[Rheumatological care in Germany : Memorandum of the German Society for Rheumatology and Clinical Immunology 2024]. / Rheumatologische Versorgung in Deutschland : Memorandum der Deutschen Gesellschaft für Rheumatologie und Klinische Immunologie 2024.

BACKGROUND: Rheumatology in Germany is facing major challenges. The need for rheumatological care is increasing and can no longer be met in some regions for capacity reasons. Too many people with an inflammatory rheumatic disease (IRD) have to forego appropriate care or receive it too late. The 4th new edition of the memorandum of the German Society for Rheumatology and Clinical Immunology (DGRh) provides information on rheumatological care in Germany. It was produced under the leadership of the DGRh together with the Professional Association of German Rheumatologists (BDRh), the Association of Acute Rheumatology Clinics (VRA), the German Rheumatism League (DRL) and the German Rheumatism Research Center (DRFZ). METHODS: The memorandum describes the current state and development of the following areas: number of people with IRD, outpatient, inpatient and rehabilitative care structures, number of specialists in rheumatology, education and training, quality of care, health economic aspects and digital care concepts. Proposals for health policy measures to safeguard rheumatological care are presented. RESULTS: Prevalence: approximately 1.8 million adults in Germany have an IRD. The prevalence is increasing, due to changes in the demographic structure of the population, improved diagnostics, treatment and longer survival. Care structures: outpatient specialist care (ASV) for rheumatic diseases is developing as a cross-sectoral care model for hospital outpatient clinics and rheumatology practices. Hospitals have been able to be certified as rheumatology centers since 2020, which enables structural developments. Specialists in rheumatology: as of 31 December 2023, there were 1164 specialists in rheumatology working in Germany. This included 715 physicians accredited to work in practices for national health assurance patients, 39% of whom were employees. In hospitals, 39% of doctors worked part-time. At least 2 rheumatology specialists per 100,000 adults are needed, i.e. around 1400, in order to provide adequate care. This means that there is a shortage of around 700 rheumatology specialists in the outpatient sector alone. Of all working specialists, 30% are currently aged 60 years old and over. Medical training: only 10 out of 38 (26%) state universities have an independent chair in rheumatology. In addition, 11 rheumatology departments are subordinate to a nonrheumatology chair. In the rheumatology-integration into student training (RISA) III study, only 16 out of 36 faculties fulfilled the recommended minimum number of compulsory hours of student rheumatology teaching. Continuing education in rheumatology: the annual postgraduate training qualifications do not cover the demand for rheumatology specialists, which is additionally increasing due to intensified workload, reduced capacities through retirement, and part-time work. Quality of care: since the introduction of highly effective medication patients with IRD have a much better chance of achieving remission of their disease. With early initiation of targeted therapy, the lives of many patients are hardly restricted at all: however, waiting times for a first rheumatological visit often last more than 3 months. Quality target is a first consultation within the first 6 weeks after the onset of symptoms. Models for early consultation, delegation of medical services, structured patient training and digital care concepts have been positively evaluated but are not covered financially. COSTS: the total annual costs for inflammatory joint diseases alone amount to around 3 billion euros. The direct costs have significantly risen since the introduction of biologics, while the indirect costs for sick leave, disability and hospitalization have fallen. CONCLUSION: The core demands of this memorandum are a significant and sustainable increase in the number of further training positions in the outpatient and inpatient sector, the creation of chairs or at least independent departments for rheumatology at all universities and the further implementation of new and cross-sectoral forms of care. This will ensure modern needs-based rheumatological care for all patients in the future.

Needs and preferences of informal caregivers regarding outpatient care for the elderly: a systematic literature review.

BACKGROUND: Informal caregivers are an essential pillar for ensuring and maintaining the outpatient care of the frail elderly. Due to demographic changes, including an increase in the number of people in need of care as well as changing social structures (full-time employment of women, increasing number of single households, etc.) these informal care structures are fraught by considerable challenges. To support and facilitate informal caregivers in their role of nursing, it is important to identify their preferences, needs, and thus create a preference-oriented system. METHODS: A systematic review was conducted to identify preferences and needs regarding the organization of informal care. The database searches were performed by using EMBASE, Scopus and Dimdi. RESULTS: A total of 44 studies were included in the present review. Studies from 17 different countries provide broad international perspectives. Besides the preferences for long-term care structure, the following four principal topics were identified: (1) informational needs; (2) support needs; (3) organizational needs, and (4) needs for societal recognition. CONCLUSION: To meet the current challenges in the outpatient or home-based care of elders, it is essential to strengthen the role of informal caregivers. Therefore, it is necessary to adopt and further develop informal care structures according to the needs of informal caregivers. However, demographic, financial and cultural aspects of each country need to be considered as these may influence the preferences and needs of informal caregivers.

Appendectomy in the pediatric population-a German nationwide cohort analysis.

BACKGROUND: Meta-analyses indicate advantages of laparoscopic compared to open appendectomy. Nationwide analyses on results of laparoscopic appendectomy are scarce and studies from Germany are not available. This observational cohort study based on a nationwide insurance database was performed to analyze results of pediatric laparoscopic versus open appendectomy in general use. METHODS: Data were extracted from the largest German statutory health insurance TK (∼9 million clients) in a 3-year period (2010-2012). All patients aged 4-17 years with International Classification of Procedures in Medicine (ICPM) code "appendectomy" were included. Logistic regression analysis for the risk of a surgical complication within 180 postoperative days was performed. RESULTS: Appendectomy was performed in 8110 patients (52.6 % male; 47.4 % female) and conducted laparoscopically in 75.0 % of the patients (conversion rate = 1.2 %). Laparoscopic compared to open surgery was associated with a shorter length of hospital stay in both uncomplicated and complicated appendicitis. Patients with complicated appendicitis had lower readmission rates for surgical complications after laparoscopic appendectomy and logistic regression analysis confirmed a significantly lower risk of readmission for surgical complications after laparoscopic compared to open operation in adolescents. Pediatric surgeons operated 23.9 % and general surgeons 76.1 % of patients. Laparoscopy was less frequently used and the conversion rate was significantly higher in pediatric surgical departments. CONCLUSION: This first nationwide German cohort study confirms that laparoscopic appendectomy is associated with a less complicated postoperative course compared to open appendectomy, particularly in patients with complicated appendicitis. Pediatric surgeons used laparoscopy less frequently compared to general surgeons. Laparoscopic appendectomy should therefore be further promoted in pediatric surgical centers in Germany.

Early complications after esophageal atresia repair: analysis of a German health insurance database covering a population of 8 million.

The treatment of esophageal atresia is not centralized in Germany. Therefore, high numbers of departments are involved. Data on the results of esophageal atresia repair from Germany are lacking. The aim of this study was to evaluate the early postoperative results after repair of esophageal atresia based on unbiased data of a German health insurance. We aimed to determine whether characteristics of the departments had an impact on outcome and compared the results from this study with the literature data from centers with a high caseload. Data of a German health insurance covering ∼10% of the population were analyzed. All patients who had undergone esophageal atresia repair from January 2007 to August 2012 were included. Follow-up data of 1 year postoperatively were analyzed. The potential impact of various characteristics of the treating surgical institutions was assessed. Results were compared with the latest international literature. Seventy-five patients with esophageal atresia underwent reconstructive surgery in 37 departments. The incidences of anastomotic leak (3%) and recurrent tracheoesophageal fistula (7%) were comparable with the literature (both 2-8%). Anastomotic stricture required dilatation in 57% of patients (mean 5.1 ± 5.6 dilatations) comparing unfavorably to most, but not all international reports. During 1-year follow-up, 93% of the patients were readmitted at least once (mean 3.9 ± 3.1 admissions). The incidence of complications did not correlate with any of the characteristics of the treating institutions such as academic affiliation, the number of consultants, beds, and preterm infants treated per year (all P > 0.05). Based on unbiased data, postoperative results after repair of esophageal atresia in Germany are comparable with recently published reports from international single centers. A correlation between the complication rate and characteristics of the treating institutions was not identified.

[Impact of guideline adherence on mortality in treatment of left heart failure]. / Auswirkung einer leitliniengerechten Behandlung auf die Mortalität bei Linksherzinsuffizienz.

BACKGROUND: The German national guidelines on chronic heart failure provide treatment recommendations to physicians and reflect the current level of evidence; however, it is questionable to what extent these recommendations are applied in the routine practice and what the effect of guideline adherence on mortality is. METHODS: In this study the claims data of a major German health insurance fund collected over a period of 4 years were analyzed. Using binary logistic regression and Cox regression analyses the influence of drug prescriptions, diagnostic measures, influenza vaccination, the New York Heart Association (NYHA) status, the age and gender on mortality were examined. RESULTS: The study population consisted of 85,465 heart failure patients. Approximately 60 % of the drugs were prescribed according to the guidelines. There was a positive correlation between a higher NYHA status and mortality with an odds ratio (OR) of 3.264. Especially pharmacotherapy with angiotensin-converting enzyme (ACE) inhibitors and beta blockers according to the guidelines was associated with a lower mortality rate (OR 0.448 resp. 0.444). Also patients diagnosed using echocardiography at regular intervals showed a lower risk of dying (OR 0.314). CONCLUSION: The results of this large sample could confirm the results of clinical trials that a therapy according to the guidelines has a significant impact on mortality. By analyzing the claims data evidence was found that in the treatment of heart failure patients the medical results could be improved by adherence to guideline recommendations.

[Age- and Gender-specific Costs as Well as Drug Therapies of ADHD Patients]. / Alters- und geschlechtsspezifische Kosten sowie die Versorgung mit medikamentösen Therapien von ADHS-Patienten.

UNLABELLED: Backround and Objectives: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed mental disorders in children and adolescents. The rate of persistence into adulthood varies up to 60% and shows the importance of the disease. Here we present age-stratified cost information on adult patients, as well as data on occupational therapy, medication and multimodal treatment. Furthermore, we also investigated retrospectively if methylphenidate was prescribed for adults already before its approval in 2011. METHODS: Claims data of a major German insurance fund (Techniker Krankenkasse) was available. Inclusion criteria were patients with ADHD diagnosis, either hospitalized or treated on an outpatient basis in 2006, 2007 and 2008 and insured over this period. This enabled identifying this disease as chronic. The data were analyzed as part of a control group design (1:3). Cost differences were examined as also the odds ratios for the burden of comorbidities and use of atomoxetine and methylphenidate. RESULTS: 77.9% of the identified ADHD patients were male (mean age: 16.5 years ±11.1). The mean total costs of patient treatment were € 2,032 (±4,112). The odds ratio was highest for the indication developmental disorders of scholastic skills (15.4) and differed between the sexes (female: 24.0 vs. male: 14.2). Drug prescription was higher in male than in female patients (atomoxetine: 7.2 vs. 5.9% and methylphenidate 59.1 vs. 48.4%). CONCLUSIONS: This study provides important insights into the importance of the adult ADHD collective. There were increasing resource consumption identified in adult ADHD patients. In addition, methylphenidate was used off-label for treating adults already before 2011 and its approval in 2011 provided increased certainty for physicians regarding prescription of this drug.

Suitability and Usability of Claims Data for Review of Guidelines for the Treatment of Chronic Heart Failure.

Background: Guidelines have special importance in medicine, however, it is questionable to what extent these recommendations are applied in daily care, and under which conditions claims data can be used for verification of guideline adherence. Method: Advantages and limitations of claims data for verification of guidelines compliance in the therapeutic area as well as the guidelines themselves were analysed and critically assessed. To substantiate these results, claims data of a major German health insurance fund (Techniker Krankenkasse) were analysed. Results: 104 236 patients were identified. With certain limitations, claims data are useful for verifying guideline adherence; it could be shown that in pharmacotherapy the beta-adrenergic receptor blocker was used to the highest extent (70.5%). In contrast, only 56.4% of patients were treated with pure ACE inhibitors and ACE combined preparation. Conclusion: In order to validate guideline adherence by means of claims data analyses, a number of conditions relating to the database, the therapeutic area and the guidelines themselves have to be considered. Guideline recommendations, which, for example, are based on clinical data, cannot be reviewed by using claims data. Despite these limitations, claims data provide a suitable tool for reviewing selected guideline recommendations. They show that the current use of pharmacotherapy as well as clinical and diagnostic interventions might be increased in accordance with the guideline recommendations.

One-year disease-related health care costs of incident vertebral fractures in osteoporotic patients.

SUMMARY: The study aims to estimate the direct disease-related costs of osteoporotic vertebral compression fractures (OVCF) in patients with newly diagnosed fracture in the first year after index in Germany. Analyses reveal that OVCFs are associated with significant costs. In light of high and increasing incidence, the results emphasize importance of research in this field. INTRODUCTION: OVCF are among the most common fractures related to osteoporosis. They have been shown to be associated with excess mortality and meaningful healthcare costs. Costs calculations have illustrated the significant financial burden to society and national social security systems. However, this information is not available for Germany. Therefore, aim of the study was to estimate the direct disease-related costs of OVCF in patients with newly diagnosed fracture in the first year after index in Germany. METHODS: Data were obtained from a claims dataset of a large German health insurance fund. Subjects ≥ 60 years with a new vertebral fracture between 2006 and 2010 were studied retrospectively compared to a matched paired OVCF-free patient group. All-cause and fracture-specific medical costs were calculated in the 1-year baseline and follow-up period. Generalized linear model (GLM) was estimated for total follow-up healthcare cost. RESULTS: A total of 2,277 pairs of matched OVCF and OVCF-free patients were included in the analysis. Baseline costs were higher in the OVCF group. Mean unadjusted all-cause healthcare cost difference in the four quarters following the index date between OVCF and OVCF-free patients was 8,200 (p < 0.001). Of the difference, almost two third was attributable to inpatient services and one quarter to prescription drug costs. The GLM procedure revealed that OVCF-related costs in the first year after the index date add up to 6,490 (p < 0.001; CI 5,809 -6,731 ). CONCLUSIONS: Despite limitations of this study, our results are consistent with other research and demonstrate that OVCFs are associated with significant costs. The results underline the importance of medical interventions that can help to prevent fractures and treatments, which are cost-effective and can prevent recurrent fractures.

[Calculation of disease-related costs in claims data analyses with the example of attention-deficit hyperactivity disorder. Comparison of methods]. / Die Berechnung indikationsspezifischer Kosten bei GKV-Routinedatenanalysen am Beispiel von ADHS. Ein Methodenvergleich.

Claims data have proven useful for carrying out cost-of-illness studies. To avoid overestimating disease-related costs, only those costs that are related to a specific disease should be considered. The present study demonstrates two basic approaches for identifying disease-related costs. Using the example of attention-deficit hyperactivity disorder (ADHD), the advantages and drawbacks of expert-based approaches and those based on control groups are compared. Anonymized data from the "Techniker Krankenkasse" for 2008 were available for the study. The study population encompassed all ADHD patients and a control group that was five times bigger. Additionally, a systematic literature review was carried out on 65 relevant studies. Compared with the control group, disease-related costs were EUR 2,902 per ADHD patient on average. However, using the expert-based approach, costs were established to be EUR 923 lower. This is mainly because a comparison with an appropriate control group incorporates all costs for possible comorbidities and concomitant diseases. Both approaches have specific advantages and drawbacks, and when planning studies the respective limitations need to be considered.

[Therapy of rheumatoid arthritis with methotrexate. Claims data analysis of treatment patterns]. / Therapie der rheumatoiden Arthritis mit Methotrexat. Analyse von Versorgungsaspekten anhand von GKV-Routinedaten.

Methotrexate (MTX) is the most important disease-modifying antirheumatic drug (DMARD) and is recommended by national and international guidelines as the first choice for treatment of rheumatoid arthritis (RA). Recent studies reporting prescription data of MTX captured only patients who were treated by rheumatologists. Therefore, the aim of the present study was to analyse several aspects of the prescription of MTX based on claims data. Outpatient and inpatient diagnoses as well as prescription data was available for 9579 RA patients for the years 2005-2008. Of the patients 45% were treated exclusively with parenteral MTX, 8% were treated exclusively with oral MTX and 48% switched between both forms of application. The average weekly dosage presribed in 70% of the patients was between 10 and 25 mg. The most common DMARD combination was MTX plus leflunomide with 16%. In 16% RA patients were treated with a combination of MTX and TNF-α inhibitors. Glucocorticoids were prescribed temporarily in 81% together with MTX and supplementation with folic acid was given only in 65%. The results of this study provide important insights into the drug supply of MTX to RA patients in the German statutory health care sector. In particular, the high frequency of prescriptions of parenteral MTX and the inadequate prescription of folic acid are different from the recently published multinational recommendations of the 3E initiative for the use of MTX.

[Implementation of the new German job role code and its application in claims data analysis. Possibilities and limitations]. / Einführung des neuen Tätigkeitsschlüssels und seine Anwendung in GKV-Routinedatenauswertungen. Möglichkeiten und Limitationen.

In recent years, claims data analyses have become of increasing importance in several scientific disciplines in Germany. In specific research projects, it can be necessary to refine and to standardize the results by socioeconomic data. Information about graduation, social status, and occupation are provided by the German job role code for all people insured by statutory health insurance. During recent years, the working scheme has changed and new professions have appeared. Therefore, there has been a discussion about actualization and modification of the job role code. Since December 2011, an actualized job role code with an extensive set of new information is available. In addition, a new classification of professions is available in Germany which was considered in the design of the new job role code. The aim of this overview is to describe the structure of the new job role code as well as to discuss possible uses and limitations.

Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs.

A mevalonate-independent pathway of isoprenoid biosynthesis present in Plasmodium falciparum was shown to represent an effective target for chemotherapy of malaria. This pathway includes 1-deoxy-D-xylulose 5-phosphate (DOXP) as a key metabolite. The presence of two genes encoding the enzymes DOXP synthase and DOXP reductoisomerase suggests that isoprenoid biosynthesis in P. falciparum depends on the DOXP pathway. This pathway is probably located in the apicoplast. The recombinant P. falciparum DOXP reductoisomerase was inhibited by fosmidomycin and its derivative, FR-900098. Both drugs suppressed the in vitro growth of multidrug-resistant P. falciparum strains. After therapy with these drugs, mice infected with the rodent malaria parasite P. vinckei were cured.

Surgery for Pediatric Ureteropelvic Junction Obstruction-Comparison of Outcomes in Relation to Surgical Technique and Operating Discipline in Germany.

INTRODUCTION: Surgery for ureteropelvic junction obstruction (UPJO) is performed by both pediatric surgeons (PS) and urologists (URO). The aim of this study was to analyze treatment modalities for UPJO and results in relation to the surgical technique and the operating discipline in Germany. MATERIALS AND METHODS: Data of patients aged 0 to 18 years were extracted from a major public health insurance (covering ∼5.7 million clients) during 2009 to 2016 and were analyzed for sociodemographic variables, surgical technique, and treating discipline. Logistic regression analysis was performed for the risk of a complication within the first postoperative year. RESULTS: A total of 229 children (31.0% female) were included. Laparoscopic pyeloplasty (LP) was performed in 58 (25.3%) patients (8.6 ± 6.4 years), and open pyeloplasty (OP) was applied in 171 (74.7%; 4.6 ± 5.9 years). LP was the dominant technique in females (p < 0.02); males preferentially underwent OP (p < 0.02). Length of hospital stay was 4.3 days (p = 0.0005) shorter in LP compared with that in OP, especially in children ≤ 2 years (6.7 days, p = 0.007). PS operated on 162 children (70.7%), and URO performed surgery on 67 patients (29.3%). The mean age of children operated by PS (3.5 ± 4.7 years) was significantly younger compared with that operated by URO (10.8 ± 6.5 years, p < 0.0001). Complication rates were independent of surgical technique or treating specialty. CONCLUSION: In Germany, UPJO was treated by LP in 25.3% of patients, which was associated with a shorter length of stay, especially in children ≤ 2 years. Complication rates were independent of the operating specialty and surgical technique. Therefore, LP should be further promoted for the treatment of UPJO in small children.

Comparative cost analysis of outpatient and inpatient rehabilitation for musculoskeletal diseases in Germany.

OBJECTIVES: To examine the costs of inpatient and outpatient rehabilitation for musculoskeletal disorders from the perspective of a major statutory health insurance fund in Germany. METHODS: A nation-wide database from a major health insurance fund in Germany was used to evaluate all rehabilitation cases in 2005. In addition, to all direct cost domains of the rehabilitation itself, costs incurred in the preceding and the following year for hospital treatment, drugs and physical therapy were analysed. A cost-cost analysis in different institutional settings was chosen for the cost comparison of inpatient and outpatient rehabilitation. To minimize the influence of possible confounders, a statistical control system was implemented. RESULTS: After a preceding hospital stay, inpatient and outpatient rehabilitation results in mean costs of euro2047 and euro1111, respectively. If the rehabilitation was not preceded by a directly related hospital treatment, mean costs for inpatient (outpatient) rehabilitation were euro2067 (euro1310). No systematic differences could be found between inpatient and outpatient rehabilitation evaluating costs for hospital treatment, drugs or physical therapy in the year preceding and the year directly following the rehabilitation. CONCLUSIONS: Assuming comparable medical outcomes, outpatient rehabilitation seems to be a superior alternative compared with inpatient rehabilitation from an economic perspective. Hence, from the perspective of the statutory health insurance, fostering a higher market share of outpatient rehabilitation may add to a better allocation of overall health care resources. For this, regional differences in rehabilitation infrastructure have to be taken into account.

Guidelines versus reality: is coronary stent application in three-vessel disease standard or the exception?

The national guidelines for treatment of chronic coronary heart disease (CHD) recommend surgical coronary aortic bypass grafting (CABG) rather than percutaneous coronary intervention (PCI) for patients with a coronary three-vessel disease. The epidemiology of three-vessel CHD and data about the application of different revascularisation strategies raise suspicion of deviation from the guidelines in the treatment of those patients. Claims data containing records of almost 10 million patients of the largest German statutory health insurance fund (Techniker Krankenkasse) were utilised to measure adherence to the guidelines for treatment of groups of patients with one-, two-, and three-vessel CHD, respectively. The impact of age, sex, and comorbidity on each patient's revascularisation procedure was investigated as well. There was no significant difference in the rate of PCI between the groups. In conclusion, the hypothesis that patients with a coronary three-vessel disease are not always treated according to the recommendations of the national guidelines could not be disproved by this study. Finally, the results of this study suggest that the best revascularisation strategy for each patient with two- and three-vessel disease should be decided upon by an interdisciplinary discussion between both cardiologists and cardiac surgeons.

A preclinical Talbot-Lau prototype for x-ray dark-field imaging of human-sized objects.

PURPOSE: Talbot-Lau x-ray interferometry provides information about the scattering and refractive properties of an object - in addition to the object's attenuation features. Until recently, this method was ineligible for imaging human-sized objects as it is challenging to adapt Talbot-Lau interferometers (TLIs) to the relevant x-ray energy ranges. In this work, we present a preclinical Talbot-Lau prototype capable of imaging human-sized objects with proper image quality at clinically acceptable dose levels. METHODS: The TLI is designed to match a setup of clinical relevance as closely as possible. The system provides a scan range of 120 × 30 cm2 by using a scanning beam geometry. Its ultimate load is 100 kg. High aspect ratios and fine grid periods of the gratings ensure a reasonable setup length and clinically relevant image quality. The system is installed in a university hospital and is, therefore, exposed to the external influences of a clinical environment. To demonstrate the system's capabilities, a full-body scan of a euthanized pig was performed. In addition, freshly excised porcine lungs with an extrinsically provoked pneumothorax were mounted into a human thorax phantom and examined with the prototype. RESULTS: Both examination sequences resulted in clinically relevant image quality - even in the case of a skin entrance air kerma of only 0.3 mGy which is in the range of human thoracic imaging. The presented case of a pneumothorax and a reader study showed that the prototype's dark-field images provide added value for pulmonary diagnosis. CONCLUSION: We demonstrated that a dedicated design of a Talbot-Lau interferometer can be applied to medical imaging by constructing a preclinical Talbot-Lau prototype. We experienced that the system is feasible for imaging human-sized objects and the phase-stepping approach is suitable for clinical practice. Hence, we conclude that Talbot-Lau x-ray imaging has potential for clinical use and enhances the diagnostic power of medical x-ray imaging.

Metabolomic Analysis Reveals Vitamin D-induced Decrease in Polyol Pathway and Subtle Modulation of Glycolysis in HEK293T Cells.

We combined 1H NMR metabolomics with functional and molecular biochemical assays to describe the metabolic changes elicited by vitamin D in HEK293T, an embryonic proliferative cell line adapted to high-glucose concentrations. Activation of the polyol pathway, was the most important consequence of cell exposure to high glucose concentration, resembling cells exposed to hyperglycemia. Vitamin D induced alterations in HEK293T cells metabolism, including a decrease in sorbitol, glycine, glutamate, guanine. Vitamin D modulated glycolysis by increasing phosphoglycerate mutase and decreasing enolase activities, changing carbon fate without changing glucose consumption, lactate export and Krebs cycle. The decrease in sorbitol intracellular concentration seems to be related to vitamin D regulated redox homeostasis and protection against oxidative stress, and helped maintaining the high proliferative phenotype, supported by the decrease in glycine and guanine and orotate concentration and increase in choline and phosphocholine concentration. The decrease in orotate and guanine indicated an increased biosynthesis of purine and pyrimidines. Vitamin D elicited metabolic alteration without changing cellular proliferation and mitochondrial respiration, but reclaiming reductive power. Our study may contribute to the understanding of the metabolic mechanism of vitamin D upon exposure to hyperglycemia, suggesting a role of protection against oxidative stress.

Cost of poor adherence to anti-hypertensive therapy in five European countries.

The financial burden for EU health systems associated with cardiovascular disease (CV) has been estimated to be nearly €110 billion in 2006, corresponding to 10% of total healthcare expenditure across EU or a mean €223 annual cost per capita. The main purpose of this study is to estimate the costs related to hypertension and the economic impact of increasing adherence to anti-hypertensive therapy in five European countries (Italy, Germany, France, Spain and England). A probabilistic prevalence-based decision tree model was developed to estimate the direct costs of CV related to hypertension (CV defined as: stroke, heart attack, heart failure) in five European countries. Our model considered adherence to hypertension treatment as a main driver of blood pressure (BP) control (BP < 140/90 mmHg). Relative risk of CV, based on controlled or uncontrolled BP group, was estimated from the Framingham Heart Study and national review data. Prevalence and cost data were estimated from national literature reviews. A national payer (NP) perspective for 10 years was considered. Probabilistic sensitivity analysis was performed in order to evaluate uncertainty around the results (given as 95% confidence intervals). The model estimated a total of 8.6 million (1.4 in Italy, 3.3 in Germany, 1.2 in Spain, 1.8 in France and 0.9 in England) CV events related to hypertension over the 10-year time horizon. Increasing the adherence rate to anti-hypertensive therapy to 70% (baseline value is different for each country) would lead to 82,235 fewer CV events (24,058 in Italy, 7,870 in Germany, 18,870 in Spain, 24,855 in France and 6,553 in England). From the NP perspective, the direct cost associated with hypertension was estimated to be 51.3 billion (8.1 in Italy, 17.1 in Germany, 12.2 in Spain, 8.8 in France and 5.0 in England). Increasing adherence to anti-hypertensive therapy to 70% would save a total of 332 million (CI 95%: €319-346 million) from the NPs perspective. This study is the first attempt to estimate the economic impact of non-adherence amongst patients with diagnosed hypertension in Europe, using data from five European countries (Italy, France, Germany, Spain and England).