Adverse childhood experiences, sexual risk-taking and non-consensual sexual experiences in a nationally representative study of 15-29-year-old Danes.

BACKGROUND: Adverse childhood experiences (ACEs) have been linked with risky health-related behaviors and poor health. OBJECTIVE: This study aimed to investigate associations of ACEs with a broad panel of sexual risk-taking behaviors and non-consensual sexual experiences among young people in Denmark. PARTICIPANTS AND SETTING: Baseline questionnaire data from 15 to 29-year-old participants in the nationally representative cohort study Project SEXUS were used in combination with data from Danish national registers to include a total of 13,132 individuals. METHODS: In logistic regression analyses, confounder-adjusted odds ratios (aORs) with 95 % confidence intervals (CIs) were obtained for associations of five ACE categories (Household challenges, Loss or threat of loss, Material deprivation, Abuse, and Neglect) and a cumulative ACE score with measures of sexual risk-taking and non-consensual sexual experiences. RESULTS: Statistically significant associations were observed between ACEs and multiple sexual risk-taking behaviors and non-consensual sexual experiences with particularly increased odds among individuals with a history of Abuse, Neglect, or an ACE score of 3 or more. Specifically, Abuse was associated with having received payment for sex (women: aOR 5.38; 95 % CI 2.73-10.61; men: aOR 2.11; 95 % CI 1.22-3.64), with having paid for sex (men: aOR 1.88; 95 % CI 1.41-2.51), and with having been the victim of a sexual assault after age 18 years (women: aOR 3.33; 95 % CI 2.36-4.68). CONCLUSIONS: In this Danish study, multiple measures of sexual risk-taking and non-consensual sexual experiences were markedly more common among young people with ACEs than in those without ACEs. This knowledge should be considered in future initiatives to promote sexual health among young people.

Smoking during pregnancy and risk of multiple sclerosis in offspring and mother: A Danish nationwide register-based cohort study.

BACKGROUND: The association between intra-uterine exposure to maternal smoking and risk of multiple sclerosis (MS) has been little studied and with conflicting results. OBJECTIVE: To examine the risk of MS in offspring exposed intra-uterine to maternal smoking. In addition, to re-examine prior observations of an elevated risk of MS among smokers, assuming that self-reported smoking during pregnancy reflects the woman's general smoking habits. METHODS: The study cohort included all Danish women, pregnant in the period 1991-2018, (n = 789,299) and singletons from these pregnancies (n = 879,135). Nationwide information on maternal smoking during pregnancy and MS cases in the study cohort were obtained from the Medical Birth Register and the National Patient Register. Cox regression analysis was used to estimate hazard ratios (HRs) for the association between smoking and MS risk. RESULTS: Women who smoked during pregnancy had a 42% increased risk of developing MS compared with non-smoking women (HR = 1.42 (1.32-1.52), n = 1,296). The risk of MS among singletons of women who smoked during pregnancy was 38% higher than that among singletons born to non-smoking women (HR = 1.38 (1.08-1.76), n = 110). CONCLUSION: Our observations add further to the evidence implicating smoking in the development of MS and suggest that intra-uterine exposure to tobacco smoke may increase MS risk.

Sexuality among young Danes treated for mental health problems: Baseline findings in a nationwide cohort study.

Mental health problems are common among adolescents and young adults (AYA), but although sexuality plays a central role in the transition from adolescence to adulthood, associations between such problems and sexuality have only been sparsely researched in AYA. The aim of this study was to investigate the association between mental health problems and various outcomes related to body and sexuality, romantic relationships, sexual functioning, and sexual risk behaviors among AYA. We used questionnaire data from 8696 Danish AYA aged 15-24 years who participated in the nationwide cohort study Project SEXUS at baseline in 2017-2018. Logistic regression analyses yielded demographically weighted, age-adjusted odds ratios for associations between mental health problems and sexual outcomes. Female AYA treated for mental health problems reported more active sex lives than other women. Treatment for mental health problems was associated with statistically significantly increased odds ratios for several sexual dysfunctions, and treated AYA significantly more often reported sexual debut before age 15 years, high sex partner numbers, sexual victimization, unsafe sex, sexually transmitted infections, induced abortions, discontentment with the appearance of body and genitalia, gender non-conformity, same-sex sexual experience, and non-heterosexual identity. Compared to healthy peers, AYA treated for mental health problems constitute a vulnerable group at increased risk of sexual adversities. Healthcare professionals should acknowledge these possible sexual challenges and offer relevant counselling to reduce the risk of adverse sexual outcomes in this group.

Associations between recalled childhood gender nonconformity and adult sexual dysfunction in Denmark: baseline assessment in the Project SEXUS cohort study.

BACKGROUND: Sexual dysfunctions may negatively affect an individual's self-perceived womanhood or manhood, but whether gender nonconformity in childhood or adolescence can influence adult sexual functioning has not been examined so far. AIM: To explore the possible link between recalled childhood gender nonconformity and sexual dysfunctions in adulthood in a large sample. METHODS: We analyzed baseline questionnaire data from Project SEXUS, a nationally representative cohort study on sexual health among 15- to 89-year-old Danish citizens. Our sample included sexually active participants aged ≥18 years who were queried about gender nonconformity in childhood or adolescence (N = 21 390). To capture sexual dysfunctions, we assessed (1) difficulties with lubrication, orgasm, vaginal cramps precluding sexual intercourse, and/or genital pain during partnered sexual activity in women and (2) difficulties with erection, premature ejaculation, orgasm, and/or genital pain during partnered sexual activity in men. Furthermore, we assessed whether such difficulties were perceived as problematic. The 6-item Female Sexual Function Index and the 5-item International Index of Erectile Function served as standardized measures. Polytomous logistic regression analyses yielded demographically weighted adjusted odds ratios (aORs) with 95% CIs for associations between childhood gender nonconformity and sexual dysfunctions, controlling for age, sociodemographics, health-related factors, and other potential confounders. OUTCOMES: Sexual difficulties and dysfunctions, as well as scores on the Female Sexual Function Index and International Index of Erectile Function. RESULTS: Age-adjusted odds ratios indicated that sexual dysfunctions were significantly more common among childhood gender-nonconforming than conforming participants. After controlling for additional potential confounders, most sexual dysfunctions-notably, vaginal cramps in women (aOR, 2.12; 95% CI, 1.25-3.60) and genital pain dysfunction in men (aOR, 2.99; 95% CI, 1.79-4.99)-remained significantly increased among childhood gender-nonconforming respondents. CLINICAL IMPLICATIONS: Findings suggest that self-perceived gender nonconformity in childhood or adolescence may negatively affect sexual functioning in adult life. If confirmed by future studies, they may warrant a clinical emphasis on such issues in sexologic treatment and care. STRENGTHS AND LIMITATIONS: Our study is the first to report associations between childhood gender nonconformity and adult sexual dysfunction, building on data from a large-scale, nationally representative cohort study. The retrospective assessment of childhood gender nonconformity via one item might have neglected significant dimensions of this construct. CONCLUSION: The present study is the first to show that individuals who recall being gender nonconforming in childhood or adolescence may be at a greater risk of experiencing sexual dysfunctions, particularly sexual pain disorders, as adults.

Transgender Identity and Suicide Attempts and Mortality in Denmark.

Importance: Prior studies have suggested that transgender individuals may be a high-risk group with respect to suicide attempt and mortality, but large-scale, population-based investigations are lacking. Objective: To examine in a national setting whether transgender individuals have higher rates of suicide attempt and mortality than nontransgender individuals. Design, Setting, and Participants: Nationwide, register-based, retrospective cohort study on all 6 657 456 Danish-born individuals aged 15 years or older who lived in Denmark between January 1, 1980, and December 31, 2021. Exposure: Transgender identity was determined through national hospital records and administrative records of legal change of gender. Main Outcomes and Measures: Suicide attempts, suicide deaths, nonsuicidal deaths, and deaths by any cause during 1980 through 2021 were identified in national hospitalization and causes of death registers. Adjusted incidence rate ratios (aIRRs) with 95% CIs controlling for calendar period, sex assigned at birth, and age were calculated. Results: The 6 657 456 study participants (50.0% assigned male sex at birth) were followed up during 171 023 873 person-years. Overall, 3759 individuals (0.06%; 52.5% assigned male sex at birth) were identified as transgender at a median age of 22 years (IQR, 18-31 years) and followed up during 21 404 person-years, during which 92 suicide attempts, 12 suicides, and 245 suicide-unrelated deaths occurred. Standardized suicide attempt rates per 100 000 person-years were 498 for transgender vs 71 for nontransgender individuals (aIRR, 7.7; 95% CI, 5.9-10.2). Standardized suicide mortality rates per 100 000 person-years were 75 for transgender vs 21 for nontransgender individuals (aIRR, 3.5; 95% CI, 2.0-6.3). Standardized suicide-unrelated mortality rates per 100 000 person-years were 2380 for transgender vs 1310 for nontransgender individuals (aIRR, 1.9; 95% CI, 1.6-2.2), and standardized all-cause mortality rates per 100 000 person-years were 2559 for transgender vs 1331 for nontransgender individuals (aIRR, 2.0; 95% CI, 1.7-2.4). Despite declining rates of suicide attempts and mortality during the 42 years covered, aIRRs remained significantly elevated in recent calendar periods up to and including 2021 for suicide attempts (aIRR, 6.6; 95% CI, 4.5-9.5), suicide mortality (aIRR, 2.8; 95% CI, 1.3-5.9), suicide-unrelated mortality (aIRR, 1.7; 95% CI, 1.5-2.1), and all-cause mortality (aIRR, 1.7; 95% CI, 1.4-2.1). Conclusions and Relevance: In this Danish population-based, retrospective cohort study, results suggest that transgender individuals had significantly higher rates of suicide attempt, suicide mortality, suicide-unrelated mortality, and all-cause mortality compared with the nontransgender population.

Sexuality Among Young Danes Treated for Long-Lasting or Severe Physical Disease: Baseline Findings in a Nationwide Cohort Study.

PURPOSE: Sexual ramifications of physical disease are well-documented in adult populations, but are scarcely investigated among adolescents and young adults (AYA). This study compared measures of sexuality and sexual health among 8,696 15-year-old to 24-year-old Danes with and without a history of treatment for long-lasting or severe physical disease. METHODS: Using baseline data from Project SEXUS, a nationally representative cohort study on sexual health in the Danish population, differences in various domains of sexual behaviors and sexual health between AYA who have and AYA who have not been treated for long-lasting or severe physical disease were investigated. Logistic regression analyses yielded demographically weighted age-adjusted odds ratios (ORs) for associations between physical diseases and sexual outcomes. RESULTS: AYA treated for long-lasting or severe physical disease resembled their healthy peers on fundamental aspects of sexual interest, activity and satisfaction. However, significantly increased odds ratios of various sexual difficulties and dysfunctions, early sexual debut, high sex partner numbers, discontentment with body or genital appearance, gender nonconformity, nonheterosexuality, and exposure to sexual assaults were observed, overall or within specific disease categories. DISCUSSION: The overall similarity in sexual profiles between AYA treated for physical disease and healthy peers indicates that clinicians should routinely address questions related to sexuality and relationships when encountering AYA with chronic health conditions. Moreover, the observed excess of certain adversities, including sexual assaults, among physically ill AYA highlights the need for preventive measures and counseling services specifically targeted at AYA afflicted by physical disease.

Symptoms of anxiety and depression in Denmark during the first year of the COVID-19 pandemic: A two-wave matched-control study.

Subsequent to the restriction measures taken to curb the COVID-19 infection rate, researchers theorized these would have detrimental mental health consequences. This two-wave matched-control study investigates depression and anxiety symptoms during the first 12 months of the pandemic (March 2020-March 2021) in Denmark with data from the I-SHARE and Project SEXUS studies. The I-SHARE study includes 1,302 (Time period 1 only n = 914, Time period 2 only n = 304, both time periods 1 and2 n = 84) Danish participants, and the sex and birth year-matched control participants from the Project SEXUS study comprise 9,980 Danes. During the first year of the pandemic, the study populations' anxiety and depression symptom mean levels did not significantly differ from pre-pandemic matched controls. Younger age, female gender, fewer children in the same household (depression only), lower education level, and not being in a relationship (depression only) were associated with increased anxiety and depression symptom scores. The key COVID-19-related variable linked with significantly higher anxiety and depression symptom scores was COVID-19-related loss of income. Contrary to initial concerns, we did not find a significant effect of the pandemic on anxiety and depression symptom scores. However, the results underscore the importance of structural resources to prevent income loss to safeguard mental health during crises such as a pandemic.

Psychosocial, sexual, reproductive and menopausal health in women with and without HIV in a high-income setting.

OBJECTIVES: To investigate psychosocial, sexual, reproductive and menopausal health in women with HIV (WWH) compared to women without HIV (WWOH) in Denmark. DESIGN: A nationwide cross-sectional study. METHODS: Data was retrieved from the SHARE study , a Danish nationwide cross-sectional survey examining psychosocial, sexual and reproductive health in people with HIV. Data from WWH, collected in 2021-2022, was matched 1:10 on age to a comparison group of WWOH from the nationally representative cohort study Project SEXUS . Associations between HIV status and psychosocial and sexual health outcomes were assessed by adjusted odds ratios (aOR) with 95% confidence intervals (95% CIs) obtained in logistic regression analyses controlling for potential confounding variables. The severity of menopausal symptoms in WWH was compared to published reference norms. RESULTS: Among 144 WWH and 1440 WWOH, recurrent loneliness was significantly more common among WWH (aOR 2.22 [95% CI: 1.25-3.96]), and WWH had significantly fewer children and close friends (aOR 0.52 [95% CI: 0.28-0.96] for 3-9 vs. 0-2 close friends). Symptoms of anxiety and depression did not differ between groups. Lack of sexual desire (aOR 2.90 [95% CI: 1.29-6.50]), low FSFI-6 score indicating sexual dysfunction (aOR 3.40 [95% CI: 1.33-8.69]), lubrication dysfunction (aOR 8.24 [95% CI: 2.83-24.00]) and genital pain dysfunction (aOR 5.13 [95% CI: 1.26-20.86]) were significantly more common in WWH compared to WWOH. No differences were seen in menopausal characteristics. CONCLUSIONS: WWH in Denmark have fewer children and close friends, and more often report recurrent loneliness, lacking sexual desire and sexual dysfunction compared to WWOH. No differences were evident in menopausal characteristics.

Siblings reduce multiple sclerosis risk by preventing delayed primary Epstein-Barr virus infection.

Epstein-Barr virus infection, and perhaps almost exclusively delayed Epstein-Barr virus infection, seems to be a prerequisite for the development of multiple sclerosis. Siblings provide protection against infectious mononucleosis by occasionally preventing delayed primary Epstein-Barr virus infection, with its associated high risk of infectious mononucleosis. Each additional sibling provides further protection according to the age difference between the index child and the sibling. The closer the siblings are in age, the higher the protection, with younger siblings being more protective against infectious mononucleosis than older siblings. If the hypothesis that delayed Epstein-Barr virus infection is necessary for the development of multiple sclerosis is true, then the relative risk of multiple sclerosis as a function of sibship constellation should mirror the relative risk of infectious mononucleosis as a function of sibship constellation. Such an indirect hypothesis test is necessitated by the fact that age at primary Epstein-Barr virus infection is unknown for practically all people who have not experienced infectious mononucleosis. In this retrospective cohort study using nationwide registers, we followed all Danes born during the period 1971-2018 (n = 2 576 011) from 1977 to 2018 for hospital contacts with an infectious mononucleosis diagnosis (n = 23 905) or a multiple sclerosis diagnosis (n = 4442), defining two different end points. Relative risks (hazard ratios) of each end point as a function of sibship constellation were obtained from stratified Cox regression analyses. The hazard ratios of interest for infectious mononucleosis and multiple sclerosis could be assumed to be identical (test for homogeneity P = 0.19), implying that having siblings, especially of younger age, may protect a person against multiple sclerosis through early exposure to the Epstein-Barr virus. Maximum protection per sibling was obtained by having a 0-2 years younger sibling, corresponding to a hazard ratio of 0.80, with a 95% confidence interval of 0.76-0.85. The corresponding hazard ratio from having an (0-2 years) older sibling was 0.91 (0.86-0.96). Our results suggest that it may be possible essentially to eradicate multiple sclerosis using an Epstein-Barr virus vaccine administered before the teenage years. Getting there would require both successful replication of our study findings and, if so, elucidation of why early Epstein-Barr virus infection does not usually trigger the immune mechanisms responsible for the association between delayed Epstein-Barr virus infection and multiple sclerosis risk.

Sexual Inactivity and Dysfunction in Denmark: A Project SEXUS Study.

Sexual dysfunctions are common experiences that often impact negatively on the health and well-being of affected individuals. We used baseline questionnaire data from 62,675 Danes aged 15-89 years, who participated in the cohort study Project SEXUS 2017-2018, to yield nationally representative estimates of the prevalence of sexual inactivity and dysfunction and to identify their sociodemographic correlates. Overall, we found that 23.0% of sexually experienced men and 28.8% of sexually experienced women had not been sexually active with another person within the last year. Sexual inactivity with another person was associated with both young and old age, single status, less favorable socioeconomic conditions, underweight and obesity, indicators of poor health, no use of alcohol, and physical inactivity. Among sexually active respondents, 18.0% of men had experienced any dysfunction within the last year, including erectile dysfunction (7.4%), premature ejaculation dysfunction (10.0%), orgasmic dysfunction (4.0%), and/or genital pain dysfunction (0.7%). Among women, 20.4% had experienced any dysfunction within the last year, including lubrication dysfunction (9.1%), orgasmic dysfunction (12.2%), genital pain dysfunction (5.0%), and/or vaginal cramp dysfunction (vaginismus) (0.8%). Additionally, 3.4% of men and 9.9% of women with a spouse/partner had experienced hypoactive sexual desire disorder within the last four weeks. Using the 5-item International Index of Erectile Function (IIEF-5) and the 6-item Female Sexual Function Index (FSFI-6) among respondents with a spouse/partner who had attempted sexual intercourse within the last four weeks, we found that 3.8% of men had experienced moderate or severe erectile dysfunction (IIEF-5 score ≤ 11) and 20.8% of women had experienced any sexual dysfunction (FSFI-6 score ≤ 19) during that period. Single status, difficulties paying bills and, among men, unemployment were positively associated with sexual dysfunction. In conclusion, we document several sociodemographic disparities in the prevalence of sexual inactivity and dysfunction in Denmark. In particular, both sexual inactivity and dysfunction were more common among singles and those reporting financial difficulties.

Adverse childhood experiences and mental health problems in a nationally representative study of heterosexual, homosexual and bisexual Danes.

Non-heterosexual persons more often report adverse childhood experiences (ACEs) than heterosexuals, and they generally bear a greater burden of mental health challenges. However, population-based data on this topic are scarce. In a nationally representative study within the Project SEXUS, one of the world's largest cohort studies on sexual health, we used data from 57,479 individuals in Denmark to explore the interplay between ACEs and mental health problems among self-identified heterosexual, homosexual and bisexual persons, and among self-identified heterosexuals with or without same-sex sexual experience. Compared to heterosexuals, non-heterosexual persons were more likely to report most of the studied ACEs, with odds ratios (ORs) for the ACE category "abuse" ranging from 1.38 to 1.75 for homosexual women, from 1.76 to 2.65 for homosexual men, from 2.52 to 3.64 for bisexual women, and from 1.58 to 6.07 for bisexual men. Furthermore, non-heterosexual persons had consistently and statistically significantly higher odds for mental health problems (ORs: 1.50 to 4.63). Combinations of ACEs with a non-heterosexual identity resulted in markedly elevated odds for mental health problems, particularly among bisexual individuals. This included high odds for suicidal thoughts/attempts among bisexual persons with a history of "neglect" (women: OR=12.82; men: OR=35.24) and "abuse" (women: OR=11.81; men: OR=11.65). Among self-identified heterosexuals, combinations of ACEs with same-sex sexual experience were associated with consistently elevated odds for mental health problems (ORs: 2.22 to 12.04). The greater burden of ACEs among self-identified homosexuals and, most notably, bisexuals may account for part of their excess risk of mental health problems. These findings emphasize the public health importance of preventive measures to minimize the burden of ACEs and avert their harmful long-term effects. Moreover, they highlight the need to safeguard the welfare of children and adolescents with non-conforming expressions of sexuality.

Peptidylarginine Deiminase 2 Gene Polymorphisms in Subjects with Periodontitis Predispose to Rheumatoid Arthritis.

Epidemiologic studies have shown associations between periodontitis and rheumatoid arthritis (RA), but a causal relationship has not been established. Citrullination of gingival proteins by human peptidylarginine deiminases (PADs) or PAD from Porphyromonas gingivalis has been proposed to generate autoantigens in anti-CCP-positive RA. This study investigated whether the association between periodontitis and RA is influenced by single nucleotide polymorphisms (SNPs) in the genes encoding PAD2 and PAD4 that catalyze aberrant citrullination in RA and often are overexpressed in inflamed gingival connective tissue in subjects with periodontitis. The study included 137 RA patients and 161 controls with self-reported periodontitis. Periodontitis onset preceded RA onset by 13 years on average and was not associated with any of the SNPs investigated. In subjects with periodontitis, carriage of the minor alleles of rs2057094 and rs2235912 in PADI2 significantly increased the risk of RA (odds ratios 1.42 [p = 0.03] and 1.48 [p = 0.02], respectively), and this effect was driven by the anti-CCP-negative RA patients. The minor alleles of these SNPs only increased risk of anti-CCP-positive RA in individuals with periodontitis and a history of smoking. These data suggest that individuals with periodontitis carrying the minor alleles of SNPs rs2057094, rs2076616 and rs2235912 in PADI2 may be at increased risk of RA.

Physical and Mental Health Problems and Their Associations With Inter-Personal Sexual Inactivity and Sexual Dysfunctions in Denmark: Baseline Assessment in a National Cohort Study.

BACKGROUND: Physical and mental health are important to sexual function and wellbeing. Yet, associations of ill-health with sexual inactivity and dysfunctions are scarcely researched at population level. AIM: To explore and document associations of self-rated health and physical and mental health problems with inter-personal sexual inactivity and sexual dysfunctions. METHODS: We used data from a probability-based, nationally representative sample of 60,958 sexually experienced Danes aged 15-89 years who participated in the 2017-18 Project SEXUS cohort study. Logistic regression analyses provided demographically weighted odds ratios for associations between health measures and sexual outcomes adjusted for partner status and other potential confounders. OUTCOMES: Inter-personal sexual inactivity and a range of male and female sexual dysfunctions. RESULTS: Inter-personal sexual inactivity was more common among individuals with bad or very bad self-rated health compared to peers rating their health as good or very good (men: adjusted odds ratio 1.93, 95% confidence interval 1.66-2.25; women: 1.66, 1.42-1.94). Individuals rating their health as bad or very bad were also consistently more likely to report sexual dysfunctions, with associated statistically significant adjusted odds ratios ranging from 1.66 to 6.38 in men and from 2.25 to 3.20 in women. Patient groups at high risk of sexual dysfunctions comprised individuals afflicted by cardiovascular diseases, pain conditions, diabetes, gastrointestinal and liver diseases, cancer, skin diseases, nervous system diseases, gynecological diseases, benign prostatic hyperplasia, other physical health problems, stress, anxiety, affective disorders, self-injury or suicide ideation and attempts, posttraumatic stress disorder, personality disorders, eating disorders, psychoses and other mental health problems. CLINICAL IMPLICATIONS: These findings warrant heightened awareness among healthcare professionals, public health promoters and researchers concerning insufficiently appreciated sexual challenges among individuals with poor health. STRENGTHS & LIMITATIONS: The major strengths of our investigation include the large size of the study cohort, the detailed assessment of health-related variables, potential confounders and sexual outcomes, and the fact that we provide new population-based knowledge about less common and sparsely researched sexual dysfunctions and diseases. Limitations of our study include its cross-sectional nature and its modest response rate (35%). CONCLUSION: Findings from our large and nationally representative cohort study provide evidence that poor self-rated health and a range of specific physical and mental health problems are associated with statistically significantly increased rates of inter-personal sexual inactivity and sexual dysfunctions. Bahnsen MK, Graugaard C, Andersson M, et al. Physical and Mental Health Problems and Their Associations With Inter-Personal Sexual Inactivity and Sexual Dysfunctions in Denmark: Baseline Assessment in a National Cohort Study. J Sex Med 2022;19:1562-1579.

Non-therapeutic male circumcision in infancy or childhood and risk of human immunodeficiency virus and other sexually transmitted infections: national cohort study in Denmark.

Whether male circumcision in infancy or childhood provides protection against the acquisition of human immunodeficiency virus (HIV) or other sexually transmitted infections (STIs) in adulthood remains to be established. In the first national cohort study to address this issue, we identified 810,719 non-Muslim males born in Denmark between 1977 and 2003 and followed them over the age span 0-36 years between 1977 and 2013. We obtained information about cohort members' non-therapeutic circumcisions, HIV diagnoses and other STI outcomes from national health registers and used Cox proportional hazards regression analyses to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) associated with foreskin status (i.e., circumcised v. genitally intact). During a mean of 22 years of follow-up, amounting to a total observation period of 17.7 million person-years, 3375 cohort members (0.42%) underwent non-therapeutic circumcision, and 8531 (1.05%) received hospital care for HIV or other STIs. Compared with genitally intact males, rates among circumcised males were not statistically significantly reduced for any specific STI. Indeed, circumcised males had a 53% higher rate of STIs overall (HR = 1.53, 95% CI: 1.24-1.89), and rates were statistically significantly increased for anogenital warts (74 cases in circumcised males v. 7151 cases in intact males, HR = 1.51; 95% CI: 1.20-1.90) and syphilis (four cases in circumcised males v. 197 cases in intact males, HR = 3.32; 95% CI: 1.23-8.95). In this national cohort study spanning more than three decades of observation, non-therapeutic circumcision in infancy or childhood did not appear to provide protection against HIV or other STIs in males up to the age of 36 years. Rather, non-therapeutic circumcision was associated with higher STI rates overall, particularly for anogenital warts and syphilis.

PADI4 Polymorphisms Confer Risk of Anti-CCP-Positive Rheumatoid Arthritis in Synergy With HLA-DRB1*04 and Smoking.

Peptidylarginine deiminases (PADs) catalyze citrullination, a post-translational modification playing a pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA). The interplay between single nucleotide polymorphisms (SNPs) in the PADI genes and known risk factors for ACPA-positive RA, including smoking, HLA-DR4 and -1, and the PTPN22 R620W polymorphism, was investigated. We typed four PADI2 SNPs, four PADI4 SNPs, and the PTPN22 R620W SNP in 445 Danish RA patients and 533 age-matched healthy controls, as well as in 200 North American RA patients and 100 age- and sex-matched controls. The HLA-DRB1 locus was typed in the Danish cohort. Logistic regression analyses, adjusted for age, sex, smoking status, and PTPN22 R620W, revealed increased risk of anti-CCP-positive RA in carriers of rs11203367(T) (OR: 1.22, p=0.03) and reduced risk in carriers of rs2240335(A) in PADI4 (OR: 0.82, p=0.04). rs74058715(T) in PADI4 conferred reduced risk of anti-CCP-negative RA (OR: 0.38, p=0.003). In HLA-DRB1*04-positive individuals, specifically, the risk of anti-CCP-positive RA was increased by carriage of PADI4 rs1748033(T) (OR: 1.54, p=0.007) and decreased by carriage of PADI4 rs74058715(T) (OR: 0.44, p=0.01), and we observed an interaction between these SNPs and HLA-DRB1*04 (p=0.004 and p=0.008, respectively) Thus, PADI4 polymorphisms associate with ACPA-positive RA, particularly in HLA-DRB1*04-positive individuals, and with ACPA-negative RA independently of HLA-DRB1*04.

Association between Salmonella infection and colon cancer: a nationwide registry-based cohort study.

Laboratory data increasingly suggest that Salmonella infection may contribute to colon cancer (CC) development. Here, we examined epidemiologically the potential risk of CC associated with salmonellosis in the human population. We conducted a population-based cohort study using four health registries in Denmark. Person-level demographic data of all residents were linked to laboratory-confirmed non-typhoidal salmonellosis and to CC diagnoses in 1994-2016. Hazard ratios (HRs) for CC (overall/proximal/distal) associated with reported salmonellosis were estimated using Cox proportional hazard models. Potential effects of serovar, age, sex, inflammatory bowel disease and follow-up time post-infection were also assessed. We found no increased risk of CC ≥1 year post-infection (HR 0.99; 95% confidence interval (CI) 0.88-1.13). When stratifying by serovar, there was a significantly increased risk of proximal CC ≥1 year post-infection with serovars other than Enteritidis and Typhimurium (HR 1.40; 95% CI 1.03-1.90). CC risk was significantly increased in the first year post-infection (HR 2.08; 95% CI 1.48-2.93). The association between salmonellosis and CC in the first year post-infection can be explained by increased stool testing around the time of CC diagnosis. The association between proximal CC and non-Enteritidis/non-Typhimurium serovars is unclear and warrants further investigation. Overall, this study provides epidemiological evidence that notified Salmonella infections do not contribute significantly to CC risk in the studied population.

Human papillomavirus vaccination and all-cause morbidity in adolescent girls: a cohort study of absence from school due to illness.

BACKGROUND: A growing body of evidence supports the safety of the human papillomavirus (HPV) vaccines. However, concerns about autonomic dysfunction syndromes and non-specific symptoms continue to linger. These conditions are not easily captured by traditional diagnostic classification schemes and call for innovative approaches to the study of vaccine safety which take more general measures of all-cause morbidity into account. METHODS: Taking advantage of the unique Danish registers, including regional registration of absence from school, we conducted a cohort study of 14 068 adolescent Danish girls attending 5th through 9th grade in public schools in the municipality of Copenhagen during 1 August 2013-23 January 2018. We obtained time-varying HPV vaccination status and demographic information from nationwide registers. Using Poisson regression with random effects, we estimated rate ratios (RRs) of absence due to illness, comparing HPV-vaccinated girls with unvaccinated girls with adjustment for grade, season, calendar period, demographic factors and random effects at the individual, class and school levels. RESULTS: Our study included 6 206 188 school days with 213 221 days of absence from school due to illness (absence rate, 3.4%). Comparing absence rates due to illness in HPV-vaccinated and unvaccinated girls yielded an adjusted RR of 1.00 (95% confidence interval [CI], 0.98-1.03). CONCLUSIONS: Our study provides an important and novel contribution to HPV vaccine safety. Using absence from school records, we were able to address important safety concerns without relying on medical diagnoses. We conclude that HPV vaccination does not increase the risk of morbidity in any manner that manifests as absence from school due to illness.