The liver-heart axis in patients with severe obesity: The association between liver fibrosis and chronic myocardial injury may be explained by shared risk factors of cardiovascular disease.

BACKGROUND: Severe obesity is associated with increased risk of non-alcoholic fatty liver disease and cardiovascular disease. We hypothesized that liver fibrosis as quantified by the Enhanced Liver Fibrosis (ELF) test would be predictive of myocardial injury and fibrosis, expressed by higher concentrations of cardiac troponin T and I measured by high-sensitivity assays (hs-cTnT and hs-cTnI, respectively). MATERIAL AND METHODS: We performed cross-sectional analyses of baseline data from 136 patients (mean age 45 years, 38 % male) with severe obesity participating in the non-randomized clinical trial Prevention of Coronary Heart Disease in Morbidly Obese Patients (ClinicalTrials.gov NCT00626964). Associations between ELF scores, hs-cTnT, and hs-cTnI concentrations were assessed using linear regression analysis. RESULTS: ELF scores were associated with hs-cTnT in the unadjusted model (B 0.381, 95 % Confidence Interval [CI] 0.247, 0.514), but the association was attenuated upon adjustment for potential confounders (B -0.031, 95 % CI -0.155, 0.093). Similarly, for hs-cTnI, an observed association with ELF scores in the unadjusted model was attenuated upon adjustment for potential confounders ((B 0.432, 95 % CI 0.179, 0.685) and (B 0.069, 95 % CI -0.230, 0.367), respectively). Age, sex, hypertension, and estimated glomerular filtration rate were amongst the shared predictors of ELF score, hs-cTnT, and hs-cTnI that provided the univariable models with the highest R-squared and lowest Akaike Information Criterion values. CONCLUSIONS: Contrary to our hypothesis, ELF score did not predict myocardial injury and fibrosis, but we rather demonstrated an association between liver fibrosis and myocardial injury and fibrosis may be explained by shared risk factors of cardiovascular disease.

The feasibility of a multidimensional intervention in lymphoma survivors with chronic fatigue.

PURPOSE: Chronic fatigue (CF) affects 25-30% of lymphoma survivors, but interventions designed to reduce fatigue are lacking. The main aim of this study was to test the feasibility of a multidimensional intervention study in lymphoma survivors with CF. Secondary aims were to describe individual changes in fatigue, quality of life (QoL) and physical performance from pre (T0) to post (T1) intervention. METHODS: This feasibility study was as a one-armed intervention study performed in 2021. Hodgkin or aggressive non-Hodgkin lymphoma survivors received mailed study information and Chalder Fatigue Questionnaire and were asked to respond if they suffered from fatigue. The 12-week intervention included patient education, physical exercise, a cognitive behavioural therapy (CBT)-based group program and nutritional counselling. Feasibility data included patient recruitment, completion of assessments, adherence to the intervention and patient-reported experience measures. Participants responded to questionnaires and underwent physical tests at T0 and T1. RESULTS: Seven lymphoma survivors with CF were included. Of all assessments, 91% and 83% were completed at T0 and T1, respectively. Adherence to the interventional components varied from 69% to 91%. At T1, all participants rated exercise as useful, of whom five rated the CBT-based program and five rated individual nutritional counselling as useful. Five participants reported improved fatigue, QoL and physical performance. CONCLUSION: Lymphoma survivors with CF participating in a multidimensional intervention designed to reduce the level of fatigue showed high assessment completion rate and intervention adherence rate. Most of the participants evaluated the program as useful and improved their level of fatigue, QoL and physical performance after the intervention. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT04931407. Registered 16. April 2021-Retrospectively registered. https://www. CLINICALTRIALS: gov/ct2/show/NCT04931407.

Financial and temporal costs of patient isolation in Norwegian hospitals.

BACKGROUND: Isolation of patients colonized or infected by antibiotic-resistant bacteria is an established infection-control measure taken in Norway. Local reliable data on the costs of this isolation are needed. METHODS: A micro-costing study from a healthcare perspective was conducted on infectious disease wards in three general acute hospitals, utilising direct observation, staff registration, interviews and survey data. FINDINGS: The daily additional cost of isolation was €56.8 (95% confidence interval (CI) 42.4-72.7) for non-bedridden patients and €87.5 (95% CI 48.3-129.6) for bedridden patients. Of these sums, labour costs accounted for the largest share (71-72%), followed by the costs of personal protective equipment (21-23%) and waste management (6-8%). Overall, isolation-specific workload amounted to 65 min/day for non-bedridden patients and 95 min/day for bedridden patients, predominantly in the form of extra time used by nurses. Higher isolation costs for bedridden patients were largely attributable to resources used for personal hygiene practices. One-time isolation costs incurred for room cleaning after patient discharge averaged at €14.0 (95% CI 10.7-17.6). CONCLUSIONS: Our study provides novel, detailed evidence on resource use attributable to patient isolation in hospitals that can be used to inform future assessments directed toward precautionary hygienic measures. Our results suggest that allocating additional nurse staffing to wards with large numbers of isolated patients should be considered.

Feasibility of reaching world health organization targets for hepatitis C and the cost-effectiveness of alternative strategies.

New drugs for treating hepatitis C have considerably increased the probability of being cured. Treatment uptake, however, is still low. The objectives of this study were to analyse the impact of initiatives that may increase the proportion of infected people on treatment and interventions aimed at reducing the incidence of new infection among people who inject drugs. A compartmental model for Norway was used to simulate hepatitis C and related complications. We analysed 2 different screening initiatives aimed to increase the proportion of infected people on treatment. Interventions aiming at reducing the hepatitis C incidence analysed were opioid substitution therapy (OST), a clean needle and syringe programme and a combination of both. The most cost-effective strategy for increasing hepatitis C treatment uptake was screening by general practitioners while simultaneously allowing for all infected people to be treated. We estimated that this intervention reduces the incidence of hepatitis C by 2030 by 63% compared with the current incidence. The 2 harm reduction strategies both reduced the incidence of hepatitis C by about 70%. Combining an increase in the current clean needles and syringe programme with OST was clearly the most cost-effective option. This strategy would reduce the incidence of hepatitis C by 80% compared with the current incidence by 2030. Thus, interventions to reduce the burden and spread of hepatitis C are cost-effective. Reaching the WHO target of a 90% reduction in hepatitis C incidence by 2030 may be difficult without combining different initiatives.

The predicted lifetime costs and health consequences of calcium and vitamin D supplementation for fracture prevention-the impact of cardiovascular effects.

UNLABELLED: Some studies indicate that calcium supplementation increases cardiovascular risk. We assessed whether such effects could counterbalance the fracture benefits from supplementation. Accounting for cardiovascular outcomes, calcium may cause net harm and would not be cost-effective. Clinicians may do well considering cardiovascular effects when prescribing calcium supplementation. INTRODUCTION: Accounting for possible cardiovascular effect of calcium and vitamin D supplementation (CaD), the aims of this study were to assess whether CaD on balance would improve population health and to evaluate the cost-effectiveness of such supplementation. METHODS: We created a probabilistic Markov simulation model that was analysed at the individual patient level. We analysed 65-year-old Norwegian women with a 2.3 % 10-year risk of hip fracture and a 9.3 % risk of any major fracture according to the WHO fracture risk assessment tool (FRAX®). Consistent with a recent Cochrane review, we assumed that CaD reduces the risk of hip, vertebral, and wrist fractures by 16, 11, and 5 %, respectively. We included the increased risk of acute myocardial infarction (AMI) and stroke under a no-, medium-, and high-risk scenario. RESULTS: Assuming no cardiovascular effects, CaD supplementation produces improved health outcomes resulting in an incremental gain of 0.0223 quality-adjusted life years (QALYs) and increases costs by €322 compared with no treatment (cost-effectiveness ratio €14,453 per QALY gained). Assuming a Norwegian cost-effectiveness threshold of €60,000 per QALY, CaD is likely to be considered a cost-effective treatment alternative. In a scenario with a medium or high increased risk of cardiovascular events, CaD produces net health losses, respectively, -0.0572 and -0.0784 QALY at additional costs of €481 and €1033. CONCLUSIONS: We conclude that the magnitude of potential cardiovascular side effects is crucial for the effectiveness and cost-effectiveness of CaD supplementation in elderly women.

Cost and health consequences of treatment of primary biliary cirrhosis with ursodeoxycholic acid.

BACKGROUND: Long-term use of ursodeoxycholic acid (UDCA) is the recommended therapy in primary biliary cirrhosis (PBC). The lifetime effectiveness and cost-effectiveness of UDCA in PBC have, however, not been assessed. AIM: To estimate the health outcomes and lifetime costs of a Norwegian cohort of PBC patients on UDCA. METHODS: Norwegian PBC patients (n = 182) (90% females; mean age 56.3 ± 8.9 years; Mayo risk score 4.38) who were included in a 5-year open-label study of UDCA therapy were subsequently followed up for up to 11.5 years. The lifetime survival was estimated using a Weibull survival model. The survival benefit from UDCA was based on a randomised clinical trial from Canada, comparing the effect of non-UDCA and UDCA. Survival and costs of standard care vs. standard care plus UDCA were simulated in a Markov model with death and liver transplantation as major events, invoking transition of a patient's state in the model. RESULTS: The gain in life expectancy for a PBC patient on UDCA compared with standard care was 2.24 years (1.19 years discounted). The lifetime treatment costs were EUR 151,403 and EUR 157,741 (EUR 102,912 and EUR 115,031 discounted) for patients with and without UDCA respectively. A probabilistic sensitivity analysis indicated an 82% probability that UDCA entails both greater life expectancy and lower costs than standard care. CONCLUSIONS: The results of this study indicate that UDCA therapy is a dominant strategy as it confers reduced morbidity and mortality, as well as cost savings, compared with standard therapy.

Metabolic syndrome predicts prostate cancer in a cohort of middle-aged Norwegian men followed for 27 years.

The aim of the study was to establish whether metabolic syndrome predicts the incidence of prostate cancer. The hypothesis was tested using the 27-year follow-up of the prospective cohort of 16,209 men aged 40-49 years who participated in the Oslo Study in 1972-1973. Men with established diabetes and men with cancer diagnosed before screening were excluded, leaving 15,933 for analyses. Metabolic syndrome is here composed of body mass index, nonfasting glucose, triglycerides, and blood pressure or drug-treated hypertension. Two analytical approaches were compared, namely, predefined (adjusted from National Cholesterol Education Program) and quartile values of risk factors. Age, body mass index, and sedentary versus intermediate physical activity at work were significant predictors in univariate proportional hazards regression analyses. Combinations of any two (relative risk = 1.23; p = 0.04) or any three (relative risk = 1.56; p = 0.00) factors of the metabolic syndrome using quartile values of risk factors were predictive of prostate cancer. The number of cases for four factors was too small for analyses. Predefined values of the risk factors were not found to be predictive. In conclusion, metabolic syndrome was found to predict prostate cancer during 27 years of follow-up, indicating an association between insulin resistance and the incidence of prostate cancer.

Controlled clinical trials in cancer pain. How controlled should they be? A qualitative systematic review.

This qualitative systematic review of the clinical methodology used in randomised, controlled trials of oral opioids (morphine, hydromorphone, oxycodone) for cancer pain underlines the difficulties of good pain research in palliative care. The current literature lacks placebo-controlled superiority trials. Recommendations for future research are discussed.

A simple correction for ties when censoring times depend on covariates.

We point out that the conventional methods for ties correction may be seriously biased when censoring times depend on covariates. A simple modification to the Efron correction method is suggested which works remarkably well in simulation studies. The method corresponds closely to breaking ties by random ordering. The modified correction method is easy to implement and computationally no more demanding than the Efron correction.

Dental anxiety, utilisation of dental services, and DMFS status in Norwegian military recruits.

The aim of the study was to assess the association between dental anxiety, oral health (evaluated by clinical and radiographic examinations), and utilisation of dental services. Results from correlation and regression analyses confirmed the generally held expectation that high dental anxiety would be associated with poorer oral health measured as numbers of decayed or filled surfaces. Significant, but weak, relationships were found between dental anxiety and utilisation measures, i.e. number of dental visits during the last year and time since last dental visit. Taken together, the data indicated that dental anxiety was a facet of more general negative oral health/preventive oral health related behaviour. Thus, high scores on this dimension were characterised by high dental anxiety, more oral health problems, inadequate dental attendance, slightly less frequent toothbrushing and larger intake of sweet soft drinks. However, the study also demonstrated that non-selected dentally anxious individuals as a group did not exhibit the almost complete avoidance pattern typical of patients seeking special treatment for dental fear. Even in the subgroup with particularly high dental anxiety, several individuals reported having been to the dentist during the last one or two years.