The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban.

The human drugs - the antibiotic linezolid (1) and the anticoagulant rivaroxaban (2) - belong among modern pharmaceutics, which contain an oxazolidine-2-one moiety bearing a stereogenic center. The chirality of these drugs is a fundamental attribute for their biological activity. Herein, one of the efficient asymmetric syntheses of these drugs was studied in detail. Highly enantioselective catalysts were tested in the key step of the synthetic procedure, i.e., the asymmetric Henry reaction, under different reaction conditions, using several starting aldehydes. The corresponding nitroaldols as chiral intermediates in the syntheses of these drugs were obtained in high yields and enantiomeric excesses of up to 91% ee.

Self-reported adherence by MARS-CZ reflects LDL cholesterol goal achievement among statin users: validation study in the Czech Republic.

RATIONALE, AIMS AND OBJECTIVES: Measuring self-reported adherence may contribute to minimizing the risk of therapy failure. Hence, the main aim of the study was to assess the psychometric properties of the Czech version of Medication Adherence Report Scale (MARS-CZ) and its appropriateness for use in long-term statin therapy where goal levels of low-density lipoprotein cholesterol (LDL-c) should be achieved. METHODS: Anonymous structured interview was performed to determine self-reported adherence by MARS-CZ in outpatients chronically treated with statins. At the same time, medication records were reviewed for inclusion of patients into groups of those who achieved and do not achieved LDL-c goal according to cardiovascular risk level. Reliability and validity of MARS-CZ were tested as well as the relationship between adherence and LDL-c goal achievement was examined. RESULTS: A total of 136 (86.6%) patients completed the interview; mean age was 66.1 years; 49.3% were male. The mean score of MARS-CZ was 24.4 and showed positive skewing. Satisfactory internal consistency (Cronbach's α=0.54), strong test-retest reliability (r=0.83, P<0.001; intra-class correlation=0.63, 95% confidence interval: 0.35-0.81) and positive correlation with eight-item Morisky Medication Adherence Scale (r=0.62, P<0.001) were indicated. Low validity values were found between MARS-CZ and 12-item Short Form Health Survey mental and physical subscales. MARS-CZ score significantly correlated with LDL-c goal achievement (P<0.05) when all patients who achieved LDL-c goal (35%) reported high adherence to statin. MARS-CZ score also correlated with cardiovascular risk level and doctor's judgments on adjusting treatment targets for each patient. CONCLUSION: This study proved MARS-CZ as an acceptable self-reported adherence measure. In routine clinical practice, MARS-CZ could be helpful to reveal medication non-adherence before the alteration of drug regimen and thereby contributing to enhancement of statin therapy management.

Chronically Ill Czech Patients' Beliefs About Medicines: The Psychometric Properties and Factor Structure of the BMQ-CZ.

The main objective of this study was to assess the factor structure and psychometric properties of the Czech translation of the Beliefs about Medicines Questionnaire (BMQ-CZ). It was hypothesized that the 4-factor structure of the BMQ-CZ would be confirmed and that psychometric properties would be verified by using positive or negative correlations with self-reported adherence, illness perceptions, and medication statements. A total of 627 people were approached, and 467 agreed to participate. The sample included chronically ill patients as well as patients seeking allopathic and homeopathic care. As a measure of criterion-related validity, the BMQ-CZ was administered along with the translated Czech versions of the Medication Adherence Report Scale (MARS-CZ) and the Brief Illness Perception Questionnaire (Brief IPQ-CZ) and additional assertions. The factor structure, reliability, and validity of the BMQ-CZ were evaluated. The internal consistency of the BMQ-CZ was satisfactory (Cronbach α = .69-.85). A factor analysis supported the BMQ-CZ's 4-factor structure, and the concurrrent validity of the BMQ-CZ was supported by positive correlations with self-reported measures of adherence and beliefs about medicines and disease. The BMQ-CZ demonstrated sufficient psychometric performance as a self-reported measure of medication beliefs among patients with hypertension, diabetes, and rheumatic disease.

Severe hypoglycaemia requiring the assistance of emergency medical services--frequency, causes and symptoms.

AIMS: To evaluate the incidence of severe hypoglycaemia (SH) requiring the assistance of Emergency Medical Services (EMS) in the general population of the Hradec Králové region, in a 1 year period; to describe the distribution of these events throughout the day, and to analyse the symptoms and causes. METHODS: The outcome data were obtained from special forms which were filled in by EMS medical staff. Incidence of SH was calculated and the distribution of events throughout the day was analysed using contingency tables. The relationship between blood glucose levels and the presence or absence of causes and symptoms of hypoglycaemia was evaluated using a general linear model and the regression tree technique. RESULTS: In all, a total of 338 events of SH were recorded in 262 patients. 150 episodes appeared in type 2 diabetic patients, 83 episodes in type 1 diabetic patients. 258 events were documented in insulin-treated patients. The incidence of SH was 2.4 and 0.4 episodes/100 patients/year for type 1 and type 2 diabetic patients, respectively. A significantly greater number of hypoglycaemic episodes was documented between 2 pm and 6 pm (P<0.001). Insulin therapy and alcohol consumption were the most dangerous causes of SH. CONCLUSIONS: Hypoglycaemia requiring the assistance of EMS represents an essential problem, especially in type 1 diabetic patients. The percentage of SH is comparable to other frequent diagnoses requiring the assistance of EMS in the region. This study reflects the behaviour of diabetic patients and highlights information which is important in the prevention of SH.