Treatment patterns and risk factor control in patients with and without metabolic syndrome in cardiac rehabilitation

Anselm Gitt1, Christina Jannowitz2, Marthin Karoff3, Barbara Karmann2, Martin Horack1, Heinz Völler4,51Institut für Herzinfarktforschung an der Universität Heidelberg, Ludwigshafen,2Medical Affairs, MSD Sharp and Dohme GmbH, Haar, 3Klinik Königsfeld der Deutschen Rentenversicherung Westfalen in Ennepetal (NRW), Klinik der Universität Witten-Herdecke, 4Kardiologie, Klinik am See, Rüdersdorf, 5Center of Rehabilitation Research, University Potsdam, GermanyAim: Metabolic syndrome (MetS) is a clustering of factors that are associated with increased cardiovascular risk. We aimed to investigate the proportion of patients with MetS in patients undergoing cardiac rehabilitation (CR), and to describe differences between patients with MetS compared to those without MetS with regard to (1) patient characteristics including demographics, risk factors, and comorbidities, (2) risk factor management including drug treatment, and (3) control status of risk factors at entry to CR and discharge from CR.Methods: Post-hoc analysis of data from 27,904 inpatients (Transparency Registry to Objectify Guideline-Oriented Risk Factor Management registry) that underwent a CR period of about 3 weeks were analyzed descriptively in total and compared by their MetS status.Results: In the total cohort, mean age was 64.3 years, (71.7% male), with no major differences between groups. Patients had been referred after a ST elevation of myocardial infarction event in 41.1% of cases, non-ST elevation of myocardial infarction in 21.8%, or angina pectoris in 16.7%. They had received a percutaneous coronary intervention in 55.1% and bypass surgery (coronary artery bypass graft) in 39.5%. Patients with MetS (n = 15,819) compared to those without MetS (n = 12,085) were less frequently males, and in terms of cardiac interventions, more often received coronary artery bypass surgery. Overall, statin use increased from 79.9% at entry to 95.0% at discharge (MetS: 79.7% to 95.2%). Patients with MetS compared to those without MetS received angiotensin converting enzyme inhibitors, angiotensin receptor blockers, oral antidiabetics, and insulin at entry and discharge more frequently, and less frequently clopidogrel and aspirin/clopidogrel combinations. Mean blood pressure was within the normal range at discharge, and did not differ substantially between groups (124/73 versus 120/72 mmHg). Overall, between entry and discharge, levels of total cholesterol, low density lipoprotein cholesterol, and triglycerides were substantially lowered, in particular in MetS patients. Thus, control rates of lipid parameters improved substantially, with the exception of high density lipoprotein cholesterol. Low density lipoprotein cholesterol rates <100 mg/dL increased from 38.7% at entry to 73.8% at discharge (MetS: from 39.4% to 74.6%) and triglycerides control rates (<150 mg/dL) from 58.1% to 70.4% (MetS: 43.7% to 62.2%). Physical fitness on exercise testing improved substantially in both groups.Conclusion: Patients with and without MetS benefited substantially from the participation in CR, as their lipid profile, blood pressure, and physical fitness improved. Treatment effects were similar in the two groups.Keywords: cardiac rehabilitation, registry, metabolism, diabetes, dyslipidemia, control rates, risk factor, lipid

Changes in the prevalence, treatment and control of hypertension in Germany? : a clinical-epidemiological study of 50.000 primary care patients

INTRODUCTION: Medical societies have developed guidelines for the detection, treatment and control of hypertension (HTN). Our analysis assessed the extent to which such guidelines were implemented in Germany in 2003 and 2001. METHODS: Using standardized clinical diagnostic and treatment appraisal forms, blood pressure levels and patient questionnaires for 55,518 participants from the cross-sectional Targets and Essential Data for Commitment of Treatment (DETECT) study (2003) were analyzed. Physician's diagnosis of hypertension (HTN(doc)) was defined as coding hypertension in the clinical appraisal questionnaire. Alternative definitions used were physician's diagnosis or the patient's self-reported diagnosis of hypertension (HTN(doc,pat)), physician's or patient's self-reported diagnosis or a BP measurement with a systolic BP≥140 mmHg and/or a diastolic BP≥90 (HTN(doc,pat,bp)) and diagnosis according to the National Health and Nutrition Examination Survey (HTN(NHANES)). The results were compared with the similar German HYDRA study to examine whether changes had occurred in diagnosis, treatment and adequate blood pressure control (BP below 140/90 mmHg) since 2001. Factors associated with pharmacotherapy and control were determined. RESULTS: The overall prevalence rate for hypertension was 35.5% according to HTN(doc) and 56.0% according to NHANES criteria. Among those defined by NHANES criteria, treatment and control rates were 56.0% and 20.3% in 2003, and these rates had improved from 55.3% and 18.0% in 2001. Significant predictors of receiving antihypertensive medication were: increasing age, female sex, obesity, previous myocardial infarction and the prevalence of comorbid conditions such as coronary heart disease (CHD), hyperlipidemia and diabetes mellitus (DM). Significant positive predictors of adequate blood pressure control were CHD and antihypertensive medication. Inadequate control was associated with increasing age, male sex and obesity. CONCLUSIONS: Rates of treated and controlled hypertension according to NHANES criteria in DETECT remained low between 2001 and 2003, although there was some minor improvement

Real-World Use, Safety, and Patient Experience of 20% Subcutaneous Immunoglobulin for Primary Immunodeficiency Diseases.

INTRODUCTION The CORE study aimed to provide a detailed understanding of real-world immune globulin subcutaneous (human) 20% solution (Ig20Gly) utilization in patients with primary immunodeficiency diseases (PIDs) in Germany and Switzerland. METHODS Patients with PIDs receiving a stable dose of any subcutaneous immunoglobulin for ≥ 3 months before enrollment were eligible for this multicenter (n = 5), phase 4, non-interventional, prospective, longitudinal cohort study. Besides baseline demographics and clinical characteristics, Ig20Gly utilization and safety data, and patient-reported outcomes (Life Quality Index/Treatment Satisfaction Questionnaire for Medication) were collected at baseline, 6 and 12 months. Statistical analysis was descriptive. RESULTS Overall, 36 patients provided data at baseline [69.4% female; mean age: 41.6 years (7-78 years)]. Totals of 23 and 26 patients attended 6- and 12-month visits, respectively; 16 attended all three visits. One patient withdrew consent before 6-month follow-up. Median maximum infusion rates of Ig20Gly at baseline, 6 months, and 12 months were 26.7, 24.5, and 40.0 mL/h, respectively (10-60 mL/h). Infusion and dosing parameters remained consistent across time points: patients used a median of two infusion sites, primarily the abdomen, and all patients used an infusion pump; all but one infused at home and most self-administered Ig20Gly (80.8-83.3%) at once-weekly intervals (69.2-73.9%). During follow-up, 10 adverse events were reported: none were rated serious, while 2 were considered probably related to Ig20Gly. Total patient-reported outcome scores remained high throughout the study. CONCLUSION The CORE study provides real-world evidence of the flexibility, feasibility, safety, and tolerability of Ig20Gly infusions, at mostly weekly intervals, over 1 year in patients with PIDs. TRIAL REGISTRATION German Clinical Trials Register, DRKS00014562. Registered April 9, 2018, https://drks.de/search/en/trial/DRKS00014562

Arterielle Hypertonie und Diabetes mellitus in der allgemeinärztlichen Praxis in Sachsen

EINLEITUNG: Die „Hypertension and Diabetes Risk Screening and Awareness (HYDRA-)-Studie“ beschrieb und quantifizierte erstmals umfassend und bundesweit in einer Reihe von Publikationen1- 10 (siehe auch www.hydra-studie.de) die hausärztliche Versorgungssituation von Patienten mit arterieller Hypertonie und Diabetes mellitus. Mit Hilfe dieser Studie konnten neue Erkenntnisse zur Häufigkeit und Schwere, zu häufigen Begleit- oder Folgeerkrankungen, sowie zur Therapie dieser beiden Erkrankungen gewonnen werden. Insgesamt wurden im September 2001 in einer bundesrepräsentativen Stichprobe von 1.912 zufällig ausgewählten primärärztlichen Praxen (auf der Grundlage des IMS-Registers, Instituts für Medizinische Statistik, Frankfurt) eine Stichtagsbefragung von 45125 nicht-selektierter, konsekutiver Patienten ab dem 16. Lebensjahr durchgeführt (60,0 Prozent Frauen; Altersgruppen: 12,7 Prozent 16 bis 29 Jahre, 21,9 Prozent 30 bis 44 Jahre, 23,2 Prozent: 45 bis 59 Jahre, 42,2 Prozent: = 60 Jahre) und ihre Erkrankungen und Interventionen dokumentiert. Im folgenden Beitrag sollen die Ergebnisse für Sachsen gesondert berichtet und den bundesdeutschen Ergebnissen gegenübergestellt werden. In Sachsen nahmen an der HYDRA-Studie n=126 Ärzte teil, die an zwei aufeinander folgenden Studientagen insgesamt 2.407 Patienten dokumentierten. Die Datenerhebung erfolgte im Rahmen eines klinischepidemiologischen Stufendesigns: (i) Zunächst wurden die teilnehmenden Ärzte in einer Voruntersuchung hinsichtlich ihrer Ausbildungsund Praxismerkmale, ihren Erfahrungen und Problemen mit Hypertonikern und Diabetikern sowie ihren Einstellungen zu diesen Patientengruppen befragt. (ii) Am Erhebungstag wurden alle Patienten, die die teilnehmenden Praxen aufsuchten, ausführlich zu ihren Beschwerden, Krankheiten sowie zu ihrem Gesundheitsverhalten befragt (Patientenfragebogen). (iii) Die Ärzte dokumentierten dann für jeden Patienten die von ihnen vergebenen klinischen Diagnosen sowie die Therapie (Arztbogen); zudem wurden ausgewählte Messwerte am Studientag erfasst (Blutdruck, Mikroalbuminurie mit Micral-Teststreifen) und weitere Laborwerte aus der Akte entnommen. Für die ärztlichen Diagnosen wurden keine Vorgaben (zum Beispiel Nennung von Grenzwerten) gemacht. Die Methodik der Studie und wesentliche Ergebnisse wurden in einer Reihe von Originalarbeiten detailliert beschrieben.

final results of the observational EXPLAIN-FXS study

Background As data on the phenotype, characteristics and management of patients with Fragile X Syndrome (FXS) are limited, we aimed to collect such data in Germany in experienced centres involved in the treatment of such patients. Methods EXPLAIN-FXS is a prospective observational (non- interventional) study (registry) performed between April 2013 and January 2016 at 18 sites in Germany. Requirements for patient participation included confirmed diagnosis of FXS by genetic testing (>200 CGG repeats) and written informed consent. Patients were followed for up to 2 years. Results Seventy- five patients (84.0 % males, mean age 16.7 ± 14.5 years, ranging from 2 - 82 years) were analysed. The mean 6-item score, determined according to Giangreco (J Pediatr 129:611-614, 1996), was 6.9 ± 2.5 points. At least one neurological finding each was noted in 53 patients (69.7 %). Specifically, ataxia was noted in 5 patients (6.6 %), lack of fine motor skills in 40 patients, (52.6 %), muscle tonus disorder in 4 patients (5.3 %), and other neurological disorders in 39 patients (51.3 %). Spasticity was not noted in any patient. Seizures were reported in 6 patients (8.1 %), anxiety disorders in 22 patients (30.1 %), depression in 7 patients (9.6 %), ADHD/ADD in 36 patients (49.3 %), impairment of social behavior in 39 patients (53.4 %), and other comorbidities in 23 patients (31.5 %). The mean Aberrant Behaviour Checklist Community Edition (ABC-C) score on behavioral symptoms, obtained in 71 patients at first documentation, was 48.4 ± 27.8 (median 45.0, range 5-115). The mean visual analogue scale (VAS) score, obtained in 59 patients at first documentation, was 84.9 ± 14.6 points (median 90; range 50 – 100). Conclusions This report describes the largest cohort of patients with FXS in Europe. The reported observations indicate a substantial burden of disease for patients and their caregivers. Based on these observations, an early expert psychiatric diagnosis is recommended for suspected FXS patients. Further recommendations include multimodal and multi-professional management that is tailored to the individual patient’s needs. Trial registration The ClinTrials.gov identifier is NCT01711606. Registered on 18 October 2012

Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry

Objective The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits (usually every 3–6 months) and collated via case report forms. Results In total, 326 patients with PAH were included in the analysis. The most common AEs in these patients were dizziness (11.7%), right ventricular (RV)/cardiac failure (10.7%), edema/peripheral edema (10.7%), diarrhea (8.6%), dyspnea (8.0%), and cough (7.7%). The most common SAEs were RV/cardiac failure (10.1%), pneumonia (6.1%), dyspnea (4.0%), and syncope (3.4%). The exposure-adjusted rate of hemoptysis/pulmonary hemorrhage was 2.5 events per 100 patient-years. Conclusion Final data from EXPERT show that in patients with PAH, the safety of riociguat in clinical practice was consistent with clinical trials, with no new safety concerns identified and a lower exposure-adjusted rate of hemoptysis/pulmonary hemorrhage than in the long-term extension of the Phase 3 trial in PAH

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified

Outcomes of medical management of peripheral arterial disease in general practice: follow-up results of the PACE-PAD Study

Aim: Peripheral arterial disease (PAD), a marker of elevated vascular risk, is highly prevalent in general practice. We aimed to investigate patient characteristics and outcomes of PAD patients treated according to the guidelines versus those who were not. Methods: The Patient Care Evaluation-Peripheral Arterial Disease Study (PACE-PAD) was a multicenter, cluster randomized, prospective, longitudinal cohort study of patients with PAD in primary care, who were followed up for death or vascular events over 18 months. Guideline orientation was assumed if patients received anticoagulant/antiplatelet therapy, exercise training, and (if applicable) advice for smoking cessation and therapy of diabetes mellitus, hypertension, or hypercholesterolemia, respectively. Results: Of the 5,099 PAD patients (mean age 68.0 ± 9.0 years, 68.5% male subjects) who were followed up, 22.5, 34.6, 30.1, 7.8, and 3.5% (1.5% not specified) were in Fontaine stages I, IIa, IIb, III, and IV. Comprehensive guideline orientation was reported in 28.4% only; however, patients in lower Fontaine stages received guideline-oriented therapy more often (I: 30.3%, IIa: 31.6%, IIb: 29.1%, III: 9.8%, IV: 18.0%). During 18 months, 457 patients died (224 due to cerebrovascular or coronary deaths), 319 had unstable angina pectoris, 116 myocardial infarction, and 140 an ischemic stroke event. In total, 24% of patients had experienced any vascular event (19.1% a first event). Event rates did not differ between patients treated according to guidelines and those who were not. Conclusion: The present PAD cohort was a high-risk sample with an unexpectedly high rate of deaths and vascular events. While physicians appear to focus on the treatment of individual risk factors, rates of comprehensive PAD management in line with guideline recommendations are still suboptimal. Factors contributing to the lacking difference between outcomes in the guideline-oriented and non-guideline-oriented groups may comprise low treatment intensity or other reasons for unsatisfactory effect of treatment, misclassification of events, and patient’s noncompliance with therapy

Raucherentwöhnung in der primärärztlichen Versorgung: Ziele, Design und Methoden der "Smoking and Nicotine Dependence Awareness and Screening (SNICAS)"-Studie

In Deutschland fehlen bislang belastbare epidemiologische Daten über sowohl die Häufigkeit nikotinabhängiger Raucher im primärärztlichen Versorgungsbereich als auch das Ausmaß der von Hausärzten angebotenen Raucherentwöhnungsmaßnahmen. Die Ziele in der "Smoking and Nicotine Dependence Awareness and Screening (SNICAS)"-Studie waren/sind: (1) die Ermittlung repräsentativer Daten zur Prävalenz des Rauchens und der Nikotinabhängigkeit in Deutschland, (2) die Beschreibung des Rauchverhaltens und der Aufhörmotivation von Rauchern in der primärärztlichen Versorgung sowie (3) die Feststellung von Einstellungen, Fertigkeiten und Erfahrungen von Hausärzten im Zusammenhang mit der Raucherentwöhnung. SNICAS basierte auf einem zweistufigen epidemiologischen Studiendesign, woran sich eine derzeit noch laufende, klinische Interventionskomponente anschloss. In Stufe I (Vorstudien-Fragebogen) wurde eine repräsentative Auswahl von 889 Ärzten (Allgemeinärzte, praktische Ärzte, Internisten) hinsichtlich Erfahrungen und Einstellungen zu Raucherentwöhnungsmethoden charakterisiert. In Stufe II wurde an einem Stichtag (7. Mai 2002) in diesen Praxen n = 28 707 unausgelesene, konsekutive Patienten zunächst mittels eines Patientenfragebogens untersucht (konservative Ausschöpfungsrate: 52,8%). Daran schloss sich für jeden einzelnen Patienten eine unabhängige, standardisierte Arztbeurteilung (Erhebung des Rauchstatus, des Gesundheitszustands, vergangener und aktueller Interventionen u.ä.) an. Der Beitrag enthält eine Darstellung von Design und Methode der SNICAS-Studie und berichtet über die Gewinnung, Ausschöpfung und Repräsentativität der Arzt- und Patientenstichprobe. Auf der Grundlage ausgewählter Daten des Vorstudien- Fragebogens, aus denen eine geringe Anzahl (17,6%) an sich intensiv mit der Raucherentwöhnung befassenden Ärzten hervorgeht, werden ärztliche Interventionsstrategien, aber auch Einstellungs- und Strukturbarrieren vorgestellt.Aims, Design and Methods of the "Smoking and Nicotine Dependence Awareness and Screening" (SNICAS) Study Germany lacks robust epidemiological data on the prevalence of smoking and nicotine dependence in primary care patients as it does on smoking cessation interventions provided by primary care physicians. Objectives of the "Smoking and Nicotine Dependence Awareness and Screening" (SNICAS) study are (1) to provide nationally representative data on the frequency of smoking and nicotine dependence among primary care patients in Germany, (2) to describe their smoking behaviour and motivation to quit as well as (3) attitudes, skills and experiences of physicians regarding smoking cessation. SNICAS is based on a 2-stage epidemiological design, supplemented by a subsequently conducted clinical intervention trial still ongoing. Stage I consists of a prestudy characterization of a nationwide sample of 889 primary care doctors (general practitioners, family doctors and internists with primary care functions). Stage II consists of a target day assessment (May 7th 2002) of n=28,707 unselected consecutive patients by means of a patient questionnaire (conservative response rate: 52.8%). For each patient a structured clinical appraisal form (screening of the patients' smoking status, physical and mental health, current and past interventions etc. ) was accomplished by the doctor. This article presents design and methods of the SNICAS study and describes its sampling strategy, its response rates and the representativity of primary care doctors and patients. By means of selected pre-study data, showing that only a small proportion of physician is extensively involved in smoking cessation (17.6%), intervention strategies of the doctors are presented as well as obstacles for smoking cessation (e.g. structures, attitudes)