BOLD and perfusion changes during epileptic generalised spike wave activity

It is unclear whether neurovascular coupling is maintained during epileptic discharges. Knowing this is important to allow appropriate inferences from functional imaging studies of epileptic activity. Recent blood oxygen level-dependent (BOLD) functional MRI (fMRI) studies have demonstrated negative BOLD responses (NBR) in frontal, parietal and posterior cingulate cortices during generalised spike wave activity (GSW). We hypothesized that GSW-related NBR commonly reflect decreased cerebral blood flow (CBF). We measured BOLD and cerebral blood flow responses using simultaneous EEG with BOLD and arterial spin label (ASL) fMRI at 3 T. Four patients with epilepsy were studied; two with idiopathic generalized epilepsy (IGE) and two with secondary generalized epilepsy (SGE). We found GSW-related NBR in frontal, parietal and posterior cingulate cortices. We measured the coupling between BOLD and CBF changes during GSW and normal background EEG and found a positive correlation between the simultaneously measured BOLD and CBF throughout the imaged volume. Frontal and thalamic activation were seen in two patients with SGE, concordant with the electro-clinical features of their epilepsy. There was striking reproducibility of the GSW-associated BOLD response in subjects previously studied at 1.5 T. Our results show a preserved relationship between BOLD and CBF changes during rest and GSW activity consistent with normal neurovascular coupling in patients with generalized epilepsy and in particular during GSW activity. Cortical activations appear to reflect areas of discharge generation whilst deactivations reflect changes in conscious resting state activity

The year in cardiology: cardiovascular prevention. The year in cardiology 2019.

No abstract available

Interdisciplinary Physician-Pharmacist Medication Review for Outpatients With Heart Failure: A Subanalysis of the PHARM-CHF Randomized Controlled Trial.

Aims: Patients with chronic heart failure (CHF) require polypharmacy and are at increased risk for drug-related problems. Interdisciplinary physician-pharmacist medication review may improve drug treatment. Our goal was to analyze the changes from the physician-documented medication plan (MP) and patient-stated medication to an interdisciplinary consolidated MP (CMP). Methods: This pre-specified subanalysis of the PHARM-CHF randomized controlled trial analyzed the medication review of CHF patients in the pharmacy care group. Community pharmacists compared the MP with the drug regimen stated by the patient and consulted with physicians on identified discrepancies and other medication-related problems resulting in a CMP. Results: We analyzed 93 patients (mean 74.0 ± 6.6 years, 37.6% female), taking a median of ten (IQR 8-13) drugs. 80.6% of patients had at least one change from MP to CMP. We identified changes in 32.7% (303/926) of drugs. The most common correction was the addition of a drug not documented in the MP to the CMP (43.2%). We also determined frequent modifications in the dosing regimens (37.6%). The omission of a drug documented in the MP but left out of the CMP accounted for 19.1%. Comparing patient-stated medication to CMP, the current drug regimen of patients was changed in 22.4% of drugs. Conclusion: The medication review resulted in changes of medication between MP and CMP in most of the patients and affected one-third of drugs. Structured physician-pharmacist interdisciplinary care is able to harmonize and optimize the drug treatment of CHF patients

Prinzip der mendelschen Randomisierung und Anwendung in der kardiovaskulären Medizin

Zusammenfassung: Hintergrund: Die Methode der mendelschen Randomisierung wird zunehmend zur Auswertung genetischer und epidemiologischer Daten genutzt. Korrekt angewendet, können wichtige Erkenntnisse für die klinische Forschung, Entwicklung neuer Pharmaka und die Patientenversorgung gewonnen werden. Ziel der Arbeit: Die vorliegende Übersichtsarbeit soll das Prinzip, Anwendungsmöglichkeiten und Limitationen der mendelschen Randomisierung anhand von Beispielen aus der kardiovaskulären Medizin aufzeigen. Material und Methode: Es erfolgte eine selektive Literaturrecherche in PudMed. Weiterhin flossen Erfahrungen der Autoren in der Anwendung der mendelschen Randomisierung ein. Ergebnisse: Mithilfe der mendelschen Randomisierung können Menschen anhand von genetischen Markern randomisiert werden. Geeignete genetische Marker sind direkt mit einer lebenslangen Exposition assoziiert. Bei Nachweis einer Assoziation zwischen dem genetischen Marker und einer Erkrankung kann man von einer kausalen Beziehung zwischen der Exposition und der Erkrankung ausgehen. Somit können aus epidemiologischen Daten Schlussfolgerungen zur Kausalität einer Assoziation und deren quantitativer Ausprägung gezogen werden. Weiterhin können mithilfe der mendelschen Randomisierung die Ergebnisse klinischer Studien antizipiert werden, was Rückschlüsse über bekannte Wirkstoffe erlaubt und der Entwicklung neuer pharmakologischer Prinzipien dient. Die Limitationen der mendelschen Randomisierung müssen bei der Interpretation der gewonnenen Erkenntnisse beachtet werden. Schlussfolgerung: Um Studien, welche auf dem Prinzip der mendelschen Randomisierung beruhen, kritisch interpretieren zu können, ist ein grundlegendes Verständnis der Möglichkeiten und Grenzen der Methode notwendig

Impact of angiotensin receptor blocker product recalls on antihypertensive prescribing in Germany.

In Germany, ~8 million patients take angiotensin receptor blockers (ARBs) and 2.25 million of them valsartan. In 2018, contamination of generic ARBs with probable carcinogenic nitrosamines resulted in more than 30 recalls. The impact of such a huge recall has never been explored in Europe. We analyzed the utilization of valsartan, all ARBs, and other alternative antihypertensive drugs in Germany. We used our database of anonymized dispensing data from >80% of community pharmacies at the expense of the statutory health insurance (SHI) funds from January 2017 to December 2019. We analyzed 290.8 million prescriptions, including all oral mono- and fixed-dose combinations of ARBs and plausible alternatives, i.e. ACE inhibitors (ACEi), beta-blockers (BB), and calcium channel blockers (CCB). Utilization was calculated by defined daily doses per 1000 SHI-insured persons per day (DID). Valsartan use decreased substantially after the recalls in July 2018 from 39.0 to 14.2 DID (-64%) in the second quarter of 2019 and to 16.9 DID (-57%) in the fourth quarter of 2019. Simultaneously, the use of alternative ARBs increased from 77.7 DID in the second quarter of 2018 to 121.9 DID (+57%) in the fourth quarter of 2019, mainly due to an increase of candesartan dispensing to 99.8 DID (+73%). There were no changes in the utilization of ACEi, BB, or CCB. The majority of recalled generic valsartan products were replaced by other ARBs, predominantly candesartan, despite documented drug shortages. In contrast to previous safety warnings/recalls, our data do not suggest an under-prescription of antihypertensives during this period

Comparison of Different Strategies to Measure Medication Adherence via Claims Data in Patients With Chronic Heart Failure.

Medication adherence correlates with morbidity and mortality in patients with chronic heart failure (CHF), but is difficult to assess. We conducted a retrospective methodological cohort study in 3,808 CHF patients, calculating adherence as proportion of days covered (PDC) utilizing claims data from 2010 to 2015. We aimed to compare different parameters' influence on the PDC of elderly CHF patients exemplifying a complex chronic disease. Investigated parameters were the assumed prescribed daily dose (PDD), stockpiling, and periods of hospital stay. Thereby, we investigated a new approach using the PDD assigned to different percentiles. The different dose assumptions had the biggest influence on the PDC, with variations from 41.9% to 83.7%. Stockpiling and hospital stays increased the values slightly. These results queries that a reliable PDC can be calculated with an assumed PDD. Hence, results based on an assumed PDD have to be interpreted carefully and should be presented with sensitivity analyses to show the PDC's possible range

The influence of statins on the free intracellular calcium concentration in human umbilical vein endothelial cells

BACKGROUND: Statins are cholesterol-lowering drugs that are widely used to reduce the risk of cardiac infarction. Their beneficial clinical effects, however, are not restricted to their influence on cholesterol production. As several studies have shown that they have a potency of relaxing blood vessels. METHODS: We measured the effects of statins on the intracellular free calcium concentration ([Ca(2+)](i)) in human umbilical vein endothelial cells (HUVEC) after acute application and 24-h-preincubation of statins. RESULTS: Incubation of the cells for 24 h with cerivastatin or fluvastatin significantly increased the resting [Ca(2+)](i). For cerivastatin this effect manifested at a concentration of 1 μM. Increase of resting [Ca(2+)](i )in the presence of cerivastatin also occurred when the nitric oxide synthase was inhibited. Transient Ca(2+ )release induced by histamine was not affected. CONCLUSIONS: The increase of resting [Ca(2+)](i )after incubation with cerivastatin or fluvastatin may provide an explanation for the direct effects of statins on the endothelial-dependent vasodilatation and restoration of endothelial activity in vivo

Development and implementation of blood pressure screening and referral guidelines for German community pharmacists.

Involvement of community pharmacists in the detection and control of hypertension improves patient care. However, current European or North-American guidelines do not provide specific guidance how to implement collaboration between pharmacists and physicians, especially when and how to refer patients with undetected or uncontrolled hypertension to a physician. The German Society of Cardiology and the ABDA - Federal Union of German Associations of Pharmacists developed and tested referral recommendations for community pharmacists, embedded in two guideline worksheets. The project included a guideline-directed blood pressure (BP) measurement and recommendations when patients should be referred to their physician. A "red flag" referral within 4 weeks was recommended when SBP was >140 mm Hg or DBP >90 mm Hg (for subjects 160 mm Hg or >90 mm Hg (≥80 years) in undetected individuals, or >130 mm Hg or >80 mm Hg (140 mm Hg or >80 mm Hg (≥65 years) in treated patients. BP was measured in 187 individuals (86 with known hypertension, mean [±SD] age 62 ± 15 years, 64% female, and 101 without known hypertension, 47 ± 16 years, 75% female) from 17 community pharmacies. In patients with hypertension, poorly controlled BP was detected in 55% (n = 47) and were referred. A total of 16/101 subjects without a history of hypertension were referred to their physician because of uncontrolled BP. Structured BP testing in pharmacies identified a significant number of subjects with undetected/undiagnosed hypertension and patients with poorly controlled BP. Community pharmacists could play a significant role in collaboration with physicians to improve the management of hypertension

“Pure” severe aortic stenosis without concomitant valvular heart diseases:echocardiographic and pathophysiological features

Purpose!#!In echocardiography the severity of aortic stenosis (AS) is defined by effective orifice area (EOA), mean pressure gradient (mPG!##!Methods and results!#!Patients (n = 306) with asymptomatic (n = 133) and symptomatic (n = 173) 'pure' severe AS (mean age 78 ± 9.5 years) defined by indexed EOA < 0.6 cm!##!Conclusion!#!In patients with 'pure' AS according to current guidelines the presence of combined LVH, DD and PAH as accepted pathophysiological sequelae of severe AS cannot be confirmed. Probably, the detection of these secondary cardiac alterations might improve the diagnostic algorithm to avoid overestimation of AS severity