Geographical variation in palliative cancer care in a tax-based healthcare system: drug reimbursement in Denmark.

BACKGROUND: In Denmark, a tax-based universal healthcare setting, drug reimbursement for terminal illness (DRTI) should be equally accessible for all terminally ill patients. Examining DRTI status by regions provides new knowledge on inequality in palliative care provision and associated factors. This study aims to investigate geographical variation in DRTI among terminally ill cancer patients. METHODS: We linked socioeconomic and medical data from 135 819 Danish cancer decedents in the period 2007-15 to regional healthcare characteristics. We analyzed associations between region of residence and DRTI. Prevalence ratios (PR) for DRTI were estimated using generalized linear models adjusted for patient factors (age, gender, comorbidity and socioeconomic profile) and multilevel models adjusted for both patient factors and regional healthcare capacity (patients per general practitioner, numbers of hospital and hospice beds). RESULTS: DRTI allocation differed substantially across Danish regions. Healthcare capacity was associated with DRTI with a higher probability of DRTI among patients living in regions with high compared with low hospice bed supply (PR 1.13, 95% CI 1.10-1.17). Also, the fully adjusted PR of DRTI was 0.94 (95% CI 0.91-0.96) when comparing high with low number of hospital beds. When controlled for both patient and regional healthcare characteristics, the PR for DRTI was 1.17 (95% CI 1.14-1.21) for patients living in the Central Denmark Region compared with the Capital Region. CONCLUSION: DRTI status varied across regions in Denmark. The variation was associated with the distribution of healthcare resources. These findings highlight difficulties in ensuring equal access to palliative care even in a universal healthcare system.

Perfusion in bone marrow lesions assessed on DCE-MRI and its association with pain in knee osteoarthritis: a cross-sectional study.

OBJECTIVE: To investigate the association between pain and perfusion in bone marrow lesions with and without cysts assessed dynamic contrast-enhanced (DCE)-MRI in patients with knee osteoarthritis. SUBJECTS AND METHODS: In a cross-sectional setting, perfusion in bone marrow lesions was assessed using 3 Tesla MRI and correlated (Spearman's rank correlation) to pain using the knee injury and osteoarthritis outcome score (KOOS). Bone marrow lesions were assessed across the whole knee with DCE-MRI using heuristic variable and non-contrast-enhanced-MRI using MRI osteoarthritis knee score. RESULTS: Data were available from 107 participants. The participants had a mean age of 60.8 years, mean BMI of 34.5 kg/m2, mean KOOS-pain of 63.7 (0-100 scale), and mean bone marrow lesion sum score of 6.5 (0-45 scale). The bivariate association between KOOS-pain and the heuristic perfusion variable time to peak in bone marrow lesions containing subchondral cysts showed a statistically significant correlation (r = 0.40; p = 0.002). The perfusion variables were not correlated with KOOS-pain in bone marrow lesions without cysts. CONCLUSION: In this cross-sectional study, the rate of perfusion (TTP) in bone marrow lesions containing subchondral cysts was associated with pain in patients with knee OA. DCE-MRI has a potential to be used for separating subtypes of OA.

Delayed gadolinium-enhanced MRI of menisci and cartilage (dGEMRIM/dGEMRIC) in obese patients with knee osteoarthritis: Cross-sectional study of 85 obese patients with intra-articular administered gadolinium contrast.

BACKGROUND: Early cartilage changes in knee osteoarthritis (OA) can be assessed by both intravenous (i.v.) and intra-articular (i.a.) delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). PURPOSE: To examine the relationship between i.a. dGEMRIC and delayed gadolinium-enhanced MRI of menisci (dGEMRIM), and to investigate if the approach can be used to assess the morphological degeneration of menisci in obese patients with knee OA. STUDY TYPE: Cross-sectional. POPULATION: Eighty-five obese patients with knee OA. FIELD STRENGTH/SEQUENCES: 1.5T. Inversion recovery sequence with four inversion times. ASSESSMENT: T1 relaxation times were calculated for posterior weight-bearing femoral cartilage and the posterior horns of the menisci. Meniscus degeneration sum score (0-2) was assessed as increased signal/no signal (1/0) and tear/no tear (1/0). STATISTICAL TESTS: T1 relaxation times were compared using Student's t-test. Comparison of cartilage and meniscus T1 relaxation times was done by regression analysis. Analysis of variance (ANOVA) was used for comparison of meniscal T1 relaxation times among the three summed morphological scores (0-2). Statistical analyses were performed with a level of significance at 0.05. RESULTS: For lateral menisci, morphology sum scores of 0, 1, and 2 were found in 13, 58, and 14 patients and for medial menisci in 2, 30, and 30 patients, respectively. Mean T1 relaxation times were 441 msec, 480 msec, and 497 msec for cartilage, lateral menisci, and medial menisci, respectively. T1 relaxation times for the menisci were similar (P = 0.53), and a weak correlation was found between dGEMRIC and dGEMRIM in the lateral compartments (R = 0.26). Comparing dGEMRIM between different morphology sum scores showed no differences (P > 0.4). DATA CONCLUSION: I.a. dGEMRIM showed no correlation between the degree of meniscal degeneration and meniscus T1 relaxation times. I.a. dGEMRIM do not seem to deliver useful information about meniscus degeneration to be suitable for clinical applications, but i.a. dGEMRIC may still be considered an alternative contrast-saving method for cartilage. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;48:1700-1706.

Is mortality after hip fracture associated with surgical delay or admission during weekends and public holidays? A retrospective study of 38,020 patients.

BACKGROUND AND PURPOSE: Hip fractures are associated with high mortality, but the cause of this is still not entirely clear. We investigated the effect of surgical delay, weekends, holidays, and time of day admission on mortality in hip fracture patients. PATIENTS AND METHODS: Using data from the Danish National Indicator Project, we identified 38,020 patients admitted from 2003 to 2010. Logistic regression analysis was used to study the association between sex, age, weekend or holiday admission, night-time admission, time to surgery, and ASA score on the one hand and mortality on the other. RESULTS: The risk of death in hospital increased with surgical delay (odds ratio (OR) = 1.3 per 24 h of delay), ASA score (OR (per point added) = 2.3), sex (OR for men 2.2), and age (OR (per 5 years) = 1.4). The mortality rate for patients admitted during weekends or public holidays, or at night, was similar to that found for those admitted during working days. INTERPRETATION: Minimizing surgical delay is the most important factor in reducing mortality in hip fracture patients.

The effect of exercise therapy on inflammatory activity assessed by MRI in knee osteoarthritis: Secondary outcomes from a randomized controlled trial.

OBJECTIVE: This study investigated the effect of exercise therapy on inflammatory activity in synovitis and bone marrow lesions (BMLs) assessed by magnetic resonance imaging (MRI) in patients with knee OA. METHODS: 60 patients with knee OA were randomized 1:1 to 12 weeks of supervised exercise therapy 3 times/week (ET) or a no-attention control group (CG). Synovitis and BMLs were assessed with static MRI with and without contrast and with dynamic contrast enhanced MRI (DCE-MRI). DCE-MRI data was quantified using pixel-by-pixel methodology based on analysis of signal intensity curves. Pain was assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Analyses of covariance were used assessing group differences in changes from baseline to week 12. RESULTS: 33 patients adhered to the protocol and had valid MRI and KOOS data (ET, n = 16, CG, n = 17). Statistically significant and clinically relevant group difference in favour of ET was seen in KOOS pain change (-11.7 points, 95%CI: -20.1 to -3.4). There were statistically significant group differences in DCE-MRI assessed synovitis in the anterior synovium with unchanged inflammatory activity in the ET group compared to the CG. There were no group differences in BMLs and static MRI. CONCLUSION: Inflammatory activity was unchanged, and pain was reduced in patients with knee OA adhering to 12 weeks of exercise therapy compared to a no-attention control group. The reduction in pain was not explained by changes in inflammatory activity. Overall, the results suggest that exercise is not harmful in knee OA. ClinicalTrials.gov number: NCT01545258.

Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA). OBJECTIVE: To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA. METHODS: The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52. RESULTS: In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P = 0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P = 0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively. CONCLUSIONS: In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.

Socioeconomic inequality in drug reimbursement during end-of-life care: a nationwide study.

BACKGROUND: In Denmark, patients who are terminally ill have the right to drug reimbursement due to terminal illness (DRTI). DRTI, a proxy marker of planned end-of-life care, is intended to be equally accessible regardless of socioeconomic position. This study examined social and socioeconomic differences in DRTI among Danish patients who are terminally ill. METHODS: This cross-sectional study based on individual-level nationwide data included all patients dying from cancer, dementia, ischaemic heart disease, chronic obstructive pulmonary disease, chronic liver disease, congestive heart failure, diabetes or stroke in 2006-2015 (n=307 188). We analysed associations between social and socioeconomic position (education, income, cohabiting status, migrant status and employment) and DRTI. Prevalence ratios (PR) and 95% CIs were estimated using log-linear models adjusted for age, gender, comorbidity, cause of death and residence. RESULTS: Overall, 27.9% of patients received DRTI (n=85 616). A substantial difference in likelihood of receiving DRTI was observed among patients with a social and socioeconomic profile associated with the highest versus lowest probability of DRTI (adjusted PR 1.44, 95% CI 1.18 to 1.75). The probability of DRTI was higher among patients with high income compared with low income (adjusted PR 1.22, 95% CI 1.17 to 1.26). Also, living with a partner and being immigrant or descendant of such were associated with higher probability of DRTI compared with living alone and of Danish origin, whereas employment was associated with lower probability of DRTI compared with retirement. CONCLUSION: Social and socioeconomic position was associated with the likelihood of receiving DRTI, which indicates that planned end-of-life care is not equally accessible in Denmark.

Effect of liraglutide on body weight and pain in patients with overweight and knee osteoarthritis: protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial.

INTRODUCTION: With an increasing prevalence of citizens of older age and with overweight, the health issues related to knee osteoarthritis (OA) will intensify. Weight loss is considered a primary management strategy in patients with concomitant overweight and knee OA. However, there are no widely available and feasible methods to sustain weight loss in patients with overweight and knee OA. The present protocol describes a randomised controlled trial evaluating the efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide in a 3 mg/day dosing in patients with overweight and knee OA. METHODS AND ANALYSIS: 150 volunteer adult patients with overweight or obesity and knee OA will participate in a randomised, double-blind, placebo-controlled, parallel-group and single-centre trial. The participants will partake in a run-in diet intervention phase (week -8 to 0) including a low calorie diet and dietetic counselling. At week 0, patients will be randomised to either liraglutide 3 mg/day or liraglutide placebo 3 mg/day for 52 weeks as an add-on to dietetic guidance on re-introducing regular foods and a focus on continued motivation to engage in a healthy lifestyle. The co-primary outcomes are changes in body weight and the Knee Injury and Osteoarthritis Outcome Score pain subscale from week 0 to week 52. ETHICS AND DISSEMINATION: The trial has been approved by the regional ethics committee in the Capital Region of Denmark, the Danish Medicines Agency and the Danish Data Protection Agency. An external monitoring committee (The Good Clinical Practice Unit at Copenhagen University Hospitals) will oversee the trial. The results will be presented at international scientific meetings and through publications in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: 2015-005163-16, NCT02905864, U1111-1171-4970 BASED ON PROTOCOL VERSION: V.6; 30 January 2017, 15:30 hours.