David Gaist - Academia.edu (original) (raw)
Papers by David Gaist
Therapeutic Drug Monitoring, 1997
Theophylline is predominantly metabolized by cytochrome P4501A2 (CYP1A2). A possible interaction ... more Theophylline is predominantly metabolized by cytochrome P4501A2 (CYP1A2). A possible interaction between griseofulvin and theophylline was reported to our laboratory, which led us to form the hypothesis that griseofulvin induces the metabolism of theophylline. One purpose of this study was to investigate this hypothesis. The study was carried out as a randomized crossover study of 12 healthy volunteers. In period A of the study, each volunteer received a single dose of 300 mg theophylline ethylenediamine orally. In period B, the subjects took fluvoxamine, 50 mg for 1 day and 100 mg for 6 days, and on day 4, the subjects ingested 300 mg theophylline ethylenediamine. Fluvoxamine is a potent inhibitor of CYP1A2, and period B was included as a positive control. In period C, the subjects took 500 mg griseofulvin for 9 days; on day 8 the subjects again ingested 300 mg theophylline ethylenediamine. Theophylline and its metabolites (1-methyluric acid [IMU], 3-methylxanthine [3MX], and 1,3-dimethyluric acid [13DMU]) in plasma and urine were assayed by high-performance liquid chromatography. During fluvoxamine intake, the median of the total clearance of theophylline decreased from 80 ml/min to 24 ml/min, and the half-life increased from 6.6 to 22 h. The partial formation clearances of the metabolites decreased from 17 to 1.7 ml/min, from 8.9 to 0.9 ml/min, and from 21 to 6.8 ml/min for 1MU, 3MX, and 13DMU, respectively. The results confirm that assessment of theophylline metabolism indeed serves as a biomarker for CYP1A2. During griseofulvin ingestion, the median of the total and partial clearances of theophylline were 84 ml/min, 22 ml/min (1MU), 9.4 ml/min (3MX), and 25 ml/min (13DMU). The half-life decreased significantly from 6.6 to 5.7 h. The increase in partial formation clearances of 1MU and 13DMU, but not of 3MX, were statistically significant. The increase in the total clearance reached only borderline significance. In four subjects a marked induction was seen for all pharmacokinetic parameters, suggesting that the susceptibility to induction is more pronounced in some subjects. This susceptibility could theoretically be explained by a polymorphism in the inducibility of the gene coding for the CYP1A2 enzyme.
Scandinavian Journal of Gastroenterology, 1994
Ugeskrift For Laeger, Nov 1, 2010
The objective of this study was to determine whether the incidence rate of Guillain-Barré syndrom... more The objective of this study was to determine whether the incidence rate of Guillain-Barré syndrome (GBS) in Funen County, Denmark, increased during the 1996-2005 period. Cases of GBS were identified retrospectively using hospital discharge diagnoses from the neurological department, Odense University Hospital, between 1996 and 2005. Hospital record data were evaluated and patients were included if they fulfilled the criteria of the National Institute of Neurological and Communicative Disorders and Stroke for GBS or the criteria for Miller Fisher syndrome (MFS). The study period was divided into two five-year intervals, 1996-2000 and 2001-2005, which were compared with regard to incidence rate. The incidence rate was 1.57/100,000 person-years in 1996-2000 and 1.73/100,000 person-years in 2001-2005. The increase in the incidence rate was 0.17/100,000 person-years (95% confidence interval (CI): -0.65-0.98). The crude incidence rate for the entire period 1996-2005 was 1.65 /100,000 person-years. An antecedent infection was reported in 56% of the cases including respiratory infection (25%), gastrointestinal infection (21%) and influenza-like symptoms (10%). There was no significant difference in preceding events between 1996-2000 and 2001-2005 (p = 0.47). There was no significant change in the incidence rate of GBS during the study period. There was no clustering in time or by antecedent event. Our finding of an incidence rate of 1.65/100,000 person-years is in line with previously published studies.
Ugeskrift For Laeger, 2010
Dmb Danish Medical Bulletin, Sep 1, 1997
The extensive computerisation of Danish pharmacies has permitted the establishment of two large p... more The extensive computerisation of Danish pharmacies has permitted the establishment of two large prescription registries: The Odense University Pharmacoepidemiological Database (OPED) and the Pharmacoepidemiological Prescription Database of North Jutland (PDNJ). The Danish prescription registries content, coverage, completeness and the quality of the data are discussed in this article. Furthermore, conditions for access to the data are presented. The two prescription registries cover a background population of approximately one million or 18% of the Danish population. The populations covered by the registries are stable and representative of the Danish population in general. The registries cover all reimbursed medicine at the level of the individual user. Registration of a unique and permanent personal identifier enables the compilation of longitudinal drug histories and allows the linking of prescription data to other population-based Danish registries. The degree of completeness of the Danish prescription registries is excellent for reimbursed prescription drugs. A small number of comparison studies also indicate high validity of the register information. The Danish prescription registries represent a useful new data source for pharmacoepidemiological studies.
Thrombosis and haemostasis, Jan 2, 2015
The study objective was to investigate the relationship between use of antithrombotic drugs and s... more The study objective was to investigate the relationship between use of antithrombotic drugs and subarachnoid haemorrhage (SAH). We identified patients discharged from Danish neurosurgery units with a first-ever SAH diagnosis in 2000 to 2012 (n=5,834). For each case, we selected 40 age-, sex- and period-matched population controls. Conditional logistic regression models were used to estimate odds ratios (aOR), adjusted for comorbidity, education level, and income. Low-dose aspirin (ASA) use for < 1 month was associated with an increased risk of SAH (aOR 1.75, 95 % confidence interval [CI] 1.28-2.40). This aOR decreased to 1.26 (95 %CI: 0.98-1.63) with 2-3 months of ASA use, and approached unity with use for more than three months (1.11, 95 %CI 0.97-1.27). Analyses with first-time users confirmed this pattern, which was also observed for clopidogrel. ASA treatment for three or more years was associated with an aOR of SAH of 1.13 (95 %CI: 0.86-1.49). Short-term use (< 1 month) of...
Thrombosis and Haemostasis
The study objective was to investigate the relationship between use of antithrombotic drugs and s... more The study objective was to investigate the relationship between use of antithrombotic drugs and subarachnoid haemorrhage (SAH). We identified patients discharged from Danish neurosurgery units with a first-ever SAH diagnosis in 2000 to 2012 (n=5,834). For each case, we selected 40 age-, sex- and period-matched population controls. Conditional logistic regression models were used to estimate odds ratios (aOR), adjusted for comorbidity, education level, and income. Low-dose aspirin (ASA) use for < 1 month was associated with an increased risk of SAH (aOR 1.75, 95 % confidence interval [CI] 1.28-2.40). This aOR decreased to 1.26 (95 %CI: 0.98-1.63) with 2-3 months of ASA use, and approached unity with use for more than three months (1.11, 95 %CI 0.97-1.27). Analyses with first-time users confirmed this pattern, which was also observed for clopidogrel. ASA treatment for three or more years was associated with an aOR of SAH of 1.13 (95 %CI: 0.86-1.49). Short-term use (< 1 month) of...
British journal of cancer, Jan 19, 2013
Few studies have examined the association between use of aspirin or other non-steroidal anti-infl... more Few studies have examined the association between use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and risk of glioma and the results have been equivocal. We therefore investigated the influence of NSAID use on glioma risk in a nationwide setting. We used national registries in Denmark to identify all patients aged 20-85 years with a first diagnosis of histologically verified glioma during 2000-2009. Each case was matched on birth year and sex to eight population controls using risk-set sampling. We used prescription data to assess NSAID use and classified exposure to low-dose aspirin or non-aspirin (NA) NSAIDs into ever use or long-term use, defined as continuous use for 5 years. Conditional logistic regression was used to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with NSAID use, adjusted for potential confounders. A total of 2688 glioma cases and 18,848 population controls were included in the study. Ever use of low...
Neuroepidemiology, 2014
We wished to examine the impact of antiplatelet drug discontinuation on recurrent stroke and all-... more We wished to examine the impact of antiplatelet drug discontinuation on recurrent stroke and all-cause mortality. We identified a cohort of incident ischaemic stroke patients in a Danish stroke registry, 2007-2011. Using population-based registries we assessed subjects' drug use and followed them up for stroke recurrence, or all-cause death. Person-time was classified by antiplatelet drug use into current use, recent use (≤150 days after last use), and non-use (>150 days after last use). Lipid-lowering drug (LLD) use was classified by the same rules. We used Cox proportional hazard models to calculate the adjusted hazard ratio (HR) and corresponding 95% confidence intervals (CIs) for the risk of recurrent stroke or death associated with discontinuation of antiplatelet or LLD drugs. Among 4,670 stroke patients followed up for up a median of 1.5 years, 237 experienced a second stroke and 600 died. Compared with current antiplatelet drug use, both recent use (1.3 (0.8-2.0)), and...
Ugeskrift for laeger, Jan 8, 2010
The objective of this study was to determine whether the incidence rate of Guillain-Barré syndrom... more The objective of this study was to determine whether the incidence rate of Guillain-Barré syndrome (GBS) in Funen County, Denmark, increased during the 1996-2005 period. Cases of GBS were identified retrospectively using hospital discharge diagnoses from the neurological department, Odense University Hospital, between 1996 and 2005. Hospital record data were evaluated and patients were included if they fulfilled the criteria of the National Institute of Neurological and Communicative Disorders and Stroke for GBS or the criteria for Miller Fisher syndrome (MFS). The study period was divided into two five-year intervals, 1996-2000 and 2001-2005, which were compared with regard to incidence rate. The incidence rate was 1.57/100,000 person-years in 1996-2000 and 1.73/100,000 person-years in 2001-2005. The increase in the incidence rate was 0.17/100,000 person-years (95% confidence interval (CI): -0.65-0.98). The crude incidence rate for the entire period 1996-2005 was 1.65 /100,000 pers...
British Journal of Clinical Pharmacology, 2014
Oral contraceptive use influences the risk for certain cancers. However, few studies have examine... more Oral contraceptive use influences the risk for certain cancers. However, few studies have examined any link with risk of central nervous system tumours. We investigated the association between hormonal contraceptive use and glioma risk among premenopausal women in a population-based setting. Using national administrative and health registries in Denmark to conduct a nationwide case-control study, we identified all women ages 15 to 49 years with a first time diagnosis of histologically verified glioma between 2000 and 2009. Each case was age-matched to eight population controls using risk set sampling. Based on prescription data, exposure until 2 years prior to the index date was categorized according to hormonal contraceptive type, i.e. combined oestrogen-progestagen or progestagen only, and duration of use (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1, 1 to &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5, ≥5 years). We used conditional logistic regression to compute odds ratios (ORs) with 95% confidence intervals (CIs) for glioma associated with hormonal contraceptive use, adjusting for potential confounders. We identified 317 cases and 2126 controls. Ever use of hormonal contraceptive was associated with an OR of 1.5 (95% CI 1.2, 2.0) and the OR increased with duration of use (long term, ≥5 years: OR 1.9; 95% CI 1.2, 2.9). The association between long term hormonal contraceptive use and glioma risk was most pronounced for progestagen only therapy (OR 2.4; 95% CI 1.1, 5.1), especially when this regimen constituted the sole hormonal contraceptive therapy (OR 4.1; 95% CI 0.8, 20.8). Long term hormonal contraceptive use may increase the risk of glioma.
Cancer Epidemiology, 2014
While some studies indicate a potential chemopreventive effect of statin use on the risk of gliom... more While some studies indicate a potential chemopreventive effect of statin use on the risk of glioma, the effect of statins on the prognosis of brain tumours has not yet been examined. We thus conducted a cohort study evaluating the influence of statin use on survival in patients with glioblastoma multiforme (GBM). We identified 1562 patients diagnosed with GBM during 2000-2009 from the Danish Cancer Registry and linked this cohort to Danish nationwide demographic and health registries. Within the GBM cohort, each patient recorded as using statins prior to diagnosis (defined as ≥ 2 redeemed prescriptions) was matched to two statin non-users (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2 redeemed prescriptions) by propensity scores based on age, gender, year of diagnosis, comorbidity, and use of selected drugs. Cox proportional hazard models were used to compute hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause death associated with prediagnostic statin use. A total of 339 GBM patients were included in the analyses. Of these, 325 died during median follow-up of 6.9 months (interquartile range: 3.8-13.4 months). Prediagnostic statin use was associated with a reduced HR of death (0.79; 95% CI: 0.63-1.00). The HRs decreased with increasing duration or intensity of prediagnostic statin use [long-term (≥ 5 years) statin use: HR 0.75 (95% CI: 0.47-1.20); high-intensity statin use: HR 0.66 (95% CI: 0.44-0.98)]. Additional adjustment for oncotherapeutic modalities yielded similar results (overall HR 0.80, 95% CI: 0.63-1.01). Long-term prediagnostic statin use may improve survival following GBM.
Twin Research, 2003
S troke is one of the leading causes of severe disability and death in the world. In the present ... more S troke is one of the leading causes of severe disability and death in the world. In the present article we outline possibilities and limitations for future stroke research within the GenomEUtwin. The combined sample of twins born before 1958 from Denmark, Finland, and Sweden, and available for follow-up into the second millennium for non-fatal and fatal stroke events through national inpatient and death registers exceeds 70,000 twin pairs. This sample size will enable the study of genetic influences on stroke and major stroke subtypes. Large samples of twins in GenomEUtwin have been followed up repeatedly through interviews and questionnaires concerning a variety of exposures and potential risk factors for stroke. We briefly outline how this information can be combined with the health register information for epidemiologic and genetic epidemiologic studies of stroke. We also present the number of twin pairs concordant and discordant for stroke in Denmark, Finland and Sweden, and time lags between events for twins concordant for stroke. This information illustrates that the number of affected sib pairs for linkage studies is relatively limited, but the sample sizes are promising for association studies.
Stroke, 2003
Background and Purpose-Subarachnoid hemorrhage (SAH) is the only type of stroke with female predo... more Background and Purpose-Subarachnoid hemorrhage (SAH) is the only type of stroke with female predominance, suggesting that reproductive factors may play a role in the etiology. We conducted a population-based study to examine the influence of parity on the risk of SAH in women. Methods-We linked data from 3 national Swedish registries to identify first-ever hospitalizations for SAH in a cohort of women followed up since first childbirth during 1973-1997. Within this cohort, we conducted a nested case-control study and estimated the odds ratio (OR) and 95% CI of SAH by parity adjusted for age, calendar period, and length of follow-up. Information on smoking habits before the subject's first childbirth was available in a subset of the data (women with first childbirths during 1982-1997).
Pharmacoepidemiology and Drug Safety, 1996
Spontaneous reporting systems (SRS) have been established to monitor drug safety problems after m... more Spontaneous reporting systems (SRS) have been established to monitor drug safety problems after marketing, especially rare, but serious adverse drug reactions (ADRs). Among these are the skin disorders erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The purpose of this study has been to evaluate the data on these serious skin disorders available in a SRS. All reports concerning these diseases submitted to the Danish Committee on ADRs during the period 1968 to 1991 were reviewed according to predefined criteria. Information was often scarce, and the diagnosis of the reporter had to be accepted at face value in 28% of cases. Two hundred cases of EM, 74 of SJS and 29 of TEN were identified. More than 60% of cases were hospitalized. The diseases had a fatal outcome in six patients with TEN, three with SJS and a single patient suffering from EM.
Pharmacoepidemiology and Drug Safety, 2013
The Health Improvement Network (THIN) is a UK healthcare database composed of computerized inform... more The Health Improvement Network (THIN) is a UK healthcare database composed of computerized information from primary care physicians (PCPs). We analyzed the validity of our method for identifying cases of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) within THIN and assessed the incidence of these events. Patients aged 20-89 years were identified and followed until (i) ICH or SAH was detected, (ii) the patient reached 90 years old (iii) death, or (iv) the end of the study. Computerized patient profiles were reviewed manually; those not discarded became potential cases. A validation study was undertaken in 400 computer-detected cases (333 confirmed as potential cases; 67 discarded). PCPs completed a questionnaire to determine the actual incidence of ICH and SAH among these cases. We also assessed the incidence of ICH and SAH in the total cohort. A total of 4330 patients with a READ code suggesting hemorrhagic stroke were identified. Computerized profiles with free-text comments were reviewed manually to identify 3633 potential cases. Responses to the PCP questionnaire were received for 306 potential cases and 63 discarded cases (92% response rate); 82% of potential cases were confirmed. Finally, we identified 3137 cases of hemorrhagic stroke. Crude incidence was 15 per 100,000 person-years for ICH and 11 per 100,000 person-years for SAH; the overall incidence increased sharply with age. Computer detection of cases of hemorrhagic stroke in THIN followed by manual review of clinical profiles is a valid method. The incidence of hemorrhagic stroke increases sharply with age.
Neuroepidemiology, 2011
We validated a new method of identifying patients with incident myasthenia in automated Danish re... more We validated a new method of identifying patients with incident myasthenia in automated Danish registers for the purpose of conducting epidemiological studies of the disorder. For residents of a Danish county (population 484,862) in 1993-2008, we identified any hospital contacts coded for myasthenia in a nationwide patient register and any prescriptions for pyridostigmine in the county prescription register. Results from an acetylcholine receptor antibody register were linked to the data. We verified the diagnosis by a review of medical records. Subjects identified in the Patient Register (n = 83) were comparable with individuals found in the Prescription Register (n = 89) with regard to age and gender, but were more often seropositive (83.1 vs. 74.2%). Seropositivity increased to 91.6% by restricting the data to individuals recorded in both Patient and Prescription Registers (n = 71). We found that for subjects identified in both Patient and Prescription Registers the positive predictive value of the register diagnosis was 92.9% (95% confidence interval, CI, 84.3-97.7), the false-positive rate was low (2.8%), and the sensitivity was acceptable (81.2%; 95% CI 71.2-88.8). Our data indicate that this novel approach of combining diagnosis register and prescription register information provides a feasible and valid method to trace incident myasthenia patients for population-based epidemiological studies.
Neuroepidemiology, 2005
Seasonal variation in the occurrence of cerebrovascular disease has been reported, but data about... more Seasonal variation in the occurrence of cerebrovascular disease has been reported, but data about subarachnoid hemorrhage (SAH) are few and inconclusive. We conducted a nationwide population-based study in Denmark to examine any seasonal pattern of hospitalization and case fatality of SAH. We identified 9,367 patients with SAH and found a modest indication of overall seasonal variation for the risk of hospitalization with this diagnosis. The seasonal pattern, with the highest incidence in January and the nadir in July, was mostly apparent for subjects aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;65 years (peak-to-trough ratio = 1.18; 95% CI 1.04-1.32). There was little difference by sex. The overall 30-day case fatality rate was 38% and showed less seasonal variation. We found evidence of weak seasonal variation in hospitalization for SAH and almost no seasonal variation in a 30-day case fatality rate after SAH.
Therapeutic Drug Monitoring, 1997
Theophylline is predominantly metabolized by cytochrome P4501A2 (CYP1A2). A possible interaction ... more Theophylline is predominantly metabolized by cytochrome P4501A2 (CYP1A2). A possible interaction between griseofulvin and theophylline was reported to our laboratory, which led us to form the hypothesis that griseofulvin induces the metabolism of theophylline. One purpose of this study was to investigate this hypothesis. The study was carried out as a randomized crossover study of 12 healthy volunteers. In period A of the study, each volunteer received a single dose of 300 mg theophylline ethylenediamine orally. In period B, the subjects took fluvoxamine, 50 mg for 1 day and 100 mg for 6 days, and on day 4, the subjects ingested 300 mg theophylline ethylenediamine. Fluvoxamine is a potent inhibitor of CYP1A2, and period B was included as a positive control. In period C, the subjects took 500 mg griseofulvin for 9 days; on day 8 the subjects again ingested 300 mg theophylline ethylenediamine. Theophylline and its metabolites (1-methyluric acid [IMU], 3-methylxanthine [3MX], and 1,3-dimethyluric acid [13DMU]) in plasma and urine were assayed by high-performance liquid chromatography. During fluvoxamine intake, the median of the total clearance of theophylline decreased from 80 ml/min to 24 ml/min, and the half-life increased from 6.6 to 22 h. The partial formation clearances of the metabolites decreased from 17 to 1.7 ml/min, from 8.9 to 0.9 ml/min, and from 21 to 6.8 ml/min for 1MU, 3MX, and 13DMU, respectively. The results confirm that assessment of theophylline metabolism indeed serves as a biomarker for CYP1A2. During griseofulvin ingestion, the median of the total and partial clearances of theophylline were 84 ml/min, 22 ml/min (1MU), 9.4 ml/min (3MX), and 25 ml/min (13DMU). The half-life decreased significantly from 6.6 to 5.7 h. The increase in partial formation clearances of 1MU and 13DMU, but not of 3MX, were statistically significant. The increase in the total clearance reached only borderline significance. In four subjects a marked induction was seen for all pharmacokinetic parameters, suggesting that the susceptibility to induction is more pronounced in some subjects. This susceptibility could theoretically be explained by a polymorphism in the inducibility of the gene coding for the CYP1A2 enzyme.
Scandinavian Journal of Gastroenterology, 1994
Ugeskrift For Laeger, Nov 1, 2010
The objective of this study was to determine whether the incidence rate of Guillain-Barré syndrom... more The objective of this study was to determine whether the incidence rate of Guillain-Barré syndrome (GBS) in Funen County, Denmark, increased during the 1996-2005 period. Cases of GBS were identified retrospectively using hospital discharge diagnoses from the neurological department, Odense University Hospital, between 1996 and 2005. Hospital record data were evaluated and patients were included if they fulfilled the criteria of the National Institute of Neurological and Communicative Disorders and Stroke for GBS or the criteria for Miller Fisher syndrome (MFS). The study period was divided into two five-year intervals, 1996-2000 and 2001-2005, which were compared with regard to incidence rate. The incidence rate was 1.57/100,000 person-years in 1996-2000 and 1.73/100,000 person-years in 2001-2005. The increase in the incidence rate was 0.17/100,000 person-years (95% confidence interval (CI): -0.65-0.98). The crude incidence rate for the entire period 1996-2005 was 1.65 /100,000 person-years. An antecedent infection was reported in 56% of the cases including respiratory infection (25%), gastrointestinal infection (21%) and influenza-like symptoms (10%). There was no significant difference in preceding events between 1996-2000 and 2001-2005 (p = 0.47). There was no significant change in the incidence rate of GBS during the study period. There was no clustering in time or by antecedent event. Our finding of an incidence rate of 1.65/100,000 person-years is in line with previously published studies.
Ugeskrift For Laeger, 2010
Dmb Danish Medical Bulletin, Sep 1, 1997
The extensive computerisation of Danish pharmacies has permitted the establishment of two large p... more The extensive computerisation of Danish pharmacies has permitted the establishment of two large prescription registries: The Odense University Pharmacoepidemiological Database (OPED) and the Pharmacoepidemiological Prescription Database of North Jutland (PDNJ). The Danish prescription registries content, coverage, completeness and the quality of the data are discussed in this article. Furthermore, conditions for access to the data are presented. The two prescription registries cover a background population of approximately one million or 18% of the Danish population. The populations covered by the registries are stable and representative of the Danish population in general. The registries cover all reimbursed medicine at the level of the individual user. Registration of a unique and permanent personal identifier enables the compilation of longitudinal drug histories and allows the linking of prescription data to other population-based Danish registries. The degree of completeness of the Danish prescription registries is excellent for reimbursed prescription drugs. A small number of comparison studies also indicate high validity of the register information. The Danish prescription registries represent a useful new data source for pharmacoepidemiological studies.
Thrombosis and haemostasis, Jan 2, 2015
The study objective was to investigate the relationship between use of antithrombotic drugs and s... more The study objective was to investigate the relationship between use of antithrombotic drugs and subarachnoid haemorrhage (SAH). We identified patients discharged from Danish neurosurgery units with a first-ever SAH diagnosis in 2000 to 2012 (n=5,834). For each case, we selected 40 age-, sex- and period-matched population controls. Conditional logistic regression models were used to estimate odds ratios (aOR), adjusted for comorbidity, education level, and income. Low-dose aspirin (ASA) use for < 1 month was associated with an increased risk of SAH (aOR 1.75, 95 % confidence interval [CI] 1.28-2.40). This aOR decreased to 1.26 (95 %CI: 0.98-1.63) with 2-3 months of ASA use, and approached unity with use for more than three months (1.11, 95 %CI 0.97-1.27). Analyses with first-time users confirmed this pattern, which was also observed for clopidogrel. ASA treatment for three or more years was associated with an aOR of SAH of 1.13 (95 %CI: 0.86-1.49). Short-term use (< 1 month) of...
Thrombosis and Haemostasis
The study objective was to investigate the relationship between use of antithrombotic drugs and s... more The study objective was to investigate the relationship between use of antithrombotic drugs and subarachnoid haemorrhage (SAH). We identified patients discharged from Danish neurosurgery units with a first-ever SAH diagnosis in 2000 to 2012 (n=5,834). For each case, we selected 40 age-, sex- and period-matched population controls. Conditional logistic regression models were used to estimate odds ratios (aOR), adjusted for comorbidity, education level, and income. Low-dose aspirin (ASA) use for < 1 month was associated with an increased risk of SAH (aOR 1.75, 95 % confidence interval [CI] 1.28-2.40). This aOR decreased to 1.26 (95 %CI: 0.98-1.63) with 2-3 months of ASA use, and approached unity with use for more than three months (1.11, 95 %CI 0.97-1.27). Analyses with first-time users confirmed this pattern, which was also observed for clopidogrel. ASA treatment for three or more years was associated with an aOR of SAH of 1.13 (95 %CI: 0.86-1.49). Short-term use (< 1 month) of...
British journal of cancer, Jan 19, 2013
Few studies have examined the association between use of aspirin or other non-steroidal anti-infl... more Few studies have examined the association between use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and risk of glioma and the results have been equivocal. We therefore investigated the influence of NSAID use on glioma risk in a nationwide setting. We used national registries in Denmark to identify all patients aged 20-85 years with a first diagnosis of histologically verified glioma during 2000-2009. Each case was matched on birth year and sex to eight population controls using risk-set sampling. We used prescription data to assess NSAID use and classified exposure to low-dose aspirin or non-aspirin (NA) NSAIDs into ever use or long-term use, defined as continuous use for 5 years. Conditional logistic regression was used to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with NSAID use, adjusted for potential confounders. A total of 2688 glioma cases and 18,848 population controls were included in the study. Ever use of low...
Neuroepidemiology, 2014
We wished to examine the impact of antiplatelet drug discontinuation on recurrent stroke and all-... more We wished to examine the impact of antiplatelet drug discontinuation on recurrent stroke and all-cause mortality. We identified a cohort of incident ischaemic stroke patients in a Danish stroke registry, 2007-2011. Using population-based registries we assessed subjects' drug use and followed them up for stroke recurrence, or all-cause death. Person-time was classified by antiplatelet drug use into current use, recent use (≤150 days after last use), and non-use (>150 days after last use). Lipid-lowering drug (LLD) use was classified by the same rules. We used Cox proportional hazard models to calculate the adjusted hazard ratio (HR) and corresponding 95% confidence intervals (CIs) for the risk of recurrent stroke or death associated with discontinuation of antiplatelet or LLD drugs. Among 4,670 stroke patients followed up for up a median of 1.5 years, 237 experienced a second stroke and 600 died. Compared with current antiplatelet drug use, both recent use (1.3 (0.8-2.0)), and...
Ugeskrift for laeger, Jan 8, 2010
The objective of this study was to determine whether the incidence rate of Guillain-Barré syndrom... more The objective of this study was to determine whether the incidence rate of Guillain-Barré syndrome (GBS) in Funen County, Denmark, increased during the 1996-2005 period. Cases of GBS were identified retrospectively using hospital discharge diagnoses from the neurological department, Odense University Hospital, between 1996 and 2005. Hospital record data were evaluated and patients were included if they fulfilled the criteria of the National Institute of Neurological and Communicative Disorders and Stroke for GBS or the criteria for Miller Fisher syndrome (MFS). The study period was divided into two five-year intervals, 1996-2000 and 2001-2005, which were compared with regard to incidence rate. The incidence rate was 1.57/100,000 person-years in 1996-2000 and 1.73/100,000 person-years in 2001-2005. The increase in the incidence rate was 0.17/100,000 person-years (95% confidence interval (CI): -0.65-0.98). The crude incidence rate for the entire period 1996-2005 was 1.65 /100,000 pers...
British Journal of Clinical Pharmacology, 2014
Oral contraceptive use influences the risk for certain cancers. However, few studies have examine... more Oral contraceptive use influences the risk for certain cancers. However, few studies have examined any link with risk of central nervous system tumours. We investigated the association between hormonal contraceptive use and glioma risk among premenopausal women in a population-based setting. Using national administrative and health registries in Denmark to conduct a nationwide case-control study, we identified all women ages 15 to 49 years with a first time diagnosis of histologically verified glioma between 2000 and 2009. Each case was age-matched to eight population controls using risk set sampling. Based on prescription data, exposure until 2 years prior to the index date was categorized according to hormonal contraceptive type, i.e. combined oestrogen-progestagen or progestagen only, and duration of use (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1, 1 to &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5, ≥5 years). We used conditional logistic regression to compute odds ratios (ORs) with 95% confidence intervals (CIs) for glioma associated with hormonal contraceptive use, adjusting for potential confounders. We identified 317 cases and 2126 controls. Ever use of hormonal contraceptive was associated with an OR of 1.5 (95% CI 1.2, 2.0) and the OR increased with duration of use (long term, ≥5 years: OR 1.9; 95% CI 1.2, 2.9). The association between long term hormonal contraceptive use and glioma risk was most pronounced for progestagen only therapy (OR 2.4; 95% CI 1.1, 5.1), especially when this regimen constituted the sole hormonal contraceptive therapy (OR 4.1; 95% CI 0.8, 20.8). Long term hormonal contraceptive use may increase the risk of glioma.
Cancer Epidemiology, 2014
While some studies indicate a potential chemopreventive effect of statin use on the risk of gliom... more While some studies indicate a potential chemopreventive effect of statin use on the risk of glioma, the effect of statins on the prognosis of brain tumours has not yet been examined. We thus conducted a cohort study evaluating the influence of statin use on survival in patients with glioblastoma multiforme (GBM). We identified 1562 patients diagnosed with GBM during 2000-2009 from the Danish Cancer Registry and linked this cohort to Danish nationwide demographic and health registries. Within the GBM cohort, each patient recorded as using statins prior to diagnosis (defined as ≥ 2 redeemed prescriptions) was matched to two statin non-users (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2 redeemed prescriptions) by propensity scores based on age, gender, year of diagnosis, comorbidity, and use of selected drugs. Cox proportional hazard models were used to compute hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause death associated with prediagnostic statin use. A total of 339 GBM patients were included in the analyses. Of these, 325 died during median follow-up of 6.9 months (interquartile range: 3.8-13.4 months). Prediagnostic statin use was associated with a reduced HR of death (0.79; 95% CI: 0.63-1.00). The HRs decreased with increasing duration or intensity of prediagnostic statin use [long-term (≥ 5 years) statin use: HR 0.75 (95% CI: 0.47-1.20); high-intensity statin use: HR 0.66 (95% CI: 0.44-0.98)]. Additional adjustment for oncotherapeutic modalities yielded similar results (overall HR 0.80, 95% CI: 0.63-1.01). Long-term prediagnostic statin use may improve survival following GBM.
Twin Research, 2003
S troke is one of the leading causes of severe disability and death in the world. In the present ... more S troke is one of the leading causes of severe disability and death in the world. In the present article we outline possibilities and limitations for future stroke research within the GenomEUtwin. The combined sample of twins born before 1958 from Denmark, Finland, and Sweden, and available for follow-up into the second millennium for non-fatal and fatal stroke events through national inpatient and death registers exceeds 70,000 twin pairs. This sample size will enable the study of genetic influences on stroke and major stroke subtypes. Large samples of twins in GenomEUtwin have been followed up repeatedly through interviews and questionnaires concerning a variety of exposures and potential risk factors for stroke. We briefly outline how this information can be combined with the health register information for epidemiologic and genetic epidemiologic studies of stroke. We also present the number of twin pairs concordant and discordant for stroke in Denmark, Finland and Sweden, and time lags between events for twins concordant for stroke. This information illustrates that the number of affected sib pairs for linkage studies is relatively limited, but the sample sizes are promising for association studies.
Stroke, 2003
Background and Purpose-Subarachnoid hemorrhage (SAH) is the only type of stroke with female predo... more Background and Purpose-Subarachnoid hemorrhage (SAH) is the only type of stroke with female predominance, suggesting that reproductive factors may play a role in the etiology. We conducted a population-based study to examine the influence of parity on the risk of SAH in women. Methods-We linked data from 3 national Swedish registries to identify first-ever hospitalizations for SAH in a cohort of women followed up since first childbirth during 1973-1997. Within this cohort, we conducted a nested case-control study and estimated the odds ratio (OR) and 95% CI of SAH by parity adjusted for age, calendar period, and length of follow-up. Information on smoking habits before the subject's first childbirth was available in a subset of the data (women with first childbirths during 1982-1997).
Pharmacoepidemiology and Drug Safety, 1996
Spontaneous reporting systems (SRS) have been established to monitor drug safety problems after m... more Spontaneous reporting systems (SRS) have been established to monitor drug safety problems after marketing, especially rare, but serious adverse drug reactions (ADRs). Among these are the skin disorders erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The purpose of this study has been to evaluate the data on these serious skin disorders available in a SRS. All reports concerning these diseases submitted to the Danish Committee on ADRs during the period 1968 to 1991 were reviewed according to predefined criteria. Information was often scarce, and the diagnosis of the reporter had to be accepted at face value in 28% of cases. Two hundred cases of EM, 74 of SJS and 29 of TEN were identified. More than 60% of cases were hospitalized. The diseases had a fatal outcome in six patients with TEN, three with SJS and a single patient suffering from EM.
Pharmacoepidemiology and Drug Safety, 2013
The Health Improvement Network (THIN) is a UK healthcare database composed of computerized inform... more The Health Improvement Network (THIN) is a UK healthcare database composed of computerized information from primary care physicians (PCPs). We analyzed the validity of our method for identifying cases of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) within THIN and assessed the incidence of these events. Patients aged 20-89 years were identified and followed until (i) ICH or SAH was detected, (ii) the patient reached 90 years old (iii) death, or (iv) the end of the study. Computerized patient profiles were reviewed manually; those not discarded became potential cases. A validation study was undertaken in 400 computer-detected cases (333 confirmed as potential cases; 67 discarded). PCPs completed a questionnaire to determine the actual incidence of ICH and SAH among these cases. We also assessed the incidence of ICH and SAH in the total cohort. A total of 4330 patients with a READ code suggesting hemorrhagic stroke were identified. Computerized profiles with free-text comments were reviewed manually to identify 3633 potential cases. Responses to the PCP questionnaire were received for 306 potential cases and 63 discarded cases (92% response rate); 82% of potential cases were confirmed. Finally, we identified 3137 cases of hemorrhagic stroke. Crude incidence was 15 per 100,000 person-years for ICH and 11 per 100,000 person-years for SAH; the overall incidence increased sharply with age. Computer detection of cases of hemorrhagic stroke in THIN followed by manual review of clinical profiles is a valid method. The incidence of hemorrhagic stroke increases sharply with age.
Neuroepidemiology, 2011
We validated a new method of identifying patients with incident myasthenia in automated Danish re... more We validated a new method of identifying patients with incident myasthenia in automated Danish registers for the purpose of conducting epidemiological studies of the disorder. For residents of a Danish county (population 484,862) in 1993-2008, we identified any hospital contacts coded for myasthenia in a nationwide patient register and any prescriptions for pyridostigmine in the county prescription register. Results from an acetylcholine receptor antibody register were linked to the data. We verified the diagnosis by a review of medical records. Subjects identified in the Patient Register (n = 83) were comparable with individuals found in the Prescription Register (n = 89) with regard to age and gender, but were more often seropositive (83.1 vs. 74.2%). Seropositivity increased to 91.6% by restricting the data to individuals recorded in both Patient and Prescription Registers (n = 71). We found that for subjects identified in both Patient and Prescription Registers the positive predictive value of the register diagnosis was 92.9% (95% confidence interval, CI, 84.3-97.7), the false-positive rate was low (2.8%), and the sensitivity was acceptable (81.2%; 95% CI 71.2-88.8). Our data indicate that this novel approach of combining diagnosis register and prescription register information provides a feasible and valid method to trace incident myasthenia patients for population-based epidemiological studies.
Neuroepidemiology, 2005
Seasonal variation in the occurrence of cerebrovascular disease has been reported, but data about... more Seasonal variation in the occurrence of cerebrovascular disease has been reported, but data about subarachnoid hemorrhage (SAH) are few and inconclusive. We conducted a nationwide population-based study in Denmark to examine any seasonal pattern of hospitalization and case fatality of SAH. We identified 9,367 patients with SAH and found a modest indication of overall seasonal variation for the risk of hospitalization with this diagnosis. The seasonal pattern, with the highest incidence in January and the nadir in July, was mostly apparent for subjects aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;65 years (peak-to-trough ratio = 1.18; 95% CI 1.04-1.32). There was little difference by sex. The overall 30-day case fatality rate was 38% and showed less seasonal variation. We found evidence of weak seasonal variation in hospitalization for SAH and almost no seasonal variation in a 30-day case fatality rate after SAH.