ABSTRACT
BACKGROUND: Reference intervals covering the whole life span for all the metabolites in the steroid hormone biosynthesis quantified by sensitive and robust analytical methods are sparse or not existing. OBJECTIVE: To develop a state-of-the-art LC-MS/MS method for simultaneous quantification of multiple steroid metabolites and to establish detailed sex- and age-specific reference intervals for 16 steroid metabolites. MATERIALS AND METHOD: An isotope diluted LC-MS/MS method was developed for simultaneous quantitation of 16 steroid hormones. Serum samples from cross-sectional cohorts of healthy infants, children, adolescents, and adults aged 0.17 months to 77 years (n = 2458) were analysed. RESULTS: With this novel, specific, and sensitive LC-MS/MS method, it was possible to quantify progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione, testosterone, dihydrotestosterone, 11-deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, and cortisone in ≥90 % of the samples, while estrone sulfate, aldosterone and dehydroepiandrosterone were quantified in 77 %, 75 % and 60 % of the samples, respectively. 21-deoxycortisol was only detectable in 2.5 % of samples from healthy subjects. Sex- and age-dependent fluctuations observed in minipuberty, puberty and adulthood including the menopausal transition were modelled. This enabled us to establish valid reference intervals from birth to late adult life for both males and females. CONCLUSION: Detailed sex- and age-specific reference intervals of multiple, simultaneously quantified steroid metabolites by a novel and specific LC-MS/MS method provides a valuable tool for clinical practice and for future research.
Subject(s)
Liquid Chromatography-Mass Spectrometry , Steroids , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Young Adult , Age Factors , Cross-Sectional Studies , Healthy Volunteers , Liquid Chromatography-Mass Spectrometry/methods , Reference Values , Sex Factors , Steroids/blood , Steroids/metabolism , Tandem Mass Spectrometry/standardsABSTRACT
OBJECTIVE: To describe the natural history of inhibin B throughout life according to sex, age, and pubertal development. METHODS: Based on serum samples from 2707 healthy controls aged 0 to 80 years, sex- and age-specific reference ranges of inhibin B concentrations were constructed. Concentrations were evaluated according to pubertal development and use of oral contraceptives (OCs). Also, measurements from 42 patients with Klinefelter syndrome were included. RESULTS: In both sexes, inhibin B concentrations were high during minipuberty, decreased in childhood, and increased significantly from Tanner stages B1 to B3 (peak: B4) in females and from G1 to G3 (peak: G3) in males. Despite variations in menstruating females, inhibin B concentrations remained relatively constant after puberty, until becoming unmeasurable at menopause. Despite a modest decrease, the inhibin B concentration in males remained relatively high from puberty onwards. At any age, males had highest concentrations. Inhibin B standard deviation (SD) scores were lower in OC-users (median SD score = -0.88) than in non-users (SD score = 0.35), p < 0.001. In patients with Klinefelter syndrome, inhibin B concentrations spanned the reference range until around 15 years of age, where they decreased to subnormal or unmeasurable levels. CONCLUSION: Valuable sex- and age-specific reference data for inhibin B concentrations were provided. In OC-users, decreased concentrations of inhibin B underlined the ovaries as the only place of inhibin B production. In patients with Klinefelter syndrome, the decline in inhibin B concentrations at puberty underlined the shift in regulation of inhibin B production at pubertal onset.
ABSTRACT
AIM: Growth reference values about mid-upper arm circumference (MUAC) are vital for assessing children's nutritional status. However, Pakistan lacks these reference values and growth charts. This study aims to develop these for children aged 6-60 months and compare them with global standards. METHODS: The data were acquired from the 2018 National Nutrition Survey of Pakistan, which was conducted by the United Nations Children's Fund (UNICEF) during 2018-2019. The final study cohort comprised 57 285 children, with 51% being boys. Percentile values and charts for MUAC-for-age were developed using generalised additive models for location, scale and shape with the Box-Cox power exponential distribution. RESULTS: The mean MUAC was 14.21 cm (±2.07 cm) and 14.13 cm (±2.12 cm) for the boys and girls, respectively. At 60 months of age, the P3 and P97 percentiles for girls were slightly higher than those for boys. The median percentiles of Pakistani children were smaller than the World Health Organisation 2007 standards and with international references. CONCLUSION: We observed disparities in MUAC-for-age growth references among Pakistani children compared to global standards, highlighting regional, age and gender variations. This underscores the need for developing countries like Pakistan to establish their growth references.
Subject(s)
Arm , Growth Charts , Humans , Male , Pakistan , Female , Infant , Arm/anatomy & histology , Child, Preschool , Reference Values , AnthropometryABSTRACT
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 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.
Subject(s)
COVID-19 , Scandinavians and Nordic People , Adolescent , Adult , Humans , Cohort Studies , COVID-19/epidemiology , Denmark/epidemiology , Ethnic and Racial Minorities , Ethnicity , Minority Groups , Post-Acute COVID-19 Syndrome , SARS-CoV-2 , North African People , Middle Eastern People , Eastern European People , Asian PeopleABSTRACT
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. No SARS-CoV-2 RNA was detected in semen at any time point. DISCUSSION AND CONCLUSION: This study showed a reduction in testicular function, which was for the first time confirmed by INSL3, in men mildly affected by SARS-CoV-2 infection. The risk of transmission of SARS-CoV-2 RNA via semen seems to be low. Febrile episodes may impact testicular function, but a direct effect of SARS-CoV-2 cannot be excluded.
Subject(s)
COVID-19 , Insulins , Adult , Humans , Male , Longitudinal Studies , Luteinizing Hormone , RNA, Viral , SARS-CoV-2 , Semen , TestosteroneABSTRACT
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.
Subject(s)
COVID-19 , Emigrants and Immigrants , Humans , COVID-19/mortality , Critical Care/statistics & numerical data , Denmark/epidemiology , Ethnic and Racial Minorities , Intensive Care UnitsABSTRACT
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.
Subject(s)
Stroke , Male , Humans , Female , Prospective Studies , Tanzania , Stroke/diagnosis , Stroke/therapy , Hospitalization , PovertyABSTRACT
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 study raises concern and suggests that exposure of pregnant women to phthalates may have long-term effects on adult reproductive health in male offspring.
Subject(s)
Phthalic Acids , Prenatal Exposure Delayed Effects , Infant , Humans , Male , Pregnancy , Female , Young Adult , Maternal Exposure , Testis , Semen Analysis , Nuclear Family , Follow-Up Studies , Adult Children , Testosterone , Luteinizing HormoneABSTRACT
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.
Subject(s)
Bacteremia , Community-Acquired Infections , Escherichia coli Infections , Sepsis , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial , Ciprofloxacin , Escherichia coli , Escherichia coli Infections/drug therapy , Escherichia coli Infections/epidemiology , Sepsis/drug therapy , Community-Acquired Infections/epidemiology , Community-Acquired Infections/drug therapy , Bacteremia/drug therapy , Bacteremia/epidemiology , Denmark/epidemiologySubject(s)
Bone Density , Bone Remodeling , Humans , Child , Adolescent , Absorptiometry, Photon , Age FactorsABSTRACT
OBJECTIVE: Self-reported psychological stress has been associated with decreased semen quality. Cortisol levels in scalp hair (hair cortisol concentration, HCC) has emerged as a potential objective marker of psychological stress. Thus, we investigated if HCC was associated with markers of testicular function. Furthermore, we examined whether three common single nucleotide polymorphisms in the glucocorticoid-receptor gene (NR3C1, chromosome 5), potentially affecting receptor sensitivity, were associated with HCC and could influence the studied association between HCC and testicular function. DESIGN: Cross-sectional study. METHODS: We analysed HCC, serum-levels of reproductive hormones, semen parameters, and the three NR3C1-polymorphisms; BclI (rs41423247), Tth111I (rs10052957), and 9ß (rs6198), in a population of 696 men from the general population. RESULTS: HCC was not associated with testicular function, and adjustment for the three NR3C1-polymorphisms did not alter the results. However, HCC increased significantly with the number of Tth111I minor-alleles (T) and decreased significantly with the number of 9ß minor-alleles (G). CONCLUSION: Given previously shown associations between stress and semen quality, and that no association between HCC and self-reported stress was observed in the current study, we speculate that negative reproductive effects of stress may not be mediated directly by cortisol. This study demonstrates associations between HCC and glucocorticoid receptor gene variants indicating that these SNPs may influence systemic glucocorticoid levels, but the potential health effects of such alterations are yet unknown.
ABSTRACT
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.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Transients and Migrants , Female , Humans , Cross-Sectional Studies , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial , Staphylococcal Infections/microbiology , Ciprofloxacin , Denmark/epidemiologyABSTRACT
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).
ABSTRACT
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. TRIAL REGISTRATION: Clinical Trials.gov NCT05212337 . Registered on 14 January 2022. EudraCT 2021-003,451-42. Registered on 23 June 2021. Ethical committee H-21040145. Registered on 23 December 2021.
Subject(s)
Denosumab , Infertility, Male , Semen Analysis , Denosumab/therapeutic use , Humans , Infertility, Male/drug therapy , Male , Pilot Projects , Randomized Controlled Trials as Topic , Sperm CountABSTRACT
OBJECTIVE: To evaluate whether optimized and standardized 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 a nationwide Danish study was estimated to be 1.9%. PATIENTS AND METHODS: This was a retrospective analysis of outcomes in 655 patients with TGCT who underwent contralateral biopsies (1996-2007) compared with those in 459 non-biopsied TGCT controls (1984-1988). The biopsies were performed using a standardized 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 (four were lost to follow-up), the cumulative incidence of metachronous TGCT was estimated in a competing risk setting using the Grey method. All cases of metachronous TGCT were re-examined using immunohistochemistry. RESULTS: Germ cell neoplasia in situ was found in 47/655 biopsied patients (7.2%, 95% confidence interval [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 on histological revision using immunohistochemistry and 2/5 biopsies were inadequate because of too small size. The estimated cumulative incidence rate of second tumour after 20 years of follow-up was 0.95% (95% CI 0.10%-1.8%) compared with 2.9% (95% CI 1.3%-4.4%) among the non-biopsied TGCT patients (P = 0.012). The estimates should be viewed with caution due to the small number of patients with metachronous TGCT. CONCLUSIONS: Optimized diagnostic procedures improved the detection rate of GCNIS in patients with TGCT and minimized their risk of developing metachronous bilateral cancer. Urologists should be aware of the importance of careful tissue excision (to avoid mechanical compression) and the need of adequate biopsy size. Performing contralateral biopsies is beneficial for patients' care and should be offered as a part of their management.
Subject(s)
Neoplasms, Germ Cell and Embryonal , Neoplasms, Second Primary , Testicular Neoplasms , Male , Humans , Neoplasms, Second Primary/diagnosis , Neoplasms, Second Primary/epidemiology , Testis/pathology , Retrospective Studies , Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/pathology , Testicular Neoplasms/pathology , Biopsy , Germ Cells/pathologyABSTRACT
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 = 0.343â, p = 0.256â). 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.
ABSTRACT
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.
Subject(s)
Mental Disorders/epidemiology , Refugees/psychology , Registries/statistics & numerical data , Schools/statistics & numerical data , Social Marginalization/psychology , Socioeconomic Factors , Unemployment/statistics & numerical data , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Refugees/statistics & numerical data , Young AdultABSTRACT
BACKGROUND: Quarterly intramuscular injections with long-acting testosterone undecanoate (TU) provide stable serum testosterone concentrations over time and are therefore preferred by many testosterone-deficient patients. However, the use of long-acting TU in elderly patients is limited due to lack of safety and feasibility studies. OBJECTIVE: To investigate long-acting TU pharmacokinetics and assess differences in treatment regimens and risk of adverse outcomes in younger versus elderly testosterone-deficient patients. MATERIALS AND METHODS: Single-center longitudinal observational study. Patients who initiated long-acting TU treatment between 2005 and 2010 were included. Elderly patients were born before 1956 and younger patients between 1965 and 1985. TU dose was adjusted yearly through shortening or prolongation of time between injections. Treatment targets were as follows: (1) free testosterone between 0 and -1 SD from the age-adjusted mean, (2) no symptoms of testosterone deficiency, and (3) hematocrit within the normal range. RESULTS: The study population consisted of 63 elderly and 63 younger patients. Median follow-up time during testosterone replacement was 12.1 years. Increasing intervals between TU injections were performed 44% more often in the elderly compared to younger patients and time between TU injections were prolonged 4% more in the elderly patients. The hematocrit, as well as the hematocrit for a given serum testosterone (hematocrit: testosterone ratio), increased with treatment time but did not differ between age groups. During follow-up, 40% of patients-both elderly and younger-experienced polycythemia. Risk of polycythemia did not differ with age. DISCUSSION AND CONCLUSION: An increased number of adjustments of TU dose are necessary in elderly patients in order to reach treatment targets. TU treatment in elderly testosterone-deficient patients is not associated with an increased risk of polycythemia compared to younger patients if age-adjusted treatment targets are reached.
Subject(s)
Age Factors , Androgens/administration & dosage , Hormone Replacement Therapy/methods , Testosterone/analogs & derivatives , Testosterone/deficiency , Aged , Humans , Injections, Intramuscular , Longitudinal Studies , Male , Middle Aged , Testosterone/administration & dosage , Testosterone/blood , Treatment OutcomeABSTRACT
CONTEXT: Vitamin D has been linked with glucose and lipid metabolism. Men with impaired gonadal function have a higher risk of metabolic syndrome and mortality, and vitamin D status may be a reversible modulator. OBJECTIVE: This work aimed to determine the effect of daily vitamin D and calcium supplementation for 150 days on glucose and lipid homeostasis in infertile men. METHODS: A single-center, double-blinded, randomized clinical trial (NCT01304927) was conducted. A total of 307 infertile men were randomly assigned (1:1) to a single dose of 300â 000 IU cholecalciferol followed by 1400 IU cholecalciferolâ +â 500 mg of calcium daily (nâ =â 151) or placebo (nâ =â 156) for 150 days. Reported metabolic parameters including fasting plasma glucose, glycated hemoglobin A1c, fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma cholesterols, and triglycerides were secondary end points. The primary end point semen quality has previously been reported. RESULTS: Men receiving vitamin D supplementation improved their vitamin D status, whereas vitamin D status was aggravated in the placebo group characterized by higher serum parathyroid hormone. At the end of the trial, men receiving vitamin D supplementation had 13% lower fasting serum insulin concentrations compared with the placebo-treated group (65 vs 74 pmol/L, Pâ =â .018) and 19% lower HOMA-IR (2.2 vs 2.7, Pâ =â .025). Moreover, men in the vitamin D group had higher high-density lipoprotein (HDL) cholesterol levels (1.38 vs 1.32 mmol/L, Pâ =â .008) compared with the placebo group. CONCLUSION: High-dose vitamin D supplementation has beneficial effects on glucose homeostasis and HDL cholesterol levels in infertile men.
Subject(s)
Cholecalciferol/administration & dosage , Dietary Supplements , Infertility, Male/diet therapy , Insulin/blood , Vitamin D Deficiency/diet therapy , Adult , Blood Glucose/analysis , Blood Glucose/metabolism , Calcium/administration & dosage , Cholesterol, HDL/blood , Cholesterol, HDL/metabolism , Fasting/blood , Fasting/metabolism , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Humans , Infertility, Male/blood , Infertility, Male/diagnosis , Infertility, Male/metabolism , Insulin/metabolism , Insulin Resistance , Male , Semen Analysis , Treatment Outcome , Triglycerides/blood , Triglycerides/metabolism , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/diagnosis , Vitamin D Deficiency/metabolismABSTRACT
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 = 498â117). 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.