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Background: Ethnic minorities living in high-income countries have been disproportionately affected by Coronavirus Disease 2019 (COVID-19) in terms of infection rates, hospitalisations, and deaths; however, less is known about long COVID in these populations. Our aim was to examine the risk of long COVID and associated symptoms among ethnic minorities. Methods and findings: We used nationwide register-based cohort data on individuals diagnosed with COVID-19 aged ≥18 years (n = 2,286,955) between January 2020 and August 2022 in Denmark. We calculated the risk of long COVID diagnosis and long COVID symptoms among ethnic minorities compared with native Danes using multivariable Cox proportional hazard regression and logistic regression, respectively. Among individuals who were first time diagnosed with COVID-19 during the study period, 39,876 (1.7%) were hospitalised and 2,247,079 (98.3%) were nonhospitalised individuals. Of the diagnosed COVID-19 cases, 1,952,021 (85.3%) were native Danes and 334,934 (14.7%) were ethnic minorities. After adjustment for age, sex, civil status, education, family income, and Charlson comorbidity index, ethnic minorities from North Africa (adjusted hazard ratio [aHR] 1.41, 95% confidence interval [CI] [1.12,1.79], p = 0.003), Middle East (aHR 1.38, 95% CI [1.24,1.55], p < 0.001), Eastern Europe (aHR 1.35, 95% CI [1.22,1.49], p < 0.001), and Asia (aHR 1.23, 95% CI [1.09,1.40], p = 0.001) had significantly greater risk of long COVID diagnosis than native Danes. In the analysis by largest countries of origin, the greater risks of long COVID diagnosis were found in people of Iraqi origin (aHR 1.56, 95% CI [1.30,1.88], p < 0.001), people of Turkish origin (aHR 1.42, 95% CI [1.24,1.63], p < 0.001), and people of Somali origin (aHR 1.42, 95% CI [1.07,1.91], p = 0.016). A significant factor associated with an increased risk of long COVID diagnosis was COVID-19 hospitalisation. The risk of long COVID diagnosis among ethnic minorities was more pronounced between January 2020 and June 2021. Furthermore, the odds of reporting cardiopulmonary symptoms (including dyspnoea, cough, and chest pain) and any long COVID symptoms were higher among people of North African, Middle Eastern, Eastern European, and Asian origins than among native Danes in both unadjusted and adjusted models. Despite including the nationwide sample of individuals diagnosed with COVID-19, the precision of our estimates on long COVID was limited to the sample of patients with symptoms who had contacted the hospital. Conclusions: Belonging to an ethnic minority group was significantly associated with an increased risk of long COVID, indicating the need to better understand long COVID drivers and address care and treatment strategies in these populations. George F. Mkoma and colleagues examine the risk of long COVID and associated symptoms among ethnic minorities in Denmark. Author summary: Why was this study done?: Evidence indicates overrepresentation of ethnic minorities among those tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), hospitalised for Coronavirus Disease 2019 (COVID-19), and died from COVID-19. After acute COVID-19 infection, many COVID-19 survivors experience a range of symptoms persisting beyond weeks or months, the condition known as long COVID. However, little is known about the risk of long COVID among ethnic minorities, and no existing studies had compared symptoms distribution before and after COVID-19 diagnosis in these populations. What did the researchers do and find?: A nationwide register-based cohort study was performed on individuals diagnosed with COVID-19 between January 2020 and August 2022 in Denmark. We found that people of North African, Middle Eastern, Eastern European, and Asian origins had a higher risk of long COVID diagnosis than native Danes, with the greatest ethnic disparities being observed in the early phase of COVID-19 pandemic (January 2020 to June 2021). People of North African, Middle Eastern, Eastern European, and Asian origins were more likely to report cardiopulmonary symptoms (including dyspnoea, cough, and chest pain) and any long COVID symptoms than native Danes, especially beyond 4 weeks to 6 months after COVID-19 diagnosis. What do these findings mean?: These findings indicate the need to understand the drivers of long COVID in ethnic minorities and tailor preventive policies to their contexts. Efforts addressing disparities in socioeconomic conditions, advocacy activities for COVID-19 vaccines, and continuation of preventive measures may help reduce the burden of long COVID in ethnic minorities. The diagnosis of long COVID was limited to the sample of patients with symptoms who had contacted the hospital after acute COVID-19 infection. [ABSTRACT FROM AUTHOR]

Migrants and ethnic minorities are disproportionately affected by the Coronavirus Disease 2019 (COVID-19) pandemic compared to the majority population. Therefore, we studied mortality and use of mechanical ventilation (MV) by country of birth and migrant status in a nationwide cohort in Denmark. Nationwide register data on all cases hospitalized for > 24-hours with COVID-19 between February 2020 and March 2021. Main outcome measures were mortality and MV within 30 days of hospitalization for COVID-19. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by region of origin and migrant status using logistic regression analyses, adjusting for age, sex, comorbidity and sociodemographic factors. Of 6,406 patients, 977 (15%) died and 342 (5%) were treated with mechanical ventilation. Immigrants (OR:0.55;95%CI: 0.44–0.70) and individuals of non-Western origin had a lower odds (OR: 0.49; 95% CI: 0.37–0.65) of death upon admission with COVID-19 compared to Danish born individuals. Immigrants and descendants (OR: 1.62; 95% CI: 1.22–2.15) as well as individuals of non-Western origin (OR: 1.83; 95% CI: 1.35–2.47) had a significantly higher odds of MV compared to Danish born individuals. Outcomes of individuals with Western origin did not differ. Immigrants and individuals of non-Western origin had a significantly lower COVID-19 associated mortality compared to individuals of Danish origin after adjustment for sociodemographic factors and comorbidity. In contrast, the odds of MV was higher for immigrants and individuals of non-Western origin compared to individuals of Danish origin. [ABSTRACT FROM AUTHOR]

We wish to study disparities in bloodstream infections in migrants and non-migrants by comparing the distribution of pathogens and their resistance patterns in long-term migrants with that in non-migrants in Denmark. The study is based on a cohort of migrants, who received residency in Denmark between 1993 and 2015 and a control group of non-migrants. The cohort was linked to a database of bloodstream infections from 2000 to 2015 covering two regions in Denmark. First-time bloodstream infections in individuals ≥18 years of age at the time of sampling were included. We calculated odds ratios adjusted for age, sex, year of sampling, comorbidity, and place of acquisition (hospital- or community-acquired). We identified 4,703 bloodstream infection cases. Family-reunified migrants and refugees had higher odds of Escherichia coli than non-migrants (OR 1.89 95%CI: 1.46–2.44 and OR 1.55 95%CI: 1.25–1.92) and lower odds of Streptococcus pneumoniae (OR 0.38 95%CI: 0.21–0.67 and OR 0.52 95%CI: 0.34–0.81). Differences in pathogen distribution were only prevalent in community-acquired bloodstream infections. Refugees had higher odds of Escherichia coli resistant to piperacillin-tazobactam, ciprofloxacin, and gentamicin compared with non-migrants. Family-reunified migrants had higher odds of Escherichia coli and other Enterobacterales resistant to ciprofloxacin. Migrants had a higher proportion of community-acquired bloodstream infections with Escherichia coli as well as higher odds of bloodstream infections with resistant Escherichia coli compared with non-migrants. These novel results are relevant for improving migrant health by focussing on preventing and treating infections especially with Escherichia coli such as urinary tract and abdominal infections. [ABSTRACT FROM AUTHOR]

Objective: To investigate differences in bacterial distribution and resistance patterns of relevant pathogens in skin and tissue infections among migrants compared to nonmigrants. Methods: The population is based on a cohort of migrants who obtained residence as refugees or family‐reunited migrants in Denmark between January 1993 and December 2015. The cohort was linked to positive swabs and tissue cultures collected from hospitals and general practitioners between the years 2000 and 2016 at the Department of Microbiology, University Hospital Hvidovre, Denmark. We calculated odds ratios for pathogen distribution and resistance patterns using logistic regression by comparing migrants with nonmigrants. Results: In total, 43,770 pathogens from 37,276 individuals were included, with Staphylococcus aureus being the most common bacterium. Migrants had higher odds of infections with Enterobacterales than nonmigrants (OR 1.42, 95% CI: 1.23–1.63) and lower odds of beta‐haemolytic Streptococci (OR 0.79, 95% CI: 0.73–0.86). Family‐reunited migrants and refugees had higher odds of methicillin‐resistant S. aureus (MRSA) than nonmigrants (OR 5.01, 95% CI: 3.73–6.73 and OR 3.66, 95% CI: 2.61–5.13). This was more pronounced in female migrants. The odds of ciprofloxacin‐resistant Enterobacterales were higher in both family‐reunited migrants and refugees than in nonmigrants (OR 2.21, 95% CI: 1.34–3.64 and OR 2.17, 95% CI: 1.34–3.52). Conclusions: The prevalence of MRSA and ciprofloxacin‐resistant Enterobacterales was higher among family‐reunited migrants and refugees than in nonmigrants. Our findings suggest an increased awareness for AMR in migrants. [ABSTRACT FROM AUTHOR]

Background Immigrants and ethnic minorities have been shown to be at increased risk of hospitalization from COVID-19. Our aim was to analyse the contribution of socioeconomic and demographic risk factors on hospital admissions for COVID-19 among immigrants and ethnic minorities compared to the majority population. Methods We used nationwide register data on all hospitalized COVID-19 cases between February and June 2020 (N  = 2232) and random controls from the general population (N  = 498 117). We performed logistic regression analyses and adjusted for age, sex, comorbidity, and socioeconomic and demographic factors. The main outcome measure was hospitalization with COVID-19 and was estimated using odds ratios (OR) and 95% confidence intervals (95% CI). Results Among 2232 COVID-19 cases, the OR of hospitalization with COVID-19 among immigrants and descendants of non-Western origin was 2.5 times higher (95% CI: 2.23–2.89) compared with individuals of Danish origin with most pronounced results among individuals from Iraq, Morocco, Pakistan and Somalia. The OR was largely attributed to comorbidity and socioeconomic factors, especially household size, occupation, and population density. Conclusion There is a significantly higher OR of hospitalization with COVID-19 among non-Western immigrants and ethnic minorities compared with ethnic Danes. This knowledge is crucial for health policymakers and practitioners in both the current and future pandemics to identify more vulnerable groups and target prevention initiatives. [ABSTRACT FROM AUTHOR]

Background: Due to the circumstances of their early lives, young refugees are at risk of experiencing adverse labour market and health outcomes. The post-settlement environment is thought to play a decisive role in determining how this vulnerability plays out. This study compared trends in labour market marginalisation in young refugees and their majority peers during early adulthood in two national contexts, Denmark and Sweden, and explored the mediating role of common mental disorders and secondary school completions. Methods: Using registry data, 13,390/45,687 refugees were included in Denmark/Sweden and 1:5 matched to majority peers. Inequalities in labour market marginalisation were investigated during 2012–2015 in each country using linear probability models and mediation analysis. Country trends were standardised to account for differences in observed population characteristics. Results: The risk of marginalisation was 2.1–2.3 times higher among young refugees compared with their majority peers, but the risk decreased with age in Sweden and increased in Denmark for refugees. Birth-cohort differences drove the increase in Denmark, while trends were consistent across birth-cohorts in Sweden. Differences in population characteristics did not contribute to country differences. Common mental disorders did not mediate the inequality in either country, but secondary school completions did (77–85% of associations eliminated). Conclusions: The findings document both the vulnerability of young refugees to labour market marginalisation and the variability in this vulnerability across post-settlement contexts. While the contrast in policy climates in Denmark and Sweden sharpened over time, the risk of marginalisation appeared more similar in younger cohorts, pointing to the importance of factors other than national immigration and integration policies. Institutional efforts to assist young refugees through secondary education are likely to have long-lasting consequences for their socio-economic trajectories. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed at examining psychiatric morbidity in the perinatal period among refugees and family-reunified immigrants compared to Danish-born women, including predictors of psychiatric morbidity according to migration history. Methods: Inclusion criteria were women who had a residence permit in Denmark and gave birth to a live child between 1 April 1998 and 31 December 2014. The study included 7804 refugee women, 21,257 family-reunified women, and 245,865 Danish-born women. We estimated Odds Ratios (ORs) of having a first-time perinatal psychiatric episode (PPE) and specific risk for affective, psychotic, and neurotic disorders. Results: Compared with Danish-born women, women family-reunified with immigrants had lower (aOR 0.37, 95% CI 0.22–0.64) and refugees had higher ORs of PPE (OR 1.46, 95% CI 1.22–1.76). In fully adjusted models, refugees no longer presented increased risk of PPE (OR 1.16, 95% CI 0.95–1.42) but showed higher ORs for psychotic (aOR 4.72, 95% CI 2.18–9.84) and neurotic disorders (aOR 1.31, 95% CI 1.01–1.72). Women family-reunified with refugees and to Nordic citizens had higher ORs of psychotic disorders. Among migrants, refugees had higher ORs of PPE. Conclusions: Results suggest that elevation in risk of PPE among refugees compared to Danish-born may be related to higher likelihood of poverty and single-parenting among refugees. Still, refugees appear to have increased risk for neurotic and psychotic disorders. In contrast, family-reunified to immigrants may have lower risk of PPE. Maternal health programs need to focus on promotion of mental health and tackle social risks that disproportionately affect immigrant women, particularly refugees. [ABSTRACT FROM AUTHOR]

Not being in employment, education or training (NEET) as a youth consistently predicts adverse educational, labour market and health outcomes. School-aged refugee children are known to be particularly vulnerable within each of these domains. Yet little is known about how these outcomes have evolved over time. This study explores trends in the risk of youth NEET status during the early twenties for refugees and their non-refugee peers in Denmark from 1995 to 2014 by utilising national registry data on demographics, income, education and diagnoses covering the full population. The analysis shows that the inequality in the probability of youth NEET status has diminished considerably from up to 20 percentage points among the oldest cohorts to less than 5 percentage points among the youngest. This development was robust to compositional differences, although much more so for girls than boys. For refugee girls, the change in the probability of youth NEET status coincided with changes in timing of family formation, but was not explained by it. In addition, the correlation between family formation and youth NEET status became considerably weaker over time. The findings suggest that some circumstances surrounding the incorporation of refugee school children into their new social contexts have improved. [ABSTRACT FROM AUTHOR]

Background: The high prevalence of psychiatric disorders among resettled refugees necessitates identification of factors that reduce the risk of mental illness. In this 22-year longitudinal cohort study, we assessed whether the length of asylum-decision waiting periods is associated with resettled refugees' risk of being diagnosed with a psychiatric disorder.Methods: We used full-population data from the Danish Civil Registration System to establish a cohort of 46 104 refugees resettled in Denmark during 1995-2016. Hazard ratios (HRs) for first-time psychiatric hospital contact (ICD-10) after residence permit issuance across varying lengths of asylum-decision waiting periods were estimated by cross-linkage with the Danish National Patient Register.Results: Long asylum-decision waiting periods were associated with an increased risk of psychiatric disorders. Compared with refugees who waited 0-6 months for their asylum decision, the HRs of any psychiatric diagnosis were 1.22 [95% confidence interval (CI): 1.12-1.33] for those who waited 13-24 months and 1.46 (95% CI: 1.27-1.69) for those who waited 25-71 months. Associations varied across diagnoses and length of follow-up: whereas the risk of nervous disorders increased with longer asylum-decision waiting periods in the follow-ups of 0-2.9, 3-5.9 and 6-11.9 years, the risk of psychotic disorders was associated with longer asylum-decision procedures only in the 0-2.9-year follow-up.Conclusion: Resettled refugees who waited longer than 1 year for an asylum decision face an increased risk of psychiatric disorders. Host countries should consider that long asylum-decision waiting periods could lead to mental illness among refugees. [ABSTRACT FROM AUTHOR]

Purpose: Migrants represent a considerable proportion of HIV diagnoses in Europe and are considered a group at risk of late presentation. This study examined the incidence of HIV diagnoses and the risk of late presentation according to migrant status, ethnic origin and duration of residence.Methods: We conducted a historically prospective cohort study comprising all adult migrants to Denmark between 1.1.1993 and 31.12.2010 (n = 114.282), matched 1:6 to Danish born by age and sex. HIV diagnoses were retrieved from the National Surveillance Register and differences in incidence were assessed by Cox regression model. Differences in late presentation were assessed by logistic regression.Results: Both refugees (HR = 5.61; 95% CI 4.45-7.07) and family-reunified immigrants (HR = 10.48; 95% CI 8.88-12.36) had higher incidence of HIV diagnoses compared with Danish born and the incidence remained high over time of residence for both groups. Migrants from all regions, except Western Asia and North Africa, had higher incidence than Danish born. Late presentation was more common among refugees (OR = 1.87; 95% CI 1.07-3.26) and family-reunified immigrants (OR = 2.30; 95% CI 1.49-3.55) compared with Danish born. Southeast Asia and Sub-Saharan Africa were the only regions with a higher risk of late presentation. Late presentation was only higher for refugees within 1 year of residence, whereas it remained higher within 10 years of residence for family-reunified immigrants.Conclusions: This register-based study revealed a higher incidence of HIV diagnoses and late presentation among migrants compared with Danish born and the incidence remained surprisingly high over time. [ABSTRACT FROM AUTHOR]

One in four asylum applicants in Europe are children, and 23% of whom are unaccompanied and may be at increased risk of mental illness. This study contributes to the limited evidence base by comparing the incidence of psychiatric disorders among unaccompanied and accompanied refugee children. We linked a cohort of refugee children who obtained right of residency in Denmark between 01 January 1993 and 31 December 2010 to the Danish Psychiatric Central Register, and calculated incidence rates per 100,000 person years and incidence rate ratios of overall psychiatric disorder, psychotic disorders, affective disorders, and neurotic disorders for accompanied and unaccompanied minors using Poisson regression. We adjusted the analyses for sex, age at residency, and age at arrival (aIRR). Stratified analyses were conducted by nationality. Unaccompanied minors had significantly higher rates of any psychiatric disorder (aIRR: 1.38, 95% CI 1.14-1.68) and neurotic disorders (aIRR: 1.67, 95% CI 1.32-2.13) than accompanied minors. Among children from Afghanistan, unaccompanied minors had significantly higher rates of any psychiatric disorder (aIRR: 2.23, 95% CI 1.26-3.93) and neurotic disorders (aIRR: 3.50, 95% CI 1.72-7.11). Among children from Iraq, unaccompanied minors had higher rates of any psychiatric disorder (aIRR: 2.02, 95% CI 1.18-3.45), affective disorders (aIRR: 6.04, 95% CI 2.17-16.8), and neurotic disorders (aIRR: 3.04, 95% CI 1.62-5.70). Unaccompanied children were found to experience a higher incidence of any psychiatric disorder and neurotic disorders. Strategies are needed to address the specific mental health and social needs of unaccompanied minors. [ABSTRACT FROM AUTHOR]

Objectives: In patients with Fabry disease (FD), left ventricular hypertrophy and arrhythmias are frequently observed and cardiac involvement is the leading cause of death. Long-term efficacy of enzyme replacement therapy (ERT) on cardiac involvement is unclear. We assessed and compared long-term progression of cardiac involvement according to ERT and non-ERT.Methods: We retrospectively assessed and compared long-term progression of cardiac involvement in adult patients with FD in the nationwide Danish cohort. We followed clinical signs, symptoms and findings by echocardiography, electrocardiography and Holter-monitoring.Results: We included 66 patients; 47 patients (27 women) received ERT (ERT group) and 19 patients (15 women) did not (non-ERT group). The groups were followed for a median of 8 [0-12] years and 6 [0-13] years, respectively. Comparison between ERT and non-ERT receiving patients by left ventricular mass (echocardiographic assessment) and Sokolow-Lyon voltage- and Cornell product criteria (electrocardiographic assessment) revealed no significant differences. In the ERT group, we observed no change in left ventricular mass but a decrease in Sokolow-Lyon voltage- and Cornell product criteria from baseline to follow-up; 30 mm [15-53] vs. 25 mm [3-44], p < 0.005 and 1710 mm·ms [480-3740] vs. 1520 mm·ms [550-5740], p < .05, respectively. There were no changes within the non-ERT group. During follow-up, cardiac symptoms and use of cardiovascular procedures and -medication increased significantly in the ERT group, whereas no differences were observed within the non-ERT group.Discussion: We raise concerns regarding the efficacy and benefit of ERT on cardiac involvement in Fabry disease and stress the need for further research. [ABSTRACT FROM AUTHOR]

Aims: Suboptimal healthcare utilisation and lower satisfaction with the patient–doctor encounter among immigrants has been documented. Immigrants’ lack of familiarity with the healthcare system has been proposed as an explanation for this. This study investigated whether a systematic delivery of information affected immigrants’ knowledge of and satisfaction with the Danish healthcare system. Methods: A prospective, randomised intervention study of 1158 adult immigrants attending two language schools in Copenhagen was conducted. Two intervention groups received written information or a 12-hour course on the Danish healthcare system, while a control group received nothing. Survey data included self-assessed knowledge, true/false questions on access and questions relating to satisfaction with the healthcare system. Data were linked to socioeconomic registry data. Logistic regression analyses were performed. Results: The course improved knowledge of who to contact in the event of an accident (odds ratio (OR) = 2.67, 95% confidence interval (CI) = 1.56–4.59) but not in the event of illness. Further, it positively affected correct answers for nine out of 11 questions on the healthcare system (varying from OR = 1.87, 95% CI = 1.08–3.24 to OR = 3.11, 95% CI = 1.58–6.11). Written information positively affected correct answers for three out of 11 questions, but negatively affected one out of 11 compared with the control group. Neither intervention affected immigrants’ satisfaction with the healthcare system. Conclusions: Knowledge of the healthcare system is necessary for optimal healthcare-seeking behaviour. The results may form the basis of national and international changes in immigrant reception and optimise immigrants’ contact with the healthcare system. [ABSTRACT FROM AUTHOR]

Background: Few human studies have examined bisphenol A (BPA) exposure in relation to semen quality and reproductive hormones in men, and results are divergent. Objectives: We examined associations between urinary BPA concentration and reproductive hormones, as well as semen quality, in young men from the general population. Methods: Our study population consisted of 308 young men from the general population. Urinary BPA concentration was measured by isotope dilution TurboFlow-liquid chromatography–tandem mass spectrometry. We used multiple linear regression analysis to estimate associations between BPA concentration and reproductive hormones and semen quality, adjusting for confounding factors. Results: We found that 98% of the men had detectable urinary levels of BPA. Median (5th–95th percentiles) BPA concentration was 3.25 ng/mL (0.59–14.89 ng/mL). Men with BPA concentrations above the lowest quartile had higher concentrations of serum testosterone, luteinizing hormone (LH), estradiol, and free testosterone compared with the lowest quartile (ptrend ≤ 0.02). Men in the highest quartile of BPA excretion had on average 18% higher total testosterone (95% CI: 8, 28%), 22% higher LH (95% CI: 6, 39%), and 13% higher estradiol (95% CI: 4, 24%) compared with lowest quartile. Men in the highest quartile of BPA also had significantly lower percentage progressive motile spermatozoa compared with men in the lowest quartile (–6.7 percentage points, 95% CI: –11.76, –1.63). BPA was not associated with other semen parameters. Adjusting for dietary patterns did not influence the results. Conclusions: The pattern of associations between BPA and reproductive hormones could indicate an antiandrogenic or antiestrogenic effect, or both, of BPA on the hypothalamic–pituitary–gonadal hormone feedback system, possibly through a competitive inhibition at the receptor level. However, additional research is needed to confirm our findings and to further test the suggested potential mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: The primary purposes of preventive child health care in Denmark are to help ensure a healthy childhood and to create preconditions for a healthy adult life. The aim of this study is to examine whether participation in age-appropriate preventative child health care affects the association between the socioeconomic position of the family and subsequent use of specialised health care outside the hospital system. Methods: The study population was children born in 1999 and living in Denmark between 1 January 2002 and 31 December 2006 (n=68,366). The study investigated whether the number of contacts with a specialist in 2006 was related to participation in preventive child health care between 2002 and 2005. To control for the potential effect of difference in GP behaviour the data were analysed using a multilevel Poisson model linking each child to the GP with whom he or she was listed. Results: If the children attended any preventive child health care visits, they had the same probability of contact with a specialist regardless of the parents’ income. However, children from low-income families not participating in any preventive care had a lower probability of contact with a specialist than children from more affluent families. Conclusions: Ensuring participation in preventive child health care at the GP may reduce the social gap in utilisation of specialised health care that exists between children from families of different income levels. [ABSTRACT FROM PUBLISHER]

During past decades, we have witnessed a remarkable decline in fertility rates (number of births per 1000 women of reproductive age) in the industrialized world. It seems beyond doubt that the enormous social changes of our societies play the major role in this decline, but can it be attributed to changing social structures alone or is a reduced fecundity in the population also a factor? To address this we have focused on trends in teenage pregnancies (which to a large extent are unplanned). During the period in question fertility rates among 15-19 year old Danish women have been falling and the decline in fertility rate is not counterbalanced by an increase in the rate of induced abortion. When seen together with recent results from Denmark, which have shown that more than 30% of 19 year old men from the general population now have sperm counts in the subfertile range, we argue that this fall may not be attributable to social factors, changes in conception practices or diminished sexual activity alone. It seems reasonable also to consider widespread poor semen quality among men as a potential contributing factor to low fertility rates among teenagers. Due to the concern caused by the low sperm count among younger Danish men, the Danish Ministries of Health and Environment have launched a surveillance programme which includes an annual examination of the semen quality in 600 young Danes from the general population. We propose that researchers in other countries with low and falling fertility rates among young women should consider the possibility that semen quality of their younger male cohorts may also have deteriorated. [ABSTRACT FROM AUTHOR]

To investigate bloodstream infection (BSI) related to migrant status by comparing the incidence and mortality in migrants with that in non-migrants. In this register-based cohort study we linked a cohort of migrants and non-migrants with a bacteraemia database covering two regions in Denmark. We included first-time BSI between January 2000 and December 2015 in individuals ≥18 years. Migrants were categorized according to status: refugees or family-reunified migrants. Incidence rate ratio and mortality rate ratio were analysed using Poisson regression. We identified 493 080 non-migrants, of which 3405 had BSI, and 80 740 migrants with 576 cases; of the latter, 40 222 were family-reunified migrants with 226 cases and 40 518 were refugees with 350 cases. Refugees had a higher risk of BSI than non-migrants (adjusted IRR 1.19, 95%CI 1.01–1.40). Family-reunified migrants and refugees had a higher risk of Gram-negative BSIs (adjusted IRR 1.23, 95%CI 1.00–1.51 and 1.57, 95%CI 1.32–1.86), respectively, and a lower risk of Gram-positive BSIs (adjusted IRR 0.65, 95%CI 0.51–0.83 and 0.77, 95%CI 0.63–0.95), respectively, compared to non-migrants. Originating from Southeast Asia and the Pacific was associated with an increased risk of BSI compared to non-migrants (adjusted IRR 1.26, 95%CI 1.07–1.49). We found no differences in the adjusted 30-day or 90-day mortality according to migrant status. Vulnerability towards BSI differs according to migrant status. Refugees had a higher risk of BSI overall. Both refugees and family-reunified migrants had a higher incidence of Gram-negative BSI than non-migrants. Similarly, migrants from Southeast Asia and the Pacific had a higher risk of BSI than non-migrants. [ABSTRACT FROM AUTHOR]

Purpose: To examine whether family separation caused by prolonged waiting for family reunification is associated with the risk of mental disorders among refugee fathers., Method: Based on full-population Danish registry data covering 1995-2015, we mapped arrival patterns among nuclear refugee family members resettled in Denmark (n = 76,776) and established a cohort of refugee fathers (n = 6176) who all arrived alone and later obtained family reunification with their wife and children. The fathers were followed for up to 24 years, from the day their residence permit was issued until their first psychiatric diagnosis, emigration, death, or study end, whichever came first. Using Cox proportional hazard regression, we estimated hazard ratios (HRs) of being diagnosed with a mental disorder (i) for the period while the fathers were still separated from their family and (ii) across varying lengths of family separation., Results: The HR of any mental disorder was 2.10 (95% confidence interval (CI): 1.57-2.81) for fathers still separated from their family compared with those who had obtained family reunification. The HR increased with longer family separation. Compared with fathers separated for < 9 months, the HR of any mental disorder was 1.43 (95% CI 1.08-1.89) for 9-11 months' separation, increasing to 2.02 (95% CI 1.52-2.68) for 18-23 months' separation. Results were driven by post-traumatic stress disorder., Conclusion: Fathers waiting for their wives and children face an increased risk of mental disorders. Countries receiving refugees should be aware that delaying family reunification can lead to adverse mental health effects., (© 2021. The Author(s).)

Background: Spermatogenesis depends on stimulation by follicle-stimulating hormone (FSH) which binds to FSH receptors (FSHR) on testicular Sertoli cells. Three FSH-related single-nucleotide polymorphisms (SNPs), FSHB -211G>T (rs10835638), FSHR -29G>A (rs1394205) and FSHR 2039A>G (rs6166) affect FSH action, and have been suggested to affect testicular function, but the evidence is uncertain., Objective: To describe the associations between the three SNPs and testicular function in a large and well-characterised cohort of men from the general population., Materials and Methods: A cross-sectional study of 2020 Danish men unselected regarding testicular function. Outcome variables were semen parameters, reproductive hormones and testis size. Genotyping was done by competitive allele-specific quantitative PCR. Differences in genotype frequencies were tested by chi-square test and associations between genotypes and outcomes were assessed by multivariate linear regressions., Results: The SNPs affected serum FSH; carriers of the variant affecting FSH secretion (FSHB -211G>T) had lower FSH levels while carriers of variants affecting receptor expression (FSHR -29G>A) and receptor sensitivity (FSHR 2039A>G) had higher FSH levels. Carriers of FSHB -211G>T had lower calculated free testosterone/LH ratio. Although both FSHB -211G>T and FSHR 2039A>G were associated with smaller testis size, no clear association was detected in relation to any semen parameters, except a lower total number of morphologically normal spermatozoa in the heterozygous carriers of the FSHB -211G>T DISCUSSION AND CONCLUSION: The studied polymorphisms have only minor modulating influence on testis size and function in healthy men. We detected subtle effects of the three SNPs on FSH levels, but also effects of FSHB -211G>T on calculated free testosterone/LH ratio, compatible with altered Leydig cell function. Thus, the role of these FSH-related polymorphisms is complex and modest in men with normal testicular function, but the possible importance of FSH polymorphisms in men with impaired testicular function should be evaluated in future studies in more detail., (© 2020 American Society of Andrology and European Academy of Andrology.)

Importance: Many young men have poor semen quality, and the causes are often unknown. Supplement intake of ω-3 polyunsaturated fatty acid has been found to improve semen quality among men with infertility, but the association with semen quality among healthy men is unknown., Objective: To determine if intake of ω-3 fatty acid supplements is associated with testicular function as measured by semen quality and reproductive hormone levels among healthy men., Design, Setting, and Participants: This cross-sectional study included young Danish men from the general population recruited between January 1, 2012, and December 31, 2017, at compulsory examinations to determine their fitness for military service. Young unselected men were approached after the examination and invited to participate in a study of reproductive function, regardless of their fitness for military service. Data analysis was conducted from September 1, 2018, to June 30, 2019., Exposures: Intake of supplements, including fish oil, during the past 3 months., Main Outcomes and Measures: Semen quality, measured as volume, concentration, total sperm count, percentage of morphologically normal spermatozoa, and motility, and serum reproductive hormone levels, measured as follicle-stimulating hormone, luteinizing hormone, testosterone, free testosterone, and inhibin B levels., Results: Among 1679 young Danish men (median [interquartile range] age, 18.9 [18.7-19.4] years) recruited to participate, 98 men (5.8%) reported use of fish oil supplements during the past 3 months, of whom 53 (54.1%) reported intake on 60 or more days. After adjustment and compared with men with no supplement intake, men with fish oil supplement intake on fewer than 60 days had semen volume that was 0.38 (95% CI, -0.03 to 0.80) mL higher, and men with fish oil supplement intake on 60 or more days had semen volume that was 0.64 (95% CI, 0.15 to 1.12) mL higher (P for trend < .001). Similarly, testicular size in men with supplement intake on fewer than 60 days was 0.8 (95% CI, -0.2 to 1.9) mL larger and in men with fish oil supplement intake on 60 or more days was 1.5 (95% CI, 0.2 to 2.8) mL larger compared with men with no supplement intake (P for trend = .007). After adjustment, men with fish oil supplement intake had a 20% (95% CI, 9%-31%) lower follicle-stimulating hormone level and 16% (95% CI, 8%-24%) lower luteinizing hormone level compared with men with no supplement intake. There were no associations of intake of other supplements with measures of testicular function., Conclusions and Relevance: These findings suggest that intake of fish oil supplements was associated with better testicular function, which is less likely to be due to confounding by indication, as no associations of intake of other supplements with testicular function were found. This cross-sectional study did not examine the actual content of ω-3 fatty acids in the supplements; therefore, these findings need confirmation in well-designed randomized clinical trials among unselected men.

Background: Fabry disease (FD) is a lysosomal storage disorder resulting in systemic accumulation of globotriaosylceramide resulting in multi-organ dysfunction e.g. cerebral, cardiac, renal and audiologic complications. The audiologic involvement in FD has often been neglected; while not a lethal aspect of the disease, hearing loss can have a significantly negative impact on quality of life., Objectives: To investigate baseline hearing status of the Danish Fabry cohort prior to treatment, compared to sex- and age-expected hearing levels and correlating hearing to renal and cerebral findings., Material and Methods: Retrospective study of baseline hearing status of the Danish Fabry cohort (n = 83, 9-72 years). Air conduction and speech discrimination scores were assessed at 6 frequencies between 0.25-8 kHz bilaterally. Data were collected between 2001-2014 and compiled in STATA using multilinear mixed modelling for statistical evaluation., Results: Hearing thresholds at all frequencies deviated from the expected thresholds of an otologically normal cohort (p<0.001) and ranged 0.5 to 1.5 standard deviations below expected values. In total 29 males and 54 females were included. Hearing loss was more pronounced in the higher frequencies. There was a trend of association between hearing loss and measured glomerular filtration rate (mGFR) (p = 0.084). No association was present between hearing loss and albuminuria (p = 0.90), Fabry related cerebral abnormalities (p = 0.84) and cardiac left ventricular mass index, (LVMi) (p = 0.67) independent of sex. Hearing thresholds were poorer for men compared to women (p = 0.001). Sex differences were present at 0.25, 4 and 8 kHz., Conclusion: Our findings demonstrated significant hearing loss in Danish FD patients before treatment initiation, being more profound than in otologically healthy individuals at all frequencies. Additionally, we observed no association between hearing loss and LVMi, albuminuria or FD cerebral abnormalities, with a trend of association to mGFR., Synopsis: Patients with Fabrys disease have hearing loss of all frequencies and most prominently at high frequencies (4-8 kHz), with no association between the hearing loss and cerebral abnormalities, and cardiac mass but with a trend of association to measured glomerular filtration rate., Competing Interests: The authors have declared that no competing interests exist.

Background: Children of refugees are often exposed to the consequences of parental post-traumatic stress disorder (PTSD), potentially leaving them vulnerable to intergenerational transmission of psychopathology. The present study aimed to determine whether parental PTSD is associated with childhood psychiatric morbidity among children of refugees., Methods: This study is a two-generation nationwide cohort study using the Danish Immigration Services database. We followed up children younger than 18 years with at least one refugee parent until psychiatric contact, end of the study, their 18th birthday, emigration, or death. We excluded children if their parents were diagnosed only with psychiatric diagnoses other than PTSD or if they had received a psychiatric contact before parental PTSD diagnosis. Information on parental PTSD and offspring psychiatric morbidity was obtained from the Danish Psychiatric Central Research Register. We used Cox proportional hazards regression models to assess the risk of psychiatric contacts among children of refugees with PTSD compared with children of refugees with no psychiatric diagnosis., Findings: Between Jan 1, 1995, and Dec 31, 2015, 102 010 refugees obtained residency permission in Denmark and 62 239 biological children of refugees were born in Denmark before Dec 31, 2015. 51 793 were eligible and included in the study (median follow-up 7·15 years [IQR 3·37-11·78]); of these, 1307 (2·5%) children had a psychiatric contact. 7486 (14·5%) children of refugees were exposed to parental PTSD. Parental PTSD significantly increased the risk of psychiatric contact in offspring (hazard ratio 1·49 [95% CI 1·17-1·89] for paternal PTSD, p=0·0011; 1·55 [1·20-2·01] for maternal PTSD, p=0·00084) after adjustment for sociodemographic variables., Interpretation: Children of refugees exposed to parental PTSD are at increased risk of psychiatric morbidity. Targeted screening and interventions are necessary to prevent psychiatric morbidity and ensure access to adequate care., Funding: Section for Immigrant Medicine, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Immigrants may face problems with accessing the Danish healthcare system due to, for example, lack of knowledge of how to navigate it, which may cause inappropriate healthcare-seeking. Danish municipalities provide a mandatory introduction and language programme for newly arrived immigrants, but no information on the healthcare system is offered. This study investigated what effects information about the Danish healthcare system may have on the hypothetical healthcare-seeking behaviour of newly arrived immigrants and their actual healthcare use., Methods: A prospective intervention study of 1572 adult immigrants attending two language schools in Copenhagen was carried out. Two intervention groups received either a course or written information on the Danish healthcare system, respectively, while the control group received neither. Survey data included three case vignettes on healthcare-seeking behaviour (flu-like symptoms, chest pain and depression) and were linked to registry data on sociodemographic characteristics and healthcare use in the year to follow. Logistic regression and binomial regression analyses were performed., Results: Appropriate hypothetical healthcare-seeking behaviour was reported by 61.8-78.8% depending on the vignette. Written information showed no effect on immigrants' hypothetical healthcare-seeking behaviour, while the course showed a positive effect on hypothetical healthcare-seeking behaviour for flu-like symptoms (adjusted odds ratio [AOR] = 1.71, 95% confidence interval [CI] = 1.01-2.91, p-value = 0.0467), but not on chest pain or depression. The interventions did not affect immigrants' actual healthcare use; all groups made lower use of health care services in the following year compared with the year where the study took place, except for the use of dental care which remained stable., Conclusions: Information on the healthcare system embedded in the language school programme has the potential to facilitate immigrants' access to healthcare. Yet, the results underscore the need for further refinement and development of educational interventions, as well as ensuring adequate utilisation of healthcare services by other means. Multi-dimensional and multi-sectional efforts are important for integration issues within healthcare in Europe., Trial Registration: Health-seeking behaviour among newly arrived immigrants in Denmark ISRCTN24905314 , May 1, 2015 (Retrospectively registered).

Context: Detailed evaluation of pubertal progression in girls from longitudinal studies is sparse, and the phenomenon of transient thelarche (TT), defined as the appearance, regression, and subsequent reappearance of breast buds, in healthy girls remains undescribed., Objective: To describe TT in terms of pubertal progression, growth, genotypes, and reproductive hormones and to apply new puberty nomograms for breast stages, pubic hair, and menarche., Design: A prospective, longitudinal population-based study., Patients or Other Participants: Ninety-eight healthy Danish schoolchildren (Caucasian girls) followed longitudinally as part of the COPENHAGEN Puberty Study were included in the evaluation of TT. A total of 1466 girls from 2 cross-sectional studies were included in the creation of the puberty nomograms., Intervention(s): None., Main Outcome Measure(s): Pubertal progression, specifically thelarche, reproductive hormones, genotype, and growth., Results: Twelve of 98 (12%) girls experienced TT. A larger proportion of girls with TT entered puberty by the pubarche pathway (50%) compared with girls with normal progression (15.4%), P = 0.014. Girls with TT progressed through puberty normally when evaluated using puberty nomograms. Reproductive hormones and growth velocity were lower at the first (transient) thelarche than the second (permanent) thelarche., Conclusion: TT is a frequent phenomenon that appears to be a peripheral occurrence independent of central puberty. It does not appear to affect subsequent pubertal progression as evaluated by our new puberty nomograms., (Copyright © 2017 by the Endocrine Society)

Context: Few data exist on the diagnostic criteria, and on the effects of puberty induction, in boys with constitutional delay in growth and puberty (CDGP)., Objective: To develop puberty nomograms based on Danish boys with normal pubertal development. To evaluate the different diagnostic criteria and the effect of oral testosterone undecanoate (TU) in boys with CDGP., Design: A cross-sectional and longitudinal study of Danish boys with normal pubertal development (COPENHAGEN puberty study). A retrospective observational study of 451 boys evaluated for delayed puberty between 1990 and 2013., Setting: Tertiary referral center for pediatric endocrinology., Participants: One hundred and sixty-four (36%) boys evaluated for CDGP were excluded due to missing data, reclassification, or associated comorbidities, yielding 287 (64%) eligible for analysis., Main Outcome Measures: The number of patients with CDGP classified by the puberty nomogram (genital stage < -2 SD for age) versus the classical criteria (genital stage 1 at ≥ 14 years). The effect of one year of oral TU treatment on pubertal progression, circulating hormones, height, and predicted adult height (PAH)., Results: Seventy-eight (27%) of the 287 boys had delayed pubertal onset according to the classical criteria, whereas 173 (60%) of the 287 boys had impaired pubertal progression according to the puberty nomogram. Ninety-six (56%) of these 173 boys were treated with oral TU for 0.8 years (0.5; 1.3) [median (25th; 75th percentiles)], which resulted in beneficial effects on pubertal progression. Height increased from -1.9 SD (-2.5; -1.2) to -1.5 SD (-2.1; -0.7) (P < .001), and PAH increased from 172.3 cm (170.3; 182.8) to 178.1 cm (171.4; 191.7) (P = .001) following one year of treatment., Conclusions: The puberty nomogram evaluates both delayed pubertal onset as well as delayed pubertal progression and allows separation of normal versus abnormal pubertal development. Oral TU treatment was followed by pubertal induction and progression and short-term growth without compromising final height.

Background: 'Remigration bias' is often referred to when explaining low mortality outcomes among migrants compared with local-born. The hypothesis suggests that severely ill migrants tend to return to their country of origin, but it has hitherto not been tested in a large-scale epidemiological study. Consequently, we studied whether migrants with severe disease were more likely to emigrate compared with migrants without severe disease., Methods: A historic prospective cohort study was conducted based on all adult refugees and family reunification immigrants (n = 114,331) who obtained residence permission in Denmark between 1 January 1993 and 31 December 2010. Migrants with severe disease were identified through the Danish National Patient Register. Emigrations during follow-up (1 January 1993 to 31 December 2011) were identified using the Danish Civil Registration System. Hazard ratios were calculated for emigration among migrants with different levels of disease severity, adjusting for sex, age and income., Results: Results showed progressively fewer emigrations with increasing disease severity. Migrants with low (HR = 0.92; 95% CI: 0.80-1.06), moderate (HR = 0.84; 95% CI: 0.67-1.06) and high (HR = 0.70; 95% CI: 0.55-0.90) disease severity had fewer emigrations to 'country of origin' compared with migrants without disease. For emigration to 'any country', results likewise showed fewer emigrations among migrants with low (HR = 0.86; 95% CI: 0.78-0.95), moderate (HR = 0.73; 95% CI: 0.62-0.87) and high (HR = 0.64; 95% CI: 0.53-0.76) disease severity. This tendency was also observed by nationality and migrant status. On the disease-specific level, no uniform tendencies in emigration patterns were identified., Conclusion: The results do not generally support the hypothesis of 'remigration bias' but rather suggest the opposite. Accordingly, remigration bias does not appear to explain lower mortality of migrants., (© The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Aim: To construct new Danish growth charts for 0- to 20-year-olds and to compare them with Danish references from 1982 and with World Health Organization (WHO) standards for children aged 0-5 years from 2006, by applying similar inclusion and exclusion criteria., Methods: Anthropometric data from three contemporary Danish population-based studies were combined. References for height were based on healthy Caucasian children born at term. A total of 12,671 height measurements (8055 in boys and 4616 in girls) were included. Reference charts were developed using the generalised additive models for location, scale and shape., Results: From prepubertal ages, a secular increase in height was observed for both genders. The differences were most pronounced in puberty, and final heights were increased by 1.4 cm in boys and 2.9 cm in girls compared to 1982 references. In boys, but not girls an upward shift in body mass index (BMI) above median levels was found. Reference curves for height were superimposable with standard curves based on the selective WHO criteria. Danish children were longer/taller and heavier and they had larger head circumferences than those reported in the recent multiethnic WHO standards., Conclusion: We recommend national implementation of these contemporary 2014 Danish references for anthropometric measurements., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: To investigate whether genetic polymorphisms in the FSH pathway (FSHB-211 G→T and FSHR 2039 A→G) affect serum levels of FSH, antimüllerian hormone (AMH), and age at pubertal onset. FSH secretion and FSH signal transduction are enhanced in carriers of FSHB GG and FSHR AA, respectively. Furthermore, the combined genotype FSHB GG+FSHR AA is the most favorable for male gonadal function, but the effect of this genotype has never been evaluated in peripubertal females. AMH is a marker of ovarian function and is negatively correlated with FSH in prepubertal girls., Design: Secondary analyses of a prospective cohort study., Setting: General community., Patient(s): We examined 78 healthy girls twice yearly for 6 years; the median age at baseline was 9.3 years., Intervention(s): None., Main Outcome Measure(s): Hormone levels were measured by immunoassays, and DNA was isolated from blood and genotyped by restriction fragment length polymorphism of polymerase chain reaction-amplified regions., Result(s): Carriers of FSHB GG+FSHR AA had higher FSH before pubertal onset (median 2.2 vs. 1.5 IU/L) and lower AMH (13.8 vs. 19.4 pmol/L) compared with carriers of other genotypes. In crude analysis, girls with FSHB GG+FSHR AA entered puberty earlier, 9.7 vs. 10.6 years. However, the difference was no longer statistically significant after including interval-, right-, and left-censored data in a probit analysis., Conclusion(s): The combined effect of FSHB GG+FSHR AA may potentiate the FSH pathway, which increases serum levels of FSH and reduces AMH. Common variations in genes regulating follicle growth may affect AMH levels independently of the number of resting primordial follicles., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: In adult women, the circulating level of anti-Müllerian hormone (AMH) is a novel marker of ovarian function, as it reflects the number of remaining ovarian follicles. Therefore, AMH has gained widespread attention in fertility clinics, and a low AMH is believed to predict impaired fertility and imminent menopause. However, the natural course of circulating AMH levels during female childhood and adolescence is not known., Methods: Serum levels of AMH and FSH were measured in girls participating in The COPENHAGEN Puberty Study. Longitudinal part: 85 healthy girls and adolescents were examined, and blood samples were drawn every 6 months for an average of 3 years: median (range) number of samples per girl was 6 (2-10), age at baseline was 9.2 (5.9-12.9) years. Cross-sectional part: 224 prepubertal girls (age 8.3, 5.6-11.7 years) were examined and each girl had one blood sample drawn., Results: The individual mean AMH levels in girls followed longitudinally ranged from 5 to 54 pmol/l (median 18 pmol/l). The mean intra-individual coefficient of variation of AMH was 22% (range 0-54%). Overall, each girl maintained her AMH level throughout childhood and adolescence although minor, but significant, changes occurred during pubertal transition. In prepubertal girls, AMH was negatively correlated with FSH (r = -0.31, P < 0.001). Twelve per cent (10/85) had mean AMH below a cut-off value of 8 pmol/l, indicating that the interpretation of low AMH as a marker of approaching menopause may not apply to pre- and peri-pubertal girls., Conclusions: Circulating AMH exhibits only minor fluctuations during childhood and adolescence, and a random AMH measurement seems representative for a given girl. The negative AMH-FSH correlation in prepubertal girls supports the notion that AMH is a quantitative marker of ovarian follicles even in young girls.

Context: In the 1990s, the American population-based study NHANES III renewed the focus on possible secular trends in male puberty. However, no conclusions could be made on pubertal onset due to the lack of compatible data., Objective: The aim of the study was to evaluate secular trends in pubertal onset during the recent 15 yr and their relation to body mass index (BMI) in boys., Design and Setting: We conducted a cross-sectional study in 1991-1993 and a combined cross-sectional and longitudinal study in 2006-2008 (The Copenhagen Puberty Study) at a tertiary center for pediatric endocrinology., Participants: A total of 1528 boys aged 5.8 to 19.9 yr participated (n = 824 in 1991-1993, and n = 704 in 2006-2008). Genital and pubic hair stages as well as testicular volume by orchidometry were evaluated. Blood samples were analyzed for LH, FSH, testosterone, and SHBG., Main Outcome Measures: We measured age at onset of pubertal markers., Results: Onset of puberty, defined as age at attainment of testicular volume above 3 ml, occurred significantly earlier in 2006-2008 [11.66 yr (11.49-11.82); mean (95% confidence interval)] than in 1991-1993 [11.92 yr (11.76-12.08); P = 0.025]. Significantly higher LH, but not testosterone, levels were found in the 11- to 16-yr-old boys from 2006-2008 compared to 1991-1993 (P = 0.020). BMI Z-score increased significantly from 1991-1993 [0.044 (-0.016 to 0.104)] to 2006-2008 [0.290 (0.219-0.361); P < 0.001]. Interestingly, pubertal onset and LH levels were no longer significantly different between study periods after adjustment for BMI., Conclusions: Estimated mean age at onset of puberty has declined significantly during the recent 15 yr. This decline was associated with the coincident increase in BMI.

Objectives: Chronic lymphocytic leukemia (CLL) is an incurable disease with a highly variable clinical course. IgV(H) mutational status, chromosomal aberrations, CD38 expression and ZAP-70 expression are prognostic markers in CLL, however, they are not exclusively confined to this disease. We recently identified a novel CLL-specific gene (CLL upregulated gene1, CLLU1) that is exclusively upregulated in CLL cells. Here we describe our evaluation of the prognostic significance of CLLU1 in CLL., Methods: A cohort of 59 previously untreated CLL patients was studied. We determined the expression levels of two CLLU1 transcripts, cDNA1 and CDS, by quantitative RT-PCR. The relation between CLLU1 expression and time to therapy, overall survival and presence or absence of ZAP-70, CD38, chromosomal aberrations or IgV(H) mutations in the 59 patients was analyzed., Results: Analyzed as a continuous, quantitative parameter CLLU1 levels significantly predicted time from diagnosis to initiation of therapy (P < or = 0.0003) Analyzed as a categorical parameter, by segregation of the patients into groups with cDNA1 or CDS expression above or below the median, the CLLU1 levels significantly predicted time from diagnosis to initiation of therapy (P = 0.001) and predicted overall survival with borderline significance (P < or = 0.05). Patient stratification according to clinical stage, cytogenetics, IgV(H) mutational status, ZAP-70 and CD38, demonstrated significantly increased CLLU1 expression in all investigated CLL poor risk groups. CLLU1 expression levels contributed additional prognostic information to ZAP-70-positive patients., Conclusions: CLLU1 is the first identified CLL specific gene. The CLLU1 mRNA expression level can predict time to initiation of treatment and survival in CLL patients.

Background: Several recent studies have reported low sperm concentration in young men recruited from the general population, but it is unknown whether the semen quality of these young men reflects that of more mature men or is reduced due to relative immaturity. We conducted a longitudinal follow-up study to address this question., Methods: We followed 158 young men (median age = 19.1 years at entry) for up to 4 years and requested quarterly semen samples (total 1838 semen samples) and yearly genital examinations. We examined longitudinal changes in sperm concentration, semen volume, percentage of immotile sperm and percentage of morphologically normal sperm. We used general linear models in which each man served as his own control which also controlled for age, smoking, urogenital infections or disorders, fever and abstinence time., Results: We found no evidence that sperm concentration, total sperm count or percentage of morphologically normal sperm changed appreciably during the 4 years of follow-up. Semen volume appeared to increase slightly with age, perhaps due to greater acceptance of the study protocol by participants. Sperm motility also improved somewhat, although this may, at least in part, reflect a trend in motility measurement., Conclusions: In this analysis of 1838 semen samples from 158 young men from the Copenhagen area, sperm concentration, total sperm count and sperm morphology did not change significantly during 4 years of follow-up, suggesting that previously reported low sperm concentration and poor sperm morphology among young Danish men are unlikely to be the result of immaturity.

Objective: To examine the relationship between body mass index (BMI) and semen quality among young men from the general population., Design: Cross-sectional study., Setting: Danish young men were approached when they attended a compulsory physical examination to determine their fitness for military service., Patient(s): From 1996-1998, 1,558 (19%) young men (mean age 19 years) volunteered., Main Outcome Measure(s): Semen volume (in milliliters), sperm concentration (in million per milliliter), percentage of motile spermatozoa, percentage of spermatozoa with normal morphology, total sperm count (in million), and testis size (in milliliters). In addition, serum reproductive hormones were measured., Result(s): Serum T, sex hormone-binding globulin (SHBG), and inhibin B all decreased with increasing BMI, whereas free androgen index and E(2) increased with increasing BMI. Serum FSH was higher among slim men. After control for confounders, men with a BMI <20 kg/m(2) had a reduction in sperm concentration and total sperm count of 28.1% (95% confidence interval [CI] 8.3%-47.9%) and 36.4% (95% CI 14.6%-58.3%), respectively, and men with a BMI >25 kg/m(2) had a reduction in sperm concentration and total sperm count of 21.6% (95% CI 4.0%-39.4%) and 23.9% (95% CI 4.7%-43.2%), respectively, compared to men with BMI between 20-25 kg/m(2). Percentages of normal spermatozoa were reduced, although not significantly, among men with high or low BMI. Semen volume and percentage of motile spermatozoa were not affected by BMI., Conclusion(s): High or low BMI was associated with reduced semen quality. It remains to be seen whether the increasing occurrence of obesity in the Western world may contribute to an epidemic of poor semen quality registered in some of the same countries. If so, some cases of subfertility may be preventable.

The present study was undertaken to assess the impact of reproductive behavior on the social class gradient in breast cancer occurrence in Denmark. Objectives were to study whether the gradient across socioeconomic groups could be explained by fertility differences, whether the gradient across educational groups could be explained by fertility differences and whether the effect of socioeconomic group on breast cancer incidence and mortality could be explained by education and vice versa. We studied 674,084 women aged 20-39 at the census on 9 November 1970 for whom we had complete data on fertility history. The cohort was followed up for breast cancer incidence and mortality until 8 November 1998. Fertility history varied considerably across socioeconomic group, where 38% of the academics were childless at the age of 30, in contrast to only 8% of women in agriculture. The academics had the highest risk of breast cancer and women in agriculture had the lowest risk. For incidence, the gradient in the relative risks was 1.74, which changed to 1.49 when fertility history was incorporated and to 1.29 when school education was also taken into account. For school education, women with > or = 12 years of schooling had the highest risk and women with < or = 7 years of schooling had the lowest risk. For incidence, the gradient in the relative risk was 1.38, which changed to 1.26 when fertility history was incorporated and to 1.22 when socioeconomic group was also taken into account., (Copyright 2004 Wiley-Liss, Inc.)

Background: Breast cancer is the most frequent cancer in women and the incidence has increased over time. Our objectives were to study: (1) the socioeconomic differences in breast cancer incidence and mortality in Denmark, (2) how different socioeconomic groups have contributed to the increasing incidence, (3) whether the diverging trend between breast cancer incidence and mortality reflects different socioeconomic distributions of breast cancer cases and breast cancer deaths, and (4) to compare measures of socioeconomic status based on own and spouses' occupation, respectively. We addressed these questions by studying the socioeconomic distribution of breast cancer incidence and breast cancer mortality in Danish women during the last 25 years., Methods: In all 1 402 225 women in Denmark were individually followed up for death, emigration, and incident breast cancer in 1970-1995. Of the 1 402 225 women included in the study, 730 549 were economically active in 1970, and 480 379 women were both married and economically active. Socioeconomic status was assessed based on the occupation in 1970., Results: For all women classified by their own socioeconomic group, the standardized incidence (SIR) and the standardized mortality ratios (SMR) were highest in academics (SIR = 1.39, SMR = 1.29), and lowest in women in agriculture (SIR = 0.77, SMR = 0.75). For married, economically active women classified by their own socioeconomic group the SIR and SMR were highest in academics (SIR = 1.40, SMR = 1.44) and lowest in women in agriculture (SIR = 0.76, SMR = 0.76). Classified by their husbands' socioeconomic group, the SIR and SMR were highest in women married to academics (SIR = 1.21, SMR = 1.16) and lowest in women married to men in agriculture (SIR = 0.79, SMR = 0.79). From 1970 to 1995, the risk of developing breast cancer increased by 38% in women aged 50-64. All social groups contributed to this increase, the increase being 45% in unskilled workers, and 26% in academics., Conclusion: During the last quarter of the 20th century academics had the highest risk of breast cancer in Denmark. The size of the social gradient in breast cancer occurrence depended on the measure used. The time trends in social distribution will result in breast cancer becoming more frequent.

Background: Denmark and Norway have a three-fold higher incidence of testicular cancer than Estonia and Finland. Groups of young men from Denmark, Norway, Finland and Estonia were investigated to elucidate whether semen parameters and other related parameters follow a gradient between these countries, as does the gradient in incidence of testicular cancer., Methods: In total, 968 young men from the general population in these four countries were investigated according to the same protocol. Possible confounders were evaluated, and included in the statistical analysis when appropriate. Inter-laboratory differences in assessment of sperm concentrations were controlled by an external quality control programme and morphology assessment was centralized to one person., Results: The Finnish and Estonian men had an adjusted median sperm concentration of 54 and 57 x 10(6)/ml, respectively and the Norwegian and Danish men 41 x 10(6)/ml. The corresponding total sperm counts were 185, 174, 133 and 144 x 10(6). The frequency of normal sperm in men from Finland was 8.9%, Estonia 9.2%, Norway 6.9% and Denmark 6.4%. Within all four groups of men, a relationship between increasing levels of inhibin-B and increasing sperm counts was observed. However, inhibin-B levels were not predictive of sperm count differences between countries., Conclusions: It is believed that the men examined were representative of the normal population of young men in all four countries as they were recruited from groups attending a compulsory medical examination, and not selected for known fertility or semen quality. Moreover, the majority of participants had no prior knowledge of their fertility potential. It appears that an east-west gradient exists in the Nordic-Baltic area with regard to semen parameters, this being in parallel with the incidences of testicular cancer. Further investigations are required to determine whether these findings are due to genetic differences, to different environments, or perhaps to a combination of both factors.