Jesper Lier Boldsen

Population based study of risk factors for underdiagnosis of asthma in adolescence: Odense schoolchild study.

Abstract Objective: To describe factors related to underdiagnosis of asthma in adolescence. Design: Subgroup analysis in a population based cohort study. Setting: Odense municipality, Denmark. Subjects: 495 schoolchildren aged 12 to 15 years were selected from a cohort of 1369 children investigated 3 years earlier. Selection was done by randomisation (n=292) and by a history indicating allergy or asthma-like symptoms in subject or family (n=203). Main outcome measures: Undiagnosed asthma defined as coexistence of asthma-like symptoms and one or more obstructive airway abnormalities (low ratio of forced expiratory volume in 1 second to forced vital capacity, hyperresponsiveness to methacholine or exercise, or peak flow hypervariability) in the absence of physician diagnosed asthma. Risk factors (odds ratios) for underdiagnosis. Results: Undiagnosed asthma comprised about one third of all asthma identified. Underdiagnosis was independently associated with low physical activity, high body mass, serious family problems, passive smoking, and the absence of rhinitis. Girls were overrepresented among undiagnosed patients with asthma (69%) and underrepresented among diagnosed patients (33%). Among the risk factors identified, low physical activity and problems in the family were independently associated with female sex. The major symptom among those undiagnosed was cough (58%), whereas wheezing (35%) or breathing trouble (50%) was reported less frequently than among those diagnosed. Less than one third of those undiagnosed had reported their symptoms to a doctor. Conclusions: Asthma, as defined by combined symptoms and test criteria, was seriously underdiagnosed among adolescents. Underdiagnosis was most prevalent among girls and was associated with a low tendency to report symptoms and with several independent risk factors that may help identification of previously undiagnosed asthmatic patients. Key messages One third of young people with asthma are not diagnosed; most are girls Undiagnosed asthma is associated with low physical activity, high body mass index, serious family problems, passive smoking, and the absence of symptoms of rhinitis Cough is the most common symptom among those with undiagnosed asthma Two thirds of those with undiagnosed asthma do not report their symptoms to a doctor, suggesting a need for targeted asthma campaigns

Genome-wide comparison of medieval and modern Mycobacterium leprae

Leprosy: Ancient and Modern In medieval Europe, leprosy was greatly feared: Sufferers had to wear bells and were shunned and kept isolated from society. Although leprosy largely disappeared from Europe in the 16th century, elsewhere in the world almost a quarter of a million cases are still reported annually, despite the availability of effective drugs. Schuenemann et al. (p. 179, published online 13 June; see the 14 June News story by Gibbons, p. 1278) probed the origins of leprosy bacilli by using a genomic capture-based approach on DNA obtained from skeletal remains from the 10th to 14th centuries. Because the unique mycolic acids of this mycobacterium protect its DNA, for one Danish sample over 100-fold, coverage of the genome was possible. Sequencing suggests a link between the middle-eastern and medieval European strains, which falls in line with social historical expectations that the returning expeditionary forces of antiquity originally spread the pathogen. Subsequently, Europeans took the bacterium westward to the Americas. Overall, ancient and modern strains remain remarkably similar, with no apparent loss of virulence genes, indicating it was most probably improvements in social conditions that led to leprosys demise in Europe. Five European individuals who lived during the Middle Ages provide a look backward at leprosy. Leprosy was endemic in Europe until the Middle Ages. Using DNA array capture, we have obtained genome sequences of Mycobacterium leprae from skeletons of five medieval leprosy cases from the United Kingdom, Sweden, and Denmark. In one case, the DNA was so well preserved that full de novo assembly of the ancient bacterial genome could be achieved through shotgun sequencing alone. The ancient M. leprae sequences were compared with those of 11 modern strains, representing diverse genotypes and geographic origins. The comparisons revealed remarkable genomic conservation during the past 1000 years, a European origin for leprosy in the Americas, and the presence of an M. leprae genotype in medieval Europe now commonly associated with the Middle East. The exceptional preservation of M. leprae biomarkers, both DNA and mycolic acids, in ancient skeletons has major implications for palaeomicrobiology and human pathogen evolution.

Transition analysis: A validation study with known‐age modern American skeletons

Transition Analysis-a recent skeletal age-estimation procedure (Boldsen et al.: Paleodemography: age distributions from skeletal samples (2002) 73-106)-is evaluated using 252 known-age modern American males and females from the Bass Donated Collection and Mercyhurst forensic cases. The pubic symphysis worked best for estimating age, followed by the sacroiliac joint and cranial sutures. Estimates based on all skeletal characteristics are influenced by the choice of prior distribution, although its effect is dwarfed by both the inaccuracy and imprecision of age estimates. Age intervals are narrowest for young adults, but are surprisingly short in old age as well. When using an informative prior distribution, the greatest uncertainty occurs from the late 40s into the 70s. Transition Analysis estimates do not perform as well as experience-based assessments, indicating the existing procedure is too narrowly focused on commonly used pelvic and cranial structures.

Suicide in patients with Parkinson's disease : an epidemiological study

The purpose of this study was to estimate the risk of suicide for patients with Parkinsons disease (PD) in Denmark compared with that in the background population. The study involved 458 patients with a PD diagnosis, 226 men and 232 women. The follow‐up period to either death or end of follow‐up on December 31, 1990 was 0 to 17 years, mean 5.7 years. Deaths in the follow‐up period amounted to 254, 135 men and 119 women. Two women committed suicide. The number of expected suicides was 1.06 for men and 0.55 for women, a total of 1.62. Neither for men nor for women was the difference between expected and observed suicides statistically significant.

Functional ovarian cysts in premenopausal and gynecologically healthy women

The present study describes 29 women coincidentally found to have ovarian cysts while participating in a cross-sectional study. The prevalence of functional ovarian cysts is determined. In this study, 428 women, aged 14-45 years, were examined by transvaginal ultrasonography. The women were gynecologically healthy and were using either no contraception, intrauterine contraceptive devices, none of which were hormone releasing, or oral contraception (OC). Cysts were defined as cystic spaces larger than 30 mm. All women were asymptomatic and regularly menstruating.The prevalence of ovarian cysts was lower for women using OC than for women using no contraception or using intrauterine contraceptive devices. The relative risk (measured as the prevalence proportion ratio) of having an ovarian cyst when using OC was 0.22 (CI: 0.13-0.39), compared to women not using OC. No difference was found in the prevalence of ovarian cysts between women using intrauterine contraceptive devices and women using no contraception. The prevalence of ovarian cyst increased throughout the menstrual cycle in women not using OC. This relation was not found in the group of users of OC. The majority of the cysts resolved within the first few days of menstruation. Sixty-five percent of the cysts persisting after menstruation had resolved at the first control examination 3 months later, independently of use of OC. Low-dose monophasic contraceptive pills seem to have a protective effect against development of functional ovarian cysts, independent of the type of gestagen and the dose of ethinylestradiol used. Ovarian cysts resolved independently of treatment with OC. The use of intrauterine contraceptive device had no influence on the occurrence of functional ovarian cysts.

Genotypes for the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human longevitY. Role of CYP2D6 and CYP2C19 in longevity.

AbstractObjective: To test whether some genotypes for CYP2D6 or CYP2C19 could contribute to longevity, we genotyped 241 Danish nonagenarians and centenarians for CYP2D6 and CYP2C19. Methods: For CYP2D6 we identified the alleles CYP2D6*1, CYP2D6*3 and CYP2D6*4 with allele-specific polymerase chain reaction (PCR). The CYP2D6*5 alleles were identified with a long PCR method. For CYP2C19 we identified the alleles CYP2C19*1, CYP2C19*2 and CYP2C19*3 with an oligonucleotide ligation assay. Results: The four alleles for CYP2D6 did not occur in Hardy-Weinberg proportions. The frequency of poor metabolism was slightly higher (10.2%) than expected [7.7%; odds ratio (OR) = 1.36 (0.75–2.40)]. The genotypes for CYP2C19 occur in Hardy-Weinberg proportions. The frequency of poor metabolism (3.8%) was not significantly different from a young control group [3.1%; OR = 1.21 (0.26–5.75)]. Conclusion: CYP2D6 could play a role in human longevity due to the lack of Hardy-Weinberg proportions. If CYP2D6 only plays a role in longevity by protecting the poor metabolizers from cancer, we should expect a rise in the frequency in these genotypes in Denmark from 7.7% among young adults to 10–11% among very old people. We found a frequency of poor metabolism of 10.2% in the very old group. CYP2C19 is – due to the occurrence of Hardy-Weinberg proportions and the expected number of poor metabolizers – unlikely to contribute to human longevity.

Regional and social analysis of height variation in a contemporary British sample

The height distributions of 11-year-old boys and girls and their parents (N = 33 000) comprising the National Child Development Study are reported. The variance in height was found to differ significantly between social classes for all three family positions (father, mother and child). Analysis of variance and cluster analysis revealed that stature distributions in all three family positions is more socially rather than regionally differentiated.

Humeral and Femoral Head Diameters in Recent White American Skeletons

Abstract:  Osteologists often rely on single measurements, such as humeral and femoral head diameters, to estimate sex, especially when skeletons are incomplete. Measurements of 237 Bass Donated Collection skeletons provide a means of distinguishing white American females from males based on a modern sample: humeral head, female mean 42.1 mm, male mean 49.0 mm; and femoral head, female mean 42.2 mm, male mean 48.4 mm. Probabilities that bones at 1‐mm increments came from females (pf) are estimated (pm = 1 − pf). An overrepresentation of one sex in the skeletons that are examined influences the probability that a bone of a certain size is from a female or male. So, probabilities are also estimated for samples consisting of an unequal number of males and females. Sample composition has its greatest effect when one sex dominates the remains that are the subject of investigation.

Birth Order and Health Status in a British National Sample

Researchers analyzed data from the National Child Development Study--a cohort of every child born in England, Scotland, and Wales during the 1st week of March 1953 with follow up studies in 1965, 1969, 1973, and 1980-1981 to examine the relationship between health status and birth order and whether children with low birth orders were less likely to experience illness than those with older siblings. 1st born children tended to have received the needed number of immunizations, but children of higher birth order did not tend to have received them. Further they were more likely to have attended infant welfare and toddler clinics for health care than children of higher birth order. The only childhood contagious disease which demonstrated a social class effect was pertussis. It tended to afflict children from nonmanual homes regardless of birth order. Absences from school lasting between 1 week-1 month of 1st born children were less frequent than for other children. The leading reasons for 1st, 3rd, and later born 11 year old children who experienced such long absences included infectious diseases; bronchitis; ear, nose, and throat complaints; pneumonia; tonsillitis, or viral influenza. After age 15, 1st and 2nd born children were less likely to be absent and, if absent, they tended to only miss 1 week of school. Significantly more 3rd and 4th born children were absent from school for 1 week-3 months. 1st and 2nd born children from more affluent families tended to have early childhood asthma. In conclusion, the health experiences of the later birth orders were different than those of the 1st born. This did not mean, however, that later birth order children were in poorer health than 1st born children.

Season of birth and recalled age at menarche.

All 8th-form schoolgirls from the municipality of Odense in Denmark were asked at what age they reached menarche, and 886 girls (97.6%) gave this information. There is no evidence for seasonality in the time of birth but for far more girls than expected menarche occurred during winter or summer and fewer than expected during spring and autumn. This pattern appears primarily in girls living in the suburbs and was not seen in those living in central Odense. The seasonality appears to be brought about by differences in mean age at menarche according to time of the year at birth.