Internet Marketing of Cardioprotective Dietary Supplements.

Objectives: Considering high prevalence of use of dietary supplements and their easy access on the internet, the aim of this research was to examine and assess the prevalence of the internet marketing of heart-protective supplements as the most popular supplements of today, and to investigate the quality and quantity of information that are available to consumers on the sale websites. Design: Three major search engines (Google, Yahoo, and Bing) and keywords "cardiovascular supportive supplements online buy" were used to identify websites that sell cardioprotective dietary supplements. Content of first 50 listed websites in each engine was evaluated for its compliance with regulatory acts while information about supplements' efficacy and safety was compared with the results of the latest scientific research. Results: Of a total of 150 listed websites, 89 selling supplements for the specific indication underwent further analysis. The most commonly registered cardioprotective dietary supplements on the internet were supplements based on omega-3 fatty acids (omega-3) (57 websites, 64.05%). Related to the websites selling omega-3 supplements, risk reduction claims were presented at 23 (40.35%), whereas structure or function claims were present at 50 (87.72%) analyzed websites, but followed with Food and Drug Administration disclaimer only on 68.00% of them. Information about adverse effects were rarely pointed out (1 website, 1.75%) unlike warnings, which were significantly more available to consumers (38, 66.67%). Conclusions: According to obtained results, most of the analyzed websites that sell omega-3 supplements did not contain all important medical information required by Dietary Supplement Health and Education Act. Since use of internet marketing is in expansion and since consumers have no access to relevant medical information about dietary supplements on the selling websites, there is a clear need for better quality control of websites and greater public awareness of these widely used products.

Levosimendan in the light of the results of the recent randomized controlled trials: an expert opinion paper.

Despite interesting and unique pharmacological properties, levosimendan has not proven a clear superiority to placebo in the patient populations that have been enrolled in the various recent multicenter randomized controlled trials. However, the pharmacodynamic effects of levosimendan are still considered potentially very useful in a number of specific situations.Patients with decompensated heart failure requiring inotropic support and receiving beta-blockers represent the most widely accepted indication. Repeated infusions of levosimendan are increasingly used to facilitate weaning from dobutamine and avoid prolonged hospitalizations in patients with end-stage heart failure, awaiting heart transplantation or left ventricular assist device implantation. New trials are under way to confirm or refute the potential usefulness of levosimendan to facilitate weaning from veno-arterial ECMO, to treat cardiogenic shock due to left or right ventricular failure because the current evidence is mostly retrospective and requires confirmation with better-designed studies. Takotsubo syndrome may represent an ideal target for this non-adrenergic inotrope, but this statement also relies on expert opinion. There is no benefit from levosimendan in patients with septic shock. The two large trials evaluating the prophylactic administration of levosimendan (pharmacological preconditioning) in cardiac surgical patients with poor left ventricular ejection fraction could not show a significant reduction in their composite endpoints reflecting low cardiac output syndrome with respect to placebo. However, the subgroup of those who underwent isolated CABG appeared to have a reduction in mortality. A new study will be required to confirm this exploratory finding.Levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties. More studies are needed to provide a higher level of proof regarding these indications.

An integrated strategy for rapid discovery and identification of quality markers in Guanxin Kangtai preparation using UHPLC-TOF/MS and multivariate statistical analysis.

BACKGROUND: Guanxin Kangtai preparation (GXKT), consisting of Panax ginseng, Panax notoginseng and Ilex pubescens, is a new proprietary Chinese medicines under development for treating coronary heart disease. Like other Chinese medicines, the components of GXKT were complex and the bioactive compounds remained unclear. PURPOSE: To discover bioactive compounds as quality markers (Q-markers) for better quality control of GXKT. STUDY DESIGN: Chinese medicines was separated into fractions. The correlation between chemical information and bioactivity of these fractions were analyzed with multivariate statistical methods to discover bioactive compounds responsible for the actions of Chinese medicine. METHOD: GXKT was separated into fractions by using high-performance liquid chromatography (HPLC). Ultra HPLC coupled with time-of-flight mass spectrometer (UHPLC-TOF/MS) was applied to detect compound information from these fractions to form a chemical database. The bioactivity of these fractions in protecting cardiomyocytes from ischemia/reperfusion injury was examined in H9c2 cells that were exposed to hypoxia followed by reoxygenation (H/R). Then, partial least square model and orthogonal projections to latent structures discriminant analysis were employed to discover bioactive compounds from the chemical database that were positively correlated with the bioactivity of GXKT fractions. Finally, the bioactivity of these compounds was confirmed by bioassay in H9c2 cells. RESULTS: The chemical information of 120 fractions separated from GXKT was detected and extracted by UHPLC-TOF/MS, and a chemical database including 61 high abundance compounds were formed from all fractions. These fractions produced different extent of protective effect to H9c2 cell underwent H/R treatment with cell viability ranging from 33.43% to 74.91%, demonstrating the separation of bioactive compounds among different fractions. The multivariate analysis discovered 16 compounds from GXKT positively correlated with the bioactivity of GXKT. Of these compounds, 6 compounds, i.e.: ginsenoside Rg1, Rb1, Rh1, Rc, ilexsaponin A1, and chikusetsusaponin IVa were chemical identified and also confirmed for their responsibility to the action of GXKT by bioassay. CONCLUSION: Ginsenoside Rg1, Rb1, Rh1, Rc, ilexsaponin A1, and chikusetsusaponin IVa were bioactive compounds and qualified as Q-markers for quality control of GXKT. This research provided a useful reference for the quality research of Chinese medicines.

Reporting on the Strategies Needed to Implement Proven Interventions: An Example From a "Real-World" Cross-Setting Implementation Study.

UNLABELLED: The objective of this study was to empirically demonstrate the use of a new framework for describing the strategies used to implement quality improvement interventions and provide an example that others may follow. Implementation strategies are the specific approaches, methods, structures, and resources used to introduce and encourage uptake of a given intervention's components. Such strategies have not been regularly reported in descriptions of interventions' effectiveness, or in assessments of how proven interventions are implemented in new settings. This lack of reporting may hinder efforts to successfully translate effective interventions into "real-world" practice. A recently published framework was designed to standardize reporting on implementation strategies in the implementation science literature. We applied this framework to describe the strategies used to implement a single intervention in its original commercial care setting, and when implemented in community health centers from September 2010 through May 2015. Per this framework, the target (clinic staff) and outcome (prescribing rates) remained the same across settings; the actor, action, temporality, and dose were adapted to fit local context. The framework proved helpful in articulating which of the implementation strategies were kept constant and which were tailored to fit diverse settings, and simplified our reporting of their effects. Researchers should consider consistently reporting this information, which could be crucial to the success or failure of implementing proven interventions effectively across diverse care settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02299791.

[Which drugs are useful during resuscitation? Which are not?]. / Welche Medikamente sind bei der Reanimation sinnvoll? Welche nicht?

INTRODUCTION: Cardiopulmonary resuscitation represents a therapeutic challenge. Evidence-based guidelines, which were updated in 2015, give detailed advice on how to treat the patient. METHODS: Basic life support consists of cardiopulmonary resuscitation (30 chest compressions interrupted briefly to provide to 2 ventilations) and, if ventricular tachyarrhythmia is present, urgent cardiac defibrillation. Administration of drugs is one of the aspects of advanced life support. Vasopressors (adrenaline, vasopressin) aim to optimize coronary and cerebral perfusion. Antiarrhythmic drugs (amiodarone or lidocaine, when amiodarone is not available) are given during cardiac arrest to treat specific cardiac arrhythmias, mainly ventricular fibrillation and ventricular tachycardia. CONCLUSION: However, even in current guidelines, there is growing ambivalence towards drug treatment in the setting of cardiopulmonary resuscitation. This is mainly due to a paucity of robust clinical data. Most of the studies that have addressed the efficacy and safety of drugs during resuscitation are observational studies; however, a few small randomized controlled studies also exist. Recently, two large randomized controlled studies addressing the efficacy and safety of adrenaline versus placebo and amiodarone or lidocaine versus placebo have started. Both are currently recruiting patients. The hope is that the results of these studies will help to better define the role of drugs administered during cardiopulmonary resuscitation.

[Impact of guideline adherence on mortality in treatment of left heart failure]. / Auswirkung einer leitliniengerechten Behandlung auf die Mortalität bei Linksherzinsuffizienz.

BACKGROUND: The German national guidelines on chronic heart failure provide treatment recommendations to physicians and reflect the current level of evidence; however, it is questionable to what extent these recommendations are applied in the routine practice and what the effect of guideline adherence on mortality is. METHODS: In this study the claims data of a major German health insurance fund collected over a period of 4 years were analyzed. Using binary logistic regression and Cox regression analyses the influence of drug prescriptions, diagnostic measures, influenza vaccination, the New York Heart Association (NYHA) status, the age and gender on mortality were examined. RESULTS: The study population consisted of 85,465 heart failure patients. Approximately 60 % of the drugs were prescribed according to the guidelines. There was a positive correlation between a higher NYHA status and mortality with an odds ratio (OR) of 3.264. Especially pharmacotherapy with angiotensin-converting enzyme (ACE) inhibitors and beta blockers according to the guidelines was associated with a lower mortality rate (OR 0.448 resp. 0.444). Also patients diagnosed using echocardiography at regular intervals showed a lower risk of dying (OR 0.314). CONCLUSION: The results of this large sample could confirm the results of clinical trials that a therapy according to the guidelines has a significant impact on mortality. By analyzing the claims data evidence was found that in the treatment of heart failure patients the medical results could be improved by adherence to guideline recommendations.

[Treatment of chronic heart failure: what's not (yet) in the guidelines]. / Therapie der chronischen Herzinsuffizienz. Was (noch) nicht in den Leitlinien steht.

2012 Scientific meeting of the European Society of Cardiology (ESC), the current Guidelines on Acute and Chronic Heart Failure were introduced whose preparation had started 18 months earlier. These guidelines integrate scientific evidence of the years 2011 and 2012, leaving several questions open due to gaps in knowledge. These questions relate, amongst others, to diagnostics and imaging, non-pharmacologic and pharmacologic therapeutic approaches, mechanical support therapy, and heart transplantation. Based on recent studies, we will address some of these questions and discuss potential impact of their results on current clinical practice. A further official update of the ESC heart failure guidelines is expected for early 2016, which will then show if today's assessment holds true.

Solid-state characterization and transformation of various creatine phosphate sodium hydrates.

Creatine phosphate sodium (CPS) salt is a first-line cardiovascular drug for severe diastolic heart failure. The drug exists in different hydrate forms. The marketed drug form was determined as CPS·4.5H2 O (H1); however, the reference standard was supplied as CPS·6H2 O (H2). In this work, we present two newly identified hydrate forms: a thermodynamically stable low hydrate form, CPS·1.5H2 O (H3), and a pressure-sensitive transit form, CPS·7H2 O (H4). The hydrate forms were discovered through a comprehensive solid-state screening experiment and fully characterized using a range of analytical techniques including X-ray powder diffraction (XRPD), FTIR, Raman spectroscopy, hot-stage microscopy (HSM), thermogravimetric analysis, and differential scanning calorimetry. Stability tests revealed that H3 was the most stable hydrate under thermal stimulation. H4 is a pressure-sensitive hydrate and easily transforms to H2 and then H1 upon grinding. The form transformation process was closely monitored using the HSM, variable-temperature XRPD (VT-XRPD), and VT-Raman spectroscopy techniques. Specifically, the transformation of H4 to H1 is characterized in a single-crystal-to-single-crystal transformation process. The newly discovered hydrate form H3 has superior physicochemical properties than the marketed forms and is worthy of further development.

A strategy for detecting optimal ratio of cardioprotection-dependent three compounds as quality control of guan-xin-er-hao formula.

AIMS: We aimed to detect optimal ratio of cardioprotection-dependent absorbed bioactive compounds (ABCs) as quality control of guan-xin-er-hao (GXEH) formula extracted by various processings. METHODS: Ferulic acid (F), tanshinol (T), hydroxysafflor yellow A (A), protocatechualdehyde (P) and paeoniflorin (E) in GXEH formula and FTA in blood from rat with acute myocardial infarction (AMI) were first identified by HPLC-MS/MS, and FTAPE in GXEH formulae with various herbs, extraction times and extraction water volumes were then quantitated only by HPLC. RESULTS: FTAPE in various GXEH were determined. FTA were selected as GXEH's ABCs. Ratios of FTA were determined, suggesting the high (1:6.1:15.6), medium (1:1.7:15.2) and low (1:0.2:15.3) ratios. Three FTA ratios and their parent formulae ratio-dependently reduced infarct size, myocardial apoptosis and caspase-3 activity. CONCLUSION: There is the optimal ratio of F:T:A among various formulae, contributing to the best cardioprotection. This FTA ratio was developed as quality control of GXEH formula.

Retrospective review of digoxin exposures to a poison control system following recall of Digitek® tablets.

BACKGROUND: In April 2008, Digitek® digoxin tablets were recalled by the manufacturer as possibly containing double the labeled amount of drug. The recall to March 2006 involved 800 million tablets. OBJECTIVE: The aim of this study was to evaluate whether there was any increase in the number of calls to a poison control system, and any increase in the severity of exposures after the recall compared with before the recall. METHODS: A retrospective review of all digoxin exposures to a poison control system from March 2004 to February 2008 was conducted, with data extracted from an electronic database (California Poison Control System). Total numbers of exposures were identified. Cases with moderate, major, and death outcomes were also identified and tallied. Chi-squared analysis was performed. RESULTS: Prior to the recall, there were 679 digoxin exposures. 148 (22%) were listed with moderate, major, or death as outcome. After the recall, there were a total of 610 cases, 165 (27%) with moderate, severe, or death as outcome. There was a statistically significant increase in the total number of moderate, major, and death outcomes after the period of the manufacturing error compared with before (p = 0.028). CONCLUSION: During the period of manufacturing error, there was a statistically significant increase in digoxin exposures with moderate, major, or death outcomes. The recall of Digitek® tablets may have increased moderate, major, or death outcomes from digoxin exposures in a poison control system database.

Generic substitution: issues for problematic drugs.

The methodology and criteria for bioequivalence testing have been firmly established by the Food and Drug Administration (FDA). For certain drugs with a narrow therapeutic index (e.g., digoxin, levothyroxine, warfarin), generic substitution may not be advisable or even allowable, depending on the substitution laws of individual states. Digoxin and levothyroxine tablets are examples of drugs for which no New Drug Applications (NDAs) currently exist. However, commercially available generic products for both of these drugs have not been determined by the FDA to be therapeutically equivalent to the innovator products. Generic versions of warfarin have been approved by the FDA as being therapeutically equivalent to the innovator products, as have generic versions of the rescue inhaler albuterol. Yet, misinformation and myths persist regarding the adequacy and proven reliability of the FDA's determination of bioequivalence for these products.