David Gaist

Genetic and environmental influences on migraine: a twin study across six countries.

Migraine is a common neurovascular brain disorder that is manifested in recurrent episodes of disabling headache. The aim of the present study was to compare the prevalence and heritability of migraine across six of the countries that participate in GenomEUtwin project including a total number of 29,717 twin pairs. Migraine was assessed by questionnaires that differed between most countries. It was most prevalent in Danish and Dutch females (32% and 34%, respectively), whereas the lowest prevalence was found in the younger and older Finnish cohorts (13% and 10%, respectively). The estimated genetic variance (heritability) was significant and the same between sexes in all countries. Heritability ranged from 34% to 57%, with lowest estimates in Australia, and highest estimates in the older cohort of Finland, the Netherlands, and Denmark. There was some indication that part of the genetic variance was non-additive, but this was significant in Sweden only. In addition to genetic factors, environmental effects that are non-shared between members of a twin pair contributed to the liability of migraine. After migraine definitions are homogenized among the participating countries, the GenomEUtwin project will provide a powerful resource to identify the genes involved in migraine.

Predictors of mortality in 2,249 nonagenarians--the Danish 1905-Cohort Survey.

Objectives: To elucidate whether well‐known predictions of mortality are reduced or even reversed, or whether mortality is a stochastic process in the oldest old.

Statins and risk of polyneuropathy A case-control study

BackgroundSeveral 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.

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.

Functional status and self-rated health in 2,262 nonagenarians: The danish 1905 cohort survey

OBJECTIVES: To describe the functional capacity and self‐rated health of a large cohort of nonagenarians.

Selective Serotonin Reuptake Inhibitors and the Risk of Stroke A Population-Based Case-Control Study

Background and Purpose— Selective serotonin reuptake inhibitors (SSRIs) have been associated with increased risk of bleeding complications, possibly as a result of inhibition of platelet aggregation. Little is known about the risk of intracerebral hemorrhage in users of SSRIs and whether the effect on platelet aggregation reduces the risk of ischemic stroke. We used population-based data to estimate the risk of hemorrhagic and ischemic stroke in users of SSRIs. Methods— We performed a nested case-control study in Funen County (465 000 inhabitants), Denmark. All patients with a first-ever stroke discharge diagnosis in the period of 1994 to 1999 were identified, and a validated diagnosis of stroke was reached in 4765 cases. In all, 40 000 controls were randomly selected from the background population. Information on drug use for cases and controls was retrieved from a prescription registry with full coverage of the county. Odds ratios were adjusted for age, sex, calendar year, and use of other medication. To evaluate the effect of various potential confounders not recorded in the register data, we performed separate analyses on data from 2 large population-based surveys with more detailed information on risk factors. Results— Of 659 patients with hemorrhagic stroke, 21 were current users of SSRIs. The adjusted odds ratio of hemorrhagic stroke in current SSRI users compared with never users was 1.0 [95% confidence interval (CI), 0.6 to 1.6]. Of 2717 patients with ischemic stroke, 100 were current users of SSRIs, and the adjusted odds ratio of ischemic stroke in cases compared with controls was 1.1 (95% CI, 0.9 to 1.4). The survey data indicated that additional confounder control would not have led to an increase in the relative risk estimates. Conclusions— Current exposure to SSRIs is not associated with increased risk of intracerebral hemorrhage and is probably not associated with a decreased risk of ischemic stroke.

The Danish 1905 Cohort A Genetic-Epidemiological Nationwide Survey

Objectives: The authors studied nonagenarians, a rapidly growing age group whose cognitive and physical abilities have yet to be investigated systematically. Methods: All Danes born in 1905 were invited to participate in a home-based 2-hour multidimensional interview, including cognitive and physical performance tests and collection of DNA, carried out by lay interviewers. Population-based registers were used to evaluate representativeness. Results: There were 2,262 participants. A total of 1,632 (72%) gave a DNA sample. Participants and nonparticipants were highly comparable with regard to marital status, institutionalization, and hospitalization patterns, but men and rural area residents were more likely to participate. Six months after the survey began, 7.2% of the participants and 11.8% of the nonparticipants had died. Discussion: Despite the known difficulties of conducting surveys among the extremely old, it was possible to conduct a nationwide survey, including collection of DNA, among more than 2,000 fairly nonselected nonagenarians using lay interviewers.

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.

Cessation of Smoking After First-Ever Stroke A Follow-Up Study

Background and Purpose— Cessation of smoking is widely recommended in patients with stroke to reduce the risk of myocardial infarction and recurrent stroke, but little is known regarding how patients modify their smoking habits after a stroke. We used data from a prospective follow-up study to assess modification of smoking habits and to identify predictors of persistent smoking after first-ever stroke. Methods— All patients admitted to the only neurology department of Funen County (465 000 inhabitants) with first-ever stroke from August 1, 1999, to January 31, 2001, were prospectively identified. A comprehensive structured interview was completed both during hospitalization and at 6-month follow-up. The interview comprised questions on education, occupation, marital status, lifestyle, concomitant diseases, and functional disability. We estimated the relative risk of persistent smoking at follow-up using unconditional logistic regression. Results— We identified 734 patients with a first-ever stroke in the study period. One hundred three patients (14%) died in the 6-month period after their admission. A total of 511 patients (81%) who participated in the interview both on admission and at follow-up were included in the present study. Among 198 patients (38.7%) who were current smokers on admission, 43 patients (21.7%) gave up smoking within 6 months of suffering a stroke. Sex, functional status, and sociodemographic characteristics were independently associated with persistent smoking. Conclusions— Our results suggest that more efficient antismoking counseling is required to reduce the proportion of persistent smokers after stroke. This counseling should take into account the increased risk of persistent smoking in men, patients with no disability, blue-collar workers, and patients living alone.