Thiazolidinediones in type 2 diabetes--have they lived up to expectations?

The thiazolidinediones have been in clinical use for the management of type 2 diabetes for the past five years. These agents reduce insulin resistance by acting as ligands that regulate gene expression related to the proliferation and differentiation of adipose tissue. Overall, data from several clinical studies suggest that their hypoglycaemic efficacy is slightly less than sulphonylureas and metformin but greater than acarbose and the glinides. In the short term, treatment with thiazolidinediones is associated with weight gain, expansion of plasma volume, fluid retention, peripheral oedema, an increased risk of congestive heart failure when combined with insulin, and an idiosyncratic hepatotoxic reaction to troglitazone. The long term consequences of these effects are not known. Contrary to expectations, despite being insulin sensitisers these agents do not favourably influence the other components of the metabolic syndrome that are believed to be aggravated by insulin resistance. Dyslipidaemia and elevated blood pressure, which are major risk factors of cardiovascular disease in type 2 diabetes, are not favourably improved with thiazolidinedione treatment. Unlike the sulphonylureas and metformin, which have been shown in recent long term randomised studies to reduce cardiovascular risk substantially, there is no data on the long term cardiovascular safety of the thiazolidinediones. At present, in the absence of long term data, the thiazolidinediones in clinical use are moderately effective hypoglycaemic drugs with no particular advantage over existing treatments in type 2 diabetes.     

Development and validation of The Cystic Fibrosis Questionnaire in the United States: a health-related quality-of-life measure for cystic fibrosis

BACKGROUND: The Cystic Fibrosis Questionnaire (CFQ) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents and adults with cystic fibrosis (CF) > or = 14 years, consisting of 44 items on 12 generic and disease-specific scales. Versions of the CFQ are also available for children with CF and their parents. This study evaluated the psychometric properties of the CFQ in a national study at 18 CF centers in the United States. PARTICIPANTS: The CFQ-teen/adult was administered to 212 patients with CF ranging in age from 14 to 53 years. Test-retest reliability was assessed in a subset of patients over a 10- to 14-day interval. RESULTS: Multitrait analysis indicated a majority of items (95%) correlated more highly with their intended scale than a competing scale, supporting the conceptual model. Internal consistency coefficients indicated the CFQ scales had good reliability (Cronbach alpha = 0.67 to 0.94), and test-retest stability was acceptable (rs = 0.45 to 0.90). Validity was demonstrated by examining relationships between the CFQ, age, pulmonary function, and body mass index. As expected, the CFQ was inversely correlated with age, with older adults reporting lower CFQ scores than younger adults, better nutritional status was positively correlated with several weight-related scales, and the measure differentiated between individuals with varying levels of disease severity. Strong associations were also found between the CFQ and similar scales on the Short Form-36 Health Questionnaire, a well-known generic HRQOL measure. CONCLUSIONS: The results demonstrated that the CFQ-teen/adult is a reliable and valid measure of HRQOL for individuals with CF. It may be utilized in clinical trials to assess the effects of new therapies, to document the progression of disease, and to inform clinical practice.     

Hyperhomocysteinemia as a risk factor for ischemic stroke: an Indian scenario

BACKGROUND: Hyperhomocysteinemia has been proposed as an important risk factor for ischemic stroke worldwide, but data available from the Indian subcontinent is scarce. AIM: To study homocysteine levels in patients with ischemic stroke and compare it with age- and sex-matched controls. SETTINGS AND DESIGN: Case-control prospective study. MATERIALS AND METHODS: Fifty-seven patients with ischemic stroke and 30 controls were recruited for the study. They were subdivided into two subgroups (< 40 years and> 40 years of age) and plasma fasting total homocysteine (tHcy) levels were measured. STATISTICAL ANALYSIS USED: Student's 't' test and chi-square test. RESULTS: The tHcy were significantly high in patients with stroke, compared to controls (9.91 +/- 2.25 vs 8.00 +/- 2.74 micromol/l; P vs 8.45 +/- 2.72 micromol/l; P = 0.01) and female patients compared to controls (9.08 +/- 1.81 vs 6.79 +/- 2.60 micromol/l; P = 0.04). The tHcy levels were significantly high in patients with hypertension compared to normotensive patients (10.96 vs 9.49 micromol/l; P = 0.01) and smokers compared to nonsmokers (11.17 vs 9.33 micromol/l; P = 0.01). CONCLUSIONS: Hyperhomo-cysteinemia emerged as an important independent risk factor for ischemic stroke. A strong positive correlation was also observed between hypertension, smoking, and high-tHcy levels in the present study.     

Superior vena cava and right atrial thrombus detected on lung perfusion scintigraphy

Ventilation and perfusion scanning is still used as the first modality for evaluating pulmonary embolism in pregnant and renal failure patients and those who are allergic to radiographic contrast. Hot spots in the right atrial area on perfusion scan are the result of the presence of thrombi. These thrombi are of 2 varieties. One type is a free-floating thrombus, which needs emergency thrombectomy, and another type is thrombus formation in the atria, predisposed by the presence of catheters. We report a study showing essentially normal perfusion but intense tracer uptake in the superior vena cava and right atrium. Noncontrast computed tomography confirmed the thrombus.     

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.