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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 = 2,287,175) 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 2,247,299 (98.3%) were nonhospitalised individuals. Of the diagnosed COVID-19 cases, 1,952,021 (85.3%) were native Danes and 335,154 (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 a, 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 = 2,287,175) 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 2,247,299 (98.3%) were nonhospitalised individuals. Of the diagnosed COVID-19 cases, 1,952,021 (85.3%) were native Danes and 335,154 (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 min

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect the male reproductive system as it uses angiotensin-converting enzyme (ACE)2, which is expressed in testicular tissue, as an entry point into the cell. Few studies have evaluated the long-term effects of mild coronavirus disease 2019 (COVID-19) on testicular function, and insulin-like factor 3 (INSL3) levels have not previously been assessed during acute SARS-CoV-2 infection. Objectives The aim of the study was to assess the impact of acute SARS-CoV-2 infection on testicular function including INSL3 and the presence of SARS-CoV-2 RNA in semen in non-hospitalised men with mild COVID-19. Materials and methods This longitudinal study included 36 non-hospitalised SARS-CoV-2-positive men (median age 29 years). Inclusion was within seven days following a positive SARS-CoV-2 reverse-transcription polymerase chain reaction test. Reproductive hormone levels, semen parameters, and the presence of SARS-CoV-2 RNA in oropharyngeal and semen samples were assessed during acute SARS-CoV-2 infection (baseline) and at three- and six-month follow-up. Wilcoxon matched-pair signed-rank (two samples) test was used to assess time-related alterations in reproductive hormone levels and semen parameters. Results Lower plasma testosterone (T) (total and calculated free (c-fT)) and higher luteinising hormone (LH) concentrations were observed during acute SARS-CoV-2 infection (baseline) compared to three- and six-month follow-up. Consequently, ratios of c-fT/LH were lower at baseline compared to three- and six-month follow-up (p < 0.001 and p = 0.003, respectively). Concomitantly, lower INSL3 concentrations were observed at baseline compared to three-month follow-up (p = 0.01). The total number of motile spermatozoa was also lower at baseline compared to six-month follow-up (p = 0.02). The alterations were detected irrespective of whether the men had experienced SARS, Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect the male reproductive system as it uses angiotensin-converting enzyme (ACE)2, which is expressed in testicular tissue, as an entry point into the cell. Few studies have evaluated the long-term effects of mild coronavirus disease 2019 (COVID-19) on testicular function, and insulin-like factor 3 (INSL3) levels have not previously been assessed during acute SARS-CoV-2 infection. Objectives: The aim of the study was to assess the impact of acute SARS-CoV-2 infection on testicular function including INSL3 and the presence of SARS-CoV-2 RNA in semen in non-hospitalised men with mild COVID-19. Materials and methods: This longitudinal study included 36 non-hospitalised SARS-CoV-2-positive men (median age 29 years). Inclusion was within seven days following a positive SARS-CoV-2 reverse-transcription polymerase chain reaction test. Reproductive hormone levels, semen parameters, and the presence of SARS-CoV-2 RNA in oropharyngeal and semen samples were assessed during acute SARS-CoV-2 infection (baseline) and at three- and six-month follow-up. Wilcoxon matched-pair signed-rank (two samples) test was used to assess time-related alterations in reproductive hormone levels and semen parameters. Results: Lower plasma testosterone (T) (total and calculated free (c-fT)) and higher luteinising hormone (LH) concentrations were observed during acute SARS-CoV-2 infection (baseline) compared to three- and six-month follow-up. Consequently, ratios of c-fT/LH were lower at baseline compared to three- and six-month follow-up (p < 0.001 and p = 0.003, respectively). Concomitantly, lower INSL3 concentrations were observed at baseline compared to three-month follow-up (p = 0.01). The total number of motile spermatozoa was also lower at baseline compared to six-month follow-up (p = 0.02). The alterations were detected irrespective of whether the men had experienced SARS-CoV-2-related fever episodes or not.

Adult patients with Klinefelter syndrome (KS) are characterized by a highly variable phenotype, including tall stature, obesity, and hypergonadotropic hypogonadism, as well as an increased risk of developing insulin resistance, metabolic syndrome, and osteoporosis. Most adults need testosterone replacement therapy (TRT), whereas the use of TRT during puberty has been debated. In this retrospective, observational study, reproductive hormones and whole-body dual-energy x-ray absorptiometry-derived body composition and bone mineral content were standardized to age-related standard deviation scores in 62 patients with KS aged 5.9–20.6 years. Serum concentrations of total testosterone and inhibin B were low, whereas luteinizing hormone and follicle-stimulating hormone were high in patients before TRT. Despite normal body mass index, body fat percentage and the ratio between android fat percentage and gynoid fat percentage were significantly higher in the entire group irrespective of treatment status. In patients evaluated before and during TRT, a tendency toward a more beneficial body composition with a significant reduction in the ratio between android fat percentage and gynoid fat percentage during TRT was found. Bone mineral content (BMC) did not differ from the reference, but BMC corrected for bone area was significantly lower when compared to the reference. This study confirms that patients with KS have an unfavorable body composition and an impaired bone mineral status already during childhood and adolescence. Systematic studies are needed to evaluate whether TRT during puberty will improve these parameters. Keywords: Klinefelter syndrome; body composition; truncal obesity; bone mineral content, Adult patients with Klinefelter syndrome (KS) are characterized by a highly variable phenotype, including tall stature, obesity, and hypergonadotropic hypogonadism, as well as an increased risk of developing insulin resistance, metabolic syndrome, and osteoporosis. Most adults need testosterone replacement therapy (TRT), whereas the use of TRT during puberty has been debated. In this retrospective, observational study, reproductive hormones and whole-body dual-energy x-ray absorptiometry-derived body composition and bone mineral content were standardized to age-related standard deviation scores in 62 patients with KS aged 5.9–20.6 years. Serum concentrations of total testosterone and inhibin B were low, whereas luteinizing hormone and follicle-stimulating hormone were high in patients before TRT. Despite normal body mass index, body fat percentage and the ratio between android fat percentage and gynoid fat percentage were significantly higher in the entire group irrespective of treatment status. In patients evaluated before and during TRT, a tendency toward a more beneficial body composition with a significant reduction in the ratio between android fat percentage and gynoid fat percentage during TRT was found. Bone mineral content (BMC) did not differ from the reference, but BMC corrected for bone area was significantly lower when compared to the reference. This study confirms that patients with KS have an unfavorable body composition and an impaired bone mineral status already during childhood and adolescence. Systematic studies are needed to evaluate whether TRT during puberty will improve these parameters.

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., 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.

Objectives: To characterise mortality and functional outcome and their relationships with socioeconomic deprivation for women and men in Zanzibar. Materials and methods: Participants in ZanStroke, a prospective observational study of patients admitted to hospital with a diagnosis of acute stroke, were followed up until one year after the stroke. The modified National Institute of Health Stroke Scale was used to assess initial stroke severity, while modified Rankin Scale (mRS) was used to assess disability at 12 months post-stroke. A multidimensional poverty index was created using individual-level data. Kaplan-Meier analysis and Cox regression model were used to examine associations of socioeconomic deprivation and death at 28 days and 12 months after stroke onset, while logistic regression analysis was used to examine associations between deprivation and functional outcome. Results: Overall mortality rate was 38.2% (CI 34.8-41.9) at 28 days, rising to 59.0% (CI 55.2-62.8) at 12 months. When adjusted for other variables, survival was higher among the least deprived (HR 0.60 CI 0.45-0.80), an association that was strongly significant for women (HR 0.46 CI 0.29-0.74). Among 12-month survivors 45.1% (n = 122) had no/low level of disability (mRS 0-2), while 22.9% (n = 62) were unable to walk independently or at all. No difference between socioeconomic deprivation and outcome was seen at one year. Conclusion: Case-fatality rates were high, and socioeconomic disparities were evident even during the acute stroke phase. Policies are needed to reduce significant health disparities, adapt evidence-based interventions, and promote equitable access to stroke care and rehabilitation.

Background Phthalate exposure during fetal life may disrupt testicular development. Congruent with this, studies have found shorter anogenital distance, reduced penile size and altered hormone levels in infant boys whose mothers were exposed to higher levels of some phthalates during pregnancy. Few studies have explored if such adverse effects persist in adulthood. Thus, we aimed to explore if there is an association between fetal phthalate exposure and markers of testicular function in young adult men. Methods In a longitudinal mother-child cohort from Copenhagen, Denmark, we examined 100 young men whose mothers during pregnancy had serum drawn and analyzed for 34 phthalate metabolites. Examinations of the young men took place at 18–20 years of age and included measurements of adult markers of testicular function (reproductive hormones, penile size, anogenital distance (AGD), testis volume, semen quality) and growth factors. Associations between maternal serum concentrations of phthalate metabolites and reproductive measures in the young men were tested using multiple linear regression. Results Most consistently, higher maternal phthalate exposure was associated with higher luteinizing hormone (LH) but unchanged testosterone in adult sons. Congruently, higher maternal exposure was associated with lower total and free testosterone/LH ratios in adult sons. For example, twice as high maternal MiNP was associated with a 7.9 % (95 % CI 1.6–13.8) lower free testosterone/LH ratio. There was no consistent pattern of associations between the different phthalate metabolites and other reproductive hormones, clinical outcomes, or semen quality. None of the tested associations was significant after multiplicity adjustment. Conclusions In this exploratory study, higher maternal exposure to some phthalates was associated with impaired testicular Leydig cell function evidenced by a lower total and free testosterone/LH ratio in adult sons., Background: Phthalate exposure during fetal life may disrupt testicular development. Congruent with this, studies have found shorter anogenital distance, reduced penile size and altered hormone levels in infant boys whose mothers were exposed to higher levels of some phthalates during pregnancy. Few studies have explored if such adverse effects persist in adulthood. Thus, we aimed to explore if there is an association between fetal phthalate exposure and markers of testicular function in young adult men. Methods: In a longitudinal mother-child cohort from Copenhagen, Denmark, we examined 100 young men whose mothers during pregnancy had serum drawn and analyzed for 34 phthalate metabolites. Examinations of the young men took place at 18–20 years of age and included measurements of adult markers of testicular function (reproductive hormones, penile size, anogenital distance (AGD), testis volume, semen quality) and growth factors. Associations between maternal serum concentrations of phthalate metabolites and reproductive measures in the young men were tested using multiple linear regression. Results: Most consistently, higher maternal phthalate exposure was associated with higher luteinizing hormone (LH) but unchanged testosterone in adult sons. Congruently, higher maternal exposure was associated with lower total and free testosterone/LH ratios in adult sons. For example, twice as high maternal MiNP was associated with a 7.9 % (95 % CI 1.6–13.8) lower free testosterone/LH ratio. There was no consistent pattern of associations between the different phthalate metabolites and other reproductive hormones, clinical outcomes, or semen quality. None of the tested associations was significant after multiplicity adjustment. Conclusions: In this exploratory study, higher maternal exposure to some phthalates was associated with impaired testicular Leydig cell function evidenced by a lower total and free testosterone/LH ratio in adult sons. This unique 18–20-year follow-up st

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. 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, Background: 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. Methods: 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). Results: 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. Conclusions: 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.

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 Staphylococcus aureus (MRSA) than nonmigrants (OR 5.01, 95%CI: 2.61-5.13 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.

OBJECTIVE: To evaluate if optimised and standardised diagnostic procedures would improve detection of germ cell neoplasia in situ (GCNIS) in the contralateral testis of patients with testicular germ cell tumour (TGCT), and decrease the rate of metachronous tumours, which in the nationwide Danish study was estimated as 1.9%.PATIENTS AND METHODS: This is a retrospective analysis of the outcome in 655 patients with TGCT who underwent contralateral biopsies (1996 - 2007), in comparison to 459 non-biopsied TGCT controls (1984 -1988). The biopsies were performed using a standardised procedure with immunohistochemical GCNIS markers and assessed by experienced evaluators. Initial histopathology reports were reviewed, and pathology and survival data were retrieved from national Danish registers. In 604/608 patients diagnosed as GCNIS-negative (4 were lost to follow-up), the cumulative incidence of metachronous TGCT was estimated in a competing risk setting by the Gray method. All cases of metachronous TGCT were re-examined by immunohistochemistry.RESULTS: GCNIS was found in 47/655 biopsied patients (7.2%, 95% CI 5.4-9.5%). During the follow-up period (median 17.3 years) five of the 604 GCNIS-negative patients developed a TGCT. In 1/5 false-negative biopsies GCNIS was found upon revision and 2/5 biopsies were too small. The estimated cumulative incidence rate of the second tumour after 20 years of follow-up was 0.95% (95%CI 0.10%-1.8%) compared with 2.9% (1.3%-4.4%) among the non-biopsied TGCT patients (p=0.012). The estimates should be taken with caution due to small numbers of men with metachronous TGCT.CONCLUSIONS: Optimised diagnostic procedures improved the detection rate of GCNIS in patients with TGCT and minimized their risk of developing metachronous bilateral cancer. Urologists must be aware of the importance of the surgical procedure and an adequate biopsy size. Performing contralateral biopsies is beneficial for the patients' care and should

Background: Ethnicity might impact out-of-hospital cardiac arrest (OHCA) risk, but it has scarcely been studied in Europe. We aimed to assess whether ethnicity influenced the risk of OHCA of cardiac cause in Danish immigrants and its interplay with risk factors for OHCA and socioeconomic status. Methods: This nationwide study included all immigrants between 18 and 80 years present in Denmark at some point between 2001 and 2020. Regions of origin were defined as Africa, Arabic countries, Asia, Eastern Europe, Latin America, and Western countries. OHCAs with presumed cardiac cause were identified from the Danish Cardiac Arrest Registry. Findings: Overall, among 1,011,565 immigrants, a total of 1,801 (0.2%) OHCAs (median age 64 (Q1-Q3 53–72) years, 72% males) occurred. The age- and sex- standardized (reference: Western countries) incidence of OHCA (/1,00,000 person-years) was 34.6 (27.8–43.4) in African, 34.1 (30.4–38.4) in Arabic, 33.5 (29.3–38.2) in Asian, 35.6 (31.9–39.6) in Eastern European, and 16.2 (9.0–27.2) in Latin American immigrants. When selecting Western origin as a reference, and after adjusting on OHCA risk factors, Arabic (HR 1.18, 95%CI 1.04–1.35; P=0.01), Eastern European (HR 1.28, 95%CI 1.13–1.46; P<0.001), and African origin (HR 1.34, 95%CI 1.10–1.63; P<0.01) were associated with higher risk of OHCA, whereas Latin American origin (HR 0.58, 95%CI 0.35–0.0.96; P=0.03) was associated with lower risk of OHCA. Comparable results were observed when adjusting on education level and economic status. Interpretation: This study emphasizes that ethnicity is associated with OHCA risk, even when considering traditional cardiac arrest risk factors. Funding: R Garcia received a grant from the Fédération Française de Cardiologie for his post-doctoral fellowship and this work was supported by the Novo Nordisk Foundation Tandem Programme 2022 (grant# 31364).

Background: Infertility is a common problem globally and impaired semen quality is responsible for up to 40% of all cases. Almost all infertile couples are treated with either insemination or assisted reproductive techniques (ARTs) independent of the etiology of infertility because no medical treatment exists. Denosumab is an antibody that blocks RANKL signaling and inhibition of testicular RANKL signaling has been suggested to improve semen quality in a pilot study. This RCT aims to assess whether treatment with denosumab can improve spermatogenesis in infertile men selected by serum AMH as a positive predictive biomarker. This paper describes the design of the study.Methods/design: FITMI is a sponsor-investigator-initiated, double-blinded, placebo-controlled 1:1, single-center, randomized clinical trial. Subjects will be randomized to receive either a single-dose denosumab 60 mg subcutaneous injection or placebo. The study will be carried out at the Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen. The primary outcome of the study is defined as the difference in sperm concentration (millions pr. mL) one spermatogenesis (80 days) after inclusion.Discussion: We describe a protocol for a planned RCT aimed at evaluating whether treatment with denosumab can improve the semen quality in infertile men selected by using serum AMH as a positive predictive biomarker. The results will provide evidence crucial for future treatment in a patient group where there is a huge unmet need.

CONTEXT: It remains unknown how the postnatal activation of the hypothalamic-pituitary-gonadal axis in infancy, also known as 'minipuberty', relates to adult testis function.OBJECTIVE: To investigate how markers of reproductive function in three-month-old boys correlate with adult reproductive health parameters.DESIGN: Population-based birth cohort study (the Copenhagen Mother-Child cohort).SETTING: Copenhagen University Hospital, Denmark.PARTICIPANTS: 259 boys examined once around three months of age and again at 18-20 years.MAIN OUTCOME MEASURES: Reproductive hormones, penile length, testis volume, and semen quality. Minipubertal markers of testis function (by tertiles, T1-T3) were explored as predictors of adult semen quality using linear regression models. Associations between reproductive outcomes in infancy and young adulthood were estimated by intra-class correlation coefficients (ICCs), describing how well measurements in infancy correlate with those in adulthood.RESULTS: Serum testosterone concentration in infancy was positively associated with adult total sperm count. Median (IQR) total sperm count was 84 (54-138) million spermatozoa for boys in T1, 141 (81-286) million spermatozoa in T2, and 193 (56-287) million spermatozoa in T3. We found the highest ICC for FSH (0.41, 95% CI 0.26-0.57), while ICCs for inhibin B, SHBG, penile length, and testis volume ranged between 0.24 and 0.27. ICCs for LH, total and free testosterone were lower and statistically non-significant.CONCLUSIONS: Serum testosterone in infancy was a predictor of adult total sperm count. Other reproductive hormones and genital measures showed good correlation between infancy and adulthood, suggesting that an individual's reproductive setpoint starts shortly after birth in boys and persists until adulthood.

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 f

Background: Fabry disease (FD) is a lysosomal storage disorder resulting in systemic accumulation of globotriaosylceramide (Gb3) causing multi-organ dysfunction. The audiologic involvement in FD has been neglected in previous studies; while not a lethal aspect of the disease, hearing loss can have a significantly negative impact on quality of life. Objective: To investigate hearing loss from baseline through 16 years follow-up of the Danish FD cohort and to compare audiometric data to other clinical variables. Methods: Data was collected prospectively and assessed retrospectively during a period of 16 years from 83 patients (age: 9–72 years; sex: 29 males and 54 females). 55 patients underwent treatment. Air conduction thresholds was assessed at six frequencies between 0.25 and 8 kHz bilaterally. Data was analyzed using multilinear models. Results: Mean follow-up period for patients undergoing a FD specific treatment was 7.8 years (0–12.8 years, SD 3.8 years, n = 55). Hearing thresholds for FD patients deviated from healthy individuals at all frequencies for both sexes (p < 0.001). Males had more profound hearing loss than females at high frequencies (4,8 kHz) (p = 0.025). There was no improvement in hearing with treatment (p = 0.343♂, p = 0.256♀). No associations between hearing loss and measured glomerular filtration rate, left ventricular wall thickness or cerebral white matter lesions were found. Lower plasma Gb3 concentration correlated with better hearing (p = 0.046) in males. Conclusion: Our findings demonstrated significant hearing loss in FD patients compared to audiologically healthy individuals at all frequencies, and no change in hearing during treatment. Lower plasma Gb3 concentrations correlated with better hearing in males.

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.

Objectives: Longitudinal assessment of testicular function after pediatric hematopoietic stem cell transplantation (HSCT) is needed to guide clinical follow-up. We investigated dynamics in male reproductive hormones after pediatric HSCT, focusing on pubertal timing and associations with testosterone deficiency and azoospermia in adulthood. Methods: This retrospective, longitudinal study included 39 survivors median 19 years after pediatric HSCT. Serum concentrations of LH, testosterone, FSH, and inhibin B from the time of HSCT, during puberty, and into adulthood were analyzed. Pubertal timing (rise in LH and testosterone) was compared to a reference cohort of 112 healthy boys. Associations between reproductive hormone levels during puberty and adult testicular function (including semen quality) were investigated. Results: Pubertal induction with testosterone was needed in 6/26 patients who were prepubertal at HSCT. In the remaining patients, pubertal timing was comparable to the reference cohort. However, 9/33 patients (without pubertal induction) developed testosterone deficiency in early adulthood, which was associated with higher LH levels from age 14 to 16 years. Azoospermia in adulthood was found in 18/26 patients without testosterone substitution. Higher FSH and lower inhibin B levels from mid-pubertal age were associated with azoospermia in adulthood, in patients being prepubertal at HSCT. Conclusion: Our results indicate a substantial risk of deterioration in testicular function after pediatric HSCT, despite normal pubertal timing. Although reproductive hormone levels from mid-puberty indicated adult testicular function, prolonged follow-up into adulthood is needed in these patients, including clinical examination, reproductive hormone analysis, and semen sample for patients interested in their fertility potential.

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.

STUDY QUESTION: Is testicular function associated within father-son pairs? SUMMARY ANSWER: Familial resemblance in testis volume and serum markers of spermatogenesis was observed in father-son pairs. WHAT IS KNOWN ALREADY: Studies suggest familial clustering of male subfertility and impaired spermatogenesis, but in men from the general population little is known about concordance in testicular function between fathers and sons. STUDY DESIGN, SIZE, DURATION: This cross-sectional study with simultaneous collection of data in fathers and sons included 72 pairs (144 fathers and sons), unselected regarding testicular function were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: A subgroup of men from the background population and participating in a study on testicular function were asked permission to invite their fathers to participate in a similar setup. Fathers (median age of 53 years) and sons (median age of 19 years) participated in the same study setup including assessment of testis size, having a blood sample taken and analysed for serum levels of reproductive hormones (FSH, inhibin B, LH, testosterone, oestradiol, sex hormone-binding globulin (SHBG) and calculated free testosterone) and delivering a semen sample for assessment of traditional semen parameters. Mixed-effects models were fitted to estimate the familial resemblance as the proportion of variance in markers of testicular function due to shared factors for fathers and sons accounted for using random-effects. Variance components were calculated from both unadjusted and adjusted models. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustments, variance component analyses showed that familial resemblance between fathers and sons accounted for 48% (P < 0.001) of the variation in testicular volume, 32% (P = 0.009) of the variation in FSH, 31% (P = 0.009) of the variation in the inhibin B/FSH ratio, 33% (P = 0.007) and 45% (P < 0.001) of the variation in testosterone and free testosterone, respecti

Purpose Insulin-like factor 3 (INSL3) is an emerging testicular marker, yet larger studies elucidating the clinical role of INSL3 in patients with hypogonadism are lacking. The aim was to describe serum INSL3 concentrations analyzed by LC-MS/MS methodology in males with hypogonadotropic hypogonadism (HH) and Klinefelter syndrome (KS).Methods This was a combined study from two tertiary centers in Denmark and France analyzing INSL3 concentrations by LC-MS/MS. In total, 103 patients with HH and 82 patients with KS were grouped into treated (HH: n = 96; KS: n = 71) or untreated (HH: n = 7; KS: n = 11). Treatment modalities included testosterone and hCG. Serum concentrations and standard deviation (SD) scores of INSL3, total testosterone, and LH according to age and treatment were evaluated.Results In both HH and KS, INSL3 concentrations were low. In HH, INSL3 was low regardless of treatment, except for some hCG-treated patients with normal concentrations. In untreated HH, testosterone was low, while normal to high in most testosterone- and hCG-treated patients. In untreated KS, INSL3 and testosterone concentrations were low to normal, while in testosterone-treated KS, serum INSL3 was low in most patients. INSL3 SD scores were significantly lower in untreated HH than in untreated KS (p = 0.01).Conclusions The dichotomy between lower INSL3 and higher testosterone concentrations, particularly observed in hCG-treated patients with HH, confirms that INSL3 is a different marker of Leydig cell function than testosterone. However, the clinical application of INSL3 in males with hypogonadism remains unclear.

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 m

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.

Context: The use of anogenital distance (AGD) in clinical and epidemiological settings is increasing; however, sex-specific reference data on AGD and data on longitudinal changes in AGD in children is scarce.Objective: To create age-, sex-, and method-related reference ranges of AGD in healthy boys and girls aged 0-24 months, to assess the age-related changes in AGD and to evaluate the 2 predominantly used methods of AGD measurement.Design: The International AGD consortium comprising 4 centers compiled data from 1 cross-sectional and 3 longitudinal cohort studies (clinicaltrials.gov [NCT02497209]).Setting: All data were collected from population-based studies, recruiting from 4 maternity or obstetric centers (United States, Cambridge [United Kingdom], Odense, and Copenhagen [Denmark]).Subjects: This study included a total of 3705 healthy, mainly Caucasian children aged 0-24 months on whom 7295 measurements were recorded.Main Outcome Measures: AGD(AS) (ano-scrotal), AGD(AF) (ano-fourchette), AGD(AP) (ano-penile), AGD(AC) (ano-clitoral), AGD body size indices (weight, body mass index [BMI], body surface area, and length), and intra- and interobserver biases.Results: We created age-specific reference ranges by centers. We found that AGD increased from birth to 6 months of age and thereafter reached a plateau. Changes in AGD/BMI during the first year of life were minor (0-6% and 0-11% in boys and girls, respectively).Conclusions: Reference ranges for AGD can be used in future epidemiological research and may be utilized clinically to evaluate prenatal androgen action in differences-in-sex-development patients. The increase in AGD during the first year of life was age-related, while AGD/BMI was fairly stable. The TIDES and Cambridge methods were equally reproducible.

BACKGROUND: The majority of tuberculosis (TB) cases in low-incidence countries occur in migrants. Only few studies have assessed the long-term TB risk in migrants after immigration, and datasets have not considered this across a range of diverse migrant groups. This nationwide study aimed to investigate long-term TB risk among migrants according to migrant status and region of origin. METHODS: This cohort study included all migrants aged ≥ 18 years who obtained residence in Denmark from 1993 to 2015, with a mean follow-up of 10.8 years [standard deviation (SD) 7.3]. Migrants were categorized based on legal status of residence and region of origin. Incidence rates (IR) and rate ratios (IRR) were estimated by Poisson regression. RESULTS: A total of 142 314 migrants were included. Across all migrants, the TB risk was highest during year 1 of residence (IR 275/100 000 person-years; 95% CI 249-305) followed by a gradual decline, though TB risk remained high for over a decade. Compared with the Danish-born population, the IRRs after 7-8 years were particularly higher among former asylum seekers (IRR 31; 95% CI 20-46), quota refugees (IRR 31; 95% CI 16-71), and family-reunified with refugees (IRR 22; 95% CI 12-44). Sub-Saharan African migrants also experienced elevated risk (IRR 75; 95% CI 51-109). The proportion of migrants with pulmonary TB was 52.4%. CONCLUSION: All migrant groups experienced an initial high TB risk, but long-term risk remained high in key migrant groups. Most European countries focus TB screening on or soon after arrival. Our study suggests that approaches to TB screening should be adapted, with migrant populations benefiting from long-term access to preventive health services.

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.

CONTEXT: The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low concentrations.OBJECTIVE: To establish sex-specific reference ranges for estrone (E1) and estradiol (E2) throughout life and to evaluate sex-differences using the state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantification of E1, E2, and estriol (E3).DESIGN: LC-MS/MS method development and construction of estrogen reference ranges.SETTINGS: Population-based cross-sectional cohorts from the greater Copenhagen and Aarhus areas.PARTICIPANTS: Healthy participants aged 3 months to 61 years (n = 1838).RESULTS: An isotope diluted LC-MS/MS method was developed and validated for measurements of serum E1, E2, and E3. Limits of detections (LODs) were 3 pmol/L (E1), 4 pmol/L (E2), and 12 pmol/L (E3), respectively. This sensitive method made it possible to differentiate between male and female concentration levels of E1 and E2 in children. In girls, E2 levels ranged from