Antipsychotic-induced extrapyramidal syndromes - Risperidone compared with low- and high-potency conventional antipsychotic drugs

Aim: To compare the risk of extrapyramidal syndromes (EPS) between patients using risperidone and those using low-potency conventional antipsychotic drugs (APDs) in outpatient clinical practice, as measured by the use of anticholinergic medication. We tried to replicate results from previous clinical trials that compared risperidone with high-potency APDs. Method: Data was obtained from the PHARMO database containing filled prescriptions of 450,000 community-dwelling people in The Netherlands from 1986 to 1998. From the patients aged 15-54 years who had been newly treated with APDs, we defined mutually exclusive cohorts according to the APD first prescribed to a patient. APD exposure was followed until the first prescription of anticholinergic medication and was censored when APD prescribing was interrupted or switched. We estimated relative risks between risperidone and commonly used low-potency and high-potency APDs using Cox proportional hazards models, adjusting for age, gender, dose and other potential confounders. Results: In 4094 patients who had been newly prescribed antipsychotic drugs, the overall incidence rate of anticholinergic drug therapy was 556 per 1000 person-years, which was dose dependent. Prescribed doses of all antipsychotics were low. While, in accordance with previous trials, risperidone showed a lower risk of EPS than the high potency APDs such as haloperidol (RR 0.26; 95% CI 0.10-0.64), we did not observe a lower EPS rate than low-potency APDs (risperidone vs thioridazine RR 1.73, 95% CI 0.49-6.13; risperidone vs pipamperone RR 2.50, 95% CI 0.78-8.04). Conclusion: The reduced EPS rates observed when comparing risperidone with high-potency antipsychotics such as haloperidol may not apply to comparisons with low-potency drugs

Prediction of survival and therapy outcome with C-11-tyrosine PET in patients with laryngeal carcinoma

Choosing the optimal treatment for an individual with squamous cell carcinoma of the head and neck is a difficult challenge because of the unpredictable clinical behavior of this malignancy. A reliable method for assessing the clinical behavior and predicting the radiocurability of tumors would assist in the therapy strategy and prognosis. This study evaluated whether quantitative PET using L-[1-C-11]-tyrosine (TYR) has predictive value for survival and therapy outcome in patients with primary squamous cell carcinoma of the larynx. Methods: Thirty-four patients with histologically confirmed laryngeal carcinomas underwent dynamic C-11-TYR PET before receiving definitive therapy. Various methods for quantification of tumor activity were used: assessment of protein synthesis rate (PSR), calculation of standardized uptake value, and estimation of tumor-to-nontumor ratio. Treatment consisted of radiotherapy (n = 20) or surgery (n 14). The median follow-up was 40 mo. Results: All malignancies were identified correctly, with no false-negative results. Cumulative survival was compared between patients with tumor PSR equal to or higher than the median (2.0 nmol/ml/min) and those with tumor PSR lower than the median and was found not to be significantly different (P 0.07). When the radiotherapy group was evaluated separately, the difference in survival was significant (P = 0.03; 5-y survival, 30% vs. 73%) and high C-11-TYR uptake correlated with poor prognosis. In multivariate analysis, PSR was an independent predictor for survival. Because differences (P = 0.08) between patients with and patients without recurrence were not significant, no predictive value of PSR for disease recurrence could be demonstrated. Conclusion: Prediction of survival of patients undergoing radiotherapy for laryngeal squamous cell carcinoma is feasible primarily by using C-11-TYR PET to quantify activity before treatment

Prognostic value of erythrocyte sedimentation rate in ST segment elevation myocardial infarction:interaction with hyperglycaemia

Objectives. Many inflammatory markers are associated with an adverse prognosis after ST segment elevation myocardial infarction (STEMI). Hyperglycaemia may exacerbate this inflammatory response. We investigated whether the erythrocyte sedimentation rate (ESR) was associated with an adverse prognosis and whether this was mediated by glucose levels. Research design and methods. It concerns a post hoc analysis of a prospective randomised trial. In 346 patients with STEMI treated with reperfusion therapy, we investigated long-term outcome. Patients with ESR in the upper quartile (> 14 mm h(-1)) were compared to patients with a normal ESR. Hyperglycaemia was defined as admission glucose >= 7.8 mmol L-1. Median follow up was 7.4 years (range: 5.7-8.3). Main outcome measures. All cause mortality, cardiovascular mortality, sudden death, death as a result of heart failure. Results. Both elevated ESR and hyperglycaemia were associated with a worse prognosis and increased mortality. Elevated ESR was particularly associated with an increased risk of sudden death (OR: 3.3, 17% vs. 6%, P <0.01) whereas hyperglycaemia was especially associated with an increased risk of death because of heart failure (OR: 6.5, 8% vs. 1%, P <0.01). There was no association between increased ESR and elevated glucose levels. Multivariate analysis did reveal that both elevated ESR and admission glucose were independent predictors of long-term mortality. Conclusions. Elevated ESR and admission glucose are independent predictors of mortality in STEMI patients treated with reperfusion therapy. There is no association or interaction between glucose levels and the inflammatory response as reflected by ESR

L-1-C-11-tyrosine PET in patients with laryngeal carcinomas: Comparison of standardized uptake value and protein synthesis rate

PET with L-1-C-11-tyrosine (TYR) can measure and quantify increased protein synthesis in tumor tissue in vivo. For quantification of the protein synthesis rate (PSR), arterial cannulation with repeated blood sampling to obtain the plasma input function and a dynamic TYR PET study to calculate a time-activity curve are necessary. In most PET studies the standardized uptake value (SUV) method is used to quantify tumor activity. The SUV can be calculated without repeated arterial blood sampling and prolonged scanning time, as required for determination of the PSR. The relationship between PSR and SUV is largely unknown and different factors can cause wide variability in the SUV. Therefore, the comparison of the absolute quantification method (PSR) with the SUV method is obligatory to determine the possible use of noninvasive PET in head and neck oncology. Methods: Twenty-four patients with proven squamous cell carcinomas of the larynx (T1-T4) were studied using dynamic TYR PET. The PSRs of tumor and nontumor (background) regions were determined. Four different methods were used to calculate the SUV: uncorrected SUV (SUVBW); and SUVs corrected for body surface area (SUVBSA), for lean body mass (SUVLBM), and for the Quetelet index (SUVQI). Correlations between PSR values and SUVs were calculated. Results: The PSR of all tumors was significantly higher (P <0.001) than the PSR of nontumor tissue. The correlations of SUVBW, SUVBSA, SUVLBM, and SUVQI with the quantitative values of the PSR were high (r = 0.84-0.90). The best correlation was observed with the SUV based on the LBM (SUVLBM), Conclusion: High correlation between the quantitative values (PSR) and the SUVs offers the possibility to use noninvasive TYR PET for detection and reliable quantification of primary head and neck tumors

Gliucose-insulin-potassium and reperfusion in acute myocardial infarction:Rationale and design of the glucose insulin-potassium study-2 (GIPS-2)

Background The combination of reperfusion therapy and high-dose glucose-insulin-potassium (GIK) infusion seems beneficial in acute myocardial infarction (MI). Current evidence, however, is not considered conclusive. Study Design The Glucose-Insulin-Potassium Study-2 (GIPS-2) will investigate whether GIK, in adjunction to reperfusion therapy, is beneficial in MI patients without signs of heart failure at admission. A total of at least 1044 patients with an acute MI treated with either thrombolysis or primary percutaneous coronary intervention will be randomized to an infusion of high-dose GIK or no infusion. The primary end point of the study is 30-day mortality. Secondary end points are mortality at 1 year, recurrence of MI, repeat intervention, and infarct size. Implications If high-dose GIK significantly reduces mortality at 30 days in all patients, the adjunction of this treatment to reperfusion therapy may become part of standard regimen for patients with acute MI without heart failure