Measurements of the aortic pulse wave velocity (PWV) with applanation tonometry is broadly accepted, but investigator-dependent, time-consuming, and expensive. Recently a new method to determine PWV derived from oscillometric pressure curves with a simple upper arm cuff has been developed. The aim of the present study was to compare the PWV derived from two well established and clinically validated tonometric methods (SphygmoCor, Complior) with the oscillometric one (Arteriograph). PWV was measured in 51 patients up to 5 times with SphygmoCor, Complior and Arteriograph, respectively. 36 patients we measured in a second session following the same protocol. We then compared the means of the PWVs for each patient per session (n = 87). The correlations of the PWV assessed by Arteriograph compared to SphygmoCor was r = 0.67 (p < 0.001) and to Complior r = 0.069 (p <0.001). SphygmoCor- and Complior-assessed PWVs showed a correlation of r = 0.87. The new oscillometric method of assessing PWV is highly correlated to the tonometrically derived PWV. Further studies are necessary to define the clinical use of the oscillometrically derived PWV.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Als Diuretika werden bei der Hypertoniebehandlung weltweit die Thiaziddiuretika Hydrochlorothiazid und Bendroflumethiazid und die „thiazidartigen“ Diuretika Chlortalidon und Indapamid eingesetzt und als eine Wirkstoffklasse zusammengefasst. Neuere Befunde weisen jedoch darauf hin, dass sowohl in Bezug auf Blutdrucksenkung als auch auf prognostische Effekte Bendroflumethiazid und Hydrochlorothiazid – zumindest in den üblichen niedrigen Dosierungen – dem Indapamid und insbesondere Chlortalidon unterlegen sind. Dies ist insofern von klinischer Bedeutung, als Hydrochlorothiazid mit großem Abstand der weltweit meistverordnete Vertreter dieser Wirkstoffklasse ist. Einer Dosiserhöhung von Hydrochlorothiazid steht jedoch eine Zunahme der meist dosisabhängigen Nebenwirkungen entgegen. Die zugrunde liegenden Mechanismen der Überlegenheit von Chlortalidon auf prognostische Parameter sind unklar. Hier könnte insbesondere eine Rolle spielen, dass Chlortalidon mit >50 h eine etwa 5-fach längere Halbwertszeit besitzt als Hydrochlorothiazid. Bei verbreitet unregelmäßiger Einnahme antihypertensiver Therapie kommt Chlortalidon als „forgiving drug“ damit ein therapeutischer Vorteil zu. Thiazidartige Diuretika, insbesondere Chlortalidon, sollten damit bei entsprechender Indikationsstellung bei der Hypertoniebehandlung vor Hydrochlorothiazid und Bendroflumethiazid präferiert werden.

Diuretika vom Thiazid-Typ sind seit über 50 Jahren verfügbar und spielen bei der Hypertoniebehandlung in Monosowie Kombinationstherapie eine herausragende Rolle [7, 9, 10]. Aus großen Hypertonie-Interventionsstudien sind Daten der beiden Thiaziddiuretika Hydrochlorothiazid und Bendroflumethiazid und der beiden Thiazid-artigen Diuretika Chlortalidon und Indapamid verfügbar [9, 10]. Die weltweit meistverordnete Substanz in dieser Wirkstoffgruppe ist Hydrochlorothiazid (HCT), das seit 1958 zugelassen ist, und in den ersten Jahrzehnten seiner Verfügbarkeit in Tagesdosen von 50–100 mg verordnet wurde. Zur Reduktion seiner Dosis-abhängigen Nebenwirkungen werden derzeit fast ausschließlich Dosen von 12,5–25 mg/Tag eingesetzt. Die Rolle der Diuretika bei der Hypertoniebehandlung wird in einigen Aspekten nach wie vor kontrovers beurteilt. Ein aktueller Aspekt betrifft die Frage, inwiefern die genannten Substanzen als eine Gruppe zusammengefasst werden dürfen oder ob nicht vielmehr eine separate Bewertung der unterschiedlichen Diuretika notwendig ist.

The overwhelming majority of hypertensive patients need two or more antihypertensive agents to normalize blood pressure. According to US and European guidelines, so-called single-pill drug combinations should be employed whenever possible in order to simplify the regimen and increase long-term medication adherence. With respect to dual-drug combinations, the recently revised European (ESC/ESH) guidelines recommend the following options: RAS blocker (ACE inhibitor and angiotensin receptor blocker) or calcium channel blocker (CCB) plus diuretic or RAS blocker plus CCB. In a head to-head comparison in patients at high cardiovascular risk, the ACCOMPLISH trial has recently shown a prognostic advantage for a RAS blocker plus CCB combination as compared to RAS blocker plus diuretic. Regarding triple-drug combinations, the revised European guidelines give preference to the combination of an ACE inhibitor or angiotensin receptor blocker plus a CCB and diuretic. Refractory hypertension is defined as the failure to achieve normal blood pressure values despite an effectively dosed triple-drug regimen containing a diuretic. In such patients, poor patient compliance and secondary hypertension should be considered before escalating therapy.

Die überwiegende Mehrzahl aller Hypertoniepatienten bedarf zur Blutdrucknormalisierung einer Therapie mit ≥2 Medikamenten. Insbesondere aus Gründen der langfristigen Therapietreue empfehlen Fachgesellschaften übereinstimmend die Verwendung sog. „fixer“ Kombinationen zur Vereinfachung des Therapieschemas. Entsprechend den aktualisierten Leitlinien der ESC/ESH sind in Bezug auf 2er-Kombinationen RAS-Blocker (ACE-Hemmer und AT1-Antagonisten) oder Kalziumantagonisten plus Diuretika oder RAS-Blocker plus Kalziumantagonisten zu präferieren. Die ACCOMPLISH-Studie konnte zeigen, dass eine RAS-Blocker/Kalziumantagonist-Kombination zumindest bei Patienten mit hohem kardiovaskulärem Gesamtrisiko günstigere prognostische Wirkungen entfaltet als eine RAS-Blocker/Diuretikum-Kombination. Für den Fall der Notwendigkeit einer 3er-Kombinationsbehandlung empfehlen die aktualisierten Europäischen Leitlinien die Kombination eines ACE/Hemmers oder AT1-Antagonisten gemeinsam mit einem Kalziumantagonisten und einem Diuretikum. Ausbleibende Blutdrucknormalisierung unter einer ausreichend dosierten 3er-Kombination rechtfertigt die Diagnose einer „therapierefraktären“ Hypertonie. Vor weiterer Therapieeskalation sollte die Therapietreue des betreffenden Patienten thematisiert und ggf. eine Suche nach sekundären Hypertonieformen initiiert werden.

For ten years, severe physical exercise in a 24 year old male patient had been an almost constant trigger of frequent attacks of pareses which were mostly accompanied by complete tetraplegia and once by the occurrence of cardiac arrest with atrial fibrillation. During the attack, the serum potassium concentration fell to 1.2 mmol/l, whereas the intraleukocytic potassium concentration rose from 136 mmol/l to 149 mmol/l. The catecholamine excretion in the urine was raised during the first 24 hours after admission as an emergency (189 micrograms noradrenalin and 54 micrograms adrenalin). After intravenous adrenalin infusion (0.01-0.1 microgram/kg X min) during the symptom-free interval, there was a major fall of the serum potassium concentration from 3.9 mmol/l to 3.1 mmol/l. This was not accompanied by a raised insulin excretion and could be prevented by prior administration of the nonselective beta blocker propranolol. On the basis of these results, the patient was treated prophylactically with three times 40 mg/d p.o. propranolol. Pareses requiring treatment no longer occurred under this therapy.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Background and objective: Autoantibodies directed against clotting factors can induce life threatening bleeding with a mortality rate up to 22%. Although the incidence of the disease is low (1-4 X10(-6)), costs of treatment due to long-term clotting factor substitution can be enormous. Aim of an optimal treatment strategy should be to control bleedings by a rapid and safe elimination of the inhibitor and reinducing long-term immune tolerance.Patients and Methods: Treatment of 48 patients with acquired haemophilia A (m=20, f =28, age 61,3 (SD 16,4)), the largest patient collective world-wide, was monitored for a mean of 48 months. Three patients received only conservative treatment. 45 patients were treated intensively by a multimodal strategy including: 1. immunoadsorption for antibody elimination; 2. FVIII substitution; 3. intravenous immunoglobulin substitution and 4. immunosuppression. The times required for inhibitor elimination, factor VIII substitution and the duration of the MBMP were documented.Results: In 45 patients with a high titre critical bleeding was controlled immediately after the initiation of MBMP. There were no deaths from bleeding or the treatment. Inhibitor levels decreased to undetectable levels within a median of 3 days (95% Cl, 3-7 days), factor substitution was terminated within a median of 13 days (95% Cl, 10-16 days) and the treatment was completed within a median of 15 days (95% Cl, 13-17 days). The overall response rate for complete remission (CR) was 91%. When cancer patients were excluded, the CR rate was 97%.Conclusion: Considering the short duration and amount of factor VIII substitution, the short time of hospitalization and the long-term median follow up of 48 months without bleeding events, the MBMP appears to have a modifiying effect on the immunological response.

Autoantibodies directed against clotting factors can induce life threatening bleeding with a mortality rate up to 22%. Although the incidence of the disease is low (1-4 x 10(-6)), costs of treatment due to long-term clotting factor substitution can be enormous. Aim of an optimal treatment strategy should be to control bleedings by a rapid and safe elimination of the inhibitor and reinducing long-term immune tolerance.Treatment of 48 patients with acquired haemophilia A (m=20, f =28, age 61.3 (SD 16.4)), the largest patient collective world-wide, was monitored for a mean of 48 months. Three patients received only conservative treatment. 45 patients were treated intensively by a multimodal strategy including: 1. immunoadsorption for antibody elimination; 2. FVIII substitution; 3. intravenous immunoglobulin substitution and 4. immunosuppression. The times required for inhibitor elimination, factor VIII substitution and the duration of the MBMP were documented.In 45 patients with a high titre critical bleeding was controlled immediately after the initiation of MBMP. There were no deaths from bleeding or the treatment. Inhibitor levels decreased to undetectable levels within a median of 3 days (95% CI, 3-7 days), factor substitution was terminated within a median of 13 days (95% CI, 10-16 days) and the treatment was completed within a median of 15 days (95% CI, 13-17 days). The overall response rate for complete remission (CR) was 91%. When cancer patients were excluded, the CR rate was 97%.Considering the short duration and amount of factor VIII substitution, the short time of hospitalization and the long-term median follow up of 48 months without bleeding events, the MBMP appears to have a modifying effect on the immunological response.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

BACKGROUND AND OBJECTIVE:Autoantibodies directed against clotting factors can induce life threatening bleeding with a mortality rate up to 22%. Although the incidence of the disease is low (1-4 x 10(-6)), costs of treatment due to long-term clotting factor substitution can be enormous. Aim of an optimal treatment strategy should be to control bleedings by a rapid and safe elimination of the inhibitor and reinducing long-term immune tolerance.PATIENTS AND METHODS:Treatment of 48 patients with acquired haemophilia A (m=20, f =28, age 61.3 (SD 16.4)), the largest patient collective world-wide, was monitored for a mean of 48 months. Three patients received only conservative treatment. 45 patients were treated intensively by a multimodal strategy including: 1. immunoadsorption for antibody elimination; 2. FVIII substitution; 3. intravenous immunoglobulin substitution and 4. immunosuppression. The times required for inhibitor elimination, factor VIII substitution and the duration of the MBMP were documented.RESULTS:In 45 patients with a high titre critical bleeding was controlled immediately after the initiation of MBMP. There were no deaths from bleeding or the treatment. Inhibitor levels decreased to undetectable levels within a median of 3 days (95% CI, 3-7 days), factor substitution was terminated within a median of 13 days (95% CI, 10-16 days) and the treatment was completed within a median of 15 days (95% CI, 13-17 days). The overall response rate for complete remission (CR) was 91%. When cancer patients were excluded, the CR rate was 97%.CONCLUSION:Considering the short duration and amount of factor VIII substitution, the short time of hospitalization and the long-term median follow up of 48 months without bleeding events, the MBMP appears to have a modifying effect on the immunological response.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study