First-line Treatment Patterns and Outcomes in Advanced Non-Small Cell Lung Cancer in Sweden: A Population-based Real-world Study with Focus on Immunotherapy.

BACKGROUND AND PURPOSE: The treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) has evolved significantly since the introduction of immunotherapies. We here describe PD-L1 testing rates, treatment patterns, and real-world outcomes for PD-(L)1 inhibitors in Sweden. MATERIALS AND METHODS: Data were obtained from the Swedish National Lung Cancer Registry for patients with advanced NSCLC and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 who initiated first-line -systemic treatment from 01 April 2017 to 30 June 2020. PD-L1 testing was available in the registry from 01 January 2018. Kaplan-Meier was used for overall survival (OS) by type treatment and histology. RESULTS: A total of 2,204 patients with pathologically confirmed unresectable stage IIIB/C or IV NSCLC initiated first-line treatment, 1,807 (82%) with nonsquamous (NSQ) and 397 (18%) with SQ. Eighty-six per cent (NSQ) or 85% (SQ) had been tested for PD-L1 expression, a proportion that increased over time. The use of platinum-based therapy as first-line treatment decreased substantially over time while there was an upward trend for PD-(L)1-based therapy. Among patients with PS 0-1 initiating a first-line PD-(L)1 inhibitor monotherapy, the median OS was 18.6 and 13.3 months for NSQ and SQ NSCLC patients, respectively, while for the PD-(L)1 inhibitor and chemotherapy combination regimen, the median OS was 24.0 months for NSQ and not evaluable for SQ patients. INTERPRETATION: The majority of advanced NSCLCs in Sweden were tested for PD-L1 expression. Real-world OS in patients with PS 0-1 receiving first-line PD-(L)1 inhibitor-based regimens was similar to what has been reported in pivotal clinical trials on PD-(L)1 inhibitors.

Increased Risk of Long-Term Disabilities Following Childhood Bacterial Meningitis in Sweden.

Importance: Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort. Objective: To describe the long-term risks of disabilities following a childhood diagnosis of bacterial meningitis in Sweden. Design, Setting, and Participants: This nationwide retrospective registry-based cohort study included individuals diagnosed with bacterial meningitis (younger than 18 years) and general population controls matched (1:9) by age, sex, and place of residence. Data were retrieved from the Swedish National Patient Register from January 1, 1987, to December 31, 2021. Data were analyzed from July 13, 2022, to November 30, 2023. Exposure: A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register between 1987 and 2021. Main Outcomes and Measures: Cumulative incidence of 7 disabilities (cognitive disabilities, seizures, hearing loss, motor function disorders, visual disturbances, behavioral and emotional disorders, and intracranial structural injuries) after bacterial meningitis in childhood. Results: The cohort included 3623 individuals diagnosed with bacterial meningitis during childhood and 32 607 controls from the general population (median age at diagnosis, 1.5 [IQR, 0.4-6.2] years; 44.2% female and 55.8% male, median follow-up time, 23.7 [IQR, 12.2-30.4] years). Individuals diagnosed with bacterial meningitis had higher cumulative incidence of all 7 disabilities, and 1052 (29.0%) had at least 1 disability. The highest absolute risk of disabilities was found for behavioral and emotional disorders, hearing loss, and visual disturbances. The estimated adjusted hazard ratios (HRs) showed a significant increased relative risk for cases compared with controls for all 7 disabilities, with the largest adjusted HRs for intracranial structural injuries (26.04 [95% CI, 15.50-43.74]), hearing loss (7.90 [95% CI, 6.68-9.33]), and motor function disorders (4.65 [95% CI, 3.72-5.80]). The adjusted HRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for Streptococcus pneumoniae infection (eg, 7.89 [95% CI, 5.18-12.02] for seizure) compared with Haemophilus influenzae infection (2.46 [95% CI, 1.63-3.70]) or Neisseria meningitidis infection (1.38 [95% CI, 0.65-2.93]). The adjusted HRs for cognitive disabilities, seizures, behavioral and emotional disorders, and intracranial structural injuries were significantly higher for children diagnosed with bacterial meningitis at an age below the median. Conclusions and Relevance: The findings of this cohort study of individuals diagnosed with bacterial meningitis during childhood suggest that exposed individuals may have had an increased risk for long-term disabilities (particularly when diagnosed with pneumococcal meningitis or when diagnosed at a young age), highlighting the need to detect disabilities among surviving children.

Clinical, economic, and humanistic burden of community acquired pneumonia in Europe: a systematic literature review.

BACKGROUND: Community-acquired pneumonia (CAP) is an infectious lung inflammation contracted outside the hospital. CAP is a leading cause of death among young children, elderly, and immunocompromised persons. Incidence can reach 14 cases/1,000 adults. Up to 50% of cases require inpatient hospitalization. Mortality is 0.7/1,000 cases or 4 million deaths per year. We sought to summarize multi-dimensional burden of CAP for selected European countries. METHODS: We conducted a systematic literature review of literature published from 2011 to 2021 whereby we sought information pertaining to the epidemiologic, clinical, economic, and humanistic burden of CAP. Findings were summarized descriptively. RESULTS: CAP incidence in Europe is variable, with the highest burden among those of advanced age and with chronic comorbidities. Etiology is primarily bacterial infection with Streptococcus pneumoniae being the most frequently implicated. Direct medical costs are primarily attributable to inpatient stay, which is exacerbated among high-risk populations. Higher mortality rates are associated with increasing age, the need for inpatient hospitalization, and antibiotic resistance. CONCLUSIONS: A better understanding of CAP is needed, specifically the economic and quality of life burden on patients and caregivers. We recommend further assessments using population-level and real-world data employing consistent disease definitions.

HTA and Reimbursement Status of Metastatic Hormone­Sensitive Prostate Cancer, Non-Metastatic Castration-Resistant Prostate Cancer, and Metastatic Castration-Resistant Prostate Cancer Treatments in Europe: A Patient Access Landscape Review.

Background: Prostate cancer is the second most common cancer in men, with up to one-third of men being diagnosed in their lifetime. Recently, novel therapies have received regulatory approval with significant improvement in overall survival for metastatic castration-resistant prostate cancer, metastatic hormone-sensitive prostate cancer, and nonmetastatic castration-resistant prostate cancer. To improve decision-making regarding the value of anticancer therapies and support standardized assessment for use by health technology assessment (HTA) agencies, the European Society for Medical Oncology (ESMO) has developed a Magnitude of Clinical Benefit Scale (MCBS). Objective: This review aimed to map HTA status, reimbursement restrictions, and patient access for 3 advanced prostate cancer indications across 23 European countries during 2011-2021. Methods: HTA, country reimbursement lists, and ESMO-MCBS scorecards were reviewed for evidence and data across 26 European countries. Results: The analysis demonstrated that only in Greece, Germany, and Sweden was there full access across all included prostate cancer treatments. Treatments available for metastatic castration-resistant prostate cancer were widely reimbursed, with both abiraterone and enzalutamide accessible in all countries. In 3 countries (Hungary, the Netherlands, and Switzerland), there was a statistically significant difference (P<.05) between status of reimbursement and ESMO-MCBS "substantial benefit" (score of 4 or 5) vs "no substantial benefit" (score <4). Conclusion: Overall, the impact of the ESMO-MCBS on reimbursement decisions in Europe is unclear, with significant variation across the countries included in this review.

Indirect Costs Due to Lung Cancer-Related Premature Mortality in Four European Countries.

INTRODUCTION: Lung cancer accounts for approximately 20% of all cancer-related deaths and for the loss of 3.2 million disability-adjusted life years (DALYs) annually across Europe. The present study investigated the productivity losses resulting from premature deaths due to lung cancer in four European countries. METHODS: The human capital approach (HCA) was used to estimate indirect cost of productivity losses due to premature death due to lung cancer (ICD-10 codes C33-34 malignant neoplasm of trachea, bronchus, and lung) in Belgium, the Netherlands, Norway, and Poland. Years of productive life lost (YPLL) and present value of future lost productivity (PVFLP) were calculated using national age-specific mortality, wages, and employment rates. Data were sourced from the World Health Organization, Eurostat, and the World Bank. RESULTS: In 2019, there were 41,468 lung cancer deaths in the included countries resulting in 59,246 YPLL and more than €981 million in productivity losses due to premature mortality. From 2010 to 2015, the PVFLP of lung cancer decreased by 14% in Belgium, 13% in the Netherlands, 33% in Norway, and 19% in Poland. From 2015 to 2019, the PVFLP of lung cancer decreased by 26% in Belgium, 27% in the Netherlands, 14% in Norway, and 38% in Poland. CONCLUSION: The results from this study illustrate a decreasing trend in productivity costs of premature mortality due to lung cancer, as illustrated by the decreasing PVFLP between 2010 and 2019. This trend could be driven by a shift in the distribution of deaths towards older age groups due to advancements in the preventative and treatment landscape. These results provide an economic measure of the lung cancer burden which may assist decision-makers in allocating scarce resources amongst competing priorities in the included countries.

Assessing the impact of kidney cancer-related premature mortality and productivity loss in Greece and Portugal.

OBJECTIVE: In 2018, 371,750 people were diagnosed with kidney cancer globally, constituting 2.2% of all cancer diagnoses. Since 2010, the number of kidney cancer deaths in Europe have decreased in people under 65. However, this is not the case in Greece and Portugal. This study estimated the mortality and lost productivity due to premature mortality from kidney cancer in Greece and Portugal. METHODS: Years of life lost (YLL) and present value of future lost productivity (PVFLP) due to kidney cancer mortality (ICD-10 code: C64 - Malignant neoplasm of kidney, except renal pelvis) were calculated using the human capital approach. Age-specific mortality, mean earnings, and labor force participation rates were used in these calculations. RESULTS: In 2019, there were 564 and 454 kidney cancer deaths in Greece and Portugal, respectively, resulting in 5,871 (3,636 in males and 2,234 in females) and 5,397 (3,100 in males and 2,297 in females) YLL, respectively. YPLL and annual PVFLP were estimated to be 1,326 and €14.8 M in Greece and 1,278 and €11.8 M in Portugal, respectively. CONCLUSION: YLL and PVFLP due to kidney cancer mortality are substantial in Greece and Portugal. These results provide new evidence to assist decision-makers in allocating resources to reduce cancer burden.

Breast cancer-related mortality in Central and Eastern Europe: years of life lost and productivity costs.

BACKGROUND: Breast cancer (BC) poses a public health challenge as the most commonly diagnosed cancer among women globally. While BC mortality has declined across Europe in the past three decades, an opposite trend has been reported in some transitional European countries. This analysis estimates the mortality burden and the cost of lost productivity due to BC deaths in nine Central and Eastern Europe (CEE) countries: Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia, that have defied the favorable cancer mortality trends. These estimates may provide relevant evidence to aid decision-makers in the prioritization of BC-targeted policies. METHODS: The human capital approach (HCA) was used to estimate years of life lost (YLL) and productivity losses due to premature death from BC (ICD-10 code: C50 Malignant neoplasm of breast). YLL and present value of future lost productivity (PVFLP) were calculated using age and gender-specific mortality, wages, and employment rates. Data were sourced from the World Health Organization (WHO), Eurostat, and the World Bank. RESULTS: In 2019, there were 19,726 BC deaths in the nine CEE countries. This study estimated BC deaths resulted in 267,184 YLL. Annual PVFLP was estimated to be €85 M in Poland, €46 M in Romania, €39 M in Hungary, €21 M in Slovakia, €18 M in Serbia, €16 M in Czech Republic, €15 M in Bulgaria, €13 M in Croatia, and €7 M in Slovenia. CONCLUSION: Premature death from BC leads to substantial YLL and productivity losses. Lost productivity costs due to premature BC-related mortality exceeded €259 million in 2019 alone. The data modeled provide important evidence toward resource allocation priorities for BC prevention, screening, and treatment that could potentially decrease productivity losses. Careful consideration should be given to BC-specific policies, such as surveillance programs and the availability of new treatments in CEE countries to decrease the medical and financial burden of the disease.

Impact of the COVID-19 Pandemic on HPV Vaccinations in Switzerland and Greece: Road to Recovery.

The COVID-19 pandemic has caused significant disruptions to healthcare, including reduced administration of routinely recommended HPV vaccines in a number of European countries. Because the extent and trends of accumulated vaccine dose deficits may vary by country, decision-makers need country-specific information regarding vaccine deficits to plan effective catch-up initiatives. To address this knowledge gap in Switzerland and Greece, this study used a previously published COVID-19 recovery calculator and historical vaccine sales data to quantify the cumulative number of missed doses and the catch-up rate required to clear the deficit in Switzerland and Greece. The resultant cumulative deficit in HPV doses for Switzerland and Greece were 24.4% and 21.7%, respectively, of the total number of doses disseminated in 2019. To clear the dose deficit by December 2025, monthly vaccination rates must be increased by 6.3% and 6.0% compared to 2019 rates in Switzerland and Greece, respectively. This study demonstrates that administration rates of routine HPV vaccines decreased significantly among Swiss and Greek adolescents during the COVID-19 pandemic and that a sustained increase in vaccination rates is necessary to recover the HPV dose deficits identified and to prevent long-term public health consequences.

Estimating the lifetime cost of vaccination in 23 European Countries: a modeling study.

BACKGROUND: All European countries have national immunization programs (NIPs) to protect gainst infectious diseases. We aimed to estimate the individual lifetime cost of vaccination in 23 European countries, assuming full compliance with NIP schedules. RESEARCH DESIGN AND METHODS: We used publicly available data to estimate the individual lifetime cost of vaccination with the vaccines that are currently recommended and funded in each country for healthy individuals and for individuals with underlying medical conditions. We included a scenario analysis for healthy individuals in which all currently recommended vaccines were universally funded, and compared the annual costs per person of vaccination to the annual per-capita costs of all-cause hospitalization and anti-infective medications. RESULTS: The individual lifetime cost of vaccination was €592-3,504 for healthy individuals (median: €1,663; 13-20 diseases), €744-9,081 for individuals with underlying conditions (median: €2,992; 13-21 diseases), and €1,225-4,832 (median: €2,565; 21-22 diseases) in the scenario analysis, with median values for vaccine acquisition of €1,203, €1,731, and €1,788, respectively. CONCLUSIONS: Our estimates show that the maximum potential cost of vaccination requires a relatively low level of investment assuming full compliance. These data could be useful for policymakers in future financial planning and evaluation of NIPs.

Auxilin is a novel susceptibility gene for congenital heart block which directly impacts fetal heart function.

OBJECTIVE: Neonatal lupus erythematosus (NLE) may develop after transplacental transfer of maternal autoantibodies with cardiac manifestations (congenital heart block, CHB) including atrioventricular block, atrial and ventricular arrhythmias, and cardiomyopathies. The association with anti-Ro/SSA antibodies is well established, but a recurrence rate of only 12%-16% despite persisting maternal autoantibodies suggests that additional factors are required for CHB development. Here, we identify fetal genetic variants conferring risk of CHB and elucidate their effects on cardiac function. METHODS: A genome-wide association study was performed in families with at least one case of CHB. Gene expression was analysed by microarrays, RNA sequencing and PCR and protein expression by western blot, immunohistochemistry, immunofluorescence and flow cytometry. Calcium regulation and connectivity were analysed in primary cardiomyocytes and cells induced from pleuripotent stem cells. Fetal heart performance was analysed by Doppler/echocardiography. RESULTS: We identified DNAJC6 as a novel fetal susceptibility gene, with decreased cardiac expression of DNAJC6 associated with the disease risk genotype. We further demonstrate that fetal cardiomyocytes deficient in auxilin, the protein encoded by DNAJC6, have abnormal connectivity and Ca2+ homoeostasis in culture, as well as decreased cell surface expression of the Cav1.3 calcium channel. Doppler echocardiography of auxilin-deficient fetal mice revealed cardiac NLE abnormalities in utero, including abnormal heart rhythm with atrial and ventricular ectopias, as well as a prolonged atrioventricular time intervals. CONCLUSIONS: Our study identifies auxilin as the first genetic susceptibility factor in NLE modulating cardiac function, opening new avenues for the development of screening and therapeutic strategies in CHB.

Recommendations and Health Technology Assessment (HTA) landscape evaluation for pediatric pneumococcal conjugate vaccines (PCV) in Europe: A systematic literature review.

National Immunization Technical Advisory Groups (NITAGs) and Health Technology Assessment (HTA) agencies evaluate the value of vaccines and provide decision-making authorities with recommendations. The availability of information on disease-burden evidence considered or required for the assessment of vaccines included in national immunization programs (NIPs) is limited. The aim of this review is to summarize the epidemiologic and health economic (HE) evidence considered by NITAGs/HTA agencies when evaluating pediatric pneumococcal conjugate vaccine (PCV) NIPs. A systematic literature review of national recommendation reports for PCV NIPs in children in 31 European countries, published since 2001, was performed using NITAG/HTA agency websites, Google, MEDLINE, and EMBASE. The presence of epidemiological data was mapped, HE data was extracted, and findings were summarized. A total of 46 records for 19 countries were identified. Fifteen countries' records included a recommendation concerning implementation of PCV NIP, switching from one PCV to another or a change in vaccination schedule within an existing NIP. All of these included epidemiological invasive pneumococcal disease data, and to varying degree epidemiological data on acute otitis media and pneumonia. HE data was referenced in 13 countries' records, with 8 countries providing in-depth details on cost-effectiveness analyses. Pediatric PCV NIP recommendations were published by 61% of European countries, with varying degree of details and decision rationale. Some countries only publish the HE aspect of their rationale. The identified material can provide insight and support local policymakers and clinicians how data influenced the decision-making process in their countries.

Estimating Potential for Drug Budget Reallocation Following Expiration of Exclusivity of Pharmaceutical Products.

Background: The prioritization of public funds in an equitable and ethically sound manner along with efficient budget allocation are key challenges for governments and budget holders. Following the introduction of generics/biosimilars, the potential total budget made available for reallocation resulting from the loss of exclusivity (LOE) in a given market has not been estimated. Objectives: This study investigated the impact of generic/biosimilar entry on drug budget in 4 countries. Methods: Pharmaceutical sales data, drug costs and LOE dates were modeled and forecast using an analytical framework (Affordability by ReallocaTing Funds model [ART]) to estimate future incremental budget availability using scenario analyses in Greece (GR), the Netherlands (NL), Norway (NO) and Sweden (SW). Results: During 2020-2022, 166 (GR), 222 (NL), 145 (NO) and 93 (SW) products facing LOE were identified. This equated to release of an estimated cumulative budget during 2020-2024 of €218 million (GR), €1319 million (NL), €340 million (NO) and €876 million (SW). The estimated average budget released per year during 2020-2024 was 1.8% (GR), 4.6% (NL), 3.4% (NO) and 3.9% (SW) of each country's total annual drug budget. Discussion: These analyses showed that LOE for pharmaceutical products between 2020 and 2022 can result in significant increase in budget availability. LOE in the retail channel was the main driver of budget availability in GR and SW, compared to LOE in the hospital channel in the NL and NO. Conclusion: Estimation of future release of budget capacity using the Affordability by ReallocaTing Funds model supports discussion on resource allocation to fund innovation and may help inform policy changes.

The demographics, clinical characteristics and quality of life of patients with chronic cough from the Isala Cough Clinic in the Netherlands.

Introduction: Chronic cough affects ∼10% of the population and adversely impacts quality of life. This retrospective observational cohort study aimed to identify the demographics, clinical characteristics and quality of life of the chronic cough population in a Dutch chronic cough clinic, at baseline and following treatment at 6 months. Patients were categorised based on the underlying phenotype and response to treatment. Methods: Retrospective data on 2397 patients who were diagnosed according to standard guidelines of the American College of Chest Physicians were analysed. Quality of life was captured via the Leicester Cough Questionnaire, the Cough Numeric Rating Scale and the Hospital Anxiety and Depression Scale. Results: Mean patient age was 59 years; 62.5% of the patients were female; and 69.1% had at least one underlying phenotype associated with chronic cough. Of the latter, 52.1% had bronchial hyperresponsiveness/airflow limitation, 33.3% had airway reflux and 20.1% had upper airway cough syndrome. 46% of patients with a phenotype, and 51% without, experienced no improvement in their quality of life or still had significant cough remaining after 6 months. Of patients with available quality-of-life data, 37.5% were categorised as having refractory chronic cough, and 9.5% were categorised as unexplained chronic cough. Discussion: This study highlights the poor quality-of-life outcomes in patients with chronic cough, despite interventions to treat underlying conditions, and indicates a need to manage chronic cough irrespective of phenotype.

Replication of Oncology Randomized Trial Results using Swedish Registry Real World-Data: A Feasibility Study.

Nationwide healthcare registries are potential important real-world data (RWD) sources for assessing drug effectiveness in oncology. However, it is unclear whether registry-derived RWD are suitable for clinical development. In this study, we replicate results from the comparator arm of two previously published oncology randomized controlled trials (RCTs) using RWD from Swedish nationwide healthcare registries. For replication 1, the RCT included 553 patients and the RWD included 283 patients treated with sorafenib for advanced hepatocellular cancer. The median overall survival (OS) was 11.2 (95% confidence interval (CI): 10.1-13.2) months in the RCT and 8.2 (95% CI: 7.0-9.9) months in the RWD, unadjusted hazard ratio (HR) 0.75 (95% CI: 0.63-0.88). For time-to-treatment discontinuation (TTD), the HR was 1.00 (95% CI: 0.87-1.16). For replication 2, the RCT included 154 patients and the RWD included 704 patients treated with melphalan, prednisone, and thalidomide for untreated multiple myeloma. The median OS was 52.6 (95% CI: 40-not applicable) months in the RCT and 36.9 (95% CI: 33.8-40.5) months in the RWD, unadjusted HR 0.67 (95% CI: 0.51-0.87). For TTD, the HR was 0.89 (95% CI: 0.74-1.06). The results were similar when applying various propensity-based confounding adjustments. In conclusion, OS was shorter in the RWD, whereas TTD was similar. Importantly, the data necessary (ex: eligibility criteria and baseline confounders) for replicating RCTs was mostly not available and these results further underscore the importance of developing frameworks for capturing relevant patient-level RWD for clinical and regulatory decision making in oncology.

Sharing Patient-Controlled Real-World Data Through the Application of the Theory of Commons: Action Research Case Study.

BACKGROUND: Technological advances have radically changed the opportunities for individuals with chronic conditions to practice self-care and to coproduce health care and research. Digital technologies enable patients to perform tasks traditionally carried out by health care professionals in a more convenient way, at lower costs, and without compromising quality. Patients may also share real-world data with other stakeholders to promote individual and population health. However, there is a need for legal frameworks that enable patient privacy and control in such sharing of real-world data. We believe that this need could be met by the conceptualization of patient-controlled real-world data as knowledge commons, which is a resource shared by a group of people. OBJECTIVE: This study aimed to propose a conceptual model that describes how patient-controlled real-world data can be shared effectively in chronic care management, in a way that supports individual and population health, while respecting personal data privacy and control. METHODS: An action research approach was used to develop a solution to enable patients, in a self-determined way, to share patient-controlled data to other settings. We chose the context of cystic fibrosis (CF) care in Sweden, where coproduction between patients, their families, and health care professionals is critical in the introduction of new drugs. The first author, who is a lawyer and parent of children with CF, was a driver in the change process. All coauthors collaborated in the analysis. We collected primary and secondary data reflecting changes during the time period from 2012 to 2020, and performed a qualitative content analysis guided by the knowledge commons framework. RESULTS: Through a series of changes, a national system for enabling patients to share patient-controlled real-world data to different stakeholders in CF care was implemented. The case analysis resulted in a conceptual model consisting of the following three knowledge commons arenas that contributed to patient-controlled real-world data collection, use, and sharing: (1) patient world arena involving the private sphere of patients and families; (2) clinical microsystem arena involving the professional sphere at frontline health care clinics; and (3) round table arena involving multiple stakeholders from different settings. Based on the specification of property rights, as presented in our model, the patient can keep control over personal health information and may grant use rights to other stakeholders. CONCLUSIONS: Health information exchanges for sharing patient-controlled real-world data are pivotal to enable patients, health care professionals, health care funders, researchers, authorities, and the industry to coproduce high-quality care and to introduce and follow-up novel health technologies. Our model proposes how technical and legal structures that protect the integrity and self-determination of patients can be implemented, which may be applicable in other chronic care settings as well.

Low-density lipoprotein-cholesterol target attainment according to the 2011 and 2016 ESC/EAS dyslipidaemia guidelines in patients with a recent myocardial infarction: nationwide cohort study, 2013-17.

AIMS: To assess low-density lipoprotein cholesterol (LDL-C) treatment target attainment among myocardial infarction (MI) patients according to the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) dyslipidaemia guidelines from 2011 (LDL-C < 1.8 mmol/L or ≥50% LDL-C reduction) and 2016 (LDL-C < 1.8 mmol/L and ≥50% LDL-C reduction). METHODS AND RESULTS: Using nationwide registers, we identified 44 890 patients aged 21-74 admitted for MI, 2013-17. We included those attending follow-up visits at 6-10 weeks (n = 25 466) and 12-14 months (n = 17 117) after the event. Most patients received high-intensity statin monotherapy [84.3% (6-10 weeks) and 69.0% (12-14 months)] or statins with ezetimibe (2.7% and 10.2%). The proportion of patients attaining the 2011 LDL-C target was 63.8% (6-10 weeks) and 63.5% (12-14 months). The corresponding numbers for the 2016 LDL-C target were 31.6% (6-10 weeks) and 31.5% (12-14 months). At the 6- to 10-week follow-up, 37% of those not attaining the 2011 LDL-C target and 48% of those not attaining the 2016 target had an LDL-C level that was ≥0.5 mmol/L from the target. When comparing LDL-C measurements performed before vs. after the release of the 2016 guidelines, attainment of the 2016 LDL-C target increased from 30.2% to 35.0% (6-10 weeks) and from 27.6% to 37.6% (12-14 months). CONCLUSION: In a nationwide register, one out of three patients with a recent MI had not attained the LDL-C target of the 2011 ESC/EAS guidelines and two out of three patients had not attained the LDL-C target of the 2016 guidelines.

Quantifying and Describing the Natural History and Costs of Alzheimer's Disease and Effects of Hypothetical Interventions.

BACKGROUND: A long-term horizon is necessary when the socioeconomic consequences and the potential effects of interventions in Alzheimer's disease (AD) are estimated. OBJECTIVES: To illustrate the potential societal costs of AD across the disease continuum and to illustrate the potential cost-effectiveness of a hypothetical intervention with disease modifying treatment (DMT). METHODS: Based on the Swedish dementia registry, a Markov model was used to simulate a virtual cohort of 100,000 people with mild cognitive impairment (MCI) due to AD (AD-MCI) in Sweden for 40 years starting at the age of 60. A simulated hypothetical intervention assumed a 25% reduction in progression rate during AD-MCI and mild AD-dementia. A comprehensive set of sensitivity analyses was included. RESULTS: The cumulative risk to develop dementia was 96%. The mean simulated survival was 19.0 years. The net present value for a person year with dementia was 252,843 SEK (about 29,500 US$). The cost effectiveness model illustrated how the hypothetical scenario of a 25% reduction in progression to AD-dementia would require 41 AD-MCI patients to be treated to prevent one case of AD-dementia (2,447 avoided AD-dementia cases of 100,000 with AD-MCI). Most scenarios illustrated hypothetical cost effectiveness (based on a willingness to pay level of 600,000 SEK (70,000 US$) per gained QALY), but not cost savings. DISCUSSION: Lifetime societal costs of AD are substantial. A future DMT may be potentially cost-effective given assumed treatment effects and costs, but cost savings are unlikely.

Eliminating viral hepatitis C in Belgium: the micro-elimination approach.

BACKGROUND: Hepatitis C virus is one of the leading causes of chronic liver disease and liver-related deaths worldwide. The estimated prevalence of chronic hepatitis C viral infection among the general Belgian population was 0.57% (n = 64,000) in 2015. Although Belgium has had a 'Hepatitis C Plan' since 2014, elimination efforts are unclear. This study employs the best available data and modelling estimates to define the burden of hepatitis C viral infection among key subgroups in Belgium, identify information gaps and propose potential approaches to screening, linkage to care and treatment, and cure. METHODS: We examined the peer-reviewed and grey literature since 2012 for data on the prevalence of hepatitis C viral infection in Belgium in key subgroups identified by national experts and in the literature. Ultimately, this research is primarily based on data provided by the key stakeholders themselves due to a lack of reliable data in the literature. Based on this, we modelled the treatment rates required to reach elimination of hepatitis C in several subgroups. RESULTS: Eleven potential subgroups were identified. There were no data available for two subgroups: generational cohorts and men who have sex with men. In six subgroups, fewer than 3000 people were reported or estimated to have hepatitis C infection. Migrants and people who inject drugs were the most affected subgroups, and children were the least affected subgroup. Only two subgroups are on target to achieve elimination by 2030: patients living with haemophilia and transplant recipients. CONCLUSIONS: Removing Belgian treatment reimbursement restrictions in January 2019 was a big step towards eliminating HCV. In addition, increasing surveillance, including with a national registry, treatment prescription by other health-care providers and availability of treatment in local pharmacies are central to improving the current situation and getting on track to reach the 2030 WHO hepatitis C elimination targets in Belgium.

Pacing therapy in children with isolated complete atrioventricular block: a retrospective study of pacing system survival and pacing-related complications in a national cohort.

AIMS: To evaluate pacing system survival and complications to pacemaker (PM) therapy in children with isolated complete atrioventricular block (CAVB). METHODS AND RESULTS: We performed a nationwide retrospective study of children diagnosed before 15 years of age with isolated CAVB and PM treatment. Between 1983 and 2012, 127 patients underwent PM-implantations at 3.2 (0-17) [median (range)] years and were followed for 11 (0.6-19) years. An endocardial or epicardial PM system was implanted in 72 and 55 patients, respectively. A total of 306 pacing leads (76% steroid-eluting) were implanted. Pacing system survival was significantly affected by age, with a higher risk of a new intervention for children aged <1 month at first implantation. Lead survival of the steroid-eluting leads at 5 and 10 years was 90 and 81%, respectively, with no difference between epicardial and endocardial systems. Complications leading to revision of the pacing system occurred in 24% of the patients. Patients aged <1 month at first PM implantation had a five-fold increased risk for a complication to occur. Dividing the cohort according to year of first procedure showed that those who had their first implantation ≥2002 had fewer complications and also lead- and pacing system survival was better in the later cohort. CONCLUSION: Pacing system survival and complications to PM therapy in young patients with isolated CAVB were significantly affected by age, with low age at PM implantation constituting a risk factor. Endocardial and epicardial pacing systems showed no significant differences in performance.