Influence of Prior Psychiatric Disorders on the Treatment Course of Gynaecological Cancer - A Nationwide Cohort Study.

AIMS: To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer. MATERIALS AND METHODS: The analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007-2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment. RESULTS: In the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62-2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77-2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03-1.54). CONCLUSIONS: We did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis.

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.

Plasma methionine, choline, betaine, and dimethylglycine in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Disturbances in one carbon metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low. PATIENTS AND METHODS: We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1367 incident CRC cases (965 colon and 402 rectum) and 2323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CRC risk were estimated by conditional logistic regression, comparing the fifth to the first quintile of plasma concentrations. RESULTS: Overall, methionine (OR: 0.79, 95% CI: 0.63-0.99, P-trend = 0.05), choline (OR: 0.77, 95% CI: 0.60-0.99, P-trend = 0.07), and betaine (OR: 0.85, 95% CI: 0.66-1.09, P-trend = 0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/l, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95% CI: 0.50-1.00, P-trend = 0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95% CI: 0.43-0.88, P-trend = 0.01). Plasma DMG was not associated with CRC risk. CONCLUSIONS: Individuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of CRC.

Pre-operative use of anti-TNF-α agents and the risk of post-operative complications in patients with Crohn's disease--a nationwide cohort study.

BACKGROUND: A possible negative role of pre-operative use of antitumour necrosis factor-alpha (anti-TNF-α) agents on post-operative outcomes in Crohn's disease (CD) patients is still debated. AIM: To examine the impact of pre-operative anti-TNF-α agents on post-operative outcomes 30 and 60 days after CD surgery in a nationwide Danish cohort. Outcomes were death, reoperation, anastomosis leakage, intra-abdominal abscess and bacteraemia. METHODS: We identified all patients having surgical procedures from 1 January 2000 to 31 December 2010 (n = 2293). Patients were classified according to use of anti-TNF-α agents within 12 weeks before surgery (exposed) or not (unexposed). Outcomes were obtained from nationwide registries and a bacteraemia registry. Sub-analyses were performed for bacteraemia and for impact of pre-operative timing of anti-TNF-α agents. RESULTS: Among surgical procedures for CD, 214 were exposed and 2079 were not. We found no increased relative risks of death or abscess drainage 30 or 60 days after follow-up. Among exposed, 7.5% had a reoperation within 30 days vs. 8.6% among unexposed, adjusted odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.52-1.63. Among exposed, 3.8% had an anastomosis leakage within 30 days after surgery vs. 2.8% among unexposed, adjusted OR = 1.33, 95% CI: 0.59-3.02. No further cases of anastomosis leakages appeared within 60 days. Sub-analyses indicated no increased risk of bacteraemia after 30 days and no increased risks when anti-TNF-α agents were given ≤14 days before surgery. CONCLUSION: We found no significantly increased relative risks of post-operative complications after use of anti-TNF-α agents either 12 weeks or ≤14 days before surgery for Crohn's disease.

Pre-operative use of anti-TNF-α agents and the risk of post-operative complications in patients with ulcerative colitis - a nationwide cohort study.

BACKGROUND: It is still controversial whether pre-operative anti-tumour necrosis factor-alpha (anti-TNF-α) agents increase post-operative complications in patients with ulcerative colitis (UC). AIM: In a nationwide Danish cohort of patients with UC, we aimed to examine the impact of pre-operative use of anti-TNF-α agents on post-operative adverse outcomes after colectomy for UC. Outcomes (within 30 and 60 days after surgery) were reoperation, anastomosis leakage, intra-abdominal abscess, bacteremia and death. METHODS: Based on the Danish National Patient Registry we identified all UC patients, aged ≥15 years, having their first surgery for UC in the period of 1 January 2003-31 December 2010 (n = 1226). Patients were classified according to use of anti-TNF-α agents within 12 weeks before surgery or not. Outcome data were obtained from Danish registries. Logistic regression analyses were used to estimate adjusted risks [with 95% confidence intervals (CI)] of post-operative outcomes among patients treated with anti-TNF-α agents, relative to those not treated. RESULTS: A total of 199 UC patients were exposed to anti-TNF-α agents within 12 weeks before colectomy, and 1027 were not. Among exposed, the adjusted odds ratio of reoperation and anastomosis leakage within 30 days after colectomy was 1.07 (95% CI: 0.71-1.59) and 0.52 (95% CI: 0.06-4.11) respectively. No deaths, cases of abscess drainage or bacteremia occurred among exposed within 30 days. Furthermore, no increased relative risks were found within 60 days after colectomy. CONCLUSIONS: Based on nationwide data on UC patients having colectomies, pre-operative use of anti-TNF-α agents did not increase the risk of post-operative complications.

Hospital admission for non-fatal poisoning with weak analgesics and risk for subsequent suicide: a population study.

BACKGROUND: Poisoning with weak analgesics is a major public health problem because of easy accessibility of the compounds; however, few studies have investigated their influence on subsequent suicide in the context of subjects' psychiatric status and other factors. METHOD: This nested case-control study was based on the entire Danish population including all 21,169 suicide cases and 423,128 matched population controls. Data on hospital admissions for poisoning and confounding factors were retrieved from national medical and administrative registries. Conditional logistic regression was used to compute relative risk. RESULTS: A prior hospital admission for poisoning with weak non-opioid analgesics significantly increased the risk of subsequent suicide [crude incidence rate ratio (IRR) 24.7, 95% confidence interval (CI) 22.1-27.6], and the effect of paracetamol poisoning was substantially stronger than that of poisoning with salicylates or non-steroidal anti-inflammatory drugs (NSAIDs). This association could not be explained by confounding from socio-economic or psychiatric factors. The elevated risk was extremely high during the first week following the overdose (adjusted IRR 738.9, 95% CI 173.9-3139.1), then declined over time but still remained significantly high 3 years later (adjusted IRR 4.2, 95% CI 3.5-5.0). Moreover, a history of weak analgesic poisoning significantly interacted with a person's psychiatric history, increasing the risk for subsequent suicide substantially more for persons with no history of psychiatric hospitalization than did it for those with such a history. CONCLUSIONS: A history of non-fatal poisoning with weak analgesics is a strong predictor for subsequent suicide. These results emphasize the importance of intensive psychiatric care of patients following overdose.

Hodgkin's disease and birth outcome: a Danish nationwide cohort study.

In a Danish nationwide cohort study of 292 births from 1973 to 2002 in women with Hodgkin's disease (HD), we compared birth outcome with 14 042 births from a cohort of mothers without cancer. We found no substantially increased risk of preterm birth, low birth weight at term, or stillbirth and no difference in proportion of male newborns for 192 children of women with HD before pregnancy. The prevalence odds ratio (POR) for congenital abnormalities was 1.7 (95% confidence interval (CI): 0.9-3.1). Among 15 newborns of mothers diagnosed during pregnancy, the POR of preterm birth was 26.6 (95% CI: 8.5-83.0), but five out of the eight preterm deliveries among these women were elective. We found no substantially increased risk of adverse birth outcome among 85 newborns of women diagnosed within 2 years postpartum, though effect estimates were imprecise. The overall findings are reassuring, they cannot exclude the possibility of an increased risk of congenital abnormalities for newborns of women diagnosed with HD before pregnancy.

Risk of peptic ulcer, oesophagitis, pancreatitis or gallstone in patients with unexplained chest/epigastric pain and normal upper endoscopy: a 10-year Danish cohort study.

BACKGROUND: No studies have examined the risk of upper gastrointestinal diseases among patients with unexplained chest/epigastric pain (UCEP) and a normal upper endoscopy. AIM: To examine the relative risk of peptic ulcer, oesophagitis, pancreatitis or gallstone in UCEP patients. METHODS: This Danish 10-year cohort study focused on UCEP patients (n = 386), diagnosed in 1992-93. Ten age- and gender-matched controls were selected per patient from Denmark's Civil Registration System (n = 3860). Kaplan-Meier analysis and Cox's regression analysis was used to calculate the risk of hospitalization for peptic ulcer, oesophagitis, pancreatitis or gallstone. RESULTS: Compared with controls, the adjusted relative risks among UCEP patients <1 and > or = 1 year after upper endoscopy were for peptic ulcer 2.0 [95% confidence interval (CI) 0.2-18.4] and 1.7 (95% CI 0.9-3.4), for oesophagitis 8.2 (95% CI 1.2-59.2) and 1.9 (95% CI 0.7-5.0), for pancreatitis 9.2 (95% CI 2.0-41.8) and 3.9 (95% CI 1.4-10.5), and for gallstone 14.1 (95% CI 5.4-37.2) and 3.3 (95% CI 1.9-5.8). CONCLUSIONS: UCEP is positively associated with all study outcomes especially in the first year after upper endoscopy, indicating that peptic ulcer, oesophagitis, pancreatitis or gallstone could be underlying early UCEP symptoms. However, the long-term association remained strong for pancreatitis and gallstone, suggesting a genuine excess risk.

Birth outcome in women treated with azathioprine or mercaptopurine during pregnancy: A Danish nationwide cohort study.

BACKGROUND: Data on birth outcome after exposure to azathioprine or mercaptopurine during pregnancy is sparse. AIM: To examine the risk of adverse birth outcome among newborns of women exposed to azathioprine or mercaptopurine during pregnancy. METHODS: Data on drug use and births were obtained from Danish population registries. We included 76 exposed pregnancies in 69 women. Of these, we used 64 pregnancies exposed 30 days before conception or during the first trimester to examine the risk of congenital abnormalities, and 65 pregnancies exposed during the entire pregnancy to examine preterm birth and low birth weight at term. Their birth outcomes were compared with outcomes among women who did not fill prescriptions for azathioprine or mercaptopurine during pregnancy. RESULTS: Azathioprine- or mercaptopurine-exposed women had a higher risk of adverse birth outcomes than unexposed controls. However, when the comparison was limited to newborns of women with the same types of underlying disease, relative risks for spontaneous and induced preterm birth, low birth weight at term, and congenital abnormalities were 1.1 (95% CI: 0.5-2.4), 4.0 (95% CI: 1.5-10.8), 1.7 (95% CI: 0.3-8.7) and 1.1 (95% CI: 0.5-2.9), respectively. CONCLUSION: Our results suggest that adverse birth outcomes were caused by the underlying disease rather than by use of azathioprine or mercaptopurine.

Birth outcome in women with breast cancer.

We investigated whether maternal breast cancer affects birth outcome in a nationwide cohort study of 695 births from 1973 to 2002 of women with breast cancer with respect to preterm birth, low birth weight at term, stillbirth and congenital abnormalities as well as mean birth weight, compared with the outcomes of 33 443 births from unaffected mothers. There was no excess risk of adverse birth outcome for the 216 newborns of women with breast cancer before pregnancy. Stratification by mother's treatment did not change the results. For 37 newborns of women diagnosed during pregnancy, the prevalence ratio (PR) of preterm birth was 8.1 (95% confidence interval (CI): 3.8-17). However, 10 of the 12 preterm deliveries among these women were elective early deliveries. Among 442 births of women diagnosed in the 2 years from time of delivery, the PR of preterm birth was 1.4 (95% CI: 1.0-2.0), and the PR of low birth weight at term for boys was 2.9 (95% CI: 1.3-6.3). Overall, our results are reassuring regarding the risks of adverse birth outcome for breast cancer patients.

The association between admission for poisoning with paracetamol or other weak analgesics and subsequent admission for psychiatric disorder: a Danish nationwide case-control study.

BACKGROUND: Many cases of paracetamol poisoning are with suicidal intent, but the association between paracetamol poisoning and subsequent psychiatric disorder is unknown. AIM: To examine the association between poisoning with paracetamol or other weak analgesics and subsequent psychiatric disorder. METHODS: The study was set in a nested case-control design and based on nationwide Danish registers. We identified all patients diagnosed with schizophrenia, affective disorder or eating disorder in 1994-1998 and matched population controls. We estimated the relative risk of these psychiatric disorders after admission for paracetamol or nonparacetamol poisoning, adjusting for income, employment and marital status. RESULTS: We included 12,603 cases with psychiatric disorder, and 1.2% had a diagnosis of poisoning compared with 0.2% of the 252,060 matched population controls. Compared with those with no diagnoses of weak analgesic poisoning, the risk of schizophrenia increased 3.9-fold after paracetamol poisoning, and 2.0-fold after nonparacetamol poisoning. The risk of affective disorder increased 12.2-fold after paracetamol poisoning and 2.6-fold after nonparacetamol poisoning. The risk of eating disorder increased 5.0-fold after paracetamol poisoning, and 2.2-fold after nonparacetamol poisoning. The risk of a diagnosis of psychiatric disorder was very high immediately after poisoning and remained increased for more than 10 years. CONCLUSIONS: Paracetamol poisoning is a strong risk marker for psychiatric disorder, particularly affective disorders.

Risk of specific congenital abnormalities in offspring of women with diabetes.

AIMS: To assess the extent to which the increased risk of congenital abnormalities seen in women with pre-gestational insulin-treated diabetes mellitus is unspecific or related to the embryology of specific organs. METHODS: Cases with congenital abnormalities were identified in the population-based Hungarian Congenital Abnormality Registry from 1980 to 1996 with two newborn children without congenital abnormality selected from the National Birth Registry as controls. We adjusted for parity, maternal age, and use of antipsychotic drugs. RESULTS: Among cases we found 63/22,843 babies with maternal diabetes compared with 50/38,151 in the control group [adjusted prevalence odds ratio (POR) 2.1; 95% CI 1.5-3.1]. The association was strongest for the following congenital abnormalities: renal agenesis (POR: 14.8; 95% CI, 3.5-62.1), obstructive congenital abnormalities of the urinary tract (POR: 4.3; 95% CI, 1.3-13.9), cardiovascular congenital abnormalities (POR: 3.4; 95% CI, 2.0-5.7), and multiple congenital abnormalities (POR: 5.0; 95% CI, 2.4-10.2). CONCLUSIONS: These data indicate that pre-gestational maternal diabetes is associated with strong teratogenic effects on the kidney, urinary tract, and heart, and strongly associated with multiple congenital abnormalities. We found no material association between diabetes and spinal congenital abnormalities and limb deficiencies.

Non-calculus suppurative cholangitis in Danish patients with inflammatory bowel disease.

BACKGROUND/AIMS: We examined the risk of non-calculus suppurative cholangitis in patients with inflammatory bowel disease in the entire Danish population. METHODOLOGY: The study included all patients discharged from Danish hospitals with a diagnosis of Crohn's disease or ulcerative colitis as registered in the Danish National Registry of Patients from January 1, 1977 to December 31, 1992. We compared the observed number of patients hospitalized with suppurative cholangitis with expected numbers on the basis of age, gender, and calendar-specific incidence rates in the general population. RESULTS: Overall, 15,317 eligible patients with inflammatory bowel disease were discharged during the study period. Among these were 52 cases of non-calculus suppurative cholangitis. The incidence rate of non-calculus suppurative cholangitis in the cohort with inflammatory bowel disease was 46.1 per 100,000 person-years. The standardized incidence ratio (SIR) for suppurative cholangitis was increased similarly for patients with Crohn's disease [SIR=6.7, 95% confidence interval (CI): 3.1-12.7] and for patients with ulcerative colitis (SIR=6.6, 95% CI: 4.7-9.1). The highest relative risk was found in male patients younger than 40 years of age, for both Crohn's disease and ulcerative colitis (SIR=70.5 and 78.7, respectively). CONCLUSIONS: Patients with inflammatory bowel disease have an increased risk of non-calculus suppurative cholangitis.

The risk of congenital abnormalities in children fathered by men treated with azathioprine or mercaptopurine before conception.

BACKGROUND: Immunosuppressive therapy with azathioprine and mercaptopurine is commonly used in patients with various chronic diseases. The few existing data on the reproductive safety of these drugs after paternal use before conception are inconclusive. AIM: To examine the risk of congenital abnormalities in children fathered by men exposed to azathioprine or mercaptopurine before conception. METHODS: This was a Danish population-based cohort study, based on data from the Prescription Database, the Medical Birth Registry and the Hospital Discharge Registry of North Jutland County, Denmark. Fifty-four exposed pregnancies, in which the father filed a prescription for azathioprine or mercaptopurine (between 1 January 1991 and 31 December 2001) before conception, were included. The controls comprised 57 195 pregnancies with no paternal azathioprine or mercaptopurine use. RESULTS: Four children with congenital abnormalities (underlying paternal diseases: glomerulonephritis and severe skin disease) were found in 54 exposed pregnancies (7.4%), compared with 2334 (4.1%) in controls. The adjusted odds ratio for congenital abnormalities in children fathered by men treated with azathioprine or mercaptopurine was 1.8 (95% confidence interval, 0.7-5.0). CONCLUSIONS: Our data may indicate that paternal use of azathioprine or mercaptopurine before conception is associated with an increased risk of congenital abnormalities. However, more data are needed to determine whether the association is causal.

COX-2-selective inhibitors and the risk of upper gastrointestinal bleeding in high-risk patients with previous gastrointestinal diseases: a population-based case-control study.

BACKGROUND: Clinical trials have suggested that cyclo-oxygenase-2-selective inhibitors are associated with a lower risk of upper gastrointestinal bleeding than are non-selective, non-aspirin, non-steroidal anti-inflammatory drugs. This has not yet been confirmed in studies of patients with an increased susceptibility to upper gastrointestinal bleeding. AIM: To examine the risk of upper gastrointestinal bleeding in high-risk patients who filled prescriptions for cyclo-oxygenase-2 inhibitors or other non-steroidal anti-inflammatory drugs. METHODS: A population-based case-control study was performed in the Danish county of North Jutland from 1 January 2000 to 31 December 2002. From the County Hospital Discharge Registry and the Civil Registration System, we identified incident cases with upper gastrointestinal bleeding (n = 780) and randomly selected controls (n = 2906), respectively. All cases and controls had previous gastrointestinal diseases. Data on drug exposure were obtained from the countywide Prescription Database. RESULTS: Thirty-five cases (4.5%) filled prescriptions for cyclo-oxygenase-2 inhibitors within 30 days of the date of upper gastrointestinal bleeding, compared with 79 controls (2.7%). Adjusted odds ratios for upper gastrointestinal bleeding according to prescription for celecoxib, rofecoxib and non-steroidal anti-inflammatory drugs were 1.3 [95% confidence interval (CI), 0.7-2.8], 2.1 (95% CI, 1.2-3.5) and 3.3 (95% CI, 2.4-4.4), respectively. CONCLUSIONS: In patients with increased susceptibility to gastrointestinal adverse events, a lower risk of upper gastrointestinal bleeding was observed in users of cyclo-oxygenase-2 inhibitors compared with users of other non-aspirin, non-steroidal anti-inflammatory drugs.