The Icelandic Heart Failure Registry-A nationwide assessment tool for HF care and intervention in HF treatment.

INTRODUCTION: The incidence of heart failure (HF) is increasing, largely because populations are both ageing and growing. Most clinical HF treatment trials are conducted on selected cohorts, only a few of which include elderly patients, among whom HF is common. HF registries can include all HF patients, independent of age or comorbidity profile, and thus reflect reality in healthcare management. METHODS: The Icelandic Heart Failure Registry (IHFR) was created in the autumn of 2019 and has operated since 1 January 2020. Based on the Swedish Heart Failure Registry (SwedeHF), it quickly acquired several extensions. All patients admitted for HF to the Department of Cardiology (DC) at Landspítali - The National University Hospital of Iceland are included. Several variables are collected, including the aetiology of HF, comorbidities, clinical assessment at admission, blood tests, imaging results, treatment given and medical therapy at discharge. RESULTS: During the 3 years from 2020 to 2022, the DC admitted 1890 patients. As some were readmitted during the study period, the true total was 2384 admissions. Because the IHFR 2023 edition includes 327 variables, automation of many of them is imperative for data collection. CONCLUSION: HF is a heterogenous disease with numerous underlying factors. HF management differs among HF phenotypes. A registry can serve as an unbiased indicator of care quality and has the potential to be studied in the future to assess the long-term effects of HF treatment. A registry like the IHFR, therefore, can impact the treatment of all patients recorded in it, reduce the rate of readmissions and even optimize HF management costs.

Trajectories of opioid use among patients with low back pain: Association to work absence.

BACKGROUND: Low back pain (LBP) is a leading reason for opioid use and a closer examination of opioid use and productivity losses among these patients is needed. We identify opioid use trajectories using a group-based trajectory model (GBTM) and estimate productivity losses across the trajectories. METHODS: Patients diagnosed with LBP in Swedish specialty care between 2011 and 2015, between the ages of 20 and 60, were included. Two GBTMs were estimated on monthly opioid use (converted to oral morphine equivalents) during the two 12-month periods preceding and following diagnosis. Productivity losses were estimated using the human-capital approach. RESULTS: In total, 147,035 patients were included. The mean age at diagnosis was 43 years of age and 49% of the patients were male. A qualitative assessment of the identified groups in the GBTM models was made based on the patterns of opioid use. We chose three pre-diagnosis groups characterized as 'Pre-low' (N = 109,492), 'Pre-increase' (N = 27,336) and 'Pre-high' (N = 10,207). Similarly, four post-diagnosis groups were chosen and characterized as 'Post-low' (N = 73,287), 'Post-decrease' (N = 39,446), 'Post-moderate' (N = 20,001) and 'Post-high' (N = 13,595). Only 50% of the patients in the 'Pre-high' group were in the 'Post-high' group. The total productivity losses by the pre-diagnosis groups were more than 2.7 billion Euros over the total 6-year study period. CONCLUSION: This study highlights how patients with LBP and high use of opioids are highly correlated before and after diagnosis. Patients with high use of opioids also exhibit high work absence and productivity losses. SIGNIFICANCE STATEMENT: This was the first study to estimate trajectories of opioids in the two time periods before and after a diagnosis of low back pain. For the first time, productivity losses were also estimated across the identified opioid use trajectories.

The costs of chronic pain-Long-term estimates.

BACKGROUND: Chronic pain is a condition with severe impact on many aspects of life, including work, functional ability and quality of life, thereby reducing physical, mental and social well-being. Despite the high prevalence and burden of chronic pain, it has received disproportionally little attention in research and public policy and the societal costs of chronic pain remain largely unknown. This study aimed to describe the long-term healthcare and work absence costs of individuals with and without self-identified chronic pain. METHODS: The study population were participants in two Norwegian population health studies (HUNT3 and Tromsø6). Participants were defined as having chronic pain based on a self-reported answer to a question on chronic pain in the health studies in 2008. Individuals in the study population were linked to four national register databases on healthcare resource use and work absence. RESULTS: In our study, 36% (n = 63,782) self-reported to have chronic pain and the average years of age was 56.6. The accumulated difference in costs between those with and without chronic pain from 2010 to 2016 was €55,003 (CI: 54,414-55,592) per individual. Extrapolating this to the entire population suggests that chronic pain imposes a yearly burden of 4% of GDP. Eighty per cent of the costs were estimated to be productivity loss. CONCLUSION: Insights from this study can provide a greater understanding of the extent of healthcare use and productivity loss by those with chronic pain and serve as an important basis for improvements in rehabilitation and quality of care, and the education of the public on the burden of chronic pain. SIGNIFICANCE: This was the first study to estimate the economic burden associated with chronic pain in the general population using linked individual-level administrative data and self-reported survey answers. We provide calculations showing that annual costs of chronic pain may be as high as €12 billion or 4% of GDP. Findings from this study highlight the need for a greater understanding of the substantial healthcare use and productivity losses among individuals with chronic pain.

Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Productivity Loss Across Socioeconomic Groups Among Patients With Low Back Pain or Osteoarthritis: Estimates Using the Friction-Cost Approach in Norway.

OBJECTIVES: Our aim was to estimate the productivity loss (PL) among patients with low back pain (LBP) or osteoarthritis (OA) across socioeconomic groups, using the friction-cost approach (FCA). METHODS: A total of 175,550 patients aged 18-65 years were included at their first diagnosis in specialty care between 2011 and 2016. PL was calculated for the year following diagnosis using individual wages, while adjusting for the friction length at 78 days per episode, a team production multiplier at 1.6, compensation mechanisms of 26.8%, and a chain-of-vacancies multiplier at 3.95. We included a simpler FCA model, omitting the latter three parameters, and a human capital approach (HCA) model. Socioeconomic stratifications were created based on education and income. One-way sensitivity analysis was used to assess the influence of the parameters in the full FCA model. RESULTS: The overall mean number of absent days was 23, while it was 25.3 and 20.1 for those with low and high education levels. The per-patient friction costs were €4395 among all patients and when extending the friction length to 98 days costs were €4342. For those with low and high education levels, the costs were €3671 and €4464, respectively. The costs in the simple FCA and HCA models were €1539 and €2088. DISCUSSION: Socioeconomic status and model design are sources of variation in PL. In health economic applications with PL and in patient populations with large socioeconomic differences, adjusting for these factors may be as important as sensitivities in parameters such as the friction length.

Problematic opioid use among osteoarthritis patients with chronic post-operative pain after joint replacement: analyses from the BISCUITS study.

OBJECTIVES: Opioids are commonly used to manage pain, despite an increased risk of adverse events and complications when used against recommendations. This register study uses data of osteoarthritis (OA) patients with joint replacement surgery to identify and characterize problematic opioid use (POU) prescription patterns. METHODS: The study population included adult patients diagnosed with OA in specialty care undergoing joint replacement surgery in Denmark, Finland, Norway, and Sweden during 1 January 2011 to 31 December 2014. Those with cancer or OA within three years before the first eligible OA diagnosis were excluded. Patients were allocated into six POU cohorts based on dose escalation, frequency, and dosing of prescription opioids post-surgery (definitions were based on guidelines, previous literature, and clinical experience), and matched on age and sex to patients with opioid use, but not in any of the six cohorts. Data on demographics, non-OA pain diagnoses, cardiovascular diseases, psychiatric disorders, and clinical characteristics were used to study patient characteristics and predictors of POU. RESULTS: 13.7% of patients with OA and a hip/knee joint replacement were classified as problematic users and they had more comorbidities and higher pre-surgery doses of opioids than matches. Patients dispensing high doses of opioids pre-surgery dispensed increased doses post-surgery, a pattern not seen among patients prescribed lower doses pre-surgery. Being dispensed 1-4,500 oral morphine equivalents in the year pre-surgery or having a non-OA pain diagnosis was associated with post-surgery POU (OR: 1.44-1.50, and 1.11-1.20, respectively). CONCLUSIONS: Based on the discovered POU predictors, the study suggests that prescribers should carefully assess pain management strategies for patients with a history of comorbidities and pre-operative, long-term opioid use. Healthcare units should adopt risk assessment tools and ensure that these patients are followed up closely. The data also demonstrate potential areas for further exploration in improving patient outcomes and trajectories.

Factors influencing quality of life in patients with osteoarthritis: analyses from the BISCUITS study.

OBJECTIVES: Osteoarthritis can have a profound effect on patients' quality of life. The Burden of Disease and Management of Osteoarthritis and Chronic Low Back Pain: Health Care Utilization and Sick Leave in Sweden, Norway, Finland and Denmark (BISCUITS) study aimed to describe the impact of osteoarthritis on quality of life and determine the association with factors such as pain severity and pharmacological treatment. METHODS: An observational study was performed with a cross-sectional design including patients with a confirmed osteoarthritis diagnosis enrolled in the National Quality Register for Better management of patients with Osteoarthritis (BOA) between 2016 and 2017 in Sweden. Patient-reported information from BOA was linked to administrative data from three national health registers. The impact of osteoarthritis on quality of life was estimated using the EQ-5D-5L and the first developed experienced-based time-trade-off value set for Sweden to calculate the EQ-5D-5L index scores. EQ-5D-3L index scores were also estimated based on a UK hypothetical value set via a crosswalk method. Ordinary least squares regression models were used to analyse the association between quality of life and potential influencing factors. RESULTS: For the 34,254 patients evaluated, mean EQ-5D-5L index score was 0.792 (SD 0.126). Stratifications showed that the index score varied across different levels of pain severity. Increased pain severity and use of pain-relieving medications remained significantly associated with a lower quality of life index score when controlled for potential confounders. The mean EQ-5D-3L index score was 0.605 (SD 0.192). CONCLUSIONS: This large population-based study from Sweden highlights the substantial impact of osteoarthritis on quality of life amongst different patient groups and that currently available treatment options for osteoarthritis pain do not appropriately address the needs for many osteoarthritis patients.

Prescription patterns and predictors of unmet pain relief in patients with difficult-to-treat osteoarthritis in the Nordics: analyses from the BISCUITS study.

OBJECTIVES: Osteoarthritis (OA) is one of the leading causes of disability worldwide. Pain is the most important symptom in OA, driving medical care, disability, reduced functionality, and decreased quality of life. The objective of this study was to describe prescription patterns of difficult-to-treat OA and explore possible predictors of unmet pain relief in Nordic patients. METHODS: This observational cohort study included patients with a confirmed diagnosis of OA (index date) in specialty care in Sweden, Norway, Finland and Denmark between 1 January 2011 and 31 December 2012 who were followed for up to 5 years. Four subgroups were pre-defined to characterize difficult-to-treat OA: (1) ≥2 chronic comorbidities in the 3-year pre-index period; (2) top 10% of healthcare resource users, 1-year post-index; (3) ≥3 types of prescription pain medications during pre-index period to first year post-index, with ≥30 days between types; (4) having a contraindication to a nonsteroidal anti-inflammatory drug (NSAID). Patient characteristics, prescription patterns and predictors of unmet pain relief (defined as persistent opioid use, using several types of opioids or long-term NSAID use) were analyzed. RESULTS: We identified 288,174 OA patients and the average age was 63.5 years at time of diagnosis and 58% of them were female. After 5 years, 35-50% of the patients defined as 'difficult-to-treat' had ≥1 prescription of opioids, compared to 20-25% of all OA patients (p-value <0.05). Comorbidities and disability pension were strong predictors of unmet pain relief (p-value <0.001). CONCLUSIONS: This study shows a substantial use of pain medications (NSAID and opioids) in difficult-to-treat OA patients. These findings suggest that pain may be inadequately managed in a considerable number of patients with OA, particularly those with contraindications to an NSAID. A high comorbid and socioeconomic burden are relevant risk factors among patients who continue to use opioids for a long period of time.

Priority setting and cross-country learning: the relevance of TO-REACH for primary care.

AIM: To inform the primary care community about priorities for research in primary care as came up from the European project TO-REACH and to discuss transferability of service and policy innovations between countries. BACKGROUND: TO-REACH stands for Transfer of Organizational innovations for Resilient, Effective, equitable, Accessible, sustainable and Comprehensive Health services and systems. This EU-funded project has put health systems and services research higher on the European agenda and has led to the current development of a European 'Partnership Transforming Health and Care Systems'. METHODS: To identify research priorities, both qualitative and quantitative approaches were used. Policy documents and strategic roadmaps were searched, and priorities were mapped. Stakeholders were involved through national roundtable consultations and online consultations. Regarding transferability, we carried out a review of the literature, guided by a conceptual framework, and using a snowballing approach. FINDINGS: Primary care emerged as an important priority from the inventory, as are areas that are conducive to strengthening primary care, such as workforce policies. The large variation in service organisation and policy around primary care in Europe is a huge potential for cross-country learning. However, the simple transfer of primary care service and policy arrangements from one health system to another has a big chance to fail, unless known conditions for successful transfer are taken into account and gaps in our knowledge about transfer are resolved.

Prevalence, characteristics, and mortality of patients with transthyretin amyloid cardiomyopathy in the Nordic countries.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive condition caused by deposition of transthyretin amyloid fibrils in the heart and is associated with poor quality of life and a shortened lifespan. This study aimed to describe the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using multiple national health registers in Denmark, Finland, Norway, and Sweden. METHODS AND RESULTS: Transthyretin amyloid cardiomyopathy patients were identified during 2008-2018 using a combination of diagnosis codes for amyloidosis and heart disease and were matched to patients with non-ATTR heart failure (HF). An identical study design was used in each country to facilitate comparison and aggregation of results. A total of 1930 ATTR-CM patients were identified from national health registers in the four countries. In 2018, prevalence of ATTR-CM per 100 000 inhabitants ranged from 1.4 in Denmark to 5.0 in Sweden; a steep increase over time was observed in Sweden and Norway. Median survival from diagnosis was 30 months for ATTR-CM patients and 67 months for matched HF patients. Survival was significantly lower for female than for male ATTR-CM patients (median survival: 22 and 36 months), while no significant difference was observed in the HF cohort. CONCLUSIONS: This study provides the first nationwide estimates of the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using identical study design across several countries. Findings corroborate previous case series showing high mortality in ATTR-CM, two-fold higher than for other HF patients and higher in women than men, highlighting the need for more precise and early diagnosis to reduce the disease burden.

Healthcare resource use of patients with transthyretin amyloid cardiomyopathy.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is the cardiac manifestation of transthyretin amyloidosis (ATTR). The aim of this study was to estimate healthcare resource use for ATTR-CM patients compared with heart failure (HF) patients, in Denmark, Finland, Norway, and Sweden. METHODS AND RESULTS: Data from nationwide healthcare registers in the four countries were used. ATTR-CM patients were defined as individuals diagnosed with amyloidosis and cardiomyopathy or HF between 2008 and 2018. Patients in the ATTR-CM cohort were matched to patients with HF but without ATTR-CM diagnosis. Resource use included number of visits to specialty outpatient and inpatient hospital care. A total of 1831 ATTR-CM and 1831 HF patients were included in the analysis. The mean number of hospital-based healthcare contacts increased in both the ATTR-CM and HF cohort during 3 years pre-diagnosis and was consistently higher for the ATTR-CM cohort compared with the HF cohort, with 6.1 [CI: 5.9-6.3] vs. 3.2 [CI: 3.1-3.3] outpatient visits and 1.03 [CI: 0.96-1.1] vs. 0.7 [CI: 0.7-0.8] hospitalizations. In the first year following diagnosis, patients with ATTR-CM continued to visit outpatient care (10.2 [CI: 10.1, 10.4] vs. 5.7 [CI: 5.6, 5.9]) and were admitted to hospital more frequently (3.3 [CI: 3.2, 3.4] vs. 2.5 [CI: 2.5, 2.6]) than HF patients. CONCLUSIONS: Transthyretin amyloid cardiomyopathy imposes a high burden on healthcare systems with twice as many outpatient specialist visits and 50% more hospitalizations in the year after diagnosis compared with HF patients without ATTR-CM. Studies to investigate if earlier diagnosis and treatment of ATTR-CM may lower resource use are warranted.

Nationwide prevalence and characteristics of transthyretin amyloid cardiomyopathy in Sweden.

OBJECTIVE: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare, progressive and fatal condition caused by deposition of transthyretin amyloid fibrils in the heart. This study aims to identify all patients diagnosed with ATTR-CM in Sweden, estimate the prevalence of ATTR-CM, describe patient characteristics and mortality, assess the importance of early symptoms (red flags) for identification of ATTR-CM, and compare with patients with heart failure (HF). METHODS: This retrospective study combined multiple national health registers covering all specialist visits and prescriptions for the entire population of Sweden. Between January 2008 and December 2018, patients with ATTR-CM were identified retrospectively based on a combination of diagnosis codes and compared with matched, all-cause non-ATTR HF patients. RESULTS: Overall, a total of 994 patients diagnosed with ATTR-CM were identified, with an average age at diagnosis of 73 years, and 30% of whom were female. The prevalence of diagnosed ATTR-CM cases in 2018 was 5.0 per 100 000. The median survival from diagnosis was 37.6 months (CI 33.8 to 43.8), with a lower median survival in women (27.9 months, CI 23.3 to 33.8) compared with men (43.5 months, CI 37.6 to 49.6). Patients with ATTR-CM demonstrated reduced survival compared with patients with HF (p<0.001). Compared with patients with HF, clinical identification of carpal tunnel syndrome, spinal stenosis, and atrioventricular and left bundle branch block can facilitate earlier diagnosis of ATTR-CM. CONCLUSIONS: This study provides the first nationwide estimates of ATTR-CM prevalence and risk factors. The results reinforce the severity of the disease and the importance of earlier diagnosis, especially for female patients, in order to allow effective treatment and prevention of disease progression.

Trust in times of health reform.

Trust is seen as an important condition for the smooth functioning of institutions, such as the health care system. In this article we describe the trust relationships between the three main actors in the Dutch health care system: patients/insured, healthcare providers and insurers. We used data from different surveys between 2006 and 2016. 2006 was the year of the introduction of an insurance reform in the Netherlands towards regulated competition. In the triangle of trust relationships between the three actors we found strong and mutual trust relationships between patients and healthcare providers and weak trust relationships between healthcare providers and insurers as well as between insured and insurance organisations. This hampers the intended role of insurers as selective purchasers of health care on the basis of quality and price.

Healthcare assistants in EU Member States: An overview.

With many European countries facing health workforce shortages, especially in nursing, and an increasing demand for healthcare, the importance of healthcare assistants (HCAs) in modern healthcare systems is expected to grow. Yet HCAs' knowledge, skills, competences and education are largely unexplored. The study 'Support for the definition of core competences for healthcare assistants' (CC4HCA, 2015-2016) aimed to further the knowledge on HCAs across Europe. This paper presents an overview of the position of healthcare assistants in 27 EU Member States (MSs) and reflects on the emerging country differences. It is shown that most learning outcomes for HCAs across Europe are defined in terms of knowledge and skills, often at a basic instead of more specialized level, and much less so in terms of competences. While there are many differences between MSs, there also appears to be a common, core set of knowledge and skills-related learning outcomes which almost all HCAs across Europe possess. Country differences can to a large extent be explained by the regulatory and educational frameworks in which HCAs operate, influencing their current and future position in the healthcare system. Further investments should be made to explore a common understanding of HCAs, in order to feed discussions at policy and organisational levels, while simultaneously investments in the development and implementation of context-specific HCA workforce policies are needed.

A call for action to establish a research agenda for building a future health workforce in Europe.

The importance of a sustainable health workforce is increasingly recognised. However, the building of a future health workforce that is responsive to diverse population needs and demographic and economic change remains insufficiently understood. There is a compelling argument to be made for a comprehensive research agenda to address the questions. With a focus on Europe and taking a health systems approach, we introduce an agenda linked to the 'Health Workforce Research' section of the European Public Health Association. Six major objectives for health workforce policy were identified: (1) to develop frameworks that align health systems/governance and health workforce policy/planning, (2) to explore the effects of changing skill mixes and competencies across sectors and occupational groups, (3) to map how education and health workforce governance can be better integrated, (4) to analyse the impact of health workforce mobility on health systems, (5) to optimise the use of international/EU, national and regional health workforce data and monitoring and (6) to build capacity for policy implementation. This article highlights critical knowledge gaps that currently hamper the opportunities of effectively responding to these challenges and advising policy-makers in different health systems. Closing these knowledge gaps is therefore an important step towards future health workforce governance and policy implementation. There is an urgent need for building health workforce research as an independent, interdisciplinary and multi-professional field. This requires dedicated research funding, new academic education programmes, comparative methodology and knowledge transfer and leadership that can help countries to build a people-centred health workforce.

Living In A Country With A Strong Primary Care System Is Beneficial To People With Chronic Conditions.

In light of the growing pressure that multiple chronic diseases place on health care systems, we investigated whether strong primary care was associated with improved health outcomes for the chronically ill. We did this by combining country- and individual-level data for the twenty-seven countries of the European Union, focusing on people's self-rated health status and whether or not they had severe limitations or untreated conditions. We found that people with chronic conditions were more likely to be in good or very good health in countries that had a stronger primary care structure and better coordination of care. People with more than two chronic conditions benefited most: Their self-rated health was higher if they lived in countries with a stronger primary care structure, better continuity of care, and a more comprehensive package of primary care services. In general, while having access to a strong primary care system mattered for people with chronic conditions, the degree to which it mattered differed across specific subgroups (for example, people with primary care-sensitive conditions) and primary care dimensions. Primary care reforms, therefore, should be person centered, addressing the needs of subgroups of patients while also finding a balance between structure and service delivery.

The common characteristics and outcomes of multidisciplinary collaboration in primary health care: a systematic literature review.

INTRODUCTION: Research on collaboration in primary care focuses on specific diseases or types of collaboration. We investigate the effects of such collaboration by bringing together the results of scientific studies. THEORY AND METHODS: We conducted a systematic literature review of PubMed, CINAHL, Cochrane and EMBASE. The review was restricted to publications that test outcomes of multidisciplinary collaboration in primary care in high-income countries. A conceptual model is used to structure the analysis. RESULTS: Fifty-one studies comply with the selection criteria about collaboration in primary care. Approximately half of the 139 outcomes in these studies is non-significant. Studies among older patients, in particular, report non-significant outcomes (p < .05). By contrast, a higher proportion of significant results were found in studies that report on clinical outcomes. CONCLUSIONS AND DISCUSSION: This review shows a large diversity in the types of collaboration in primary care; and also thus a large proportion of outcomes do not seem to be positively affected by collaboration. Both the characteristics of the structure of the collaboration and the collaboration processes themselves affect the outcomes. More research is necessary to understand the mechanism behind the success of collaboration, especially on the exact nature of collaboration and the context in which collaboration takes place.

Choosing your health insurance package: a method for measuring the public's preferences for changes in the national health insurance plan.

With rising healthcare expenditure and limited budgets available, countries are having to make choices about the content of health insurance plans. The views of the general population can help determine such priorities. In this article, we investigate whether preferences of the general population regarding the content of health insurance plans could be measured with the help of a stated preference method: the Basket Method (BM). In this method, people use an online tool to include or exclude healthcare interventions from their hypothetical insurance package; this then affects their monthly premium. The study was conducted in the Netherlands. In total, 1007 members of two panels managed by the NIVEL filled out an online questionnaire that included the BM. The suitability of the BM was tested with the help of five criteria, e.g. the BM's ability to distinguish between healthcare interventions. Our results suggest that the BM is suitable for measuring preferences of the general population regarding the content of the health insurance plan, as it performs well on most criteria. Policy makers can use these preferences when deciding the content of the health insurance plan. Its contents will then be more aligned to the population's needs and preferences.

Digital image analysis of membrane connectivity is a robust measure of HER2 immunostains.

The purpose of this study was to develop and validate a new software, HER2-CONNECT(TM), for digital image analysis of the human epidermal growth factor receptor 2 (HER2) in breast cancer specimens. The software assesses immunohistochemical (IHC) staining reactions of HER2 based on an algorithm evaluating the cell membrane connectivity. The HER2-CONNECT algorithm was aligned to match digital image scorings of HER2 performed by 5 experienced assessors in a training set and confirmed in a separate validation set. The training set consisted of 167 breast carcinoma tissue core images in which the assessors individually and blinded outlined regions of interest and gave their HER2 score 0/1+/2+/3+ to the specific tumor region. The validation set consisted of 86 core images where the result of the automated image analysis software was correlated to the scores provided by the 5 assessors. HER2 fluorescence in situ hybridization (FISH) was performed on all cores and used as a reference standard. The overall agreement between the image analysis software and the digital scorings of the 5 assessors was 92.1% (Cohen's Kappa: 0.859) in the training set and 92.3% (Cohen's Kappa: 0.864) in the validation set. The image analysis sensitivity was 99.2% and specificity 100% when correlated to FISH. In conclusion, the Visiopharm HER2 IHC algorithm HER2-CONNECT(TM) can discriminate between amplified and non-amplified cases with high accuracy and diminish the equivocal category and thereby provides a promising supplementary diagnostic tool to increase consistency in HER2 assessment.