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Biomedical subjects

Mads Melbye

Publications and source records attributed to Mads Melbye.

At least 55 records · Page 3Linked to original sources
PubMed2004

Childhood vaccination and type 1 diabetes.

BACKGROUND: A link between childhood vaccinations and the development of type 1 diabetes has been proposed. METHODS: We evaluated a cohort comprising all children born in Denmark from January 1, 1990, through December 31, 2000, for whom detailed information on vaccinations and type 1 diabetes was available. Using Poisson regression models, we estimated rate ratios according to vaccination status, including the trend associated with the number of doses, among all children and in a subgroup of children who had siblings with type 1 diabetes. Given recent claims of clustering of cases of diabetes two to four years after vaccination, we also estimated rate ratios during the period after vaccination. RESULTS: Type 1 diabetes was diagnosed in 681 children during 4,720,517 person-years of follow-up. The rate ratio for type 1 diabetes among children who received at least one dose of vaccine, as compared with unvaccinated children, was 0.91 (95 percent confidence interval, 0.74 to 1.12) for Haemophilus influenzae type b vaccine; 1.02 (95 percent confidence interval, 0.75 to 1.37) for diphtheria, tetanus, and inactivated poliovirus vaccine; 0.96 (95 percent confidence interval, 0.71 to 1.30) for diphtheria, tetanus, acellular pertussis, and inactivated poliovirus vaccine; 1.06 (95 percent confidence interval, 0.80 to 1.40) for whole-cell pertussis vaccine; 1.14 (95 percent confidence interval, 0.90 to 1.45) for measles, mumps, and rubella vaccine; and 1.08 (95 percent confidence interval, 0.74 to 1.57) for oral poliovirus vaccine. The development of type 1 diabetes in genetically predisposed children (defined as those who had siblings with type 1 diabetes) was not significantly associated with vaccination. Furthermore, there was no evidence of any clustering of cases two to four years after vaccination with any vaccine. CONCLUSIONS: These results do not support a causal relation between childhood vaccination and type 1 diabetes.

Birth Weight↗
PubMed2004

A comparison of reproductive risk factors for CIS lesions and invasive breast cancer.

A differential effect of reproductive factors on the incidence of carcinoma in situ of the breast (CIS) and invasive cancer may indicate that hormonal factors related to reproductive history not only influence the initial steps towards breast cancer but also preinvasive malignant lesions. A comparison of reproductive factors was performed using a population-based cohort of 1.5 million Danish women born between 1935 and 1978. Between 1983 and 1998, 15,590 cases of invasive breast cancer and 871 cases of CIS were identified using a database with extensive clinical information. Number of births and age at first birth were similarly associated with the risk of being diagnosed with ductal carcinoma in situ (DCIS) compared to invasive breast cancer [RR(DCIS)(per birth)/RR(invasive)(per birth) = 1.03(0.93-1.14), RR(DCIS)(per 5yr) /RR(invasive)(per 5yr) = 1.06(0.96-1.17)]. Also, the short-term risk the first 10 years after birth was similar for DCIS and invasive cancer [RR(DCIS) /RR(invasive) = 0.90 (0.74-1.09)]. Additional analyses were performed according to characteristics of the DCIS lesion (size, malignancy grade, noncomedo or comedo type). In conclusion, our observations do not support the theory that reproductive history is associated with progression from noninvasive to invasive breast cancer.

Adolescent↗
PubMed2004

Effect of breast-conserving therapy versus radical mastectomy on prognosis for young women with breast carcinoma.

BACKGROUND: Among middle-aged and older women with early breast carcinoma, breast-conserving therapy (BCT) has been shown to have an effect on survival that is similar to that of modified radical mastectomy (RM). Nonetheless, it remains to be established whether BCT also is the optimal treatment option for early breast carcinoma in young women, because these women generally have more aggressive disease and a higher frequency of local recurrence compared with older women. METHODS: We investigated a cohort of 9285 premenopausal women with primary breast carcinoma who were age < 50 years at diagnosis. These women were identified from a population-based Danish breast carcinoma database containing detailed information on patient and tumor characteristics, predetermined treatment regimens, and survival. RESULTS: In total, 7165 patients (77.2%) were treated with RM, and 2120 patients (22.8%) were treated with BCT. We calculated the relative risk of death within the first 10 years after diagnosis according to surgical treatment and age, both before and after adjustment for known prognostic factors. No increased risk of death was observed among women who received BCT compared with women who underwent RM, regardless of age at diagnosis (< 35 years, 35-39 years, 40-44 years, or 45-49 years), despite the increased risk of local recurrence among young women. Restricting the analysis to women with small tumors (size < 2 cm) yielded similar results. CONCLUSIONS: Despite having a higher rate of local recurrence, young women with breast carcinoma who receive BCT are similar to young women treated with RM in terms of survival.

Adult↗
PubMed2004

Association between HLA-G genotype and risk of pre-eclampsia: a case-control study using family triads.

Pre-eclampsia affects 2-7% of all pregnancies with varying severity and is a leading cause of maternal and fetal mortality and morbidity. The aetiology involves almost certainly a combination of genetic predisposition with maternal and fetal contributions and environmental factors. Research points towards pathologies in the placenta as the triggering factor which leads to systemic endothelial dysfunction in the mother, probably as the result of interaction with released placental factors circulating in the maternal blood. One prominent hypothesis regarding the aetiology of pre-eclampsia suggests that it is caused by immune- maladaptation. The MHC class Ib gene, HLA-G, is expressed in the placenta and seems to have immunomodulatory functions. Aberrant HLA-G mRNA and protein expression in pre-eclamptic placentas have been reported. Here, we have investigated detailed HLA-G genotypes in a case-control study of 155 family triads of mother, father and newborn. Among primiparas, an overrepresentation of a homozygous HLA-G genotype was detected in the 40 pre-eclamptic offspring compared to the 70 controls [P = 0.002, Fisher's exact test; odds ratio 5.57 (95% CI 1.79-17.31)]. Further analyses suggested that the differences between pre-eclamptic cases and controls primarily were accomplished by a different transmission from the father of a 14 bp deletion/insertion polymorphism in exon 8 (P = 0.006, Fisher's exact test), which previously has been linked to differences in the levels of HLA-G expression and in HLA-G mRNA splicing. The results may also indicate that combined mother-child HLA-G genotypes could influence the risk of developing pre-eclampsia. Overall, the study suggests that HLA-G genotypes and expression might have a significant influence on development of pre-eclampsia.

Case-Control Studies↗
PubMed2004

Impact of routine vaccination with a conjugate Haemophilus influenzae type b vaccine.

Based on a unique nationwide registration of vaccinated children, we studied the impact of routine Hib vaccination with special emphasis on vaccine uptake and adherence, vaccine effectiveness with respect to Hib meningitis, and indirect effects with respect to Hib meningitis among the unvaccinated children. Uptake and adherence was generally satisfactory. We estimated >97% effectiveness for all three doses of vaccine and observed herd-immunity in unvaccinated children comparable to a vaccine effectiveness of 94% 3.5 years into the programme. In conclusion, nationwide routine Hib vaccination is highly effective in protecting against Hib meningitis, and rapid achievement of herd immunity is possible with catch-up vaccination of older children.

Adolescent↗
PubMed2004

Alcohol intake and risk of non-Hodgkin lymphoma in men and women.

OBJECTIVE: The effect of alcohol intake on risk of NHL is unclear. We therefore conducted a population-based case-control study to examine the association between alcohol and NHL risk. METHODS: 613 NHL cases and 480 population controls in Sweden reported their average consumption of beer, wine, and liquor 2 years before the study. Unconditional logistic regression was used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (CI) for associations between alcohol intake and NHL risk. RESULTS: Intake of total alcohol, beer, wine, or liquor was not associated with risk of overall NHL. There was no difference in risk of NHL among those who habitually consumed above 19.1 g of ethanol per day, compared to those who consumed on average 0-2.2 g of ethanol per day (OR = 1.2 (95% CI: 0.8, 1.7); Ptrend = 0.29). However, the association was significantly positive among males (OR = 1.8 (95% CI: 1.1, 2.9); Ptrend = 0.06). Total alcohol, beer, wine, or liquor intake was not associated with any major histopathologic subtype of NHL examined, apart from an association between high wine consumption and increased risk of chronic lymphocytic leukemia. CONCLUSIONS: Alcohol does not appear to be a major etiologic factor for overall NHL, nor its common subtypes.

Adult↗
PubMed2004

A nationwide Danish study of 1027 cases of congenital/infantile cataracts: etiological and clinical classifications.

OBJECTIVE: To study the distribution of congenital/infantile cataract in the entire population of Denmark according to etiological and clinical classifications. DESIGN: Population-based cohort study with retrospective chart review. PARTICIPANTS: All children (0 to 17 years old) who were born between 1959 and 2001 and registered with congenital/infantile cataract in Denmark during the period 1977 to 2001. Cases were ascertained from the mandatory Danish National Register of Patients, and all medical records were reviewed. METHODS: Etiological and clinical classifications of the cataract cases were based on information from the medical records. MAIN OUTCOME MEASURES: Classification of congenital/infantile cataract according to presumed etiology; gender; clinical appearance, including laterality and morphology; and the time trends according to etiology and laterality. RESULTS: A total of 1027 children with congenital/infantile cataract, 529 boys and 498 girls, were included, of whom 64% were bilateral. Males predominated with bilateral cataract, whereas females predominated with unilateral cases. Isolated cataract was the most frequent clinical presentation (71% of all cases), followed by an even proportion of cataract associated with additional ocular dysmorphology and cataract associated with systemic anomalies. Almost two thirds of all cases had an unknown etiology (idiopathic). Idiopathic cases showed a higher proportion of unilateral cataract and of additional ocular dysmorphology compared with cases of known etiology. The etiology was unknown in 87% of unilateral cases and in 50% of bilateral cases. The distribution by presumed etiology was stable during the study period, except for cataract caused by maternal infections, which decreased mainly due to the elimination of congenital rubella. CONCLUSIONS: With the exception of the decline of congenital rubella, the proportion of congenital/infantile cataract cases of unknown, genetic, and infectious origins has been stable since the late 1970s. The causes of 87% of unilateral cataracts and 50% of bilateral congenital/infantile cataracts remain unknown, making the prevention of the disease a continuing challenge.

Adolescent↗
PubMed2004

Human metapneumovirus and respiratory syncytial virus in hospitalized danish children with acute respiratory tract infection.

The newly discovered human metapneumovirus (hMPV) has been shown to be associated with respiratory illness. We determined the frequencies and clinical features of hMPV and respiratory syncytial virus (RSV) infections in 374 Danish children with 383 episodes of acute respiratory tract infection (ARTI). Study material comprised routine nasopharyngeal aspirates obtained during 2 winter seasons (November-May) 1999-2000 and 2001-2002 from children hospitalized at the Departments of Paediatrics, Hvidovre Hospital and Amager Hospital, Denmark. hMPV was detected in 11 (2.9%) and RSV in 190 (49.6%) ARTI episodes by real-time reverse transcription-polymerase chain reaction using primers targeting the hMPV N gene and the RSV L gene. Two children were co-infected with hMPV and RSV. They were excluded from statistical analysis. Hospitalization for ARTI caused by hMPV was restricted to very young children 1-6 months of age. Asthmatic bronchitis was diagnosed in 66.7% of hMPV and 10.6% of RSV-infected children (p < 0.001). Overall symptoms and clinical findings were similar among hMPV and RSV positive episodes, but more RSV-infected children required respiratory support. hMPV is present in young Danish children hospitalized with ARTI although less frequent than RSV and with a tendency to a milder clinical course.

Acute Disease↗
PubMed2004

Reproductive factors and extreme levels of maternal serum alpha-fetoprotein: a population-based study.

BACKGROUND: Levels of maternal alpha-fetoprotein (AFP) are increased during multiple gestations and preeclampsia but little is known regarding AFP levels in relation to other reproductive factors. Consequently, the objective of this work was to describe the possible relationship between AFP levels during pregnancy and maternal age at birth, maternal age at first birth, parity, time since previous birth and gender of the offspring. METHODS: Based on national registries we obtained the reproductive history on a population-based cohort of 44 227 women who had serum AFP levels determined in gestational weeks 14-21 and whose present and previous pregnancies resulted in live-born singletons. RESULTS: Many previous births and an interval of less than 2 years since last birth were significantly associated with extremely low levels of AFP in the mother. However, age at first birth and age at present pregnancy did not influence the AFP level. Women who gave birth to a girl had AFP levels that were 5%[95% confidence interval (CI) 4-6%] lower than those of women who had a boy. Adjustment for birthweight did not significantly affect the estimate. CONCLUSIONS: Low serum AFP levels in pregnancy are significantly correlated with high parity and with a short interval between births. The significantly lower levels of AFP in women who gave birth to girls could indicate a possible gender-specific regulatory mechanism.

Adolescent↗
PubMed2004

Incidence and cumulative risk of childhood cataract in a cohort of 2.6 million Danish children.

PURPOSE: To determine the incidence and cumulative risk of childhood cataract in Denmark during 1980 to 2000. METHODS: A cohort of 2,616,439 Danish children born between 1962 and 2000 was followed from 1980 or from the day of birth, whichever occurred later, until their 18th birthday, death, emigration, or diagnosis of cataract, whichever occurred first. Cases were ascertained from the Danish National Register of Patients (NRP) and validated by reviewing the medical records. They were divided into four groups: congenital/infantile (CI) cataract, traumatic cataract, complicated cataract, and "other" types of cataract. RESULTS: After diagnostic validation, 1311 children with cataract (59% with CI cataract) were included in the study. During 1995 to 2000 the overall cumulative risk of childhood cataract was 108.4 per 100,000 children. There was no significant difference in incidence between girls and boys or over time (1980 to 2000) for CI, complicated, and "other" types of cataract. In contrast, the incidence of traumatic cataract was significantly higher among boys. It remained increased during the entire study period despite a 23% decrease per 5 years among boys. Sixty-six percent of the children diagnosed with CI cataract below 2 years of age underwent surgery within 1 year. CONCLUSIONS: The stable incidence during a 20-year period of CI cataract and complicated cataract indicates that risk factors for these conditions have remained unchanged, whereas the marked drop of traumatic cataract among boys most likely reflects changed behavior and an increased focus on preventive measures.

Adolescent↗
PubMed2004

Intussusception in early childhood: a cohort study of 1.7 million children.

OBJECTIVE: To describe incidence and temporal trends of intussusceptions in Danish children during 1980 to 2001. METHODS: A population-based cohort study was conducted of 1.67 million children who were younger than 5 years during 1980 to 2001 and were followed up for 6.66 million person-years. The Danish National Patient Registry was used to identify cases of intussusception in the cohort. Age-specific incidence rates were main outcome measure. RESULTS: A total of 1814 cases of intussusception among children who were younger than 5 years were reported from 1980 to 2001. The incidence rate remained fairly constant during 1980 to 1990 but decreased by 55% (95% confidence interval: 43%-65%) from 1990 to 2001. The reduction was most pronounced among children aged 3 to 5 months. CONCLUSIONS: The incidence of intussusception among Danish children declined significantly during the 1990s, particularly among infants 3 to 5 months of age.

Age Distribution↗
PubMed2004

A population-based registry study of infant mortality in the Arctic: Greenland and Denmark, 1973-1997.

OBJECTIVES: We sought to determine precise estimates of infant mortality rates and to describe overall trends in infant mortality in Greenland and Denmark from 1973 to 1997. METHODS: We analyzed data from population-based registries of all live-born infants in Greenland and Denmark to calculate infant mortality rates from 1973 to 1997. RESULTS: Between the periods of 1973-1977 and 1993-1997, neonatal mortality rates in Greenland declined from 20.9 per 1000 live-born infants to 15.7, and postneonatal mortality rates declined from 20.9 per 1000 to 5.9. Infant mortality rates were significantly higher in Greenland than in Denmark, and the excess mortality was uniformly distributed over all birthweight percentiles. In Greenland, the risk of infant death was significantly lower if the mother was born outside Greenland. CONCLUSIONS: Postneonatal mortality rates in Greenland have decreased significantly during the past 25 years, but little progress has been made in decreasing neonatal mortality rates. Disparities exist among children with different maternal origins.

Arctic Regions↗
PubMed2004

The Greenlandic research database: a population-based research resource.

Information on past exposures is often warranted in health studies in Greenland, as living conditions have changed markedly in this century. To provide a longitudinal population-based research tool with such information the Department of Epidemiology Research at Statens Serum Institut has established 'The Greenlandic Research Database', a comprehensive population-based database comprising data from Greenland from national registers, population-based longitudinal and cross-sectional studies and human biological samples from 1979 to the present day.

Adult↗
PubMed2004

Cancer in Greenlandic Inuit 1973-1997.

OBJECTIVES: During the second half of the 20th century living conditions of the Inuit populations in the Arctic have undergone major transitions. The objective was to investigate how the cancer pattern was affected by these changes, using data from the Danish Cancer Registry and the Civil Registration System. RESULTS: In the period 1973-1997 total cancer incidence increased by 4% per 5 years for men and 6% per 5 years for women. The incidence of lung, stomach, breast and colon cancer increased in both sexes, whereas the incidence of cervical cancer decreased. CONCLUSIONS: Thus, the overall cancer incidence among Greenlandic Inuit is increasing as a result of increases in several cancers that are common in Western populations. In contrast to global trends, a significant increase in the incidence of stomach cancer in both sexes was observed.

Female↗
PubMed2003

Birth weight and risk of breast cancer in a cohort of 106,504 women.

The possible association between prenatal factors and breast cancer has been discussed for more than a decade. Birth weight has been used commonly as a proxy measure for intrauterine growth. Whereas some previous studies have found support for an association between birth weight and breast cancer, others have been inconclusive or found no association. We investigated the relationship between birth weight and risk of female breast cancer in a cohort of 106,504 Danish women. Birth weights were obtained from school health records on girls born between 1930-1975. Information on breast cancer came from linking the cohort with the Danish Cancer Registry and the Danish Breast Cancer Cooperative Groups Registry. A total of 2,334 cases of primary breast cancer were diagnosed in the cohort during 3,255,549 person-years of follow-up among women with birth weight between 500-6,000 g. Of these, 922 (40%) were diagnosed with primary breast cancer at the age of 50 years or older. A significant association between birth weight and breast cancer was found equivalent to an increase in risk of 9% per 1,000 g increase in birth weight (95% CI 2-17). The increase was observed for all age groups, representing both pre- and post-menopausal women, and irrespective of tumor characteristics. Adjustment for age at first birth and parity did not influence the results. Birth weight is positively associated with risk of breast cancer, indicating that prenatal factors are important in the etiology of breast cancer.

Adolescent↗
PubMed2003

Cancer in Greenlandic Inuit 1973-1997: a cohort study.

The increasing westernization of the Arctic countries may influence the very particular cancer profile of these populations. Our objective was to investigate the development in cancer incidence from 1973 to 1997 in a large and well-defined Inuit population in Greenland. Greenland is part of the Danish Kingdom, and population statistics covering both countries are available from the same registry resource. Data from the Danish Civil Registration System and from the Danish Cancer Registry were used to calculate age-standardized cancer incidence rates for the periods 1973-1987 and 1988-1997 for persons born in Greenland. Using rates for Denmark, sex-specific standardized incidence ratios (SIRs) for 1988-1997 were calculated. Furthermore, age- and sex-specific incidence rates in the 2 periods were calculated for selected cancers. Total cancer incidence increased from 248.5 to 277.9 per 100,000 person-years in men and from 269.4 to 302.2 per 100,000 person-years in women. The incidence of lung, stomach, breast and colon cancer increased, whereas the incidence of cervical cancer decreased. Compared to the Caucasian population in Denmark, high SIRs were found for cancers of the nasopharynx, salivary gland, esophagus, stomach and cervix and low SIRs for testis, bladder, prostate, breast and hematologic cancers. Overall cancer incidence among Greenlandic Inuit is increasing as a result of increases in several cancers that are common in Western populations. A significant increase in the incidence of stomach cancer in both sexes, which contrasts global trends for this cancer, warrants further investigation.

Cohort Studies↗
PubMed2003

Birth weight as a risk factor for childhood leukemia: a meta-analysis of 18 epidemiologic studies.

Evidence has emerged that childhood leukemia is initiated in utero. High birth weight is one of the few birth-related factors that has been associated with childhood leukemia, albeit not consistently. The authors conducted a meta-analysis of studies of the association between birth weight and childhood leukemia risk. Study-specific odds ratios for leukemia were calculated, using a cutoff at 4,000 g of birth weight. The authors also evaluated whether the association between birth weight and leukemia followed a log-linear dose-response-like pattern. They calculated summary estimates using weighted averages of study-specific odds ratios from dichotomous and trend analyses. Eighteen studies (published between 1962 and 2002) were included, encompassing 10,282 children with leukemia. Children weighing 4,000 g or more at birth were at higher risk of acute lymphoblastic leukemia than children weighing less (odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.17, 1.37). Furthermore, data were consistent with a dose-response-like effect (OR = 1.14/1,000-g birth weight increase, 95% CI: 1.08, 1.20). Studies of acute myeloid leukemia indicated a similar increase in risk for children weighing 4,000 g or more at birth (OR = 1.27, 95% CI: 0.73, 2.20) and a dose-response-like effect (OR = 1.29/1,000 g, 95% CI: 0.80, 2.06), but results varied across studies. Our findings support a relation between birth weight and childhood acute lymphoblastic leukemia risk and emphasize the need for additional studies of the biologic mechanisms underlying this association.

Adolescent↗