Pharmacology and Therapeutics Education in the European Union Needs Harmonization and Modernization: A Cross-sectional Survey Among 185 Medical Schools in 27 Countries.

Effective teaching in pharmacology and clinical pharmacology and therapeutics (CPT) is necessary to make medical students competent prescribers. However, the current structure, delivery, and assessment of CPT education in the European Union (EU) is unknown. We sent an online questionnaire to teachers with overall responsibility for CPT education in EU medical schools. Questions focused on undergraduate teaching and assessment of CPT, and students' preparedness for prescribing. In all, 185 medical schools (64%) from 27 EU countries responded. Traditional learning methods were mainly used. The majority of respondents did not provide students with the opportunity to practice real-life prescribing and believed that their students were not well prepared for prescribing. There is a marked difference in the quality and quantity of CPT education within and between EU countries, suggesting that there is considerable scope for improvement. A collaborative approach should be adopted to harmonize and modernize the undergraduate CPT education across the EU.

Essential competencies in prescribing: A first european cross-sectional study among 895 final-year medical students.

European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed.

Should medical students learn to develop a personal formulary? An international, multicentre, randomised controlled study.

OBJECTIVE: This study was performed to determine whether students who are trained in developing a personal formulary become more competent in rational prescribing than students who have only learned to use existing formularies. METHODS: This was a multicentre, randomised, controlled study conducted in eight universities in India, Indonesia, the Netherlands, the Russian Federation, Slovakia, South Africa, Spain and Yemen. Five hundred and eighty-three medical students were randomised into three groups: the personal formulary group (PF; 94), the existing formulary group (EF; 98) and the control group (C; 191). The PF group was taught how to develop and use a personal formulary, whereas e the EF group was taught how to review and use an existing formulary. The C group received no additional training and participated only in the tests. Student's prescribing skills were measured by scoring their treatment plans for written patient cases. RESULTS: The mean PF group score increased by 23% compared with 19% for the EF group (p < 0.05) and 6% for controls (p < 0.05). The positive effect of PF training was only significant in universities that had a mainly classic curriculum. CONCLUSION: Training in development and use of a personal formulary was particularly effective in universities with a classic curriculum and with traditional pharmacology teaching. In universities with a general problem-based curriculum, pharmacotherapy teaching can be based on either existing or personal formularies.

Quantitative analysis of pork dry-cured sausages to quality control by NIR spectroscopy.

Near infrared spectroscopy technology (diode array instrument) was used to study the feasibility of applying quality controls to typical Spanish sausages by performing a proximate analysis (fat, moisture and protein) on the finished product (intact and homogenized). This could be used to provide quality controls at various stages once the finished product was obtained: finished product, storage, distribution and marketing. The selected models were calibrated and evaluated by cross and external validation. For intact products, coefficients of determination for calibration (R(2)) for fat, moisture and protein were 0.98, 0.93 and 0.97, respectively. These values for homogenised products were 0.99, 0.98 and 0.97, respectively. The standard errors of prediction (SEP) for external validation in intact products were 1.47%, 0.97% and 1.08% for fat, moisture and protein, respectively. In homogenised products, these values were lower: 0.71%, 0.41% and 0.95%, respectively.

Are psychotropics drugs used in pregnancy?

PURPOSE: To assess the prevalence and characteristics of psychiatric drug use in pregnancy. METHODS: A prospective observational study was performed on a total of 1332 consecutive women admitted for delivery, during a 3 months period, in the public obstetric services of Tenerife Island (covering a population of 1 000 000 inhabitants). RESULTS: Less than 4% (3.6%) of the women recognised having a psychiatric disorder, and only 2.5% were receiving psychiatric drug treatment at the moment they knew they were pregnant; of those, 68.7% introduced substantial modifications in their treatment at that moment, 47.9% did not report any change with respect to the period before pregnancy and 35.4% recognised that their mood was worse than previously. Although patients affected by a psychiatric disorder registered a higher rate of abdominal delivery, no differences in delivery or obstetric complications were found between women with and without psychiatric illness or in relation to psychiatric drug treatment. CONCLUSIONS: Compared to the literature, the studied population shows a lower rate of psychiatric problems and pharmacological treatment. This might reflect underrecognition or undertreatment.

La polimedicación de los pacientes psiquiátricos como alternativa a la escasez de recursos asistenciales / Polypharmacy in psychiatric patients as an alternative to limited mental health resources

Introducción. La polimedicación con fármacos psicoactivos es una polémica práctica habitual en psiquiatría que hasta el momento presente está más basada en la experiencia que en la evidencia. El objetivo del presente estudio es valorar la prevalencia y los posibles determinantes de la polimedicación de los pacientes psiquiátricos residentes en un área sanitaria con importantes carencias asistenciales. Método. La totalidad (n = 352) de los pacientes psiquiátricos bajo tratamiento psicofarmacológico residentes en la isla de La Gomera fueron evaluados a través de una auditoría de historias clínicas y de una segunda fase que incluyó una entrevista personal con cada paciente confirmadora del consumo de los fármacos prescritos. Resultados. El número medio de fármacos psicoactivos consumidos por paciente fue de 2,22 +/- 0,7 (rango: 1-6). La tasa de polimedicación registrada fue del 67 %, con un 34,1 % de los pacientes consumidores de dos fármacos, un 20,5 % consumidores de tres y un 12,5 % consumidores de cuatro o más fármacos psicoactivos al mismo tiempo. El análisis de regresión múltiple realizado puso de manifiesto que ninguna de las variables consideradas (edad, sexo, estado civil, nivel cultural, actividad laboral y diagnóstico) resultó ser un predictor fiable o factor de riesgo para el desarrollo de polimedicación. Las benzodiazepinas fueron el fármaco más prevalerte en monoterapia, mientras que los antidepresivos y los antipsicóticos fueron los más empleados en combinación. Una cuestionable alta polimedicación con fármacos de la misma clase farmacológica fue puesta de manifiesto, mientras que la polimedicación con fármacos de distinta clase o la auxiliar demostraron ser más adecuadas. Conclusión. La práctica clínica psiquiátrica necesita desarrollar indicadores que permitan una polimedicación adecuada de los trastornos mentales. Todavía se necesita más investigación que permita identificar a los pacientes en riesgo de polimedicación para poder minimizar los riesgos asociados a esta extendida práctica asistencial

Introduction. Polypharmacy with psychoactive drugs is an increasingly common and debatable contemporary practice in clinical psychiatry more probably based on experience than evidence. The objective of this study was to evaluate the prevalence and estimators of polypharmacy in psychiatric patients living in an area with very limited mental health resources. Method. All patients (n = 352) with mental disorders receiving psychotropic medication living in La Gomera were studied through an audit of case records and a second phase confirmation strategy through personal interviews. Results. The mean number of psychoactive drugs prescribed was 2.22 +/- 0.70 (range: 1-6). The rate of polypharmacy was 67 %, with 34.1 % of patients receiving two drugs, 20.5 % receiving three drugs and 12.5 % of the patients receiving four or more psychotropic drugs at the same time. Multiple regression analysis shows that none of the variables considered (age, sex, marital status, educational level, work activity and diagnosis) had predictive value in regards to the number of psychotropic drug used. Benzodiazepines were the most prevalent drugs in single drug therapy, while antidepressants and antipsychotics were the most used in combination with other treatment. A questionably very high degree of same-class polypharmacy was observed, while multiclass, adjunctive and augmentation polypharmacy seems to be more appropriate. Conclusion. The psychiatric clinical practice needs to develop indicators for an appropriate polypharmacy of mental disorders. More research is still needed to identify patients at risk of polypharmacy in order to develop interventions that minimize the risks associated to this treatment alternative

[Polypharmacy in psychiatric patients as an alternative to limited mental health resources]. / La polimedicación de los pacientes psiquiátricos como alternativa a la escasez de recursos asistenciales.

INTRODUCTION: Polypharmacy with psychoactive drugs is an increasingly common and debatable contemporary practice in clinical psychiatry more probably based on experience than evidence. The objective of this study was to evaluate the prevalence and estimators of polypharmacy in psychiatric patients living in an area with very limited mental health resources. METHOD: All patients (n = 352) with mental disorders receiving psychotropic medication living in La Gomera were studied through an audit of case records and a second phase confirmation strategy through personal interviews. RESULTS: The mean number of psychoactive drugs prescribed was 2.22 +/- 0.70 (range: 1-6). The rate of polypharmacy was 67 %, with 34.1 % of patients receiving two drugs, 20.5 % receiving three drugs and 12.5 % of the patients receiving four or more psychotropic drugs at the same time. Multiple regression analysis shows that none of the variables considered (age, sex, marital status, educational level, work activity and diagnosis) had predictive value in regards to the number of psychotropic drug used. Benzodiazepines were the most prevalent drugs in single drug therapy, while antidepressants and antipsychotics were the most used in combination with other treatment. A questionably very high degree of same-class polypharmacy was observed, while multiclass, adjunctive and augmentation polypharmacy seems to be more appropriate. CONCLUSION: The psychiatric clinical practice needs to develop indicators for an appropriate polypharmacy of mental disorders. More research is still needed to identify patients at risk of polypharmacy in order to develop interventions that minimize the risks associated to this treatment alternative.

Meat mixture detection in Iberian pork sausages.

Five homogenized meat mixture treatments of Iberian (I) and/or Standard (S) pork were set up. Each treatment was analyzed by NIRS as a fresh product (N=75) and as dry-cured sausage (N=75). Spectra acquisition was carried out using DA 7000 equipment (Perten Instruments), obtaining a total of 750 spectra. Several absorption peaks and bands were selected as the most representative for homogenized dry-cured and fresh sausages. Discriminant analysis and mixture prediction equations were carried out based on the spectral data gathered. The best results using discriminant models were for fresh products, with 98.3% (calibration) and 60% (validation) correct classification. For dry-cured sausages 91.7% (calibration) and 80% (validation) of the samples were correctly classified. Models developed using mixture prediction equations showed SECV=4.7, r(2)=0.98 (calibration) and 73.3% of validation set were correctly classified for the fresh product. These values for dry-cured sausages were SECV=5.9, r(2)=0.99 (calibration) and 93.3% correctly classified for validation.

Pharmacogenetic profile of xenobiotic enzyme metabolism in survivors of the Spanish toxic oil syndrome.

In 1981, the Spanish toxic oil syndrome (TOS) affected more than 20,000 people, and over 300 deaths were registered. Assessment of genetic polymorphisms on xenobiotic metabolism would indicate the potential metabolic capacity of the victims at the time of the disaster. Thus, impaired metabolic pathways may have contributed to the clearance of the toxicant(s) leading to a low detoxification or accumulation of toxic metabolites contributing to the disease. We conducted a matched case-control study using 72 cases (54 females, 18 males) registered in the Official Census of Affected Patients maintained by the Spanish government. Controls were nonaffected siblings (n =72) living in the same household in 1981 and nonaffected nonrelatives (n = 70) living in the neighborhood at that time, with no ties to TOS. Genotype analyses were performed to assess the metabolic capacity of phase I [cytochrome P450 1A1 (CYP1A1), CYP2D6] and phase II [arylamine N-acetyltransferase-2 (NAT2), GSTM1 (glutathione S-transferase M1) and GSTT1] enzyme polymorphisms. The degree of association of the five metabolic pathways was estimated by calculating their odds ratios (ORs) using conditional logistic regression analysis. In the final model, cases compared with siblings (72 pairs) showed no differences either in CYP2D6 or CYP1A1 polymorphisms, or in conjugation enzyme polymorphisms, whereas cases compared with the unrelated controls (70 pairs) showed an increase in NAT2 defective alleles [OR = 6.96, 95% confidence interval (CI), 1.46-33.20] adjusted by age and sex. Glutathione transferase genetic polymorphisms (GSTM1, GSTT1) showed no association with cases compared with their siblings or unrelated controls. These findings suggest a possible role of impaired acetylation mediating susceptibility in TOS.

The Severity of Dependence Scale (SDS) as screening test for benzodiazepine dependence: SDS validation study.

AIMS: To assess the validity of the Severity of Dependence Scale (SDS) as a screening test to detect benzodiazepine dependence in regular benzodiazepine users. METHOD: One hundred regular benzodiazepine users, recruited from neurotic benzodiazepine users attending the Mental Health Outpatient Services of the Canary Islands Health Service, were administered the SDS and responses were compared with the Composite International Diagnostic Interview (CIDI) diagnosis of benzodiazepine dependence. Receiver Operating Characteristic (ROC) analysis was used to determine which cut-off score on SDS allowed the best trade-off between sensitivity and specificity. RESULTS: SDS was shown to have high diagnostic utility, and a score higher than six on the scale appears to be an appropriate threshold for problematic benzodiazepine use. The SDS had a specificity of 94.2% and a sensitivity of 97.9%, and the area under the curve was of 0.991. CONCLUSION: The SDS was found to be a valid brief self-report questionnaire for the assessment of benzodiazepine dependence in patients using benzodiazepines.

Drug use in non-hospitalized children.

The knowledge of the characteristics of the use of drugs in non-hospitalized children is of paramount importance since clinical trials are seldom (and sometimes should not be) performed in such patients. The source of drug prescriptions varies a lot: 'self-administration' through parents accounts for as much as formal physician's orders or pharmacist's counselling. Data can be collected through the whole drug chain: drug prescription--drug dispensing--drug attainment--drug consumption. Both qualitative and quantitative data are to be collected in order to draw a complete picture of drug use in non-hospitalized children. Longitudinal collection methods, as well as time-point or cross-sectional studies can be carried out. The particular role of each of these methods of performing a drug utilization study in children are analysed and discussed.

Methodological approaches to ADR detection in out-patient children.

Drugs are extensively used in both ill and healthy people, all over the world and at all ages. But, in fact, children are prone to receive a drug after every consultation. As drugs are not just "healing substances" but also chemicals able to interfere with the body and cause harm, the physician has to keep a balance between effects and side-effects: a risk/benefit analysis. Two potential ways of causing harm can be distinguished: the classical "Adverse Drug Reactions" (ADR), based upon the biochemical and physiological interactions between the drug and the body, and the so called "Drug Related Problems" (DRP). The last ones are situations in which a patient gets worse because a good medication has been stopped or the adequate treatment was never prescribed, overdosages and intoxications, or even the changes in the patient's conceptions and attitudes to drugs due to an unhealthy use of medicines. The incidence of ADR in children is very low (0.7 to 4% in outpatient children), but some methods for detecting and controlling these adverse effects must be at hand for making it possible to discover new, serious, unexpected ADRs. The most important characteristics of the main system used, such as the "Spontaneous Reporting System", "Record Linkage in Computerized Databases", "Prescription-Event Monitoring" or the "Sample Monitoring" and Therapeutic Audits", are discussed in the paper. (Fig. 2, Ref. 29.)

d-Propoxyphene is a potent inhibitor of debrisoquine, but not S-mephenytoin 4-hydroxylation in vivo.

The debrisoquine and S-mephenytoin 4-hydroxylation phenotyping tests were performed in 14 healthy subjects. All were extensive metabolizers of both drugs. After at least 4 weeks, they received a 150 mg tablet of d-propoxyphene and 5 h later the debrisoquine-mephenytoin test was repeated. This single dose of d-propoxyphene caused no change in mephenytoin S/R ratio, but increased the debrisoquine metabolic ratio (MR) in each subject (p less than 0.025). The four subjects with a relatively high MR (5.1-8.3) in the first test had an MR of debrisoquine in the second test ranging between 22 and 40, falsely classifying them as "poor metabolizers" of debrisoquine. This shows that d-propoxyphene is a potent inhibitor of debrisoquine, but not of S-mephenytoin 4-hydroxylase in vivo. A previous in vitro study has shown that d-propoxyphene inhibits the hydroxylation of desipramine, which is a substrate of the debrisoquine hydroxylase.

S-mephenytoin hydroxylation phenotypes in a Swedish population determined after coadministration with debrisoquin.

Mephenytoin (100 mg) and debrisoquin (10 mg) were administered orally, both separately and together, to 41 healthy subjects. The ratios between the S and R enantiomers of mephenytoin and between debrisoquin and 4-OH-debrisoquin in urine were determined by use of GC. These ratios were used as measures of drug hydroxylation. There was no change in the phenotypic trait values of the two drugs when they were coadministered. Mephenytoin and debrisoquin then were coadministered to 253 healthy Swedish subjects, before bedtime, and urine samples were collected at periods of 0 to 8, 8 to 24, and 24 to 32 hours after drug administration. In the first sample, seven of the 253 subjects (2.8%, 95% confidence interval 0.8% to 4.8%) had an S/R ratio of greater than 0.8; this indicated that they were poor hydroxylators of S-mephenytoin. In the two consecutive samples, the S/R ratios of mephenytoin did not change in these seven persons, whereas it decreased to less than 0.2 in the third sample in the extensive hydroxylators. As was reported before, there was no relationship between the mephenytoin S/R ratio and the debrisoquin metabolic ratio (rs = 0.01). Coadministration of debrisoquin and mephenytoin before bedtime and urine collection during two consecutive nights allow for an accurate determination of both phenotypes in the population.

Paediatric drug prescribing. A comparison of Tenerife (Canary Islands, Spain) and Sweden.

The prescribing of medicines for ambulant children below 14 years of age has been compared between Tenerife (Spain) and Sweden. Data obtained from a random sample of 1327 children in a prospective study in Tenerife were compared with data from 3901 children in a Swedish survey linking diagnosis and therapy. Upper respiratory tract infection was the main diagnosis in both countries and antibiotics was the most frequently prescribed drug group (28.2% in Tenerife and 28.8% in Sweden). Half of the children in Sweden did not receive any medication, but only 10% of those in Tenerife did not receive a prescription. Children who received a prescription on average got 1.4 drugs in Sweden and 2.3 in Spain. Amongst the ten most commonly prescribed products in Sweden there were 11 active pharmacological principles as compared to 25 in Spain. These most frequently used preparations accounted for two thirds of all the prescriptions for children in Sweden and one third in Tenerife. In conclusion, drugs were significantly more often used to treat paediatric outpatients in Tenerife than in Sweden. The prescribing physician in Spain also chose a wider variety of drugs and more commonly used fixed combination products.

Drug utilization by children in Tenerife Island.

Drug utilization was studied in children below 14 years of age in Tenerife, Canary Islands, who were seen as outpatients by 15 paediatricians and 10 general practitioners. Data on diagnosis, previous drug exposure and prescriptions were collected from a random sample of 1327 children. Nose and throat infections (40.1%), respiratory diseases (10.2%) and miscellaneous symptoms, namely common cold, influenza or nasal congestion (10.5%), were the most frequent reasons for visiting a physician. Antibiotics represented 28.5% of the prescriptions. The youngest group (0-2 years) received more drugs than the other two groups (2-6 and 6-14 years), and 8.4% of the children did not receive any drug. Only 358 (5.1%) of the 7,000 pharmaceutical specialities available were used, and the 10 most frequently prescribed drug products constituted more than 30% of all prescriptions. Combination drugs accounted for 42.4% of the prescribed items. Healthy children presenting only for check up were frequently treated with drugs.