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Research Interests: Cardiology, Medicine, Electrocardiography, Humans, Internal Medicine, and 12 moreFemale, Atrial Fibrillation, Clinical Sciences, Middle Aged, Coronary Angiography, Public health systems and services research, Circulation, Coronary Artery Disease, accessory pathway, Wolff-Parkinson-White Syndrome, Cardiovascular medicine and haematology, and Diverticulum
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Objective: The Swiss Hypertension Cohort Study (HccH) is a prospective observational study initiated by the Institute of Primary Care at the University of Basel to investigate current hypertension management in Switzerland. The objective... more
Objective: The Swiss Hypertension Cohort Study (HccH) is a prospective observational study initiated by the Institute of Primary Care at the University of Basel to investigate current hypertension management in Switzerland. The objective of this sub-analysis of HccH was to compare risk stratification according to two established cardiovascular (CV) risk assessment models in Swiss hypertensive patients. Design and method: 1004 patients aged 18 years or older and diagnosed with/treated for arterial hypertension were enrolled by 91 general practitioners from 12 cantons in Switzerland between 2005 and 2013. Blood pressure, medical history, comorbidities, laboratory results, lifestyle measures, medication, and clinical events were recorded at baseline and during annual follow-up visits. CV risk was graded into low, moderate, high, and very high risk using the 2013 European Society of Hypertension (ESH) risk chart for 10 year CV mortality and morbidity risk and the SCORE chart for 10 year CV mortality risk according to the 2016 European Society of Cardiology prevention guidelines. Patients with diabetes mellitus, reported CV diseases and/or missing data required for CV risk stratification were excluded from the analysis. Furthermore, patients with missing data that are necessary for risk stratification were also excluded. Interrater agreement between CV risk models was determined using Cohen's kappa. Results: Baseline parameters of 367 patients were included into this sub-analysis of HccH. Distribution of CV risk categories according to ESH and SCORE risk charts is given in Table 1. There was a poor agreement (Cohen's &kgr; = 0.117, p < 0.01) between the SCORE and ESH risk stratification models. Table 1: Figure. No caption available. Conclusions: Important discrepancies were found between the results of CV risk stratification according to ESH and SCORE models. The SCORE risk model classified about half of the study Population into a lower risk category compared to the ESH risk model, with the majority of misclassified patients being female. The results of this analysis indicate that the application of the SCORE CV risk stratification model alone may lead to significant underestimation of CV risk leading to inadequate therapeutic management and worsening of prognosis in, particularly high or very high risk, hypertensive patients.
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Background: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with disease progression, worsening health status, more hospitalizations and COPD-related mortality. During stable COPD, the identification of patients... more
Background: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with disease progression, worsening health status, more hospitalizations and COPD-related mortality. During stable COPD, the identification of patients at high risk for exacerbations has a high impact for clinical management. Several biomarkers hold promise to predict exacerbation episodes, however, the assessment of the individual risk of exacerbation is challenging. Objective: The goal of this study was to investigate the impact of different biomarkers and genetic single nucleotide polymorphisms (SNPs) as predictors of frequent exacerbations (=/> 2/y). Methods: In 270 patients (mean age 63 years; 67% male) with COPD enrolled in The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland (TOPDOCS) biomarkers such as concentrations of serum mannose-binding lectin (MBL), immunoglobulins and IgG subclasses were quantified, IFN-lambda-genotypes (rs8099917) were determined and associated in COPD patients with frequent (≥2/year) and less frequent (0-1/year) exacerbations. Results: Conclusions: We observed that IgG, in particular IgG2 subclass concentrations but not serum MBL levels are associated with an increased risk of COPD exacerbations. Genotyping of the IFN-lambda-gen showed that GG-genotype may be linked to higher exacerbation risk as well. Therefore, measuring IgG2 and determining the IFN-lambda-genotype may be helpful to predict the risk of exacerbation in patients with COPD and thus to prevent complications and disease progression in these patients.
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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... more
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.
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Research Interests: Primary Care, Primary Health Care, Medicine, Metabolic syndrome, Clinical Practice, and 14 moreHumans, Internal Medicine, Hypertension, Diabetes mellitus, Blood Pressure, Female, Male, Switzerland, Clinical Sciences, Aged, Kidney Disease, Proteinuria, Metabolic Syndrome X, and Antihypertensive agents
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Abstract Significant variability in adherence to COPD management recommendations has been reported. We aimed to evaluate real-life COPD pharmacotherapy prescribing patterns and adherence to the 2017 Global Initiative for Chronic... more
Abstract Significant variability in adherence to COPD management recommendations has been reported. We aimed to evaluate real-life COPD pharmacotherapy prescribing patterns and adherence to the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) global strategy in Switzerland. A questionnaire-based survey was conducted among Swiss general practitioners (GPs) and pulmonologists (PULs) from May 1 to November 30, 2017. Participants were invited to complete a questionnaire on their next 5–10 consecutive patients already receiving a pharmacological treatment for COPD. They were requested to assess dyspnea using the modified Medical Research Council (mMRC) dyspnea scale and to determine whether a treatment adjustment was indicated. Fifty-three PULs and 39 GPs completed questionnaires on 511 COPD patients. Dyspnea with mMRC grade ≥2 was reported in 62.5% of the patients, and 31.9% had had at least two exacerbations (or at least one with hospital admission) in the last 12 months. The vast majority (87.1%) of GOLD A patients were overtreated. In the GOLD B group, 52.2% of prescriptions were concordant with GOLD 2017 recommendations, but 37% of patients were overtreated. Among GOLD C patients, 49.2% received GOLD-adherent treatment and 47.5% were overtreated. In the GOLD D category, 78.8% of the patients received a treatment consistent with recommendations but 15.2% were undertreated. After reassessment of patient status, treatment was modified in 50.3% of the patients. This study confirms that discordance of real-world prescription patterns with international guidance is frequent. Further educational efforts are required to improve adherence to COPD management recommendations.
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. 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... more
. 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 &lt;0.005) as patient-related predictors. The MDCs respiratory system, cardiovascular system, and gastrointestinal/hepatobiliary system were identified as high-risk categories (each p &lt;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.
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s: Johannes Hecker Denschlag (University of Ulm) Observation of spin-orbit dependent electron scattering using long-range Rydberg molecules We present experimental evidence for spin-orbit interaction of an electron as it scatters from a... more
s: Johannes Hecker Denschlag (University of Ulm) Observation of spin-orbit dependent electron scattering using long-range Rydberg molecules We present experimental evidence for spin-orbit interaction of an electron as it scatters from a neutral atom. The scattering process takes place within a Rb2 ultralong-range Rydberg molecule, consisting of a Rydberg atomic core, a Rydberg electron and a ground state atom. The spin-orbit interaction leads to characteristic level splittings of vibrational molecular lines which we directly observe via photoassociation spectroscopy. We benefit from the fact that molecular states dominated by resonant p-wave interaction are particularly sensitive to the spin-orbit interaction. Our work paves the way for studying novel spin dynamics in ultralong-range Rydberg molecules. Furthermore, it shows that the molecular setup can serve as a micro laboratory to perform precise scattering experiments in the lowenergy regime of a few meV. Thomas Dieterle (Univers...
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3029 Background: Immunoliposomes (ILs) combine antibody-mediated tumor recognition with liposomal delivery and, when designed for target cell internalization, provide intracellular drug release in order to increase specificity and... more
3029 Background: Immunoliposomes (ILs) combine antibody-mediated tumor recognition with liposomal delivery and, when designed for target cell internalization, provide intracellular drug release in order to increase specificity and efficacy of the encapsulated drug. In animal studies we have shown the ILs approach to be active and promising when targeting the epidermal growth factor receptor (EGFR). METHODS ILs were modularly manufactured under GMP conditions with Fab' fragments from MAb C225 (cetuximab), covalently linked to pegylated liposomes containing doxorubicin (PLD). This first in man single-center phase I clinical trial of anti-EGFR ILs-dox was designed for patients (pts) with various solid tumors, overexpressing EGFR (DAKO EGFR pharmDx-test). ILs-dox was administered i.v. q 4 weeks at a doxorubicin (dox) dose of 5, 10, 20, 30, 40, 50 and 60 mg/m2, 3 pts per dose level, for a maximum of 6 cycles. In addition to weekly safety monitoring, echocardiography was performed q 2 cycles, and pharmacokinetic assessments during cycle 1. The primary objective of this study was the establishment of MTD; secondary objectives included PK, tumor response, and time-to-progression. RESULTS After failure of standard treatments 26 pts were included between January 2007 and May 2010. Median age was 62 years, WHO PS-0 in 3, PS-1 in 19 and PS-2 in 4 pts. Most common histologies included pancreatic, H&N, colorectal and urothelial cancer. Two cases of neutropenia, defined as a dose limiting toxicity, occurred on dose level 7 (= 60 mg dox/m2). On all lower doses the compound was very well tolerated, e.g. skin toxicity grade 1 in 2 pts, no hand-foot-syndrome, no alopecia, no cardio-toxicity, no cumulative toxicity. Therefore, 50 mg dox/m2 was defined as the maximum recommended dose for further phase II development. Best response to treatment included 1 CR, 1 PR and 8 SD lasting 2-12 mo (median 5.75 mo). Mean total dox half-life was calculated to be 31.0 h (+/- 7.6 h) and for the attached monoclonal antibody fragment of C225 17.7 h (+/- 4.3 h), respectively. CONCLUSIONS Anti-EGFR dox-loaded ILs are safe and well tolerated up to 50 mg dox/m2. Clear evidence of clinical activity was observed warranting further evaluation in phase II trials.
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DESCRIPTION The diagnostic industry faces environmental changes that will require more focus on the Medical Value (MV) component in the future. MV products deliver actionable and medically relevant information enabling support and... more
DESCRIPTION The diagnostic industry faces environmental changes that will require more focus on the Medical Value (MV) component in the future. MV products deliver actionable and medically relevant information enabling support and guidance in decision-making and justifying the change of current disease management by addressing unmet medical needs. This article analyzes the perception of customers from Emerging (EM) and Developed Markets (DM) on the MV-component in an online-based survey. 231 physicians from 8 countries participated in a survey with 3 pivotal multiple choice questions on MV. Responses from countries have been allocated to income levels according to world-bank data. Answers have been statistically analyzed according to the market subgroups. Clinically validated treatment algorithms were rated as the most important factor qualifying for a MV-product. Physicians emphasized the need for algorithms, predominantly for existing markers. Lower priority has been given to tech...
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Although they have been marketed widely, few data about the diagnostic accuracy of blood pressure monitors are available. Repeated measurements of blood pressures in 85 patients were performed in random sequence with two oscillometric... more
Although they have been marketed widely, few data about the diagnostic accuracy of blood pressure monitors are available. Repeated measurements of blood pressures in 85 patients were performed in random sequence with two oscillometric blood pressure monitors around the upper arm (Visomat OZ2) and the wrist (Omron R3( and with a standard sphygmomanometer. The oscillometric blood pressure monitors were validated according to protocols of the British Hypertension Society (BHS) and the American Association for the Advancement of Medical Instrumentation (AAMI). Subsequently, sensitivity and specificity of these monitors for the diagnosis of hypertension or exclusion of the possibility of its presence in a general medical outpatient population were calculated. Sphygmomanometric readings exceeded oscillometric blood pressure measurements by 3.7+/-7.5/4.8+/-5.6 mmHg (systolic/diastolic) for the upper arm and 5.7+/-6.2/6.8+/-6.8 mmHg for the wrist. Deviations occurred in both directions and ...
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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... more
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...
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Background Chronic obstructive pulmonary disease (COPD) is a major public health issue affecting approximately four to seven percent of the Swiss population. According to current inpatient guidelines, systemic corticosteroids are... more
Background Chronic obstructive pulmonary disease (COPD) is a major public health issue affecting approximately four to seven percent 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 five to seven days. Several studies suggest that corticosteroids accelerate the recovery of the FEV1 (forced expiratory volume in one second), enhance oxygenation, decrease duration of hospitalization and improve clinical outcome. However, the additional therapeutic benefit on FEV1 recovery appears to be most apparent in the first three to five days. No data are available on the minimal necessary corticosteroid dose and treatment duration in primary care patients with acute COPD exacerbations. Given that many COPD patients are treated on an outpatient basis, there is an urgent need to improve evidence about COPD management in this setting. The aim of this study is to investigate ...
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Research Interests: Adolescent, Medicine, Humans, Hypertension, Blood Pressure, and 15 moreFemale, Male, Hydrochlorothiazide, Ambulatory, Aged, Middle Aged, Adult, Amlodipine, Imidazoles, Ambulatory Blood Pressure, Olmesartan, Diastole, Antihypertensive agents, Cardiovascular medicine and haematology, and Drug combinations
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Additional file 2. Results of adjusted Cox regression and Poisson regression.