It is unknown whether comorbidity interacts with colorectal cancer (CRC) to increase the rate of mortality beyond that explained by the independent effects of CRC and comorbid conditions.
We conducted a cohort study (1995-2010) of all Danish CRC patients (n=56963), and five times as many persons from the general population (n=271670) matched by age, gender, and specific comorbidities. To analyse comorbidity, we used the Charlson Comorbidity Index (CCI) scores. We estimated standardised mortality rates per 1000 person-years, and calculated interaction contrasts as a measure of the excess mortality rate not explained by the independent effects of CRC or comorbidities.
Among CRC patients with a CCI score=1, the 0-1 year mortality rate was 415 out of 1000 person-years (95% confidence interval (CI): 401, 430) and the interaction accounted for 9.3% of this rate (interaction contrast=39 out of 1000 person-years, 95% CI: 22, 55). For patients with a CCI score of 4 or more, the interaction accounted for 34% of the mortality (interaction contrast=262 out of 1000 person-years, 95% CI: 215, 310). The interaction between CRC and comorbidities had limited influence on mortality beyond 1 year after diagnosis.
Successful treatment of the comorbidity is pivotal and may reduce the mortality attributable to comorbidity itself, and also the mortality attributable to the interaction.
National population-based medical registries in Denmark offer a unique opportunity to study eosinophilic oesophagitis (EoE) epidemiology.
To determine the incidence and prevalence of EoE in Denmark, and evaluate whether an increase in endoscopy with biopsy activity explains changes in these trends.
The Danish National Pathology Registry, Danish National Patient Registry and Danish Registry of Medicinal Product Statistics were queried from 1997 to 2012. Using an EoE case-finding algorithm validated for Danish patients, EoE cases were identified during each year of the study period; we also identified all patients with oesophageal eosinophilia. Using the known population of Demark, the annual incidence and prevalence of EoE were determined. We also determined the number of oesophageal biopsies performed each year in Denmark, and compared the change in the incidence rate to the change in biopsy rate.
Between 1997 and 2012, 1708 patients had oesophageal eosinophilia, of whom 844 met the case definition of EoE. There were seven new cases of EoE in 1997 and 145 new cases in 2012, corresponding to a 19.5-fold increase in incidence (0.13/100 000 to 2.6/100 000). There were 769 total cases in 2012 (prevalence of 13.8/100 000). Over the same time frame, the oesophageal biopsy rate increased only 1.9 fold, from 91.1/100 000 to 175.3/100 000.
The incidence and prevalence of EoE markedly increased in Denmark over the past 15 years. This increase far outpaced the increase in oesophageal biopsy utilisation, indicating that changes in the frequency of EoE are not due to changes in biopsy rates alone.
Cites: World J Gastroenterol. 2013 Jan 28;19(4):503-1023382628
There is conflicting evidence regarding bisphosphonates and atrial fibrillation (AF) risk in osteoporosis patients. However, bisphosphonates are used in much higher doses in treatment of bone metastasis and hypercalcemia, but little is known about the AF risk in cancer patients.
We conducted a nationwide population-based cohort study using Danish databases. All cancer patients exposed to intravenous bisphosphonates during 2000-2008 were matched with two non-exposed cancer patients by cancer type, distant metastasis presence at diagnosis, age, and gender. We used Cox proportional hazard regression to estimate hazards ratios (HRs) of AF/flutter adjusting for important confounding factors.
Of the 3981 cancer patients exposed to intravenous bisphosponates, 128 (3.2%) developed AF/flutter. This condition occurred in 192 (2.4%) of the 7906 non-exposed cancer patients, corresponding to an adjusted HR of 1.7 (95% CI: 1.2-2.4).
Intravenous bisphosphonates may increase AF/flutter risk in cancer patients.
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Little is known about the risk of colorectal cancer among patients with irritable bowel syndrome (IBS).
We conducted a nationwide cohort study using data from the Danish National Registry of Patients and the Danish Cancer Registry from 1977 to 2008. We included patients with a first-time hospital contact for IBS and followed them for colorectal cancer. We estimated the expected number of cancers by applying national rates and we computed standardised incidence ratios (SIRs) by comparing the observed number of colorectal cancers with the expected number. We stratified the SIRs according to age, gender, and time of follow-up.
Among 57,851 IBS patients, we identified 407 cases of colon cancer during a combined follow-up of 506,930 years (SIR, 1.14 (95% confidence interval (CI): 1.03-1.25) and 115 cases of rectal cancer, corresponding to a SIR of 0.67 (95% CI: 0.52-0.85). In the first 3 months after an IBS diagnosis, the SIR was 8.42 (95% CI: 6.48-10.75) for colon cancer and 4.81 (95% CI: 2.85-7.60) for rectal cancer. Thereafter, the SIRs declined and 4-10 years after an IBS diagnosis, the SIRs for both colon and rectal cancer remained below 0.95.
We found a decreased risk of colorectal cancer in the period 1-10 years after an IBS diagnosis. However, in the first 3 months after an IBS diagnosis, the risk of colon cancer was more than eight-fold increased and the risk of rectal cancer was five-fold increased. These increased risks are likely to be explained by diagnostic confusion because of overlapping symptomatology.
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Patients with Barrett's oesophagus may be at increased risk of mortality overall, and cardiovascular disease has been suggested as the main underlying cause of death.
To examine cause-specific mortality and risk of cardiovascular events among patients with Barrett's oesophagus.
Utilising existing Danish data sources (1997-2011), we identified all patients with histologically verified Barrett's oesophagus (n = 13 435) and 123 526 members of the general population matched by age, sex and individual comorbidities. We calculated cause-specific mortality rates and incidence rates of cardiovascular diseases. We then compared rates between patients with Barrett's oesophagus and the general population comparison cohort, using stratified Cox proportional hazard regression.
Patients with Barrett's oesophagus had a 71% increased risk of overall mortality. The cause-specific mortality rate per 1000 person-years for patients with Barrett's oesophagus was 8.5 for cardiovascular diseases, 14.7 for non-oesophageal cancers, and 5.4 for oesophageal cancer. Compared to the general population cohort, corresponding hazard ratios were 1.26 (95% confidence interval (CI): 1.15-1.38), 1.77 (95% CI: 1.65-1.90), and 19.4 (95% CI: 16.1-23.4), respectively. The incidence rates of cardiovascular diseases per 1000 person-years for Barrett's oesophagus patients and for persons from the general population cohort, respectively, varied from 0.4 and 0.2 for subarachnoid bleeding (hazard ratio 1.10, 95% CI: 0.87-1.39) to 8.1 and 5.9 for congestive heart failure (hazard ratio 1.33, 95% CI: 1.21-1.46).
Prophylactic measures targeted at cardiovascular diseases and non-oesophageal cancers potentially could be more important than measures against oesophageal cancer, for improving prognosis among patients with Barrett's oesophagus.
Previous studies indicate that pre-admission glucocorticoids increase the risk of perioperative complications.
To examine whether pre-admission use of glucocorticoids affects 30-day mortality after colorectal cancer (CRC) surgery.
We conducted a nationwide population-based cohort study by linking Danish medical registries. All residents in Denmark who underwent CRC surgery from 2001 to 2011 were included. We characterised subjects who filled their most recent glucocorticoid prescription =90, 91-365 and >365 days before their surgery date as prevalent, recent and former users, respectively. Prevalent users were subgrouped into new (first-ever prescription =90 days before surgery date) and continuing users. We estimated 30-day cumulative mortality by the Kaplan-Meier method and corresponding mortality rate ratios (MRRs) using Cox proportional hazard regression, adjusting for potential confounders.
Of the 34 641 CRC patients included, 3966 (11.5%) had filled one or more prescriptions of glucocorticoids within the year before the surgery date. Thirty-day mortality among prevalent users of oral glucocorticoids was 15.0% vs. 7.3% among non-users [MRR = 1.28; 95% confidence interval (CI): 1.03, 1.58]. Among new users, the 30-day mortality was 17.8% (MRR = 1.92; 95% CI: 1.30, 2.83) while it was 14.2% among continuing users (MRR = 1.13; 95% CI: 0.88, 1.44). No associations were found for recent or former use of oral glucocorticoids nor for use of inhaled, intestinal-acting, and mixed glucocorticoids.
Prevalent use, particulary new use, of oral glucocorticoids was associated with markedly increased 30-day mortality after colorectal cancer surgery compared to patients not exposed to any glucocorticoids.
Proton pump inhibitors (PPIs) may activate the immune system and cause asthma.
To investigate the association of prenatal exposure to PPIs and histamine 2-receptor antagonists (H2RAs) with risk of asthma.
In this cohort study, 197,060 singletons born between 1996 and 2008 in northern Denmark were followed until the end of 2009. Data were obtained through Danish medical registries. Asthma in offspring was defined as at least two prescriptions of both a ß-agonist and an inhaled glucocorticoid and/or a hospital diagnosis of asthma during the follow-up. Cox proportional-hazard regression was used to compute incidence rate ratios, adjusting for covariates.
A total of 2238 (1.1%) children were prenatally exposed to PPIs and 24,506 (12.4%) children developed asthma during follow-up (median follow-up = 6.8 years). The adjusted IRR (aIRR) of asthma associated with prenatal exposure to PPIs was 1.41 (95% confidence interval (CI): 1.27-1.56), compared with those unexposed. The association did not vary by trimester of exposure, and prenatal exposure to H2RAs was associated with similar increase in risk. The aIRR for maternal PPI and H2RA use in the year after, but not during pregnancy was 1.32 (95% CI: 1.20-1.46) and 1.13 (0.93-1.36), respectively, compared with non-use during and in the year after pregnancy.
Prenatal exposure to both PPIs and H2RAs was associated with an increased risk of asthma in our study. Because the observed association is not drug specific and also observed for maternal postnatal use it may be explained by a 'class effect' or maternal underlying condition.
This study examined the quality of International Classification of Diseases-10 colorectal cancer (CRC) diagnosis coding in the Danish National Registry of Patients (DNRP), using the Danish Cancer Registry (DCR) as a reference. We included all patients in Denmark with a CRC diagnosis in the DNRP and/or in the DCR from 2001 through 2006. Data quality was evaluated by estimating completeness and positive predictive value (PPV) of data in different subcategories of patients. We estimated mortality and date of diagnosis, to evaluate the effect of potential differences in data quality. Overall completeness of data in the DNRP for CRC was 93.4% [95% confidence interval (CI): 93.1-93.7] and the PPV was 88.9% (95% CI: 88.5-89.2). Completeness and PPV improved during the study period. However, the completeness of data for patients >75 years in the 2001-2003 period [88.8% (95% CI: 87.8-89.6)] was lower than average, and cancers in more unspecific locations and cancers in the colorectal junction also had lower estimates (below 90%). There were no differences in survival estimates in the DNRP compared to the DCR. In conclusion, this study shows high CRC data quality in the DNRP measured by completeness and PPV, except in a few subgroups.
Systemic glucocorticoids are potent immunosuppressants, potentially facilitating carcinogenesis. Studies examining glucocorticoids and colorectal cancer risk are few.
To investigate the association between use of systemic glucocorticoids and colorectal cancer risk, both overall and by cancer stage (localised versus metastatic).
We conducted a nested population-based case-control study in Northern Denmark (1.8 million people) using medical registries. The study included 14,158 patients with a first-time diagnosis of colorectal cancer from 1991 through 2010. Using risk set sampling, we identified 141,580 population controls, matched on age and gender. Logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for covariates.
Frequent use of systemic glucocorticoids (defined as >2 prescriptions) was not associated with overall colorectal cancer risk [adjusted OR (aOR) = 0.93 (95% CI: 0.85-1.00)], compared with never/rare use (=2 prescriptions). Associations according to duration of use and doses (quartiles of cumulative prednisolone equivalents) were also near the null. Examining colorectal cancer by stage, no substantial associations were found between long-term use (>5 years) of high-dose (>5500 mg) systemic glucocorticoids and localised [aOR = 1.12 (95% CI: 0.81-1.55)] or metastatic [aOR = 0.82 (95% CI: 0.59-1.14)] cancer.
Despite immunological and metabolic effects of frequent use of systemic glucocorticoids, which would be expected to increase colorectal cancer risk, we found no substantial association between the two.