To investigate the temporal relationships between a range of neurological diseases and affective disorders.
Data derived from linkage of the Danish Psychiatric Central Register and the Danish National Hospital Register. Seven cohorts with neurological index diagnoses and two control group diagnoses were followed for up to 21 years. The incidences of affective disorders in the different groups were compared with the control groups, using competing risks to consider the risk of affective disorder and the risk of death in the same analysis.
We found an increased incidence of affective disorders in dementia, Parkinson's disease, epilepsy, stroke and intracerebral haemorrhage compared with control groups. The association was found to be the strongest for dementia and Parkinson's disease. In hospitalized patients, with incident multiple sclerosis, the incidence of affective disorder was lower than the incidence in the control groups.
In neurological diseases there seems to be an increased incidence of affective disorders. The elevated incidence was found to be particularly high for dementia and Parkinson's disease (neurodegenerative diseases).
Treatment with some types of antidepressants has been associated with sudden cardiac death. It is unknown whether the increased risk is due to a class effect or related to specific antidepressants within drug classes. All patients in Denmark with an out-of-hospital cardiac arrest (OHCA) were identified (2001-2007). Association between treatment with specific antidepressants and OHCA was examined by conditional logistic regression in case-time-control models. We identified 19,110 patients with an OHCA; 2,913 (15.2%) were receiving antidepressant treatment at the time of OHCA, with citalopram being the most frequently used type of antidepressant (50.8%). Tricyclic antidepressants (TCAs; odds ratio (OR) = 1.69, confidence interval (CI): 1.14-2.50) and selective serotonin reuptake inhibitors (SSRIs; OR = 1.21, CI: 1.00-1.47) were both associated with comparable increases in risk of OHCA, whereas no association was found for serotonin-norepinephrine reuptake inhibitors/noradrenergic and specific serotonergic antidepressants (SNRIs/NaSSAs; OR = 1.06, CI: 0.81-1.39). The increased risks were primarily driven by: citalopram (OR = 1.29, CI: 1.02-1.63) and nortriptyline (OR = 5.14, CI: 2.17-12.2). An association between cardiac arrest and antidepressant use could be documented in both the SSRI and TCA classes of drugs.
BACKGROUND: The occurrence of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) during childhood may be influenced by factors operating in fetal life. Furthermore, childhood ALL has been suggested to be linked to patterns of infection during infancy. PURPOSE: To explore these hypotheses and other associations, we studied the impact of sibling patterns (e.g., birth order) and birth characteristics (e.g., birth weight) on the risk of childhood ALL and AML. METHODS: By linkage of records of population-based registries, a cohort of all children whose mothers were born in Denmark from April 1935 through March 1978 was established. Children who developed ALL or AML during the period from April 1968 through December 1992 were identified by linkage with the Danish Cancer Registry. Birth weights were obtained for children born during the period from January 1973 through December 1992 by linkage with the Medical Birth Registry. RESULTS: The cohort of approximately 2.0 million children was followed for the diagnosis of ALL or AML for 20.9 million person-years. A total of 704 cases of childhood ALL were identified. Among 0-4 year olds, the relative risks (RRs) of ALL for birth order positions 1, 2, 3, and 4+ were 1.00 (reference), 0.85 (95% confidence interval [CI] = 0.68-1.07), 0.91 (95% CI = 0.66-1.25), and 0.57 (95% CI = 0.30-1.06), respectively (P for trend = .09). A decreasing trend was not observed among 5-14 year olds. A significant log-linear association between birth weight and the risk of ALL was observed for both age groups. Overall, the RR of ALL increased by a factor of 1.46 (95% CI = 1.18-1.81) (P = .0005) for each kilogram of increase in birth weight. A total of 114 cases of childhood AML were identified. Children born second or later in the birth order had an increased risk of AML (RR = 1.53; 95% CI = 1.01-2.32) compared with firstborns. A particularly high risk of AML at ages 2 (RR = 2.53; 95% CI = 1.46-4.40) and 3 years was associated with having siblings compared with being an only child at those ages. Similar to the findings for ALL risk, there was a significant association between birth weight and AML risk. The relative increase in AML risk per 1-kg increase in birth weight was 2.14 (95% CI = 1.19-3.85; P = .009). CONCLUSION AND IMPLICATIONS: The association between birth weight and childhood leukemia suggests the importance of intrauterine factors. A plausible explanation may be that increasing birth weight is associated with a higher rate of cell proliferation and/or a larger number of precursor cells being at risk of malignant transformation. The inverse association between birth order and ALL risk among 0-4 year olds was weak, but it was compatible with the hypothesis that delayed exposure to infection may increase the risk of ALL in this age group. The association of childhood AML with birth order and sibship size at young ages deserves further attention in the search for environmental factors that affect childhood AML risk.
It has been proposed that Hodgkin's disease (HD) may have an infectious origin and that delayed exposure to infection may increase the risk of HD in young adults. This hypothesis is addressed by studying the family structure among children and young adults. The Civil Registration System was used to establish a population-based cohort consisting of all persons whose mothers were born in Denmark since 1935. Persons who developed HD were identified by linkage with the Danish Cancer Registry. HD incidence rate ratios were estimated based on a log-linear Poisson regression model. The cohort of 2.1 million persons (aged 0-42 years) was followed for 31.1 million person years, during which period 378 cases of HD occurred. Among children ( or = 15 years, n = 306) the risk of HD, on the contrary, tended to decrease with increasing sibship size [trend = 0.91 (95% CI, 0.81-1.03)] and birth order (trend = 0.85 (95% CI, 0.71-1.01). These trends among young adults were significantly different from the corresponding trends among children (p
STUDY OBJECTIVES: To identify possible modifiable mediators of familial predisposition to myocardial infarction (MI) by assessing the risk factor profile in individuals without MI in relation to parental occurrence of MI. DESIGN AND METHODS: Cross sectional survey of the general population. The odds of an adverse cardiovascular risk factor profile in subjects reporting parental occurrence of MI versus subjects not reporting parental occurrence were estimated by logistic regression models. SETTING: The Copenhagen Centre for Prospective Population Studies, where subjects investigated in three Danish prospective population studies are integrated. PARTICIPANTS: Subjects were 9306 females and 11,091 males aged 20-75 years with no history of MI. A total of 1370 subjects reported maternal MI and 2583 reported paternal MI. MAIN RESULTS: Increased systolic and diastolic blood pressure, increased cholesterol level, low ratio between high density lipoprotein (HDL) and total cholesterol (TC), and heavy smoking, were more frequent in subjects with parental occurrence of MI than in controls irrespective of sex and age of the subjects. Maternal MI was more predictive for increased cholesterol and decreased HDL/ TC ratio than paternal MI, and the risk of an increased cholesterol level was higher in subjects aged 20-39 years than in older subjects. No differences in body mass index, triglycerides, and physical inactivity were observed. CONCLUSIONS: Subjects free of previous MI who reported a parental occurrence of MI had an adverse cardiovascular risk factor profile regarding systolic and diastolic blood pressure, total cholesterol, the ratio between HDL and total cholesterol, and smoking. Thus, these modifiable risk factors may be mediators of the familial predisposition to MI.
Assortative mating has been demonstrated in mental disorders but the extent of cohabitation between patients with clinically diagnosed psychiatric disease has been poorly explored. Method We conducted a register-based study of all Danes between 18 and 70 years of age in a 13-year observational period, linking data on individuals' contacts with psychiatric services with data on individuals' cohabitation status. Two different Poisson regression analyses were performed: the first comparing the rates of commencing cohabitation with a psychiatric patient between individuals, depending on whether the individuals themselves had, or did not have, a psychiatric diagnosis; the second comparing the incidence rates of psychiatric diagnoses for individuals cohabitating with psychiatric patients with the similar rates for individuals living with unaffected cohabitants.
In total, 159 929 (5.0%) out of 3 204 633 individuals were given a psychiatric diagnosis during the study period. Diagnosed individuals had an overall rate ratio (RR) of commencing cohabitation with a psychiatric patient of 1.95 [95% confidence interval (CI) 1.90-2.00] for women and 1.65 (95% CI 1.61-1.69) for men, when compared with unaffected individuals. The overall RR of receiving a psychiatric diagnosis while cohabitating with a psychiatric patient was 2.40 (95% CI 2.31-2.49) for women and 2.91 (95% CI 2.81-3.01) for men, when compared with those cohabitating with unaffected individuals. Individuals with schizophrenia and men with bipolar disorder had the highest RR of commencing cohabitation with a cohabitant with a similar diagnosis.
Cohabitation among individuals with severe psychiatric disorders is increased. This has implications for research and for the clinical management of patients.
A nested case-control study was undertaken in the Maribo County cohort of 27,811 women with negative cervical smears. Fifty-three women who later developed invasive cervical cancer constituted the cases, and five matched controls were selected from the cohort for each case. A total of 633 previous negative smears for the cases and controls were reviewed independently by two pathologists. The review showed misclassification to be frequent in these smears, which were collected in the period 1966-82, and the odds ratio for patients compared with controls for having at least one positive smear was 22.12 (95% CI 7.54-64.94). The study thus shows that more cancer cases could have been prevented by the screening programme were the test to have been more sensitive. The study also shows, however, that the participating women would have to pay a considerable price in the form of unnecessary extra tests if the sensitivity was too high.
BACKGROUND: Persistent infection with certain types of human papillomavirus (HPV) is believed to be a prerequisite for the development of cervical neoplasia. Persistence may depend on certain characteristics, such as viral load, which has so far been given little attention. We investigated the association between HPV 16 viral load and cervical carcinoma in situ. METHODS: We did a nested case-control study of women participating in cytological screening in Sweden. We used a sensitive quantitative PCR assay to estimate HPV 16 load in multiple smears for each woman, taken during a period of up to 26 years before diagnosis. We calculated C, values, which decrease as the number of viral DNA copies increases. FINDINGS: 2081 smears from 478 cases and 1754 smears from 608 controls were tested. Among cases, we found a consistently increased load of HPV 16 already 13 years or more before diagnosis, and when many smears were still cytologically normal. Women with high HPV 16 viral loads were at least 30 times the relative risk of HPV-16-negative women more than a decade before diagnosis. The increase in relative risk was constant over time. About 25% of women (95% CI 0.12-0.32) infected with a high viral load before age 25 years developed cervical carcinoma in situ within 15 years. INTERPRETATION: Cervical carcinoma in situ associated with HPV 16 occurs mainly in HPV-16-positive women who have consistently high viral loads long term. Women at high risk could be identified by use of a quantitative HPV test in addition to cytological screening.
Comment In: ACP J Club. 2001 Jan-Feb;134(1):35
Comment In: Lancet. 2000 Jun 24;355(9222):2179-8010881885
A Cox-type regression model for the ratio between the mortality in a cohort and that in a reference population is introduced. By means of the model it is possible to include in the survival analysis both individual (possibly time-dependent) characteristics for the study cohort and changing trends in the mortality in the reference population. This is particularly relevant in long-term follow-up studies where there may be considerable changes in the mortality in the reference population. Estimation procedures in the model are discussed and large-sample properties of the estimators are outlined. The model is applied to the analysis of two sets of data concerning the survival among insulin-dependent diabetics in Denmark.