight gain. Study Selection And Data Extraction:: Two prospective trials were identified that evaluated the effect of quetiapine in primary insomnia. In addition, 2 retrospective cohort studies were identified that evaluated the safety of low doses of quetiapine when used for Insomnia. Several case reports on adverse effects with low doses of the drug were also Included. Data Synthesis: Quetiapine is commonly used off-label for treatment of insomnia. When used for sleep, doses typically seen are less than the Food and Drug Administration-recommended dosage of 150-800 mg/day; those evaluated in the studies reviewed here were 25-200 mg/day). At recommended doses, atypical antipsychotics such as quetiapine are associated with metabolic adverse events (diabetes, obesity, hyperlipidemia). Adverse effects in the prospective trials were patient-reported and were minor, including drowsiness and dry mouth; however, tha trials were limited by their small sample size and short duration. The retrospective cohort studies found that quetiapine was associated with significant increases in weight compared to baseline. Serious adverse events identified from case reports included fatal hepatotoxicity, restless legs syndrome, akathisia, and weight gain. Conclusions: There are potential safety concerns when using low-dose quetiapine for treatment of insomnia. These concerns should be evaluated in further prospective studies. Based on limited data and potential safety concerns, use of low-dose quetiapine for insomnia is not recommended.

Staphylococcus aureus small-colony variants (SCVs) often persist despite antibiotic therapy. Against a 10 8 -CFU/ml methicillinresistant S. aureus (MRSA) (strain COL) population of which 0%, 1%, 10%, 50%, or 100% was an isogenic hemB knockout (Ia48) subpopulation displaying the SCV phenotype, vancomycin achieved maximal reductions of 4.99, 5.39, 4.50, 3.28, and 1.66 log 10 CFU/ml over 48 h. Vancomycin at >16 mg/liter shifted a population from 50% SCV cells at 0 h to 100% SCV cells at 48 h, which was well characterized by a Hill-type model (R 2 > 0.90). Staphylococcus aureus is a virulent pathogen responsible for a myriad of infections ranging from minor community-acquired skin and soft tissue infections to severe nosocomial infections (1). While the current IDSA guidelines recommend vancomycin as the primary agent for treatment of methicillin-resistant S. aureus (MRSA) infections, the utility of the drug has been brought into question due to increasing reports of heterogeneous resistance, treatment failure, and nephrotoxicity (2-4). Despite the global decrease in vancomycin susceptibility, the exact mechanism by which S. aureus develops resistance is not well understood (5). It has been suggested that S. aureus adapts by utilizing an array of genotypic alterations that arise stepwise during the selective pressure of antimicrobial therapy (6, 7).One pathway that S. aureus may exploit during the evolution of antimicrobial resistance is the development of small-colony variants (SCVs) that grow slowly relative to strains of the normal phenotype (NP) (8-10). In vitro testing and macrophage models have confirmed that the SCV phenotype is less susceptible to vancomycin (11, 12). Studies with other antibiotics also suggest that SCV subpopulations may cooperate with NP S. aureus to attenuate antimicrobial activity (13). At present, it is unknown whether SCVs alter vancomycin pharmacodynamics through interactions with NP S. aureus or how the selection of a vancomycin regimen influences the relationship between the two phenotypes. The objective of the current study was, therefore, to utilize reconstructive population biology to determine how the interplay of both phenotypes alters vancomycin pharmacodynamics.The MRSA strain COL (NP) and its isogenic hemB knockout Ia48 (COL hemB::ermB, a stable SCV phenotype) were utilized. The creation of the mutant strain and its features were previously characterized (14). Prior to each experiment, a solution of vancomycin was prepared using analytical-grade powder (Sigma Chemical, St. Louis, MO) in the following concentrations: 0, 0.5, 1, 2, 4, 8, 16, 32, 64, and 128 mg/liter. Brain heart infusion (BHI) broth supplemented with magnesium (12.5 mg/liter) and calcium (25 mg/liter) was used for every experiment. SCV and NP cell suspensions were volumetrically titrated to achieve 5 different starting compositions, with a total bacterial load of 10 8 CFU/ml. Two experiments were conducted exclusively investigating the NP or the SCV phenotype (0% SCV/100% NP cells and 100% SCV/0% NP cells), an...

Background Second generation antipsychotics (SGAs) are thought to have a lower likelihood of inducing extrapyramidal symptoms (EPS) than first generation antipsychotics (FGAs). Clinical observations suggest that younger patients may be more sensitive to SGA-associated EPS than adults and require therapy with anticholinergic agents, which are known to impair cognitive performance. The scope of anticholinergic use in this patient population and differences in utilization across SGAs (as well as FGAs) has not been extensively studied. Objective The primary objective of this study was to determine the proportion of patients five to 18 years of age who received anticholinergic therapy during the initial stages of antipsychotic treatment. A secondary objective was to compare anticholinergic use across patients receiving aripiprazole, risperidone, and quetiapine, SGAs previously identified to be the most commonly prescribed at the academic institution studied. Methods Patients five to 18 years of age initiating a trial of an antipsychotic between January 1, 2005 and September 1, 2008 were identified in a retrospective review of prescription and medical records. Demographic characteristics, antipsychotic and anticholinergic utilization, indications, diagnoses, and concomitant medications and doses were collected from the electronic medical record. For patients who received more than one therapeutic course of an antipsychotic during the identified timeframe, only the first course identified in the medical record was used for analyses. Anticholinergic utilization at antipsychotic initiation and after 30 days was assessed. Variables associated with anticholinergic use and differences across agents were identified. Results A total of 235 antipsychotic treatment courses were identified. Of these, 152 patients met our inclusion criteria and represented the first documented use of an antipsychotic at the present institution. Anticholinergic use at any time during the first 30 days of treatment was identified in 32 patients (21%) while EPS was documented for 12 patients (7.8%). FGA or polypharmacy defined as simultaneous use of ≥1 scheduled antipsychotic versus SGA (OR=18.98; 95% CI:4.74 – 75.95) was the primary characteristic significantly associated with anticholinergic use 30 days after initiation. Risperidone, quetiapine, and aripiprazole were the three most commonly prescribed antipsychotics. Of these SGAs, anticholinergic use was most frequently prescribed with risperidone treatment (p=0.03). Conclusion Anticholinergic use exceeded the incidence of EPS as documented in the electronic medical record (21% vs 8%) and differed across individual medications as well as antipsychotic class. Use of an FGA or polypharmacy was a key predictor of anticholinergic use.

Objective: Electronic media use is highly prevalent among today's youth, and its overuse in the general population has been consistently associated with the presence of psychiatric symptoms. In contrast, little information exists about electronic media use among youth with psychiatric disorders. Our study aims to compare patterns of television and computer and gaming station use among youth in psychiatric clinic and community-based school populations.Method: Surveys were completed by 210 youth and parents, from school (n = 110) and psychiatric clinic (n = 100) populations. Duration and frequency of television, video gaming, and nongaming computer activities were ascertained, along with addictive features of use. Descriptive and comparative analyses were conducted, with a statistical threshold of P < 0.05. Results:Quantitative and qualitative differences were identified between the patterns of use reported by the 2 groups. The mean reported daily duration of exposure to electronic media use was 6.6 hours (SD 4.1) for the clinic sample and 4.6 hours (SD 2.6) for the school sample (P < 0.01). Self-reported rates of addictive patterns related to computer and gaming station use were similar between the 2 populations. However, the clinically based sample favoured more violent games, with 29% reporting playing mature-rated games, compared with 13% reported by the school-based sample (P = 0.02). Youth with externalizing disorders expended greater time video gaming, compared with youth with internalizing disorders (P = 0.01). Conclusions:Clinically based samples of youth with mental illnesses spend more time engaged in electronic media activities and are more likely to play violent video games, compared with youth in the general population. Further research is needed to determine the long-term implications of these differences. W W WObjectif : L'utilisation des médias électroniques est hautement prévalente chez les adolescents d'aujourd'hui, et leur surutilisation dans la population générale est régulièrement associée à la présence de symptômes psychiatriques. Par contre, il existe peu d'information sur l'utilisation des médias électroniques chez les adolescents souffrant de troubles psychiatriques. Notre étude vise à comparer les modèles d'utilisation de la télévision, de l'ordinateur et des sites de jeux vidéo chez les adolescents dans les cliniques psychiatriques et dans les populations scolaires communautaires.Méthode : Des sondages ont été remplis par 210 adolescents et parents, dans les populations scolaires (n = 110) et des cliniques psychiatriques (n = 100). La durée et la fréquence des activités liées à la télévision, aux jeux vidéo et autres à l'ordinateur ont été estimées, ainsi que les caractéristiques de la dépendance à l'utilisation. Des analyses descriptives et comparatives ont été menées, dont le seuil statistique est de P < 0,05.

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