Pharmacology Portal: An Open Database for Clinical Pharmacologic Laboratory Services.

PURPOSE: More than 50 Norwegian public and private laboratories provide one or more analyses for therapeutic drug monitoring or testing for drugs of abuse. Practices differ among laboratories, and analytical repertoires can change rapidly as new substances become available for analysis. METHODS: The Pharmacology Portal was developed to provide an overview of these activities and to standardize the practices and terminology among laboratories. The Pharmacology Portal is a modern dynamic web database comprising all available analyses within therapeutic drug monitoring and testing for drugs of abuse in Norway. Content can be retrieved by using the search engine or by scrolling through substance lists. The core content is a substance registry updated by a national editorial board of experts within the field of clinical pharmacology. This ensures quality and consistency regarding substance terminologies and classification. FINDINGS: All laboratories publish their own repertoires in a user-friendly workflow, adding laboratory-specific details to the core information in the substance registry. The user management system ensures that laboratories are restricted from editing content in the database core or in repertoires within other laboratory subpages. The portal is for nonprofit use, and has been fully funded by the Norwegian Medical Association, the Norwegian Society of Clinical Pharmacology, and the 8 largest pharmacologic institutions in Norway. IMPLICATIONS: The database server runs an open-source content management system that ensures flexibility with respect to further development projects, including the potential expansion of the Pharmacology Portal to other countries.

Impairment based legislative limits for driving under the influence of non-alcohol drugs in Norway.

AIMS: When non-alcohol drugs are detected in blood samples from apprehended drivers in Norway, individualised expert opinions are required to evaluate degree of impairment. For alcohol, legislative limits have been in use since 1936. To harmonize the current practice for driving under the influence of alcohol and non-alcohol drugs, a judicial reform with legislative limits for non-alcohol drugs has been suggested. METHODS: Impairment limits, representing drug concentrations in blood likely to be accompanied by a degree of impairment comparable to a blood alcohol concentration (BAC) of 0.02%, were proposed for 20 psychotropic drugs, including the most prevalent benzodiazepines, cannabis, GHB, hallucinogens and opioids. Limits for graded sanctions, representing drug concentrations in blood likely to induce impairment comparable to BACs of 0.05% and 0.12%, were defined for 13 of the 20 substances. The suggested limits were based on assessments of impairment after single doses of the drugs in naïve individuals. The proposed limits will not apply to individuals with valid prescriptions for medicinal drugs, where the present system with individualised expert evaluations will be maintained. CONCLUSION: Norway is the first country planning to implement legislative limits for non-alcohol drugs corresponding to impairment seen at increasing BACs. The background and justification for the suggested limits are presented herein.

[Sex differences and cardiovascular drugs]. / Kjønnsforskjeller og kardiovaskulaere legemidler.

In the western world, cardiovascular disease is the leading cause of death for both sexes. These diseases show substantial differences between the sexes with respect to epidemiology, biology and clinical aspects. In recent years, more attention has been directed towards sex differences in pharmacological effects. Although both sexes are included in most pharmacological trials, the proportion of women is often too low to enable sex-specific analyses.

Health-related quality of life after myocardial infarction is associated with level of left ventricular ejection fraction.

BACKGROUND: The objective was to explore the relationship between left ventricular ejection fraction (LVEF) assessed during hospitalization for acute myocardial infarction (MI) and later health-related quality of life (HRQoL). METHODS: We used multivariable linear regression to assess the relationship between LVEF and HRQoL in 256 MI patients who responded to the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D Index, and the EuroQol Visual Analogue Scale (EQ-VAS) 2.5 years after the index MI. RESULTS: 167 patients had normal LVEF (>50%), 56 intermediate (40%-50%), and 33 reduced (<40%). The mean (SD) KCCQ clinical summary scores were 85 (18), 75 (22), and 68 (21) (p <0.001) in the three groups, respectively. The corresponding EQ-5D Index scores were 0.83 (0.18), 0.72 (0.27), and 0.76 (0.14) (p = 0.005) and EQ-VAS scores were 72 (18), 65 (21), and 57 (20) (p = 0.001). In multivariable linear regression analysis age > or = 70 years, known chronic obstructive pulmonary disease (COPD), subsequent MI, intermediate LVEF, and reduced LVEF were independent determinants for reduced KCCQ clinical summary score. Female sex, medication for angina pectoris at discharge, and intermediate LVEF were independent determinants for reduced EQ-5D Index score. Age > or = 70 years, COPD, and reduced LVEF were associated with reduced EQ-VAS score. CONCLUSION: LVEF measured during hospitalization for MI was a determinant for HRQoL 2.5 years later.

High mortality in diabetic patients with acute myocardial infarction: cardiovascular co-morbidities contribute most to the high risk.

BACKGROUND: High mortality rates have been reported in diabetic patients after acute myocardial infarction (AMI). The excess mortality has been attributed to the diabetic state itself. We aimed to investigate how other risk factors along with diabetes per se may predict mortality in an unselected AMI population. METHODS: A representative sample of an unselected AMI population was collected over a three-month period. Data on patients' histories, co-morbidity, presenting features and treatment were collected from medical records. The data sets included outcome variables at discharge, after 6 months and after 2.5 years. Patients with confirmed diabetes on admission to hospital were registered as diabetic patients. RESULTS: Of the 901 patients admitted to hospital with AMI, 121 (14%) were diabetic patients. Compared with the nondiabetic patients significantly fewer of the diabetic patients were alive at discharge (78% vs 86%), after 6 months (64% vs 78%) and after 2.5 years (42% vs 65%). In multiple logistic regression analyses adjusted for age, sex and smoking status, the most important predictor of death at 2.5 years was heart failure, followed by previous MI, diabetes, and angina pectoris. The population attributable risk (PAR) of death after 2.5 years was 7% for diabetes, 17% for previous MI, 13% for heart failure and 12% for angina pectoris. CONCLUSION: Among patients with diabetes suffering an AMI the already established cardiovascular co-morbidities, which previously partly or fully might have been caused by diabetes, contributed more than diabetes per se to high mortality in-hospital and in the follow-up period.

Treatment with statins after acute myocardial infarction in patients >or=80 years: underuse despite general acceptance of drug therapy for secondary prevention.

PURPOSE: It has not been decided to what extent the results from statin trials should be transferred to clinical practice in the very old. The aim of the study was to assess the use of cardiovascular drugs after an acute myocardial infarction (MI), with particular focus on statins, in very old patients as compared to younger patients. METHOD: A sample of 901 acute MI patients was drawn from 16 hospitals in 1999/2000; the patients were followed up for 2.5 years. Information on demographic variables and drug therapy was obtained from hospital records, and in the follow-up period by direct patient contact or questionnaire. The main indications for prescribing the various cardiovascular drugs were recorded. RESULTS: At discharge, drug use in patients >or=80 and <80 years, respectively, was as follows: ACE-inhibitors 48 versus 32%, nitrates 55 versus 32%, diuretics 64 versus 26%, aspirin 72 versus 86%, and beta-blockers 67 versus 85%. A striking difference was found for statins: 9% in the very old and 72% in younger patients. The pattern of drug use generally remained unchanged after 2.5 years. Survival rates for patients >or=80 and <80 years: at discharge 72 versus 90%, after 2.5 years 34 versus 73%. CONCLUSIONS: Drug therapy was widely accepted for the indication secondary prevention after MI in patients above 80 years of age. The various cardiovascular drugs were prescribed to about the same extent for very old and younger patients. The exception was lipid lowering drugs which, despite the physicians' recognition of the indication secondary prevention in the very old patients, were prescribed to a limited extent.

The problem of underdosing of angiotensin-converting enzyme inhibitors is markedly overrated: results from a study of patients discharged from hospital after an acute myocardial infarction.

OBJECTIVE: The use of angiotensin-converting enzyme (ACE) inhibitors has increased markedly during the last decade. It has been claimed that doses of ACE inhibitors prescribed in clinical practice are considerably lower than the target doses used in randomized clinical trials. The aim of the study was to investigate dosing of ACE inhibitors in patients discharged from the hospital after an acute myocardial infarction (AMI) and, furthermore, to compare these doses with the doses actually reached in clinical trials. METHODS: From 16 hospitals, we drew a sample of patients who were discharged alive with the diagnosis of AMI during a 3-month period in 1999/2000. From medical records, physicians in each hospital obtained the observed rate of cardiovascular drugs at discharge, including type and doses of ACE inhibitors. The clinicians' main indication for ACE inhibitor use was also reported. Outcome variables, including deaths and drug utilization with dosing after 6 months, were collected. RESULTS: Of a total of 767 patients discharged alive, 274 patients received an ACE inhibitor. The daily mean doses of the four ACE inhibitors used in the study were as follows: captopril 69.8+/-36.9 mg (n=44), enalapril 13.6+/-8.1 mg (n=75), lisinopril 11.0+/-7.2 mg (n=114), and ramipril 8.4+/-4.5 mg (n=38). The doses were unchanged after 6 months except for captopril, which showed a rise in mean daily dose to 84.4+/-36.7 mg. Ramipril compared most favorably with clinical trial medications, while captopril deviated most. The indication of hypertension was associated with slightly higher doses than the indication of secondary prevention. CONCLUSION: AMI patients were discharged from the hospital with ACE inhibitor doses fairly close to the ones achieved in clinical trials showing survival benefits for ACE inhibitors. A distinction should be made between target doses and doses actually obtained in clinical trials.

Angiotensin-converting enzyme (ACE) inhibitor therapy after myocardial infarction in relation to left ventricular function.

OBJECTIVE: To investigate to what extent and by what methods clinicians assess left ventricular (LV) function after an acute myocardial infarction (AMI) and how the results of the assessments relate to the use of angiotensin-converting enzyme (ACE) inhibitors; furthermore, to explore which main indications caused the clinicians to initiate ACE inhibitor therapy. DESIGN: From 16 hospitals we drew a sample of patients who were discharged with the diagnosis of AMI during a 3-month period in 1999/2000. Physicians in each hospital obtained the observed rate of use of cardiovascular drugs at discharge and also information on ejection fraction (EF) measurements. The results of the EF recordings were classified into three categories: >0.50, 0.40-0.50 and <0.40. The clinicians' main indications for drug use were reported. RESULTS: Among 767 patients discharged alive, EF was measured in 409 (53%), by echocardiography in 53% and by radionuclide ventriculography in 47%. Of the 409 patients 227 (55%) had EF >0.50, 95 (24%) EF 0.40-0.50 and 87 (21%) EF <0.40. Adjusted odds ratio for ACE inhibitor therapy being initiated during the AMI was 13.5 for those with EF <0.40 compared with those with EF >0.50. The main indication for starting ACE inhibitor therapy was heart failure (50%) followed by secondary prevention (42%). CONCLUSION: Measuring EF appears to be an important tool in the evaluation of AMI patients prior to discharge from hospital. Initiation of ACE inhibitor therapy related strongly to the results of the assessments.

Antihypertensive therapy at the onset of an acute myocardial infarction predicts in-hospital mortality.

Several studies, which have compared the efficacy of conventional antihypertensive drugs (thiazide diuretics and beta-blockers) with the newer agents [calcium blockers and angiotensin-converting enzyme (ACE) inhibitors], have shown that they are almost equally efficacious with regard to effects on blood pressure, and in preventing cardiovascular morbidity and mortality. The potential value of these drugs when hypertensive patients suffer an acute myocardial infarction (AMI) has, however, not been fully elucidated. The objective of the present observational study was to investigate whether prior use of different antihypertensive drugs could modify or influence in-hospital death in hypertensives suffering an AMI. A total of 299 hypertensive patients with the diagnosis of AMI were included. The demographic data were obtained from medical records. Variables were entered into a logistic regression model. The main predictors of death were age (adjusted odds ratio (ORa) 1.07, p = 0.002 (per each year), and the use of diuretics (ORa 2.54, p = 0.018) and calcium blockers (ORa 2.54, p = 0.010). On the other hand, the use of ACE inhibitors was associated with a marked reduction of in-hospital death (ORa 0.44, p = 0.045). The present study indicates that while the use of ACE inhibitors was associated with a reduced risk of in-hospital death in hypertensive patients suffering an AMI, the use of diuretics and calcium blockers was associated with increased risks.

Use of cardiovascular drugs after acute myocardial infarction: a marked shift towards evidence-based drug therapy.

OBJECTIVE: To investigate the prescription pattern for cardiovascular drugs among patients discharged after an acute myocardial infarction (AMI) in hospitals that had participated in a corresponding study seven years earlier, and examine what the indications were for use of the different drugs. METHODS: From 16 hospitals we drew a sample of patients who were discharged with a diagnosis of AMI during a three months period in 1999/2000. Physicians in each hospital obtained from the medical records the observed rate of use of cardiovascular drugs at discharge. The drug use was compared with findings from a corresponding sample drawn in 1993. The main indication for use of the different cardiovascular drugs was recorded for the 1999/2000 sample. RESULTS: 399 patients discharged alive were included in the first study and 767 in the second. The use of beta-blockers, ACE inhibitors and statins rose substantially during the period. For patients aged 70 were: beta-blockers 45% vs 74%, ACE inhibitors 19% vs 38%, statins not recorded vs 35%. Aspirin/anticoagulant use was largely unchanged; 93% and 70% of patients aged 70 respectively used these drugs at the second survey. The use of regular nitrates and calcium antagonists had decreased. Nearly half of the >70 group and one-fifth of persons