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Background: The objective of this study was to test whether baseline echocardiography in newly detected hypertension improves left ventricular mass index and blood pressure control. This is a randomized trial with primary care patients. Methods: After routine clinical work-up 177 consecutive patients with newly detected hypertension were randomized according to result of their echocardiogram (echo group and control group). Treating physicians were encouraged to prescribe angiotensin II receptor antagonist therapy for patients with evidence of hypertensive target organ damage. Mean blood pressure (BP) and echocardiographic left ventricular mass index were measured at baseline and after 6 months of therapy in both groups. Results: More patients with hypertensive target organ damage were identified in the echo group as compared to the control group (58 of 91 [64%] v 42 of 86 [49%] patients (difference 15%, 95% CI 1%–29%). In the echo group, 41 patients (45%) received angiotensin II receptor antagonist therapy as compared to 27 patients (31%) in the control group (difference 14%, 95% CI 0–28%). After 6 months, there were no differences in mean left ventricular mass index, mean diastolic 24-h ambulatory BP monitoring, or mean systolic and diastolic office BP between the two groups. Conclusions: In patients with newly detected hypertension, baseline echocardiography detects more patients with hypertensive target organ damage, but does not lead to a reduction in left ventricular mass index or improved BP control after 6 months of therapy. [Copyright &y& Elsevier]

Abstract: Background: Abnormalities of intracellular calcium handling are widely recognized as a common hallmark of heart failure in animal models and humans. Modifying the interaction of phospholamban (PLB) with the sarcoplasmic reticulum ATPase (SERCA) by PLB mutants improves cardiac function but may also lead to heart failure. In this study we describe the in vivo effects of a new approach to modify the PLB–SERCA interaction using a recombinant, intracellularly expressed chicken-antibody derived protein (PLADP) targeting the cytoplasmic domain of PLB in the cardiomyopathic BIO 14.6 hamster. Methods and results: In vivo gene transfer was performed in 12–14-week-old BIO 14.6 cardiomyopathic hamsters using intracoronary delivery of adenovirus containing the PLADP or the β-galactosidase (LacZ) gene (8×109 PFU per animal). A third group was injected with saline (Sham). Echocardiography was performed before and, together with hemodynamic measurements, repeated 4–5 days after gene transfer. Indo-1 calcium transients and myocyte contractility were measured in isolated cardiomyocytes from the BIO 14.6 hamster transfected with the PLADP. Gene expression (LacZ) was found in 54±15% of cells throughout the heart without any signs of myocardial inflammation. Echocardiographic and hemodynamic indices of left ventricular function were significantly increased after gene transfer with the PLADP, compared to controls. Measurements of myocyte contractility and calcium transients in isolated cardiac myocytes from BIO 14.6 hamsters revealed improved intracellular calcium handling and contractility. Conclusion: In vivo adenoviral gene transfer with the PLADP resulted in short-term intracellular expression of a PLADP, improving LV function and enhancing myocardial contractility in the failing cardiomyopathic hamster heart. The PLADP enhanced contractility and cardiac function by improving intracellular calcium handling. Expression of antibody-derived protein represents a new approach to modify protein–protein interactions at the cellular level. [Copyright &y& Elsevier]

Background: The burden of asthma and COPD among patients is high and people affected are frequently hospitalized due to exacerbations. There are numerous reasons for the lack of disease control in asthma and COPD patients. It is associated with non-adherence to guidelines on the part of the health care provider and with poor inhalation technique and/or non-adherence to the prescribed treatment plan by the patient. This study aims to present data on inhaler technique and its impact on quality of life (QoL) and symptom control in a typical population of patients with chronic lung disease from a randomized controlled trial on medication adherence.Methods: For this cross-sectional analysis, 165 asthma and COPD patients were analyzed. Correct application of inhaler devices was tested using pre-defined checklists for each inhaler type. QoL and symptom control were investigated using COPD Assessment Test (CAT) and Asthma Control Test (ACT). Spirometry was used to measure forced vital capacity (FVC) and forced expiratory volume in one second (FEV1).Results: Overall, incorrect inhalation technique ranged from 0 to 53% depending on the type of inhaler. COPD patients with incorrect device application had a higher CAT sum score compared to those with a correct device application (P = .02). Moreover, COPD patients with incorrect device application were more likely to suffer from cough (P = .03) and were more breathless while walking uphill or a flight of stairs (P = .02). While there was no significance found in asthma patients, COPD patients who used their devices correctly had a significantly better mean FEV1% predicted at baseline compared to those who applied their devices incorrectly (P = .04).Conclusions: Correct inhalation of prescribed medication is associated with improved health status and lung function. These findings should encourage health professionals to provide instructions on correct inhalation technique and to regularly re-evaluate the patients' inhalation technique.Trial Registration: ClinicalTrials.gov: NCT0238672 , Registered 14 February 2014. [ABSTRACT FROM AUTHOR]

Primary lymphoedema, axillary web syndrome (AWS) and yellow nail syndrome may be related. Mr B is a 66-year-old gentleman with genital lymphoedema and lymphoedema of all four extremities. In 2023, he was diagnosed with non-Hodgkin lymphoma and also underwent cardiac surgery. In November 2023, he completed an inpatient rehabilitation at the Földi clinic in Germany, where he received intensive treatment for his lymphoedema and was also diagnosed with bilateral AWS. The presence of AWS in a patient with primary lymphoedema and no history of axillary surgery is unique. Although AWS typically presents after axillary surgery, this case highlights that it can also occur in patients without lymph node surgery. While the precise cause of this presentation of AWS is not known, it may be connected to yellow nail syndrome or potentially the recent chemotherapy treatment. This article will describe the clinical case, highlighting the need for further research on AWS present in primary lymphoedema. [ABSTRACT FROM AUTHOR]

Long‐term, intense endurance exercise training can occasionally induce endothelial micro‐damage and cardiac fibrosis. The underlying mechanisms are incompletely understood. Twenty healthy, well‐trained male participants (10 runners and 10 cyclists) performed a strenuous high‐intensity interval training (HIIT) session matched by age, height, weight and maximal oxygen consumption. We assessed the acute exercise response of novel cardiac biomarkers of fibrosis [e.g., galectin‐3 (Gal‐3) and soluble suppression of tumorigenicity 2 (sST2)] per exercise modality and their relationship with haemodynamic contributors, such as preload, afterload and cardiac contractility index (CTi), in addition to endothelial damage by sustained activation and shedding of endothelial cells (ECs). Serum Gal‐3 and sST2 concentrations were investigated by enzyme‐linked immunosorbent assays; haemodynamics were analysed via impedance plethysmography and circulating ECs by flow cytometry. The Gal‐3 and sST2 concentrations and ECs were elevated after exercise (P < 0.001), without interaction between exercise modalities. Circulating Gal‐3 and sST2 concentrations both showed a positive relationship with ECs (rrm = 0.68, P = 0.001 and rrm = 0.57, P = 0.010, respectively, both n = 18). The EC association with Gal‐3 was significant only in cyclists, but equally strong for both modalities. Gal‐3 was also related to exercise‐induced CTi (rrm = 0.57, P = 0.011, n = 18). Cardiac wall stress is increased after an acute HIIT session but does not differ between exercise modalities. Exercise‐released Gal‐3 from cardiac macrophages could very probably drive systemic endothelial damage, based on an enhanced CTi. The importance of acute exercise‐induced vascular resistances and cardiac contractility for the release of fibrotic biomarkers and any long‐term pathological endothelial adaptation should be investigated further, also relative to the exercise modality. New Findings: What is the central question of this study?Circulating biomarkers of cardiac wall stress and fibrosis are influenced by physical exercise. The underlying mechanisms per exercise modality are still unclear.What is the main finding and its importance?We show that galectin‐3 (Gal‐3) and soluble suppression of tumorigenicity 2 (sST2) are increased after acute exercise but do not differ between running and cycling. One haemodynamic contributor to the secretion of Gal‐3 is an enhanced cardiac contractility. Acute exercise‐released Gal‐3 and sST2 are linked to sustained endothelial activation and cell shedding. This could be relevant in the context of fibrosis development and could identify athletes at risk for pathological endothelial adaptations. [ABSTRACT FROM AUTHOR]

Since the introduction of the reimbursement system based on diagnosis-related groups (DRG) in Swiss hospitals in 2012, most readmissions occurring within 18 days and appertaining to the same major diagnostic category (MDC) are merged and thus often reimbursed to a lesser extent. While readmissions reflect increased distress for patients and their relatives, the causes are mainly patient-related and difficult to influence. However, it may be possible to identify cases at higher risk for readmission. Therefore, the aim of this study was to find predictors for early readmissions in the same MDC, to identify high-risk index hospitalizations and possibly prevent unnecessary readmissions. The data of all patients admitted to the Clinic of Internal Medicine at the University Hospital of Basel, Switzerland, hospitalized for longer than 24 hours during the pre-DRG period between October 2009 and September 2010 were retrospectively collected. Data were examined for predictors of unplanned readmission within 18 days under the same MDC ('relevant readmission') by means of logistic regression. 7479 patients (median age 67.8 years, 56% male) were admitted to the Clinic of Internal Medicine, with 232 patients (3.1%) being readmitted at least once. Logistic regression revealed male sex (p =0.035) and a high number of prescribed drugs at discharge (p <0.005) as patient-related predictors. The MDCs respiratory system, cardiovascular system, and gastrointestinal/hepatobiliary system were identified as high-risk categories (each p <0.005). Age and length of index hospital stay added no significant explanatory value to the regression model. Unplanned readmissions under the same MDC within 18 days were infrequent and not related to patients' age or length of hospital stay. Overall, multimorbid patients, and hospitalizations regarding the cardiovascular, respiratory, or gastrointestinal system appear to be most at risk and should therefore be specifically targeted in the prevention of early readmissions. [ABSTRACT FROM AUTHOR]

Background and Objective: Whether immunological biomarkers combined with clinical characteristics measured during an exacerbation-free period are predictive of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) frequency and severity is unknown. Method: We measured immunological biomarkers and clinical characteristics in 271 stable chronic obstructive pulmonary disease (COPD) patients (67% male, mean age 63 years) from "The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland" cohort on a single occasion. One-year follow-up data were available for 178 patients. Variables independently associated with AECOPD frequency and severity were identified by multivariable regression analyses. Receiver operating characteristic analysis was used to obtain optimal cutoff levels and measure the area under the curve (AUC) in order to assess if baseline data can be used to predict future AECOPD. Results: Higher number of COPD medications (adjusted incident rate ratio [aIRR] 1.17) and platelet count (aIRR 1.03), and lower FEV1% predicted (aIRR 0.84) and IgG2 (aIRR 0.84) were independently associated with AECOPD frequency in the year before baseline. Optimal cutoff levels for experiencing frequent (>1) AECOPD were ≥3 COPD medications (AUC = 0.72), FEV1 ≤40% predicted (AUC = 0.72), and IgG2 ≤2.6 g/L (AUC = 0.64). The performance of a model using clinical and biomarker parameters to predict future, frequent AECOPD events in the same patients was fair (AUC = 0.78) but not superior to a model using only clinical parameters (AUC = 0.79). The IFN-lambda rs8099917GG-genotype was more prevalent in patients who had severe AECOPD. Conclusions: Clinical and biomarker parameters assessed at a single point in time correlated with the frequency of AECOPD events during the year before and the year after assessment. However, only clinical parameters had fair discriminatory power in identifying patients likely to experience frequent AECOPD. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a major public health issue affecting approximately 4% to 7% of the Swiss population. According to current inpatient guidelines, systemic corticosteroids are important in the treatment of acute COPD exacerbations and should be given for 5 to 7 days. Several studies suggest that corticosteroids accelerate the recovery of FEV1 (forced expiratory volume in 1 second), enhance oxygenation, decrease the duration of hospitalization, and improve clinical outcomes. However, the additional therapeutic benefit regarding FEV1 recovery appears to be most apparent in the first 3 to 5 days. No data are available on the optimum duration of corticosteroid treatment in primary-care patients with acute COPD exacerbations. Given that many COPD patients are treated as outpatients, there is an urgent need to improve the evidence base on COPD management in this setting. The aim of this study is to investigate whether a 3-day treatment with orally administered corticosteroids is non-inferior to a 5-day treatment in acute exacerbations of COPD in a primary-care setting.Methods/design: This study is a prospective double-blind randomized controlled trial conducted in a primary-care setting. It is anticipated that 470 patients with acutely exacerbated COPD will be recruited. Participants are randomized to receive systemic corticosteroid treatment of 40 mg prednisone daily for 5 days (conventional arm, n = 235) or for 3 days followed by 2 days of placebo (experimental arm, n = 235). Antibiotic treatment for 7 days is given to all patients with CRP ≥ 50 mg/l, those with a known diagnosis of bronchiectasis, or those presenting with Anthonisen type I exacerbation. Additional treatment after inclusion is left at the discretion of the treating general practitioner. Follow-up visits are performed on days 3 and 7, followed by telephone interviews on days 30, 90, and 180 after inclusion in the study. The primary endpoint is the time to next exacerbation during the 6-month follow-up period.Discussion: The study is designed to assess whether a 3-day course of corticosteroid treatment is not inferior to the conventional 5-day treatment course in outpatients with exacerbated COPD regarding time to next exacerbation. Depending on the results, this trial may lead to a reduction in the cumulative corticosteroid dose in COPD patients.Trial Registration: ClinicalTrials.gov, NCT02386735. Registered on 12 March 2015. [ABSTRACT FROM AUTHOR]

Purpose Solid tumors modulate their environment to keep non-malignant stromal cells in a tumor-promoting state. The main cells in the stroma of epithelial derived tumors are cancer associated fibroblasts (CAF) that are critical to tumorigenesis and angiogenesis. CAFs also supply the tumor cells with growth factors and extracellular matrix (ECM) degrading enzymes. They are thus essential for tumor initiation as well as tumor progression and metastasis, suggesting that they represent an ideal cellular target of an integrative tumor therapy. Fibroblast activation protein (FAP) is a well-defined marker, expressed at high levels on the cell surface of CAFs. FAP, a constitutively active serine peptidase with both dipeptidyl peptidase IV (DPP IV) and collagenase/gelatinase activity, promotes malignant and invasive behavior of epithelial cancers. High stromal expression levels of FAP correlate with poor prognosis. FAP is difficult to detect in non-diseased adult tissue, but it is generally expressed at sites of tissue remodeling. Materials and methods In our experiments, we aimed for a reduction of the pro-tumorigenic activities of CAFs by depleting FAP from fibroblasts growing in a composite environment with epithelial tumor cells. Results FAP depletion was achieved by two therapeutically relevant approaches: a novel internalizing anti-FAP IgG1 antibody and FAP gene knock-down by siRNA delivery. The antibody effectively removed FAP from the cell surface and was capable of reversing the FAP mediated migratory and invasive capacity. FAP RNA interference was equally effective when compared to the antibody. Conclusions Thus, targeting FAP on CAF suppresses pro-tumorigenic activities and may result in a clinically effective reduction of tumor progression and dissemination. [ABSTRACT FROM AUTHOR]

Background: The Swiss COPD cohort was established in 2006 to collect data in a primary care setting. The objective of this study was to evaluate possible predictive factors for exacerbation and re-exacerbation. Methods: In order to predict exacerbation until the next visit based on the knowledge of exacerbation since the last visit, a multistate model described by Therneau and Grambsch was performed. Results: Data of 1,247 patients (60.4% males, 46.6% current smokers) were analyzed, 268 (21.5%) did not fulfill spirometric diagnostic criteria for COPD. Data of 748 patients (63% males, 44.1% current smokers) were available for model analysis. In order to predict exacerbation an extended Cox Model was performed. Mean FEV1/FVC-ratio was 53.1% (±11.5), with a majority of patients in COPD GOLD classes 2 or 3. Hospitalization for any reason (HR1.7; P = 0.04) and pronounced dyspnea (HR for mMRC grade four 3.0; P < 0.001) at most recent visit as well as prescription of short-acting bronchodilators (HR1.7; P < 0.001), inhaled (HR1.2; P = 0.005) or systemic corticosteroids (HR1.8; P = 0.015) were significantly associated with exacerbation when having had no exacerbation at most recent visit. Higher FEV1/FVC (HR0.9; P = 0.008) and higher FEV1 values (HR0.9; P = 0.001) were protective. When already having had an exacerbation at the most recent visit, pronounced dyspnea (HR for mMRC grade 4 1.9; P = 0.026) and cerebrovascular insult (HR2.1; P = 0.003) were significantly associated with re-exacerbation. Physical activity (HR0.6; P = 0.031) and treatment with long-acting anticholinergics (HR0.7; P = 0.044) seemed to play a significant protective role. In a best subset model for exacerbation, higher FEV1 significantly reduced and occurrence of sputum increased the probability of exacerbation. In the same model for re-exacerbation, coronary heart disease increased and hospitalization at most recent visit seemed to reduce the risk for re-exacerbation. Conclusion: Our data confirmed well-established risk factors for exacerbations whilst analyzing their predictive association with exacerbation and re-exacerbation. This study confirmed the importance of spirometry in primary care, not only for diagnosis but also as a risk evaluation for possible future exacerbations. Trial registration: Our study got approval by local ethical committee in 2006 (EK Nr. 170/06) and was registered retrospectively on ClinicalTrials.gov (NCT02065921, 19th of February 2014). [ABSTRACT FROM AUTHOR]

Introduction: Serial N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements have proven to be useful for therapy monitoring in patients hospitalized for acute decompensated heart failure (ADHF). The POC-HF pilot study investigated whether serial NT-proBNP measurements influenced treatment decisions in these patients., Methods: Patients hospitalized for ADHF were randomly assigned to an intervention group (serial NT-proBNP measurements made available to treating physicians) or a control group (care as usual). HF therapy was administered at the discretion of the treating physician. The primary endpoint was dose changes in HF therapy during hospitalization. Secondary endpoints included changes in NT-proBNP levels, recovery from HF symptoms, length of hospital stay, and quality of life., Results: 52 patients (35% female; mean age 81.8 years) were included. The availability of serial NT-proBNP values was associated with higher dosages of ACE inhibitors (relative treatment effect (RTE) day 11:0.74, p  = 0.007) and loop diuretics (RTE day 11:0.77, p  = 0.005), and lower dosages of beta-blockers (RTE day 11:0.43, p   =  0.002). NT-proBNP levels decreased (-752 pg/ml, p  = 0.162) and recovery rates from ADHF symptoms were more pronounced in the intervention group, but without statistical significance. No differences were found in terms of the length of hospital stay and quality of life., Conclusion: The results of this pilot trial indicate that serial NT-proBNP measurements are possibly associated with faster up-titration of HF medication, more pronounced NT-proBNP decrease, and faster recovery from symptoms than symptom-guided therapy in patients hospitalized for ADHF. These preliminary findings require further validation through larger studies., Trial Registration: http://www.swissethics.ch BASEC-ID 2017-01030, registered on 28 December 2017., Competing Interests: TD received a project grant from SynlabSuisse AG (Switzerland). JDL reports grants from Swiss National Science Foundation (SNF 160072 and 18559), as well as unrestricted grants from Astra Zeneca AG Switzerland, GSK AG Switzerland, and Sanofi AG Switzerland. Both TD and JDL received a project grant within the Swiss Personalized Health network Driver Project CREATE-PRIMA (Project No. 2018DRI08). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright ©2024 The Author(s).)

Primary lymphoedema, axillary web syndrome (AWS) and yellow nail syndrome may be related. Mr B is a 66-year-old gentleman with genital lymphoedema and lymphoedema of all four extremities. In 2023, he was diagnosed with non-Hodgkin lymphoma and also underwent cardiac surgery. In November 2023, he completed an inpatient rehabilitation at the Földi clinic in Germany, where he received intensive treatment for his lymphoedema and was also diagnosed with bilateral AWS. The presence of AWS in a patient with primary lymphoedema and no history of axillary surgery is unique. Although AWS typically presents after axillary surgery, this case highlights that it can also occur in patients without lymph node surgery. While the precise cause of this presentation of AWS is not known, it may be connected to yellow nail syndrome or potentially the recent chemotherapy treatment. This article will describe the clinical case, highlighting the need for further research on AWS present in primary lymphoedema.

Despite important advances in diagnosis and medical therapy of heart failure (HF), disease monitoring and therapy guidance remains to be based on clinical signs and symptoms. NT-proBNP was repeatedly demonstrated to be a strong and independent predictor of morbidity and mortality in patients with HF. Only few - and conflicting - data are available on the efficacy of serial measurement of NT-proBNP as a tool for treatment monitoring in HF. These data are limited to the outpatient setting. Currently, no data are available on the effects of this approach in patients hospitalized for acute decompensated HF. The goal of this study is to explore whether the availability of serial NT-proBNP measurements may influence treatment decisions in patients with acute decompensated HF, and whether this leads to more rapid dose adjustments of prognostically beneficial medical therapies and earlier hospital discharge. In the intervention group, serial measurements of NT-proBNP every second business day are performed and made available to the treating physician, while no serial measurements are available in control group. HF therapy is left at the discretion of the treating physician. The primary endpoints are defined as the effects of monitoring NT-proBNP on medical HF therapy decisions, including type and dosing of medical therapies and the rapidity of adjustments, length of hospital stay, and evaluation of the changes in NT-proBNP values. Additional secondary endpoints include incidence of electrolyte imbalances and renal failure, changes in NYHA functional class, vital signs, body weight, quality of life, incidence of adverse events, transfer to Intensive Care Units, and mortality., (© 2021 Published by Elsevier Inc.)

Background: Poor medication-adherence is common in chronic lung patients, resulting in reduced health-outcomes and increased healthcare-costs. This study aimed to investigate the impact of an acoustic reminder and support calls on adherence to inhaled therapy in asthma and COPD patients and to determine their effect on exacerbations., Methods: This single-blinded randomized controlled trial investigated asthma and COPD patients during 6 months in an ambulatory setting. The intervention consisted of daily alarm clock and support phone calls, whenever use of rescue medication doubled or inhaled medication was not taken as prescribed. Primary outcome was time to next exacerbation. Frequency of exacerbations, adherence to inhaled medication and quality of life scores were secondary outcomes. Cox and Poisson regression were used to determine intervention effect on time to exacerbation and frequency of exacerbations, respectively., Results: Seventy-five participants were assigned to the intervention group and 74 to usual follow-up care. During a median follow-up of 6.2 months, 22 and 28% in the intervention and control groups respectively, experienced at least one exacerbation. Intervention had no effect on time to first exacerbation (HR 0.65, 95% CI 0.21 to 2.07, P = .24), but showed a trend toward a 39% decreased frequency of exacerbations (RR = 0.61, 95% CI 0.35 to 1.03, P = .070) for the adjusted models, respectively. The intervention group had significantly more days with 80-100% taking adherence regarding puff inhalers (82 ± 14% vs. 60 ± 30%, P < .001) and dry powder capsules (90 ± .10% vs. 80 ± 21%, P = .01). Timing adherence in participants using puff inhalers was higher in the intervention group (69 ± 25% vs. 51 ± 33%, P < .001). No significant differences in QoL were found between the two groups., Conclusion: Participants assigned to the intervention group had significantly better taking and timing adherence of inhaled medication resulting in a trend towards a decreased frequency of exacerbations. However, no effect on time to next exacerbation was observed., Trial Registration: ClinicalTrials.gov: NCT02386722, Registered 14 February 2014.

Background: Cardiovascular (CV) diseases including heart failure are the leading causes of morbidity, with age being the primary risk factor. The combination of age-related organic functional impairment and reduced physical fitness can drastically impact an individual's healthspan. One's lifespan can potentially be prolonged by the preservation or improvement of physical fitness. However, it remains unclear as to which biomarkers are most suitable for distinguishing between healthy aging and the impaired organ function associated with heart failure. Therefore, a comprehensive assessment of the components of physical fitness and CV function will be performed to identify the most important factors contributing to aging in relation to both health and disease., Methods: This cross-sectional investigation will consist of two parts: COmPLETE-Health (C-Health) and COmPLETE-Heart (C-Heart). C-Health will examine the aging trajectories of physical fitness components and CV properties in a healthy population sample aged between 20 and 100 years (n = 490). Separately, C-Heart will assess the same markers in patients at different stages of chronic heart failure (n = 80). The primary outcome to determine the difference between C-Health and C-Heart will be cardiorespiratory fitness as measured by cardiopulmonary exercise testing on a bicycle ergometer. Secondary outcomes will include walking speed, balance, isometric strength, peak power, and handgrip strength. Physical activity as a behavioural component will be assessed objectively via accelerometry. Further, CV assessments will include pulse wave velocity; retinal, arterial, and venous diameters; brachial and retinal arterial endothelial function; carotid intima-media thickness; and systolic and diastolic function. The health distances for C-Health and C-Heart will be calculated using the methodology based on statistical (Mahalanobis) distance applied to measurements of quantitative biomarkers., Discussion: This research seeks to identify physical fitness and CV biomarkers that best resemble underlying CV risk with age. Further, it will examine which physical fitness markers are impaired most in heart failure. The presented integrative approach could define new recommendations for diagnostic guidance in aging. Ultimately, this study is expected to offer a better understanding of which functional characteristics should be specifically targeted in primary and secondary prevention to achieve an optimal healthspan.

Background: The burden of asthma and COPD among patients is high and people affected are frequently hospitalized due to exacerbations. There are numerous reasons for the lack of disease control in asthma and COPD patients. It is associated with non-adherence to guidelines on the part of the health care provider and with poor inhalation technique and/or non-adherence to the prescribed treatment plan by the patient. This study aims to present data on inhaler technique and its impact on quality of life (QoL) and symptom control in a typical population of patients with chronic lung disease from a randomized controlled trial on medication adherence., Methods: For this cross-sectional analysis, 165 asthma and COPD patients were analyzed. Correct application of inhaler devices was tested using pre-defined checklists for each inhaler type. QoL and symptom control were investigated using COPD Assessment Test (CAT) and Asthma Control Test (ACT). Spirometry was used to measure forced vital capacity (FVC) and forced expiratory volume in one second (FEV 1 )., Results: Overall, incorrect inhalation technique ranged from 0 to 53% depending on the type of inhaler. COPD patients with incorrect device application had a higher CAT sum score compared to those with a correct device application (P = .02). Moreover, COPD patients with incorrect device application were more likely to suffer from cough (P = .03) and were more breathless while walking uphill or a flight of stairs (P = .02). While there was no significance found in asthma patients, COPD patients who used their devices correctly had a significantly better mean FEV 1 % predicted at baseline compared to those who applied their devices incorrectly (P = .04)., Conclusions: Correct inhalation of prescribed medication is associated with improved health status and lung function. These findings should encourage health professionals to provide instructions on correct inhalation technique and to regularly re-evaluate the patients' inhalation technique., Trial Registration: ClinicalTrials.gov: NCT0238672 , Registered 14 February 2014.

Scientific advances and innovative targeted drugs, especially biologics, have revolutionised the treatment of many diseases. In oncology in particular, previously acute or lethal conditions have come to be considered chronic as new treatments have led to longer life expectancies and a lower rate of years lived with disability. These advances, however, come with rising costs in a resource-constrained environment. To achieve cost containment, reimbursement for in-vitro diagnostics (IVDs) is increasingly coming under pressure because they are perceived as a cost factor rather than as a tool to reduce expenditure in the long term. In this conceptual paper, we propose four possible interventions from an industry perspective that may contribute to increase effectiveness of IVD use to counteract increasing healthcare expenditures. These are: (1) fostering prevention, screening, early diagnosis and therapy; promoting (2) comprehensive and (3) stratified disease management; and (4) using targeted treatment alongside companion diagnostics. We conclude that the implementation of policies that promote a fee-for-outcome model rather than fee-for-service reimbursement can support sustainable healthcare.

Due to the high prevalence of cardiovascular diseases and the corresponding prescription of cardiac drugs, side effects and interactions may occur in a substantial number of patients. They can be explained by either pharmacokinetic or pharmaco-dynamic drug interactions which may be desired, but may also be life-threatening. Despite the fact that the novel oral anticoagulants are well tolerated, several factors restricting the use of these drugs, such as renal failure, have to be considered. The use of antihypertensive drugs may be limited by concomitant use of drugs that either induce of inhibit enzymatic metabolism, respectively inhibit renal drug, electrolyte, and/or water excretion. In this respect, the interaction between beta-blockers, ACE inhibitors, angiotensin receptor blockers and thiazide diuretics with non-steroidal antiinflammatory drugs is especially important. Muscle disorders are frequent side effects in patients undergoing statin therapy and affect up to 5% of patients. They may manifest as mild myalgia, but also as life-threatening rhabdomyolysis.

European and North-American guidelines for the diagnosis and therapy of arterial hypertension refer to hypertensive crisis as an acute and critical increase of blood pressure>180/120 mmHg. Presence of acute hypertensive target organ damage, such as stroke, myocardial infarction or heart failure, in this situation defines a “hypertensive emergency”. In these patients, immediate lowering of blood pressure (about 25% within one to two hours) in an intensive care setting is mandatory to prevent further progression of target organ damage. In contrast to hypertensive emergencies, hypertensive urgencies are characterized by an acute and critical increase in blood pressure without signs or symptoms of acute hypertensive target organ damage. In these patients, blood pressure should be lowered within 24 to 48 hours in order to avoid hypertensive target organ damage. In general, hospitalization is not required, and oral antihypertensive therapy usually is sufficient. However, further and continuing outpatient care has to be ensured.

To improve the prevention of cardiovascular complications and events in hypertensive patients, it is of major importance to estimate the patient's individual risk for cardiovascular events. Antihypertensive treatment should not only be based on blood pressure values anymore, but also on the patient's comorbidities and risk profile. Risk stratification takes into account cardiovascular risk factors, diabetes, asymptomatic organ damage and established cardiovascular or renal disease. The most important markers for asymptomatic organ damage which should be searched for are microalbuminuria and LVH. Current guidelines emphasize the importance of the adaption and selection of treatment according to asymptomatic and established organ damage and provide assistance for treatment decisions. They focus also on the different non-pharmacological therapy options and lifestyle modifications. The goal of this article is to summarize the most important innovations and to point out the importance of simple tools for the implementation of cardiovascular risk stratification in hypertensive patients.

Arterial hypertension remains the most important risk factor for cardiovascular and renal diseases. In view of an increasing prevalence with older age and an increasingly aging population, the treatment of elderly patients with arterial hypertension will become increasingly important in daily practice. Arterial hypertension in the elderly differs in many aspects from arterial hypertension in younger patients. For example, isolated systolic hypertension is the predominant form of arterial hypertension in the elderly. In comparison to younger patients, treatment of hypertension in the elderly is less well investigated. However, available data suggest that lowering of blood pressure in the elderly and very elderly reduces the risk of heart failure, stroke, and even mortality. The best evidence for the treatment of hypertension in the elderly exists for diuretics and calcium antagonists. However, the primary choice of antihypertensive therapy should be guided by the presence of existing cardiovascular and/or renal comorbidities.

Therapy-resistant hypertension is a frequent finding in clinical practice. It is associated with a significantly increased risk for cardiovascular and renal events. Causes include but are not limited to erroneous blood pressure measurements, compliance issues, blood pressure increasing co-medication, and secondary hypertension. During the last years, several medical and interventional therapeutic approaches have been described and introduced into clinical practice. The goal of this paper is to summarize the clinically relevant diagnostic and therapeutic aspects related to therapy-resistant hypertension and to give an overview on the rational approach to this clinical problem.

The recommendations of international scientific societies for the treatment of hypertension in the geriatric population are different. Lack of outcome trials, non-standardised terminology as well as differing levels of evidence contribute to the inconsistencies in the guidelines. This review article compares six international guidelines (ESH-ESC 2007/2009, SHG 2009, DHL 2008, CHEP 2010, NICE 2011 and JNC7 2003) as well as the consensus document of the ACCF/AHA 2011 in terms of their recommendations of drug classes, target blood pressure values and the use of combination therapy. Generally, antihypertensive therapy appears to be clinically beneficial in geriatric patients. Target blood pressure values of <140-150/90 mm Hg and <140/90 mm Hg can be used as a general guideline for octogenarians (80-89 yrs) and septuagenarians (70-79 yrs) respectively. While angiotensin-II converting enzyme inhibitors and diuretics appear to be advantageous in treating combined systolic-diastolic hypertension, calcium-channel blockers and diuretics are to be recommended in the management of isolated systolic hypertension. Combination therapy often increases the efficacy of the treatment as well as patient medication adherence. Furthermore, by making the most of drug combination synergy, lower doses may be used resulting in fewer side-effects.