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Thyroid cancer risk after thyroid examination with 131I: a population-based cohort study in Sweden.

Ionizing radiation is the only established cause of thyroid cancer, though the effect of diagnostic administration of (131)I on thyroid cancer risk appears minimal. The annual number of thyroid examinations using radioiodine is currently 5 per 1,000 individuals worldwide, so this issue is of public health importance. Our objective was to evaluate the excess risk of thyroid cancer following a range of known doses of (131)I administered for diagnostic purposes. We conducted a nationwide, population-based cohort study in Sweden including all 36,792 individuals who received (131)I for diagnostic purposes during 1952-1969 and were alive and free of thyroid cancer 2 years after exposure. Accrual of person-time at risk commenced 2 years after the first (131)I administration. Follow-up for cancer was to the end of 1998. Standardized incidence ratios (SIRs) were calculated as the ratio between the observed and expected numbers of thyroid cancers. Estimates were stratified by previous exposure to external radiation therapy to the neck, reason for thyroid examination, (131)I dose, sex, age at exposure and time since exposure. Thyroid cancers (n = 129) were diagnosed during 886,618 person-years at risk. Excess thyroid cancers were observed only among the 1,767 patients who reported previous external radiation therapy to the neck [SIR = 9.8, 95% confidence interval (CI) 6.3-14.6] and among those originally referred due to suspicion of a thyroid tumor (SIR = 3.5, 95% CI 2.7-4.4 for 11,015 patients without previous external radiation therapy). The 24,010 patients without previous exposure to external radiation therapy to the neck who were referred for a reason other than suspicion of a thyroid tumor received an estimated dose to the thyroid of 0.94 Gy. Among these patients, 36 thyroid cancers were observed compared to 39.5 expected (SIR = 0.91, 95% CI 0.64-1.26). We found no evidence that administration of (131)I for diagnostic purposes increases risk of thyroid cancer. However, our study included few patients under age 20, so the results apply primarily to exposure among adults. Our data suggest that protraction of dose may result in a lower risk than brief X-ray exposure of the same total dose.

Adolescent↗

Seasonal variation in the diagnosis of Hodgkin lymphoma in Sweden.

Epidemiologic evidence suggests a seasonal pattern in the occurrence of Hodgkin lymphoma (HL), with an incidence peak around the month of March. This pattern may reflect seasonal variation in the prevalence of an infectious agent involved in HL development. Using Poisson regression, we examined monthly variation in HL diagnosis in Sweden between 1958 and 1998, based on data from the population-based Swedish Cancer Registry. Older adults (50 to 79 years) were marginally more likely to be diagnosed in February, but there was no monthly variation after stratifying by sex. Young adult males (15 to 49 years) presented more often in February, whereas young adult females presented less often in August and December. Among children (<15 years), boys were significantly more likely to have been diagnosed in March, whereas there was no seasonal incidence pattern among girls. The seasonal pattern in HL diagnosis among young adults and boys is consistent with an infectious origin, whereas the results among older adults neither support nor dispute the possibility of an infectious etiology in this age group.

Adolescent↗

Incidence of intracranial meningiomas in Denmark, Finland, Norway and Sweden, 1968-1997.

It has been reported that the incidence of meningioma increased in several industrialized countries in the late 1970s and early 1980s. The aim of this study was to evaluate the time trends in incidence of meningiomas in Denmark, Finland, Norway and Sweden, with emphasis on the age distribution and sex ratio. Information about cases of meningiomas in people aged 15-84 years was obtained from the cancer registries of these Nordic countries for the years 1968-1997, and estimates of person-years at risk were calculated from information provided by the national population registries. Age-specific incidence rates per 100,000 and incidence rate ratios were calculated for 3-year periods. The female:male ratios were also evaluated. The combined incidence among men increased from 1.4 to 1.9 per 100,000 during the follow-up period, the corresponding rates for women were 2.6 and 4.5. The female:male ratio increased over time for several age groups and was as high as 3.5:1 in the group aged 40-44 years in the latest follow-up period (1993-1997). In summary, our results provide some support for the idea that the introduction of computed tomography in the late 1970s has had an impact on the detection of cases in people aged 60 and over. The decrease in the rate or detection postmortem has affected the incidence time trend, but it also coincides with widespread use of new imaging technologies. The increasing trend shown for the female:male ratio in the group aged 35-59 years is consistent with the possibility that increasing use of hormones may affect the incidence of meningiomas in women.

Adolescent↗

Epidemiology of Kaposi's sarcoma in Sweden prior to the acquired immunodeficiency syndrome.

We studied retrospectively 529 cases of Kaposi's sarcoma (KS) reported to the Swedish Cancer Registry between 1958 and 1982 to determine incidence rates, survival and rate ratios, together with the frequency and types of associated malignancies. The age-standardized (Swedish population 1970) incidence rate generally increased over the time period, with a mean of 0.27 cases per 100,000 population per year (males 0.40, females 0.14). The incidence rate ratio (based on 5-year intervals and relative to the earliest period) reached 2.06 for males and 3.76 for females in the 1968-1972 interval, while the actual peak occurred between 1971 and 1974 for both sexes. Poisson regression modelling suggested a transient shift in the age-specific male incidence rate pattern with a relative increase of the disease in younger age groups (p = 0.05) up to 1968-1972. The age-adjusted male:female ratio did not change significantly from 2.9 during the period of study. In relation to the general population, 18% fewer men and 24% fewer women were alive 10 years after the diagnosis had been made. Ninety-nine (19%) cases had other primaries, of which 17 were neoplasms of lymphocytic origin. Lymphoproliferative malignancy was 2.5 times (95% CI 1.38, 4.37) more common than expected in patients with KS (in particular in females) but a definite increase in other malignancies was not apparent. It is questionable whether immune dysfunction due to other malignant disease or drug therapy can account for the epidemiologic changes in KS, which began almost 2 decades prior to the AIDS epidemic in Sweden.

Acquired Immunodeficiency Syndrome↗

Trends in thyroid cancer incidence in Sweden, 1958-1981, by histopathologic type.

Time trends in the incidence of malignant neoplasms of the thyroid were examined for Sweden for the period 1958-81, 5,838 cases being studied. Autopsy-diagnosed cases were excluded. Mean annual changes in the age-standardized rates over this period were 1.9% and 1.2% for women and men, respectively, for all thyroid carcinomas combined; 4.9% and 2.1% for papillary carcinoma; 0.9% and 2.1% for follicular carcinoma; and -1.0% and -2.1% for anaplastic carcinoma. Age, period and cohort models were fitted. There was a progressive increase in papillary cancer incidence for cohorts born since 1919. This increase cannot be satisfactorily explained as an artefact of trends in classification, and probably reflects a real increase in incidence. A less marked increase was seen for follicular cancer, and there was a decline for cohorts born since 1939. While the risk of papillary and anaplastic carcinoma was lower in iodine-deficient areas, follicular cancer risk was twice as high in these areas, for men only. There was a steady decline of anaplastic cancer in both sexes after 1965, largely attributable to a decline in cohorts born since 1924.

Age Factors↗

Maternal and perinatal risk factors for Wilms' tumor: a nationwide nested case-control study in Sweden.

This report describes maternal and perinatal risk factors for Wilms' tumor analyzed in a case-control study nested in a nationwide cohort in Sweden. The Swedish National Cancer Registry ascertained 110 cases from among successive birth cohorts from 1973 through 1984, identified by the Swedish Medical Birth Registry, the latter based on medical records. From the Birth Registry, we matched 5 controls without cancer to each case by sex and date of birth. Wilms'-tumor children were more likely to have mothers who had been exposed to penthrane (methoxyflurane) anesthesia during delivery than mothers of controls (odds ratio (OR) = 2.4; 95% confidence interval (CI) 1.1 to 5.1); this excess risk was higher in females than males and increased with age at diagnosis. Wilms'-tumor cases were also more likely to have had physiologic jaundice (OR = 2.3; 95% CI 1.1 to 5.0). Higher parity of the mother decreased the risk of Wilms' tumor among females (OR = 0.7; 95% CI 0.5 to 1.0). We were unable to confirm the reported increased risks of Wilms' tumor for those with high birth weights or with a maternal history of hypertension or fluid retention during pregnancy, nor did we find any association with mother's age at delivery, previous stillbirth, previous live birth, gestational length or height of the child.

Anesthesia, Obstetrical↗

Diet and risk of gastric cancer. A population-based case-control study in Sweden.

A case-control study to evaluate risk factors of gastric cancer was carried out in areas with contrasting incidence rates in Sweden. Face-to-face interviews were conducted with 338 of 456 eligible histologically confirmed gastric-cancer cases and 669 of 880 eligible control subjects, sampled from population registers and frequency-matched by age and gender. We focused on 2 periods, adolescence and 20 years prior to interview. The association of gastric-cancer risk with dietary habits during adolescence were similar to that found for the period 20 years before interview; high consumption of wholemeal bread, fruit and vegetables was associated with reduced gastric-cancer risk. In addition, cheese, fish and tea had a protective effect during adolescence. Increased gastric-cancer risk was related to whole-milk consumption, but this association decreased substantially in a multivariate analysis including vegetables. There was a positive relationship between gastric-cancer risk and the age at which the interviewees started using refrigerators. This population-based study confirmed the protective effect of a high consumption of vegetables and fruit in the development of gastric cancer, but failed to find any association between intake of meat, sausage, cold cuts, liver, salt, coffee, the habit of frying, smoking or grilling foods, and risk of gastric cancer.

Adult↗

Parity and hepatocellular carcinoma. A population-based study in Sweden.

The association between parity and hepatocellular carcinoma (HCC) was studied using a data-base generated by linking 2 Swedish nation-wide registries; the Cancer Registry and the Fertility Registry. Among women born between 1925 and 1960, 133 patients with HCC recorded in the Cancer Registry between 1958 and 1984 were compared with 665 age-matched controls. In this nested case-control study there was no positive association between parity, age at first birth or frequency of twinning on the one hand, and risk of HCC on the other. It appears that the positive association between parity and HCC previously reported is limited to cases of HCC caused by chronic infection with hepatitis B virus; these cases represent only a small fraction of HCC cases in Sweden.

Adult↗

Nutrients and gastric cancer risk. A population-based case-control study in Sweden.

A population-based case-control study of gastric cancer was conducted in areas with contrasting incidence rates in Sweden. Face-to-face interviews were carried out with 338 (74.1%) of all eligible cases and 679 (77.3%) of the selected controls. Consumption of selected nutrients during adolescence and 20 years prior to interview was estimated, together with life-time intake of vitamin supplements. Ascorbic acid and beta-carotene had an unequivocal protective effect, but alpha-tocopherol and nitrate were also negatively associated with gastric-cancer risk. In a multivariate analysis including all of these factors, only ascorbic acid remained a significant protective factor. The only macronutrient positively associated with the risk of gastric cancer was fat: intake 20 years prior to interview, but not during adolescence, was found to have a significant impact. Supplementation with vitamins almost halved the risk after adjustment for dietary intake of the corresponding vitamins. While the protective effect of vitamin C and beta-carotene could conceivably be ascribed to other agents in the diet, the strong negative association between supplementation with vitamin C and risk of gastric cancer supports the hypothesis of a protective role of this anti-oxidant.

Age Factors↗

Low-fat diets may prevent weight gain in sedentary women: prospective observations from the population study of women in Gothenburg, Sweden.

The Population Study of Women in Gothenburg, Sweden is an ongoing prospective study of female residents who were recruited from the local registry in 1968-1969 when they were 38-60 years old. The data presented here were collected from 361 healthy women who underwent a baseline physical examination including a supplementary dietary history interview and returned for a second general health examination 6 years later. This report identifies a subgroup of 57 women who were sedentary during their leisure time and appear to have been particularly susceptible to gaining weight as a function of the fat content of their diets. Specifically, longitudinal analysis of body weights in the whole sample revealed a statistical interaction between leisure-time physical activity and habitual dietary fat intake (energy%), as reported at the baseline examination, in the prediction of subsequent weight change. Further stratified analysis suggested that weight changes were significantly dependent on dietary fat intake among the sedentary women only. High energy intake also predicted weight gain in the sedentary group, although the predictive value for a high-fat diet was of marginal significance after adjusting for total energy consumption. These results suggest that sedentary recreational activity plus a low-fat diet may have a combined contribution to weight change that is not equivalent to the sum of the separate effects. Such a synergy between two modifiable lifestyle factors seems highly relevant for prevention of obesity.

Adult↗

Molecular epidemiology of rotavirus infections in Uppsala, Sweden, 1981: disappearance of a predominant electropherotype.

The molecular epidemiology of rotavirus infections was studied in children with acute gastroenteritis in Uppsala, Sweden, during 1981. Altogether 118 virus strains were investigated by analysis of the RNA migration pattern in silver-stained polyacrylamide gels. Six different electropherotypes were seen: two with "short" and four with "long" RNA migration patterns. Forty-two strains (36%) exhibited "short" patterns. The seasonal distribution showed that strains with "long" and "short" RNA patterns cocirculated in equal frequency during the first seven months of the year, until the predominant "short" RNA electropherotype suddenly disappeared. More than 11 RNA segments were seen in two stool specimens. A complete correlation was found between the electrophoretic migration of segments 10 and 11 and the serological defined subgroup specificity.

Adolescent↗

Occurrence of respiratory syncytial virus subtypes A and B strains in Sweden.

The subtype characteristics of 22 strains of respiratory syncytial (RS) virus isolated in Sweden were determined by the use of monoclonal antibodies. Eleven antibodies specific for distinct epitopes on five different structural proteins were used in immunofluorescence and radioimmune precipitation assays. One group of 12 isolates were derived from a three-month epidemic during 1984, whereas the other ten virus isolates were recovered during a time period of 13 years (1971-1983). All isolates could be allocated to the previously defined groups of subtype A and B strains of RS virus. During the single epidemic season, five subtype A and seven subtype B strains were found. During the 13-year period a randomly alternating appearance of six subtype A and four subtype B strains was observed. Thus RS virus strains of different subtype characteristics may occur alternately or concomitantly. The possible significance of consecutive infections with RS virus subtypes for immunopathological events deserves further studies.

Aged↗

Antibody prevalence and immunoglobulin IgG subclass pattern to Norwalk virus in Sweden.

The antibody prevalence in Sweden to Norwalk virus (NV) was investigated using a baculovirus expressed capsid antigen. One hundred thirty-two serum samples were examined for IgA, total IgG and IgG subclass antibodies to Norwalk virus. In young children, NV IgG antibody prevalence was higher than the IgA prevalence, whereas no difference was found in individuals older than 21 years. The IgG antibody prevalence was 50% in children below 5 years of age and increased to > 80% in individuals older than 10 years of age. To examine the IgG antibody response in more detail, IgG subclass patterns were characterized. IgG 1 predominated in all age groups. IgG 4, usually detected after repeated exposure to antigen, was the second most prevalent subclass, but was only found in individuals older than 21 years of age. IgG 3 subclass antibodies were found in 13% and IgG 2 in 3% of the sera examined. IgG 3 subclass antibodies have been recognized as a marker for recent or ongoing viral infections.

Adolescent↗

What are the obstacles to generic substitution? An assessment of the behaviour of prescribers, patients and pharmacies during the first year of generic substitution in Sweden.

PURPOSE: The aim of the present study was to investigate obstacles to generic substitution and savings achieved during the first year after Sweden introduced generic substitution in October 2002. METHODS: Normal prescriptions encompassed by generic substitution were included. Data on dispensed prescriptions in the Vastra Gotaland region was obtained from the National Corporation of Swedish Pharmacies. The outcome variables were investigated in three categories of drugs represented by two indicator drugs each. RESULTS: In total, 501,400 dispensed prescriptions of six indicator drugs were analysed. The prescriber opposed substitution in 1-8% of the dispensed prescriptions, varying between the indicator drugs. Patients declined substitution more frequently when the average saving per substitution was low. Substitution occurred most frequently in indicator drugs where the average saving per substitution was high. The total possible saving was 26 million Swedish krona (Swedish krona 1=U.S. $0.13) for the indicator drugs. The actual saving achieved by substitution was on average 60% of the total possible savings and was largely dependent on the extent to which the pharmacies kept the cheapest brand in stock. CONCLUSIONS: Generic substitution has been implemented in practice although it did not reach full dividend during the first year. The potential savings from extended use of generic substitution are substantial.

Choice Behavior↗

Paediatric adverse drug reactions reported in Sweden from 1987 to 2001.

PURPOSE: To describe frequency, seriousness and recovery of the patient in reported suspected paediatric adverse drug reactions (ADRs) in Sweden using data from a nation-wide ADR reporting system. METHODS: Data from ADR reports submitted to the Swedish Medical Products Agency (MPA) were collected from the database SWEDIS and analysed for the period from 1987 to 2001. All reports with certain, probable or possible causality assessments referring to paediatric patients < 16 years of age were included. RESULTS: In 5771 children an ADR report was documented during the whole 15-year period in a paediatric population of about 1.7 million individuals. The annual reporting frequency was about 385 reports per year. The most frequently reported reactions were application site reaction (24%) followed by fever (12%) and exanthema (6.7%). The clearly most frequently reported group of drugs were the vaccines (63.8%) followed by antibiotics for systemic use (10.1%). The proportion of children that suffered from a serious ADR was 13.0% and that for drug related deaths 0.14%. Nine per cent of the children had not recovered at the time of reporting and 1% recovered with sequelae. A male overrepresentation was observed regarding the total number of reports. About two-third of the reports concerned outpatients less than 4 years of age. CONCLUSIONS: In respect of the limited number of paediatric drug safety studies or availability of record-linkage databases, nation-wide reporting systems of ADRs represent a valuable hypothesis generating tool in evaluating the characteristics of ADRs occurring in the orphan paediatric population.

Adolescent↗

Budesonide-treated asthmatic adolescents attain target height: a population-based follow-up study from Sweden.

PURPOSE: To examine final height in relation to target height in asthmatic patients with and without glucocorticoid treatment while growing up compared with healthy individuals. METHODS: In 1990 and 1993, questionnaires were distributed to all individuals born in 1974 and 1977 in the counties of Jämtland and Gästrikland in Sweden. All individuals reporting use of anti-asthmatic drugs or symptoms indicating possible obstructive airway disease, and a sample of healthy volunteers were invited to a clinical examination. RESULTS: Overall, 356 asthmatic patients and 384 healthy individuals were identified. In 1998-1999, all subjects were invited to a follow-up study and final height was analysed in relation to target height in 152 asthmatic patients and 131 healthy individuals. It was found that both men and women achieved a higher mean final height than the calculated mean target height. There were no significant differences between controls and asthma patients treated either with or without glucocorticoids. Most of the patients treated with glucocorticoids started their therapy during adolescence and 92% had used inhaled budesonide. There was no trend towards a decrease in final height in relation to target height when inhaled budesonide treatment was initiated prior to adolescence or with lifelong cumulative dose of inhaled budesonide. CONCLUSIONS: Asthmatic adolescents treated with inhaled budesonide achieve normal final height in relation to their target height.

Adolescent↗

Adverse drug reactions and off-label prescribing for paediatric outpatients: a one-year survey of spontaneous reports in Sweden.

PURPOSE: To investigate the extent and characteristics of off-label prescribing for paediatric outpatients among drugs reported to have caused an adverse reaction. METHODS: A retrospective, cross-sectional, observational analysis of spontaneous adverse drug reaction (ADR) reports in Sweden in the year 2000. We included all reports concerning drugs prescribed for outpatients younger than 16 years. Each ADR was classified with respect to its causality, seriousness and type of reaction. Off-label prescribing was evaluated with respect to age, dose, indication, formulation and route and frequency of administration. RESULTS: We identified 112 patient-linked reports corresponding to 158 ADRs of which 31% were serious. Antiasthmatic drugs were most frequently suspected as a cause of almost every third adverse reaction. The average proportion of off-label drug prescribing amounted to 42.4%. It was more frequently associated with serious than non-serious ADRs and mostly due to a non-approved age or dose. The most common clinical manifestations were psychiatric disorders and mucocutaneous inflammatory reactions. CONCLUSIONS: Off-label prescribing for paediatric outpatients is common among drugs reported to have caused an ADR. It is suggested to further identify unlabelled drugs frequently contributing to, in particular serious ADRs in children for a proper benefit-risk assessment of off-label drug use.

Adolescent↗

Assessment of intra-individual variation in prostate-specific antigen levels in a biennial randomized prostate cancer screening program in Sweden.

BACKGROUND: The degree of variability in prostate-specific antigen (PSA) measurements is important for interpreting test results in screening programs, and particularly for interpreting the significance of changes between repeated tests. This study aimed to determine the long-term intra-individual variation for PSA in healthy men. METHODS: A randomly selected cohort of men in a biennial prostate cancer screening program (ERSPC) conducted in Sweden from 1995-1996 to 2001-2002. We studied men who had total PSA (tPSA) levels < 2.0 ng/ml in 2001-2002. This included 791 men with tPSA < or = 0.61 ng/ml (group A), 1,542 men with tPSA < or = 0.99 ng/ml (group B), and 1,029 men with tPSA 1.00-1.99 ng/ml (group C). The intra-individual variability of free PSA (fPSA) and tPSA was assessed by calculating coefficients of variation (CV) for each individual's PSA measurements from the first and second round of screening (1995-1996 and 1997-1998). RESULTS: Intra-individual CV (geometric means) for tPSA were 13.7%, 12.7%, and 11.5% in groups A, B, and C, respectively. Corresponding CVs for fPSA were significantly lower, ranging from 12.1% to 10.4%. The estimated biological variation of tPSA and fPSA in groups A to C were 12.5%, 11.4%, 10.0% and 9.7%, 7.8%, 7.5%, respectively. CONCLUSIONS: In healthy men with PSA levels less than 2 ng/ml, the natural long-term variability for tPSA was less than 14%, and with 95% probability, a change in tPSA greater than 30% indicates a change beyond normal random variation.

Aged↗