Anton Pottegård

The use of medication against attention deficit hyperactivity disorder in Denmark: a drug use study from a national perspective

PurposeThe purpose of the study was to characterize the utilization of medication against attention deficit hyperactivity disorder (ADHD) in Denmark between 1995 and 2011 from a national perspective, by using population-based prescription data.MethodsNational data on drug use in Denmark between 1 January 1995 and 30 September 2011 were extracted from the Registry of Medicinal Product Statistics (RMPS). Drug utilization was characterized using descriptive statistics.ResultsA total of 1,085,090 prescriptions issued to 54,020 persons were identified. The incidence rate was stable in the last 3 years of the study period, and a slightly decreasing incidence rate and a stabilizing prevalence were observed towards the end of this period. The therapeutic intensity was 6.7 defined daily dose/person/day, with large regional differences that ranged from 64 to 145 % of the national average. Methylphenidate accounted for 92.6 % of DDDs used. The general practitioner (GP) rarely initiated treatment, although treatment initiation based on the GP’s advice increased with older age of the patient. Maintenance treatment was found to be distributed roughly equally between prescriber types. For methylphenidate, 1 % of users accounted for 6.1 % of the drug volume and 50 % of users accounted for 84.4 %. The data therefore do not suggest a high proportion of heavy users.ConclusionThe findings of this analysis are mostly reassuring, with the data indicating a seemingly stagnant incidence and prevalence rate and lacking evidence of heavy users. However, the prescriber profile for incident users and the large regional variances raise concerns. It is therefore vital that the use of ADHD drugs is closely monitored.

Data Resource Profile: The Danish National Prescription Registry

Data Resource Profile: The Danish National Prescription Registry Anton Pottegård,* Sigrun Alba Johannesdottir Schmidt, Helle Wallach-Kildemoes, Henrik Toft Sørensen, Jesper Hallas and Morten Schmidt Clinical Pharmacology and Pharmacy, University of Southern Denmark, Odense, Denmark, Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark, Social and Clinical Pharmacy, University of Copenhagen, Copenhagen, Denmark and Department of Internal Medicine, Regional Hospital of Randers, Randers, Denmark

Use of self-controlled designs in pharmacoepidemiology

Self‐controlled observational study designs, such as the case–crossover design and the self‐controlled case series, are reviewed, and their respective rationale, strengths and limitations are compared. Although no single design is generally superior to the others, they share the trait of being robust towards confounders that are stable over time. The self‐controlled designs can be particularly useful when using secondary healthcare data for pharmacoepidemiological research and might be useful in screening for adverse drug effects. The main limitations of self‐controlled designs are that they are amenable only to transient effects; some may be inefficient with long‐term exposure; and they may be sensitive towards trends in exposure.

Use of Antibiotics and Risk of Type 2 Diabetes: A Population-Based Case-Control Study

CONTEXT AND OBJECTIVE Evidence that bacteria in the human gut may influence nutrient metabolism is accumulating. We investigated whether use of antibiotics influences the risk of developing type 2 diabetes and whether the effect can be attributed to specific types of antibiotics. METHODS We conducted a population-based case-control study of incident type 2 diabetes cases in Denmark (population 5.6 million) between January 1, 2000, and December 31, 2012. Data from the Danish National Registry of Patients, the Danish National Prescription Registry, and the Danish Person Registry were combined. RESULTS The odds ratio (OR) associating type 2 diabetes with exposure to antibiotics of any type was 1.53 (95% confidence interval 1.50-1.55) with redemption of more than or equal to 5 versus 0-1 prescriptions. Although no individual group of antibiotics was specifically associated with type 2 diabetes risk, slightly higher ORs for type 2 diabetes were seen with narrow-spectrum and bactericidal antibiotics (OR 1.55 and 1.48) compared to broad-spectrum and bacteriostatic types of antibiotics (OR 1.31 and 1.39), respectively. A clear dose-response effect was seen with increasing cumulative load of antibiotics. The increased use of antibiotics in patients with type 2 diabetes was found up to 15 years before diagnosis of type 2 diabetes as well as after the diagnosis. CONCLUSIONS Our results could support the possibility that antibiotics exposure increases type 2 diabetes risk. However, the findings may also represent an increased demand for antibiotics from increased risk of infections in patients with yet-undiagnosed diabetes.

Alcohol and Breastfeeding

While the harmful effects of alcohol during pregnancy are well-established, the consequences of alcohol intake during lactation have been far less examined. We reviewed available data on the prevalence of alcohol intake during lactation, the influence of alcohol on breastfeeding, the pharmacokinetics of alcohol in lactating women and nursing infants and the effects of alcohol intake on nursing infants. A systematic search was performed in PubMed from origin to May 2013, and 41 publications were included in the review. Approximately half of all lactating women in Western countries consume alcohol while breastfeeding. Alcohol intake inhibits the milk ejection reflex, causing a temporary decrease in milk yield. The alcohol concentrations in breast milk closely resemble those in maternal blood. The amount of alcohol presented to nursing infants through breast milk is approximately 5-6% of the weight-adjusted maternal dose, and even in a theoretical case of binge drinking, the children would not be subjected to clinically relevant amounts of alcohol. Newborns metabolize alcohol at approximately half the rate of adults. Minute behavioural changes in infants exposed to alcohol-containing milk have been reported, but the literature is contradictory. Any long-term consequences for the children of alcohol-abusing mothers are yet unknown, but occasional drinking while breastfeeding has not been convincingly shown to adversely affect nursing infants. In conclusion, special recommendations aimed at lactating women are not warranted. Instead, lactating women should simply follow standard recommendations on alcohol consumption.

Assigning exposure duration to single prescriptions by use of the waiting time distribution

The purpose of this study is to develop and present a method to calculate which exposure duration should be assigned to single prescriptions for use in databases where information on expected duration is not recorded.

Use of benzodiazepines or benzodiazepine related drugs and the risk of cancer: a population-based case-control study

AIM Studies of the carcinogenic potential of benzodiazepines and related drugs (BZRD) have been equivocal. A recent study reported a 35% excess cancer risk among users of hypnotics, including benzodiazepines. METHOD Using Danish nationwide registers, we conducted a matched case-control study of the association between BZRD and cancer risk. During 1 January 2002 and 31 December 2009, we identified 152 510 cases with a first time cancer who were matched (1:8) by age and gender to 1,220,317 cancer-free controls. A new-user design was applied by excluding all subjects who had used anxiolytics, hypnotics or sedatives during the first 2 years of available prescription data (1995-6). Odds ratios (ORs) with 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for potential confounders. In the primary analysis, long term use of BZRD was defined by a cumulative amount of ≥500 defined daily doses of BZRD within a period of 1 to 5 years prior to the index date. RESULTS The adjusted OR for cancer associated with BZRD use was 1.09 (95% CI 1.04, 1.14). ORs were close to unity for most cancer sites, except stomach 1.40 (95% CI 1.05, 1.88), oesophagus 1.43 (95% CI 1.01, 2.02), liver 1.81 (95% CI 1.18, 2.80), lung 1.38 (95% CI 1.23, 1.54), pancreas 1.35 (95% CI 1.02, 1.79) and kidney 1.39 (95% CI 1.01, 1.91). For tobacco-related cancers, the OR was 1.15 (95% CI 1.09, 1.22) and for the remaining cancer sites 1.01 (95% CI 0.94, 1.08). Sub-group analyses revealed only small differences between different levels of exposure or different patient subgroups. CONCLUSION BZRD use was not associated with an overall increase in cancer risk, except for what is likely explained by minor lifestyle confounding, e.g. smoking.

Use of proton-pump inhibitors among adults: a Danish nationwide drug utilization study

Background: The use of proton-pump inhibitors (PPIs) has increased over the last decade. The objective of this study was to provide detailed utilization data on PPI use over time, with special emphasis on duration of PPI use and concomitant use of ulcerogenic drugs. Methods: Using the nationwide Danish Prescription Registry, we identified all Danish adults filling a PPI between 2002 and 2014. Using descriptive statistics, we reported (i) the distribution of use between single PPI entities, (ii) the development in incidence and prevalence of use over time, (iii) measures of duration and intensity of treatment, and (iv) the prevalence of use of ulcerogenic drugs among users of PPIs. Results: We identified 1,617,614 adults using PPIs during the study period. The prevalence of PPI use increased fourfold during the study period to 7.4% of all Danish adults in 2014. PPI use showed strong age dependency, reaching more than 20% among those aged at least 80 years. The proportion of users maintaining treatment over time increased with increasing age, with less than10% of those aged 18–39 years using PPIs 2 years after their first prescription, compared with about 40% among those aged at least 80 years. The overall use of ulcerogenic drugs among PPI users increased moderately, from 35% of users of PPI in 2002 to 45% in 2014. Conclusions: The use of PPIs is extensive and increasing rapidly, especially among the elderly.

Increasing use of antibiotics in pregnancy during the period 2000–2010: prevalence, timing, category, and demographics

The aim of this study was to describe the use of antibiotics in a national population‐based cohort of pregnant Danish women between 2000 and 2010.

Association of Antithrombotic Drug Use With Subdural Hematoma Risk

Importance Incidence of subdural hematoma has been reported to be increasing. To what extent this is related to increasing use of antithrombotic drugs is unknown. Objectives To estimate the association between use of antithrombotic drugs and subdural hematoma risk and determine trends in subdural hematoma incidence and antithrombotic drug use in the general population. Design, Setting, and Participants Case-control study of 10 010 patients aged 20 to 89 years with a first-ever subdural hematoma principal discharge diagnosis from 2000 to 2015 matched by age, sex, and calendar year to 400 380 individuals from the general population (controls). Subdural hematoma incidence and antithrombotic drug use was identified using population-based regional data (population: 484 346) and national data (population: 5.2 million) from Denmark. Conditional logistic regression models were used to estimate odds ratios (ORs) that were adjusted for comorbidity, education level, and income level. Exposures Use of low-dose aspirin, clopidogrel, a vitamin K antagonist (VKA), a direct oral anticoagulant, and combined antithrombotic drug treatment. Main Outcomes and Measures Association of subdural hematoma with antithrombotic drug use, subdural hematoma incidence rate, and annual prevalence of treatment with antithrombotic drugs. Results Among 10 010 patients with subdural hematoma (mean age, 69.2 years; 3462 women [34.6%]), 47.3% were taking antithrombotic medications. Current use of low-dose aspirin (cases: 26.7%, controls: 22.4%; adjusted OR, 1.24 [95% CI, 1.15-1.33]), clopidogrel (cases: 5.0%, controls: 2.2%; adjusted OR, 1.87 [95% CI, 1.57-2.24]), a direct oral anticoagulant (cases: 1.0%, controls: 0.6%; adjusted OR, 1.73 [95% CI, 1.31-2.28]), and a VKA (cases: 14.3%, controls: 4.9%; adjusted OR, 3.69 [95% CI, 3.38-4.03]) were associated with higher risk of subdural hematoma. The risk of subdural hematoma was highest when a VKA was used concurrently with an antiplatelet drug (low-dose aspirin and a VKA: 3.6% of cases and 1.1% of controls; adjusted OR, 4.00 [95% CI, 3.40-4.70]; clopidogrel and a VKA: 0.3% of cases and 0.04% of controls; adjusted OR, 7.93 [95% CI, 4.49-14.02]). The prevalence of antithrombotic drug use increased from 31.0 per 1000 individuals from the general population in 2000 to 76.9 per 1000 individuals in 2015 (P < .001 for trend). The overall subdural hematoma incidence rate increased from 10.9 per 100 000 person-years in 2000 to 19.0 per 100 000 person-years in 2015 (P < .001 for trend). The largest increase was among older patients (>75 years; n = 4441) who experienced an increase from 55.1 per 100 000 person-years to 99.7 per 100 000 person-years (P < .001 for trend). Conclusions and Relevance In Denmark, antithrombotic drug use was associated with higher risk of subdural hematoma; and the highest odds of subdural hematoma was associated with combined use of a VKA and an antiplatelet drug. The increased incidence of subdural hematoma from 2000 to 2015 appears to be associated with the increased use of antithrombotic drugs, particularly use of a VKA among older patients.