Risk and Outcome of Venous and Arterial Thrombosis in Patients With Cirrhosis: A Danish Nation-wide Cohort Study.

BACKGROUND AND AIMS: Cirrhosis affects hemostasis, but its effects across the spectrum of thromboses remain poorly understood. We examined risks and outcomes of venous and arterial thrombosis. APPROACH AND RESULTS: We used nation-wide Danish health care registries to identify outpatients with cirrhosis and a sex- and age-matched comparison cohort without cirrhosis from the general population. Patients with cirrhosis and comparators were followed until they had a venous thromboembolism (VTE), acute myocardial infarction (AMI), or ischemic stroke (IS) or died. We computed absolute risks and HRs of thrombosis and compared outcomes after thrombosis. We included 5,854 patients with cirrhosis (median Model for End-Stage Liver Disease score, 9; interquartile range, 7-13), and their risk of any of the thrombotic events was 0.8% after 1 year and 6.3% after 10 years. They were more likely than the 23,870 matched comparators to have a VTE (adjusted hazard ratio [aHR], 2.0; 95% CI, 1.5-2.6) or IS (aHR, 1.7; 95% CI, 1.3-2.3), but not AMI (aHR, 0.7; 95% CI, 0.5-0.9). Among patients with cirrhosis, decompensation increased the risk of AMI, but not the other thromboses. Following thrombosis, patients with cirrhosis had higher 90-day mortality than comparators (after VTE: 17% vs. 7%; after AMI: 27% vs. 5%; after IS: 10% vs. 7%) and were less likely to receive antithrombotic treatment. CONCLUSIONS: Patients with cirrhosis had an increased risk of VTE and IS, but not AMI. Among patients with cirrhosis, decompensation increased the risk of AMI, exclusively. Mortality after thrombosis was higher in patients with cirrhosis than in other patients. These findings are relevant for decisions about antithrombotic prophylaxis in patients with cirrhosis.

Risk Factors for Hepatic Hydrothorax in Cirrhosis Patients with Ascites - A Clinical Cohort Study.

BACKGROUND: The risk factors for hepatic hydrothorax are unknown. METHODS: We used data from three randomized trials of satavaptan treatment in patients with cirrhosis and ascites followed for up to 1 year. We excluded patients with previous hepatic hydrothorax or other causes for pleural effusion. The candidate risk factors were age, sex, heart rate, mean arterial pressure, diuretic-resistant ascites, a recurrent need for paracentesis, diabetes, hepatic encephalopathy, International Normalized Ratio, creatinine, bilirubin, albumin, sodium, platelet count, use of non-selective beta-blockers (NSBBs), spironolactone, furosemide, proton pump inhibitors, and insulin. We identified risk factors using a Fine and Gray regression model and backward selection. We reported subdistribution hazard ratios (sHR) for hepatic hydrothorax. Death without hepatic hydrothorax was a competing risk. RESULTS: Our study included 942 patients, of whom 41 developed hepatic hydrothorax and 65 died without having developed it. A recurrent need for paracentesis (sHR: 2.55, 95% CI: 1.28-5.08), bilirubin (sHR: 1.18 per 10 µmol/l increase, 95% CI: 1.09-1.28), diabetes (sHR: 2.49, 95% CI: 1.30-4.77) and non-use of non-selective beta-blockers (sHR: 2.27, 95% CI: 1.13-4.53) were risk factors for hepatic hydrothorax. Development of hepatic hydrothorax was associated with a high mortality-hazard ratio of 4.35 (95% CI: 2.76-6.97). CONCLUSIONS: In patients with cirrhosis and ascites, risk factors for hepatic hydrothorax were a recurrent need for paracentesis, a high bilirubin, diabetes and non-use of NSBBs. Among these patients with cirrhosis and ascites, development of hepatic hydrothorax increased mortality fourfold.

Spontaneous bacterial peritonitis has no effect on the long-term prognosis of cirrhosis patients with ascites.

INTRODUCTION AND OBJECTIVES: Spontaneous bacterial peritonitis (SBP) is a frequent complication to cirrhosis with an unclear long-term prognosis. We aimed to examine its effect on mortality in two independent patient cohorts. PATIENTS AND METHODS: We used Danish healthcare data on cirrhosis patients with a first-time paracentesis in 2000-2014 and data from three randomized controlled trials on satavaptan treatment of ascites conducted in 2006-2008. We used the Kaplan-Meier method to estimate cumulative mortality, and Cox regression to compare the confounder-adjusted mortality hazard for patients with vs. without SBP. RESULTS: In the Danish Healthcare Cohort, we included 1.282 patients of whom 133 (10.4%) had SBP. The SBP patients' cumulative 4-month mortality was 51.2% (95% CI: 43.0-59.9%) vs. 34.7% (95% CI: 32.0-37.6) in those without SBP. The SBP patients' confounder-adjusted mortality hazard was 1.54-fold higher (95% CI: 1.18-2.00) in the four months after paracentesis, but was not increased thereafter (confounder-adjusted mortality hazard 1.02, 95% 0.72-1.46). In the satavaptan trial data of 1,198 cirrhosis patients with ascites, the 93 patients with SBP had a cumulative 4-month mortality of 38.6% (95% CI: 29.3-49.7) compared with 11.4% (95% CI: 8.5-15.2) in those without. The SBP patients' confounder-adjusted mortality hazard ratio was 3.86 (95% CI: 2.44-6.12) during the first four months, and was 1.23 (95% CI: 0.54-2.83) thereafter. CONCLUSIONS: In both cohorts of patients with cirrhosis, an SBP episode had a high short-term mortality compared to patients without SBP, and had no lasting effect on the long-term mortality.

Time-dependent incidence and risk for myocardial infarction in patients with alcoholic cirrhosis.

BACKGROUND: It remains unsettled whether alcoholic cirrhosis is a risk factor for myocardial infarction (MI). METHODS: We used data from nationwide healthcare registries to study all Danes diagnosed with alcoholic cirrhosis in 1996-2014, and five controls were matched to each of them on gender and age. We excluded everyone with ischaemic heart disease and used Cox regression to estimate the incidence rate ratio of MI adjusted for potential cardiovascular confounders. Further, we described the MI-risk with non-MI death as a competing risk. RESULTS: We included 22 867 patients (67% men) with a median age of 57 years. During the first year of follow-up, their incidence rate ratio of MI was increased to 1.24 (95% CI: 0.94-1.62), driven by the effect among women (2.13, 95% CI: 1.17-3.87) and those with most severe cirrhosis (1.32, 95% CI: 0.91-1.90). After the first year, the overall incidence rate ratio fell to (0.89, 95% CI: 0.76-1.05). Patients were more likely to die from non-MI causes (33.7% vs 1.0%), which protected them against MI. The overall 1-year MI-risk was similar in patients and controls: 0.38% (95% CI: 0.30-0.47%) vs 0.34% (95% CI: 0.31-0.38%). After five years of follow-up, male patients had lower MI-risk than their controls, whereas women with cirrhosis had an increased MI-risk throughout follow-up. CONCLUSIONS: The incidence rate of MI was increased the first year following a diagnosis of alcoholic cirrhosis, in particular in women and those with most severe liver disease. Due to the competing risk of non-MI mortality, the MI-risk was not increased.

Hip fracture risk in patients with alcoholic cirrhosis: A population-based study using English and Danish data.

BACKGROUND & AIMS: Cirrhosis, the prevalence of which is increasing, is a risk factor for osteoporosis and fractures. However, little is known of the actual risk of hip fractures in patients with alcoholic cirrhosis. Using linked primary and secondary care data from the English and Danish nationwide registries, we quantified the hip fracture risk in two national cohorts of patients with alcoholic cirrhosis. METHODS: We followed 3,706 English and 17,779 Danish patients with a diagnosis of alcoholic cirrhosis, and we identified matched controls from the general populations. We estimated hazard ratios (HR) of hip fracture for patients vs. controls, adjusted for age, sex and comorbidity. RESULTS: The five-year hip fracture risk was raised both in England (2.9% vs. 0.8% for controls) and Denmark (4.6% vs. 0.9% for controls). With confounder adjustment, patients with cirrhosis had fivefold (adjusted HR 5.5; 95% CI 4.3-6.9), and 8.5-fold (adjusted HR 8.5; 95% CI 7.8-9.3) increased rates of hip fracture, in England and Denmark, respectively. This association between alcoholic cirrhosis and risk of hip fracture showed significant interaction with age (p <0.001), being stronger in younger age groups (under 45 years, HR 17.9 and 16.6 for English and Danish patients, respectively) than in patients over 75 years (HR 2.1 and 2.9, respectively). In patients with alcoholic cirrhosis, 30-day mortality following a hip fracture was 11.1% in England and 10.0% in Denmark, giving age-adjusted post-fracture mortality rate ratios of 2.8(95% CI 1.9-3.9) and 2.0(95% CI 1.5-2.7), respectively. CONCLUSIONS: Patients with alcoholic cirrhosis have a markedly increased risk of hip fracture and post-hip fracture mortality compared with the general population. These findings support the need for more effort towards fracture prevention in this population, to benefit individuals and reduce the societal burden. LAY SUMMARY: Alcoholic cirrhosis creates a large public health burden and is a risk factor for bone fractures. Based on data from England and Denmark, we found that hip fractures occur more than five times more frequently in people with alcoholic cirrhosis than in people without the disease. Additionally, the aftermath of the hip fracture is severe, such that up to 11% of patients with alcoholic cirrhosis die within 30 days after their hip fracture. These results suggest that efforts directed towards fracture prevention in people with alcoholic cirrhosis could be beneficial.

Risk for alcoholic liver cirrhosis after an initial hospital contact with alcohol problems: A nationwide prospective cohort study.

Alcoholic liver cirrhosis is usually preceded by many years of heavy drinking, in which cessation in drinking could prevent the disease. Alcohol problems are not consistently managed in hospital patients. We followed all Danish patients with an initial hospital contact with alcohol problems (intoxication, harmful use, or dependence) during 1998-2002 for alcoholic liver cirrhosis development (n = 36,044). In this registry-based cohort, we identified predictors of the absolute risk for alcoholic liver cirrhosis. Incidence rate ratios (IRRs) were estimated as the incidence rate of alcoholic liver cirrhosis in these patients relative to the general population. Age and alcohol diagnosis were significant predictors of alcoholic liver cirrhosis risk in men and women, whereas civil status, education, and type of hospital care were not. In men, the 15-year absolute risk was 0.7% (95% confidence interval [CI], 0.4, 0.8) for 20-29 years, 5.5% (95% CI, 4.9, 6.2) for 30-39 years, 9.8% (95% CI, 9.0, 11) for 40-49 years, 8.9% (95% CI, 8.1, 9.8) for 50-59 years, 6.2% (95% CI, 5.1, 7.2) for 60-69 years, and 2.5% (95% CI, 1.7, 3.3) for 70-84 years. According to alcohol diagnosis in men, the 15-year absolute risk was 2.6% (95% CI, 2.3, 2.9) for intoxication, 7.7% (95% CI, 6.4, 7.9) for harmful use, and 8.8% (95% CI, 8.2, 9.4) for dependence. The IRR for alcoholic liver cirrhosis in the cohort relative to the general population was 11 (95% CI, 10, 12) in men and 18 (95% CI, 15, 21) in women. CONCLUSION: Hospital patients with alcohol problems had a much greater risk for alcoholic liver cirrhosis compared to the general population. The risk was particularly increased for patients 40-59 years and for patients diagnosed with harmful use or dependence. (Hepatology 2017;65:929-937).

Decreasing Mortality Among Danish Alcoholic Cirrhosis Patients: A Nationwide Cohort Study.

OBJECTIVES: Clinical management of certain cirrhosis complications has improved over the last two decades. In this study we aimed to examine whether mortality among Danish alcoholic cirrhosis patients has decreased during this period. METHODS: In this historical cohort study we used nationwide hospital data to identify Danish alcoholic cirrhosis patients diagnosed in 1996-1998, 1999-2001, 2002-2004, 2005-2007, 2008-2010, and 2011-2013. We used Cox regression to examine time trends in mortality after cirrhosis diagnosis, adjusting for confounding by age, gender, and prevalence of variceal bleeding, ascites, hepatorenal syndrome, alcoholic hepatitis, infection, hepatocellular carcinoma, comorbidity, and in-patient status at the time of cirrhosis diagnosis. RESULTS: We included 22,734 patients (69% men). The adjusted mortality hazard ratio (HR) for patients diagnosed in each period compared with those diagnosed in 1996-1998 was 0.99 (95% confidence interval (CI): 0.92-1.06) in 1999-2001, 1.00 (95% CI: 0.94-1.08) in 2002-2004, 0.97 (95% CI: 0.90-1.04) in 2005-2007, 0.94 (95% CI: 0.88-1.01) in 2008-2010, and finally 0.84 (95% CI: 0.79-0.90) in 2011-2013. CONCLUSIONS: In recent years, mortality among Danish alcoholic cirrhosis patients has decreased.

Cirrhosis is a risk factor for total hip arthroplasty for avascular necrosis.

Background and purpose - There are limited data on risk factors for avascular necrosis of the hip, but cirrhosis has been proposed as a risk factor. We examined the association between cirrhosis and incidence of total hip arthroplasty for avascular necrosis. Methods - We used nationwide healthcare data to identify all Danish residents diagnosed with cirrhosis in 1994-2011, and matched them 1:5 by age and sex to non-cirrhotic reference individuals from the general population. We excluded people with a previous total hip arthroplasty, a previous hip fracture, or a previous diagnosis of avascular necrosis. We used stratified Cox regression to estimate the hazard ratio (HR) for cirrhosis patients relative to reference individuals, adjusting for potential confounders. We used the cumulative incidence function to compute 5-year risks. Results - We included 25,421 cirrhosis patients and 114,052 reference individuals. Their median age was 57 years, and 65% were men. 45 cirrhosis patients and 44 reference individuals underwent total hip arthroplasty for avascular necrosis. Cirrhosis patients' HR for a total hip arthroplasty for avascular necrosis was 10 (95% CI: 6-17), yet their 5-year risk of avascular necrosis was only 0.2%. For the reference individuals, the 5-year risk was 0.02%. Interpretation - Cirrhosis is a strong risk factor for avascular necrosis of the hip, but it is rare even in cirrhosis patients.

Epidemiology of alcoholic liver disease in Denmark 2006-2011: a population-based study.

AIMS: To describe incidence, prevalence, hospitalization rates and survival for alcoholic liver disease (ALD) in Denmark 2006-2011. METHODS: Using nationwide healthcare registries we identified all Danish residents with a hospital diagnosis of ALD and computed standardized incidence, prevalence, and hospitalization rates in 2006-2011, age- and birth cohort-specific incidence for the 1930-1974 birth cohorts, and 1- and 5-year survival. RESULTS: In 2006-2011, the overall standardized ALD incidence decreased from 343 to 311 per 1,000,000 population per year. ALD incidence increased among women aged 65 years or older, but decreased in younger persons and men. Persons born in 1950-1959 had higher age-specific incidence than earlier and later birth cohorts. The prevalence (0.2% of the Danish adult population) and hospitalization rate were constant. The 1- and 5-year survival were 43 and 70%, respectively. CONCLUSION: In Denmark, persons born in 1950-1959 have had the highest age-specific incidence. The overall ALD incidence has been decreasing (along with per capita consumption). Despite increases in affordability during the study period, Denmark did not experience the increase in ALD seen, for example, in the UK. It is possible that this is due to the greater impact of government recommendations on safer drinking in Denmark than the UK.

Cirrhosis patients have increased risk of complications after hip or knee arthroplasty.

BACKGROUND AND PURPOSE: The risk of complications in cirrhosis patients after orthopedic surgery is unclear. We examined this risk after total hip arthroplasty (THA) or total knee arthroplasty (TKA). PATIENTS AND METHODS: Using Danish healthcare registries, we identified all Danish residents who underwent a THA or TKA for primary osteoarthritis in the period 1995-2011. We compared the risk of complications in patients with or without cirrhosis. RESULTS: The surgical technique was similar in the 363 cirrhosis patients and in 109,159 reference patients, but cirrhosis patients were more likely to have been under general anesthesia (34% vs. 23%), were younger (median age 66 vs. 69 years), had a predominance of males (54% vs. 41%), had more comorbidity, and had had more hospitalizations preoperatively. Their risk of intraoperative complications was similar to that for reference patients (2.5% vs. 2.0%), but they had greater risk of dying during hospitalization or within 30 days of discharge (1.4% vs. 0.4%; aOR = 3.9, 95% CI: 1.5-10); greater risk of postoperative transfer to an intensive care unit (0.6% vs. 0.06%; aOR = 5.8, CI: 1.3-25) or a medical department (4.4% vs. 2.5%; aOR = 1.7, CI: 0.99-2.9); greater risk of readmission within 30 days of discharge (15% vs. 8%; aOR = 1.8, CI: 1.3-2.4); and greater risk of deep prosthetic infection (3.1% vs. 1.4%) or revision (3.7% vs. 1.7%) within 1 year. The chance of having an uncomplicated procedure was 81.0% (CI: 76.6-85.0) for cirrhosis patients and 90.0% (CI: 89.6-90.0) for reference patients. INTERPRETATION: Cirrhosis patients had a higher risk of postoperative complications after THA or TKA for primary osteoarthritis than patients without cirrhosis. This may have implications for orthopedic surgeons' postoperative management of cirrhosis patients, and preoperative assessment by a hepatologist may be indicated.

A rare Danish case of Yersinia pseudotuberculosis pyogenic liver abscess.

Yersinia pseudotuberculosis is a rare Gram-negative bacillus that cause enterocolitis and terminal ileitis. We report the first Danish case with Y. pseudotuberculosis multiple pyogenic liver abscess presenting with 6 weeks intermittently fever, fatigue, and weight loss. The patient was successfully treated with percutaneous drainage and intravenous piperacillin/tazobactam and oral ciprofloxacin.

Decreasing Incidence of Alcohol-Related Liver Disease in Denmark: A 25-Year Nationwide Study.

PURPOSE: Alcohol consumption has decreased in Denmark in recent years. We aimed to illustrate and investigate the developments in the incidence, hospital care, and mortality of alcohol-related liver disease (ALD) in Denmark during the last 25 years. PATIENTS AND METHODS: Through nationwide healthcare registries, we identified all Danish patients with incident ALD in 1994-2018. We computed standardized incidence rates by sex, age, and geography, age-specific incidence rates by birth cohort, and standardized prevalence. We enumerated inpatient admissions, days of admission, outpatient visits, and emergency room visits. Lastly, we estimated relative risks of mortality, standardized mortality rates, and the proportion of deaths caused by ALD. RESULTS: The standardized incidence rate decreased from its peak at 357 per 1,000,000 in 2009 to 240 per 1,000,000 in 2018, and the decrease was evident for both sexes and all age groups below 70 years. The standardized prevalence was stable around 0.22% from 2011 onwards. There was an almost fivefold geographic variation in standardized incidence by municipalities, and age-specific incidence rates decreased sequentially with each 5-year birth cohort after 1960. The number of inpatient admissions, days of admission, and emergency room visits decreased during the study period, while the number of outpatient visits was stable. For patients diagnosed in 2014-2018 compared to 1994-1998, the relative risk of 1-year mortality was 0.83 (95% confidence interval: 0.78-0.87), and the standardized mortality along with the proportion of deaths caused by ALD decreased during the study period. CONCLUSION: The incidence of ALD decreased from 357 to 240 per 1,000,000 over the last 10 years in Denmark. During the same period, the prevalence remained stable around 0.22% and mortality decreased. Additionally, the burden of ALD on hospital care decreased significantly between 1994 and 2018. We anticipate a further decrease in the incidence of ALD in the future.

Hospital admissions and mortality in the 15 years after a first-time hospital contact with an alcohol problem: a prospective cohort study using the entire Danish population.

BACKGROUND: Potential benefits of preventing continued alcohol intake in individuals presenting at the hospital with an alcohol problem can be highlighted by studying their excess risk of subsequent morbidity and mortality. METHODS: All Danish residents with a first-time hospital contact with alcohol problems (intoxication, harmful use or dependence) in 1998-2002 were followed through 2012 using healthcare registries. We compared their cause-specific rates of hospital admission and mortality to the expected rates derived from the general population by calculating standardized incidence rate ratios. RESULTS: The 26 716 men and 12 169 women who were hospitalized with alcohol problems (median age 44 years) had more than 10 times the rate of subsequent admission to psychiatric departments and three times the rate of subsequent admission to somatic departments compared with the general population. In particular, the hospital admission rates for gastroenterological disease and injuries were high. The cumulative all-cause 10-year mortality risk was 29% [95% confidence interval (CI), 28-30] in men and 26% (95% CI, 24-27) in women with alcohol problems. The ratios of observed to expected death rate for all-cause mortality were 4.0 (95% CI, 3.8-4.1) in men and 4.3 (95% CI, 4.0-4.7) in women and, for causes of death fully attributable to alcohol, 16 (95% CI, 15-17) in men and 33 (95% CI, 29-38) in women. CONCLUSIONS: Individuals hospitalized with alcohol problems have much higher rates of subsequent alcohol-related hospital admission and mortality than the general population. Increased focus on preventing continued alcohol consumption in these individuals may reduce their subsequent morbidity and mortality.

No Increased Risk for Primary Osteoarthritis in Liver Cirrhosis - A Danish Nationwide Cohort Study.

OBJECTIVE: Chronic synovial inflammation causes primary osteoarthritis, but it is unknown whether chronic systemic inflammation does, too. Patients with cirrhosis have chronic systemic inflammation and therefore we examined the association between cirrhosis and primary osteoarthritis of the hip and knee. METHODS: In Danish healthcare databases we identified all residents over 60 years diagnosed with cirrhosis in 1994-2011, and for each of them we sampled five age- and gender-matched reference persons from the general population. We excluded everyone with risk factors for secondary osteoarthritis and computed incidence rates of primary osteoarthritis of the hip or knee. We used stratified Cox regression to estimate the hazard ratios of primary osteoarthritis for cirrhosis patients vs. reference persons in strata defined by gender, age, cirrhosis etiology, and ascites vs. no ascites. We also computed separate HRs for primary osteoarthritis of the hips or knees. RESULTS: We identified 10,049 cirrhosis patients. Their median age was 67 years, and 65% were men. Among the cirrhosis patients the crude incidence rate of primary osteoarthritis was 8.40 (95% CI: 7.30-9.63) per 1000 person-years. The rate was similar in the reference persons: 8.76 (95% CI: 8.43-9.12) per 1000 person-years. Accordingly, the hazard ratio for primary osteoarthritis for cirrhosis patients vs. reference persons was 0.99 (95% CI: 0.85-1.16), and we found the same null association in all patient strata and in both joints. CONCLUSION: Cirrhosis, and thus chronic systemic inflammation, is not a risk factor for primary osteoarthritis.

Comorbidity and survival of Danish lung cancer patients from 2000-2011: a population-based cohort study.

OBJECTIVE: To examine lung cancer survival and the impact of comorbidity in the Central Denmark Region from 2000 to 2011. METHODS: We performed a population-based cohort study of lung cancer patients diagnosed during four 3-year calendar periods (2000-2002, 2003-2005, 2006-2008, and 2009-2011) in the Central Denmark Region. The Danish National Registry of Patients was used to identify 9,369 incident lung cancer patients, and to obtain data on their Charlson comorbidity index score, categorized as no (score = 0), medium (score = 1-2), or high (score ≥3) level comorbidity. We calculated 1- and 5-year survival in different calendar time periods overall, and by age, sex, and level of comorbidity, and used Cox regression to compute mortality rate ratios (MRR) for each level of comorbidity versus no comorbidity in different calendar time periods. RESULTS: Overall 1-year survival increased from 31% in 2000-2002 to 37% in 2009-2011, while the 5-year survival increased from 10% in 2000-2002 to predicted 13% in 2009-2011 with the largest improvement observed for women and patients less than 80 years. The adjusted 1-year MRR in patients with high comorbidity compared with those without comorbidity was 1.23 (95% confidence interval [CI]: 1.05-1.46) in 2000-2002 and 1.35 (95% CI: 1.17-1.56) in 2009-2011. The corresponding adjusted 5-year MRRs were 1.21 (95% CI: 1.04-1.40) in 2000-2002 and 1.26 (95% CI: 1.11-1.42) in 2009-2011. CONCLUSION: Lung cancer patients' survival increased from 2000 to 2011 in the Central Denmark Region, most prominently for women under 80 years and patients with no, or medium level of comorbidity. Their prognosis remained nonetheless dismal with overall 5-year survival of 13%, and comorbidity remained a negative prognostic factor.

Validity of the Danish National Registry of Patients for chemotherapy reporting among colorectal cancer patients is high.

BACKGROUND: The Danish National Registry of Patients (DNRP) is a potentially valuable resource for monitoring national trends in the use of chemotherapy and evaluating the benefits and harms of alternative treatments among colorectal cancer (CRC) patients in Denmark. However, the validity of chemotherapy reporting in the DNRP is unknown. In this study, we evaluated the validity of the DNRP for identifying the receipt of chemotherapy and specific treatments, and the timing and number of treatments among CRC patients, using medical records and pharmacy data as the reference standard. METHODS: We selected a random sample of CRC patients with lymph node involvement who were diagnosed at Aarhus University Hospital (n = 25) or Aalborg University Hospital (n = 25) from 2009 to 2010. Administration dates, specific treatments, and number of treatment courses were abstracted for the 180 days post diagnosis from the DNRP, medical records, and pharmacy production databases. The prevalence of chemotherapy, timing of first administration, and number of courses were described. DNRP data were compared with the reference standard for each hospital, and the kappa, sensitivity, specificity, positive and negative predictive values, and 95% confidence intervals were calculated for the receipt of any chemotherapy and specific treatments. RESULTS: The prevalence of chemotherapy was 72% and 68% among CRC patients treated in Aarhus and Aalborg, respectively, with >90% of patients without distant metastasis receiving treatment within 90 days from diagnosis. Patients received on average 4.6 and 4.7 treatment courses in Aarhus and Aalborg, respectively. Kappa, sensitivity, and specificity of chemotherapy reporting in the DNRP was high (≥0.88), but the sensitivity of individual chemotherapies varied by hospital. CONCLUSION: The validity of chemotherapy reporting in the DNRP was high, although some variation by hospital exists. The DNRP represents a population-based nationwide resource that can be used to provide timely and accurate evaluations of chemotherapy use among CRC patients in Denmark.

Completeness of TNM staging of small-cell and non-small-cell lung cancer in the Danish cancer registry, 2004-2009.

OBJECTIVE: We examined the completeness of TNM staging of small-cell (SCLC) and nonsmall- cell (NSCLC) lung cancer in the national Danish Cancer Registry (DCR) and whether staging varied by year of diagnosis, gender, age, degree of comorbidity, or presence of histopathological diagnosis. METHODS: We identified all patients with SCLCs and NSCLCs registered in the DCR during 2004-2009 and examined the completeness of their TNM registrations. Completeness was defined as the number of recorded individuals with TNM divided by the total number of patients. Completeness was calculated for TNM, T, N, and M individually, overall, and by year of diagnosis, gender, age at diagnosis, and comorbidity. Data regarding comorbidity was obtained from the Danish National Patient Register (DNPR). We performed separate analyses for patients with a histopathologically verified diagnosis of NSCLC. Finally, we designed an algorithm to categorize tumors with missing TNM components as limited, extensive, or distant disease. RESULTS: Overall TNM staging completeness was 77.5% (95% confidence interval (CI): 76.1%-78.8%) for SCLC and 77.9% (95% CI: 77.3%-78.4%) for NSCLC. Completeness did not vary by gender and increased during the study period. The proportion of staged patients was lower among patients above 80 years of age or with medium to high levels of comorbidity. CONCLUSION: Overall TNM completeness for SCLC and NSCLC in the Danish Cancer Registry is high, but decreases with increasing levels of comorbidity and at ages greater than 80 years. Researchers should be aware of these potential sources of bias.

Support for a bipolar affective disorder susceptibility locus on chromosome 12q24.3.

OBJECTIVE: Linkage and association studies of bipolar affective disorder (BAD) point out chromosome 12q24 as a region of interest. METHODS: To investigate this region further, we conducted an association study of 22 DNA markers within a 1.14 Mb region in a Danish sample of 166 patients with BAD and 311 control individuals. Two-hundred and four Danish patients with schizophrenia were also included in the study. RESULTS: We observed highly significant allelic and genotypic association between BAD and two highly correlated markers. The risk allele of both markers considered separately conferred an odds ratio of 2 to an individual carrying one risk allele and an odds ratio of 4 for individuals carrying both risk alleles assuming an additive genetic model. These findings were supported by the haplotype analysis. In addition, we obtained a replication of four markers associated with BAD in an earlier UK study. The most significantly associated marker was also analyzed in a Scottish case-control sample and was earlier associated with BAD in the UK cohort. The association of that particular marker was strongly associated with BAD in a meta-analysis of the Danish, Scottish and UK sample (P=0.0003). The chromosome region confined by our most distant markers is gene-poor and harbours only a few predicted genes. This study implicates the Slynar locus. We confirmed one annotated Slynar transcript and identified a novel transcript in human brain cDNA. CONCLUSION: This study confirms 12q24.3 as a region of functional importance in the pathogenesis of BAD and highlights the importance of focused genotyping.