Increasing melanoma incidence with unchanged mortality: more sunshine, better treatment, increased diagnostic activity, overdiagnosis or lowered diagnostic threshold?

BACKGROUND: Increasing melanoma incidence with less increasing mortality is observed in several countries. This discrepancy is not well understood. OBJECTIVE: In this study, our aim was to discuss factors (UV exposure, melanoma treatment, diagnostic activity, overdiagnosis, pathologists' diagnostic threshold and clinicians' propensity to remove suspect skin lesions) that may influence melanoma incidence and mortality in Denmark. METHODS: This was a register study with the number of melanocyte-related lesions and melanoma mortality based on comprehensive national pathology and mortality databases for the period 1999-2019. We investigated melanocyte-related diagnoses and mortality in a population of 5.5 million with national health care system. Age adjusted melanoma mortality and age-adjusted incidence of benign nevi, atypical lesion, or melanoma-in-situ and of invasive melanoma were computed for data analysis. RESULTS: In total 1,434,798 biopsies were taken from 704,682 individuals (65% female). Mean age at biopsy was 39.8 years in men and 37.6 in women. In men and women, the incidence of invasive melanoma increased by 87% during the period 1999-2011. During the subsequent period it increased by 9% in men but remained unchanged in women. The incidence of melanoma in-situ increased by 476% in men and 357% in women during the study period, while the increases for atypical melanocytic lesions were 1928% and 1686%, respectively. Biopsy rates increased by 153% in men and 118% in women from 1999 through 2011 but fell by 20% in men and 22% in women during the subsequent period. Mortality varied slightly from year to year without any significant time trend for men or women.We identified no evidence of increased UV exposure over the latest 30 years in Denmark. Immunotherapy of advanced melanoma was introduced in Denmark in 2010 and came in general use in 2014. CONCLUSIONS: Comprehensive national data demonstrate increasing melanoma incidence correlated with increasing biopsy rates, but with no change in mortality. Previously suggested explanations for such a trend are lowered threshold of melanoma diagnosis among pathologists, increased diagnostic activity in the presence of overdiagnosis and improved melanoma treatment. Because the study is observational and because we have more explanatory factors than outcomes, the findings do not warrant conclusions about causal relationships.

The epidemiology and societal costs of myasthenia gravis in Norway: A non-interventional study using national registry data.

BACKGROUND AND PURPOSE: With the emergence of new treatment options for myasthenia gravis (MG), there is a need for information regarding epidemiology, healthcare utilization, and societal costs to support economic evaluation and identify eligible patients. We aimed to enhance the understanding of these factors using nationwide systematic registry data in Norway. METHODS: We received comprehensive national registry data from five Norwegian health- and work-related registries. The annual incidence and prevalence were estimated for the period 2013-2021 using nationwide hospital and prescription data. The direct, indirect (productivity losses) and intangible costs (value of lost life-years [LLY] and health-related quality of life [HRQoL]) related to MG were estimated over a period of 1 year. RESULTS: In 2021, the incidence of MG ranged from 15 to 16 cases per year per million population depending on the registry used, while the prevalence varied between 208.9 and 210.3 per million population. The total annual societal costs of MG amounted to EUR 24,743 per patient, of which EUR 3592 (14.5%) were direct costs, EUR 8666 (35.0%) were productivity loss, and EUR 12,485 (50.5%) were lost value from LLY and reduced HRQoL. CONCLUSION: The incidence and prevalence of MG are higher than previously estimated, and the total societal costs of MG are substantial. Our findings demonstrate that productivity losses, and the value of LLY and HRQoL constitute a considerable proportion of the total societal costs.

Intravitreal anti-vascular endothelial growth factor therapy for retinal diseases in Norway from 2011 to 2021: A combined registry and survey study.

PURPOSE: To investigate the use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in Norway from 2011 to 2021 and explore how the eye departments organized their injection services. METHODS: We combined data from the Norwegian Patient Registry (NPR) with survey responses from Norway's 22 eye departments. The NPR data encompassed all registered intravitreal injection episodes from 2011 to 2021. The survey contained questions about local treatment practices and emphasized neovascular age-related macular degeneration (nAMD), retinal vein occlusion and diabetic macular edema. RESULTS: A total of 47247 unique patients received 841 646 intravitreal injections in the study period. The number of patients per year increased from 6522 in 2011 to 20 635 in 2021. The number of injections per year increased from 30 926 in 2011 to 125 258 in 2021. The most frequent diagnosis was nAMD. In 2021, the age-adjusted treatment activity in Norway's 11 counties ranged from 47.8 to 75.5 injections per 1000 inhabitants aged ≥50 years. The use of aflibercept gradually exceeded bevacizumab, but the aflibercept proportion per county ranged from 38 to 82% in 2021. The survey revealed varying treatment practices, local guidelines were often absent, and only half of the departments defined a lower visual limit for initiating or maintaining treatment. CONCLUSION: The use of intravitreal anti-VEGF therapy increased considerably from 2011 to 2021, but there was considerable regional variation in treatment activity, drug utilization and organization of injection services. These findings emphasize the need for strengthened governance and national guidelines to ensure equal treatment nationally.

Danish Women Want to Participate in a Hypothetical Breast Cancer Screening with Harms and No Reduction in Mortality: A Cross-Sectional Survey.

INTRODUCTION: Informed decision making is recommended in breast cancer screening. Decision aids with balanced information on harms and benefits are recommended to support informed decision making. However, informed screening decision making may be challenged by overly positive attitudes toward cancer screening. We hypothesized that a substantial proportion of Danish women would want to participate in screening regardless of the presented information. Therefore, we aimed to estimate the prevalence of Danish women wanting to participate in a hypothetical breast cancer screening offering no reduction in breast cancer mortality but potential harms related to unnecessary treatment. METHODS: In a cross-sectional study, we invited a random sample of 751 women in the nonscreening population aged 44 to 49 y in the Central Denmark Region to an online questionnaire using the official digital mailbox system. The questionnaire included a description of a hypothetical screening and questions about thoughts on breast cancer, health literacy, and questions on the assessment of the hypothetical screening including intended participation, understanding, and belief in information. Data were linked to register data on sociodemographic factors. RESULTS: In total, 43.0% (323/751) responded to the questionnaire. Of these, 247 (82.3% [95% confidence interval: 77.5-86.5]) wanted to participate in the hypothetical breast cancer screening (participation group). More than two-thirds in both the participation group and nonparticipation group seemed to understand the presented information. Half of the women who understood the information disbelieved it. CONCLUSIONS: Exceeding our expectations, a majority of women wanted to participate in a hypothetical screening with potential harms but no reduction in breast cancer mortality. A large proportion understood but disbelieved the screening information. This could indicate that Danish women make their screening decisions based on beliefs rather than presented screening information. This study was registered at ClinicalTrials.gov (Identifier: NCT04509063). HIGHLIGHTS: The majority of Danish women wanted to participate in a hypothetical breast cancer screening with potential harms related to unnecessary treatment but no reduction in mortality.A large proportion of women understood but disbelieved the hypothetical screening information.Informed decision making may be challenging when women disbelieve the information they receive.Enthusiasm for cancer screening and potential disbelief in information are important factors when developing and improving screening information and invitation.

Gaps and discontinuation of statin treatment in Norway: potential for optimizing management of lipid lowering drugs.

Aims: In clinical practice, many patients do not reach the recommended treatment targets for LDL-cholesterol levels. We aimed to examine treatment patterns and adherence for patients on lipid lowering drugs in Norway to inform future strategies to improve therapies. Methods and results: We obtained information on all dispensed statins, ezetimibe, and proprotein convertase subtilisin/-kexin 9 (PCSK9) inhibitors 2010-2019 from the Norwegian Prescription Database. Treatment gaps were assessed assuming patients take one tablet per day and were defined to occur if a patient did not refill a prescription when the previous one should have been depleted. Treatment was defined as discontinued when the preceding prescription would have been used and no new subsequent prescription was filled. The mean proportion of days covered (PDC) was calculated by aggregating the total number of tablets dispensed during each calendar year and dividing by 365. Patients 80 years were excluded. A considerable proportion of statin users in Norway had long treatment gaps or discontinuation in treatment. The 19.6% of the patients had treatment gaps of 180 days or more, and 10.8% had gaps or greater than 365 days. Similar results were found for patients on antidiabetics and hypertensives. PDC ranged from 84.9% for simvastatin to 72.2% for ezetimibe (2019). The most common lipid lowering drugs in 2019 were atorvastatin, simvastatin, and ezetimibe. Conclusion: There is a great potential for improving drug adherence and optimizing lipid lowering therapy by switching to more effective statins in greater doses, and more often add ezetimibe and PCSK9 inhibitors to treatment.

Societal cost of cancer in Norway -Results of taking a broader cost perspective.

BACKGROUND: The broader cost consequences of diseases may be of interest for a wide range of stakeholders. We aimed to estimate all relevant societal costs of cancer and to provide insight into the relative magnitude of the different cost categories. METHOD: We used data from eight different health and work-related registries in Norway. Direct, indirect, and intangible costs (value of lost life years) were estimated over a period of one year with a combination of a top-down and a bottom-up costing approach. RESULTS: The indirect costs (EUR 1,997 million per year) are almost as high as direct costs (EUR 2,154 million), and the value of lost life years and quality of life represents the greatest cost related to cancer (EUR 18,200 million). In addition, cancer is associated with other costs which are commonly omitted from cost-of-illness analyses, including informal nursing (EUR 306 million), patient time costs (EUR 85 million), and excess costs of using public funds (EUR 439 million). Breast and cervical cancer had relatively high work absenteeism costs, while pancreatic and lung cancer had relatively high production costs due to premature deaths. DISCUSSION: Direct health care costs represent small proportions of the total societal costs of cancer. Costs commonly omitted in cost-of-illness analyses represent a significant cost and should be measured and valued in these analyses.

Phase- and gender-specific, lifetime, and future costs of cancer: A retrospective population-based registry study.

ABSTRACT: Valid estimates of cancer treatment costs are import for priority setting, but few studies have examined costs of multiple cancers in the same setting.We performed a retrospective population-based registry study to evaluate phase-specific (initial, continuing, and terminal phase) direct medical costs and lifetime costs for 13 cancers and all cancers combined in Norway. Mean monthly cancer attributable costs were estimated using nationwide activity data from all Norwegian hospitals. Mean lifetime costs were estimated by combining phase-specific monthly costs and survival times from the national cancer registry. Scenarios for future costs were developed from the lifetime costs and the expected number of new cancer cases toward 2034 estimated by NORDCAN.For all cancers combined, mean discounted per patient direct medical costs were Euros (EUR) 21,808 in the initial 12 months, EUR 4347 in the subsequent continuing phase, and EUR 12,085 in the terminal phase (last 12 months). Lifetime costs were higher for cancers with a 5-year relative survival between 50% and 70% (myeloma: EUR 89,686, mouth/pharynx: EUR 66,619, and non-Hodgkin lymphoma: EUR 65,528). The scenario analyses indicate that future cancer costs are highly dependent on future cancer incidence, changes in death risk, and cancer-specific unit costs.Gender- and cancer-specific estimates of treatment costs are important for assessing equity of care and to better understand resource consumption associated with different cancers.Cancers with an intermediate prognosis (50%-70% 5-year relative survival) are associated with higher direct medical costs than those with relatively good or poor prognosis.

Men receive more end-of-life cancer hospital treatment than women: fact or fiction?

BACKGROUND: An important goal of health care systems is equitable access to health care. Previous research, however, indicates that men receive more cancer care and health care resources than women. The aim of this study was to investigate whether there is a gender difference in terms of end-of-life cancer treatment in hospitals in Norway. MATERIAL AND METHODS: We used nationwide patient-level data from the Norwegian Patient Registry (2013-2017, n = 64,694), and aggregated data from the Norwegian Cause of Death Registry (2013-2018, n = 66,534). We described direct medical costs and utilization of cancer treatment in hospitals (in-patient stays and out-patient clinics) and specialized palliative home care teams by the means of the following variables: gender, type of cancer, age, region of residence, place of death, and use of pharmaceutical anti-cancer treatment last month before death. Generalized linear models with a gamma distribution and log-link function were fitted to identify determinants of direct medical costs in hospital's last year of life. RESULTS: Women aged 0-69 years had an average direct medical cost in hospitals of €26,117 during the last year of life, compared to €29,540 for men, while they were respectively €19,889 and €22,405 for those aged 70 years or older. These gender differences were confirmed in regression models with gender as the only covariate. Adjusted additionally for the type of cancer, the difference was 11%, while including age as a covariate reduced the difference to 6%. When the place of death was also included, the difference was down to 4%. DISCUSSION: The gender difference in hospital costs last year of life can largely be explained by age at death and the proportion dying in hospitals. When adjusting for confounding factors, the differences in end-of-life costs in hospitals are minimal.

Negative controls to detect uncontrolled confounding in observational studies of mammographic screening comparing participants and non-participants.

BACKGROUND: When comparing mammography-screening participants and non-participants, estimates of reduction in breast-cancer mortality may be biased by poor baseline comparability. We used negative controls to detect uncontrolled confounding. METHODS: We designed a closed cohort of Danish women invited to a mammography-screening programme at age 50-52 years in Copenhagen or Funen from 1991 through 2001. We included women with a normal screening result in their first-invitation round. Based on their second-invitation round, women were divided into participants and non-participants and followed until death, emigration or 31 December 2014, whichever came first. We estimated hazard ratios (HRs) of death from breast cancer, causes other than breast cancer and external causes. We added dental-care participation as an exposure to test for an independent association with breast-cancer mortality. We adjusted for civil status, parity, age at first birth, educational attainment, income and hormone use. RESULTS: Screening participants had a lower hazard of breast-cancer death [HR 0.47, 95% confidence interval (CI) 0.32, 0.69] compared with non-participants. Participants also had a lower hazard of death from other causes (HR 0.43, 95% CI 0.39, 0.46) and external causes (HR 0.35, 95% CI 0.23, 0.54). Reductions persisted after covariate adjustment. Dental-care participants had a lower hazard of breast-cancer death (HR 0.75, 95% CI 0.56, 1.01), irrespective of screening participation. CONCLUSIONS: Negative-control associations indicated residual uncontrolled confounding when comparing breast-cancer mortality among screening participants and non-participants.

Effect of a pharmacist-led intervention on adherence among patients with a first-time prescription for a cardiovascular medicine: a randomized controlled trial in Norwegian pharmacies.

OBJECTIVE: To examine whether a pharmacist-led intervention improves medication adherence among patients who have filled a first-time prescription for a cardiovascular medicine. METHODS: Design: Unblinded randomized controlled trial. SETTING: 67 Norwegian pharmacies, October 2014-June 2015. PARTICIPANTS: 1480 adults with a first-time prescription for a cardiovascular medicine. INTERVENTION: Participants in the intervention group received two consultations with a pharmacist 1-2 and 3-5 weeks after filling the prescription. Participants in the control group received care according to usual practice. MAIN OUTCOME MEASURE: The primary outcome was self-reported adherence as measured by the 8-item Morisky Medication Adherence Scale (MMAS-8), at 7 and 18 weeks after filling the prescription. Adherence from baseline to week 52 was estimated using data from the Norwegian Prescription Database (NPD). KEY FINDINGS: Data from MMAS-8 showed that 91.3% of the patients in the intervention group were adherent after 7 weeks versus 86.8% in the control group (4.5% difference, 95% CI 0.8-8.2, P = 0.017). The corresponding proportions were 88.7% versus 83.7% after 18 weeks (5.0% difference, 95% CI 0.8-9.2, P = 0.021). NPD data (n = 1294) showed no significant difference in adherence after 52 weeks (95% CI -2.0 to 7.8, P = 0.24). However, adherence among statin users (n = 182) was 66.5% in the intervention group versus 57.4% among new statin users in the general population (n = 1500) (difference 9.1%, 95% CI 1.5-16.0, P = 0.019). CONCLUSION: The main outcome measure indicates that a short, structured pharmacist-led intervention may increase medication adherence for patients starting on chronic cardiovascular medication. However, these findings could not be confirmed by the NPD data analysis.

Intravitreal therapy for retinal diseases in Norway 2011-2015.

PURPOSE: During the past decade, intravitreally administered biologic drugs have advanced the treatment of retinal diseases, such as wet age-related macular degeneration (AMD), diabetic macular oedema and retinal venous occlusions. The drugs as well as the necessary disease management imply considerable economic burden on healthcare systems. This Norwegian study documents the rates of use of intravitreal therapies and intercounty variation over a 5-year period. METHODS: We collected data from the Norwegian Patient Register for all episodes of care encompassing intravitreal therapy during the period 2011-2015. For each episode, we received information on patient age, sex, county of residence, diagnosis and name of drug injected. RESULTS: During the study period, 21 277 patients had in total 236 857 episodes of care. The number of intravitreal injections doubled from 2011 to 2015, reaching 63 601 injections in 2015, of which 77% were for diagnosed wet AMD. In 2015, the age-adjusted number of episodes varied from 19 to 55 per 1000 population aged 50+ across Norway's 19 counties. The age-adjusted number of patients treated per 1000 population aged 50+ varied from 5.22 to 8.35. CONCLUSION: The use of intravitreal injections increased rapidly with wet AMD as the most frequent diagnosis and with varying utilization across Norway's 19 counties. The causes of the varying use of intravitreal therapies could not be established but may reflect variation in disease prevalence, treatment capacity, travel distance to the nearest ophthalmic service and lack of national treatment guidelines. The geographic variation in utilization may challenge policy goals of equitable care and warrants further studies.

Economic evaluation of lipid lowering with PCSK9 inhibitors in patients with familial hypercholesterolemia: Methodological aspects.

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have proved to reduce low density lipoprotein cholesterol levels in numerous clinical trials. In two large clinical trials, PCSK9 inhibitor treatment reduced the risk of cardiovascular disease. Our aim was to explore the impact of varying assumptions about clinical effectiveness on health and economic outcomes for patients with familial hypercholesterolemia. METHODS: We used a previously published and validated Norwegian model for cardiovascular disease. The model was updated with recent data from the world's second largest registry of patients with genetically confirmed familial hypercholesterolemia. We performed analyses for 24 different subgroups of patients based on age, gender, statin tolerance and previous history of cardiovascular disease. RESULTS: In 1 out of 24 subgroups, PCSK9 inhibitors were cost-effective when effectiveness was modelled using direct relative efficacy as reported in the FOURIER trial. When using assumptions, as suggested in a recent consensus statement from the European Atherosclerosis Society, 14 subgroups were cost-effective. CONCLUSIONS: Cost-effectiveness of PCSK9 inhibitors depends highly on assumptions regarding effectiveness. Basing assumptions only on randomised controlled trials, and not taking into account varying effects based on baseline cholesterol level, results in much fewer groups being cost-effective.

Utilization of etoricoxib in dental patients in the Nordic countries: a population-based register study.

Background: Etoricoxib is a second-generation cyclooxygenase-2-inhibitor approved in 2012 for short-term treatment of pain associated with dental surgery. Objectives: To evaluate etoricoxib utilization in dental patients in the Nordic countries, including its off-label use. Methods: The entire populations of Denmark, Finland, Sweden and Norway with etoricoxib prescriptions written by dentists and dispensed in 2012-2014 were evaluated using national register data. Nationwide estimates of etoricoxib utilization were generated according to year, gender, age, dose and package size. Off-label use in paediatric patients, prescribed doses >90 mg/day or for dental contacts not associated with surgical procedures, and concomitant administration with anticoagulants were evaluated. Results: Utilization of etoricoxib for dental pain was low (1615 prescriptions: Finland, 907; Sweden, 359; Norway, 337; Denmark, 12). Overall, 70% of the prescriptions were without an associated dental procedure. Moreover, 58%, 55%, 10% and 58% of the prescriptions in Denmark, Finland, Sweden and Norway, respectively, were for >90 mg/day doses. Few paediatric prescriptions were dispensed (n < 10), and only a small overlap (n = 21) was observed between etoricoxib and anticoagulant prescriptions. Conclusions: Given the low overall number of prescriptions, it is unlikely that off-label use of etoricoxib within dentistry in the Nordic countries is an important public health concern.