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Biomedical subjects

Ivar Aursnes

Publications and source records attributed to Ivar Aursnes.

13 recordsLinked to original sources

Even more suicide attempts in clinical trials with paroxetine randomised against placebo.

BACKGROUND: Following our previous publication we have received critical comments to our conclusions as well as new data that are strengthening our findings. RESULTS: With the new data, 11 suicide attempts among patients on paroxetine against 1 among patients on placebo, we found with a Bayesian technique that the posterior probability that medication with paroxetine is associated with an increased intensity per year of a suicide attempt is from 0.98 to 0.99, depending on the prior. We found that the comment to our article by GSK representatives contained errors, misunderstanding and unwillingness to accept Bayesian principles in the analysis of clinical trials. CONCLUSION: We were in our previous publication, with preliminary data and a Bayesian approach, able to raise a concern that suicide attempts might be connected with the use of paroxetine. This suspicion has now been confirmed.

Adult↗

[Attitudes to estrogen replacement therapy among Norwegian women].

BACKGROUND: The aim of the study was to investigate women's attitudes towards hormone treatment (HT), their judgment of the various sources of information, and their knowledge of indications for HT. METHODS: We posted questionnaires to 1000 Norwegian women between 45 and 60 years of age, randomly selected from the National Register. We received replies from 386 women (38.6%). RESULTS: Of those who replied, 28% reported that they were currently using HT, 22% were previous users, 24% were considering starting, whereas 26% refused ever to use HT. One half of current and previous users had obtained their prescriptions from a gynaecologist, the other half from their general practitioner. Mean age at start of HT was 47 years. 65% of the women started the medication before menopause. The women thought HT to be useful for treatment of hot flushes, prevention of osteoporosis, well-being, improved mood and sex life. The women were also asked about the rating of importance that they would give to the various sources of information. The highest ratings were given to their gynaecologist or general practitioner. Also reading about HT and the opinion of other health personnel obtained high ratings. CONCLUSIONS: The indications for HT given by the women correspond well with the prevailing guidelines. The recent observation about a possible negative effect of HT on cardiovascular disease seems to have reached the respondents. Many women begin to use HT several years before menopause.

Adult↗

Suicide attempts in clinical trials with paroxetine randomised against placebo.

BACKGROUND: Inclusion of unpublished data on the effects of antidepressants on children has suggested unfavourable risk-benefit profiles for some of the drugs. Recent meta-analyses of studies on adults have indicated similar effects. We obtained unpublished data for paroxetine that have so far not been included in these analyses. METHODS: The documentation for drug registration contained 16 studies in which paroxetine had been randomised against placebo. We registered the number of suicides, suicide attempts and ideation. We corrected for duration of medication and placebo treatment and used a standard Bayesian statistical approach with varying priors. RESULTS: There were 7 suicide attempts in patients on the drug and 1 in a patient on placebo. We found that the probability of increased intensity of suicide attempts per year in adults taking paroxetine was 0.90 with a "pessimistic" prior, and somewhat less with two more neutral priors. CONCLUSION: Our findings support the results of recent meta-analyses. Patients and doctors should be warned that the increased suicidal activity observed in children and adolescents taking certain antidepressant drugs may also be present in adults.

Adult↗

[Mercury, fish, fish oil and the risk of cardiovascular disease].

BACKGROUND: Several clinical studies have documented that intake of fish may reduce mortality from coronary heart disease, and two epidemiological investigations have shown a 50% reduction in the incidence of sudden death and of "primary cardiac arrest" in subjects eating fish. However, in some studies no beneficial effects of fish intake on coronary heart disease could be found; one Finnish study even found a positive correlation between intake of freshwater fish and coronary heart disease. One possible explanation for this paradox could be a high content of mercury in fish. MATERIAL AND METHODS: We have studied the relevant literature describing beneficial, less beneficial and negative effects of fish intake on the development of coronary heart disease. Furthermore, we have studied reports that mercury may have properties that enhance the development of coronary heart disease. RESULTS AND INTERPRETATION: Several studies have shown an inverse correlation between omega-3 fatty acids from fish in serum/adipose tissue and coronary heart disease. However, a high content of mercury in hair/toe nail had a negative effect, and in one study the odds ratio for myocardial infarction in those with the highest content of mercury was 2.16. A positive correlation between mercury in hair and the progression of carotid atherosclerosis has been found. Intake of fish is a major source of exposure to mercury, and a high content of mercury probably inhibits the beneficial effects of omega-3 fatty acids on the development of coronary artery disease.

Animals↗

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.

Adrenergic beta-Antagonists↗

Clinical efficacies of antihypertensive drugs.

OBJECTIVE: According to published data, the ability to prevent various hypertension-related events differs between the various antihypertensive drug groups. Although absolute drug effects differ among studies, relative drug effects could be considered constant. We therefore explored the possibility of drawing statistically valid conclusions about the differences in clinical efficacy between various drug groups by doing an overview of published data. DESIGN: We made a meta-analysis with a Bayesian fixed effect model in which we related the drug effects to the effects of placebo drugs. We selected 27 clinical trials from the literature according to specific criteria, including results from studies reporting the effects of the newer drugs when tested against diuretics and beta-blockers, and from studies in which diuretics and beta-blockers had been tested against placebo. We calculated the posterior probability distributions of the relative effects of angiotensin-converting enzyme (ACE) inhibitors vs calcium antagonists with three different endpoints: stroke, coronary disease and heart failure with point estimates of effects and with 95% credibility intervals. As an intermediate step in this procedure we obtained similar information about the effects of the three groups of active drugs, ACE inhibitors, calcium antagonists and diuretics or beta-blockers, tested against placebo. For coronary disease we also tested calcium antagonists against diuretics or beta-blockers. RESULTS: ACE inhibitors and calcium antagonists have an almost identical ability to prevent stroke in hypertensive individuals with a risk ratio (RR) of 1.04. On the other hand, calcium antagonists reduce coronary disease by only 8% relative to placebo. When ACE inhibitors and calcium antagonists are compared with the Bayesian method, the outcome is a 14% difference in favor of the ACE inhibitors to prevent coronary disease, with a credibility interval almost reaching identity. Nor do calcium antagonists do as well as diuretics or beta-blockers in this respect, RR = 1.12 with 95% credibility interval 1.01-1.24. All the tested drug groups have a profound preventive effect on the occurrence of heart failure when given to hypertensive patients, showing reductions of 42-54%. When ACE inhibitors are compared with calcium antagonists RR = 0.79, with a credibility interval 0.65-0.95. CONCLUSION: There is statistically an indisputable difference between ACE inhibitors and calcium antagonists in respect of effects on coronary disease and heart failure when treating hypertensive individuals, ACE inhibitors being more efficacious. There are no differences in the effect on stroke. Moreover, beta-blockers or diuretics are also superior to calcium antagonists in preventing coronary events.

Adrenergic beta-Antagonists↗

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.

Aged↗

[Bayesian thinking on its way into medical statistics?].

BACKGROUND: Bayesian statistical analysis is a paradigm quite different from traditional statistical inference. We wanted to show the usefulness of this approach for some medical problems. MATERIALS AND METHODS: We started with Bayes equation as it is used for estimating the probability of illness based on a specific laboratory test. We also looked into a recent Cochrane report on mammography that accepted two studies as valid and five others as biased. In comparison we used examples of clinical trials from other areas that have been misinterpreted by the use of a traditional statistical approach only. RESULTS: We found that by taking into account our prior beliefs about the likely effects on breast cancer mortality of routine radiological screening programmes, the new data fit well into an estimate of a 5% mortality reduction with a 77% chance that there is a positive effect of screening. INTERPRETATION: Bayesian statistics is helpful in making decisions on the basis of experimental evidence by taking into account our prior knowledge, whereas p-values in traditional statistics only give information on how often we will end up with a false positive conclusion in the long run.

Bayes Theorem↗

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 drug use in respectively 1993 and 1999/2000 was as follows: beta-blockers 73% vs 89%, ACE inhibitors 14% vs 29%, statins not recorded vs 82%; corresponding figures 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 and >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 </=70 used 5-9 cardiovascular drugs. CONCLUSIONS: At the end of the 1990s a substantial shift in drug therapy after AMI occurred, with a markedly increased use of drugs proven to be effective in clinical trials and less use of other cardiovascular drugs. The most frequently reported main indication for use of drugs was secondary prevention. The principles of evidence-based drug therapy became increasingly adopted among clinicians during the 1990s.

Adrenergic beta-Antagonists↗