Assessment of Markov-dependent stochastic models for drug administration compliance

OBJECTIVE: There are few analytical results that describe patient compliance with drug administration regimens. The purpose of this paper is to develop and assess stochastic approaches for mathematical modelling of patient compliance with administration regimens. METHODS: Two stochastic models based on Markov-dependent random variables and on the Ising model were assessed for their ability to describe the variable nature of drug compliance. RESULTS: Both models use only experimentally accessible data, and their predictions were tested against published clinical compliance data obtained from electronic monitoring devices. The models satisfactorily fitted administration interval distribution data from several patients treated with diltiazem, a calcium channel antagonist, or zidovudine, an antiretroviral agent. The Ising model provides additional analytical expressions for the distribution of success runs and 'drug holidays' in administration regimens. These distribution predictions were tested with success run data for diltiazem and drug holiday data for two nonsteroidal anti-inflammatory drugs, piroxicam and tenoxicam. CONCLUSIONS: Stochastic models can provide useful insights into drug compliance, and can be used to identify the administration patterns that are more likely to occur during drug self-administration in populations.     

Cat-scratch disease presenting as multifocal osteomyelitis with thoracic abscess

The case of a 4-year-old girl who presented with fever and back pain after being scratched by a kitten is presented. The diagnosis of cat scratch disease osteomyelitis was made by the detection of Bartonella henselae DNA by PCR analysis of a rib abscess aspirate.     

Generic evaluation methods for disaster drills in developing countries

Disaster simulations (drills) are widely used throughout the world and are considered a fundamental tool for evaluation and improvement of local disaster response capacity. Despite this, no generally accepted methodology exists for quantitative evaluation of the medical response to a disaster drill. We therefore set out to develop and prospectively test a comprehensive method to assess both medical provider and organizational performance during a disaster simulation. Because disasters disproportionately affect the populations of developing countries, we designed these methods to be sufficiently flexible to be applicable in both the developed and the developing world. Objective outcome measures were identified for each component of disaster medical response and were incorporated into 3 data collection instruments. The derived methods were applied to a multiagency disaster simulation in Guatemala City, Guatemala. On the basis of this pilot study, suggested modifications and recommendations were made. The ability to objectively identify the specific strengths and weaknesses of an emergency medical services systems' medical response to a disaster is an important step toward optimizing system performance. On the basis of our experience, we recommend the incorporation of objective evaluation methods such as these into every disaster simulation.     

The effects of repeated antenatal glucocorticoid therapy on the developing brain

Antenatal glucocorticoid (GC) therapy improves infant outcome following preterm birth. As approximately 50% of women given a first course of antenatal GCs remain undelivered 7-14 d later, many clinicians administer further courses. GCs are known to be neurotoxic and there is concern that exposure during early development may have adverse effects on the immature brain. The aim of this investigation was to compare magnetic resonance (MR) indices of brain maturation in infants exposed to repeated antenatal GC therapy and born at or close to term, with non-GC exposed control infants. MR images were obtained during quiet sleep without sedation. T1 weighted volume images were obtained in the sagittal plane and T1, T2 weighted spin echo and inversion recovery images in the transverse plane. Brain volume and surface area were calculated from segmented image slices, and a measure of the complexity of cortical folding, the whole cortex convolution index (WCCI), from computerized analysis of a vector coded contour following algorithm. Analysis of covariance was used to compare the two groups after allowing for the effect of postmenstrual age. There were 10 infants in the GC group (range of antenatal GC exposure, 3-11 courses) and 6 controls. Each GC course comprised two 12-mg IM doses of betamethasone 24 h apart. GC exposed infants had a significantly lower WCCI (p = 0.001) and smaller surface area (p = 0.02), after allowing for postmenstrual age. There was no significant difference in brain volume (p = 0.5). Repeated antenatal GC exposure results in measurable differences in brain maturation when compared with gestational age matched non-GC exposed controls. The clinical relevance of these observations is not known.     

Effects of lithium chloride on induction and expression of methylphenidate sensitization

Repeated administration of psychomotor stimulants produces an enduring and progressively enhanced behavioral response known as behavioral sensitization, which has been implicated as a model for psychiatric disorders such as mania, schizophrenia, and drug addiction. The objective of the study was to determine whether lithium chloride (LiCl), an anti-manic agent, is effective in blocking the development and/or the expression of behavioral sensitization to methylphenidate. Male Sprague-Dawley rats (n=64) weighing 170-190 g were randomly divided into seven treatment groups. A computerized animal activity monitor system continuously recorded locomotor activity for 16 days. Effects of LiCl on induction of methylphenidate sensitization were studied by giving LiCl before or during six daily methylphenidate administrations. Effects of LiCl on the expression of methylphenidate sensitization were studied by injecting LiCl after sensitization to methylphenidate was induced. It was shown that LiCl treatment modulated the acute methylphenidate effects by transiently attenuating the locomotor response to methylphenidate during the six daily methylphenidate administrations but neither single nor multiple treatments with LiCl blocked the development or the expression of behavioral sensitization.     

Duration of influenza A virus shedding in hospitalized patients and implications for infection control.

OBJECTIVE: To assess the duration of shedding of influenza A virus detected by polymerase chain reaction (PCR) and cell culture among patients hospitalized with influenza A virus infection. SETTING: Mayo Clinic (Rochester, Minnesota) hospitals that cater to both the community and referral populations. METHODS: Patients 18 years old and older who were hospitalized between December 1, 2004, and March 15, 2005, with a laboratory-confirmed (ie, PCR-based) diagnosis of influenza A virus infection were consecutively enrolled. Additional throat swab specimens were collected at 2, 3, 5, and 7 days after the initial specimen (if the patient was still hospitalized). All specimens were tested by PCR and culture (both conventional tube culture and shell vial assay). Information on demographic characteristics, date of symptom onset, comorbidities, immunosuppression, influenza vaccination status, and receipt of antiviral treatment was obtained by interview and medical record review. Patients were excluded if informed consent could not be obtained or if the date of symptom onset could not be ascertained. RESULTS: Of 149 patients hospitalized with influenza A virus infection, 50 patients were enrolled in the study. Most patients were older (median age, 76 years), and almost all (96%) had underlying chronic medical conditions. Of 41 patients included in the final analysis, influenza A virus was detected in 22 (54%) by PCR and in 12 (29%) by culture methods at or beyond 7 days after symptom onset. All 12 patients identified by culture also had PCR results positive for influenza A virus. CONCLUSION: Hospitalized patients with influenza A virus infection can shed detectable virus beyond the 5- to 7-day period traditionally considered the duration of infectivity. Additional research is needed to assess whether prolonging the duration of patient isolation is warranted to prevent nosocomial outbreaks during the influenza season.