Type 1 diabetes in children born after assisted reproductive technology: a register-based national cohort study.

STUDY QUESTION: Do children born after assisted reproductive technology (ART) have an increased risk of developing type 1 diabetes? SUMMARY ANSWER: Children born after ART were found to have an increased risk of type 1 diabetes in the unadjusted analysis, while after adjustment this association was only significant in children born after frozen embryo transfer. WHAT IS KNOWN ALREADY?: Some studies raise concerns as to whether fertility treatments may influence long-term morbidity in children born after ART. Elevated blood pressure and altered glucose metabolism have been found after ART in a few studies. STUDY DESIGN, SIZE, DURATION: A register-based national cohort study that included all children born in Sweden between 1985 and 2015-in total, 3 138 540 children-was carried out. PARTICIPANTS/MATERIAL, SETTING, METHODS: The study was population-based and all live-born singleton children born after ART (n = 47 938) or spontaneous conception (SC) (n = 3 090 602) were included. The ART cohort comprised 36 727 children born after fresh embryo transfer and 11 211 children born after frozen embryo transfer. Several national registries were used together with data from Statistics Sweden. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 202 children born after ART and 17 916 children born after SC developed type 1 diabetes, corresponding to 43.4 and 35.5 per 100 000 person-years at risk (hazard ratio [HR] 1.23; 95% confidence interval [CI], 1.07 to 1.42). Mean follow-up was 9.7 (SD 6.4) years for ART children and 16.3 (SD 9.2) years for SC children. After adjustment for calendar year of birth, HR for type 1 diabetes was 1.13; 95% CI, 0.98-1.30. After further adjustment for sex, maternal age, country of birth, educational level, smoking and parental diabetes, HR was 1.07; 95% CI, 0.93-1.23. In subgroup analyses, an association was found between frozen embryo transfer and type 1 diabetes (adjusted HR 1.52; 95% CI, 1.08-2.14 and 1.41; 95% CI, 1.05-1.89 for frozen versus fresh and frozen versus SC, respectively). When comparing intracytoplasmic sperm injection to in vitro fertilization, no difference was found (adjusted HR 1.08; 95% CI, 0.77-1.51). LIMITATIONS, REASONS FOR CAUTION: Limitations were the missing data and residual confounding caused by unknown confounders. Furthermore, the control group consisted of all children not conceived by ART and not non-ART children from subfertile mothers. The study was also performed in only singletons and not in the total ART population. WIDER IMPLICATIONS OF THE FINDINGS: Type 1 diabetes is a serious disease, affecting human life in several ways, including risk of serious complications, reduced life span and a life-long treatment. Our results are generally reassuring, showing no increase in diabetes in ART children compared to children born after SC after adjustment for relevant confounders. The observation of an association between children born after frozen embryo transfer and type 1 diabetes, although based on subgroup analyses with a limited number of children and modest in size, is however a reason for concern. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Nordforsk 71450, the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement 70940, and the Hjalmar Svensson Foundation. The authors have no competing interests. TRIAL REGISTRATION NUMBER: ISRCTN 11780826.

Time to revise the paradigm of hantavirus syndromes? Hantavirus pulmonary syndrome caused by European hantavirus.

Hantaviruses have previously been recognised to cause two separate syndromes: hemorrhagic fever with renal syndrome in Eurasia, and hantavirus pulmonary syndrome (HPS) in the Americas. However, increasing evidence suggests that this dichotomy is no longer fruitful when recognising human hantavirus disease and understanding the pathogenesis. Herein are presented three cases of severe European Puumala hantavirus infection that meet the HPS case definition. The clinical and pathological findings were similar to those found in American hantavirus patients. Consequently, hantavirus infection should be considered as a cause of acute respiratory distress in all endemic areas worldwide.

Insomnia is more common among subjects living in damp buildings.

BACKGROUND: Insomnia is a condition with a high prevalence and a great impact on quality of life. Little is known about the relation between and sleep disturbances and the home environment. AIM: To analyse the association between insomnia and building dampness. METHODS: In a cross-sectional, multicentre, population study, 16 190 subjects (mean age 40 years, 53% women) were studied from Reykjavik in Iceland, Bergen in Norway, Umeå, Uppsala, and Göteborg in Sweden, Aarhus in Denmark, and Tartu in Estonia. Symptoms related to insomnia were assessed by questionnaire. RESULTS: Subjects living in houses with reported signs of building dampness (n = 2873) had a higher prevalence of insomnia (29.4 v 23.6%; crude odds ratio 1.35, 95% CI 1.23 to 1.48). The association between insomnia and different indicators of building dampness was strongest for floor dampness: "bubbles or discoloration on plastic floor covering or discoloration of parquet floor" (crude odds ratio 1.96, 95% CI 1.66 to 2.32). The associations remained significant after adjusting for possible confounders such as sex, age, smoking history, housing, body mass index, and respiratory diseases. There was no significant difference between the centres in the association between insomnia and building dampness. CONCLUSION: Insomnia is more common in subjects living in damp buildings. This indicates that avoiding dampness in building constructions and improving ventilation in homes may possibly have a positive effect on the quality of sleep.

Metal artefact reduction in CT imaging of hip prostheses­an evaluation of commercial techniques provided by four vendors.

OBJECTIVE: The aim of this study was to evaluate commercial metal artefact reduction (MAR) techniques in X-ray CT imaging of hip prostheses. METHODS: Monoenergetic reconstructions of dual-energy CT (DECT) data and several different MAR algorithms, combined with single-energy CT or DECT, were evaluated by imaging a bilateral hip prosthesis phantom. The MAR images were compared with uncorrected images based on CT number accuracy and noise in different regions of interest. RESULTS: The three MAR algorithms studied implied a general noise reduction (up to 67%, 74% and 77%) and an improvement in CT number accuracy, both in regions close to the prostheses and between the two prostheses. The application of monoenergetic reconstruction, without any MAR algorithm, did not decrease the noise in the regions close to the prostheses to the same extent as did the MAR algorithms and even increased the noise in the region between the prostheses. CONCLUSION: The MAR algorithms evaluated generally improved CT number accuracy and substantially reduced the noise in the hip prostheses phantom images, both close to the prostheses and between the two prostheses. The study showed that the monoenergetic reconstructions evaluated did not sufficiently reduce the severe metal artefact caused by large orthopaedic implants. ADVANCES IN KNOWLEDGE: This study evaluates several commercially available MAR techniques in CT imaging of large orthopaedic implants.

The relationship between indicators of building dampness and respiratory health in young Swedish adults.

Several epidemiological studies have indicated that building dampness affects the respiratory health of the inhabitants. In this study we investigated the relationship between building dampness and respiratory symptoms in young Swedish adults. In 1993, as a part of the European Community Respiratory Health Survey stage II, subjects were invited to participate in a detailed interview-led questionnaire, spirometry, methacholine challenge and measurement of total and specific IgE. A total of 1853 of the 2084 selected subjects participated in this study (88.9%). One hundred and thirty-six (7.4%) subjects reported water damage in their homes in the last year and 318 (17.3%) subjects reported visible molds during the same period. Seventy-four (4%) subjects reported both water damage and visible molds in the last year. This subgroup, with 74 subjects had significantly more attacks of breathlessness both when resting (OR 3.2 (95% CI 1.4-7.2)) and after effort (OR 2.7 (95% CI 1.3-5.6)) compared to subjects reporting no water damage or molds. Long-term cough was also more common in this group (OR 2.2 (95% CI 1.2-4.0)). This study adds evidence to a relationship between damp buildings and respiratory symptoms.

Prevalence of bronchial hyper-responsiveness in the southern, central and northern parts of Sweden.

Studies have suggested that there is a higher prevalence of asthma in northern Sweden than in southern Sweden. Bronchial hyper-responsiveness (BHR) has been shown to be associated with asthma. The aim of this study was to explore the prevalence of bronchical hyper-responsiveness in different parts of Sweden. As part of the European Community Respiratory Health Survey (ECRHS), interviews, skin prick tests, lung function tests and methacholine provocation tests of the airways were performed in 1448 randomly selected subjects in southern, central and northern Sweden. The Mefar dosimeter was used according to the ECRHS protocol. The responsiveness was calculated both as the PD20 and as the dose response slope (DRS). BHR was defined as a PD20 of < or = 1.6 mg. Atopy was defined as at least one skin prick test of > or = 3 mm. The prevalence of BHR was 12.7%, 10.6% in men and 15.0% in women. No difference in prevalence was found between the three different regions of Sweden. The prevalence of BHR was higher in women than in men and higher in smokers than in non-smokers. Using multiple logistic regression, with BHR as the dependent variable, atopy, being female, having a low FEV1 (% predicted) and smoking (both own and passive) increased the odds of having BHR, while age and the region of Sweden did not influence BHR. Defining BHR as a PD20 of < or = 1.0 mg or a PD20 of < or = 2.0 mg did not change this. Multiple regression using log DRS as the dependent variable produced the same result. Both BHR and increasing DRS were associated with self-reported wheezing, attacks of shortness of breath during the daytime at rest or after strenuous activity, being awakened by a feeling of tightness in the chest or an attack of shortness of breath. In subjects without self-reported asthma, BHR was associated with self-reported wheezing and attacks of shortness of breath after strenuous activity. In conclusion, we found that the prevalence of BHR in the three investigated areas was 12.7%. We found a trend towards a higher prevalence of BHR in the most northerly of the study areas, but the difference between the areas was not statistically significant. BHR and DRS were associated with atopy, smoking, female sex and FEV1 (% predicted). The reporting of symptoms from the airways was associated with the degree of bronchical responsiveness.

Is birth weight related to lung function and asthma symptoms in Nordic-Baltic adults?

Studies of birth characteristics and respiratory outcomes show contradictory findings. We wanted to investigate the association of birth weight with adult lung function as well as asthma symptoms while addressing the influence of demographic and environmental factors. Data was collected from the birth records of 1683 men and women born in 1947-1973 who were included in 6 Nordic-Baltic population samples investigated within the European Community Respiratory Health Survey (ECRHS). In the adults, an increase in birth weight from below 2500 g to above 4000 g was associated with an increase from 96% to 104% predicted one-second forced expiratory volume (P<0.01) and from 1.00% to 107% predicted forced vital capacity (P<0.01). However, birth weight was not associated with symptoms of asthma. After adjustment for birth length, gender, age, study centre, adult BMI, allergic rhinitis, parental and adult tobacco smoke exposure in multivariate regression analyses, birth weight was not associated with adult lung function or asthma symptoms. Further sub-sample analyses revealed no influence of gestational age, gender, age or geographical area. In this historic prospective cohort study an association was neither found between birth weight and adult lung function nor between birth weight and asthma symptoms.

Optimizing the tube potential for lumbar spine radiography with a flat-panel digital detector.

The purpose of this study was to find the optimal settings for lumbar spine radiography with a flat-panel detector. A CDRAD contrast-detail phantom was imaged at various tube potentials, system speeds and filtration settings. Factorial experiments yielded a range of optimized exposure settings, which were submitted to visual grading analysis with images of an Alderson phantom. The first optimized settings involved a system speed increase from 400 to 800. For anteroposterior projection, the optimal tube potential was reduced from the default of 77 kV to 60 kV to give the best image quality without increasing the effective dose, or to 66 kV to give the lowest dose without reducing image quality. For lateral projection, the tube potential was similarly reduced from the default of 90 kV to 70 kV or 77 kV. Visual grading analysis confirmed the results, with significantly better image quality when optimizing for image quality. The study thus shows that the tube potential can be reduced as long as the system speed is increased simultaneously. This leads to a lower effective dose and/or increased image quality depending on the settings chosen. The factorial experiments provided a powerful way to evaluate several parameters concomitantly.

Remission of asthma: a prospective longitudinal study from northern Europe (RHINE study).

The aim of the present study was to investigate the remission rate of adult asthma in a general population sample in relation to age, sex, asthma symptoms, allergic rhinitis and smoking. A follow-up of the random population samples from the European Community Respiratory Health Survey in Northern Europe was conducted from 1999-2001 on 1,153 individuals (aged 26-53 yrs) with reported asthma. Remission was defined as no asthmatic symptoms in two consecutive years and no current use of asthma medication. Remission rates per 1,000 person-yrs were calculated and Cox regression models, adjusting for confounders, were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). An average remission rate of 20.2 per 1,000 person-yrs was found. There was no significant difference according to sex; the remission rates were 21.7 and 17.8 per 1,000 person-yrs in females and males, respectively. An increased remission rate was observed among subjects who quit smoking during the observation period. Subjects not reporting any asthma symptom at baseline had an increased remission rate. In the Cox regression model, ex-smoking (HR 1.65, 95% CI 1.01-2.71) was associated with increased remission rate, and reporting any asthma symptom at baseline was associated with decreased remission rate (HR 0.7, 95% CI 0.40-0.90). In conclusion, the present prospective longitudinal study showed that quitting smoking and the presence of mild disease appeared to favour remission.

Prevalence and incidence of respiratory symptoms in relation to indoor dampness: the RHINE study.

BACKGROUND: An association between indoor dampness and respiratory symptoms has been reported, but dampness as a risk factor for the onset or remission of respiratory symptoms and asthma is not well documented. METHOD: This follow up study included 16 190 subjects from Iceland, Norway, Sweden, Denmark, and Estonia who had participated in the European Community Respiratory Health Survey (ECRHS I). Eight years later the same subjects answered a postal questionnaire that included questions on respiratory symptoms and indicators of indoor dampness. RESULTS: Subjects living in damp housing (18%) had a significantly (p<0.001) higher prevalence of wheeze (19.1% v 26.0%), nocturnal breathlessness (4.4% v 8.4%), nocturnal cough (27.2% v 36.5%), productive cough (16.6% v 22.3%) and asthma (6.0% v 7.7%). These associations remained significant after adjusting for possible confounders. Indoor dampness was a risk factor for onset of respiratory symptoms but not for asthma onset in the longitudinal analysis (OR 1.13, 95% CI 0.92 to 1.40). Remission of nocturnal symptoms was less common in damp homes (OR 0.84, 95% CI 0.73 to 0.97). CONCLUSIONS: Subjects living in damp housing had a higher prevalence of respiratory symptoms and asthma. Onset of respiratory symptoms was more common and remission of nocturnal respiratory symptoms was less common in subjects living in damp housing.

A clinical evaluation of the image quality computer program, CoCIQ.

To provide an objective way of measuring image quality, a computer program was designed that automatically analyzes the test images of a contrast-detail (CD) phantom. The program gives a quantified measurement of image quality by calculating an Image Quality Figure (IQF). The aim of this work was to evaluate the program and adjust it to clinical situations in order to find the detectable level where the program gives a reliable figure of the contrast resolution. The program was applied on a large variety of images with lumbar spine and urographic parameters, from very low to very high image qualities. It was shown that the computer program produces IQFs with small variations and there were a strong linear statistical relation between the computerized evaluation and the evaluation performed by human observers (R2= 0.98). This method offers a fast and easy way of conducting image quality evaluations.

Association of asthma and hay fever with irregular menstruation.

BACKGROUND: There is some evidence that asthmatic women are more likely to have abnormal sex hormone levels. A study was undertaken to determine whether asthma and allergy were associated with irregular menstruation in a general population, and the potential role of asthma medication for this association. METHODS: A total of 8588 women (response rate 77%) participated in an 8 year follow up postal questionnaire study of participants of the ECRHS stage I in Denmark, Estonia, Iceland, Norway, and Sweden. Only non-pregnant women not taking exogenous sex hormones were included in the analyses (n = 6137). RESULTS: Irregular menstruation was associated with asthma (OR 1.54 (95% CI 1.11 to 2.13)), asthma symptoms (OR 1.47 (95% CI 1.16 to 1.86)), hay fever (OR 1.29 (95% CI 1.05 to 1.57)), and asthma preceded by hay fever (OR 1.95 (95% CI 1.30 to 2.96)) among women aged 26-42 years. This was also observed in women not taking asthma medication (asthma symptoms: OR 1.44 (95% CI 1.09 to 1.91); hay fever: OR 1.27 (95% CI 1.03 to 1.58); wheeze preceded by hay fever: OR 1.76 (95% CI 1.18 to 2.64)). Irregular menstruation was associated with new onset asthma in younger women (OR 1.58 (95% CI 1.03 to 2.42)) but not in women aged 42-54 years (OR 0.62 (95% CI 0.32 to 1.18)). The results were consistent across centres. CONCLUSIONS: Younger women with asthma and allergy were more likely to have irregular menstruation. This could not be attributed to current use of asthma medication. The association could possibly be explained by common underlying metabolic or developmental factors. The authors hypothesise that insulin resistance may play a role in asthma and allergy.

The association between birth size and atopy in young North-European adults.

BACKGROUND: There is evidence that atopic disorders may begin in intra-uterine life; however, studies of birth characteristics and atopy show conflicting results. METHODS: We wanted to investigate the association of birth weight and head circumference with serum total or specific IgE, allergic rhinitis or eczema while addressing the influence of demographic and geographical factors. In this historic prospective cohort study, data were collected from birth records for 1683 men and women born in 1947-1973, from six Nordic-Baltic populations participating in the European Community Respiratory Health Survey. Blood tests for the measurement of serum total and specific IgE were available for 1494 subjects. In multiple regression analyses, adjustments were made for birth length, gender, age, study centre, adult body mass index, level of education, parental and adult smoking. RESULTS There was no association of birth weight (n=1230) and head circumference (n=285) with serum total IgE, specific IgE antibodies, allergic rhinitis or eczema. There were neither significant interactions by gender or age, nor heterogeneity between the study centres in the analyses of birth weight and adult atopy. CONCLUSION: Birth size was not associated with atopy among adults in this large Nordic-Baltic population study.

[The selenium content of milk]. / Mjölkens innehåll av selen.

The selenium content in milk of dairy cows from different countries varies between 2 and 60 micrograms/kg, because of differences in the selenium content in the feeds. With an increasing selenium content in the feed a decreasing part is secreted into the milk. A bigger part is utilized from natural selenium compounds in the feed than from selenite. In own investigations milk from Swedish cows had significantly lower selenium content during summer and autumn than during winter and spring (p less than 0,0001). The LS-means between different regions also differed significantly (p less than 0,0001). From the autumn of 1980 the feed manufacturers have been allowed to add sodium-selenite to concentrates and mineral feeds in amounts permitting a selenium content of 0,1 mg/kg DM in the total ration of dairy cows. The year after the selenium fortification was allowed, the LS-means for the selenium content of milk were 1 microgram/kg higher than the year before (p less than 0,001). In the southern parts of Sweden the selenium content was 8-10 and in the central and northern parts 7-9 micrograms/kg. These means were substantially lower than the figure of 15 micrograms/kg which was reported from the central part of Sweden two decades ago. The low selenium content in the milk during summer in some parts of Sweden could possibly mean that there is still a risk of selenium deficiency among the cattle. Anyhow the milk will not always cover the selenium requirement of the sucking or milkfed calf.

Tuberculosis infection transmitted at autopsy.

Tuberculosis can be a risk to staff and students in the autopsy room. We report three medical students and one technician who were infected with tuberculosis during two autopsies. In both cases pulmonary tuberculosis had not been diagnosed before death.

Development of increased airway responsiveness in two nurses performing methacholine and histamine challenge tests.

Two nurses who frequently examined patients with methacholine or histamine challenge tests developed increased airway responsiveness and symptoms of asthma. It is important to use a good system for evacuating the test aerosol during challenge tests.

Prevalence and incidence of asthma and rhinoconjunctivitis in Swedish teenagers.

In 1987, we studied the prevalence of asthma and rhinoconjunctivitis in 1112 grade-eight students in the town of Umeå, northern Sweden. The present study is based on the same cohort, reinvestigated in 1991. We aimed to estimate the changes in the prevalence of asthma and rhinoconjunctivitis and to examine some presumed risk factors of asthma and rhinoconjunctivitis. A postal questionnaire on present asthma, rhinoconjunctivitis, symptoms from the upper and lower airways, and the need for medication was used. Questions about living conditions, smoking, and present education were also included. The questionnaire was answered by 89% (990) of the subjects. The prevalence of self-reported asthma was 10.8% (boys 7.9%, girls 13.7%). The incidence rate/year was 1.1%, the remission rate/year was 5.7%, and the relapse rate/year was 10%. The risk factors for developing asthma appeared to be atopy, having a family history of asthma or rhinoconjunctivitis, and smoking. The prevalence of self-reported rhinoconjunctivitis was 14.3% (boys 15.6%, girls 13.1%). The incidence rate/year was 1%, the remission rate/year was 22%, and the relapse rate/year was 11%. Stopping smoking and having no family history of rhinoconjunctivitis or asthma appeared to favor remission in rhinoconjunctivitis.

Bronchoalveolar lavage is better than gastric lavage in the diagnosis of pulmonary tuberculosis.

Bronchoalveolar lavage was performed in 62/63 patients with suspected pulmonary tuberculosis and gastric lavage in 60 of the 63. Mycobacteria could be cultured from 14 of the patients. Cultures on bronchoalveolar lavage were positive in 13 of them, while gastric lavage was positive in only 7. Our conclusion is that bronchoalveolar lavage should be performed instead of gastric lavage when pulmonary tuberculosis is suspected.

High prevalence of asthma and related symptoms in teenagers in northern Sweden.

Recent reports have suggested an increased asthma prevalence in the Nordic countries. The prevalence of asthma and related symptoms from lower airways in Umeå, Northern Sweden, was investigated in 1987. We used a questionnaire and a skin prick test in 1,112 teenagers. Individuals with symptoms or positive skin prick tests were examined further. The clinical examination included an interview, a ventilatory lung function test, serum specific immunoglobulin E (IgE) test, and a physical examination. Individuals with symptoms from the lower airways underwent a methacholine inhalation test. Asthma was defined as recurrent attacks of dyspnoea and/or wheezing, triggered by known stimuli (excluding infections), and at least one of the following: signs of obstructive airways at examination or provocation concentration giving a 20% fall in forced expiratory volume in one second (PC20) < 8 mg.ml-1. Using this definition, the prevalence of asthma was 6.8%, with a significantly higher prevalence in girls (9.6%) than in boys (4.1%). Furthermore, 16.4% had dyspnoea, wheeze or prolonged cough but did not fulfil our criteria for asthma. The prevalence of asthma and of symptoms from lower airways is higher than has previously been found in Sweden.

Prevalence of positive skin prick tests, allergic asthma, and rhinoconjunctivitis in teenagers in northern Sweden.

The prevalence of positive skin prick tests (SPT) for common allergens and symptoms of allergic rhinoconjunctivitis or asthma was investigated in Umeå in northern Sweden in 1987. Skin prick tests with 10 allergens common in Sweden and a questionnaire were used to examine 1112 teenagers. All subjects with a positive skin prick test or symptoms were interviewed, and they were further investigated by a serum specific IgE test, a ventilatory lung function test, and a physical examination. At least one skin prick test was positive in 43% of the subjects. Ninety-three percent had at least one positive skin prick test to one of the three most common allergens: cat, timothy grass, and birch. The prevalence of current allergic rhinoconjunctivitis was 17%, current allergic asthma 2.8%, and current asthma (both allergic and nonallergic) 6.8%. Multiple logistic regression analysis showed that the most important risk factors for current asthma were sex (being a girl) and atopy. Heredity of asthma or rhinoconjunctivitis and being born in the winter (October-March) also increased the risk. In atopic subjects, having a mother who smoked and heredity of asthma increased the risk. For allergic rhinoconjunctivitis, heredity increased the risk of getting rhinoconjunctivitis.