Retrospective evaluation of systemic corticosteroids for the management of acute exacerbations of chronic obstructive pulmonary disease.

PURPOSE: The use of systemic corticosteroids for the management of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) was studied. METHODS: Medical charts of patients admitted to the hospital between July 2002 and November 2003 with a primary diagnosis of AECOPD were retrospectively reviewed. The primary objective was to characterize the drug, dosage, route, frequency, and duration of systemic corticosteroids prescribed for the management of AECOPD. The secondary objective was to compare the mean length of stay (LOS) and 30-day relapse rate between patients who received lower and higher dosages of corticosteroids. RESULTS: One hundred forty-five admissions (123 patients) for AECOPD (mean +/- S.D. age, 65 +/- 11 years) were evaluated. Higher dosages of systemic corticosteroids (>80 mg of prednisone equivalent [PE] per day) were prescribed for 51% and i.v. therapy for 56% of admissions. The mean +/- S.D. total systemic corticosteroid exposure during hospitalization for all admissions was 759 +/- 971 mg of PE (mean +/- S.D. daily exposure = 134 +/- 111 mg of PE per day). The mean LOS was significantly longer for the higher-dosage group than for the lower-dosage group (6.1 versus 4.2 days, p = 0.0004). A tapered regimen was prescribed for 79% of discharges. Twenty-seven percent of the discharges with routine follow-up care had a relapse of disease within 30 days. CONCLUSION: This retrospective observational study confirmed a wide variability in the dosages of systemic corticosteroids for the inpatient management of AECOPD, including the use of higher dosages and tapered regimens. Prospective randomized studies are needed to determine the most effective regimen of systemic corticosteroids in patients with AECOPD.     

Cross-neutralisation of Australian brown and tiger snake venoms with commercial antivenoms: Cross-reactivity or antivenom mixtures?

Recently it has been suggested that the Australian snake antivenoms made by CSL Ltd. are in fact not truly monovalent and may contain antibodies to other snake venoms because the horses are injected with multiple snake venoms. It is unclear to what extent various monovalent antivenoms can neutralise the effect of other venoms, whether this is due to a mixture of antibodies or true cross-reactivity, and whether this has any clinical significance. We aimed to study the immunological and functional properties of brown snake (Pseudonaja spp.) antivenom (BSAV) and tiger snake (Notechis spp.) antivenom (TSAV) against their respective venoms using enzyme immunoassays (EIA) and in vitro clotting studies. There was significant overlap between the two antivenoms with both TSAV and BSAV being detected by EIA on brown snake venom (BSV)-coated and tiger snake venom (TSV)-coated wells, respectively. In a competition EIA, increasing amounts of immunoaffinity-purified hen anti-brown antibodies (IgYp) mixed with TSAV reduced TSAV measured on TSV-coated wells. Both BSAV and TSAV prevented the clotting activity of both venoms. IgYp also prevented the clotting activity of TSV, suggesting true cross-reactivity. The cross-reactivity of TSAV and BSAV with BSV and TSV, respectively, was likely due to each being a mixture of anti-brown and anti-tiger antibodies, but there was partial cross-reactivity demonstrated by the effect of IgYp. Single-polyvalent antivenom for brown snake and tiger snake may be feasible in the future.     

Adaptive group sequential design for phase II clinical trials: A Bayesian decision theoretic approach

Bayesian decision theoretic approaches (BDTAs) have been widely studied in the literature as tools for designing and conducting phase II clinical trials. However, full Bayesian approaches that consider multiple endpoints are lacking. Since the monitoring of toxicity is a major goal of phase II trials, we propose an adaptive group sequential design using a BDTA, which characterizes efficacy and toxicity as correlated bivariate binary endpoints. We allow trade‐off between the two endpoints. Interim evaluations are conducted group sequentially, but the number of interim looks and the size of each group are chosen adaptively based on current observations. We utilize a loss function consisting of two components: the loss associated with accruing, treating, and monitoring patients, and the loss associated with making incorrect decisions. The performance of our Bayesian modeling, and the operating characteristics of decision rules under a wide range of loss function parameters are evaluated using seven scenarios in a simulation study. Our method is illustrated in the context of a single‐arm phase II trial of bevacizumab, gemcitabine, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma. Copyright © 2009 John Wiley & Sons, Ltd.     

Evidence for reduced cerebellar volumes in trichotillomania.

BACKGROUND: Limited knowledge exists regarding the neurobiology of trichotillomania (TTM). Cerebellum (CBM) volumes were explored, given its role in complex, coordinated motor sequences. METHODS: Morphometric magnetic resonance imaging (MRI) scans were obtained for 14 female subjects with DSM-IV diagnoses of TTM and 12 age-, education-, and gender-matched normal control (NC) participants. Parcellation was performed utilizing a recently developed methodology to measure subterritory volumes of the CBM. Regions were defined based on knowledge of the structural and functional subunits of the CBM. RESULTS: As predicted, significant group differences were reported for CBM raw cortical volumes (p = .008) that survived correction for total brain volume (TBV; p = .037) and head circumference (HC; p = .011). A priori and post hoc group raw volume comparisons for CBM subterritories and functional clusters revealed many significant differences. However, most differences failed to withstand correction for total CBM volumes (TCV). Smaller volumes were consistently reported for the TTM versus NC cohorts. Total Massachusetts General Hospital Hair Pulling Scale (MGHHPS) scores were significantly inversely correlated with left primary sensorimotor cluster volumes (p = .008), with smaller volumes associated with more severe TTM symptoms. CONCLUSIONS: These findings implicate the CBM in the neurobiology of TTM, with reduced subterritory volumes reported for the TTM versus NC groups.     

Sensorimotor gating deficits in adults with autism.

BACKGROUND: Prepulse inhibition (PPI) is an operational measure of sensorimotor gating and is impaired in a family of neuropsychiatric disorders characterized by abnormalities of inhibitory function. Adults with autistic disorder (AD) exhibit clinical features of inhibitory deficits, such as restrictive and repetitive behaviors, that may be explained by deficits in sensorimotor gating. METHODS: Acoustic startle reactivity, habituation, and PPI (30-, 60-, 120-msec interstimulus intervals) were assessed in 14 adult men diagnosed with AD and 16 typically developing normal comparison (NC) participants. All participants were administered measures of intelligence and frontal-executive functioning. RESULTS: Adults with AD exhibited significantly less PPI in the 60-msec condition than NC participants, which was correlated with increased ratings of restricted and repetitive behaviors. The groups did not differ on measures of startle amplitude or overall habituation. There was, however, a significant group-by-block habituation effect. Furthermore, PPI was not related to intelligence but was moderately associated with performance on a measure of frontal-executive functioning. CONCLUSIONS: Adults with AD have sensorimotor gating deficits similar to other neurodevelopmental disorders, implicating a failure of normal inhibitory regulation of sensory, motor, and attentional mechanisms. Thus, PPI deficits may be indirectly linked to one of the hallmark features of AD.     

Detecting possible vaccine adverse events in clinical notes of the electronic medical record

The Vaccine Safety Datalink (VSD) is a collaboration between the CDC and eight large HMOs to investigate adverse events following immunization through analyses of clinical data. We modified an existing system, called MediClass, that uses natural language processing to identify clinical events recorded in electronic medical records (EMRs). We customized MediClass so it could detect possible vaccine adverse events (VAEs) generally, and gastrointestinal-related VAEs in particular, in the text clinical notes of encounters recorded in the EMR of a large HMO. Compared to methods that use diagnosis and utilization codes assigned to encounters by clinicians and administrators, the MediClass system can both find more adverse events and improve the positive predictive value for detecting possible VAEs.