Societal costs and survival of patients with biopsy-verified non-alcoholic steatohepatitis: Danish nationwide register-based study.

INTRODUCTION AND OBJECTIVES: Studies on the societal burden of patients with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) are sparse. This study examined this question, comparing NAFLD with matched reference groups. MATERIALS AND METHODS: Nationwide Danish healthcare registers were used to include all patients (≥18 years) diagnosed with biopsy-verified NAFLD (1997-2021). Patients were classified as having simple steatosis or non-alcoholic steatohepatitis (NASH) with or without cirrhosis, and all matched with liver-disease free reference groups. Healthcare costs and labour market outcomes were compared from 5 years before to 11 years after diagnosis. Patients were followed for 25 years to analyse risk of disability insurance and death. RESULTS: 3,712 patients with biopsy-verified NASH (n = 1,030), simple steatosis (n = 1,540) or cirrhosis (n = 1,142) were identified. The average total costs in the year leading up to diagnosis was 4.1-fold higher for NASH patients than the reference group (EUR 6,318), 6.2-fold higher for cirrhosis patients and 3.1-fold higher for simple steatosis patients. In NASH, outpatient hospital contacts were responsible for 49 % of the excess costs (EUR 3,121). NASH patients had statistically significantly lower income than their reference group as early as five years before diagnosis until nine years after diagnosis, and markedly higher risk of becoming disability insurance recipients (HR: 4.37; 95 % CI: 3.17-6.02) and of death (HR: 2.42; 95 % CI: 1.80-3.25). CONCLUSIONS: NASH, simple steatosis and cirrhosis are all associated with substantial costs for the individual and the society with excess healthcare costs and poorer labour market outcomes.

Burden of Disease of Duchenne Muscular Dystrophy in Denmark - A National Register-Based Study of Individuals with Duchenne Muscular Dystrophy and their Closest Relatives.

Background: Duchenne Muscular Dystrophy (DMD) is a progressive genetic disease with a prevalence of 1 per 3,600-6,000 male births. Individuals with DMD are typically diagnosed at age 4-7 years; median survival is 30 years. They require multidisciplinary care, personal assistance, and often special education. Objective: The aim was to assess the burden of disease in DMD in Denmark. This includes incidence, prevalence, use of healthcare services, labour market participation, educational outcomes, and overall attributable costs due to DMD. Impact on the closest relatives (siblings and parents) was also investigated. Methods: The comprehensive Danish national health and administrative registers were used to assess the burden of disease following individuals with DMD and closest relatives from five years before, and up to 20 years after DMD diagnosis. Individuals with DMD (and relatives) from 1994-2021 were included. All outcomes were compared to matched control groups without the disease drawn from the Danish population. Results: 213 unique individuals with DMD were identified. They had lower grades in school, required more special education and more healthcare and home care compared to their control group. The extra costs of special education summed to EUR 180,900 over the course of 11 years elementary school. They had an annual average productivity loss of EUR 20,200 between the age of 18 to 30. The extra healthcare costs of DMD in the 20 years after diagnosis were estimated to EUR 1,524,000. If an individual with DMD lives to be 30, total extra costs sum to EUR 2,365,800. Conclusions: Using national register data this study presented detailed results on the burden of disease of DMD, including impact on closest relatives. With 60 additional hospital admissions and 200 extra outpatient contacts in 20 years healthcare costs, but also costs of home care and special education, increases as disease progresses.

A retrospective, non-interventional study of breast cancer patients diagnosed with ER+/HER2 negative, locally advanced or metastatic breast cancer treated with palbociclib in Denmark.

BACKGROUND: The recommended first-line treatment for advanced, ER+/HER2 negative breast cancer is a CDK 4/6 inhibitor in combination with an endocrine backbone. This study investigated the use of palbociclib, as first- or second-line therapy for advanced breast cancer patients in a real-world setting. MATERIAL AND METHODS: This retrospective, population-based study included all Danish, advanced breast cancer patients with ER+/HER2 negative disease who initiated first- or second-line treatment with palbociclib from January 1st, 2017, until December 31st, 2020. The primary outcomes were PFS and OS. RESULTS: The study included 1054 advanced breast cancer patients with a mean age of 66.8 years. Median OS was 51.7 months (95% CI, 44.9-54.6) for all patients in the first-line setting (n = 728) and median PFS was 24.3 months (95% CI, 21.7-27.8). Patients treated in second line (n = 326) had a median OS of 32.5 months (95% CI, 29.9-35.9) and a median PFS of 13.6 months (95% CI, 11.5-15.7). In first-line setting, the PFS and OS were significantly different for endocrine sensitive patients treated with AI (aromatase inhibitor) (n = 423) vs. fulvestrant (n = 158) as endocrine backbone to palbociclib (median PFS AI 31.3 months vs fulvestrant 19.9 months, p = 0.002 and median OS AI 56.9 months vs. fulvestrant 43.6 months, p = 0.001). In endocrine resistant patients (n = 145), no statistically significant difference in PFS was shown (median PFS AI 21.5 months vs. fulvestrant 12.0 months, p = 0.09), whereas OS was significantly different (median OS AI 43.5 months vs. fulvestrant 28.8 months, p = 0.02). CONCLUSION: In this real-world study, treatment with palbociclib combination therapy met the standards of efficacy set by the phase III trials, PALOMA-2 and PALOMA-3, and the standards set by real-world studies in other countries. The study showed significantly different outcomes in terms of PFS and OS in endocrine sensitive patients comparing AI vs. fulvestrant as endocrine backbone to palbociclib as first-line therapy.

Small-Area Analysis of Treatment and Clinical Outcomes in Patients with Venous Thromboembolism in Denmark: A Nationwide Cohort Study.

OBJECTIVES: To investigate geographical variation in initiation and extended treatment with anticoagulants and clinical outcomes among patients hospitalized with first-time venous thromboembolism (VTE) in Denmark between 2007 and 2018. METHODS: Using nationwide health care registries, we identified all patients with a first-time VTE hospital diagnosis supported by imaging data from 2007 to 2018. Patients were grouped according to residential region (5) and municipality (98) at the time of VTE diagnosis. Cumulative incidence of initiation of and extended (beyond 365 days) anticoagulation treatment as well as clinical outcomes, including recurrent VTE, major bleeding, and all-cause death, were assessed. Sex- and age-adjusted relative risks (RRs) of the outcomes were computed when comparing across individual regions and municipalities. Overall geographic variation was quantified by computing the median RR. RESULTS: We identified 66,840 patients with a first-time VTE hospitalization. A difference in initiation of anticoagulation treatment of more than 20 percentage points between regions was observed (range: 51.9-72.4%, median RR: 1.09, 95% confidence interval [CI]: 1.04-1.13). Variation was also observed for extended treatment (range: 34.2-46.9%, median RR: 1.08, 95% CI: 1.02-1.14). The cumulative incidence of recurrent VTE ranged from 3.6 to 5.3% at 1 year (median RR: 1.08, 95% CI: 1.01-1.15). The difference remained after 5 years, and variation was also observed for major bleeding (median RR: 1.09, 95% CI: 1.03-1.15), whereas it appeared smaller for all-cause mortality (median RR: 1.03, 95% CI: 1.01-1.05). CONCLUSION: Substantial geographical variation in anticoagulation treatment and clinical outcomes occurs in Denmark. These findings indicate a need for initiatives to ensure uniform high-quality care for all VTE patients.

Improvements in Survival and Early Retirement Rates - Real-World Evidence on Danish Breast Cancer Patients 2004-2018.

Background: Historically, Denmark has had poor survival for cancer patients relative to other western countries with comparable health-care systems. In this study, we examine the long-term cancer impact of a nationwide reform addressing all cancer diagnostics, implemented in 2006. The analyses include patients diagnosed with breast cancer and their spouses (informal caregivers). Patients and their spouses diagnosed before and after the reform were compared. Focus is on the potential impact on overall survival, early retirement, sick leave, unemployment as well as earnings (income). Methods: In a nationwide retrospective cohort study utilizing the Danish National Patient Register we identified 77,474 breast cancer patients between 1st January 2002 and 31st December 2018. Data was merged with the National Cancer Register, the Central Person Register, the Education Register, the DREAM Register and the Income Register using citizens' personal identification number. Spouses of cancer patients were identified through the Central Person Register. Propensity score matching was applied to match populations before and after the reform. Analyses on matched as well as unmatched populations were performed. Results: In a matched sample, risk of mortality was reduced by 15% for breast cancer patients diagnosed after the reform. Moreover, there was a 15% reduced risk of early retirement. The patients diagnosed after the reform had reduced income three to five years after diagnosis relative to those diagnosed before the reform, likely due to survival bias and labor market conditions. In an unmatched sample of patients diagnosed two years before or after the reform, mortality was reduced by 7%. Conclusion: Implementation of the nationwide cancer reform together with advancement in new cancer treatments had a positive impact on survival and reduced risk of early retirement. The results from this study are reassuring that relevant health-care reforms improve cancer outcome.

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in Denmark compared with PPV23.

BACKGROUND: A new 20-valent pneumococcal conjugate vaccine (PCV20) provides protection against 20 pneumococcal serotypes. The vaccine has the potential to decrease the impact of pneumococcal diseases in society and to increase health among vulnerable persons. AIM: This study investigates the cost-effectiveness of vaccinating Danish adults in different age groups and risk of pneumococcal disease with PCV20 compared to the 23-valent pneumococcal polysaccharide vaccine (PPV23) - either as PCV20 compared to PPV23 or as PPV23 followed by PCV20 compared to PPV23. METHODS: A Markov model adapted to the Danish setting was developed to estimate clinical outcomes and costs of vaccinating the Danish population in specific age and risk groups. The model used a restricted societal perspective and estimated outcomes and costs using a lifetime time horizon. To estimate the clinical outcomes and costs, inputs on vaccine effectiveness and waning were retrieved from other studies whereas data on risk groups, coverage and costs were based on real-world data. RESULTS: The results showed that in all scenarios the incidence and mortality of pneumococcal disease were reduced when vaccinating with PCV20, resulting in lower costs. For the vaccine target group of adults aged ≥18 years at moderate or high risk and all adults aged ≥65 years both in the case of PPV23+PCV20 compared to PPV23 and in case of PCV20 compared to PPV23 vaccination with PCV20 was found to be a dominant strategy gaining 1,350 or 5,821 quality-adjusted life years (QALYs), respectively, and reducing total costs by 60 or 396 million EUR, respectively, as compared to PPV23 vaccination alone. Similar results of dominant PCV20 strategy were found for other age and risk group comparisons. Both deterministic and probabilistic sensitivity analyses confirmed the results being robust to changes in input parameters and applied assumptions. LIMITATIONS: Like other modelling studies, this analysis has limitations such as lack of detailed data for some inputs. CONCLUSION: Vaccination with PCV20 reduced the incidence and mortality of pneumococcal diseases in Danish adults compared to PPV23. This reduction has the potential to reduce the financial burden related to managing diseases while also increasing public health.

Feasibility of screening for atrial fibrillation in a domiciliary setting: opportunistic one-time screening at preventive home visits in municipalities.

Current evidence base for atrial fibrillation (AF) screening is insufficient. An important finding in the STROKESTOP study was that non-participants had significantly worse outcomes. In a group of potentially non-participants feasibility of opportunistic screening in a domiciliary setting with municipality preventive home visits to citizens ≥75 years was investigated. Handheld ECG device was used by trained municipality caregivers followed by cardiologist assessment. Eighty-five percent consented to being screened, and seven of 477 screened were found with AF. Opportunistic screening in preventive home visits had a high participation rate and was feasible. Randomized trials are needed before making any firm conclusions.

The cost-effectiveness of one-time opportunistic screening for atrial fibrillation in different age cohorts of inhabitants in Denmark aged 65 years and above: a Markov modelled analysis.

AIMS: The objective was to evaluate the cost-effectiveness of one-time opportunistic screening for atrial fibrillation (AF) in general practice in citizens aged ≥65 years in Denmark compared to a no-screening alternative following current Danish practice. METHODS AND RESULTS: A decision tree and a Markov model were designed to simulate costs and quality-adjusted life years (QALYs) in a hypothetical cohort of citizens aged ≥65 years equivalent to the Danish population (1 M citizens) over the course of 19 years, using a healthcare and societal perspective. Share of detected AF patients following opportunistic screening was retrieved from a recent Danish screening study, whereas the risk stroke and bleedings in AF patients were based on population data from national registries and their associated costs was obtained from published national registry studies. The present study showed that one-time opportunistic screening for AF was more costly, but also more effective compared to a no-screening alternative. The analysis predicts that one-time opportunistic screening of all Danes aged ≥65 years potentially can identify an additional 10 300 AF patients and prevent 856 strokes in the period considered. The incremental cost of such a screening programme is €56.4 M, with a total gain of 6000 QALYs, resulting in an incremental cost-effectiveness ratio of €9400 per QALY gained. CONCLUSION: Opportunistic screening in general practice in citizens aged ≥65 years in Denmark is cost-effective compared to a willingness-to-pay threshold of €22 000. The study and its findings support a potential implementation of opportunistic screening for AF at the general practitioner level in Denmark.

Cardiovascular disease in women with breast cancer - a nationwide cohort study.

BACKGROUND: There is increasing concern about cardiovascular disease (CVD) after breast cancer (BC). The aim of this study was to estimate the prevalence of different types of CVD in women diagnosed with BC compared to cancer-free controls as well as the incidence of CVD after BC diagnosis. METHODS: We performed a cohort study based on data from national registries covering the entire Danish population. We followed 16,505 cancer-naïve BC patients diagnosed from 2003 to 2007 5 years before and up to 10 years after BC diagnosis compared to 165,042 cancer-free controls. RESULTS: We found that 15.6% of BC patients were registered with at least one CVD diagnosis in hospital records before BC diagnosis. Overall, BC patients and controls were similar with regard to CVD comorbidity before BC diagnosis. After BC diagnosis, the incidence of all CVD diagnoses combined was significantly higher in BC patients than controls up to approximately 6 years after the index date (BC diagnosis). After 10 years, 28% of both BC patients and controls (without any CVD diagnosis up to 5 years before the index date) had at least one CVD diagnosis according to hospital records. However, the incidence of heart failure, thrombophlebitis/thrombosis and pulmonary heart disease including pulmonary embolism remained higher in BC patients than controls during the entire 10-year follow-up period. After 10 years, 2.7% of BC patients compared to 2.5% of controls were diagnosed with heart failure, 2.7% of BC patients compared to 1.5% of controls were diagnosed with thrombophlebitis/thrombosis, and 1.5% of BC patients compared to 1.0% of controls were diagnosed with pulmonary heart disease according to hospital records. Furthermore, we found that the risk of heart failure and thrombophlebitis/thrombosis was higher after chemotherapy. CONCLUSIONS: Focus on CVD in BC patients is important to ensure optimum treatment with regard to BC as well as possible CVD. Strategies to minimise and manage the increased risk of heart failure, thrombophlebitis/thrombosis and pulmonary heart disease including pulmonary embolism in BC patients are especially important.

Mortality from cardiovascular disease in women with breast cancer - a nationwide registry study.

BACKGROUND: Only few existing studies have investigated the mortality from cardiovascular disease (CVD) in women with breast cancer (BC). The aim of this study was to investigate CVD mortality in patients with BC compared with a matched control group without BC using national registry data. MATERIAL AND METHODS: We followed 16,505 Danish women diagnosed with BC in 2003-2007 up to 10 years after BC diagnosis compared with 165,042 matched controls from the general Danish population. The matching criteria included gender, age, region of residence, and education. We performed multivariate Cox regression analyses to investigate the influence of preexisting CVD on mortality. Moreover, we used the cumulative incidence and conditional probability functions to study the risk of CVD-related death in the presence of competing risk, i.e., the risk of dying from other causes than CVD. RESULTS: We found that preexisting CVD increased both overall mortality and CVD mortality in both patients with BC and controls. Furthermore, we found that patients with BC were at lower risk of dying from CVD up to 10 years after BC diagnosis compared with controls. The cumulative incidence of CVD as underlying cause of death was 4.0% in patients with BC and 5.7% in controls after 10 years. The most common CVD-related causes of death were ischemic heart disease including acute coronary syndrome, cerebrovascular accident, heart failure, and atrial fibrillation. DISCUSSION: Our study contributes to the growing body of work on BC and comorbidities and highlights the importance of CVD in individuals with BC. Further studies are needed to confirm our finding that patients with BC are at lower risk of dying from CVD up to 10 years after BC diagnosis compared with a matched control group without BC.

First case of community acquired giardiasis in Nuuk, Greenland.

We report a case of community acquired giardiasis, in Nuuk, Greenland. Likely source of infection being consumption of untreated water from a local reservoir, alternatively through contact with sewage. Giardia is widespread worldwide but has not commonly been considered a cause of gastrointestinal distress in patients in Greenland, without relevant travel history. This may be due to under diagnosis, or historically low prevalence of Giardia in the region. Climate change with increasing temperatures, growing tourism and pet travel may influence the presence of Giardia in the region. This case highlights the need to include giardiasis as a differential diagnosis in patients presenting with suspected infectious gastroenteritis in Greenland.

Purification and initial characterization of Plasmodium falciparum K+ channels, PfKch1 and PfKch2 produced in Saccharomyces cerevisiae.

Resistance towards known antimalarial drugs poses a significant problem, urging for novel drugs that target vital proteins in the malaria parasite Plasmodium falciparum. However, recombinant production of malaria proteins is notoriously difficult. To address this, we have investigated two putative K+ channels, PfKch1 and PfKch2, identified in the P. falciparum genome. We show that PfKch1 and PfKch2 and a C-terminally truncated version of PfKch1 (PfKch11-1094) could indeed be functionally expressed in vivo, since a K+-uptake deficient Saccharomyces cerevisiae strain was complemented by the P. falciparum cDNAs. PfKch11-1094-GFP and GFP-PfKch2 fusion proteins were overexpressed in yeast, purified and reconstituted in lipid bilayers to determine their electrophysiological activity. Single channel conductance amounted to 16 ± 1 pS for PfKch11-1094-GFP and 28 ± 2 pS for GFP-PfKch2. We predicted regulator of K+-conductance (RCK) domains in the C-terminals of both channels, and we accordingly measured channel activity in the presence of Ca2+.

Societal costs of venous thromboembolism and subsequent major bleeding events: a national register-based study.

AIMS: Detailed evidence on the societal costs of venous thromboembolism (VTE), i.e. deep vein thrombosis (DVT) and pulmonary embolism (PE), and of subsequent major bleeding events, e.g. intracranial and gastrointestinal bleedings, is limited. The objective was to estimate the average 3-year societal event costs attributable to VTE and subsequent major bleedings in Denmark. METHODS AND RESULTS: Based on nationwide Danish registers, each incident patient diagnosed with VTE in the period from 2004 to 2016 was identified and matched with four non-VTE patients by nearest-neighbour propensity score matching. For bleeding patients, the reference cohort was VTE patients without bleedings. Event costs in terms of VTE, DVT, PE, and major bleedings in VTE patients were measured by the 'difference-in-actual-cost' method within 3 years after the incidence. Societal costs included healthcare costs (primary care, hospital, and prescription medicine), municipality home care services, and production loss. The study population included 74 137 VTE incident patients (DVT: 43 099; PE: 31 038), and 4887 VTE patients with a major bleeding within 3 years from VTE diagnosis. The 3-year attributable societal VTE event costs were 40 024 EUR (DVT: 34 509 EUR; PE: 50 083 EUR) with 53% of these costs appearing in the first incident year. Similar results for major bleedings were 51 168 EUR with 46% of these costs appearing in the first incident year. CONCLUSION: The societal costs of VTE and subsequent major bleedings are substantial and ought to be considered. Estimated costs of events may be informative in evaluating the impact of preventive interventions targeting VTE and subsequent major bleedings.

Susceptibility patterns in Neisseria gonorrhoeae in Nuuk, Greenland, 2015-2018: a short communication.

Antimicrobial resistance in Neisseria gonorrhoeae (GC) has made gonorrhoea control and treatment more complex globally. In Greenland, the incidence of gonorrhoea is high and there is a need for continued surveillance of antimicrobial susceptibility.This study investigated gonococcal isolates obtained in Greenland's capital Nuuk between January 2015 and June 2018. Subsequent to collection, isolates were tested for ciprofloxacin and ceftriaxone susceptibility in order to monitor the resistance pattern among GC strains. 150 GC strains were isolated in Nuuk during the observation period (139 males, 93%; 11 females, 7%). All strains were fully susceptible to ceftriaxone. 49% of the GC strains were susceptible to ciprofloxacin. The median minimal inhibitory concentration (MIC) for ceftriaxone among GC strains resistant to ciprofloxacin was higher than among GC strains susceptible to ciprofloxacin. No differences in ciprofloxacin susceptibility and median MICs for ceftriaxone were observed by collection year. In conclusion no ceftriaxone resistance has been found in Nuuk to date. Continued easy access to diagnostics and treatment combined with increased and more systematic surveillance of antimicrobial susceptibility in Nuuk is recommended. Further, it is advisable to investigate the possibilities for intermittent sampling in Greenland outside of Nuuk, if obstacles in relation to sending sampling material to Nuuk can be bypassed.

Total costs of treating venous thromboembolism: implication of different cost perspectives in a Danish setting.

Aim: Optimal use of scarce resources is a focus in the healthcare sector, as resources devoted to health care are limited. Costs and health economic analyses can help guide decision-making concerning treatments. One important factor is the choice of cost perspective that can range from a focus on narrow drug budget costs to broader economic perspectives. In the case of treatment with oral anticoagulants in patients with venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, the aim of this cost analysis was to illustrate the differences in costs when applying different cost perspectives.Methods: In a cost analysis, pairwise comparisons of average costs of 6 months standard treatment with either a low molecular weight heparin parenteral anticoagulant (LMWH) and a Vitamin K Antagonist (VKA) versus one of the non-vitamin K oral anticoagulants [NOACs; dabigatran etexilate, rivaroxaban, apixaban, and edoxaban) used in daily clinical practice in Denmark for VTE patients were carried out. Each analysis included the results from five different cost analyses with increasingly broader cost perspectives going from the narrowest "drug cost only" perspective to the broadest "societal" perspective.Results: Focusing on "drug costs only", LMWH/VKA was associated with the lowest costs compared to all NOACs. However, including the economic impact of preventing recurrent VTE and limit bleedings, apixaban and rivaroxaban resulted in slightly lower health care costs than LMWH/VKA. When applying the "societal perspective", the total costs saved with apixaban and rivaroxaban compared to LMWH/VKA further increased, with apixaban having the lowest total costs.Conclusions: The present study's case of oral anticoagulants in VTE treatment illustrated the importance of the cost perspective in the choice of therapy. If decision-making were based on drug costs only, instead of applying a health care sector or societal cost perspective, suboptimal decisions may be likely.

Societal costs due to meningococcal disease: a national registry-based study.

PURPOSE: Limited detailed evidence exists on the societal costs of meningococcal disease. The objective of this study was to estimate the average 5-year societal cost of events attributable to meningococcal disease in Denmark. METHODS: The study was based on the nationwide Danish registries. Incident patients diagnosed with meningococcal disease were identified and each matched with two controls, using direct matching on age, gender, and level of education. Siblings constituted a secondary control population where one patient was matched with one sibling control without meningococcal disease. Costs related to health care in the primary and secondary sectors, prescription medicine, municipality home care services and costs of production loss, ie, estimated loss of yearly earnings, were included (1997-2015). RESULTS: The incidence of meningococcal disease fluctuated between 1980 and 2015. The average attributable societal costs were highest the first year after diagnosis, with costs equaling USD 18,920 per event in the primary study population (matched controls) and USD 16,169 in the secondary study population (sibling controls). Hospital admission costs accounted for 65% and production loss for 30%; however, having a lifetime perspective and including loss due to premature death further increase the costs of meningococcal disease events. CONCLUSION: The costs of meningococcal disease are substantial, and the estimated costs of event may be informative in evaluating the impact of preventive interventions targeting meningococcal disease.

Genetic Analysis of Signal Generation by the Rgt2 Glucose Sensor of Saccharomyces cerevisiae.

The yeast S. cerevisiae senses glucose through Snf3 and Rgt2, transmembrane proteins that generate an intracellular signal in response to glucose that leads to inhibition of the Rgt1 transcriptional repressor and consequently to derepression of HXT genes encoding glucose transporters. Snf3 and Rgt2 are thought to be glucose receptors because they are similar to glucose transporters. In contrast to glucose transporters, they have unusually long C-terminal tails that bind to Mth1 and Std1, paralogous proteins that regulate function of the Rgt1 transcription factor. We show that the C-terminal tail of Rgt2 is not responsible for its inability to transport glucose. To gain insight into how the glucose sensors generate an intracellular signal, we identified RGT2 mutations that cause constitutive signal generation. Most of the mutations alter evolutionarily-conserved amino acids in the transmembrane spanning regions of Rgt2 that are predicted to be involved in maintaining an outward-facing conformation or to be in the substrate binding site. Our analysis of these mutations suggests they cause Rgt2 to adopt inward-facing or occluded conformations that generate the glucose signal. These results support the idea that Rgt2 and Snf3 are glucose receptors that signal in response to binding of extracellular glucose and inform the basis of their signaling.

Opportunistic screening for atrial fibrillation in a real-life setting in general practice in Denmark-The Atrial Fibrillation Found On Routine Detection (AFFORD) non-interventional study.

Atrial fibrillation (AF) is a chronic disease with an incidence increasing steeply by age and affecting more than 11 million patients in Europe and the United States. Diagnosing AF is essential for the prevention of stroke by oral anticoagulation. Opportunistic screening for AF in patients ≥65 years of age is recommended by the European and Danish Societies of Cardiology. The study aim was to examine the detection rate of AF in consecutively screened patients in the primary care setting in Denmark. In an open, non-interventional, cluster, multicenter, cross-sectional, observational study patients ≥65 years of age entering consecutively into general practice clinics were invited to nurse-assisted opportunistic screening for AF. The General Practice (GP) clinics participating were randomized to patient inclusion in three age groups: 65-74, 75-84, and ≥85 years respectively. All patients underwent pulse palpation followed by 12-led electrocardiogram in case of irregular pulse. Two cardiologists validated all electrocardiogram examinations. Forty-nine general practice clinics recruited in total 970 patients split into three age groups; 480 patients (65-74 years), 372 (75-84 years), and 118 patients ≥85 years of age. Co-morbidities increased by age with hypertension being most frequent. Eighty-seven patients (9%) were detected with an irregular pulse, representing 4.4%, 10.5% and 22.9%, respectively in the three age groups. Assessment of electrocardiograms by the GP showed suspicion of AF in 13 patients with final verification of electrocardiograms by cardiologists revealing 10 AF-patients. The highest detection rate of AF was found in the ≥85 age group (3.39%) followed by the 65-74 age group (0.83%) and the 75-84 age group (0.54%). Opportunistic screening of AF in primary care is feasible and do result in the detection of new AF-patients. Close collaboration with cardiologists is advisable to avoid false positive screening results.

Setting priorities in the health care sector - the case of oral anticoagulants in nonvalvular atrial fibrillation in Denmark.

AIM: Resources devoted to health care are limited, therefore setting priorities is required. It differs between countries whether decision-making concerning health care technologies focus on broad economic perspectives or whether focus is narrow on single budgets ("silo mentality"). The cost perspective as one part of the full health economic analysis is important for decision-making. With the case of oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF), the aim is to discuss the implication of the use of different cost perspectives for decision-making and priority setting. METHODS: In a cost analysis, the annual average total costs of five oral anticoagulants (warfarin and non-vitamin K oral anticoagulants [NOACs; dabigatran, rivaroxaban, apixaban, and edoxaban]) used in daily clinical practice in Denmark for the prevention of stroke in NVAF patients are analyzed. This is done in pairwise comparisons between warfarin and each NOAC based on five potential cost perspectives, from a "drug cost only" perspective up to a "societal" perspective. RESULTS: All comparisons of warfarin and NOACs show that the cost perspective based on all relevant costs, ie, total costs perspective, is essential for the choice of therapy. Focusing on the reimbursement costs of the drugs only, warfarin is the least costly option. However, with the aim of therapy to prevent strokes and limit bleedings, including the economic impact of this, all NOACs, except rivaroxaban, result in slightly lower health care costs compared with warfarin. The same picture was found applying the societal perspective. CONCLUSION: Many broad cost-effectiveness analyses of NOACs exist. However, in countries with budget focus in decision-making this information does not apply. The present study's case of oral anticoagulants has shown that decision-making should be based on health care or societal cost perspectives for optimal use of limited resources. Otherwise, the risk is that suboptimal decisions will be likely.