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Biomedical subjects

D Gaist

Publications and source records attributed to D Gaist.

At least 19 recordsLinked to original sources

Early exposure to smoking and future fecundity among Danish twins.

Several studies have examined the effect of in utero exposure to smoking and fecundity among the offspring but the findings are contradictory. We therefore studied the waiting time to first pregnancy (TTP) and exposure to smoking in utero and childhood among Danish twins born between 1931 and 1952. Information about TTP, exposure to mothers smoking in pregnancy, exposure to smoking in childhood and current smoking among the male twins and smoking in their own pregnancy among female twins was collected by interview. Fecundability odds ratio (FOR) estimating the odds of conception in a cycle among exposed compared to the unexposed were calculated separately for female and male twins. A total of 1653 female and 1598 male twins reported a TTP. Female twins, exposed in utero, had reduced fecundability after control for confounders (FOR = 0.81; 95% CI 0.67-0.99). A nonsignificant increase in fecundity among male twins exposed to smoking in utero was found (FOR = 1.12; 95% CI 0.89-1.40). Among dizygotic twins of opposite sex sharing the same in utero exposures, the future fecundity of the male twin was unaffected by in utero exposure (FOR = 0.97; 95% CI 0.60-1.55) whereas the female twin had reduced fecundity (FOR = 0.65; 95% CI 0.47-0.91). This study supports that smoking is hazardous to the female fetus not only in the short term but also affects her future ability to conceive and makes it even more important to advise pregnant women to stop smoking.

Adult↗

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. MATERIALS AND METHODS: We retrieved prescription data from Odense University Pharmacoepidemiological Database, in Funen County, Denmark (population in 2002: 472,869). Within each calendar year we estimated period prevalence, incidence rate and monotherapy rate. Based on co-medication we defined 'epilepsy' when only AEDs were prescribed, 'pain' with co-prescription of opioids, and 'mood disorder' with co-prescription of antipsychotics or antidepressants. RESULTS: We identified 15,604 AED users. The prevalence of using AED increased from 9.3 (95% CI, 9-9.5) to 12.1 (11.8-12.4)/1000 persons. The incidence rate increased from 1.4 (1.3-1.6) to 1.7 (1.6-1.9)/1000 personyears. The monotherapy rate was 79-82%. AED use for 'epilepsy' declined by 19.7%, whereas the proportion of 'pain' and 'mood disorder' treatment increased by 11.2% and 8.4% respectively. CONCLUSIONS: Antiepileptic drug utilization increased during the study period, the increase probably caused by expanding use in areas other than epilepsy.

Adolescent↗

Long-term effects of migraine on cognitive function: a population-based study of Danish twins.

OBJECTIVE: To investigate the cognitive functioning of migraineurs vs nonmigraineurs in a large population-based sample of middle-aged twins where headache diagnoses were established by neurologists. METHODS: Twins identified through the population-based Danish Twin Registry participated in face-to-face structured interviews, which included cognitive tests and two previously validated questions screening for migraine. Twins who screened positive for migraine and their co-twins were invited to participate in a telephone-based interview conducted by neurologists, who established headache diagnoses according to the International Headache Society criteria. Cognitive scores on fluency, digit span, delayed word recall, and symbol digit substitution test were compared between migraineurs and nonmigraineurs. Comparisons within monozygotic and dizygotic same sex twin pairs discordant for migraine were also performed. RESULTS: Of the 1,789 twins who were eligible for inclusion in the present study, 1,393 (77.8%) were interviewed. A diagnosis of migraine was established in 536 twins (migraine without aura n = 347; migraine with aura n = 157). Average scores on cognitive tests in twins with migraine or one of the migraine subtypes did not differ from those of nonmigraineurs in any of the tests. Comparisons within twin pairs discordant for migraine produced highly comparable results. Adjustment for possible confounders and stratification by cumulated number of lifetime attacks did not influence the results. CONCLUSIONS: A lifetime diagnosis of migraine was not associated with cognitive deficits in middle-aged subjects.

Aged↗

Appendicectomy has no beneficial effect on admission rates in patients with ulcerative colitis.

BACKGROUND AND AIMS: Those who have had an appendicectomy have a reduced risk of developing ulcerative colitis. However, the effect of appendicectomy on disease activity in patients with ulcerative colitis has not been established. METHODS: We used the Danish National Patient Registry to identify all incident cases of ulcerative colitis in Denmark during the period 1981 to 1999. Of these, 202 had an appendicectomy after their first admission with ulcerative colitis. In these patients, we compared the incidence rate of hospitalisations with ulcerative colitis as first diagnosis during the period between the onset of ulcerative colitis and appendicectomy, with the rate of such hospitalisations after appendicectomy. To adjust for the clinical course of ulcerative colitis unrelated to appendicectomy, we extracted a reference cohort (n = 808), matched to the index subjects with respect to age, sex, and year of first admission, but with an intact appendix. RESULTS: The rate of admission with ulcerative colitis as first diagnosis decreased by 47% after appendicectomy (rate ratio 0.53 (95% confidence interval (CI) 0.36-0.80)). However, the reference cohort showed a similar decline in admission rate (rate ratio 0.51). Thus appendicectomy had no apparent beneficial effect on admission rate after adjustment for the clinical course of disease unrelated to appendicectomy (adjusted rate ratio 1.05 (95% CI 0.67-1.67)). CONCLUSIONS: Appendicectomy had no significant beneficial effect on admission rates in patients with ulcerative colitis.

Adult↗

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↗

Frequency and heritability of depression symptomatology in the second half of life: evidence from Danish twins over 45.

BACKGROUND: Self-reported depressive symptoms among the elderly have generated considerable interest because they are readily available measures of overall well-being in a population often thought to be at special risk for mental disorder. METHOD: The heritability of depression symptoms was investigated in a sample of 2169 pairs of Danish twins (1033 MZ and 1136 same sex DZ) ranging in age from 45 to over 95. Twins completed an interview assessment that identified symptoms of depression, which were scored on Affective, Somatic and Total scales. RESULTS: Overall heritability estimates (a2) for the Affective (a2 = 0.27, (95% CI 0.22-0.32)). Somatic (a2 = 0.26, (0.21-0.32)), and Total (a2 = 0.29, (0.22-0.34)) scales were all moderate, statistically significant and similar to results from other studies. To assess possible variations in heritability across the wide age span, the sample was stratified into age groups in increments of 10 years. The magnitude of heritable influence did not vary significantly with age or sex. Somatic scale heritability tended to be greater for females than for males, though this difference was not statistically significant. The genetic correlation between the Affective and Somatic scales was 0.71, suggesting substantial common genetic origins. CONCLUSIONS: Though the frequency of self-reported depressive symptoms increased with age in this sample, their heritability did not.

Aged↗

Association of mutations in the hemochromatosis gene with shorter life expectancy.

BACKGROUND: To investigate whether the frequency of carriers of mutations in the HFE gene associated with hereditary hemochromatosis diminishes with age as an indication that HFE mutations are associated with increased mortality. It is of value in the debate concerning screening for hereditary hemochromatosis to determine the significance of heterozygosity. METHODS: Genotyping for mutations in exons 2 and 4 of the HFE gene using denaturing gradient gel electrophoresis in 1784 participants aged 45 to 100 years from 4 population-based studies: all 183 centenarians from the Danish Centenarian Study, 601 people aged 92 to 93 years from the Danish 1905 Cohort, 400 aged 70 to 94 years from the Longitudinal Study of Aging Danish Twins, and 600 aged 45 to 67 years from a study of middle-aged Danish twins. RESULTS: All participants (N=1784) were screened for mutations in exon 4, and a trend toward fewer heterozygotes for the C282Y mutation-the mutation most often associated with hereditary hemochromatosis-was found. This was significant for the whole population (P=.005) and for women (P=.004) but not for men (P=.26). A group of 599 participants was screened for mutations in exon 2, and there was no variation in the distribution of mutations in exon 2 in the different age groups. CONCLUSIONS: In a high-carrier frequency population like Denmark, mutations in HFE show an age-related reduction in the frequency of heterozygotes for C282Y, which suggests that carrier status is associated with shorter life expectancy.

Age Distribution↗

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↗

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↗

Diagnostic yield by testing small fiber function in patients examined for polyneuropathy.

We assessed the diagnostic yield of adding quantitative sensory testing to the standard work-up for polyneuropathy in unselected patients. All patients aged 18 to 70 years referred to our department for electrodiagnosis with a tentative diagnosis of polyneuropathy and symptoms complying with predefined criteria were included in the study. We performed near nerve conduction studies in 4 nerves and determined heat and cold detection thresholds on hand and foot with a Thermotest (Somedic AB, Sweden). In order to uncover CNS diseases, somatosensory-evoked potentials were recorded in patients with abnormal quantitative sensory testing and normal nerve conduction studies. A total of 198 patients completed the study and 149 were considered to have polyneuropathy. Twenty-five patients remained undiagnosed and in 24 patients, other diseases were responsible for the symptoms. Of the patients with either polyneuropathy or no other diagnosis, 76% (n = 174) had abnormal nerve conduction. Abnormal cold sensation, heat sensation or abnormality in at least 1 of these and normal nerve conduction were found in 14, 12 and 17 patients. Of the 174 patients, 86% (95% CI 80-90%) had an abnormality in at least 1 of the tests (i.e. abnormal nerve conduction and/or abnormal quantitative testing of temperature sensation). In conclusion, quantitative testing of temperature sensation improves the diagnostic yield in patients examined for chronic polyneuropathy.

Adult↗

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. DESIGN: A cross-sectional survey of all Danes born in 1905 (92-93 years of age), carried out August to October 1998. SETTING: Participants' homes. PARTICIPANTS: Two thousand two hundred and sixty-two nonagenarians, corresponding to a participation rate of 63% (of these, 20% participated by proxy). MEASUREMENTS: Activities of daily living (ADLs) and self-rated health were assessed by interview. Five items from Katz's ADLs (bathing, dressing, transfer, toileting, and eating) were used to construct a three-level five-item ADL scale (not disabled (no disabilities), moderately disabled (1-2 disabilities), severely disabled (3-5 disabilities)). From responses to a more extensive list of questions on ADLs (26 items), we identified scales of strength and agility by means of factor analysis. Furthermore, a 26-item ADL scale was made. Physical performance tests (chair stand, timed walk, lifting a 2.7 kg box, maximum grip-strength, and flexibility tests) were performed among nonproxy responders. RESULTS: According to the five-item ADL scale, 50% of the men and 41% of the women were categorized as not disabled, while 19% and 22%, respectively, were categorized as severely disabled. The five-item ADL scale correlated highly with the 26-item ADL scale (r = 0.83). The ADL scales showed moderate-to-good correlation with each other (r = 0.74-0.83), and with the physical performance tests (r = 0.31-0.58). Only 3.7% of the women and 6.3% of the men walked (normal pace) with a speed of at least 1 meter per second, which is the minimum walking speed required to cross signaled intersections in Denmark. A total of 56% considered their health to be excellent or good. Of the participants, 74% were always or almost always satisfied with their lives, even though only 45% reported that they "felt well enough to do what they wanted." The analyses showed that no single ADL item seemed to be of particular importance for how the participants rated their health. CONCLUSION: The Danish 1905 cohort survey is the largest and the only nationwide survey of a whole birth-cohort of nonagenarians. A total of 2,262 fairly nonselected nonagenarians participated. The level of both self-reported disability and functional limitations measured by physical performance tests among nonagenarians was high. Despite their lower mortality, women were more disabled than men and did not perform as well as men in the physical performance tests. Nevertheless, the majority of the participants considered their health to be good and were satisfied with their lives.

Activities of Daily Living↗

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↗

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.

Aged↗

Risk of subarachnoid haemorrhage in first degree relatives of patients with subarachnoid haemorrhage: follow up study based on national registries in Denmark.

OBJECTIVE: To estimate the risk of occurrence of subarachnoid haemorrhage in first degree relatives (parents, siblings, children) of patients with subarachnoid haemorrhage. DESIGN: Population based cohort study using data from the Danish National Discharge Registry and the Central Person Registry. SUBJECTS: Incident cases of subarachnoid haemorrhage admitted to hospital from 1977 to 1995 (9367 patients) and their first degree relatives (14 781). MAIN OUTCOME MEASURES: The incidence rate of subarachnoid haemorrhage was determined for the relatives and compared with that of the entire population, standardised for age, sex, and calendar period. This process was repeated for patients discharged from neurosurgery units, as diagnoses from these wards had high validity (93%). RESULTS: 18 patients had a total of 19 first degree relatives with subarachnoid haemorrhage during the study period, corresponding to a standardised incidence ratio of 2.9 (95% confidence interval 1.9 to 4.6). Patients discharged from neurosurgery wards had a higher standardised incidence ratio (4.5, 2.7 to 7.3). CONCLUSIONS: First degree relatives of patients with subarachnoid haemorrhage have a threefold to fivefold increased risk of subarachnoid haemorrhage compared with the general population.

Adolescent↗

Strength and anthropometric measures in identical and fraternal twins: no evidence of masculinization of females with male co-twins.

Sharing of intrauterine environment in twins of opposite sex has been hypothesized to result in masculinization of the female twin. We tested this hypothesis by comparing strength (maximum hand-grip pressure) and various anthropometric measures in a newly established survey panel comprising 4,314 middle-aged twins identified through a Danish population-based twin registry. Sex- and zygosity-specific mean values of handgrip strength, height, weight, body mass index, and waist circumference were highly comparable between fraternal twins of opposite sex and fraternal twins of same sex. Our results provide no support for the hypothesis of masculinization of female twins from opposite sex twin pairs.

Anthropometry↗

Statins and peripheral neuropathy.

Within the past 3 years seven cases of reversible peripheral neuropathy apparently caused by statins have been reported. Here we report seven additional cases associated with long-term statin therapy, in which other causes of neuropathy were thoroughly excluded. The neuropathy was in all cases axonal and with affection of both thick and thin nerve fibers. The symptoms of neuropathy persisted during an observation period lasting from 10 weeks to 1 year in four cases after statin treatment had been withdrawn. We suggest that long-term statin treatment may be associated with chronic peripheral neuropathy.

Action Potentials↗

Use and overuse of sumatriptan. Pharmacoepidemiological studies based on prescription register and interview data.

The serotonin agonist sumatriptan was marketed in Denmark in 1992 for the treatment of acute attacks of migraine and cluster headache. The clinical development program of the drug was impressive. However, knowledge of the long-term use of sumatriptan in unselected patients was lacking. Misuse of sumatriptan was reported in single patients shortly after the introduction of the drug. The aim of the present thesis was, therefore, to provide an epidemiological description of sumatriptan use with particular emphasis on overuse. The author conducted three studies, two of which were exclusively based on population-based data from a regional (Odense Pharmacoepidemiological Database) and a national (Registry of Drug Statistics, Danish Medicines Agency) prescription registry. Both registries record patient-specific information, thus enabling the conduct of longitudinal studies of drug use. The regional registry covers the county of Funen (reimbursable prescription drugs only), while the national registry records information on all prescriptions presented in the entire country. Consumption was described by means of the Defined Daily Dose (DDD) unit. One DDD of sumatriptan amounts to 100 mg orally or 6 mg subcutaneously. Subjects were classified as recipients of single or multiple prescriptions. Individuals in the latter category were characterized by the 30-day period with the most intensive dispensing of sumatriptan (peak use): low (less than 30 DDD/30 days), intermediate (30-59 DDD/30 days) and high-peak users (60 or more DDD/30 days). In 1995, 33,206 users of sumatriptan were identified in Denmark, corresponding to a 1-year period prevalence of use of 7.8 per 1,000 inhabitants (only persons aged > or = 16 years were included). A female-to-male ratio of 3.8:1 was found. Use was most common among women aged 35-54 years and was highest among 45 to 49-year-olds for both sexes. The standardized period prevalence of sumatriptan use varied regionally between the Danish counties from 6.4 to 9.6 per 1,000 inhabitants. The period prevalence of sumatriptan use in the county of Funen was highly comparable with that of the entire nation. Among the 43,389 sumatriptan users presenting prescriptions for sumatriptan in Denmark in 1994 and 1995, 507 (1.1%) and 1726 (4.0%) belonged to the high and intermediate-peak-use group, respectively. Patients belonging to these two groups were responsible for 38% of the total consumption of sumatriptan. For patients in the high-peak-use group the median span between first and last prescription was 693 days while the median quantity of sumatriptan purchased was 648 DDD. Highly comparable patterns of long-term intense sumatriptan use were found in the data from the regional registry, which covered the 27-month period after the introduction of the drug (February 1992). The register data were highly suggestive of overuse, but lacked essential information, e.g., the indication for use. A third study was therefore conducted using a combination of register and interview data. During a 14-day period, current users of sumatriptan were recruited through community pharmacies in the county of Funen. Respondents returned a signed consent form, including their unique personal identification number (CPR), allowing us to retrieve patient-specific data from the regional registry. For each respondent, all available relevant prescription data for the period 1992-96 were retrieved. Subjects were classified into high, intermediate, and low-peak-use groups according to register data from the 4-year period. The register data were used to evaluate representativity after anonymizing nonrespondent data. The response rates were 33% (7/21) in the high-peak-use group, 47% (30/64) in the intermediate-peak-use group, and 56% (196/350) in the low-peak-use group. Respondents and nonrespondents in the three groups were comparable with regard to age and use of other drugs. (ABSTRACT TRUNCATED)

Cluster Headache↗