Lars Bjerrum

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

AbstractObjective: 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= 466 567). 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).

Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem.

Antimicrobial resistance is a global public health challenge, which has accelerated by the overuse of antibiotics worldwide. Increased antimicrobial resistance is the cause of severe infections, complications, longer hospital stays and increased mortality. Overprescribing of antibiotics is associated with an increased risk of adverse effects, more frequent re-attendance and increased medicalization of self-limiting conditions. Antibiotic overprescribing is a particular problem in primary care, where viruses cause most infections. About 90% of all antibiotic prescriptions are issued by general practitioners, and respiratory tract infections are the leading reason for prescribing. Multifaceted interventions to reduce overuse of antibiotics have been found to be effective and better than single initiatives. Interventions should encompass the enforcement of the policy of prohibiting the over-the-counter sale of antibiotics, the use of antimicrobial stewardship programmes, the active participation of clinicians in audits, the utilization of valid rapid point-of-care tests, the promotion of delayed antibiotic prescribing strategies, the enhancement of communication skills with patients with the aid of information brochures and the performance of more pragmatic studies in primary care with outcomes that are of clinicians’ interest, such as complications and clinical outcomes.

Exposure to potential drug interactions in primary health care.

Harmful drug interactions may occur if one drug alters the effect of another drug. During the course of one year, about one-third of the population are exposed to the concurrent use of two or more drugs (polypharmacy). On average, 15% of individuals with polypharmacy are exposed to drugs carrying a risk of potential interactions. Elderly patients exposed to polypharmacy are at highest risk and should therefore be kept under intensified monitoring. Objective - To analyse the prevalence of potential drug interactions, and to identify patients particularly prone to drug interaction. Design - Database study (Odense University Pharmacoepidemiologic Database). Setting - Individuals exposed to polypharmacy in 1999 were examined for potential drug interactions. Subjects - Inhabitants of the County of Funen (n=471 t 732). Main outcome measures - Prevalence of potential drug interactions. Results - One-third of the population were exposed to polypharmacy and among these 15% were exposed to drugs carrying a risk of harmful interaction. Among the elderly with polypharmacy, 25% aged 60-79 years and 36% over 80 years received drugs carrying the risk of interaction. Among individuals exposed to potential drug interaction, 62% were exposed only to one drug interaction and 38% to two or more different drug interactions. The drugs accounting for the highest number of potential interactions were diuretics, NSAIDs, ACE-inhibitors, digoxin, oral antidiabetics, calcium channel blockers, anticoagulants and beta-blockers. When focusing only on major drug interactions, potassium-sparing diuretics and oral anticoagulants were the most frequently involved drugs. Conclusion - Elderly patients exposed to polypharmacy should be kept under intensified monitoring as they are at increased risk of clinically significant drug interactions.

Methods for estimating the occurrence of polypharmacy by means of a prescription database

AbstractObjective: Concurrent use of multiple drugs (polypharmacy, PP) may cause health risks such as adverse drug reactions, medication errors and poor compliance. The objective of this study, based on data from a prescription database, was to evaluate estimators of PP in the general population. Methods: Data were retrieved from Odense Pharmacoepidemiological Database (OPED) and consisted of all prescriptions in 1994 from a 10% random sample of drug users (n=26977) in the county of Funen, Denmark. For each prescription, the period of consumption was calculated by setting the duration of treatment to equal the amount of drug purchased, as measured in defined daily doses (DDD), thereby assuming a daily intake of one DDD. PP was defined as overlapping periods of consumption for different drugs. A Venn diagram was used to illustrate and compare this estimator of PP with two other indicators of multiple-drug use: the number of drugs purchased in 3 months and the mean number of drugs used in 1 year. A receiver operating curve (ROC) was used to evaluate the possibility of predicting episodes of PP from the number of drugs purchased in 3 months. Results: The proposed estimator of PP was robust towards changes in DDD. On an average day in 1994, the prevalence of PP was 9.9% and the standard deviation (SD) between days was 0.3%. Two to four drugs (minor PP) were used by 8.7% of the population (SD, 0.2%) and five or more drugs (major PP) by 1.2% (SD, 0.1%). The number of individuals displaying PP for the first time in 1994 stabilised after approximately 6 months, resulting in an incidence of major PP of 0.2% and of minor PP of 1.2% per month. For individuals exposed to PP, the median number of days of exposure was 61 and 10.5% were exposed for more than 350 days of the year. Purchase of five or more drugs in the first 3 months of 1994 predicted episodes of major PP in the same year with a positive predictive value of 80%. Conclusion: Epidemiological measures of multiple drug use can be estimated from data in a prescription database. From a conceptual point of view, an estimator based on the number of simultaneously used drugs (calculated from the date of purchase and the number of DDD) is preferable, but the number of drugs purchased in a 3-month period may also be a useful estimator.

Trends in utilization of antiepileptic drugs in Denmark

Objectives –  To describe utilization of antiepileptic drugs (AEDs) in Denmark during 1993–2002, with special emphasis on oxcarbazepine, and to assess probable indications for AED use.

The waiting time distribution as a graphical approach to epidemiologic measures of drug utilization.

The emergence of large, computerized pharmacoepidemiologic databases has enabled us to study drug utilization with the individual user as the statistical unit. A recurrent problem in such analyses, however, is the overwhelming volume and complexity of data. We here describe a graphical approach that effectively conveys some essential utilization parameters for a drug. The waiting time distribution for a group of drug users is a charting of their first prescription presentations within a specified time window. For a drug used for chronic treatment, most current users will be captured at the beginning of the window. After a few months, the graph will be dominated by new, incident users. As examples, we present waiting time distributions for insulin, ulcer drugs, systemic corticosteroids, antidepressants, and disulfiram. Appropriately analyzed and interpreted, the waiting time distributions can provide information about the period prevalence, point prevalence, incidence, duration of use, seasonality, and rate of prescription renewal or relapse for specific drugs. Each of these parameters has a visual correlate. The waiting time distributions may be an informative supplement to conventional drug utilization statistics, and possibly also a useful screening tool for unusual prescribing patterns.

Health Alliance for prudent antibiotic prescribing in patients with respiratory tract infections (HAPPY AUDIT) -impact of a non-randomised multifaceted intervention programme

BackgroundExcessive use of antibiotics is worldwide the most important reason for development of antimicrobial resistance. As antibiotic resistance may spread across borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious impact on all countries. Initiatives have been taken to improve the quality of antibiotic prescribing in primary care, but only few studies have been designed to determine the effectiveness of multifaceted strategies across countries with different practice setting. The aim of this study was to evaluate the impact of a multifaceted intervention targeting general practitioners (GPs) and patients in six countries with different health organization and different prevalence of antibiotic resistance.MethodsGPs from two Nordic countries, two Baltic Countries and two Hispano-American countries registered patients with respiratory tract infections (RTIs) in 2008 and 2009. After first registration they received individual prescriber feedback and they were offered an intervention programme that included training courses, clinical guidelines, posters for waiting rooms, patient brochures and access to point of care tests (Strep A and C-Reactive Protein). Antibiotic prescribing rates were compared before and after the intervention.ResultsA total of 440 GPs registered 47011 consultations; 24436 before the intervention (2008) and 22575 after the intervention (2009). After the intervention, the GPs significantly reduced the percentage of consultations resulting in an antibiotic prescription. In patients with lower RTI the GPs in Lithuania reduced the prescribing rate by 42%, in Russia by 25%, in Spain by 25%, and in Argentina by 9%. In patients with upper RTIs, the corresponding reductions in the antibiotic prescribing rates were in Lithania 20%, in Russia 15%, in Spain 9%, and in Argentina 5%.ConclusionA multifaceted intervention programme targeting GPs and patients and focusing on improving diagnostic procedures in patients with RTIs may lead to a marked reduction in antibiotic prescribing. The pragmatic before-after design used may suffer from some limitations and the reduction in antibiotic prescribing could be influenced by factors not related to the intervention.

Respiratory tract infections in general practice: considerable differences in prescribing habits between general practitioners in Denmark and Spain

ObjectiveThe prevalence of antibiotic resistance in a country reflects the local consumption of antibiotics. The majority of antibiotics are prescribed in general practice and most prescriptions are attributable to treatment of respiratory tract infections (RTIs). The aim of this study was to compare general practitioners’ (GPs’) prescribing of antibiotics for respiratory tract infections in a country with a high prevalence of antibiotic resistance (Spain) with a country with a low prevalence of antibiotic resistance (Denmark).MethodsA group of GPs in Copenhagen and Barcelona registered all contacts (n=2833) with patients with RTIs during a 3-week period between 1 November 2001 and 31 January 2002.ResultsOverall, Spanish GPs treated a higher proportion of patients than Danish GPs. After adjusting for unequal distribution of age and sex, we found that Spanish GPs prescribed significantly more antibiotics to patients with focus of infection in tonsils and bronchi/lungs. Narrow-spectrum penicillin was the most used antibiotic in Denmark, representing 58% of all prescriptions issued, followed by macrolide and broad-spectrum penicillin. In Spain, prescriptions were distributed among a great number of compounds, with broad-spectrum penicillins and combinations of amoxicillin plus betalactamase inhibitors most frequently used.ConclusionThe substantial difference in the way GPs manage respiratory tract infections in Denmark and Spain cannot be explained by different patterns of RTIs in general practice. The discrepancies indicate variations in national recommendations, different treatment traditions or different impact of pharmaceutical marketing.

Hormone therapy and cerebrovascular events: a population-based nested case-control study

Objective: The relationship between postmenopausal hormone therapy (HT) and cerebrovascular disease has been examined in several epidemiological studies and clinical trials with conflicting results. The authors aimed to evaluate the association between the use of HT and the incidence of first cerebrovascular event. Design: The study cohort comprised 158,031 women 50 to 69 years old registered in the U.K. General Practice Research Database between 1991 and 1997. The authors conducted a nested case-control analysis using all 920 confirmed cases of cerebrovascular events identified during the follow-up (536 of transient ischemic attack [TIA]; 259 of ischemic stroke; 125 of hemorrhagic stroke) and 10,000 controls. Results: The odds ratios of TIA, ischemic stroke, and hemorrhagic stroke among women currently using HT were 1.48 (95% CI, 1.17-1.87), 1.12 (95% CI, 0.78-1.59) and 1.21 (95% CI, 0.76-1.93), respectively, compared to never users. The overall risk estimate for having a cerebrovascular event was 1.34 (95% CI, 1.11-1.61). The risk of TIA was greater (1.96) among women using high doses of estrogen (95% CI, 1.34-2.87). Conclusion: Overall, a small increased risk of stroke associated with HT use of comparable magnitude to the one observed in recent clinical trials was found. The increased risk was more apparent for TIA than for stroke and was greater at higher doses.

Risk factors for potential drug interactions in general practice

Objective: To identify patient- and practice-related factors associated with potential drug interactions. Methods: A register analysis study in general practices in the county of Funen, Denmark. Prescription data were retrieved from a population-based prescription database (Odense University Pharmacoepidemiologic Database, OPED) covering prescriptions to all inhabitants in the county of Funen, Denmark. All individuals exposed to concurrent use of two or more drugs (polypharmacy) were identified. Combinations of drugs with potential interactions were registered and classified as major, moderate, or minor, depending on the severity of outcome and the quality of documentation. A two-level random coefficient logistic regression model was used to investigate factors related to potential drug interactions. Results: One-third of the population was exposed to polypharmacy, and 6% were exposed to potential drug interactions during 1 year. Patient factors associated with increased risk of potential drug interactions were high age, a high number of concurrently used drugs, and a high number of prescribers. Practice factors associated with potential drug interactions were a high percentage of elderly patients and a low percentage of female patients listed. Conclusion: Prescription data may be useful in quality-improvement programmes to identify groups of patients and practices at increased risk of drug interactions.