To investigate the extent to which fecundability is associated with active smoking, time since smoking cessation, and passive smoking.
Prospective cohort study.
A total of 3,773 female pregnancy planners aged 18-40 years.
Self-reported pregnancy. Fecundability ratios (FRs) and 95% confidence intervals (CIs) were estimated using a proportional probabilities model that adjusted for menstrual cycle at risk and potential confounders.
Among current smokers, smoking duration of =10 years was associated with reduced fecundability compared with never smokers (FR, 0.85, 95% CI 0.72-1.00). Former smokers who had smoked =10 pack-years had reduced fecundability regardless of when they quit smoking (1-1.9 years FR, 0.83, 95% CI 0.54-1.27; =2 years FR, 0.73, 95% CI 0.53-1.02). Among never smokers, the FRs were 1.04 (95% CI 0.89-1.21) for passive smoking in early life and 0.92 (95% CI 0.82-1.03) for passive smoking in adulthood.
Among Danish pregnancy planners, cumulative exposure to active cigarette smoking was associated with delayed conception among current and former smokers. Time since smoking cessation and passive smoking were not appreciably associated with fecundability.
To investigate to what extent alcohol consumption affects female fecundability.
Prospective cohort study.
Denmark, 1 June 2007 to 5 January 2016.
6120 female Danish residents, aged 21-45 years, in a stable relationship with a male partner, who were trying to conceive and not receiving fertility treatment.
Alcohol consumption was self reported as beer (330 mL bottles), red or white wine (120 mL glasses), dessert wine (50 mL glasses), and spirits (20 mL) and categorized in standard servings per week (none, 1-3, 4-7, 8-13, and =14). Participants contributed menstrual cycles at risk until the report of pregnancy, start of fertility treatment, loss to follow-up, or end of observation (maximum 12 menstrual cycles). A proportional probability regression model was used to estimate fecundability ratios (cycle specific probability of conception among exposed women divided by that among unexposed women).
4210 (69%) participants achieved a pregnancy during follow-up. Median alcohol intake was 2.0 (interquartile range 0-3.5) servings per week. Compared with no alcohol consumption, the adjusted fecundability ratios for alcohol consumption of 1-3, 4-7, 8-13, and 14 or more servings per week were 0.97 (95% confidence interval 0.91 to 1.03), 1.01 (0.93 to 1.10), 1.01 (0.87 to 1.16) and 0.82 (0.60 to 1.12), respectively. Compared with no alcohol intake, the adjusted fecundability ratios for women who consumed only wine (=3 servings), beer (=3 servings), or spirits (=2 servings) were 1.05 (0.91 to1.21), 0.92 (0.65 to 1.29), and 0.85 (0.61 to 1.17), respectively. The data did not distinguish between regular and binge drinking, which may be important if large amounts of alcohol are consumed during the fertile window.
Consumption of less than 14 servings of alcohol per week seemed to have no discernible effect on fertility. No appreciable difference in fecundability was observed by level of consumption of beer and wine.
Cites: Stat Med. 1989 May;8(5):551-612657958
Cites: J Natl Cancer Inst. 1993 May 5;85(9):722-78478958
In earlier studies of the influence of hydroxymethylglutaryl-coenzyme A reductase inhibitors (also known as statins) on colorectal cancer prognosis, investigators reported a reduced rate of cancer-specific mortality. Studies of recurrence are few and small. Using data from Danish registries, we followed 21,152 patients diagnosed with stage I-III colorectal cancer from 2001 to 2011. We estimated the association between statin use in the preceding year and cancer recurrence, cancer-specific mortality, and all-cause mortality rates. We identified 5,036 recurrences, 7,084 deaths from any cause, and 4,066 deaths from colorectal cancer. After adjustment for potential confounders, statin use was not associated with recurrence (adjusted hazard ratio (aHR) = 1.01, 95% confidence interval (CI): 0.93, 1.09), but it was associated with death from colorectal cancer (aHR = 0.72, 95% CI: 0.65, 0.79) and death from any cause (aHR = 0.72, 95% CI: 0.67, 0.76). Statin use in the year preceding recurrence was associated with a reduced risk of cancer-specific mortality (aHR = 0.83, 95% CI: 0.74, 0.92) but also a reduced risk of death from any other cause (aHR = 0.78, 95% CI: 0.61, 1.00). Statin use was not associated with a reduced rate of colorectal cancer recurrence, but it was associated with a reduced rate of cancer-specific mortality, which suggests that there is no cancer-directed benefit; therefore, there is no basis to prescribe statins to colorectal cancer patients who do not have cardiovascular indications.
To study whether use of ß-blockers increases survival in patients with malignant melanoma because experimental data suggest that catecholamine hormones may be involved in stimulating the aggressiveness of malignant melanoma.
A total of 4,179 patients diagnosed with malignant melanoma in Denmark with a median follow-up of 4.9 years and identified in the Danish Cancer Registry participated. Data on ß-blocker use, comorbidity, and survival were obtained from medical and administrative databases. Cox proportional hazards models were used to estimate HRs for all-cause mortality with 95% CIs with adjustment for prognostic factors.
A total of 372 (8.9%) patients with malignant melanoma were treated with ß-blockers within 90 days of melanoma diagnosis. The median ß-blocker duration for exposure within 90 days of melanoma diagnosis, more than 90 days, and no prior exposure was 7.6, 1.4, and 0 years, respectively. The patients receiving ß-blockers were older, had more comorbidities, and more cardiovascular and psychotropic drug user than the patients receiving no ß-blockers prior to melanoma diagnosis. After adjustment for age and comorbidity index, the HR for melanoma death was 0.87 (95% CI: 0.64-1.20) and for all-cause mortality was 0.81 (95% CI: 0.67-0.97).
Increased survival time of patients with melanoma receiving ß-blockers suggests that this class of drugs may hold promise in treatment strategy for these patients.
The observations described here suggest that catecholamines may retard melanoma progression and that ß-blockers may have unrecognized potential as a therapeutic intervention for melanoma.
Cites: J Clin Oncol. 2001 Jan 15;19(2):577-8311208853
Cites: Cancer. 2002 Aug 15;95(4):808-1512209725
Cites: Clin Cancer Res. 2003 Oct 1;9(12):4514-2114555525
Cites: Cancer Causes Control. 2004 Aug;15(6):535-4115280632
Clopidogrel therapy increases bleeding risk, but whether it influences short-term mortality after peptic ulcer bleeding (PUB) is unknown. The objective was to examine whether clopidogrel use at the time of PUB increases 30-day mortality. We conducted this cohort study in northern Denmark (population 1.7 million). We used the Danish National Patient Registry, covering all hospitals, to identify all patients with a first-ever inpatient diagnosis of endoscopically or surgically confirmed PUB between 1998 and 2008 and their comorbidities. From the prescription database in the region, we ascertained the use of clopidogrel at the time of admission (current use) or before admission (former use) and use of concurrent medications. We obtained mortality data from the Danish Civil Registration System. We used regression modeling to compute mortality rate ratios (MRRs) with 95% confidence intervals (CIs), controlling for potential confounders. We identified 6951 patients with bleeding peptic ulcers. At admission, 122 (1.8%) were current users of clopidogrel, 143 (2.1%) were former users, and 6686 (96.2%) were nonusers. Thirty-day mortality was 5.7% for current users, 7.0% for former users, and 8.0% for nonusers. The adjusted 30-day MRR was reduced in both current and former users, compared with nonusers (MRR = 0.72, 95% CI 0.34, 1.52 and MRR = 0.71, 95% CI 0.38, 1.32, respectively). There was no notable modification of the association within gender or age strata. Although the use of clopidogrel increases the risk of PUB, former use and current use of clopidogrel were not associated with increased short-term mortality after admission for this condition.
Selection bias is a potential concern in all epidemiologic studies, but it is usually difficult to assess. Recently, concerns have been raised that internet-based prospective cohort studies may be particularly prone to selection bias. Although use of the internet is efficient and facilitates recruitment of subjects that are otherwise difficult to enroll, any compromise in internal validity would be of great concern. Few studies have evaluated selection bias in internet-based prospective cohort studies. Using data from the Danish Medical Birth Registry from 2008 to 2012, we compared six well-known perinatal associations (e.g., smoking and birth weight) in an internet-based preconception cohort (Snart Gravid n = 4,801) with the total population of singleton live births in the registry (n = 239,791). We used log-binomial models to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for each association. We found that most results in both populations were very similar. For example, maternal obesity was associated with an increased risk of delivering a macrosomic infant in Snart Gravid (RR = 1.5; 95% CI: 1.2, 1.7) and the total population (RR = 1.5; 95% CI: 1.45, 1.53), and maternal smoking of >10 cigarettes per day was associated with a higher risk of low birth weight (RR = 2.7; 95% CI: 1.2, 5.9 vs. RR = 2.9; 95% CI: 2.6, 3.1) in Snart Gravid and the total population, respectively. We cannot be certain that our results would apply to other associations or different populations. Nevertheless, our results suggest that recruitment of reproductive aged women via the internet may be no more prone to selection bias than traditional methods of recruitment.
Cites: J Med Internet Res. 2013;15(9):e20524036068
Cites: Int J Epidemiol. 2013 Aug;42(4):1012-424062287
Cites: Int J Epidemiol. 2013 Aug;42(4):1016-724062289
Cites: Int J Epidemiol. 2013 Aug;42(4):1022-624062291
To examine the association between folic acid (FA) supplementation obtained through either single FA tablets or multivitamins (MVs) and menstrual cycle characteristics among 5386 women aged 18-40 years, enrolled in an Internet-based study of Danish women attempting pregnancy during 2007-2011.
In a cross-sectional study, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of FA supplementation with menstrual cycle regularity; short (
Little is known about the role of heritable factors in diverticular disease. We evaluated the contribution of heritable factors to the development of diverticular disease diagnosed at a hospitalization or outpatient visit.
Using nationwide patient registries, we identified 142,123 incident cases of diverticular disease diagnosed at a hospitalization (1977-2011) or an outpatient hospital visit (1995-2011) in Denmark, including cases in 10,420 index siblings and 923 twins. We calculated standardized incidence ratios for siblings versus the general population and concordance rates for monozygotic versus dizygotic twin pairs as measures of relative risk (RR).
The RR for diverticular disease in siblings of index cases was 2.92 (95% confidence interval [CI], 2.50-3.39) compared with the general population. The RRs were similar irrespective of the sex of the sibling or index case and were particularly strong in siblings of hospitalized cases and cases that underwent surgery. The proband-wise concordance rate for monozygotic twins was double that of dizygotic twins (0.16 [95% CI, 0.11-0.22] vs 0.07 [95% CI, 0.05-0.11], respectively). The RR of diverticular disease in one twin when the other had diverticular disease was 14.5 (95% CI, 8.9-23) for monozygotic twins compared with 5.5 (95% CI, 3.3-8.6) for dizygotic twins. Associations were stronger in female monozygotic twins compared with male twins (tetrachoric correlation, 0.60 [95% CI, 0.49-0.70] vs 0.33 [95% CI, 0.13-0.51]; P = .03 in an analysis stratified by sex and zygosity). We estimate that 53% (95% CI, 45%-61%) of susceptibility to diverticular disease results from genetic factors.
Based on a population-based study in Denmark, genetic factors appear to contribute to development of diverticular disease.
To examine the association between pregravid oral contraceptive (OC) use and spontaneous abortion (SAB).
In an Internet-based preconception cohort study of 4862 Danish pregnancy planners, we used Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals (CIs) for the association between OC use and SAB. We controlled for maternal age, physical activity, parity, education, alcohol and caffeine consumption, body mass index, and smoking.
Compared with women who discontinued OCs >1 year before conception, HRs were 0.95 (95% confidence interval (CI) = 0.77-1.17), 0.99 (95% CI = 0.82-1.19), and 0.80 (95% CI = 0.60-1.06) for women who discontinued OCs 7-12, 2-6, and 0-1 months before conception, respectively. Compared with less than 4 years of OC use, HRs for 4-7, 8-11, and 12 years or more of OC use were 1.05 (95% CI = 0.80-1.37), 0.92 (95% CI = 0.71-1.19), and 0.88 (95% CI = 0.65-1.19), respectively. Dose of estrogen and generation of progestin were not materially associated with SAB risk.
We found no evidence that pregravid OC use is associated with an increase in SAB. Use within 1 month of conception was associated with a slightly lower risk of SAB, but this may be due to increased reproductive fitness in women who conceive quickly after discontinuation of OCs.
Cites: Cancer Causes Control. 2001 Jan;12(1):47-5911227925
Cites: Am J Epidemiol. 2013 Jul 1;178(1):70-8323788671
Cites: Stat Med. 2001 May 15-30;20(9-10):1541-911343373
Cites: Am J Public Health. 2003 Feb;93(2):299-30612554590
Cites: N Engl J Med. 1977 Sep 1;297(9):468-71887128
Cites: Am J Obstet Gynecol. 1978 Feb 1;130(3):274-8623166
A recent comprehensive review concluded that additional research is needed to determine the optimal use of aspirin for cancer prevention.
To assess associations between the use of low-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) and colorectal cancer risk.
Population-based, case-control study.
Patients with first-time colorectal cancer in northern Denmark between 1994 and 2011. Population control participants were selected by risk set sampling.
Data on drug use, comorbid conditions, and history of colonoscopy were obtained from prescription and patient registries. Use of low-dose aspirin (75 to 150 mg) and nonaspirin NSAIDs was defined according to type, estimated dose, duration, and consistency of use.
Among 10 280 case patients and 102 800 control participants, the adjusted odds ratios (ORs) for colorectal cancer associated with ever use (=2 prescriptions) of low-dose aspirin and nonaspirin NSAIDs were 1.03 (95% CI, 0.98 to 1.09) and 0.94 (CI, 0.90 to 0.98), respectively. Continuous long-term use (=5 years) of low-dose aspirin was associated with a 27% reduction in colorectal cancer risk (OR, 0.73 [CI, 0.54 to 0.99]), whereas the overall OR for cumulative long-term use (continuous or noncontinuous) was close to unity. Nonaspirin NSAID use was associated with a substantial reduction in colorectal cancer risk, particularly for long-term, high-intensity use (average defined daily dose =0.3) of agents with high cyclooxygenase-2 selectivity (OR, 0.57 [CI, 0.44 to 0.74]).
Data were unavailable on over-the-counter purchases of high-dose aspirin and low-dose ibuprofen or NSAID dosing schedules, there were several comparisons, and the authors were unable to adjust for confounding by some risk factors.
Long-term, continuous use of low-dose aspirin and long-term use of nonaspirin NSAIDs were associated with reduced colorectal cancer risk. Persons who continuously used low-dose aspirin comprised only a small proportion of the low-dose aspirin users.
Danish Cancer Society, Aarhus University Research Foundation.