The 1-year economic burden of community-acquired pneumonia (CAP) initially managed in the outpatient setting in the USA.

Aim: To assess the annual economic burden of community-acquired pneumonia (CAP) initially managed in the outpatient setting. Patients & methods: Patients with an outpatient diagnosis of CAP between January 2012 and December 2016 were identified from the IQVIA (Danbury, CT & Durham, NC, USA) Real-World Data Adjudicated Claims - US Database. All-cause and CAP-related healthcare resource utilization and costs were assessed over the 1-year follow-up. Generalized linear model examined adjusted total cost. Results: Among 256,916 patients with outpatient CAP, a tenth (10.6%) had ≥1 hospitalization and, of these, 18.7% had ≥1 CAP-related hospitalization. The mean total cost per patient was US$14,372; 10.9% was CAP-related and 26.1% was due to inpatient care. The adjusted mean total all-cause cost was US$13,788. Conclusion: Patients with outpatient CAP incurred a substantial annual economic burden.

The annual economic burden among patients hospitalized for community-acquired pneumonia (CAP): a retrospective US cohort study.

Objective: To assess the 1-year economic burden among patients hospitalized for community-acquired pneumonia (CAP) in the US.Methods: Adult patients hospitalized for CAP between 1/2012 and 12/2016 were identified from the IQVIA hospital charge data master (CDM) linked to the IQVIA Real-World Data Adjudicated Claims - US Database (date of admission = index date). Patients had continuous enrollment 180-days pre- and 360-days post-index, and empiric antimicrobial treatment (monotherapy [EM] or combination therapy [EC]) and chest x-ray on the index date or day after. All-cause and CAP-related healthcare resource utilization and cost were assessed over the 1-year follow-up. Generalized linear models (GLM) examined adjusted total cost.Results: The cohort comprised 1624 patients hospitalized for CAP (mean age 50.3; 52.8% female). The majority (78.2%) initiated EC, most frequently with beta-lactams + macrolides (30.4%). The index hospitalization was associated with a mean length of stay (LOS) of 5.7 days and mean cost of $17,736; 22.7% had a transfer to the intensive care unit (ICU). All-cause readmission rates at 30- and 180-days were 8.8% and 20.1%, respectively. Mean annual all-cause total cost was $61,928; one-third (33.8%, $20,954) was related to CAP. The primary cost driver was inpatient care, which accounted for more than half (56.0%) of total all-cause cost and 94.3% of total CAP-related cost. Mean total inpatient cost was significantly higher among EC versus EM patients ($37,106 versus $25,999, p = .0399). Adjusted mean total all-cause cost was $55,391.Conclusions: Patients hospitalized for CAP incurred a significant annual economic burden, driven substantially by the high cost of hospitalizations.

Drug-refractory aggression, self-injurious behavior, and severe tantrums in autism spectrum disorders: a chart review study.

Aggression, self-injurious behavior, and severe tantrums are impairing symptoms frequently experienced by individuals with autism spectrum disorders. Despite US Food and Drug Administration approval of two atypical antipsychotics targeting these symptoms in youth with autistic disorder, they remain frequently drug refractory. We define drug-refractory aggression, self-injurious behavior, and severe tantrums in people with autism spectrum disorders as behavioral symptoms requiring medication adjustment despite previous trials of risperidone and aripiprazole or previous trials of three psychotropic drugs targeting the symptom cluster, one of which was risperidone or aripiprazole. We reviewed the medical records of individuals of all ages referred to our clinic for autism spectrum disorder diagnostic evaluation, as well as pharmacotherapy follow-up notes for all people meeting autism spectrum disorder criteria, for drug-refractory symptoms. Among 250 consecutively referred individuals, 135 met autism spectrum disorder and enrollment criteria, and 53 of these individuals met drug-refractory symptom criteria. Factors associated with drug-refractory symptoms included age 12 years or older (p < 0.0001), diagnosis of autistic disorder (p = 0.0139), and presence of intellectual disability (p = 0.0273). This pilot report underscores the significance of drug-refractory aggression, self-injurious behavior, and severe tantrums; suggests the need for future study clarifying factors related to symptom development; and identifies the need for focused treatment study of this impairing symptom domain.

Body mass index change in autism spectrum disorders: comparison of treatment with risperidone and aripiprazole.

OBJECTIVE: The purpose of this study was to assess change in body mass index (BMI) and age- and gender-adjusted BMI Z-score in subjects ages 2-20 years with autism spectrum disorders (ASD), who were treated longitudinally with risperidone or aripiprazole at a tertiary care ASD clinic. METHOD: As part of a larger project involving longitudinal drug treatment data in ASD, detailed demographic and treatment data were collected for 142 subjects ages 2-20 years who had been started on risperidone or aripiprazole for treatment of irritability. Mean age at start of treatment, treatment duration, final Clinical Global Impressions-Improvement Scale score, BMI change per year of treatment, and BMI Z-score change per year of treatment (primary outcome measure) were calculated for each drug treatment group. Group means were compared using t tests and Wilcoxon rank sum tests. RESULTS: There was a statistically significant BMI and BMI Z-score increase in the risperidone and aripiprazole treatment groups individually. No statistically significant difference between the two treatment groups was noted in mean BMI change per year of treatment or BMI Z-score change per year of treatment. CONCLUSIONS: In our review of long-term naturalistic treatment of irritability using risperidone versus aripiprazole in persons with ASD, a significant increase in both BMI and age- and gender-adjusted BMI Z-score was noted for each treatment group. No significant difference in BMI or BMI Z-score change was noted when the two treatment groups were compared. We conclude that in our patient population at a tertiary care ASD clinic, the effects of risperidone and aripiprazole on body weight gain in naturalistic long-term treatment are no different.

Brief report: Pilot single-blind placebo lead-in study of acamprosate in youth with autistic disorder.

RATIONALE: An excitatory/inhibitory (E:I) imbalance marked by enhanced glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission may contribute to the pathophysiology of autism spectrum disorders (ASD). OBJECTIVES: We report on the first single-blind placebo lead-in trial of acamprosate, a drug with putative mechanisms restoring E:I imbalance, in twelve youth with ASD. MATERIALS AND METHODS: We conducted a 12-week single-blind, placebo lead-in study of acamprosate in youth age 5-17 years with autistic disorder. RESULTS: Six of nine subjects who received active drug treatment were deemed treatment responders (defined by a score at final visit of "very much improved" or "much improved" on the Clinical Global Impressions Improvement scale) and ≥25% improvement on the Aberrant Behavior Checklist Social Withdrawal subscale. CONCLUSION: Future larger-scale dose finding studies of acamprosate in ASD may be warranted given this preliminary indication of benefit.

Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome.

RATIONALE: Fragile X syndrome (FXS) is an inherited form of developmental disability and a single gene cause of autism. As a disorder with increasingly understood pathophysiology, FXS is a model form of developmental disability for targeted drug development efforts. Preclinical animal model findings have focused targeted drug treatment development in FXS on an imbalance between excessive glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission. METHODS: We conducted a prospective open-label 10-week trial of acamprosate in 12 youth aged 6-17 years (mean age: 11.9 years) with FXS. RESULTS: Acamprosate use (mean dose: 1,054 ± 422 mg/day) was associated with treatment response (defined by a Clinical Global Impressions Improvement (CGI-I) scale score of "very much improved" or "much improved") in nine of 12 (75 %) subjects. Improvement was noted in social behavior and inattention/hyperactivity using multiple standard behavioral outcome measures. No significant adverse effects or changes in vital signs, including weight or laboratory measures, occurred during treatment with acamprosate. Additionally, pre- and post-treatment blood biomarker analyses looking at brain-derived neurotrophic factor (BDNF) levels found a significant increase in BDNF with treatment. In our pilot sample, treatment response did not correlate with change in BDNF with treatment. CONCLUSIONS: Acamprosate was generally safe and well tolerated and was associated with a significant improvement in social behavior and a reduction in inattention/hyperactivity. The increase in BDNF that occurred with treatment may be a useful pharmacodynamic marker in future acamprosate studies. Given these findings, a double-blind, placebo-controlled study of acamprosate in youth with FXS is warranted.

Orexin 1 receptors are a novel target to modulate panic responses and the panic brain network.

BACKGROUND: Although the hypothalamic orexin system is known to regulate appetitive behaviors and promote wakefulness and arousal (Sakurai, 2007 [56]), this system may also be important in adaptive and pathological anxiety/stress responses (Suzuki et al., 2005 [4]). In a recent study, we demonstrated that CSF orexin levels were significantly higher in patients experiencing panic attacks compared to non-panicking depressed subjects (Johnson et al., 2010 [9]). Furthermore, genetically silencing orexin synthesis or blocking orexin 1 receptors attenuated lactate-induced panic in an animal model of panic disorder. Therefore, in the present study, we tested if orexin (ORX) modulates panic responses and brain pathways activated by two different panicogenic drugs. METHODS: We conducted a series of pharmacological, behavioral, physiological and immunohistochemical experiments to study the modulation by the orexinergic inputs of anxiety behaviors, autonomic responses, and activation of brain pathways elicited by systemic injections of anxiogenic/panicogenic drugs in rats. RESULTS: We show that systemic injections of two different anxiogenic/panicogenic drugs (FG-7142, an inverse agonist at the benzodiazepine site of the GABA(A) receptor, and caffeine, a nonselective competitive adenosine receptor antagonist) increased c-Fos induction in a specific subset of orexin neurons located in the dorsomedial/perifornical (DMH/PeF) but not the lateral hypothalamus. Pretreating rats with an orexin 1 receptor antagonist attenuated the FG-7142-induced anxiety-like behaviors, increased heart rate, and neuronal activation in key panic pathways, including subregions of the central nucleus of the amygdala, bed nucleus of the stria terminalis, periaqueductal gray and in the rostroventrolateral medulla. CONCLUSION: Overall, the data here suggest that the ORX neurons in the DMH/PeF region are critical to eliciting coordinated panic responses and that ORX1 receptor antagonists constitute a potential novel treatment strategy for panic and related anxiety disorders. The neural pathways through which ORX1 receptor antagonists attenuate panic responses involve the extended amygdala, periaqueductal gray, and medullary autonomic centers.

Case report: 16-Year-old male with autistic disorder with preoccupation with female feet.

This paper highlights clinical challenges faced when diagnosing and then treating an individual presenting to a child and adolescent psychiatry clinic because of unwelcome comments he made to female peers about their feet. Novel use of exposure therapy helped him effectively decrease his comments from 1 to 2 times per month to once every 6 months. Conceptualizing this case as the individual's failed attempts toward relationships with females instead of sexual harassment led to diminution of problematic behavior. Implications for diagnosis and treatment of individuals with Autistic Disorder displaying problematic behaviors are presented.

An open-label naturalistic pilot study of acamprosate in youth with autistic disorder.

To date, placebo-controlled drug trials targeting the core social impairment of autistic disorder (autism) have had uniformly negative results. Given this, the search for new potentially novel agents targeting the core social impairment of autism continues. Acamprosate is U.S. Food and Drug Administration-approved drug to treat alcohol dependence. The drug likely impacts both gamma-aminobutyric acid and glutamate neurotransmission. This study describes our initial open-label experience with acamprosate targeting social impairment in youth with autism. In this naturalistic report, five of six youth (mean age, 9.5 years) were judged treatment responders to acamprosate (mean dose 1,110 mg/day) over 10 to 30 weeks (mean duration, 20 weeks) of treatment. Acamprosate was well tolerated with only mild gastrointestinal adverse effects noted in three (50%) subjects.