Bo V. Pedersen

Appendicitis, mesenteric lymphadenitis, and subsequent risk of ulcerative colitis: cohort studies in Sweden and Denmark

Objective To determine whether the repeatedly observed low risk of ulcerative colitis after appendicectomy is related to the appendicectomy itself or the underlying morbidity, notably appendicitis or mesenteric lymphadenitis. Design Nationwide cohort studies. Setting Sweden and Denmark. Participants 709 353 Swedish (1964-2004) and Danish (1977-2004) patients who had undergone appendicectomy were followed up for subsequent ulcerative colitis. The impact of appendicectomy on risk was also studied in 224 483 people whose parents or siblings had inflammatory bowel disease. Main outcome measures Standardised incidence ratios and rate ratios as measures of relative risk. Results During 11.1 million years of follow-up in the appendicectomy cohort, 1192 patients developed ulcerative colitis (10.8 per 100 000 person years). Appendicectomy without underlying inflammation was not associated with reduced risk (standardised incidence ratio 1.04, 95% confidence interval 0.95 to 1.15). Before the age of 20, however, appendicectomy for appendicitis (0.45, 0.39 to 0.53) or mesenteric lymphadenitis (0.65, 0.46 to 0.90) was associated with significant risk reduction. A similar pattern was seen in those with affected relatives, whose overall risk of ulcerative colitis was clearly higher than the background risk (1404 observed v 446 expected; standardised incidence ratio 3.15, 2.99 to 3.32). In this cohort, appendicectomy without underlying appendicitis did not modify risk (rate ratio 1.04, 0.66 to 1.55, v no appendicectomy), while risk after appendicectomy for appendicitis was halved (0.49, 0.31 to 0.74). Conclusions In individuals with or without a familial predisposition to inflammatory bowel disease, appendicitis and mesenteric lymphadenitis during childhood or adolescence are linked to a significantly reduced risk of ulcerative colitis in adulthood. Appendicectomy itself does not protect against ulcerative colitis.

Associations of Unhealthy Lifestyle Factors with Sexual Inactivity and Sexual Dysfunctions in Denmark

INTRODUCTION Studies have linked obesity, a sedentary lifestyle, and tobacco smoking to erectile dysfunction, but the evidence linking unhealthy lifestyle factors to other sexual dysfunctions or to sexual inactivity is conflicting. AIM To examine associations between unhealthy lifestyle factors and sexual inactivity with a partner and four specific sexual dysfunctions in each sex. METHODS We used nationally representative survey data from 5,552 Danish men and women aged 16-97 years in 2005. Cross-sectional associations of lifestyle factors with sexual inactivity and sexual dysfunctions were estimated by logistic regression-derived, confounder-adjusted odds ratios (ORs). MAIN OUTCOME MEASURES We calculated ORs for sexual inactivity with a partner and for sexual dysfunction and sexual difficulties overall in both sexes, for erectile dysfunction, anorgasmia, premature ejaculation, and dyspareunia in men, and for lubrication insufficiency, anorgasmia, dyspareunia, and vaginismus in women. RESULTS Obesity (body mass index [BMI]≥30 kg/m(2) ) or a substantially increased waist circumference (men ≥102 cm; women ≥88 cm), physical inactivity, and, among women, tobacco smoking were each significantly associated with sexual inactivity in the last year. Among sexually active men, both underweight (BMI <20 kg/m(2) ) and obesity, a substantially increased waist circumference, physical inactivity in leisure time, high alcohol consumption (>21 alcoholic beverages/week), tobacco smoking, and use of hard drugs were each significantly positively associated with one or more sexual dysfunctions (ORs between 1.71 and 22.0). Among sexually active women, the only significant positive association between an unhealthy lifestyle factor and sexual dysfunction was between hashish use and anorgasmia (OR 2.85). CONCLUSION In both sexes, several unhealthy lifestyle factors were associated with sexual inactivity with a partner in the last year. Additionally, among sexually active participants, men with unhealthy lifestyles were significantly more likely to experience sexual dysfunctions. Considering the importance of a good sex life, our findings may be useful in attempts to promote healthier lifestyles.

The risk of developing Crohn’s disease after an appendectomy: a population-based cohort study in Sweden and Denmark

Background: The relationship between appendectomy and Crohn’s disease is controversial. A Swedish–Danish cohort study was conducted to assess the risk of developing Crohn’s disease after an appendectomy. Methods: 709 353 appendectomy patients in Sweden (since 1964) and Denmark (since 1977) were followed for first hospitalisations for Crohn’s disease to 2004. Standardised incidence ratios (SIR) served as relative risks. Results: Overall, 1655 Crohn’s disease cases were observed during 11.1 million person-years of follow-up. Whereas appendectomy before the age of 10 years was not associated with the risk of Crohn’s disease (SIR 1.00; 95% CI 0.80–1.25), the overall SIR of developing Crohn’s disease was 1.52 (95% CI 1.45–1.59), being highest in the first 6 months (SIR 8.69; 95% CI 7.68–9.84). SIR diminished rapidly thereafter, with the risk of Crohn’s disease reaching background levels after 5–10 years for Crohn’s disease overall, as well as for Crohn’s ileitis, ileocolonic Crohn’s disease, Crohn’s colitis and other/unspecified Crohn’s disease. A long-term increased risk of Crohn’s disease up to 20 years after the appendectomy was seen only in appendectomy patients without appendicitis or mesenteric lymphadenitis. Conclusion: The transient increased risk of Crohn’s disease after an appendectomy is probably explained by diagnostic bias.

Increased risk of inflammatory bowel disease in women with endometriosis: a nationwide Danish cohort study

Background An association between endometriosis and certain autoimmune diseases has been suggested. However, the impact of endometriosis on risk of inflammatory bowel disease (IBD) remains unknown. Objective To assess the risk of Crohns disease (CD) and ulcerative colitis (UC) in an unselected nationwide Danish cohort of women with endometriosis. Design By use of national registers, 37 661 women hospitalised with endometriosis during 1977–2007 were identified. The relative risk of developing IBD after an endometriosis diagnosis was calculated as observed versus expected numbers and presented as standardised incidence ratios (SIRs) with 95% CIs. Results Women with endometriosis had a increased risk of IBD overall (SIR=1.5; 95% CI 1.4 to 1.7) and of UC (SIR=1.5; 95% CI 1.3 to 1.7) and CD (SIR=1.6; 95% CI 1.3 to 2.0) separately, even 20 years after a diagnosis of endometriosis (UC: SIR=1.5; 95% CI 1.1 to 2.1; CD: SIR=1.8; 95% CI 1.1 to 3.2). Restricting analyses to women with surgically verified endometriosis suggested even stronger associations (UC: SIR=1.8; 95% CI 1.4 to 2.3; CD: SIR=1.7; 95% CI 1.2 to 2.5). Conclusion The risk of IBD in women with endometriosis was increased even in the long term, hence suggesting a genuine association between the diseases, which may either reflect common immunological features or an impact of endometriosis treatment with oral contraceptives on risk of IBD.

The co-occurrence of endometriosis with multiple sclerosis, systemic lupus erythematosus and Sjögren syndrome

BACKGROUND In a previous study, women with endometriosis were found to be at a 7-24-fold increased risk of multiple sclerosis (MS), systemic lupus erythematosus (SLE) and Sjögren syndrome (SS). We examined these associations in a large population-based cohort study. METHODS We followed 37 661 women registered with endometriosis in the Danish Hospital Discharge Register 1977-2007 for subsequent hospitalizations with MS, SLE or SS. As measures of relative risk, we used ratios of observed to expected incidence rates of first hospitalizations for MS, SLE and SS among women with endometriosis, i.e. standardized incidence ratios (SIR) with accompanying 95% confidence intervals (CIs). RESULTS During slightly more than 456 000 person-years of follow-up, we identified 130, 54 and 86 cases of MS, SLE and SS, respectively, yielding SIRs of 1.2 (95% CI 1.05-1.5) for MS, 1.6 (1.2-2.1) for SLE and 1.6 (1.3-2.0) for SS. In a supplementary analysis restricted to 9191 women with laparoscopy or laparotomy confirmed endometriosis, associations were unchanged for MS (SIR = 1.4; 1.04-1.9), but lost statistical significance for SLE (SIR = 1.1; 0.6-2.1) and SS (SIR = 1.4; 0.9-2.3). CONCLUSIONS Our national cohort-based findings do not support prior claims of markedly increased risks of MS, SLE and SS in women with endometriosis. However, whether women with endometriosis are truly at a modestly (20-60%) elevated risk of one or more of the studied autoimmune diseases must await clarification in future large-scale prospective studies.

Reproductive history and risk of multiple sclerosis.

Background: It has been suggested that reproductive factors may be involved in the etiology of multiple sclerosis (MS). We studied associations of reproductive history with MS risk in a population-based setting. Methods: Using national databases, we established a cohort comprising 4.4 million Danish men and women born between 1935 and 1989 and alive in 1968 or later. We obtained information about their live-born children, pregnancy losses, pregnancy complications, and infertility diagnoses. MS cases in the cohort were identified through 2004 in the Danish Register of Multiple Sclerosis. Associations between reproductive factors and MS risk were evaluated using rate ratios (RRs) obtained in log-linear Poisson regression analysis. Results: MS was diagnosed in 6332 women and 3426 men. In both sexes, parents had a lower risk of MS compared with childless persons (in women, RR = 0.76 [95% confidence interval = 0.71–0.82]; in men, 0.89 [0.80–0.98]). RRs were inversely associated with number of children, age at first childbirth, and proximity in time since most recent birth. Among women, MS risk was unrelated to histories of pregnancy loss, pregnancy complications, or infertility. A supplementary analysis in which the date of MS diagnosis was backdated by 5 years to address the possibility of reverse causality did not confirm a protective effect of parenthood (in women, 0.95 [0.88–1.03]; in men, 1.08 [0.98–1.20]). Conclusions: Similar findings in women and men argue against a biologic role of pregnancy in the etiology of MS. Moreover, the observed differences in childbearing patterns were restricted to the 5 years before MS diagnosis, suggesting that reverse causality (ie, reduced reproductive activity in persons with yet-undiagnosed MS) might explain the observed associations.

Multiple human papilloma virus types in cervical infections: competition or synergy?

Coinfection with multiple human papilloma virus (HPV) types is common in cervical HPV infection. To evaluate if infections with different HPV types occur independently, we examined 3558 women above 15 years of age suspected of cervical HPV infection. Among them, 1842 (52%) women were HPV negative and 1716 (48%) were HPV positive as analysed by a PCR-based commercial microarray assay for mucosal types. Of the HPV-positive samples, 824 (48%) had single infections, while 892 (52%) had multiple infections. Observed numbers of concurrent HPV types differed from expected numbers under the assumption of independence between infections by the various HPV types. Significant positive associations were observed for 16 pairs of HPV types in statistical analysis accounting for mass significance. Significant negative associations were also found, i.e. women with HPV-16 infection had 0.4 times the odds of having HPV-51 compared with women not infected with HPV-16. HPV-16 was the only type with odds ratios <1 for all pairwise combinations. While our findings of statistically significant coexistence do not prove biological dependence among HPV types, they do suggest that infections with some HPV types may depend on the existence of certain other HPV types. Any interaction between coexisting HPV types could either decrease or increase the efficacy of current HPV vaccines that offer mainly type-specific protection, depending on whether the types vaccinated against compete with other HPV types or not.

Multiple human papilloma virus types in cervical infections: competition or synergy?: HPV COMPETITION

Mejlhede N, Pedersen BV, Frisch M, Fomsgaard A. Multiple human papilloma virus types in cervical infections: competition or synergy? APMIS 2010; 118: 346–52.

Fatherhood status and prostate cancer risk.

Whether fatherhood status affects prostate cancer risk remains controversial. Recently, it was proposed that childless men are at lower prostate cancer risk than men with children and that men with sons may be at lower risk than men with daughters only.

Associations between Physical and Mental Health Problems and Sexual Dysfunctions in Sexually Active Danes

INTRODUCTION Studies have shown a high prevalence of sexual dysfunctions among individuals with a variety of health problems. AIM To obtain a population-based assessment of these matters, we studied associations between indicators of physical and mental health problems and sexual dysfunctions in Denmark. METHODS We used questionnaire data from 4,415 sexually active men (mean age 48 years) and women (mean age 45 years) who participated in a nationally representative survey in 2005. Cross-sectional associations of overall health and physical and mental health problems with sexual dysfunctions in the last year were estimated by logistic regression-derived, confounder-adjusted odds ratios (OR(adj) ). MAIN OUTCOME MEASURES We calculated OR(adj) with 95% confidence intervals (CI) for erectile dysfunction, anorgasmia, premature ejaculation, and dyspareunia in men, for lubrication insufficiency, anorgasmia, dyspareunia, and vaginismus in women, and for sexual dysfunction and sexual difficulties overall in both sexes. RESULTS Sexual dysfunction was significantly more common among participants with poor self-rated health (OR(adj) 1.86, 95% CI 1.05-3.33 in men, OR(adj) 1.91, 1.08-3.37 in women). Physical health problems were significantly associated with male sexual dysfunctions (OR(adj) 1.75, 1.18-2.61), whereas mental health problems were significantly associated with female sexual dysfunctions (OR(adj) 2.59, 1.60-4.22). CONCLUSION Among sexually active Danes, poor self-reported overall health is associated with increased rates of sexual dysfunction in both sexes, with physical health problems mainly affecting mens sex lives, and mental health problems being strongly associated with female sexual dysfunction.