PubMed Health⌕ Search

Biomedical subjects

J Hallas

Publications and source records attributed to J Hallas.

At least 19 recordsLinked to original sources

Statins and risk of polyneuropathy: a case-control study.

BACKGROUND: Several case reports and a single epidemiologic study indicate that use of statins occasionally may have a deleterious effect on the peripheral nervous system. The authors therefore performed a population-based study to estimate the relative risk of idiopathic polyneuropathy in users of statins. METHOD: The authors used a population-based patient registry to identify first-time-ever cases of idiopathic polyneuropathy registered in the 5-year period 1994 to 1998. For each case, validated according to predefined criteria, 25 control subjects were randomly selected among subjects from the background population matched for age, sex, and calendar time. The authors used a prescription register to assess exposure to drugs and estimated the odds ratio of use of statins (ever and current use) in cases of idiopathic polyneuropathy compared with control subjects. RESULTS: The authors verified a diagnosis of idiopathic polyneuropathy in 166 cases. The cases were classified as definite (35), probable (54), or possible (77). The odds ratio linking idiopathic polyneuropathy with statin use was 3.7 (95% CI 1.8 to 7.6) for all cases and 14.2 (5.3 to 38.0) for definite cases. The corresponding odds ratios in current users were 4.6 (2.1 to 10.0) for all cases and 16.1 (5.7 to 45.4) for definite cases. For patients treated with statins for 2 or more years the odds ratio of definite idiopathic polyneuropathy was 26.4 (7.8 to 45.4). CONCLUSIONS: Long-term exposure to statins may substantially increase the risk of polyneuropathy.

Aged↗

Conducting pharmacoepidemiologic research in Denmark.

Denmark has one of the worlds most comprehensive registration of its citizens' use of medical and social services. Most databases are population-based and of very high quality. Virtually all employ a mutual person identifier, which renders it technically possible to link any of them with others. There are two prescription registries of interest for research, the OPED and the NJPD, each covering 0.5 million persons. The content of these are described in brief. The most recent Danish data protection act can be viewed as a liberalization of prevailing registry practice. Our most important obstacles for performing record-linkage studies are costs, academic resources and a lack of generally accepted guidelines on the ethics of observational research.

Access to Information↗

Are users of lipid-lowering drugs at increased risk of peripheral neuropathy?

OBJECTIVE: To estimate the risk of peripheral neuropathy associated with use of lipid-lowering drugs. METHODS: Population-based dynamic cohort study based on data from general practices in the United Kingdom from 1991 to 1997. Three cohorts of individuals aged 40-74 years were identified: a cohort of 17,219 persons who received at least one prescription for lipid-lowering drugs in the period; a second cohort of patients with a hyperlipidaemia diagnosis who had not been prescribed lipid-lowering drugs (n = 28,974) and a third cohort comprised of 50,000 individuals from the general population. The incidence rates of peripheral neuropathy in the three cohorts were calculated and the relative risk of peripheral neuropathy in users of lipid-lowering drugs was compared with non-users from the general population cohort. RESULTS: The incidence rate of idiopathic peripheral neuropathy in users of lipid-lowering drugs was higher [0.73 per 10,000 person-years, 95% confidence interval (CI) 0.01-2.62] than in the hyperlipidaemia non-treated cohort (0.40 per 10,000 person-years, CI 0.05-1.46) and the general population cohort (0.46 per 10,000 person-years, CI 0.13-1.18). The raised risk of idiopathic peripheral neuropathy in users of lipid-lowering drugs was confined to current users of statins (relative risk 2.5, CI 0.3-14.2). These figures suggest one excess case of neuropathy for every 14,000 person-years of statin treatment. CONCLUSIONS: Because of the wide CIs, these results are inconclusive and should be interpreted with caution. However, although peripheral neuropathy as an adverse effect of the use of lipid-lowering drugs cannot be excluded, the magnitude of this untoward effect appears to be small.

Adult↗

Drug prescribing among Danish children: a population-based study.

OBJECTIVES: To characterise the pattern of drug prescribing in Danish children below 19 years of age. METHODS: We used the Odense Pharmacoepidemiologic Database to identify all individual prescriptions for 0- to 19-year-olds in the County of Funen, Denmark, in 1998. The drug consumption was analysed by the defined daily dose methods and anatomical chemical classification system, using analytical templates for individual-based drug utilisation statistics. RESULTS: Of the examined population, 52.6% had one or more prescriptions issued. Overall, 10% of the children accounted for 67.5% of drug prescriptions. Approximately 40% of the children had a prescription issued before they were 1 year old. In 1- to 2-year-olds, 85% received a prescription. Thereafter, the 1-year prevalence of drug use declined to 40%. The total drug consumption was similar between boys and girls until the early teens; thereafter the girls had a prescription issued twice as often as boys. In all age groups, respiratory drugs dominated and drugs used in dermatology was the second largest group. The third largest group was systemic anti-infective agents for children below 12 years of age, whereas it was psychotropic drugs among the oldest children. CONCLUSION: There is the same skewness of drug consumption among Danish children as among Danish adults, but the types of medication differ. Drug use is most extensive among children below 2 years but drug prescribing was considerable in all age groups.

Adolescent↗

Antiepileptic drug utilization: a Danish prescription database analysis.

OBJECTIVES: The purpose of the study was to use prescription data from a Danish database to analyse and evaluate antiepileptic drug (AED) utilization, and compare with other prevalence studies. METHODS: A Danish research database covering outpatient prescription data from a population of 471,873 persons was used. Prescription records on all patients prescribed AEDs during 1998 were retrieved. A cohort was extracted from the group of AED users. RESULTS: We identified 5426 AED users. A total of 3756 of the 5426 AED users were included in our cohort. Of the subjects in the cohort 74% were on monotherapy, 19% used two AEDs and only 7% used three or more AEDs. The eight most frequent regimens were all monotherapy: carbamazepine, oxcarbazepine, phenobarbital, valproic acid, lamotrigine, clonazepam, phenytoin and primidon in that order. The estimated crude 1-year prevalence of AED use was 0.77% for women and 0.83% for men (P<0.001), and it increased with age for both genders. CONCLUSIONS: The prescription pattern reported here is in accordance with the general guidelines for the treatment of epilepsy in Denmark, except for a surprisingly extensive use of phenobarbital. With specific reservations the figures appear to be reasonable estimates of the prevalence of epilepsy.

Adolescent↗

Lipid-lowering drugs and risk of myopathy: a population-based follow-up study.

We conducted a population-based cohort study to estimate the risk of myopathy associated with use of lipid-lowering drugs. Using data from general practices in the United Kingdom in 1991 through 1997, we identified three cohorts of individuals 40 to 74 years of age. One cohort comprised 17,219 persons who had received at least one prescription for lipid-lowering drugs in the period; a second cohort consisted of patients with a hyperlipidemia diagnosis who had not been prescribed lipid-lowering drugs (N = 28,974); and a third cohort comprised 50,000 individuals from the general population with no diagnosis of hyperlipidemia. The incidence rate of myopathy in the cohort of users of lipid-lowering drugs was 2.3 per 10,000 person-years [95% confidence interval (95% CI) = 1.2-4.4], which exceeded the incidence rates observed in the nontreated hyperlipidemia cohort [0 per 10,000 person-years (95% CI = 0.0-0.4)] and the general population [0.2 per 10,000 person-years (95% CI = 0.1-0.4)]. The relative risks of myopathy in current users of fibrates and statins compared with nonusers were 42.4 (95% CI = 11.6-170.5) and 7.6 (95% CI = 1.4-41.3), respectively. Potential risk factors other than drug use could not explain our findings in the nested case-control analysis. We conclude that use of lipid-lowering drugs is associated with a substantially greater risk of myopathy, which is most pronounced for fibrates. The absolute risk of myopathy in users of lipid-lowering drugs is, however, small.

Adult↗

[Big differences in the frequency of polypharmacy between physicians].

Polypharmacy, the simultaneous use of multiple drugs, is associated with adverse drug reactions, medication errors, and increased risk of hospitalisation. When the number of drugs is five or more (major polypharmacy), a significant risk may be present. We analysed the prevalence of major polypharmacy among listed patients, and identified possible predictors of major polypharmacy related to the practice. Prescription data were retrieved from the Odense Pharmaco-epidemiological Database and the age and sex standardised prevalence rate of major polypharmacy was calculated for each practice (n = 173). Possible predictors of major polypharmacy related to the GPs were analysed by backward stepwise linear multiple regression. A six-fold variation between practices in the prevalence of major polypharmacy was found, i.e. from 16 to 96 per 1000 listed patients (median: 42). Predictors related to the practice structure, workload, clinical work profile, and prescribing profile could explain 56% of the variation.

Adult↗

Pharmacovigilance based on prescription databases.

Prescription databases are indispensible in drug safety research and surveillance. For suspected rare serious adverse drug reactions, the confirmation and quantitative risk assessment requires proper epidemiological studies. Often prescription databases provide the information on drug exposure for such studies. Aberrant drug utilization in terms of overuse, underuse, polypharmacy etc. may be a threat to the health of the patient, and these aspects can best be studied by prescription databases. In cases of international drug safety alerts, prescription databases may provide information required for rational actions to be taken.

Aged↗

Drug-induced symptoms of functional dyspepsia and nausea. A symmetry analysis of one million prescriptions.

BACKGROUND: A large variety of drugs have been implicated in causing dyspepsia. Due to the high background incidence of dyspepsia it is impossible to distinguish between spontaneous and truly drug-related symptoms. Most patients with dyspeptic symptoms are treated empirically. Drug-induced dyspepsia might therefore be reflected in the sequencing of prokinetics relative to other medications. AIM: To screen a large prescription database for signs of drug-induced functional dyspepsia, applying a symmetry principle. METHODS: Prescription data on all incident users of cisapride and metoclopramide were used to identify individuals who had started their first therapies with a prokinetic drug and an index drug within a 100-day span. A dyspepsia-provoking effect of the index drug would manifest as an excess of persons with the prokinetic drug prescribed last in this selected population. Relative to conventional analyses based on case-control or cohort design, this principle is robust to confounders that are stable over time. RESULTS: In the cisapride analysis (1825 persons) no single drug had adjusted rate ratios significantly above unity. An inverse signal for antidepressants (rate ratio 0.57; 95% CI: 0.39-0.84) suggests that these drugs may have a therapeutic effect against functional dyspepsia. In the metoclopramide analysis (6126 persons) positive signals were found for 14 drugs, all well-known for causing nausea as a side-effect, with the exception of insulin (rate ratio 2.91, 95% CI: 1.40-8.11). CONCLUSIONS: Drug-induced symptoms of functional dyspepsia are rare and do not contribute to the use of cisapride. The start of insulin treatment may induce nausea.

Adult↗

[National surveillance of Helicobacter pylori eradication in Denmark. Results based on registration of 34.582 drug prescriptions].

We wanted to characterize the use of H. pylori eradication therapy in Denmark (inhabitants 5,227,862). All H. pylori eradication treatments from a nation wide database covering all drug prescriptions in the period January 1994-June 1996 were identified. We found 28,784 out-patients having a prescription with drugs for H. pylori eradication, accounting for 34,582 prescriptions in total. The incidence of new consumers was 220 per 10(5) inhabitants per year, with a maximum at 70-79 years of age. Eighty-six percent of the patients had only one treatment course. Forty-five percent had an anti-ulcer drug prescribed 1-12 months after the H. pylori eradication therapy. Consumption of antibiotics used for H. pylori eradication accounted for 1.4% of the total consumption of antibiotics. In conclusion, the incidence of H. pylori eradication therapy was fairly stable but with changes in the pattern of drug regimens used. Anti-ulcer drugs were often given after H. pylori eradication therapy, suggesting an inappropriate use of eradication treatment.

Adult↗

[Polypharmacy estimated by means of a population-based prescription database].

The aim was to investigate estimators of polypharmacy (PP) from a population based prescription database. Data were retrieved from Odense Pharmacoepidemiological Database and contained a 10% random sample (n = 26,977) of drug users in 1994. PP was defined as simultaneous treatment with different drugs, and the duration of treatment was calculated from the date of purchase and the number of defined daily doses prescribed. This estimator was compared with an estimator based on the number of drugs purchased during a three month period. On an average day 8.7% were exposed to minor PP (two to four drugs) and 1.2% to major PP (five or more drugs). Purchase of five or more drugs during a three month period predicted episodes of major PP with a positive predictive value of 80%. Epidemiological measures of multiple drug use can be estimated from a prescription database. Conceptually, an estimator based on the number of simultaneously used drugs is preferable, but the number of drugs purchased during a three month period may be a useful alternative estimator.

Databases, Factual↗

Helicobacter pylori and risk of ulcer bleeding among users of nonsteroidal anti-inflammatory drugs: a case-control study.

BACKGROUND & AIMS: Peptic ulcer complications related to use of nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common serious adverse drug reactions. Whether Helicobacter pylori infection potentiates this gastrointestinal toxicity of NSAIDs is still unresolved. In this study, we investigated the role of H. pylori as a cause of bleeding peptic ulcer among NSAID users. METHODS: A case-control study of current users (n = 132) of NSAIDs (including acetylsalicylic acid), admitted because of bleeding peptic ulcer, was performed. Controls were 136 NSAID users without gastrointestinal complications. H. pylori was diagnosed by either increased levels of serum immunoglobulin G or by 13C-urea breath test. RESULTS: Fifty-eight (44%) case subjects had a bleeding gastric ulcer, 54 (41%) had a bleeding duodenal ulcer, 12 (9%) had both gastric and duodenal ulcers, and 8 (6%) had hemorrhagic gastritis. H. pylori was present in 75 (57%) cases compared with 59 (43%) controls. The adjusted odds ratio of bleeding peptic ulcer among NSAID users associated with H. pylori infection was 1.81 (95% confidence interval, 1.02-3.21). H. pylori accounted for approximately 24% of bleeding peptic ulcers among elderly NSAID users. CONCLUSIONS: NSAID users infected with H. pylori have an almost twofold increased risk of bleeding peptic ulcer compared with NSAID users without H. pylori.

Adult↗

Polypharmacy in general practice: differences between practitioners.

BACKGROUND: Polypharmacy, the simultaneous use of multiple drugs, is associated with adverse drug reactions, medication errors, and increased risk of hospitalization. When the number of concurrently used drugs totals five or more (major polypharmacy), a significant risk may be present. AIM: To analyse the interpractice variation in the prevalence of major polypharmacy among listed patients, and to identify possible predictors of major polypharmacy related to the practice. METHOD: Prescription data were retrieved from the Odense Pharmacoepidemiological Database, and individuals subject to major polypharmacy were identified. The age- and sex-standardized prevalence rate of major polypharmacy was calculated for each practice in the County of Funen in Denmark (n = 173), using the distribution of age and sex of the background population as a reference. The practice characteristics were retrieved from the Regional Health Insurance System. Possible predictors of major polypharmacy related to the general practitioners (GPs) were analysed using backward stepwise linear multiple regression. RESULTS: A six-fold variation between the practices in the prevalence of major polypharmacy was found (16 to 96 per 1000 listed patients; median = 42). Predictors related to the practice structure, workload, clinical work profile, and prescribing profile could explain 56% of the variation. CONCLUSION: A substantial part of the variation in major polypharmacy between practices can be explained by predictors related to practice.

Adult↗

[Antabus treatment in general practice. A pharmaco-epidemiological study of prescription patterns based on a prescription database].

Denmark has a long tradition for the use of alcohol-aversive drugs in the treatment of alcoholism, most commonly disulfiram (Antabuse). The purpose of this study was to examine the prescription patterns for disulfiram in Danish general practice on an individual level. By means of a prescription database we analysed 150,787 prescriptions on reimbursed medicine to persons who had redeemed prescriptions for alcohol-aversive drugs during the period 1.1.1993 to 31.12.1995 in the County of Funen. Prevalence of disulfiram treatment was 12 per 10,000 inhabitants, three-year prevalence 75 per 10,000 inhabitants and incidence 21 per 10,000 inhabitants per year. Eighty-seven percent of treatments were stopped at (or before) the expiration of one prescription, and relapse was frequent (46%).

Adult↗

Polypharmacy: correlations with sex, age and drug regimen. A prescription database study.

OBJECTIVE: To analyse the occurrence of multiple drug use (polypharmacy, PP) in the population and to identify individuals particularly prone to PP. METHODS: Data were derived from the Odense Pharmacoepidemiological Database (OPED) and covered all subsidised prescriptions during 1994 presented by inhabitants in the county of Funen (n = 466567). The number of individuals concurrently using two to four drugs (minor PP) and five or more drugs (major PP) was calculated on a random day in 1994. Drugs were classified according to the Anatomical Therapeutical Chemical (ATC) classification index. The main therapeutic class (second level of the ATC code) was used as an indicator for the type of health problem. A stepwise backwards logistic regression was used to identify predictors of major PP. Odds ratios were calculated for different drug classes, and the age and sex of all drug users. RESULTS: On a random day, 8.3% of the population were exposed to minor PP and 1.2% to major PP. The prevalence of PP increased with age, and from the age of 70 years, two thirds of all drug users were PP users. Drug use was 50% more prevalent among women than men, but over the age of 70, the sexes did not differ in the prevalence of major PP. Many different drug combinations were found, and among major PP users (n = 5443), two thirds had their own unique drug regimen, different from all other drug users. Cardiovascular drugs and analgesics were often involved in PP among the elderly, while asthma drugs, psychotropic drugs and anti-ulcer drugs were predominant among young individuals exposed to PP. The odds ratio (OR) for major PP was substantially increased for individuals treated for cardiovascular diseases (OR, 4.5), anaemia (OR, 4.1) and respiratory diseases (OR, 3.6). CONCLUSIONS: PP is widespread in the population. Clinicians and organisers who are responsible for quality assurance programmes should intensify their surveillance of the groups most prone to PP (the elderly and those using analgesics or drugs for cardiovascular disease, anaemia, asthma and diabetes).

Adolescent↗

National surveillance of Helicobacter pylori eradication therapy in Denmark. Results from registration of 34,582 prescriptions.

BACKGROUND: We wanted to characterize the use of Helicobacter pylori eradication therapy in Denmark (5,227,862 inhabitants). METHODS: All H. pylori eradication treatments from a nationwide database including all redeemed drug prescriptions in the period January 1994 to June 1996 were identified. So were all outpatients receiving a drug prescription for H. pylori eradication. RESULTS: We recorded 34,582 prescriptions for H. pylori eradication therapy given to 28,784 patients. The incidence of new consumers was 220 per 10(5) inhabitants per year, with a maximum at 70-79 years of age. Eighty-six per cent of the patients had only one treatment course. In 16% of the eradication therapies, nonsteroid anti-inflammatory drugs had been prescribed within the previous 3 months, and 45% had an anti-ulcer drug prescribed 1-12 months after the H. pylori eradication therapy. Consumption of antibiotics used for H. pylori eradication accounted for 1.4% of the total consumption of antibiotics. CONCLUSIONS: The incidence of H. pylori eradication therapy was fairly stable but with changes in the pattern of drug regimens used. Anti-ulcer drugs were often given after H. pylori eradication therapy, suggesting an inappropriate use of treatment.

Adolescent↗

Screening for drug related dyspepsia: an analysis of prescription symmetry.

OBJECTIVE: Most patients with severe upper dyspepsia are treated empirically with ulcer drugs. Drug-induced dyspepsia might therefore be reflected in the sequencing of ulcer drugs relative to other medications. Our aim was to screen a large population-base prescription database for evidence of drug-induced dyspepsia. METHODS: Prescription data on 31,232 incident users of ulcer drugs were drawn from a research database, covering the county of Funen, Denmark. We identified all individuals who had started their first recorded therapies with an ulcer drug and another non-ulcer drug within a 100 day span. In this selected group, there would normally be an equal number starting either drug first, while a dyspepsia-provoking effect of the non-ulcer drug would manifest as an excess of individuals with the ulcer drug prescribed last. This screening method is robust to confounders that are stable over time. RESULTS: Only non-steroidal antiinflammatory drugs (adjusted rate ratio (RR) 1.8, 95% confidence interval (CI), 1.6-2.0), calcium blockers (RR 1.4, CI 1.2-1.7), corticosteroids (RR 1.1, CI 1.0-1.3), angiotensin converting enzyme inhibitors (RR 1.4, CI 1.1-1.7) and methylxanthines (RR 1.5, CI 1.1-2.2) showed a significant asymmetry suggesting a dyspepsia-provoking effect. An analysis of effect modifiers suggested that the signals for corticosteroids and for angiotensin converting enzyme inhibitors were explained by concurrent use of non-steroidal anti-inflammatory drugs and by underlying congestive heart failure. The signal for non-steroidal anti-inflammatory drugs may be explained by the known reputation of non-steroidal antiinflammatory drugs for causing ulcers. CONCLUSION: There are hardly any important unknown drug effects that mimic acid related dyspepsia. Drug-induced dyspepsia contributes little to the overall use of ulcer drugs.

Aged↗