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Detection and assessment of clusters of disease: an application to nuclear power plant facilities and childhood leukaemia in Sweden.

We review some recent statistical methods for examining geographic patterns of disease incidence for the presence of clusters. General methods search for clusters throughout the study area and then assess the statistical significance of any clusters detected. Focused methods check for elevated incidence rates close to prespecified locations of putative sources of hazard. We apply the methods to leukaemia incidence data for children aged 0-15 years in Sweden (1980-1990), particularly in reference to locations of nuclear power facilities. Unlike some other studies, notably in the United Kingdom, we do not find any significant clusters.

Adolescent↗

Missense mutations associated with familial Alzheimer's disease in Sweden lead to the production of the amyloid peptide without internalization of its precursor.

Production of soluble amyloid peptide precursor (APP) and amyloid peptide (A beta) was measured in CHO cells transfected by the wild-type APP 695 cDNA sequence or by the same sequence carrying missense mutations associated with familial Alzheimer's disease in Sweden. Deletion of the C-terminal domain of the protein corresponding to residues 654 to 695 of APP 695 not only inhibited very significantly the internalization of APP at 37 degrees C, but also led to the secretion of an uncleaved APP in the culture medium of CHO cells. This deletion did not affect A beta production from the Swedish APP but was able to inhibit the production of the wild-type APP. These results demonstrate that, in CHO cells, the internalization of the wild-type APP is needed for A beta production, while the production of the amyloid peptide from Swedish APP is independent of the internalization process.

Alzheimer Disease↗

Ovarian cancer in young women in Sweden, 1989-1991.

The present study is an evaluation of the symptoms and gynecological status, at the time of seeking medical advice, among women of reproductive age diagnosed with ovarian malignancies. The study was based on the medical records of all women in Sweden between 15 and 40 years of age who were diagnosed with ovarian malignancies during a 3-year period (1989-1991). The study focused on the diagnosis and panorama of symptoms. These data were compared to the records of more than 10,000 women in this age group during the same period of time who underwent surgery for ovarian changes that resulted in benign diagnoses. The 152 cases of ovarian cancer included only 1 patient who was without symptoms, had normal pelvic status upon manual examination, and a sonographically diagnosed simple cyst. These data support the conclusion that the majority of young women with ovarian cancer have symptoms and/or clinically detectable adnexal masses at the time when medical advice is sought. These studies suggest that diagnosis of ovarian cancer is unlikely in young healthy women lacking subjective symptoms and an adnexal mass upon pelvic examination. In conclusion, programs for the management of simple cysts and development of noninvasive diagnostic methods for ovarian changes found in patients in the reproductive age group are needed in order to reduce the number of patients subjected to operative intervention.

Adolescent↗

Deletion in the cardiac troponin I gene in a family from northern Sweden with hypertrophic cardiomyopathy.

The cardiac troponin I gene has been described to be associated with hypertrophic cardiomyopathy. Until now, mutations in this gene have been found only in the Japanese population. We now present the first non-Japanese family, from northern Sweden, with a mutation in the cardiac troponin I gene. Clinical diagnose was based on echocardiography, with a maximum left ventricular wall thickness of >13 mm, or major electrocardiographic abnormalities, excluding subjects with other known causes of cardiac hypertrophy. Mutation screening was performed with a single-strand conformation polymorphism analysis and identification of mutation by direct DNA sequencing. We have identified a 33-bp deletion in exon 8 encompassing the stop codon. Nine individuals in three generations were tested, and four were carriers of this deletion. The mother was genetically affected and died of heart failure aged 90. Echocardiography at 71 years of age revealed no hypertrophy, but the electrocardiogram showed signs of left ventricular hypertrophy. Her two sons, also genetically affected, had left ventricular hypertrophy, with maximum wall thickness of 15 and 16 mm, respectively. One daughter and four grandchildren were clinically unaffected, but one of them, a 27-year-old woman with maximum wall thickness of 8 mm and normal electrocardiogram, was found to be genetically affected. In conclusion, we describe a non-Japanese family in which hypertrophic cardiomyopathy is due to a genetic defect in the cardiac troponin I gene. This mutation is a deletion of 33 bp in the last exon, whereas the previously described mutations in this gene are single nucleotide changes and a single codon deletion. The deletion of the C-terminal part of the cardiac troponin I protein, seems in this particular family to be associated with a mild phenotypic expression of familial hypertrophic cardiomyopathy.

Adult↗

Reasons women do not attend screening for cervical cancer: a population-based study in Sweden.

BACKGROUND: With an improved compliance with screening a larger reduction of cervical cancer incidence would be within reach. We aimed at investigating why certain women do not attend Pap smear screening and at validating the reliability of self-reported screening. METHODS: In 1998 in the county of Uppsala, Sweden, information was collected through telephone interviews with 430 nonattendees and 514 attendees to Pap smear screening, who were all sampled from a population-based database. The women's recall of attendance was validated against the database. The main outcome measures used were odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Non-attendance was positively associated with nonuse of oral contraceptives (OR = 3.56, 95% CI 2.18-5.83), seeing different gynecologists (OR = 1.90, 95% CI 1.34-2.70), and seeing a physician very often (OR = 3.12, 95% CI 1.45-6.70) or not at all (OR = 1.78, 95% CI 1.09-2.90). Frequent condom use (OR = 1.88, 95% CI 1.02-3.47), living in rural/semirural areas (OR = 1.55, 95% CI 1.07-2.21), and not knowing the recommended screening interval (OR = 2.16, 95% CI 1.20-3.89) were all associated with nonattendance, whereas socioeconomic status was not, when tested in a multivariate model. Among the nonattendees, 57% underestimated the time lapse since last smear. CONCLUSIONS: Seeing a gynecologist on a regular basis and information guiding women to have a Pap smear on their own initiative are important factors for recurrent screening. Therefore, information should be given to all women about the purpose and benefits of Pap smear testing. Self-reports on screening should be treated with caution.

Adult↗

Risk comparisons between limit values for ionizing radiation, PAH, and benzene in Sweden.

The background of regulatory limit values for carcinogenic agents in Sweden is discussed and exemplified with the ambient and occupational air pollutants benzene and PAH (especially benzo[a]pyrene, BaP), ionizing radiation, and radon. The estimated cancer risks at different limit values are compared, as is the estimated number of cancer cases annually due to existing pollutant levels. Although the individual lifetime cancer risks are much higher at the occupational limit values for benzene and BaP than what is recommended for the general public, the estimated number of cancer cases annually is lower at existing pollutant levels. The individual cancer risk at the occupational dose limit for ionizing radiation is comparable to the occupational cancer risk with BaP, but higher than the one for benzene. At the dose limit for the general public, the radiation risk would be higher than what is recommended for individual air pollutants. However, doses from man-made radiation are usually much lower than the dose limit due to optimization. Thus, the estimated number of cancer cases annually due to radiation is low and comparable to the estimated number due to the chemical air pollutants discussed. In contrast, the lung cancer risk with radon in dwellings both at limit values and existing levels is high and comparable to occupational limits for the chemical carcinogens and for radiation. The estimated number of cancer cases annually at existing radon concentrations (1100 cases) is much higher than for the other discussed pollutants (0.03-7 cases each) and also higher than the estimated number of lung cancer cases due to total air pollution (approximately 100 cases).

Benzene↗

Epidemiology of head injuries in Sweden.

The estimated number and cause of head injuries in Sweden are discussed. Head injuries are common in many activities and the need of head protection is stressed.

Accidents, Occupational↗

Occupational exposure to electromagnetic fields in relation to leukemia and brain tumors: a case-control study in Sweden.

Occupational exposure to low-frequency electromagnetic fields (EMF) was studied in 250 leukemia patients and 261 brain-tumor cases, diagnosed in 1983-87 and compared with a control group of 1,121 randomly selected men, from the mid-region of Sweden, 1983-87. We based the exposure assessment on measurements from 1,015 different workplaces. On the basis of the job held longest during the 10-year period before diagnosis, we found an association between the average, daily, mean level of EMF and chronic lymphocytic leukemia (CLL). The risk increased with increasing level of exposure. The odds ratios (OR) and the 95 percent confidence interval (CI) for three consecutive levels of exposure were: 1.1 (CI = 0.5-2.3); 2.2 (CI = 1.1-4.3); 3.0 (CI = 1.6-5.8), respectively. No association was observed for acute myeloid leukemia (OR = 1.0, CI = 0.5-1.8; OR = 0.8, CI = 0.4-1.6; OR = 1.0, CI = 0.6-1.9). For brain tumors, the corresponding risk estimates were 1.0 (CI = 0.7-1.6); 1.5 (CI = 1.0-2.2); 1.4 (CI = 0.9-2.1). Different EMF indices were tested. Tasks with frequent or large variations between high and low field-densities (high standard deviation) were more common among CLL subjects. For brain tumors, a prolonged high level (high median values) showed the strongest association. Confounding by place of residence, smoking, benzene, ionizing radiation, pesticides, and solvents was evaluated, and these factors did not seem to have a decisive influence on the associations. We also analyzed other potential sources of bias. For CLL, there were indications of an excess number of low-exposure subjects among non-responders, which, to some extent, may have enhanced but not caused the risk estimates obtained. Our conclusion is that the study supports the hypothesis that occupational EMF exposure is a hazard in the development of certain cancers.

Acute Disease↗

Maternal risk of breast cancer following multiple births: a nationwide study in Sweden.

The association between multiple births and subsequent maternal breast cancer risk was explored in a nested case-control study in Sweden encompassing 19,368 parous women with breast cancer diagnosed up to age 65 years, and 100,459 parous controls. Among cases and controls, there were 329 and 2,031 women, respectively, with a history of at least one live multiple birth. Compared with singleton mothers, breast cancer risk was 12 percent lower (odds ratio = 0.88, 95 percent confidence interval = 0.78-0.99) in women who had had a multiple birth. After stratification for age at diagnosis, evidence of a significant inverse association was found only in women aged 54 years or younger. Birth order of the multiple pregnancy had no apparent risk-modifying effect. Age at earliest multiple birth was unrelated to breast cancer risk. The inverse association between twinning and breast cancer risk may reflect protective physiological features of twin pregnancies. Further research is needed to investigate the role, if any, of increased levels of steroid hormone-binding globulins in mothers of twins and the proposed inhibitory effects of human chorionic gonadotropin and alpha-fetoprotein, both of which are increased during multiple gestations, on breast carcinogenesis. Breast feeding patterns in mothers of twins also may modify their risk of developing breast cancer.

Adult↗

Cancer incidence among male railway engine-drivers and conductors in Sweden, 1976-90.

During recent years, the relationship between exposure to magnetic fields and cancer has attracted increasing interest. In Sweden, train personnel are exposed to comparatively strong magnetic fields in their work. The aim of the present study was to investigate cancer incidence, particularly leukemia and brain tumors, among male railway engine drivers and conductors, respectively, and to compare their cancer incidence with that of the general male population. The study population comprised all male railway engine drivers (n = 7,466) and conductors (n = 2,272) who were ever employed at the Swedish State Railways during the period 1976-90. The study population was observed with regard to cancer incidence by means of the National Cancer Register for the period 1976-90. The total cancer incidence (all tumors included) among railway engine drivers was lower than in the general Swedish population. An increased incidence of lymphocytic leukemia was observed among railway engine drivers and conductors combined (relative risk = 2.3; 95 percent confidence interval = 1.3-3.2), with the same point estimate for both occupational groups. For brain tumor (astrocytoma), the observed relative risk was close to one. The study provides evidence of an excess risk of lymphocytic leukemia in railway engine drivers and conductors, workers with known occupational exposure to magnetic fields.

Adult↗

Trends in endometrial cancer incidence and mortality in Sweden, 1960-84.

Trends in incidence of and mortality from invasive endometrial cancer in Sweden in 1960-84 were analyzed. The study was based on virtually all 20,371 patients given this diagnosis and 4,887 patients who died of the disease in that period. Only minor changes occurred in age-standardized incidence in pre-menopausal women, in whom the rates declined consistently during the last 15 years, especially in the youngest age groups. Among post-menopausal women, an early increase was followed by stable rates in women over 60 and decreasing rates at ages 50-59 years. In contrast, mortality rates decreased consistently over the study period. Multivariate regression analyses indicated that birth cohort was a more important determinant of incidence and mortality than was time period. The relative risk of developing endometrial cancer increased by about 20 percent in women born around 1900 as compared with 1880, and by an additional 40 percent from the 1910 cohort to the maximum risk attained in those born around 1930. In successively younger birth cohorts, the risk markedly and continuously declined. These strong birth-cohort effects after 1910 may be reasonably explained by the change from the risk-increasing estrogen-only replacement therapy introduced in the 1960s to the less harmful use, starting about 10 years later, of combined estrogen-progestogen regimens; and further, by the protective exposure of a large proportion of pre-menopausal women to oral contraceptives. Mortality, however, decreased steadily in successive cohorts from those born in 1890, indicating that the increase in incidence was referable mainly to non-lethal cancers.

Aged↗

A case-control study of major congenital heart defects in Sweden--1981-1986.

This paper reports the results of a case-control study of major congenital heart defects (CHD) in Sweden. During the period 1981-1986, 1,324 such cases were identified and 2,648 controls were selected. Some common maternal characteristics and exposures were studied using information from prospectively collected data. Possible associations with CHD were found for previous perinatal death, maternal diabetes, epilepsy, hydramnios and disproportion between fetus and pelvis. More specific associations were observed between previous spontaneous abortion, epilepsy, hydramnios and truncus anomalies and between diabetes and septal anomalies. However, no associations were found with involuntary childlessness, contraceptive use, or smoking.

Abortion, Induced↗

An interview study to estimate prevalence of asthma and chronic bronchitis. The obstructive lung disease in northern Sweden study.

A questionnaire of respiratory symptoms and diseases completed by 6610 adults in 3 age cohorts (35-36 y; 50-51 y and 65-66 y) in northern Sweden was followed-up by interview and lung function testing of 1243 subjects with asthmatic or bronchitic symptoms and 263 subjects assessed from the postal questionnaire as being healthy. We report the results of this follow-up study. According to the criteria used, 292 subjects (5.1% of the original study sample) were diagnosed as having asthma. Out of the 1243 subjects 334 (5.9% of the original study population) were diagnosed as having chronic bronchitis. However, examination of the 263 subjects who were healthy according to the postal questionnaire showed that elderly smokers, in particular, under-reported bronchitic symptoms; taking this into account, the prevalence of chronic bronchitis is estimated to be of the order of 9%. Diagnostic difficulties were noted in 70 subjects (corresponding to 1.2% of the original study sample) in whom asthma or chronic bronchitis were strongly suspected. Further investigation of these subjects was considered necessary. In this cross-sectional study, FEV1 < 80% of predicted values was found in 36% of subjects diagnosed as having asthma and in 31% of those with chronic bronchitis. Among subjects with attacks of breathlessness and wheezing, diagnostic criteria often used for asthma in questionnaire studies, 70% were diagnosed as having asthma. Of those with chronic productive cough, 62% were diagnosed as having chronic bronchitis. We consider that trained nurses provide reliable data that may be used in epidemiological surveys of obstructive lung diseases.

Adult↗

The third birth in Sweden.

"This paper considers the formulation, estimation and interpretation of microdynamic models of fertility. Our model explains parity choices, sterility, childlessness, interbirth intervals and initiation of pregnancy within a unified framework. We develop a general methodology for estimating the determinants of transition times to births of different orders. Our procedure incorporates time-varying explanatory variables and unobservables. We present conditions that justify conventional formulae relating hazards to survivor functions when time-varying variables enter hazards. We also consider the validity of widely-used piecemeal estimation strategies that focus on one birth at a time. We consider methods for selecting a best model among a class of non-nested models. Two criteria are set forth and used to evaluate the determinants of third births in Sweden."

Birth Order↗

Age standardisation of drug utilisation: comparisons of different methods using cardiovascular drug data from Sweden and Spain.

In drug utilisation studies, the units of defined daily doses (DDD) and DDD/1000 inhabitants per day standardise for differences in dosage and population size, but not for age-related differences in drug utilisation. There is no consensus as to how age standardisation of DDD data should be carried out. Using cardiovascular drug utilisation data from Sweden and Spain, the current study compared the outcome of different methods of age standardisation. Both indirect methods (based on a comparison of observed and expected drug usage) and direct methods (using different weighting for the age categories) were used. The largest impact of standardisation was seen for diuretics. The crude rate for men and women combined was 26 DDD/1000 inhabitants per day in Costa de Ponent and 98 DDD/1000 inhabitants per day in Värmland. The corresponding figures when standardising the Costa de Ponent population were 26 and 58, respectively. Using the equivalent average rate (EAR) method, the rate for Värmland was 129 DDD/1000 inhabitants per day. Lesser but still important differences were found for beta-adrenoceptor and antihypertensives. Thus, the results of standardisation differ depending on which method is used and which drugs are evaluated. EAR is recommended for direct standardisation because of its ease of use and because it does not require the choice of a standard population.

Adolescent↗

Neoplastic disease in a medicolegal autopsy material. A retrospective study in northern Sweden.

Only a small fraction of sudden unexpected deaths are caused by neoplastic disease and thus subject ot medicolegal autopsy. The medicolegal autopsy forms an opportunity to study not only medically diagnosed and treated neoplasms, but also the natural evolution of untreated disease. In a series of 7,020 consecutive medicolegal autopsies in northern Sweden, we found 171 cases with malignant and/or intracranial neoplasms. In 41 cases, sudden death was caused by previously unknown tumors. The most common mechanisms of death in this group were disseminated cancer, intracranial tumors, pulmonary thromboembolism, hemoptysis, and aspiration of blood, and the most common locations were the bronchi and the lung. In some of these cases, the mechanism was sometimes dramatic, raising a question of violent death or intoxication. In 30 cases, sudden unexpected death was caused by previously known tumors, and also in this group disseminated cancer was the most common cause of death, and the most common locations were the bronchi and the lung. In 22 cases, tumors were found suicidal cases; in 14 of these, the tumor was considered to be a major causative factor to the suicide, while in eight cases the tumor was considered to be an incidental finding. The expected number of cancers in the 1,060 suicides investigated in this series was 27, according to the official cancer prevalence data. Thus, a possible over-representation of suicides among persons with cancer seems doubtful and needs further exploration.

Adult↗

Islet cell and other organ-specific autoantibodies in all children developing type 1 (insulin-dependent) diabetes mellitus in Sweden during one year and in matched control children.

The majority (about 90%) of children developing Type 1 (insulin-dependent) diabetes mellitus do not have a first-degree relative with the disease. Nearly all (389/405, 96%) children (0-14 years) in Sweden, who developed diabetes during one year, were therefore studied to compare islet cell, thyroid peroxidase, thyroglobulin, and gastric H+, K+-ATPase antibodies with 321 age, sex, and geographically matched, but non-related, control children. Islet cell (cytoplasmic) antibodies were found in 81% (316/389) of the patients and in 3% (9/321) of the control children (p less than 0.001). The median islet cell antibody levels were 70 (range 3-8200) Juvenile Diabetes Foundation (JDF) Units in the islet cell antibody positive patients, and 27 (range 17-1200) JDF Units in the control children (NS). Autoantibodies against thyroid peroxidase (8%), thyroglobulin (6%), and gastric H+, K+-ATPase (3%) were all increased in the patients compared with the control children, being 2% (p less than 0.001), 2% (p less than 0.01), and 0.3% (p less than 0.01), respectively. During an observation time of 20-34 months, two of the nine islet cell antibody positive control children developed Type 1 diabetes, after 8 and 25 months respectively, while the others remained healthy and became islet cell antibody negative. None of the islet cell antibody negative control children developed diabetes during the same time of observation. This first investigation of an unselected population of diabetic children and matched control children shows: that islet cell antibodies are strongly associated with newly diagnosed childhood diabetes, that other autoantibodies are more frequent among diabetic children than control children, and that the frequency of islet cell antibodies in the background population of children is higher than previously documented, and could also be transient, underlining that factors additional to islet cell antibodies are necessary for the later development of Type 1 diabetes.

Autoantibodies↗

HLA as a marker of the hemochromatosis gene in Sweden.

The frequency of HLA-A3 and HLA-B14 antigens was found to be significantly (P = less than 0.0001) higher in a series of 50 unrelated and unselected Swedish patients with idiopathic hemochromatosis (IH) than in controls, being 66% and 32% for A3 and 22% and 2% for B14. The haplotype A3B14 was associated with the highest risk in this material (relative risk 23.4). One family with this haplotype was traced back to the end of the seventeenth century. The pattern of HLA antigens associated with IH in Sweden shows remarkable similarity to those reported from England and Brittany.

Female↗