Treatment patterns, survival, and healthcare utilisation and costs in patients with locally advanced and metastatic bladder cancer in Denmark 2015-2020.

BACKGROUND: Treatment patterns in locally advanced and metastatic urothelial bladder cancer (La/mUBC) is changing, but little is known about current treatment patterns, survival, and costs of these patients. Our aim was to describe treatment patterns, survival, and healthcare utilisation/costs in Danish La/mUBC patients in a routine clinical care setting. METHODS: Registry-based nationwide cohort study including all bladder cancer patients aged 18 years or older with a La/mUBC tumour in the pathology register and a concomitant bladder cancer diagnosis in the Danish National Patient Registry in the period 2015-2020. We categorised the patients according to (1) La/mUBC at time of first bladder cancer diagnosis (de novo La/mUBC) and (2) non-invasive or localised muscle-invasive bladder cancer at time of diagnosis which had progressed to La/mUBC. All patients were included at date of pathology-confirmed La/mUBC. Follow-up ended 30 September 2022. RESULTS: We identified 1278 patients (69% men) with La/mUBC and no other previous cancer. Of these, 212 (17%) had de novo La/mUBC, while 1066 (83%) had progressed to La/mUBC. Median age was 72 years. Patients were followed for a median of 13.0 months (interquartile range 4.7;32.0). During follow-up, 651 (51%) patients started first-line treatment, of these, 285 progressed to second-line treatment, and 112 also started third-line treatment. Median survival was 13.0 months from La/mUBC diagnosis, 12.1 months from start of first-line treatment, 9.8 months from start of second-line treatment, and 8.6 months from start of third-line treatment. The mean number of days admitted to hospital was 3.47, 3.97, and 4.07 per month following initiation of first-line, second-line, and third-line treatment, respectively. CONCLUSION: Patients with La/mUBC have a poor prognosis, and in routine clinical care only around half of the patients received systemic anti-cancer treatment suggesting an unmet need for novel treatments. The overall costs only increased slightly from first to third-line treatment.

Cost of non-communicable diseases in people living with HIV in the Central Denmark Region.

OBJECTIVE: To estimate the economic burden of non-communicable diseases (NCDs) in people living with HIV (PLWH) in Denmark. METHODS: We conducted a cohort study using population-based Danish medical registries including all adult residents of the Central Denmark Region registered with a first-time HIV-diagnosis during the period 2006-2017. For each PLWH, we matched 10 persons without HIV from the background population by birth year, sex and municipality of residence. Information on healthcare utilization and costs for the PLWH and non-HIV cohorts was retrieved from register data. For each cohort, we estimated the annual costs for major disease categories (HIV care, other somatic care, and psychiatric care) in the period from 3 years before to 9 years after diagnosis/matching date. RESULTS: We identified 407 PLWH and 4070 persons from the background population. The total healthcare costs during the study period were approximately three times higher for PLWH compared to the non-HIV cohort (€76 198 vs. €23 692). Average annual cost of hospital care, primary care and selected prescription medicine was estimated to be €6987 per year in the years after the diagnosis compared to €2083 per year in the non-HIV cohort. In PLWH, the cost of NCDs and psychiatric care was approximately two times higher than the cost of HIV care. CONCLUSION: PLWH have higher healthcare costs stemming from three areas: excess cost due to the HIV infection, the treatment of NCDs, and psychiatric care.

Prognostic and discriminative accuracy of the quick Sepsis-related Organ Failure Assessment compared with an early warning score: a Danish cohort study.

BACKGROUND: The clinical benefit of implementing the quick Sepsis-related Organ Failure Assessment (qSOFA) instead of early warning scores (EWS) to screen all hospitalised patients for critical illness has yet to be investigated in a large, multicentre study. METHODS: We conducted a cohort study including all hospitalised patients ≥18 years with EWS recorded at hospitals in the Central Denmark Region during the year 2016. The primary outcome was intensive care unit (ICU) admission and/or death within 2 days following an initial EWS. Prognostic accuracy was examined using sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). Discriminative accuracy was examined by the area under the receiver operating characteristic curve (AUROC). RESULTS: Among 97 332 evaluated patients, 1714 (1.8%) experienced the primary outcome. The qSOFA ≥2 was less sensitive (11.7% (95% CI: 10.2% to 13.3%) vs 25.1% (95% CI: 23.1% to 27.3%)) and more specific (99.3% (95% CI: 99.2% to 99.3%) vs 97.5% (95% CI: 97.4% to 97.6%)) than EWS ≥5. The NPV was similar for the two scores (EWS ≥5, 98.6% (95% CI: 98.6% to 98.7%) and qSOFA ≥2, 98.4% (95% CI: 98.3% to 98.5%)), while the PPV was 15.1% (95% CI: 13.8% to 16.5%) for EWS ≥5 and 22.4% (95% CI: 19.7% to 25.3%) for qSOFA ≥2. The AUROC was 0.72 (95% CI: 0.70 to 0.73) for EWS and 0.66 (95% CI: 0.65 to 0.67) for qSOFA. CONCLUSION: The qSOFA was less sensitive (qSOFA ≥2 vs EWS ≥5) and discriminatively accurate than the EWS for predicting ICU admission and/or death within 2 days after an initial EWS. This study did not support replacing EWS with qSOFA in all hospitalised patients.

ß-Blocker Use in Pregnancy and the Risk for Congenital Malformations: An International Cohort Study.

Background: ß-Blockers are a class of antihypertensive medications that are commonly used in pregnancy. Objective: To estimate the risks for major congenital malformations associated with first-trimester exposure to ß-blockers. Design: Cohort study. Setting: Health registries in the 5 Nordic countries and the U.S. Medicaid database. Patients: Pregnant women with a diagnosis of hypertension and their offspring. Measurements: First-trimester exposure to ß-blockers was assessed. Outcomes were any major congenital malformation, cardiac malformations, cleft lip or palate, and central nervous system (CNS) malformations. Propensity score stratification was used to control for potential confounders. Results: Of 3577 women with hypertensive pregnancies in the Nordic cohort and 14 900 in the U.S. cohort, 682 (19.1%) and 1668 (11.2%), respectively, were exposed to ß-blockers in the first trimester. The pooled adjusted relative risk (RR) and risk difference per 1000 persons exposed (RD1000) associated with ß-blockers were 1.07 (95% CI, 0.89 to 1.30) and 3.0 (CI, -6.6 to 12.6), respectively, for any major malformation; 1.12 (CI, 0.83 to 1.51) and 2.1 (CI, -4.3 to 8.4) for any cardiac malformation; and 1.97 (CI, 0.74 to 5.25) and 1.0 (CI, -0.9 to 3.0) for cleft lip or palate. For CNS malformations, the adjusted RR was 1.37 (CI, 0.58 to 3.25) and the RD1000 was 1.0 (CI, -2.0 to 4.0) (based on U.S. cohort data only). Limitation: Analysis was restricted to live births, exposure was based on dispensed medication, and cleft lip or palate and CNS malformations had few outcomes. Conclusion: The results suggest that maternal use of ß-blockers in the first trimester is not associated with a large increase in the risk for overall malformations or cardiac malformations, independent of measured confounders. Primary Funding Source: The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Söderström König Foundation.

Effects of Education and Income on Treatment and Outcome in Patients With Acute Myeloid Leukemia in a Tax-Supported Health Care System: A National Population-Based Cohort Study.

Purpose Previous US studies have shown that socioeconomic status (SES) affects survival in acute myeloid leukemia (AML). However, no large study has investigated the association between education or income and clinical characteristics, treatment, and outcome in AML. Methods To investigate the effects of education and income in a tax-supported health care system, we conducted a population-based study using individual-level SES and clinical data on all Danish patients with AML (2000 to 2014). We compared treatment intensity, allogeneic transplantation, and response rates by education and income level using logistic regression (odds ratios). We used Cox regression (hazard ratios [HRs]) to compare survival, adjusting for age, sex, SES, and clinical prognostic markers. Results Of 2,992 patients, 1,588 (53.1%) received intensive chemotherapy. Compared with low-education patients, highly educated patients more often received allogeneic transplantation (16.3% v 8.7%). In intensively treated patients younger than 60 years of age, increased mortality was observed in those with lower and medium education (1-year survival, 66.7%; adjusted HR, 1.47; 95% CI, 1.11 to 1.93; and 1-year survival, 67.6%; adjusted HR, 1.55; CI, 1.21 to 1.98, respectively) compared with higher education (1-year survival, 76.9%). Over the study period, 5-year survival improvements were limited to high-education patients (from 39% to 58%), increasing the survival gap between groups. In older patients, low-education patients received less intensive therapy (30% v 48%; adjusted odds ratio, 0.65; CI, 0.44 to 0.98) compared with high-education patients; however, remission rates and survival were not affected in those intensively treated. Income was not associated with therapy intensity, likelihood of complete remission, or survival (high income: adjusted HR, 1.0; medium income: adjusted HR, 0.96; 95% CI, 0.82 to 1.12; low income: adjusted HR, 1.06; CI, .88 to 1.27). Conclusion In a universal health care system, education level, but not income, affects transplantation rates and survival in younger patients with AML. Importantly, recent survival improvement has exclusively benefitted highly educated patients.

No-fault compensation for treatment injuries in Danish public hospitals 2006-12.

OBJECTIVE: We aimed to determine the incidence rate and time trend of approved treatment injuries in Danish public hospitals from 2006 to 2012 and also to identify independent predictors of severe treatment injuries among patient and system factors and characterize the injuries. DESIGN AND SETTING: We performed a nationwide, historical observational study on data from the Danish Patient Compensation Association, which receives all compensation claims from Danish health care. All approved closed claims of treatment injuries occurring in public hospitals 2006-12 were included. Health care activity information was obtained through Statistics Denmark. MAIN OUTCOME MEASURES: Incidence rates were determined as treatment injuries per year by population and by public hospital contacts. By using a multivariable logistic regression model, we calculated mutually adjusted odds ratios to assess the association between potential predictors and severe injuries among approved claims. RESULTS: We identified 10,959 approved treatment injury claims in 2006-12. The total payout was USD 339 million. The mean incidence rate medians were 27.9 injuries/100,000 inhabitants/year and 0.21 injuries/1000 public hospital contacts/year. These did not increase overtime. Severe injuries and preventable cases comprised 11.0 and 41.0%, respectively. Predictors of severe injury included age 0 and above 40 years, male gender and higher level of comorbidity. CONCLUSION: The incidence rate of approved closed claims at Danish public hospitals appears stable. A high proportion of injuries are preventable and both patient- and system-related factors may predict severe injuries.

Rheumatoid Arthritis: Trends in Antirheumatic Drug Use, C-reactive Protein Levels, and Surgical Burden.

OBJECTIVE: Over the past decade, the therapeutic approach used to treat patients with rheumatoid arthritis (RA) has considerably changed. It remains unclear whether these changes have been accompanied by decreased disease severity and surgical treatment burden at the population level. Therefore, we investigated time trends in antirheumatic drug consumption, C-reactive protein (CRP) levels, and use of orthopedic surgery among Danish patients with RA. METHODS: Using medical databases, we identified all patients with RA living in Northern Denmark during 1996-2012. For each calendar year, we computed the annual rate of antirheumatic drug use (1996-2010), the median CRP value in mg/l (1996-2011), and the proportions of patients who underwent hip replacement and other orthopedic procedures (1996-2012). RESULTS: Antirheumatic drug consumption per patient increased 5-fold, from 145.0 defined daily doses (DDD) in 1996 to 695.4 DDD in 2010. Median CRP declined from 20.5 mg/l [interquartile range (IQR), 10.0 to 43.5 mg/l] in 1996 to 10.0 mg/l (IQR, 4.2-17.8 mg/l) in 2011. From 1996 to 2012, declining proportions of patients with RA underwent hip replacement (14.9% to 10.1%) and other joint operations (29.1% to 23.4%), while the annual proportion of patients who underwent soft tissue procedures increased from 20.7% to 23.4%. CONCLUSION: Antirheumatic drug consumption has substantially increased among patients with RA since 1996, in association with reduced disease activity (i.e., lower CRP levels), fewer joint procedures (including hip replacements), and more soft tissue procedures.

Compliance with hospital accreditation and patient mortality: a Danish nationwide population-based study.

OBJECTIVE: To examine the association between compliance with hospital accreditation and 30-day mortality. DESIGN: A nationwide population-based, follow-up study with data from national, public registries. SETTING: Public, non-psychiatric Danish hospitals. PARTICIPANTS: In-patients diagnosed with one of the 80 primary diagnoses. INTERVENTION: Accreditation by the first version of The Danish Healthcare Quality Programme for hospitals from 2010 to 2012. Compliance were assessed by surveyors on an on-site survey and awarded the hospital as a whole; fully (n = 11) or partially accredited (n = 20). A follow-up activity was requested for partially accredited hospitals; submitting additional documentation (n = 11) or by having a return-visit (n = 9). MAIN OUTCOME MEASURES: All-cause mortality within 30-days after admission. Multivariable logistic regression was used to compute odds ratios (ORs) for 30-day mortality adjusted for six confounding factors and for cluster effect at hospital level. RESULTS: A total of 276 980 in-patients were identified. Thirty-day mortality risk for in-patients at fully (n = 76 518) and partially accredited hospitals (n = 200 462) was 4.14% (95% confidence interval (CI):4.00-4.28) and 4.28% (95% CI: 4.20-4.37), respectively. In-patients at fully accredited hospitals had a lower risk of dying within 30-days after admission than in-patients at partially accredited hospitals (adjusted OR of 0.83; 95% CI: 0.72-0.96). A lower risk of 30-day mortality was observed among in-patients at partially accredited hospitals required to submit additional documentation compared with in-patients at partially accredited hospitals requiring a return-visit (adjusted OR 0.83; 95% CI: 0.67-1.02). CONCLUSION: Admissions at fully accredited hospitals were associated with a lower 30-day mortality risk than admissions at partially accredited hospitals.

Socioeconomic inequalities in risk of hospitalization for community-acquired bacteremia: a Danish population-based case-control study.

In a Danish population-based case-control study, we examined the association between socioeconomic status (SES) and risk of community-acquired bacteremia, as well as the contribution of chronic diseases and substance abuse to differences in bacteremia risk. Analyses were based on 4,117 patients aged 30-65 years who were hospitalized with first-time community-acquired bacteremia during 2000-2008 and 41,170 population controls matched by sex, age, and region of residence. Individual-level information on SES (education and income), chronic diseases, and substance abuse was retrieved from public and medical registries. Conditional logistic regression was used to compute odds ratios for bacteremia. Persons of low SES had a substantially higher risk of bacteremia than those of high SES (for short duration of education vs. long duration, odds ratio = 2.30 (95% confidence interval: 2.10, 2.52); for low income vs. high income, odds ratio = 2.77 (95% confidence interval: 2.54, 3.02)). A higher prevalence of chronic diseases and substance abuse in low-SES individuals versus high-SES individuals explained 43%-48% of the socioeconomic differences in bacteremia risk. In a country with a universal welfare system, differences in the burden of chronic diseases and substance abuse seem to have major importance in explaining inequalities in bacteremia risk.

Effect of socioeconomic status on mortality after bacteremia in working-age patients. A Danish population-based cohort study.

OBJECTIVES: To examine the effect of socioeconomic status (SES) on mortality in patients with bacteremia and the underlying factors that may mediate differences in mortality. METHODS: We conducted a population-based cohort study in two Danish regions. All patients 30 to 65 years of age with first time bacteremia from 2000 through 2008 were identified in a population-based microbiological bacteremia database (n = 8,653). Individual-level data on patients' SES (educational level and personal income) and comorbid conditions were obtained from public and medical registries. We used Cox regression to examine mortality within 30 days after bacteremia with and without cumulative adjustment for potential mediators. RESULTS: Bacteremia patients of low SES were more likely to live alone and be unmarried than patients of high SES. They also had more pre-existing comorbidity, more substance abuse, more Staphylococcus aureus and nosocomial infections, and more admissions to small nonteaching hospitals. Overall, 1,374 patients (15.9%) died within 30 days of follow-up. Patients of low SES had consistently higher mortality after bacteremia than those of high SES crude hazard ratio for low vs. high education, 1.38 [95% confidence interval (CI), 1.18-1.61]; crude hazard ratio for low-income vs. high-income tertile, 1.58 [CI, 1.39-1.80]. Adjustment for differences in social support, pre-existing comorbidity, substance abuse, place of acquisition of the infection, and microbial agent substantially attenuated the effect of SES on mortality (adjusted hazard ratio for low vs. high education, 1.15 [95% CI, 0.98-1.36]; adjusted hazard ratio for low-income vs. high-income tertile, 1.29 [CI, 1.12-1.49]). Further adjustment for characteristics of the admitting hospital had minimal effect on observed mortality differences. CONCLUSIONS: Low SES was strongly associated with increased 30-day mortality after bacteremia. Less social support, more pre-existing comorbidity, more substance abuse, and differences in place of acquisition and agent of infection appeared to mediate much of the observed disparities in mortality.

Use of penicillin and other antibiotics and risk of multiple sclerosis: a population-based case-control study.

A 2006 study from the United Kingdom found that penicillin use may decrease the risk of multiple sclerosis (MS). To confirm this finding, the authors conducted a nationwide case-control study in Denmark, using the Danish Multiple Sclerosis Registry to identify 3,259 patients with MS onset from 1996 to 2008, and selected 10 population controls per case (n = 32,590), matched on sex and age. Through the National Prescription Database, prescriptions for antibiotics redeemed from 1995 to 2008 and before the date of first MS symptom/index date were identified. Conditional logistic regression analysis was used to compute odds ratios associating antibiotic use with MS occurrence. In total, 1,922 patients (59%) redeemed penicillin prescriptions before the index date and 2,292 (70%) redeemed any type of antibiotic prescription. Penicillin use was associated with an increased risk of MS (odds ratio = 1.21, 95% confidence interval: 1.10, 1.27). Use of any type of antibiotic was similarly associated with an increased risk of MS (odds ratio = 1.41, 95% confidence interval: 1.29, 1.53). The odds ratios for different types of antibiotics ranged between 1.08 and 1.83. Thus, this study found that penicillin use and use of other antibiotics were similarly associated with increased risk of MS, suggesting that the underlying infections may be causally associated with MS.

National Background is Associated with Disparities in Initiation and Persistence to Statin Treatment in Subjects with Diabetes in Denmark.

BACKGROUND: To investigate the effects of statin use over the last 10 years among diabetic patients who initiated glucose-lowering medications (GLMs) in Denmark. METHODS: we identified all Danish citizens 30 years and older who claimed their first GLM between 1997 and 2006, with follow-up until 2007. Use of medications, national background, income, and hospitalizations were obtained by cross-linkage of national registries in Denmark. We analyzed factors related to initiation and interruption of statin treatment. The analyses included country of birth, citizenship and, as proxy for ethnic origin, we constructed variables based on both the subjects and on their parent's country of birth. Countries were grouped as Denmark, Western countries, Eastern countries, and Africa. RESULTS: the cohort included 143,625 subjects. Compared with persons of Danish origin, the initiation of a statin medication during follow-up was significantly lower among patients of non-Danish origin: Odds ratio for subjects of Eastern origin 0.61 [CI 0.49-0.76] and 0.37 for subjects of African origin, [CI 0.24-0.59], both p < 0.001. The risk of interrupting statin treatment once it had been initiated was also higher in these groups (hazard ratio 2.03, [CI 1.91-2.17] for Eastern subjects and 1.94, [CI 1.63-2.32] for African subjects, both p < 0.0001). Combination of ethnic parameters to refine identification of the cohort led to the same conclusions as the analysis based only on country of birth or citizenship respectively. CONCLUSION: diabetes patients of African and Eastern origin in Denmark have less chance of being treated with a statin than those of western and Danish origin despite similar access to the Danish health care system.

[Hospital standardised mortality ratios based on data from administrative registries. A pilot project]. / Beregning af standardiseret mortalitet efter hospitalsindlaeggelse. Et pilotprojekt.

INTRODUCTION: Hospital standardised mortality ratios (HSMR) are widely used in quality improvement campaigns. No data exist on whether HSMR can be computed based on Danish administrative registries. We therefore used data from Danish registries to compute HSMRs. MATERIALS AND METHODS: By linking hospital discharge registries with the Danish Civil Registration System, we identified 77 primary discharge diagnoses that accounted for 80% of all deaths within 30 days of admission. We calculated overall death rates stratified by the 77 primary discharge diagnoses, age, gender, and type of admission and used these to compute the expected number of deaths. HSMR for each hospital was calculated as the ratio of observed to expected number of deaths. RESULTS: Pneumonia, non-specified was the diagnosis that accounted for most deaths within 30 days after admission. The crude mortality rate varied from 5.7% to 6.3%. HSMR varied little--from 95 and 98 in Hospitals B and D to 102 and 103 in Hospitals A and C, respectively. CONCLUSION: We found that it was possible to use data from Danish administrative registries to compute HSMR and that HSMR varied little between hospitals with comparable case-mixes.