Model-based interpretation of cardiac beats by evolutionary algorithms: signal and model interaction

This paper presents a new approach for cardiac beat interpretation, based on a direct integration between a model and observed ECG signals. Physiological knowledge is represented by means of a semi-quantitative model of the cardiac electrical activity. The interpretation of cardiac beats is formalized as an optimization problem, by minimizing an error function defined between the model's output and the observations. Evolutionary algorithms (EAs) are used as the search technique in order to obtain the set of model parameters reproducing at best the observed phenomena. Examples of model adaptation to three different kinds of cardiac beats are presented. Preliminary results show the potentiality of this approach to reproduce and explain complex pathological disorders and to better localize their origin.     

An audit of the effectiveness of acupuncture on musculoskeletal pain in primary health care

Little is known about the use of acupuncture in general practice. We performed a retrospective review of the use of acupuncture in relieving musculoskeletal pain, a condition that is commonly encountered in general practice. A sample of 116 patient records was reviewed, from which 92 patients (mean age 52 years, 64% female) met the inclusion criterion of musculoskeletal pain. Information obtained included age, sex, diagnosis, duration of the problem, length of treatment (weeks), number of treatments, duration of each treatment (minutes), number of needles used, level of benefit obtained from the treatment, and recurrence of pain. There were many different conditions encountered. We found an association between the general practitioner using fewer needles and patients experiencing greater pain relief. This could be a reflection of treating myofascial pain syndromes, which often appear to respond well to a single needle in the key trigger point. Overall, we found that sixty-nine percent of patients had a good or excellent response to acupuncture treatment. We recommend acupuncture as a treatment option for patients who do not respond to the usual therapies (non-steroidal anti-inflammatory drugs) for musculoskeletal conditions.     

Generic carbamazepine-induced subacute adrenal insufficiency?

Iatrogenic causes of adrenal insufficiency in Addison's disease are exceptional. We report the case of a patient with a history of epilepsy (taking carbamazepine, Tégrétol LP) and Addison's disease (treated by hydrocortisone (HDC) 30 mg/d, Dectancyl 0,5 mg/d, Florinef 50 mg/d). Recent digestive disorders required emergency hospitalization. The physical examination was normal and laboratory tests showed hyponatremia, hyperkalemia, and elevated serum ACTH. The course was rapidly favorable after rehydration and up-titration of the drug regimen. No triggering factor was identified, but the Tégrétol LP had been replaced for 3 months by a generic drug with the same quantity of active ingredients and the same bioavailability, but with a different excipient (the generic drug was not encapsulated). Could these differences have increased the serum level of carbamazepine and lead to more rapide HDC metabolism by enzymatic induction? Could poorer digestive tolerance have decreased HDC absorption? The hypothesis of carbamazepine overdosage is unlikely because the assay remained within the therapeutic range and hyperkaliemia would favor adrenal decompensation. In conclusion, this single case cannot prove drug interaction but does point out the importance of being prudent when modifying a well--tolerated regimen in a patient with Addison's disease.     

Estimation and implications of random errors in whole-body dosimetry for targeted radionuclide therapy

For targeted radionuclide therapy, the level of activity to be administered is often determined from whole-body dosimetry performed on a pre-therapy tracer study. The largest potential source of error in this method is due to inconsistent or inaccurate activity retention measurements. The main aim of this study was to develop a simple method to quantify the uncertainty in the absorbed dose due to these inaccuracies. A secondary aim was to assess the effect of error propagation from the results of the tracer study to predictive absorbed dose estimates for the therapy as a result of using different radionuclides for each. Standard error analysis was applied to the MIRD schema for absorbed dose calculations. An equation was derived to describe the uncertainty in the absorbed dose estimate due solely to random errors in activity-time data, requiring only these data as input. Two illustrative examples are given. It is also shown that any errors present in the dosimetry calculations following the tracer study will propagate to errors in predictions made for the therapy study according to the ratio of the respective effective half-lives. If the therapy isotope has a much longer physical half-life than the tracer isotope (as is the case, for example, when using 123I as a tracer for 131I therapy) the propagation of errors can be significant. The equations derived provide a simple means to estimate two potentially large sources of error in whole-body absorbed dose calculations.     

The role of whole blood viscosity in premature coronary artery disease in women

BACKGROUND: Impaired hemorheology has been demonstrated in atherosclerotic disease and has shown a relationship with classical risk factors. Blood viscosity (eta), being the ratio of shear stress over shear rate, is an important parameter of hemorheology. In women with premature coronary artery disease (CAD), the underlying risk factors are a matter of debate and the role of whole blood viscosity in its pathogenesis has not been documented. AIM: To investigate the association of whole blood viscosity with premature CAD in women, with complaints suggestive of angina pectoris. METHODS: Eighty-eight women (mean age 53 years) were divided into two groups, those with a high likelihood of CAD (LIKELI+) and those with a low likelihood of CAD (LIKELI-), based on medical history and technical investigations. Assessment of risk factors comprised smoking, diabetes mellitus, arterial hypertension, left ventricular hypertrophy (LVH), systolic and diastolic blood pressures, total low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, triglycerides, body mass index, menopause, hormone replacement therapy, uric acid and creatinine, and predicted 10-year cardiovascular risk according to the Framingham study was calculated. Whole blood viscosity was determined at 37 degrees C using a rotational cone-and-plate viscosimeter. RESULTS: Baseline characteristics did not differ significantly between the groups except for antiplatelet therapy (P=0.001), prevalence of diabetes mellitus (P=0.002), predicted 10-year cardiovascular risk (P=0.007), essential hypertension (P=0.02), LVH (P=0.03) and smoking habits (P=0.04). LIKELI+ women had a significantly higher whole blood viscosity at all shear rates compared with LIKELI- women (P<0.05). All blood viscosities measured from 25 to 125 s(-1) were highly significantly (P<0.0001) correlated with eta(250s(-1)). Univariate correlates with eta(250s(-1)) comprised triglycerides (P=0.006) and haematocrit (P=0.026). Binary logistic multivariate regression analysis for high likelihood of CAD revealed that only presence of arterial hypertension (P<0.0001) was predictive. Multiple regression analysis demonstrated that haematocrit (P=0.001) and likelihood of CAD (P=0.01) were the only significant determinants of eta(250s(-1)). CONCLUSION: In this study, blood viscosity did not appear as an independent risk factor for the prediction of premature CAD in women. Viscosity may act as a marker of CAD or of classical risk factors.     

An investigation of the steady-state pharmacokinetics of oral valacyclovir in immunocompromised children

Valacyclovir was administered to 28 immunocompromised children (ages 5-12 years) to obtain preliminary pharmacokinetic and safety information. Patients were randomized to valacyclovir regimens of 250 mg (9.4-13.3 mg/kg) or 500 mg (13.9-27.0 mg/kg) twice daily or 500 mg (13.2-21.7 mg/kg) 3 times a day. Acyclovir pharmacokinetics were evaluated at steady state. Valacyclovir was rapidly absorbed and converted to acyclovir. Mean (+/-SD) acyclovir peak concentrations from 250 mg and 500 mg valacyclovir were 4.11+/-1.41 and 5.19+/-1.96 microg/mL, respectively. Corresponding single dose area-under-curve values were 12.14+/-6.60 and 14.49+/-4.69h microg/mL. By using historical data for intravenous acyclovir as reference, the overall estimate of acyclovir bioavailability from valacyclovir was 48%, 2- to 4-fold greater than for oral acyclovir. In general, adverse events were not attributable to valacyclovir and were consistent with disease-related expectations and concomitant therapies. Dosage options for using valacyclovir in children are discussed.