Macrophage-derived insulin antagonist ImpL2 induces lipoprotein mobilization upon bacterial infection.

The immune response is an energy-demanding process that must be coordinated with systemic metabolic changes redirecting nutrients from stores to the immune system. Although this interplay is fundamental for the function of the immune system, the underlying mechanisms remain elusive. Our data show that the pro-inflammatory polarization of Drosophila macrophages is coupled to the production of the insulin antagonist ImpL2 through the activity of the transcription factor HIF1α. ImpL2 production, reflecting nutritional demands of activated macrophages, subsequently impairs insulin signaling in the fat body, thereby triggering FOXO-driven mobilization of lipoproteins. This metabolic adaptation is fundamental for the function of the immune system and an individual's resistance to infection. We demonstrated that analogically to Drosophila, mammalian immune-activated macrophages produce ImpL2 homolog IGFBP7 in a HIF1α-dependent manner and that enhanced IGFBP7 production by these cells induces mobilization of lipoproteins from hepatocytes. Hence, the production of ImpL2/IGFBP7 by macrophages represents an evolutionarily conserved mechanism by which macrophages alleviate insulin signaling in the central metabolic organ to secure nutrients necessary for their function upon bacterial infection.

Glucose and trehalose metabolism through the cyclic pentose phosphate pathway shapes pathogen resistance and host protection in Drosophila.

Activation of immune cells requires the remodeling of cell metabolism in order to support immune function. We study these metabolic changes through the infection of Drosophila larvae by parasitoid wasp. The parasitoid egg is neutralized by differentiating lamellocytes, which encapsulate the egg. A melanization cascade is initiated, producing toxic molecules to destroy the egg while the capsule also protects the host from the toxic reaction. We combined transcriptomics and metabolomics, including 13C-labeled glucose and trehalose tracing, as well as genetic manipulation of sugar metabolism to study changes in metabolism, specifically in Drosophila hemocytes. We found that hemocytes increase the expression of several carbohydrate transporters and accordingly uptake more sugar during infection. These carbohydrates are metabolized by increased glycolysis, associated with lactate production, and cyclic pentose phosphate pathway (PPP), in which glucose-6-phosphate is re-oxidized to maximize NADPH yield. Oxidative PPP is required for lamellocyte differentiation and resistance, as is systemic trehalose metabolism. In addition, fully differentiated lamellocytes use a cytoplasmic form of trehalase to cleave trehalose to glucose and fuel cyclic PPP. Intracellular trehalose metabolism is not required for lamellocyte differentiation, but its down-regulation elevates levels of reactive oxygen species, associated with increased resistance and reduced fitness. Our results suggest that sugar metabolism, and specifically cyclic PPP, within immune cells is important not only to fight infection but also to protect the host from its own immune response and for ensuring fitness of the survivor.

JAK/STAT mediated insulin resistance in muscles is essential for effective immune response.

BACKGROUND: The metabolically demanding nature of immune response requires nutrients to be preferentially directed towards the immune system at the expense of peripheral tissues. We study the mechanisms by which this metabolic reprograming occurs using the parasitoid infection of Drosophila larvae. To overcome such an immune challenge hemocytes differentiate into lamellocytes, which encapsulate and melanize the parasitoid egg. Hemocytes acquire the energy for this process by expressing JAK/STAT ligands upd2 and upd3, which activates JAK/STAT signaling in muscles and redirects carbohydrates away from muscles in favor of immune cells. METHODS: Immune response of Drosophila larvae was induced by parasitoid wasp infestation. Carbohydrate levels, larval locomotion and gene expression of key proteins were compared between control and infected animals. Efficacy of lamellocyte production and resistance to wasp infection was observed for RNAi and mutant animals. RESULTS: Absence of upd/JAK/STAT signaling leads to an impaired immune response and increased mortality. We demonstrate how JAK/STAT signaling in muscles leads to suppression of insulin signaling through activation of ImpL2, the inhibitor of Drosophila insulin like peptides. CONCLUSIONS: Our findings reveal cross-talk between immune cells and muscles mediates a metabolic shift, redirecting carbohydrates towards immune cells. We emphasize the crucial function of muscles during immune response and show the benefits of insulin resistance as an adaptive mechanism that is necessary for survival.

The Impact of Subclinical Hypothyroidism on the Quality of Life During Pregnancy: Mapping 5-Level Version of EQ-5D and ThyPRO-39.

OBJECTIVES: To describe how subclinical hypothyroidism (SubHypo) influences the quality of life (QoL) during pregnancy. METHODS: In primary data collection (NCT04167423), thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase antibodies, generic quality of life (QoL; 5-level version of EQ-5D [EQ-5D-5L]), and disease-specific QoL (ThyPRO-39) were measured among pregnant women. SubHypo during each trimester was defined according to the 2014 European Thyroid Association guidelines (TSH > 2.5, 3.0, and 3.5 IU/L, respectively; with normal FT4). Path analysis described relationships and tested mediation. Linear ordinary least squares, beta, tobit, and two-part regressions were used to map ThyPRO-39 and EQ-5D-5L. Alternative SubHypo definition was tested in sensitivity analysis. RESULTS: A total of 253 women at 14 sites (31 ± 5 years old, 15 ± 6 weeks pregnant) completed the questionnaires. Sixty-one (26%) had SubHypo and differed from 174 (74%) euthyroid women in smoking history (61% vs 41%), primiparity (62% vs 43%) and TSH level (4.1 ± 1.4 vs 1.5 ± 0.7 mIU/L, P < .001). EQ-5D-5L utility in SubHypo (0.89 ± 0.12) was lower than that in euthyroid (0.92 ± 0.11; P = .028) even after adjustment (difference -0.04, P = .033), whereas ocular (P = .001, ThyPRO-39), cognitive symptoms (P = .043), anxiety (P < .0001), and the composite score were higher. The impact of SubHypo on utility was mediated by anxiety. Results were confirmed by sensitivity analysis. Final mapping equation (ordinary least squares) includes goiter symptoms, anxiety, upset stomach, composite score (ThyPRO-39), FT4 levels, and week of pregnancy (determination coefficient 0.36). CONCLUSION: This is the first QoL mapping of SubHypo during pregnancy and the first evidence that SubHypo is associated with a negative impact on QoL. The effect is mediated by anxiety. EQ-5D-5L utilities can be generated based on ThyPRO-39 scores collected in pregnant euthyroid and patients with SubHypo.

Novel approach to decision making for orphan drugs.

BACKGROUND: Out of 185 orphan medicinal products (OMPs) registered in 2015-2021, a mere 110 (59 percent) were available to Czech patients, and only 54 (29 percent) were officially reimbursed. Moreover, this proportion has steadily decreased over time. After years of public debate induced by this unsatisfactory OMP patient access, the national viewpoint shifted toward creating a special pathway for the reimbursement of OMP. Thus, a rigorous pricing and reimbursement procedure with strict timelines and elaborated methodology has been recently adopted in Czechia. METHODOLOGY: The innovative legislation follows the recommendations for value assessment and funding processes for rare diseases and incorporates additional elements of value, such as the societal perspective. First, the application with clinical evidence, cost-effectiveness, and budget impact analyses is submitted to the governmental health technology assessment (HTA) agency by the Marketing Authorization Holder or a Health Insurance Fund. Moreover, professional associations and patients' organizations are rightful participants in the proceeding, providing evidence and comments. Then, the HTA agency performs the assessment/appraisal of the evidence. It subsequently publishes the assessment report summarizing available information. The report is then forwarded to the Ministry of Health and its advisory body consisting of patients, clinical experts, health insurance funds, and the State. They critically evaluate the documents and issue a binding opinion following prespecified decision-making criteria. Based on this binding opinion, the decision is issued by the HTA agency. Thus, the role of the advisory body in this process is crucial. CONCLUSION: We believe that this novel approach may offer satisfactory patient access to orphan drugs. Moreover, it serves as a real-world example of "value-based" decision making.

The way to data: opinions and recommendations for the provision of health data for secondary use.

Healthcare data held by state-run organisations is a valuable intangible asset for society. Its use should be a priority for its administrators and the state. A completely paternalistic approach by administrators and the state is undesirable, however much it aims to protect the privacy rights of persons registered in databases. In line with European policies and the global trend, these measures should not outweigh the social benefit that arises from the analysis of these data if the technical possibilities exist to sufficiently protect the privacy rights of individuals. Czech society is having an intense discussion on the topic, but according to the authors, it is insufficiently based on facts and lacks clearly articulated opinions of the expert public. The aim of this article is to fill these gaps. Data anonymization techniques provide a solution to protect individuals' privacy rights while preserving the scientific value of the data. The risk of identifying individuals in anonymised data sets is scalable and can be minimised depending on the type and content of the data and its use by the specific applicant. Finding the optimal form and scope of deidentified data requires competence and knowledge on the part of both the applicant and the administrator. It is in the interest of the applicant, the administrator, as well as the protected persons in the databases that both parties show willingness and have the ability and expertise to communicate during the application and its processing.

Time in remission as an alternative outcome measure for rheumatoid arthritis: a 10-year prospective study of 2618 new users of anti-TNF.

OBJECTIVE: Achieving targeted disease activity (DA) is the primary therapeutic strategy in RA. Point measurements of DA are done at out-patient visits, however true DA between visits remains unobserved. This study sought to describe and validate a new outcome measure, i.e. time in remission (TIR). METHODS: Patients were enrolled in the Czech ATTRA-RA registry. TIR was calculated using linear interpolation of the DAS28-ESR determined at outpatient visits. Correlation coefficients were computed between TIR and DAS28-CRP, HAQ, Simple Disease Activity Index (SDAI), patient global assessment (PGA) and physician global assessment (PhGA). Using logistic regression, TIR was used as a predictor of remission (SDAI ≤3.3) and non-disability (HAQ <0.5). The predictive value of TIR was compared with point and sustained remission using the cross-validated area under receiver-operating curves. RESULTS: Since 2010, 2618 RA patients started anti-TNF therapy and were followed until 2020 or until treatment discontinuation. During the first 6 months of therapy, 56% of patients had no remission (TIR = 0), and 22% of patients reached sustained remission (TIR = 1), while 22% of patients had point remissions with 0 < TIR < 1. EULAR good responders and moderate/non-responders spent 64 ± 42% and 6 ± 18% of time in remission, respectively. The mean TIR grew during the follow-up and was correlated with DAS28-CRP, SDAI, HAQ, PGA, and PhGA (P < 0.0001). TIR at 3 and 6 months predicted remission (SDAI ≤3.3) and non-disability (HAQ <0.5) at 13 and 19 months better than point or sustained remission. CONCLUSIONS: TIR is an intuitive way of estimating unobserved DA between scheduled visits; its calculation only requires two consecutive DA values (https://www.medevio.cz/tir-calculator/). TIR is a valid predictor of RA outcomes.

Efficacy of switches within the class of IL-17 inhibitors: An analysis of data from the Czech nationwide registry of psoriatic patients receiving biological/targeted therapy (BIOREP).

The IL-17 cytokine family encompasses six different homodimers and heterodimers referred to as IL-17A-F. Due to some differences in the mechanism of IL-17 inhibition, aninsufficient effect of one IL-17 inhibitor does not necessarily imply lack of efficacy of the other agent of the same class. Aim of study was analysis of the success rate of switches among IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) in patients treated in the Czech Republic. Data were obtained from the Czech nationwide registry of psoriatic patients receiving biological/targeted therapy (BIOREP). Our analysis involved data of a total of 90 patients with severe chronic plaque psoriasis and baseline PASI scores >10 both prior to first-line biological therapy initiation and after switch to another agent of the class of IL-17 inhibitors. The most effective switch was that from secukinumab to brodalumab, with PASI 90 reached by 64.7% and 73.3% of patients at weeks 12 and 24. Among patients switched from secukinumab to ixekizumab target PASI 90 responses were achieved (at weeks 12 and 24) by 41.2% and 55.2% of patients. Among patients switched from ixekizumab to brodalumab target PASI 90 responses were achieved, at the above time points, by 30.8% and 38.5% of patients. Our analysis showed a high success rate of switches from secukinumab to ixekizumab and brodalumab, followed by the ixekizumab-to-brodalumab switch. Importantly, the therapeutic response and success rates of individual switches are independent of the patient's body weight and presence of psoriatis arthritis.

Real-life experience in the effectiveness, impact on quality of life and safety of dupilumab treatment in patients with moderate to severe atopic dermatitis in the Czech Republic.

OBJECTIVES: The aim of the study was to assess the effectiveness and safety of dupilumab therapy in patients with moderate-to-severe atopic dermatitis (AD) in a real-life Czech bicentric cohort. METHODS: We retrospectively analysed 50 patients with moderate-to-severe AD treated with dupilumab in two centres in the Czech Republic. Baseline characteristics, the Eczema Area and Severity Index (EASI) score and Dermatology Life Quality Index (DLQI) were collected at baseline and each 3 following months. The proportion of patients achieving EASI50, EASI75, EASI90 and EASI100 were analysed. Levels of immunoglobulin E (IgE) were collected before and after 6 and 12 months of therapy. Adverse events were recorded as well. RESULTS: Thirty-two men and 18 women with mean body mass index (BMI) of 25.7 were enrolled in our analysis. The mean age of the patients was 37.6 years and the mean time from diagnosis until the initiation of dupilumab therapy was 35.0 years. After 4 months, EASI75 was achieved by 75.7%, out of which 40.5% achieved EASI90 and 10.8% achieved complete clearance. Improvement continued with time, and the proportion of patients with EASI90 increased to 71.4% at the 6th month and at the 12th month of therapy the EASI90 was 65.2%. EASI100 was achieved by 14.3% and 13.0% at the 6th and 12th month, respectively. A marked reduction was observed in the DLQI and also in IgE levels. EASI responses were independent of BMI. No new safety issues were identified. Adverse events were experienced by 44% (22/50) of the patients and they were all mild in intensity. Conjunctivitis and herpes simplex virus infection were the most common adverse events. CONCLUSION: Our results confirmed the effectiveness and safety of dupilumab in a real-life setting in adult patients with moderate-to-severe AD in the Czech Republic. Dupilumab was well-tolerated and resulted in a significant clinical improvement in combination with improvement of quality of life.

Direct costs in patients with nonvalvular atrial fibrillation newly indicated to apixaban: a retrospective prospective single arm cohort study.

BACKGROUND: Atrial fibrillation (AF) affects 46.3 million people; its prevalence has tripled over the last 50 years. AF leads to formation of blood clots increasing four-fold the risk of a stroke. Preventive anticoagulant therapy with warfarin has been well established for over 50 years but has efficacy and safety limitations. New anticoagulants do not require laboratory monitoring of prothrombin time, have low risk of adverse events, yet are more costly. METHODS: This non-interventional (Act 378/2007 Coll.) retrospective-prospective single-arm cohort study consisted of 3 visits. The primary objective was to compare the total direct cost of treatment with warfarin and apixaban. Patients with non-valvular AF were enrolled at the time of discontinuation of warfarin and switching to apixaban. Costs were derived from the care provided and the list of medical procedures (Decrees 268/ 2019 Coll.). Satisfaction was assessed using SAFUCA® questionnaire. RESULTS: Between February 2017 and June 2019, 499 patients were enrolled in 29 Czech internal medicine clinics. The mean age of the patients was 73.6 ± 10.2 years, 36.5% were at high risk of bleeding (HAS-BLED score). Previous warfarin treatment lasted 5.9 ± 2.7 months, 63% were unable to achieve target prothrombin time, 18% switched due to adverse reactions. New apixaban treatment was followed for the first 6 months. Treatment with warfarin was associated with higher rates of major bleeding and adverse events (22 vs. 2), stroke (17 vs. 0), ischemic heart attack (11 vs. 0), and minor bleeding (173 vs. 2). The average daily cost following the switch to apixaban decreased from CZK 65.2 to CZK 4.8 (p.

Smoking in women with chronic vaginal discomfort is not associated with decreased abundance of Lactobacillus spp. but promotes Mobiluncus and Gardnerella spp. overgrowth - secondary analysis of trial data including microbio-me analysis.

BACKGROUND: Smoking is considered a risk factor for bacterial vaginosis. It is currently unknown which parameters of the vaginal environment are affected and how smoking triggers the disease. AIM OF THE STUDY: The primary objective is to estimate the effect size of smoking on vaginal pH and the Nugent score in patients with chronic vulvovaginal discomfort prior to the development of episode of vaginosis. The secondary goal is to investigate the effect of smoking on individual microscopic parameters of the vaginal environment and on subjectively reported symptoms of vaginal discomfort. METHODS: Smoking reported by patients was tested as a predictor, using multivariate logistic and ordinal logistic regression analysis on a dataset from the first visit of a randomized trial NCT04171947, which enrolled patients with intermediate vaginal environment. We tested the primary hypothesis (odds ratio (OR) for vaginal pH > 4.5 and Nugent score > 3 in smokers) at the significance level á = 5%. For exploratory analyses of the effect of smoking on the parameters of the vaginal environment, á was corrected as per Bonferoni. RESULTS: In a cross-sectional sample of 250 women after adjusting for other risk factors, smoking had an impact on the Nugent score (OR = 3.3 (1.3-8.5), P = 0.011), while pH was not affected (OR = 1.2 (0.5-2.8), P = 0.698). Smoking was associated with the prevalence of clue cells (P < 0.000), Gardnerella spp. (P = 0.001) and Mobiluncus spp. (P = 0.001), while the prevalence of Lactobacillus remained unchanged (P = 0.049). CONCLUSION: Contrarily to common assumptions, vaginal Lactobacillus is not directly affected by smoking, which rather promotes the growth of bacteria of Gardnerella and Mobiluncus spp. Given that other parameters remained unaffected, it appears that smoking leads to vaginal dysbio-sis by creating specific favourable conditions for these two opportunistic  pathogens.

Allocation of scarce resources in a pandemic.

The allocation of scarce medical resources during a pandemic is one of the most challenging medical doctors' decisions. Although these decisions are based on the best medical knowledge and lege artis practice, they are inextricably intertwined with ethical and prudential (related to the patients' well-being) values. This article stresses the importance of ethical decision making during the whole process of allocation. First, it sets out to lay down a set of moral principles governing the allocation of scarce resources (mechanical ventilation, ECMO, etc.). This way it paves the way for more concrete ethical recommendations. Second, it analyses and describes in elaborate detail the criteria for admission to the ICU and two triage phases. The first reflects egalitarian concerns, and the second considers age as a proxy for the badness of death and other age-related considerations. Lastly, the paper offers a legal analysis of the process of allocation in the context of the Czech legal system.

Factors influencing the end-of-life decisionmaking process about care in hospitalized patients.

The quality of end-of-life care of hospitalized patients is an important topic, but so far little explored in the Czech Republic. The aim of this study was to map the factors influencing the end-of-life care decision-making process in selected Czech hospitals and to describe it based on data from medical records and from the perspective of a doctor. The research included data obtained from the medical records of 240 deceased patients (mean age 76.9 years, 41.6% women). The research sample of medical doctors who commented on the decision-making about end-of-life care for these patients consisted of 369 physicians (mean age 35.9 years, 61% women). The results pointed to persistent deficiencies in the written recording of the care goals, prognosis, and possible decision to limit care. Medical doctors limit health care primarily based on consensus among physicians, the patient is usually not invited to the decision-making process. Patient preferences for the end-of-life period are in most cases not ascertained or this question is postponed. The institute of a previously stated wish did not appear in the examined group at all. It can be concluded that decisions about end-of-life care usually take place without knowledge of patients' values ​​and preferences. The results indicate the need to improve the training of doctors and medical students, which should, in addition to building professional competencies, include training in effective communication with patients at the end of life.

Competence and informed consent.

The issue of a patient´s competence is often solved in practice without a major theoretical concept. Such an approach, focused only on the basis of intuitions and experiences of physicians, however, may lead in some cases to an inadequate assessment of competence of a particular patient. Ultimately, it can happen that the decision of an incompetent person will be respected or that the decision of the competent person will be disrespected. Both possibilities can have ethical as well as legal consequences. This article addresses both theoretical and practical issues of competence in adult patients.

Extracellular adenosine modulates host-pathogen interactions through regulation of systemic metabolism during immune response in Drosophila.

Phagocytosis by hemocytes, Drosophila macrophages, is essential for resistance to Streptococcus pneumoniae in adult flies. Activated macrophages require an increased supply of energy and we show here that a systemic metabolic switch, involving the release of glucose from glycogen, is required for effective resistance to S. pneumoniae. This metabolic switch is mediated by extracellular adenosine, as evidenced by the fact that blocking adenosine signaling in the adoR mutant suppresses the systemic metabolic switch and decreases resistance to infection, while enhancing adenosine effects by lowering adenosine deaminase ADGF-A increases resistance to S. pneumoniae. Further, that ADGF-A is later expressed by immune cells during infection to regulate these effects of adenosine on the systemic metabolism and immune response. Such regulation proved to be important during chronic infection caused by Listeria monocytogenes. Lowering ADGF-A specifically in immune cells prolonged the systemic metabolic effects, leading to lower glycogen stores, and increased the intracellular load of L. monocytogenes, possibly by feeding the bacteria. An adenosine-mediated systemic metabolic switch is thus essential for effective resistance but must be regulated by ADGF-A expression from immune cells to prevent the loss of energy reserves and possibly to avoid the exploitation of energy by the pathogen.

Propensity Score Weighting Using Overlap Weights: A New Method Applied to Regorafenib Clinical Data and a Cost-Effectiveness Analysis.

BACKGROUND: In situations of markedly different population characteristics and weak population overlap, inverse propensity score (PS) weights suffer from extreme values. The new propensity score weighting method using overlap weights (PSOW) overcomes this limitation by estimating the overlap population at the point of highest mutual overlap, thus may be preferred to other balancing methods (trimming, target, or inverse weights) in some situations. OBJECTIVES: To evaluate the performance of PSOW with regorafenib effectiveness data from previously treated patients with metastatic colorectal cancer based on the Czech national registry data (regorafenib) and a global phase 3 randomized clinical trial (RCT) (placebo). The second goal was to assess the cost-effectiveness of regorafenib versus placebo. METHODS: Individual data on progression-free survival (PFS)/overall survival (OS) were balanced via PSOW for age, sex, Eastern Cooperative Oncology Group performance status, number of treatment lines, metastatic colorectal cancer location, KRAS mutation, and time from metastases estimated using logistic regression. The weighted Kaplan-Meier PFS/OS curves were used in a 3-state partitioned survival model. The R code is provided. RESULTS: In comparison with target or inverse PS weights, PSOW showed remarkable performance measured by effective sample size and PS weight distribution or extreme weights despite the weak overlap between the registry and RCT. In the registry or RCT cohort, regorafenib provided better survival compared with the RCT. The new PSOW hazard ratio for OS was 0.53 (RCT: 0.79), which is conservative compared with inverse or target weights with a hazard ratio of 0.44 and 0.27, respectively. CONCLUSION: This is the first use of PSOW for clinical data and cost-effectiveness analysis. It is promising in cases of weak or small population overlap and makes pharmacoeconomic modeling, in such cases, feasible.

Extracellular adenosine mediates a systemic metabolic switch during immune response.

Immune defense is energetically costly, and thus an effective response requires metabolic adaptation of the organism to reallocate energy from storage, growth, and development towards the immune system. We employ the natural infection of Drosophila with a parasitoid wasp to study energy regulation during immune response. To combat the invasion, the host must produce specialized immune cells (lamellocytes) that destroy the parasitoid egg. We show that a significant portion of nutrients are allocated to differentiating lamellocytes when they would otherwise be used for development. This systemic metabolic switch is mediated by extracellular adenosine released from immune cells. The switch is crucial for an effective immune response. Preventing adenosine transport from immune cells or blocking adenosine receptor precludes the metabolic switch and the deceleration of development, dramatically reducing host resistance. Adenosine thus serves as a signal that the "selfish" immune cells send during infection to secure more energy at the expense of other tissues.

Mammaplasty and reduction mammaplasty - significant change in quality of life.

Breast shape, symmetry and size significantly influence womens psyche, if there is any deviation in generally recognized standard. Currently cosmetic breast defects belong to most common problems in the field of the aesthetic surgery. The target of the mammaplasty is the restoration of the shape, volume and position of the nippleareolar complex. One of the most important factors of the well-done surgery is the protection of the nippleareolar complex. The knowledge of the arterial blood supply and the venous drainage of the breast is the integral part of the successful surgery. In aesthetic breast surgeries its always necessary not to concentrate just at health aspect of mammaplasty, but mainly at the its psychological aspect, which has a significant role in whole process. Keywords: mammaplasty, breast reduction, aesthetic surgery, nippleareolar complex.

New insights into the burden and costs of multiple sclerosis in Europe: Results of the Czech Republic.

INTRODUCTION: In order to estimate the value of interventions in multiple sclerosis (MS) - where lifetime costs and outcomes cannot be observed - outcome data have to be combined with costs. This requires that cost data be regularly updated. OBJECTIVES AND METHODS: This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption and work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of severity, in the societal perspective, in CZK 2015. RESULTS: A total of 747 patients (mean age 47 years) participated; 86% were below retirement age and of these, 49% were employed. Employment was related to disease severity, and MS affected productivity at work for 82% of those working. Overall, 92% and 66% of patients experienced fatigue and cognitive difficulties as a problem. Mean utility and annual costs were 0.832 and 257,000CZK at Expanded Disability Status Scale (EDSS) 0-3, 0.530 and 425,500CZK at EDSS 4-6.5 and 0.141 and 489,000CZK at EDSS 7-9. The average cost of a relapse was estimated at 12,600CZK. CONCLUSION: This study provides current data on MS in the Czech Republic that are important for the development of health policies.

[Clinical and economic benefits of the new antidiabetic drugs in the Czech Republic]. / Klinické a ekonomické prínosy nových antidiabetik v Ceské republice.

GOAL: Description of efficiency, safety and cost-effectiveness of the therapy with new antidiabetics from the incretins group for the patients whose treatment with DPP4 inhibitors and GLP1 receptor agonists respectively, commenced based on the real data from the routine clinical practice in the Czech Republic. METHODOLOGY: Collection of clinical data before the commencement of treatment and in the following 12 months. The following data was collected for all patients: demographic data, time elapsed from diagnosis, body weight, BMI, HbA1c, systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. After that a pharmaco-economic model was analyzed which can predict long-term incidence of microvascular and macrovascular complications, life span and a quality-adjusted life-year (QALY) span of life. RESULTS: The data of 320 patients followed for 12 months was analyzed (255 treated with DPP4 inhibitors and 65 treated with GLP1 receptor agonists). The patients average age was 60.4/57.9 years and this innovative therapy was commenced for them after 9.1 years on average from their being diagnosed with diabetes. The initial glycated hemoglobin was higher (7.0%, or 7.6% HbA1c/IFCC). The previous therapy had been mainly based on metformin and on sulfonylurea derivatives. After 12 months of treatment statistically significant decreases were recorded in glycated hemoglobin (by 1.4% and 1.8% resp.), systolic blood pressure (by 4.7 mm Hg and 4.6 mm Hg resp.), diastolic blood pressure (by 1.8 mm Hg and 3.0 mm Hg resp.), LDL-cholesterol (by 0.3 mmol/l), triglycerides (by 0.4 mmol/l and 0.2 mmol/l resp.), body weight (by 1.6 kg and 4.5 kg resp.) and BMI (by 0.5 and 1.6 resp.). The pharmacoeconomic model predicted that the improvement of diabetes compensation in the group of DPP4 inhibitors would lead in one diabetic patient to life extension by 0.36 year and by 0.31 QALY, and in the group of GLP1 agonists by 0.45 year and by 0.39 QALY. CONCLUSION: The analysis has shown that the treatment based on modern antidiabetic medications in the conditions of the Czech Republic reduces the incidence of microvascular and macrovascular complications, extends the life span and the standard quality (QALY) life span and, due to the prevented complications, also reduces health insurance spending.