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.

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.

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.

Choosing wisely: a model-based analysis evaluating the trade-offs in cancer benefit and diagnostic referrals among alternative HPV testing strategies in Norway.

BACKGROUND: Forthcoming cervical cancer screening strategies involving human papillomavirus (HPV) testing for women not vaccinated against HPV infections may increase colposcopy referral rates. We quantified health and resource trade-offs associated with alternative HPV-based algorithms to inform decision-makers when choosing between candidate algorithms. METHODS: We used a mathematical simulation model of HPV-induced cervical carcinogenesis in Norway. We compared the current cytology-based strategy to alternative strategies that varied by the switching age to primary HPV testing (ages 25-34 years), the routine screening frequency (every 3-10 years), and management of HPV-positive, cytology-negative women. Model outcomes included reductions in lifetime cervical cancer risk, relative colposcopy rates, and colposcopy rates per cervical cancer prevented. RESULTS: The age of switching to primary HPV testing and the screening frequency had the largest impacts on cancer risk reductions, which ranged from 90.9% to 96.3% compared to no screening. In contrast, increasing the follow-up intensity of HPV-positive, cytology-negative women provided only minor improvements in cancer benefits, but generally required considerably higher rates of colposcopy referrals compared to current levels, resulting in less efficient cervical cancer prevention. CONCLUSIONS: We found that in order to maximise cancer benefits HPV-based screening among unvaccinated women should not be delayed: rather, policy makers should utilise the triage mechanism to control colposcopy referrals.

Practice variation in surgical procedures and IUD-insertions among general practitioners in Norway - a longitudinal study.

BACKGROUND: Studies of Primary Health Care (PHC) reveal considerable practice variations in terms of the range of services provided. In Norway, general practitioners (GPs) are traditionally expected to perform IUD-insertions and several surgical procedures as a part of comprehensive PHC. We aimed to investigate variation in the provision of surgical procedures and IUD-insertions across GPs and over time and explore determinants of such variation. METHODS: Retrospective registry study of Norwegian GPs. From a comprehensive database of GPs' reimbursement claims, we obtained procedure codes and GP characteristics such as age, gender, list size and municipality characteristics from 2006 through 2013. Multivariable logistic regression models were fitted to explore determinants of practice variation. RESULTS: We extracted data from 4,828 GPs. In 2013, 91.0, 76.1 and 74.8% were reimbursed at least once for minor and major surgical procedures and IUD-insertion, respectively. Female GPs had lower odds for performing major surgical procedures (OR 0.38, 95% CI 0.32-0.45) and higher odds for performing IUD-insertions (OR 6.28, 95% CI 4.47-8.82) than male GPs. Older GPs and GPs with shorter patient lists were less likely to perform surgical procedures. GPs with longer patient lists had higher odds for performing IUD-insertions. The proportion of GPs performing surgical procedures increased over time, while the proportion decreased for IUD-insertions. The number of IUD-insertions in specialist care increased from 12,575 in 2011 to 15 216 (+21.0%) in 2014. CONCLUSION: We observed a large variation in the provision of surgical procedures and IUD-insertions amongst GPs in Norway. The GPs' age, gender, list size and size of municipality were associated with performing the procedures. Our findings suggest a shift of IUD-insertions from primary to specialist care.

Influenced from the start: anchoring bias in time trade-off valuations.

PURPOSE: The de facto standard method for valuing EQ-5D health states is the time trade-off (TTO), an iterative choice procedure. The TTO requires a starting point (SP), an initial offer of time in full health which is compared to a fixed offer of time in impaired health. From the SP, the time in full health is manipulated until preferential indifference. The SP is arbitrary, but may influence respondents, an effect known as anchoring bias. The aim of the study was to explore the potential anchoring effect and its magnitude in TTO experiments. METHODS: A total of 1249 respondents valued 8 EQ-5D health states in a Web study. We used the lead time TTO (LT-TTO) which allows eliciting negative and positive values with a uniform method. Respondents were randomized to 11 different SPs. Anchoring bias was assessed using OLS regression with SP as the independent variable. In a secondary experiment, we compared two different SPs in the UK EQ-5D valuation study TTO protocol. RESULTS: A 1-year increase in the SP, corresponding to an increase in TTO value of 0.1, resulted in 0.02 higher recorded LT-TTO value. SP had little impact on the relative distance and ordering of the eight health states. Results were similar to the secondary experiment. CONCLUSION: The anchoring effect may bias TTO values. In this Web-based valuation study, the observed anchoring effect was substantial. Further studies are needed to determine whether the effect is present in face-to-face experiments.

Using Decision-Analytic Modeling to Isolate Interventions That Are Feasible, Efficient and Optimal: An Application from the Norwegian Cervical Cancer Screening Program.

BACKGROUND: Decision makers often need to simultaneously consider multiple criteria or outcomes when deciding whether to adopt new health interventions. OBJECTIVES: Using decision analysis within the context of cervical cancer screening in Norway, we aimed to aid decision makers in identifying a subset of relevant strategies that are simultaneously efficient, feasible, and optimal. METHODS: We developed an age-stratified probabilistic decision tree model following a cohort of women attending primary screening through one screening round. We enumerated detected precancers (i.e., cervical intraepithelial neoplasia of grade 2 or more severe (CIN2+)), colposcopies performed, and monetary costs associated with 10 alternative triage algorithms for women with abnormal cytology results. As efficiency metrics, we calculated incremental cost-effectiveness, and harm-benefit, ratios, defined as the additional costs, or the additional number of colposcopies, per additional CIN2+ detected. We estimated capacity requirements and uncertainty surrounding which strategy is optimal according to the decision rule, involving willingness to pay (monetary or resources consumed per added benefit). RESULTS: For ages 25 to 33 years, we eliminated four strategies that did not fall on either efficiency frontier, while one strategy was efficient with respect to both efficiency metrics. Compared with current practice in Norway, two strategies detected more precancers at lower monetary costs, but some required more colposcopies. Similar results were found for women aged 34 to 69 years. CONCLUSIONS: Improving the effectiveness and efficiency of cervical cancer screening may necessitate additional resources. Although efficient and feasible, both society and individuals must specify their willingness to accept the additional resources and perceived harms required to increase effectiveness before a strategy can be considered optimal.

Decisions on statin therapy by patients' opinions about survival gains: cross sectional survey of general practitioners.

BACKGROUND: Guidelines for primary prevention of cardiovascular disease provide little guidance on how patients' preferences should be taken into account. We wanted to explore whether general practitioners (GPs) are sensitive to patient preferences regarding survival gains from statin therapy. METHODS: In a cross sectional, online survey 3,270 Norwegian GPs were presented with a 55 year old patient with an unfavourable cardiovascular risk profile. He expressed preferences for statin therapy by indicating a minimum survival gain that would be considered a substantial benefit. This survival gain varied across six versions of the vignette: 8, 4 and 2 years, and 12, 6 and 3 months, respectively. Participants were randomly allocated to one version only. We asked whether the GPs would recommend the patient to take a statin. Subsequently we asked the GPs to estimate the average survival gain of life long simvastatin therapy for patients with a similar risk profile. RESULTS: We received 1,296 responses (40 %). Across levels of survival gains (8 years to 3 months) the proportion of GPs recommending statin therapy did not vary significantly (OR per level 1.07, 95 % CI 0.99 to 1.16). The GP's own estimate of survival gain was a statistically significant predictor of recommending therapy (OR per year adjusted for the GPs' age, sex, speciality attainment and number of patients listed 3.07, CI 2.55 to 3.69). CONCLUSION: GPs were insensitive to patient preferences regarding survival gain when recommending statin therapy. The GPs' recommendations were strongly associated with their own estimates of survival gain.

Dynamic modeling of cost-effectiveness of rotavirus vaccination, Kazakhstan.

The government of Kazakhstan, a middle-income country in Central Asia, is considering the introduction of rotavirus vaccination into its national immunization program. We performed a cost-effectiveness analysis of rotavirus vaccination spanning 20 years by using a synthesis of dynamic transmission models accounting for herd protection. We found that a vaccination program with 90% coverage would prevent ≈880 rotavirus deaths and save an average of 54,784 life-years for children <5 years of age. Indirect protection accounted for 40% and 60% reduction in severe and mild rotavirus gastroenteritis, respectively. Cost per life year gained was US $18,044 from a societal perspective and US $23,892 from a health care perspective. Comparing the 2 key parameters of cost-effectiveness, mortality rates and vaccine cost at

Does the primary screening test influence women's anxiety and intention to screen for cervical cancer? A randomized survey of Norwegian women.

BACKGROUND: Countries must decide whether or not to replace primary cytology-based screening with primary human papillomavirus (HPV)-based screening. We aimed to assess how primary screening for an HPV infection, a sexually transmitted infection (STI), and the type of information included in the invitation letter, will affect screening intention. METHODS: We randomized a representative sample of Norwegian women to one of three invitation letters: 1) Pap smear, 2) HPV testing or 3) HPV testing with additional information about the nature of the infection. Intention to participate, anxiety level and whether women intend to follow-up abnormal results were measured between groups using chi-squared and nonparametric Kruskal-Wallis tests. Determinants of intention were explored using logistic regression. RESULTS: Responses from 3540 women were representative of the Norwegian population with respect to age, civil status and geographic location. No significant difference across invitation letters was found in women's stated intention to participate (range: 91.8-92.3%), anxiety (39-42% were either quite or very worried) or to follow-up after an abnormal result (range: 97.1-97.6%). Strength of intention to participate was only marginally lower for HPV-based invitation letters, albeit significant (p-value = 0.008), when measured on a scale. Only 36-40% of respondents given the HPV invitations correctly understood that they likely had an STI. CONCLUSIONS: We found that switching to primary HPV screening, independent of additional information about HPV infections, is not likely to reduce screening participation rates or increase anxiety; however, women lacked the ability to interpret the meaning of an HPV-test result.

Time trade-off and attitudes toward euthanasia: implications of using 'death' as an anchor in health state valuation.

PURPOSE: Health state values are by convention anchored to 'perfect health' and 'death.' Attitudes toward death may consequently influence the valuations. We used attitudes toward euthanasia (ATE) as a sub-construct for attitudes toward death. We compared the influence on values elicited with time trade-off (TTO), lead-time TTO (LT-TTO) and visual analogue scale (VAS).Since the 'death' anchor is most explicit in TTO, we hypothesized that TTO values would be most influenced by ATE. METHODS: Respondents valued eight EQ-5D health states with VAS, then TTO (n = 328) or LT-TTO (n = 484). We measured ATE on a scale from -2 (fully disagree) to 2 (fully agree) and used multiple linear regressions to predict VAS, TTO, and LT-TTO values by ATE, sex, age, and education. RESULTS: A one-point increase on the ATE scale predicted a mean TTO value change of -.113 and LT-TTO change of -.072. Demographic variables, but not ATE, predicted VAS values. CONCLUSIONS: TTO appears to measure ATE in addition to preferences for health states. Different ways of incorporating death in the valuation may impact substantially on the resulting values. 'Death' is a metaphysically unknown concept, and implications of attitudes toward death should be investigated further to evaluate the appropriateness of using 'death' as an anchor.

Impact of effectiveness information format on patient choice of therapy and satisfaction with decisions about chronic disease medication: the "Influence of intervention Methodologies on Patient Choice of Therapy (IMPACT)" cluster-randomised trial in general practice.

BACKGROUND: Risk communication is an integral part of shared decision-making in health care. In the context of interventions for chronic diseases it represents a particular challenge for all health practitioners. By using two different quantitative formats to communicate risk level and effectiveness of a cholesterol-lowering drug, we posed the research question: how does the format of risk information influence patients' decisions concerning therapy, patients' satisfaction with the communication as well as confidence in the decision. We hypothesise that patients are less prone to accept therapy when the benefits of long-term intervention are presented in terms of prolongation of life (POL) in months compared to the absolute risk reduction (ARR). We hypothesise that patients presented with POL will be more satisfied with the communication and confident in their decision, suggesting understanding of the time-related term. METHODS/DESIGN: In 2009 a sample of 328 general practitioners (GPs) in the Region of Southern Denmark was invited to participate in a primary care-based clinical trial among patients making real-life clinical decisions together with their GP. Interested GPs were cluster-randomised to inform patients about cardiovascular disease (CVD) risk and the effectiveness of statin therapy using either POL or ARR. The GPs attended a training session before informing their patients. Before training and after the trial period they received a questionnaire about their attitudes to risk communication and the use of numerical information. Patients' redemptions of statin prescriptions will be registered in a regional prescription database to evaluate a possible association between redemption rates and effectiveness format. The Combined Outcome Measure for Risk Communication And Treatment Decision Making Effectiveness (COMRADE) questionnaire will be used to measure patients' confidence and satisfaction with the risk communication immediately after the conversation with their GPs. DISCUSSION: This randomised clinical trial compares the impact of two effectiveness formats on real-life risk communication between patients and GPs, including affective patient outcomes and actual choices about acceptance of therapy. Though we found difficulties in recruiting GPs, according to the study protocol we have succeeded in engaging sufficient GPs for the trial, enabling us to perform the planned analyses.

What professional activities do general practitioners find most meaningful? Cross sectional survey of Norwegian general practitioners.

BACKGROUND: Health reforms in many countries affect the scope and nature of primary care. General Practitioners (GPs) are expected to spend more time developing public health, preventive health care, coordination of care and teamwork. We aimed to explore which professional activities GPs consider to be meaningful and how they would like to prioritise tasks. METHODS: In a cross sectional online survey 3,270 GPs were invited to consider twenty different activities in general practice. They were asked to rate each of them on a Likert scale anchored from 1 (not meaningful) to 5 (very meaningful). They then selected three activities from the item list on which they would like to spend more time and three activities on which they would like to spend less time. We used multinomial logistic regression to explore associations between the GPs' preferences for time spent on preventive health care activities and age, gender and practice characteristics. RESULTS: Approximately 40% (n=1,308) responded. The most meaningful activities were handling common symptoms and complaints (94% scored 4 or 5), chronic somatic diseases (93%), terminal care (80%), chronic psychiatric diseases (77%), risk conditions (76%) and on call emergency services (70%). In terms of priority the same items prevailed except that GPs would like to spend less time on emergency services. Items with low priority were health certificates, practice administration, meetings with local health authorities, medically unexplained symptoms, addiction medicine, follow up of people certified unfit for work, psychosocial problems, preventive health clinics for children and school health services. In multivariate regression models physician and practice characteristics explained no more than 10% of the variability in the GPs' preferences for time spent on preventive health care services. CONCLUSIONS: The GPs found diagnosis and treatment of diseases most meaningful. Their priorities were partly at odds with those of the health authorities and policy makers.