Increased Use of Medications for Erectile Dysfunction in Men With Ulcerative Colitis and Crohn's Disease Compared to Men Without Inflammatory Bowel Disease: A Nationwide Cohort Study.

BACKGROUND: Men with inflammatory bowel disease (IBD) may have decreased sexual function due to factors related to the underlying disease, medication, and/or surgery. We aimed to examine the use of erectile dysfunction (ED) medications in men with IBD. METHODS: This is a nationwide cohort study based on the Danish registries, comprising all men >18 years old with IBD during 1 January 1995 through December 2016. The cohorts included 31,498 men with IBD and 314,980 age-matched men without IBD. Our main outcome was a first prescription of an ED medication. Cox regression analyses were used to estimate the hazard rate (HR) for use of ED medications, controlled for multiple time-varying covariates. RESULTS: Overall, 21,966 (69.7%) men had ulcerative colitis (UC) while 9532 (30.3%) had Crohn's disease (CD). Men with a first ED prescription numbered 3749 (11.9%) (men with IBD) and 30,635 (9.7%) (men without IBD). Adjusting for central nervous system and intestinal anti-inflammatory medications, systemic corticosteroids and co-morbidities, the HR was 1.19 (95% CI: 1.13-1.26) (IBD and no prior IBD operation), and 1.31 (95% CI: 1.20-1.43) (IBD and prior IBD operation). The adjusted HR for UC was 1.17 (95% CI: 1.10-1.24) (no operation) and 1.43 (95% CI: 1.27-1.61) (prior operation), and for CD 1.26 (95% CI: 1.15-1.38) (no operation) and 1.20 (95% CI: 1.06-1.35) (prior operation). DISCUSSION: Men with IBD are more likely to fill an ED prescription than men without IBD. This result is significant regardless of a history of IBD surgery.

Paternal use of azathioprine/6-mercaptopurine or methotrexate within 3 months before conception and long-term health outcomes in the offspring-A nationwide cohort study.

PURPOSE: We examined the effect of preconception paternal use of azathioprine (AZA)/6-mercaptopurine (6-MP) or methotrexate (MTX) and the risk of adverse long-term outcomes in the offspring. METHODS: This study included all children born in Denmark from 1 January 1997 through 2013. Exposed cohort: children fathered by men who used AZA/6-MP (N=735) or MTX (N=209) within three months before conception; unexposed cohort: children fathered by men who did not use AZA/6-MP/MTX (N=1,056,524). OUTCOMES: malignancies, autism spectrum disorders (ASD)/schizophrenia/psychosis, and attention deficit hyperactivity disorder (ADHD). RESULTS: Outcomes: of children: AZA/6-MP exposure: one with leukemia (0.14%), one with ASD/schizophrenia (0.14%) and three with ADHD (0.41%); MTX exposure: three with ADHD (1.4%). Unexposed: 1710 with malignancies (0.16%), 2107 with ASD/schizophrenia (0.20%), 2799 with ADHD (0.26%). Median follow up times were 6.7 [IQR:3.6-11.3] and 9.9 [IQR:5.7-14.3] years respectively. CONCLUSIONS: There was no negative impact of paternal preconception use of AZA/6-MP/MTX on selected childhood health outcomes.

Reassuring results on birth outcomes in children fathered by men treated with azathioprine/6-mercaptopurine within 3†months before conception: a nationwide cohort study.

OBJECTIVE: Information on the safety of paternal use of azathioprine (AZA) and 6-mercaptopurine (6-MP) prior to conception is limited. Based on nationwide data from the Danish health registries, we examined the association between paternal use of AZA/6-MP within 3 months before conception and adverse birth outcomes. DESIGN: This nationwide cohort study is based on data from all singletons born in Denmark from 1 January 1997 through 2013. Children fathered by men who used AZA/6-MP within 3 months before conception constituted the exposed cohort (N=699), and children fathered by men who did not use AZA/6-MP 3 months prior to conception constituted the unexposed cohort (N=1 012 624). The outcomes were congenital abnormalities (CAs), preterm birth and small for gestational age (SGA). We adjusted for multiple covariates and performed a restricted analysis of men with IBD. RESULTS: There were no significantly increased risks of CAs, preterm birth or SGA in exposed versus unexposed cohorts of children. The adjusted ORs were 0.82 (95% CI 0.53 to 1.28) for CAs, 1.17 (95% CI 0.72 to 1.92) for preterm birth and 1.38 (95% CI 0.76 to 2.51) for SGA. Restricting our analysis to fathers with IBD showed similar results with no significantly increased risk of adverse birth outcomes. CONCLUSIONS: This nationwide study is the largest to date, examining the effect of preconceptual paternal use of AZA/6-MP on birth outcomes in live born singletons. The results of no significantly increased risks of adverse birth outcomes are reassuring and support the continuation of paternal AZA/6-MP treatment during conception.

Live birth and adverse birth outcomes in women with ulcerative colitis and Crohn's disease receiving assisted reproduction: a 20-year nationwide cohort study.

OBJECTIVE: To examine the chance of live births and adverse birth outcomes in women with ulcerative colitis (UC) and Crohn's disease (CD) compared with women without inflammatory bowel disease (IBD) who have undergone assisted reproductive technology (ART) treatments. METHODS: This was a nationwide cohort study based on Danish health registries, comprising all women with an embryo transfer during 1 January 1994 through 2013. The cohorts comprised 1360 ART treatments in 432 women with UC, 554 ART treatments in 182 women with CD and 148,540 treatments in 52,489 women without IBD. Our primary outcome was live births per ART treatment cycle. We controlled for multiple covariates in the analyses. Our secondary outcomes were adverse birth outcomes. RESULTS: The chance of a live birth for each embryo transfer was significantly reduced in ART treatments in women with UC (OR=0.73, 95% CI 0.58 to 0.92), but not significantly reduced in the full model of ART treatments in women with CD (OR=0.77, 95% CI 0.52 to 1.14). Surgery for CD before ART treatment significantly reduced the chance of live birth for each embryo transfer (OR=0.51, 95% CI 0.29 to 0.91). In children conceived through ART treatment by women with UC, the OR of preterm birth was 5.29 (95% CI 2.41 to 11.63) in analyses including singletons and multiple births; restricted to singletons the OR was 1.80, 95% CI 0.49 to 6.62. CONCLUSIONS: Our results suggest that women with UC and CD receiving ART treatments cannot expect the same success for each embryo transfer as other infertile women. Women with CD may seek to initiate ART treatment before needing CD surgery. Increased prenatal observation in UC pregnancies after ART should be considered.

Dynamics of vitamin K antagonist and new oral anticoagulants use in atrial fibrillation: a Danish drug utilization study.

BACKGROUND: Detailed data on real-life utilization of vitamin K antagonists (VKAs) and new oral anticoagulants (NOACs) in atrial fibrillation are sparse. OBJECTIVES: To describe the dynamics of VKA and NOAC use: that is, (i) how patients moved in and out of, as well as between, use of VKAs and NOACs; (ii) how patients adhered to treatment; and (iii) which type of prescriber initiated, maintained, and changed treatment with VKAs and NOACs. METHODS: We conducted a drug utilization study in the region of southern Denmark (population 1.2 million) using prescription data. We included all subjects using VKAs or NOACs during the period of August 22, 2011, through June 30, 2013, restricted to subjects with a diagnosis of atrial fibrillation. RESULTS: We identified 20,911 subjects, of whom 20,769 and 1639 used VKAs and NOACs, respectively. The number of VKA users was stable at ~ 14,000 subjects during the study period, whereas the number of NOAC users increased to 903. The majority of NOAC users had previously used VKAs (n = 974), whereas 389 anticoagulant-naïve users initiated NOAC therapy. Among the latter, 51.2% had changed to VKAs within 6 months. 57.3% of VKA users were initiated by a hospital physician, whereas maintenance treatment was predominantly handled by the patient's general practitioner (97.6%). Switches from NOAC to VKA were initiated by a general practitioner in 69.2% of the cases. For users of NOACs, these numbers were 73.5%, 94.0%, and 63.3%. CONCLUSIONS: A large proportion of NOAC users switch to a VKA within a short time frame. The reasons for this are not clear.

Bactofection of lung epithelial cells in vitro and in vivo using a genetically modified Escherichia coli.

Bacteria-mediated gene transfer ('bactofection') has emerged as an alternative approach for genetic vaccination and gene therapy. Here, we assessed bactofection of airway epithelial cells in vitro and in vivo using an attenuated Escherichia coli genetically engineered to invade non-phagocytic cells. Invasive E. coli expressing green fluorescent protein (GFP) under the control of a prokaryotic promoter was efficiently taken up into the cytoplasm of cystic fibrosis tracheal epithelial (CFTE29o-) cells and led to dose-related reporter gene expression. In vivo experiments showed that following nasal instillation the vast majority of GFP-positive bacteria pooled in the alveoli. Further, bactofection was assessed in vivo. Mice receiving 5 x 10(8) E. coli carrying pCIKLux, in which luciferase (lux) expression is under control of the eukaryotic cytomegalovirus (CMV) promoter, showed a significant increase (P<0.01) in lux activity in lung homogenates compared to untransfected mice. Surprisingly, similar level of lux activity was observed for the non-invasive control strain indicating that the eukaryotic CMV promoter might be active in E. coli. Insertion of prokaryotic transcription termination sequences into pCIKLux significantly reduced prokaryotic expression from the CMV promoter allowing bactofection to be detected in vitro and in vivo. However, bacteria-mediated gene transfer leads to a significantly lower lux expression than cationic lipid GL67-mediated gene transfer. In conclusion, although proof-of-principle for lung bactofection has been demonstrated, levels were low and further modification to the bacterial vector, vector administration and the plasmids will be required.

The effects of environmental conditions on the lipolytic activity of strains of Penicillium roqueforti.

The lipolytic activity of 30 strains of Penicillium roqueforti was investigated by agar diffusion tests on tributyrin (esterase activity) and olive oil agar (lipase activity), by titration of the free fatty acids (FFA) produced and by gas chromatographic analysis of the individual FFA released after growth at 25 or 10 degrees C in butterfat emulsions containing 0, 2 or 7% NaCl. All strains investigated by the agar diffusion tests possessed esterase activity and 23 strains were also able to hydrolyse olive oil, but differences in esterase activity were seen. The agar diffusion tests and the titration of FFA showed that the amount of FFA released by a strain of P. roqueforti is determined by both esterase and lipase activity. A large release of FFA was only seen for strains with the ability to hydrolyse both short- and long-chained fatty acids, while strains with esterase activity produced smaller amounts of FFA. Between 7 and 14 days of incubation a steep increase in the release of FFA was observed both by the titration and by GC analysis, and then a decline from 14 to 21 days, probably caused by conversion of FFA to methyl ketones. Identical FFA profiles were found for two strains with different lipolytic activity. Long-chained fatty acids dominated the profile, while the short-chained fatty acids only were detected in small amounts and mainly in the end of incubation. Both strains were stimulated by NaCl in the emulsions.

Characterization of the proteolytic activity of starter cultures of Penicillium roqueforti for production of blue veined cheeses.

Thirty strains of Penicillium roqueforti used for the production of blue cheeses were examined for proteolytic activity by agar diffusion on casein agar, by the azocasein test and by capillary zone electrophoresis (CE). Distinct differences were seen between the strains by all three methods applied and the 30 strains could be subdivided in three groups being significantly different in their proteolytic activity as measured by the agar diffusion test. The quantitative differences seen in the agar diffusion test were confirmed by the azocasein test. However, a negative result on casein agar, i.e., no clearing of the agar was observed for one strain while it showed low proteolytic activity in the azocasein test. CE proved to be a valuable method for revealing qualitative differences between strains of P. roqueforti in the breakdown of casein. Three strongly proteolytic strains broke down the specific casein fractions differently: one strain broke down betaA1-casein faster than betaA2-casein, the second preferred alpha s1-casein while the last strain broke down the casein fractions at equal rates. For a strain with medium proteolytic activity, the degradation of casein was seen by the appearance of a peak with migration time similar to alpha s1-I casein, a peptide normally produced by chymosin.

A simple method of sample size calculation for linear and logistic regression.

A sample size calculation for logistic regression involves complicated formulae. This paper suggests use of sample size formulae for comparing means or for comparing proportions in order to calculate the required sample size for a simple logistic regression model. One can then adjust the required sample size for a multiple logistic regression model by a variance inflation factor. This method requires no assumption of low response probability in the logistic model as in a previous publication. One can similarly calculate the sample size for linear regression models. This paper also compares the accuracy of some existing sample-size software for logistic regression with computer power simulations. An example illustrates the methods.