Jacob Jacobsen

The impact of comorbidity on survival of Danish colorectal cancer patients from 1995 to 2006--a population-based cohort study.

PURPOSE: The impact of comorbidity on the outcome of colorectal cancer is poorly understood. We examined the prevalence of comorbidity and its impact on survival among Danish colorectal cancer patients. METHODS: The hospital discharge registries in northern Denmark were used to identify 13,190 patients diagnosed with colorectal cancer between 1995 and 2006, and to assess their comorbidity using the Charlson Comorbidity Index. We obtained product limit estimates of 1-year and 5-year crude survival based on three levels of comorbidity. To quantify the impact of comorbidity on mortality, we used Coxs proportional hazards regression analysis to compute the mortality rate ratio. RESULTS: One-third of the patients had recorded comorbid conditions. Patients with moderate and severe comorbidity (Charlson scores 1-2 and score 3+) had considerably higher 1-year and 5-year mortality rates compared to patients without comorbidity. For colon cancer patients, 1-year estimates in 2004 to 2006 were mortality rate ratio1-2 = 1.2 (95 percent confidence interval, 1.0-1.5) and mortality rate ratio3+ = 1.8 (95 percent confidence interval, 1.4-2.3). For rectal cancer patients with severe comorbidity, the negative impact on survival increased over time. CONCLUSIONS: Comorbidity was a strong negative prognostic factor for survival among colorectal cancer patients.

Comorbidity and survival of Danish breast cancer patients from 1995 to 2005

Comorbid diseases can affect breast cancer prognosis. We conducted a population-based study of Danish women diagnosed with a first primary breast cancer from 1995 to 2005 (n=9300), using hospital discharge registry data to quantify comorbidities by Charlson score. We examined the influence of comorbidities on survival, and quantified their impact on relative mortality rates. The prevalence of patients with a Charlson score=‘0’ fell from 86 to 81%, with an increase in those with Charlson score=‘1–2’ from 13 to 16%, and score=‘3+’ from 1 to 2%. One- and five-year survival for patients with Charlson score=‘0’ and ‘1–2’ was better for those diagnosed in 1998–2000 than in 1995–1997. Overall, patients diagnosed in 2001–2004 (mortality ratio (MR)=0.80, 95% CI=0.68–0.95) and 1998–2000 (MR=0.92, 95% CI=0.78–1.09) had lower 1-year age-adjusted mortality compared to those diagnosed in 1995–1997 (reference period). Patients with Charlson scores ‘1–2’ and ‘3+’ had higher age-adjusted 1-year mortality than those with a Charlson score=‘0’ in each time period (2001–2004: MR‘1–2’=1.76, 95% CI=1.35–2.30, and MR‘3+’=3.78, 95% CI=2.51–5.68; and 1998–2000: MR‘1–2’=1.60, 95% CI=1.36–1.88 and MR‘3+’=2.34, 95% CI=1.65–3.33). Similar findings were observed for 5-year age-adjusted mortality. Additional analyses, adjusted for stage, indicated that confounding by stage could not explain these findings. Despite continued improvements in breast cancer survival, we found a trend of poorer survival among breast cancer patients with severe comorbidities even after adjusting for age and stage. Such poorer survival is an important public health concern and can be expected to worsen as the population ages.

Valproic acid and risk of acute pancreatitis : A population-based case-control study

To examine whether acute pancreatitis is associated with use of valproic acid. Through the population-based hospital discharge registries we identified all patients with an incident hospitalization of acute pancreatitis in the counties of North Jutland (data 1991 to 2003), Aarhus (data 1996 to 2003), and Viborg (data 1998 to 2003), Denmark. From the Danish Civil Registration System, we selected 10 sex-matched and age-matched population controls per case on the basis of risk set sampling. All prescriptions of valproic acid and other antiepileptic drugs within 90 days (present users) or 91 to 365 days (past users) before hospital admission with acute pancreatitis, or index date among controls, were collected from the prescription databases in the counties. We performed conditional logistic regression to estimate the relative risk of acute pancreatitis after exposure to valproic acid or other antiepileptic drugs, adjusting for gallstone diseases, alcohol-related diseases, hyperlipidemia, and hypercalcemia. We included 3083 cases of acute pancreatitis and 30,830 population controls. The adjusted odds ratio (OR) for acute pancreatitis in present users of valproic acid was 1.9 [95% confidence interval (CI), 1.1-3.3); for past users, the adjusted OR was 2.6 (95% CI, 0.8-8.7). For users of other antiepileptic drugs, the corresponding adjusted ORs were 1.6 (95% CI, 1.2-2.2) and 1.8 (95% CI, 1.1-3.0). Use of valproic acid is associated with an elevated relative risk estimate for acute pancreatitis, but it was not materially different from past use or use of other antiepileptic drugs. Therefore, our data challenge the hypothesis that valproic acid is an independent risk factor for acute pancreatitis.

Time trends in incidence and prognosis of primary liver cancer and liver metastases of unknown origin in a Danish region, 1985-2004.

Objectives Changes, over the last 20 years, in the diagnostic procedures and treatment of primary liver cancer (PLC) and liver metastases of unknown origin (LMUO) may have affected the clinical course of both cancers. Few longitudinal studies examined this issue. In a population-based setting, we studied changes in the incidence and prognosis of PLC and LMUO over time. Methods Between 1985 and 2004, we identified 2675 patients with PLC and LMUO in three Danish counties, with a population of 1.4 million. We computed the standardized incidence rate (SIR), ratio of PLC to LMUO diagnoses, median survival, and estimated mortality rate ratio adjusted for age, sex, and comorbidity. Results The SIR of PLC increased from 3.2 in 1985 to 5.0 in 2003, and the SIR of LMUO increased from 3.7 to 6.4. No increase was noted in the PLC-to-LMUO ratio over time (P=0.1 for trend). From 1985 to 2004, the median survival of PLC patients increased from 1.6 to 2.9 months whereas that of LMUO patients decreased from 1.7 to 1.3 months. Adjusting for age, sex, and comorbidity did not affect the mortality rate ratio estimates. Conclusions The incidence of both PLC and LMUO increased over time, whereas the PLC-to-LMUO ratio remained unchanged. Median survival of PLC patients has increased whereas that of LMUO patients remained practically unchanged.

Selective serotonin reuptake inhibitors and risk of acute pancreatitis: a population-based case-control study

To examine whether use of selective serotonin reuptake inhibitors (SSRIs) is associated with acute pancreatitis, a population-based case-control study was conducted in the counties of North Jutland (data 1991-2003), Aarhus (data 1996-2003), and Viborg (data 1998-2003), Denmark. Through hospital discharge registries, we identified all patients with an incident hospitalization of acute pancreatitis. From the Civil Registration System, we selected 10 sex- and age-matched population controls per case using risk set sampling. All prescriptions of SSRI and other antidepressant drugs within 90 days (present users) or 91 to 365 days (former users) before admission with acute pancreatitis, or index date among controls, were collected from prescription databases. First-time users were defined as those who redeemed their first SSRI prescription within 14 days before admission/index date. We estimated the relative risk of acute pancreatitis after exposure to SSRI or other antidepressants, adjusting for potential confounders. We included 3083 cases of acute pancreatitis and 30,830 controls. The adjusted odds ratio (OR) for acute pancreatitis in present users of SSRI was 1.2 (95% confidence interval [CI], 1.0-1.5); for former users, the adjusted OR was 1.2 (95% CI, 0.9-1.7). For current and former users of other antidepressant drugs, the corresponding adjusted ORs were 1.4 (95% CI, 1.1-1.7) and 1.4 (95% CI, 1.0-1.9), respectively. The adjusted OR of acute pancreatitis in first-time users of SSRI was 2.8 (95% CI, 1.1-7.0). We found use of SSRIs to be associated with increased risk for acute pancreatitis. However, the estimate did not differ between present or former users of SSRI and was not materially different from the estimate in users of other antidepressant drugs. Therefore, our data suggest that the increased risk is related to confounding by lifestyle factors or the underlying depression.

Survival of patients with colon and rectal cancer in central and northern Denmark, 1998–2009

Objective The prognosis for colon and rectal cancer has improved in Denmark over the past decades but is still poor compared with that in our neighboring countries. We conducted this population-based study to monitor recent trends in colon and rectal cancer survival in the central and northern regions of Denmark. Material and methods Using the Danish National Registry of Patients, we identified 9412 patients with an incident diagnosis of colon cancer and 5685 patients diagnosed with rectal cancer between 1998 and 2009. We determined survival, and used Cox proportional hazard regression analysis to compare mortality over time, adjusting for age and gender. Among surgically treated patients, we computed 30-day mortality and corresponding mortality rate ratios (MRRs). Results The annual numbers of colon and rectal cancer increased from 1998 through 2009. For colon cancer, 1-year survival improved from 65% to 70%, and 5-year survival improved from 37% to 43%. For rectal cancer, 1-year survival improved from 73% to 78%, and 5-year survival improved from 39% to 47%. Men aged 80+ showed most pronounced improvements. The 1- and 5-year adjusted MRRs decreased: for colon cancer 0.83 (95% confidence interval CI: 0.76–0.92) and 0.84 (95% CI: 0.78–0.90) respectively; for rectal cancer 0.79 (95% CI: 0.68–0.91) and 0.81 (95% CI: 0.73–0.89) respectively. The 30-day postoperative mortality after resection also declined over the study period. Compared with 1998–2000 the 30-day MRRs in 2007–2009 were 0.68 (95% CI: 0.53–0.87) for colon cancer and 0.59 (95% CI: 0.37–0.96) for rectal cancer. Conclusion The survival after colon and rectal cancer has improved in central and northern Denmark during the 1998–2009 period, as well as the 30-day postoperative mortality.

Tamoxifen Treatment in Danish Breast Cancer Patients and 5-Year Risk of Arterial Atherosclerotic Events: A Null Association

Although the effectiveness of tamoxifen in preventing the recurrence of breast cancer is well established, associations between tamoxifen and the occurrence of atherosclerotic events are not as clear. Breast cancer patients taking tamoxifen have lower serum cholesterol and other lipid levels than those not taking tamoxifen, suggesting that tamoxifen might prevent atherosclerotic events, but the existing studies are conflicting. We examined the relation between tamoxifen and incident hospitalization of angina pectoris, acute myocardial infarction, heart failure, and stroke. The study population of 16,289 women was identified from the Danish Breast Cancer Cooperative Group nationwide clinical database and includes women diagnosed with stage I or II estrogen receptor–positive breast cancer between 1990 and 2004 at ages 45 to 69. Use of a large population-based sample with complete outcome ascertainment allowed us to calculate precise measures of risks, risk ratios, and adjusted hazard ratios comparing tamoxifen-treated patients with untreated patients. We found strong evidence for null associations for each of the four outcomes of interest during the first year and first 5 years after the start of therapy. These findings are important in risk/benefit analyses as tamoxifen therapy in postmenopausal women is being replaced with aromatase inhibitors. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2509–11)

Postmenopausal Hormone Replacement Therapy and Risk of Acute Pancreatitis: A Population-Based Case-Control Study

OBJECTIVES:To examine whether acute pancreatitis is associated with the use of postmenopausal hormonal replacement therapy in Danish women over 45 yr of age.METHODS:We based this population-based case-control study on data from three Danish counties for the years 1991–2003. We identified all women (>45 yr of age) with a first hospital discharge diagnosis of acute pancreatitis in the county hospital discharge registries (N = 1,054). Using the Danish Civil Registration System, we selected 10 age-matched population controls for each case, using risk set sampling (N = 10,540). Data on all prescriptions for estrogens or combined estrogen/progestins redeemed within 90 days before the hospitalization (current users) and 91–365 days before (former users) were collected from the prescription databases. Conditional logistic regression was used to estimate the relative risk of acute pancreatitis after exposure to estrogen or combined estrogen/progestin, adjusted for other risk factors for acute pancreatitis.RESULTS:The adjusted relative risk for acute pancreatitis in current users of menopausal estrogens was 1.1 (95% confidence interval [CI] 0.8–1.4), and 1.1 (95% CI 0.8–1.5) in former users. For current users of combined estrogen/progestins, the adjusted relative risk was 1.2 (95% CI 0.9–1.6), and for former users, 1.6 (95% CI 1.0–2.5).CONCLUSIONS:Our data did not support a substantial association between acute pancreatitis and the use of postmenopausal hormone therapy.

Moderate mitral regurgitation in patients undergoing CABG - the MoMIC trial

Background. The presence of mild to moderate ischemic mitral regurgitation (IMR) marks a significantly reduced long-term survival and increased hospitalizations due to heart-failure. However, it is common practice in many institutions to refrain from repairing the mitral valve in these patients. There are no available conclusive data to support this practice, and thus there is a need for an adequately powered randomized trial. Study design. The Moderate Mitral Regurgitation In Patients Undergoing CABG (MoMIC) trial is the first international multi-center, large-scale study to clarify whether moderate IMR in CABG patients should be corrected. A total of 550 CABG patients with moderate IMR are to be randomized to treatment of either CABG alone or CABG plus mitral valve correction. The primary end point is a composite end point of mortality and rehospitalization for heart failure at five years. The inclusion and randomization of patients started in February 2008. Implication. If correction of moderate IMR in CABG patients proves to be the superior strategy, most patients should be treated accordingly. Trial registration: ClinicalTrial.gov identifier: NCT00613548.

Perinatal characteristics and breast cancer risk in daughters: a Scandinavian population-based study

The in utero origins of breast cancer are an increasing focus of research. However, the long time period between exposure and disease diagnosis, and the lack of standardized perinatal data collection makes this research challenging. We assessed perinatal factors, as proxies for in utero exposures, and breast cancer risk using pooled, population-based birth and cancer registry data. Birth registries provided information on perinatal exposures. Cases were females born in Norway, Sweden or Denmark who were subsequently diagnosed with primary, invasive breast cancer (n = 1419). Ten controls for each case were selected from the birth registries matched on country and birth year (n = 14,190). Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using unconditional regression models. Breast cancer risk rose 7% (95% CI 2-13%) with every 500 g (roughly 1 s.d.) increase in birth weight and 7% for every 1 s.d. increase in birth length (95% CI 1-14%). The association with birth length was attenuated after adjustment for birth weight, while the increase in risk with birth weight remained with adjustment for birth length. Ponderal index and small- and large-for-gestational-age status were not better predictors of risk than either weight or length alone. Risk was not associated with maternal education or age, gestational duration, delivery type or birth order, or with several pregnancy complications, including preeclampsia. These data confirm the positive association between birth weight and breast cancer risk. Other pregnancy characteristics, including complications such as preeclampsia, do not appear to be involved in later breast carcinogenesis in young women.